Smart Economy

Carbon 60 or fullerenes and the origin of life

Is Carbon 60 the template for life? --how it all started on earth and around the universe 

Fullerene and the Origin of Life  http://www.ima.org.il/FilesUpload/IMAJ/0/41/20771.pdf

ABSTRACT:

The role of carbon in the development of life and as the structural backbone of all organisms is universally accepted and an essential part of evolution. However, the molecular basis is largely unknown and the interactions of carbon with nitrogen and oxygen in space are enigmatic.

In 1985, the previously unknown form of carbon, coined fullerene, was discovered. We hypothesize that by virtue of the unique properties of fullerene, this hollow, ultra-robust, large, purely carbon molecule was the earliest progenitor of life. It acted as a stable universal biologic template on which small molecules spontaneously assembled and then formed, by further assembly, a surface mantle (here termed rosasome) of larger molecules.

 

Killing Cancer by changing body pH from acidic to neutral or basic

 DIY Cancer treatment....baking soda or apple cider vinegar

Killing Cancer by changing body PH from acidic back to neutral or basic with sodium bicarbinate
or baking soda....old wive's tale confirmed by scientists at Cancer Center.

 

Tumor cells engineer acidity to drive cell invasion, Moffitt Cancer Center
researchers say

Using buffers to increase pH may inhibit cancer growth

Researchers at Moffitt Cancer Center and colleagues at Wayne State University School of Medicine investigated the acidity in solid tumors to determine if pH levels play a role in cancer cell
invasion in surrounding tissues. They found that an acidic microenvironment can
drive cancer cells to spread and propose that neutralizing pH would inhibit
further invasion, providing a therapeutic opportunity to slow the progression
of cancers.

Their study appeared in the Jan. 3 online release of Cancer Research, a publication of the
American Association for Cancer Research.

According to the study's corresponding author, Robert J. Gillies, Ph.D., chair of the Department of
Cancer Imaging & Metabolism at Moffitt, acidity in solid tumors is theresult of an increased fermentative metabolism combined with poor delivery of blood to tissues.

In this study, tumor invasion and pH were monitored in immunodeficient laboratory mice hosting a
variety of tumors. "We monitored the test animals over time using
microscopy and found that the highest regions of tumor invasion corresponded to
areas with the lowest pH," Gillies explained. "Tumor invasion did not
occur in regions with normal or near normal pH levels. Furthermore, when we neutralized the acidity with oral sodium bicarbonate, the invasion was halted."

Researchers proposedthat the acidic pH of the tumor microenvironment represents a "niche
engineering" strategy on the part of tumor cells, promoting invasion and
growth of malignant tumors into surrounding tissue. Niche engineering is a
concept in ecology describes how plants and animals alter their environment to
in ways that promote their own growth and survival over their competitors.
"We have long regarded cancers cells as an invading species," said study co-author Robert Gatenby, M.D., chair of the Diagnostic Imaging Services and Integrated Mathematical Oncology departments at
Moffitt.

A key to this process of adaptation and invasion is increased glucose metabolism in
the tumor. "The vast majority of malignant tumors metabolize glucose at
high rates," Gillies said. "We have proposed that there is a direct,
causative link between increased glucose metabolism and the ability of cancer
cells to invade and metastasize."

According to the research, elevated glucose metabolism is the cause of increased acidity in the
tumor microenvironment. Most tumors develop an abnormal vascular network that
tends to be poorly organized and leaky, disrupting blood flow and hampering the
delivery of oxygen.

"This poorly organized vascular system has a two-fold effect on tumor acidity,"
explained Gatenby. "First, it subjects tumor regions to poor perfusion,
which restricts oxygen and increases the rate of glucose fermentation. Second,
the poor perfusion hampers the ability to eliminate the resulting acids,
resulting in very low pH in surrounding tissues."

As tumor cells adapt to increasing acidity, niche engineering through normal cell death and new blood
vessel formation occurs in the tumor and the immune response is suppressed.

"Tumor cells perform niche engineering by creating an acidic environment that is not toxic to
the malignant cells but, through its negative effects on normal cells and
tissues, promotes local invasion of malignant cells," Gatenby said.

The researchers suggested that targeting this activity with buffers and other mechanisms aimed
at increasing pH levels will likely provide a valuable alternative to
traditional therapies focused entirely on killing tumor cells.

###

Funding for this study came from federal grants U54 CA143970; R01 CA 077575; R01 CA 131990S.

About Moffitt Cancer Center

Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's excellence in research, its contributions
to clinical trials, prevention and cancer control. Since 1999, Moffitt has been
listed in U.S. News & World Report as one of "America's Best Hospitals" for
cancer. With more than 4,200 employees, Moffitt has an economic impact on the
state of nearly $2 billion. For more information, visit MOFFITT.org, and follow
the Moffitt momentum on Facebook, twitter and YouTube.

Media release by Florida
Science Communications

Public release date: 25-Jan-2013

http://www.eurekalert.org/pub_releases/2013-01/hlmc-tce012413.php



Contact: Kim Polacek

kim.polacek@moffitt.org

813-745-7408

H. Lee Moffitt Cancer Center &
Research Institute

 

 http://www.eurekalert.org/pub_releases/2013-01/hlmc-tce012413.php

Children’s complex thinking skills begin forming before they go to school

By William Harms

January 23, 2013

New research at the University of Chicago and the University of North Carolina at Chapel Hill shows that children begin to show signs of higher-level thinking skills as young as age 4 ½. Researchers have previously attributed higher-order thinking development to knowledge acquisition and better schooling, but the new longitudinal study shows that other skills, not always connected with knowledge, play a role in the ability of children to reason analytically.

The findings, reported in January in the journal Psychological Science, show for the first time that children’s executive function has a role in the development of complicated analytical thinking. Executive function includes such complex skills as planning, monitoring, task switching, and controlling attention. High early executive function skills at school entry are related to higher than average reasoning skills in adolescence.

Growing research suggests that executive function may be trainable through pathways, including preschool curriculum, exercise and impulse control training. Parents and teachers may be able to help encourage development of executive function by having youngsters help plan activities, learn to stop, think, and then take action, or engage in pretend play, said lead author of the study, Lindsey Richland, assistant professor of comparative human development at the University of Chicago.

Although important to a child’s education, “little is known about the cognitive mechanisms underlying children’s development of the capacity to engage in complex forms of reasoning,” Richland said.

The new research is reported in the paper “Early Executive Function Predicts Reasoning Development” and follows the development of complex reasoning in children from before the time they go to school until they are 15. Richland’s co-author is Margaret Burchinal, senior scientist at the Frank Porter Graham Child Development Institute at the University of North Carolina at Chapel Hill.

The two studied the acquisition of analogical thinking, one form of complex reasoning. “The ability to see relationships and similarities between disparate phenomena is fundamental to analytical and inductive reasoning, and is closely related to measurements of general fluid intelligence,” said Richland. Developing complex reasoning ability is particularly fundamental to the innovation and adaptive thinking skills necessary for a modern workforce, she pointed out.

Richland and Burchinal studied a database of 1,364 children who were part of the Early Child Care and Youth Development study from birth through age 15. The group was fairly evenly divided between boys and girls and included families from a diverse cross-section of ethnic and income backgrounds.

The current study examined tests children took when they were 4 ½, when they were in first grade, third grade, and when they were 15.  Because the study was longitudinal, the same children were tested at each interval. Among the tests they took were ones to measure analytical reasoning, executive function, vocabulary knowledge, short-term memory and sustained attention.

Children were tested at 4 ½ on their ability to monitor and control their automatic responses to stimuli. In first grade they worked on a test that judged their ability to move objects in a “Tower of Hanoi” game, in which they had to move disks between pegs in a specific order.

In third grade and at 15 years old, they were tested on their ability to understand analogies, asked in third grade for instance to complete the question “dog is to puppy as cat is to__?” As 15-year-olds they were asked to complete written tests of analogies.

The study found a strong relationship between high scores among children who as preschoolers had strong vocabularies and were good at monitoring and controlling their responses (executive function) to later ability on tests of understanding analogies.

“Overall, these results show that knowledge is necessary for using thinking skills, as shown by the importance of early vocabulary, but also inhibitory control and executive function skills are important contributors to children’s analytical reasoning development,” Richland said.

The National Academy of Education/Spencer Foundation, the Office of Naval Research and the National Science Foundation supported the research.

Tags

Early childhood development, Early Executive Function Predicts Reasoning Development, Lindsey Richland, Psychological science

Russian Academy of Sciences (RAS) confirms Ukrainian breakthrough in Alzheimer's treatment with Hydrated Fullerenes or C60-HYFNs or Water Soluble Buckyballs

Russian Academy of Sciences confirms Ukrainian break-though in treating Alzheimer’s
with Carbon 60 or C-60 or hydrated fullerenes (C60HYFns) or Buckeyballs. 

After the discovery of C-60 in 1985 and the awarding of the Nobel prize in 1995 to Kroto, Smalley and Curl, Ukrainian scientists, then discovered a way to make Carbon 60 or C-60 or fullerenes or buckeyballs water soluble about 15 years ago, have made progress on the Alzheimer’s front
treating it with Fullerene Water Solution (FWS) and with conventional treatment.
This was approved as a “dietary supplement” by the Ukrainian Ministry of Health
in 2010, and just several weeks ago they started producing a water drink in
Ukraine with .0002mg/100ml of C-60.

Walter  Derzko

WATER  SOLUBLE C60 FOR DEVELOPING ALZHEIMER'S DISEASE  TREATMENT

I.Ya.Podolskiy1) E.G.Makarova 1) R.Ya.Gordon2) V.V.Vorobev2) L.G.Bobyleva 1) A.G.Bobylev1)
Z.A.Podlubnaya1) , A.B.Geht3) O.A.Mishulina4)


1) Institute of Theoretical and Experimental Biophysics, Pushchino
2) Institute of Cell Biophysics, Pushchino
3) The Russian State Medical University, Moscow
4) National Research Nuclear University MEPI, Moscow


Creation of drugs for the  prevention and treatment of Alzheimer's disease (AD) is the most important
challenge to biomedical research in the XXI century. Synthesis of water-soluble
fullerenes and carbon nanotubes opened a new direction for drug development,
which is growing rapidly in the U.S., Europe and Asia.

* Rationale. One key element in the pathogenesis of Alzheimer's disease is increased formation of aggregated forms in the brain of amyloid β-peptide (1-42) (Aβ1-42). Create antiamiloid drugs is
the main thrust of development of asthma therapy.

^ The project aims to investigate the properties of stable antiamiloidn molecular colloidal aqueous
solution of fullerene C60HyFn.

Results. By transmission electron microscopy in vitro for the first time on a visual level, it was shown that
water-soluble C60 prevent and destroy the beta-amyloid. These findings led to
the conclusion that the fullerene in vitro anti-aggregation has a strong effect
on the β-amyloid peptides. Microinjection C60HyFn (0.46 nmol / μl) into the
hippocampus significantly reduced β-amyloid deposits in the pyramidal neurons of
hippocampal CA1 neurons and warned neurodegeneration. Fluorescence microscopy of
hippocampal pyramidal neurons with acridine orange and microfluoremetric
analysis will provide quantitative data on the restoration protein synthesizing
activity of pyramidal neurons in the hippocampus, impaired Aβ. Microinjection
C60HyFn (0.46 nmol/1μl) to prevent violations of spatial memory, due to the
introduction of the hippocampus Aβ1-42 (1.6 nmol / μl). On surviving hippocampal
slices fullerene increases the activity of pyramidal neurons in rats modified
EEG frontal cortex, impaired Aβ1-42.

Conclusion. Functionalized C60 direction slowly act on one of the key molecular targets of Alzheimer's disease, aggregated amyloid β-peptides, and are of great interest for the development of
Alzheimer's disease therapy. We assume that in the first half of the XXI century
will be based on fullerenes developed an effective prevention and treatment of
Alzheimer's disease.

This work was supported by a grant of the Presidium of RAS "basic sciences Medicine" and the state contract the Ministry of Higher Education and Science of the Russian Federation №
P1052.

http://rudocs.exdat.com/docs/index-417897.html?page=47

More in Russian

http://www.c60water.com/index.php?option=com_content&view=article&id=9&Itemid=33

Ukrainian scientists, who discovered a way to make Carbon 60 or C-60 or fullerenes or buckeyballs
water soluble about 15 years ago, have made progress on the Alzheimer’s front
treating it with Fullerene Water Solution (FWS) and with conventional treatment.
This was approved as a “dietary supplement” by the Ukrainian Ministry of Health
in 2010, and just several weeks ago they started producing a water drink in
Ukraine with .0002mg/100ml of C-60.

Below is a very rough
Google Translation from the Russian original.

Obviously, this
research is not on the radar of most western
researchers.

Walter
Derzko

http://www.c60water.com/index.php?option=com_content&view=article&id=9&Itemid=33

One of the diseases elderly is Alzheimer's disease or senile dementia.
More common after
sixty, but sick and young people. The disease is characterized by a steady
deterioration of memory until the complete disintegration of the personality.
Already in the beginning of the disease, recognizing the gradual loss of memory,
a person experiences great emotionally shaken. This neurodegenerative disease
affects more than thirty million people. Nicholas Sparks romantic drama "The
Notebook" and the same film shows the tragedy of close people who are sick of
this terrible disease.
Unfortunately, at present, has not yet found drugs
that can stop or reverse the development of cause neurodegenerative process.
Search for drugs for the treatment of this disease are engaged in the world. The
Institute of
Theoretical and
Experimental Biophysics studies in experimental models of Alzheimer's disease
are conducted under the direction of Igor Jakovljevic Podolsky. In 2007, he
first discovered the neuroprotective properties of water molecules with the most
beautiful. His work, published in January 2012, revealed the influence of
fullerene water very cause of the neurodegenerative process of memory
loss.
Alzheimer's disease is
associated with a decrease in the water content in the brain and increased
formation of amyloid protein (beta-amyloid peptide Aβ1-42). The threads of this
protein like vines entwine the neurons of the brain, disrupting their work and
worsening memory. In November 2011, Podolsky reported to the Presidium of RAS
results of their work done in accordance with the program "Fundamental science -
medicine." It was shown that the water has a fullerene antiamiloidnymi
properties. Microinjection of water prevents the formation of amyloid by
fullerene and destroyed "threads" of amyloid protein. This led to a reduction of
neurodegenerative changes in the brain of rats and restore lost
memory.
Interview with Igor Yakovlevich under "great discovery" was broadcast
on Channel One Russian TV from 18 to 23 March 2012.

The obtained results
allow us to begin clinical studies of fullerene water as a means for the
treatment and prevention of Alzheimer's disease. It is assumed that patients
will spray water fullerene as a spray in the nasal passages and to drink a
certain pattern.
Increased production of amyloid protein is the cause of not
only Alzheimer's disease. In addition to degenerative changes in the brain, it
can cause malfunction of other organs such as the pancreas, which is considered
as a possible cause of diabetes type. Amyloid proteins provoke the development
of many serious human diseases, the methods of treatment which at the moment
does not exist.
The Institute of Theoretical and Experimental Biophysics of
amyloidosis research conducted by Professor Zoya Alexandrovna Podlubnaya. Her
studies show that water prevents the formation of fullerene and destroying
amyloids in striated muscle. Antiamiloidnye fullerene properties of water can
allow the creation of new drugs for the treatment of previously incurable
diseases. This stimulates interest in studying biomedical properties of
fullerene water in many research centers. 

Oxygen Chamber Can Boost Brain Repair

Wednesday, January 23, 2013

Hyperbaric treatment has significantly resuscitated activity in damaged brains, TAU researchers find

Stroke, traumatic injury, and metabolic disorder are major causes of brain damage and permanent disabilities, including motor dysfunction, psychological disorders, memory loss, and more. Current therapy and rehab programs aim to help patients heal, but they often have limited success.

Now Dr. Shai Efrati of Tel Aviv University's Sackler Faculty of Medicine has found a way to restore a significant amount of neurological function in brain tissue thought to be chronically damaged — even years after initial injury. Theorizing that high levels of oxygen could reinvigorate dormant neurons, Dr. Efrati and his fellow researchers, including Prof. Eshel Ben-Jacob of TAU's School of Physics and Astronomy and the Sagol School of Neuroscience, recruited post-stroke patients for hyperbaric oxygen therapy (HBOT) — sessions in high pressure chambers that contain oxygen-rich air — which increases oxygen levels in the body tenfold.

Analysis of brain imaging showed significantly increased neuronal activity after a two-month period of HBOT treatment compared to control periods of non-treatment, reported Dr. Efrati in PLoS ONE. Patients experienced improvements such as a reversal of paralysis, increased sensation, and renewed use of language. These changes can make a world of difference in daily life, helping patients recover their independence and complete tasks such as bathing, cooking, climbing stairs, or reading a book.

Oxygen breathes new life into neurons

According to Dr. Efrati, there are several degrees of brain injury. Neurons impacted by metabolic dysfunction have the energy to stay alive, but not enough to fire electric signals, he explains. HBOT aims to increase the supply of energy to these cells.

The brain consumes 20 percent of the body's oxygen, but that is only enough oxygen to operate five to ten percent of neurons at any one time. The regeneration process requires much more energy. The tenfold increase in oxygen levels during HBOT treatment supplies the necessary energy for rebuilding neuronal connections and stimulating inactive neurons to facilitate the healing process, explains Dr. Efrati.

For their study, the researchers sought post stroke patients whose condition was no longer improving. To assess the potential impact of HBOT treatment, the anatomical features and functionality of the brain were evaluated using a combination of CT scans to identify necrotic tissue, and SPECT scans to determine the metabolic activity level of the neurons surrounding damaged areas.

Seventy-four participants spanning 6 to 36 months post-stroke were divided into two groups. The first treatment group received HBOT from the beginning of the study, and the second received no treatment for two months, then received a two-month period of HBOT treatment. Treatment consisted of 40 two-hour sessions five times weekly in high pressure chambers containing oxygen-rich air. The results indicate that HBOT treatment can lead to significant improvement in brain function in post stroke patients even at chronically late stages, helping neurons strengthen and build new connections in damaged regions.

A potential avenue for prevention

Although the study focuses on patients only through three years post-stroke, Dr. Efrati has seen similar improvement in patients whose brain injuries occurred up to 20 years before, belying the concept that the brain has a limited window for growth and change. "The findings challenge the leading paradigm since they demonstrate beyond any doubt that neuroplasticity can still be activated for months and years after acute brain injury, thus revealing that many aspects of the brain remain plastic into adulthood," says Prof. Ben-Jacob.

This study also "opens the gate into a new territory of treatment," adds Dr. Efrati. The researchers are currently conducting a study on the benefits of HBOT for those with traumatic brain injury. This treatment also has potential as an anti-aging therapy, applicable in other disorders such as Alzheimer's disease and vascular dementia at their early stages.

"It is now understood that many brain disorders are related to inefficient energy supply to the brain," explains Dr. Efrati. "HBOT treatment could right such metabolic abnormalities before the onset of full dementia, where there is still potential for recovery."

---

For more neuroscience news from Tel Aviv University, click here.

Keep up with the latest AFTAU news on Twitter: http://www.twitter.com/AFTAUnews.

 

Job Posting for Instructors/consultants to teach cognitive skills and opportunity recognition in a business /scientific environment

Job Posting for  Instructors/consultants  to teach cognitive skills and opportunity recognition
in a business /scientific environment

Job opening for part time instructors/ consultants to teach critical and creative cognitive skills in a
business and scientific environment, in various cities across  Canada  on a project/contract basis.

Experience in teaching in  the secondary school gifted program, entrepreneurship programs or a background  in cognitive science, complexity science, behavior economics or neuro-economics
desirable.

Send resume and cover  letter to  the Strategic Foresight Group, 116 Galley Ave Toronto,
Ontario M6R 1H1 by Feb 5, 2013

Massive animals may hold secrets of cancer suppression-Peto’s paradox

Theory suggests trade-off between cancer risk and reproductive potential.

• Virginia
       Gewin

21 January 2013

 

Large animals such as humpback whales may have evolved cancer-fighting mechanisms that smaller
animals lack — but one flip-side could be lower rates of reproduction.

Sue Flood / naturepl.com

 

If every living cell had an equal chance of becoming cancerous, whales and elephants should have a
greater risk of developing cancer than do humans or mice. But across species,
the occurrence of cancer does not show a correlation with body mass. According
to a new model, the paradox could be explained if animals were striking a
balance between reducing cancer risk and other priorities, such as maximising
the number of offspring.

 

The lack of correlation between body mass and cancer risk is known as Peto’s paradox, after epidemiologist Richard Peto of Oxford University in the UK, who noted it in the 1970s.
Evolutionary biologists think that it results from larger animals using
protective mechanisms that many smaller animals do not¹.

In an attempt to identify how greater body mass might foster such mechanisms, evolutionary biologist Benjamin Roche at the Institute of Research for Development in Montpellier, France, and
his colleagues created a theoretical model to simulate which of 100 possible
genetic-mutation strategies would become most prevalent over 4,000 generations.

The model included two gene types: proto-oncogenes, which can cause normal cells to become cancerous, and tumour-suppressor genes, which repair cellular damage that could otherwise lead
to cancer. For carcinogenesis to occur, the team assumed that proto-oncogenes
must be activated and tumour-suppressor genes must be rendered inactive.

“We found that tumour-suppressor genes and proto-oncogenes react differently along a gradient of body masses,” says Roche. “Their evolutionary dynamics are linked.” Proto-oncogene activation
decreased steadily with increasing body mass, the team found.

Cost–benefit ratio

In their model, evolution did not
always favour tumour-suppressor genes. Although these mechanisms could reduce
cancer mortality in any animal, they may come at a cost — reduced fertility, in
the case of the team's model. The result was that for intermediate-sized
animals, the evolutionary cost of having many tumour suppressor genes was
greater than the benefits of cancer protection they offered.

As a consequence, mutations would arise to keep tumour-suppressors in check.
“At this point, it is better for the population, evolutionarily, to tolerate
more deaths from cancer rather than investing in more costly mechanisms to
avoid cancer development,” says Roche.

The results, published in a special issue of Evolutionary Applications focused on cancer biology², could explain why, for example, the incidence of
cancer in humans stands at one in three, whereas it is only 18% in beluga whales³.

Roche and colleagues' is not the
only proposed explanation for Peto’s paradox. “There are a number of different
hypotheses,” says Carlo Maley, director of the Center for Evolution and Cancer
at the University of California, San
  Francisco. “For example, rather than body mass
influencing the number of tumour suppressors and oncogenes, maybe there are
less reactive oxygen species in larger organisms due to their lower metabolic
rate."

Maley and his colleagues are
sequencing the humpback whale genome, which they plan to compare with others,
including the elephant genome, to determine which hypotheses might be valid —
and whether nature has already come up with cancer-prevention mechanisms that
could be translated to the clinic.

Still, some biologists question
whether there is a paradox at all, saying that variations in cancer rates
across species — which range between 20% and 46% — are more similar than
different. “All species get cancer at about the same rate, typically in the
latter part of life span,” says James DeGregori, a molecular biologist at the University of Colorado
in Denver. “We
simply don’t have the data yet to back up the notion that larger animals have
come up with a way to avoid oncogenic mutations.”

Journal name:

Nature

DOI:

doi:10.1038/nature.2013.12258

References

1. 
   Caulin
   A.F., & Maley, C.C., Trends
   Ecol Evol 26, 175–182 (2011).

1.  
   • Article
   • ISI

Show context

1. 
   Roche, B., et
   al., Evo Appl. DOI: 10.1111/eva.12025 (2013).

Show context

1. 
   Martineau, D. et
   al. Environ Health Perspect. 110, 285–292 (2002).

1.  
   • Article
   • PubMed
   • ISI

Show context

 

 

Mathematicians aim to take publishers out of publishing

Episciences Project to launch series of community-run, open-access journals.

17 January 2013

Jean-Pierre Demailly is a leader in an effort to create a researcher-run publishing system.

Mathematicians plan to launch a series of free open-access journals that will host their peer-reviewed
articles on the preprint server arXiv. The project was publicly revealed yesterday in a blog post by Tim Gowers, a Fields Medal winner and mathematician at the University of Cambridge, UK.

 

The initiative, called the Episciences Project, hopes to show that researchers can organize the peer
review and publication of their work at minimal cost, without involving commercial publishers.

“It’s a global vision of how the research community should work: we want to offer an alternative to traditional mathematics journals,” says Jean-Pierre Demailly, a mathematician at the University of Grenoble, France, who is a leader in the effort. Backed by funding from the French government, the initiative may launch as early as April, he says.

Many mathematicians — and researchers in other fields — claim that they already do most of the work
involved in publishing their research. At no cost, they type up and format
their own papers, post them to online servers, join journal editorial boards
and review the work of their peers. By creating journals that publish links to
peer-reviewed work on servers such as arXiv, Demailly says, the community could
run its own publishing system. The extra expense involved would be the cost of
maintaining websites and computer equipment, he says.

That cost is not small, but it
could eventually be provided in part by the journals' users. The arXiv server,
for example, costs about US$826,000 a year to run, and is funded by the Cornell
University Library in Ithaca, New
York; the Simons Foundation in New York and institutional members.

Demailly says that he first thought of open-access electronic journals that overlay arXiv eight years ago, but the concept became a reality only last June, when he was contacted by the
Centre for Direct Scientific Communication (CCSD), based in Villeurbanne,
France. The CCSD, a unit of the French National Centre for Scientific Research,
develops open-access repositories such as the multidisciplinary archive HAL,
which mirrors the arXiv site.

For the Episciences Project, the CCSD plans to create a publishing platform that will support online
peer-reviewed journals. Each journal, or ‘epijournal’, would have its own
editor and editorial board, and authors could submit their arXiv-posted papers
to their journal of choice. The journal would then organize peer review,
perhaps using workflow software provided by the CCSD. Peer-reviewed papers
would be posted on arXiv alongside their un-reviewed versions. A central
committee (led by Demailly) would manage new journal candidates and make
recommendations on paper formatting, but each journal would be free to set its
own policies (including whether to charge for publication).

Gowers plans to start a journal in the interdisciplinary field of additive combinatorics; Demailly would not
say what other early epijournals might be. Gowers has strong views on shaking
up research publishing — last year, he kick-started
a boycott of the Dutch publishing giant Elsevier (see also Nature’s
profile of Gowers).

The idea of overlaying arXiv is
not new: some mathematics journals tried it in the early 2000s but scrapped the
idea because libraries began dropping print subscriptions, says Demailly.
Meanwhile, there are already some free, community-organized mathematics
journals, such as Documenta Mathematica, funded by the German Mathematical Society. “They are doing things on their own with a small website; we will have a global platform
capable of drastically reducing an individual journal’s administration costs,”
Demailly says.

Demailly says that he expects to adjust the concept with feedback from the mathematics community. “If people want larger reviews linked to papers, or the possibility of online comments and
blogs, we can offer this with only minor changes to the platform,” he says. At
the moment, the model's success or failure hinges on buy-in from mathematicians
— but the involvement of Gowers and other prominent mathematicians, such as
Terence Tao of the University of California, Los
  Angeles, may help to build support.

Journal name: Nature

DOI:doi:10.1038/nature.2013.12243

 

 

Four decades of business scenarios: what can experience teach?

Four decades of business scenarios: what can experience teach?

Authors: Stephen M. Millett

Article Type: Conceptual paper

Keywords: Future unknowns, Futuring and visioning, Long-term risk,
Research-based scenarios, Scenario learning, Scenario methodology, Scenarios,
Scenarios as hypotheses, Scenarios for desirable futures, Subject experts

Strategy & Leadership, Volume 41, Issue 1

Page Numbers: 29 - 33

Year: 2013

La Jolla Institute identifies molecular switch enabling immune cells to better fight disease

Finding on killer cells opens new avenue for combating AIDS, cancer and other diseases

SAN DIEGO – (January 20th, 2013) A research team led by the La Jolla Institute for Allergy & Immunology has discovered the mechanism that enables CD4 helper T cells to assume the more aggressive role of killer T cells in mounting an immune attack against viruses, cancerous tumors and other damaged or infected cells.   The finding, made in collaboration with researchers from the RIKEN Institute in Japan, could enable the development of more potent drugs for AIDS, cancer and many other diseases based on using this mechanism to trigger larger armies of killer T cells against infected or damaged cells. 

CD4 helper T cells, which normally assist other cells of the immune system during an infection, and CD8 killer T cells, which directly attack and eliminate infected cells, are two of the body's most important immune cells for defending against diseases.  Earlier research studies have shown that helper T cells can become killer cells in some instances.  However, the specific mechanism of action that allowed this to occur was not known until now.

"We have identified the molecular switch that enables CD4 T cells to override their programming as helper cells and transform into cytolytic (killer) cells," said La Jolla Institute scientist and study co-leader Hilde Cheroutre, Ph.D.  "Our team also showed that these transformed helper T cells represent a separate and distinct population of cells.  They are not a subset of TH-1 helper cells as previously thought."

Jay A. Berzofsky, M.D., Ph.D., chief of the Vaccine Branch at the National Cancer Institute's Center for Cancer Research, called the finding "a major advance" that provides new understanding about the cell's lineage and basic mechanisms.  Dr. Berzofsky was among the researchers whose work in the 1980s first demonstrated that helper cells could convert to killer cells.  "Understanding how these cells derive and what causes them to switch from helper T cells to cytolytic T cells is an important step to learning how to manipulate them in disease," he said, noting it could lead to novel approaches "either to turn these cells off in autoimmune disease or turn them on in infectious diseases."

He added that the finding could also have important implications in cancer. "We need all of the cytolytic machinery that we can get to try to destroy cancers," he said. "If we can learn to turn them on, I think it's reasonable to believe that these cytolytic T cells can play an important role in controlling cancer."

The findings were published today in Nature Immunology in a paper entitled "Transcriptional reprogramming of mature CD4 helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes."  Dr. Cheroutre is co-senior author on the study together with Dr. Ichiro Taniuchi of the RIKEN Research Center for Allergy and Immunology in Yokohama, Kanagawa, Japan.  First authors on the paper are: Mohammad Mushtaq Husain, Ph.D., of the La Jolla Institute; Daniel Mucida, Ph.D., formerly of the La Jolla Institute, now at Rockefeller University; Femke van Wijk, Ph.D., formerly of the La Jolla Institute, now at the University Medical Center Utrecht, The Netherlands, and Sawako Muroi, of the RIKEN Institute.

Mitchell Kronenberg, Ph.D., La Jolla Institute president & chief scientific officer, said the study reflects the very successful collaboration between the La Jolla Institute and RIKEN in Japan, which have joined efforts on a number of projects over the years.

In the study, the researchers found that a certain transcription factor, which are molecules in the cell nucleus that control  the activity of cells, continually suppresses the killer T cell lineage in helper T cells.  Using mice, the team showed that turning off this transcription factor (ThPOK) enabled the helper cells in the body's peripheral areas, like the blood, spleen and the intestine, to override their original programming and to become killer T cells.  "While our work focused on the intestines, we found that helper T cells in all tissues of the body have the potential to become killer cells in response to recognition of viral, tumor or other antigens in the context of cytokines such as IL-15," said Dr. Cheroutre.

Jonathan Braun, M.D., chair of the Department of Pathology and Laboratory Medicine at UCLA's David Geffen School of Medicine, praised the study as laying the groundwork for using T helper cells in a much more aggressive manner.  "Helper T cells are mainly understood for their role in regulating other immune cells," he said.  "This work reveals how they themselves can be triggered to become the action cells in the immune response.  This opens new possibilities for how to manipulate them therapeutically in disease."

Dr. Cheroutre said the transformation of CD 4 helper T cells into killer cells already occurs in the body naturally.  "Our finding could help to explain a number of occurrences that we haven't really understood up to this point, such as why some people can be chronically infected with HIV without developing AIDS."  In these instances, Dr. Cheroutre is convinced that CD4 helper T cells must be taking over the role of killer cells after the CD8 T cells become exhausted.  "It's like the helper cells can come in as reinforcements to keep the virus under control.  If we can develop ways to artificially trigger that process, we may be able to significantly help people with HIV and other chronic infections." 

While scientists would want to trigger a larger army of virus-specific killer cells in the case of infections, the opposite would be true in inflammation-fueled autoimmune diseases, like rheumatoid arthritis or multiple sclerosis, said Dr. Cheroutre.  "The CD4 T cells are the bad wolves in inflammatory diseases because they often trigger more pro-inflammatory cells which worsen these conditions," she said.  "With this knowledge, we may be able to prevent that by coaxing the CD4 killer cells to become regulatory cells instead, which is another one of their potential functions.  In regulatory mode, the CD4 T cells suppress the immune system.  This suppression reduces inflammatory cells, which is what we want to do in autoimmune diseases." 

However in cancer, the CD4 T cell's regulatory function becomes problematic because they inhibit the killer T cells from destroying cancerous cells.  This is because of their built-in mechanism to keep T cells from attacking the body's own cells, said Dr. Cheroutre.   "Cancer cells develop from our own cells and only look a little different from healthy cells," she explained.  "The killer T cells can sense that they are different and decide to eliminate them.  However, the CD4 regulatory T cells frequently suppress the killer T cells and prevent them from destroying the cancerous cells.  This is often how cancer cells can escape the immune system's normal action of stamping out bad cells."

Dr. Cheroutre said she believes it may be possible, using the newly discovered mechanism, to turn the CD4 regulatory T cells into killer cells that would aid, rather than block, the immune system's attack on cancerous cells.

 

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Scripps Research Institute Chemists Devise Inexpensive, Benchtop Method for Marking and Selecting Cells

LA JOLLA, CA – January 8, 2013 - Chemists at The Scripps Research Institute (TSRI) have found an easier way to perform one of the most fundamental tasks in molecular biology. Their new method allows scientists to add a marker to certain cells, so that these cells may be easily located and/or selected out from a larger cell population.

The technique, which is described in a recent issue of the chemistry journal Angewandte Chemie International Edition,makes use of the tight binding of two proteins that are cheaply obtainable but are not found in human or other mammalian cells. As such, it has advantages over existing cell-marking techniques.

“This new technique is cheap, easy and sensitive,” said TSRI Institute Professor Richard A. Lerner, who is the senior author of the new report. “The method should be useful in a variety of applications that require separating out certain types of cells.”

Looking for a Better Way

The best-known cell marker in use today is GFP (green fluorescent protein), a jellyfish protein that emits a distinctive green light when illuminated by certain other light wavelengths. When scientists want to add a new gene to cells, for example to produce a therapeutic protein, they often construct a genetic sequence that also includes the GFP gene. Thus the cells that successfully produce the new protein will also produce GFP, whose fluorescence allows these cells to be identified and even sorted out from a larger population.

But fluorescence-based cell sorting is relatively expensive and cumbersome. Alternative cell-marking techniques use marker molecules to which antibodies or metals will bind tightly, but these are apt to have unwanted side effects on the cells that they mark. Lerner’s team, led by first author Yingjie Peng, a postdoctoral fellow, set out to invent a better method.

The new method exploits a special property of chitinase enzymes, which evolved to break down chitin—a tough, sugar-derived material found, for example, in crab shells, squid beaks and the cell walls of fungi. In addition to a main chitin-breaking domain, chitinases have another active structure, a “chitin binding domain”(ChBD). “It makes a super-strong bond with chitin,” said Peng. In recent years, scientists have begun to use this high-affinity binding of ChBD and chitin as a marker system, typically for selecting ChBD-tagged proteins in a lab dish. The new method uses ChBD to mark and select cells.

A Powerful Tool

In the basic technique, a new gene can be added to cells within a larger DNA vector that also includes the genetic sequences for ChBD and GFP. The ChBD molecule will be produced in such a way that it ends up being held on the outer surface of its host cell’s plasma membrane—and the GFP molecule will sit just inside the membrane. The GFP serves as a visual beacon, while the ChBD serves as a handy gripping point for cell selection.

After exposing a culture of test cells to this experimental ChBD-containing vector, the scientists was able to see, via the GFP tags, which cells were expressing them, and was able to select them out easily, with high sensitivity, using magnetic beads coated with chitin. “This is a relatively easy benchtop method,” Peng said. Importantly, these selected cells could produce progeny cells that seemed normal and healthy.

Because the ChBD marker, in the vector, is produced in a way that anchors it to a cell’s membrane, it also can serve as a powerful tool for selecting just the membrane fraction of a sample of cellular material. Peng and his colleagues demonstrated this using chitin beads to quickly isolate a pure fraction of membrane material from ChBD-marked test cells.

Cellulase enzymes, which break down the ubiquitous plant compound cellulose, also have a high-affinity cellulase-binding domain, which can be employed in the same way as the ChBD.

The scientists expect that the new cell-marking method will help to streamline another major molecular biology technique, which was pioneered by the Lerner laboratory in parallel with the group of Sir Gregory Winter at the Laboratory of Molecular Biology in Britain. This technique allows scientists to produce very large and diverse libraries of antibody arms, and to sift through them, or“pan”—as gold miners pan for nuggets—for those that might be of use, for example in therapies. ChBD-based markers should be useful in boosting the efficiency of this panning process, said Peng.

The Lerner laboratory is also investigating the potential use of ChBD-based cell marking in living animals, for example to track the fates of selected cell types throughout an animal’s lifespan.

Those interested in using the new technology are invited to contact TSRI’s Office of Technology Development, at (858) 784-8140 or through the department’s webpage at http://www.scripps.edu/research/technology/contactus.html.

Other contributors to the study, “Engineering Cell Surfaces for Orthogonal Selectability,”were Teresa M. Jones and Diana I. Ruiz of the TSRI Department of Chemistry, and Dae Hee Kim of the Scripps Korea Antibody Institute. For more information on the paper, see http://onlinelibrary.wiley.com/doi/10.1002/anie.201201844/abstract

The research was supported by a grant from Scripps Korea Antibody Institute.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, TSRI has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

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For information:
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Tel: 858-784-8134
Fax: 858-784-8136
press@scripps.edu

Researchers discover how underground rodent wards off cancer

 

Second mole rat species has different mechanism for resisting
cancer

Biologists at the University of Rochester have determined how blind mole
rats fight off cancer—and the mechanism differs from what they discovered three
years ago in another long-lived and cancer-resistant mole rat species, the
naked mole rat.

The team of researchers, led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, found that abnormally growing cells in blind mole rats secrete the interferon beta
protein, which causes those cells to rapidly die. Seluanov and Gorbunova hope
the discovery will eventually help lead to new cancer therapies in humans.
Their findings are being published this week in the Proceedings of the
National Academy of Sciences.

Blind mole rats and naked mole rats—both subterranean rodents with long life spans—are the only
mammals never known to develop cancer. Three years ago, Seluanov and Gorbunova
determined the anti-cancer mechanism in the naked mole rat. Their research found
that a specific gene—p16—makes the cancerous cells in naked mole rats
hypersensitive to overcrowding, and stops them from proliferating when too many
crowd together.

"We expected blind mole rats to have a similar mechanism for stopping the spread of cancerous
cells," said Seluanov. "Instead, we discovered they've evolved their
own mechanism."

Gorbunova and Seluanov made their discovery by isolating cells from blind mole rats and forcing them
to proliferate in culture beyond what occurs in the animal. After dividing
approximately 15-20 times, all of the cells in the culture dish died rapidly.
The researchers determined that the rapid death occurred because the cells
recognized their pre-cancerous state and began secreting a suicidal protein,
called interferon beta. The precancerous cells died by a mechanism which kills
both abnormal cells and their neighbors, resulting in a "clean
sweep."

"Not only were the cancerous cells killed off, but so were the adjacent cells, which may also be
prone to tumorous behavior," said Seluanov.

"While people don't use the same cancer-killing mechanism as blind mole rats, we may be able
to combat some cancers and prolong life, if we could stimulate the same clean
sweep reaction in cancerous human cells," said Gorbunova.

The research team also included Christopher Hine, Xiao Tian, and Julia Ablaeva in Rochester,
Andrei Gudkov at Roswell Park Cancer Institute in Buffalo,
NY, and Eviatar Nevo at the University of Haifa
in Israel.

Gorbunova and Seluanov say they next want to find out exactly what triggers the secretion of
interferon beta after cancerous cells begin proliferating in blind mole rats.

Gorbunova believes the anti-cancer mechanism is an adaptation to subterranean life. "Blind mole
rats spend their lives in underground burrows protected from predators,"
said Gorbunova. "Living in this environment, they could perhaps afford to
evolve a long lifespan, which includes developing efficient anti-cancer
defenses."

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Possibility of surfaces that can be manipulated

Using new combinations of well-known polymers is one way of producing new materials.For this work, the use of polymers that respond to external stimuli are of particular interest, and is the line followed by the chemist Leire Ruiz-Rubio in the research for her PhD thesis. She has studied the blending of certain polymers that can be controlled when the conditions of their medium (the pH or temperature, for example) have been altered.Once the behaviour of these polymers is known, it is possible to design new materials to use in many different applications.“We do basic chemistry; in other words, we study the behaviour of these polymers in more and more advanced conditions, and then the applications that can be developed thanks to these materials will be sought.” Ruiz has in fact studied the polymer blends first of all in solution and then when they are on a solid surface.

 

The aim was to find out the conditions in which polymer chains disperse and when they end up joined together.Having examined that, Ruiz went on to study how the conditions can be manipulated, so that the material formed by the polymer blend can be altered from a dense layer to one with holes.

The blends in this research were produced by adding one of eachof thetwo polymer groups.In one group there were polyacids, in other words, proton donors (acrylic polyacid and methacrylicpolyacid and phenolic polyvinyl). In the second group there are several poly(N-vinylamides), in other words, polymers that can create hydrogen bridges with the protons of the ones before them.

“We have studied the relationship between polymers.In other words, to see whether polymers of one blend move away from each other, or whether, by contrast they become adhered to each other."And they studied that relationship first in solution, because the solvent can greatly influence that.Polymer chains will move away from each other if they have a greater tendency to attach themselves to the molecules of the solvent (dispersive tendency).By contrast, if the hydrogen bridges between the polymers are more stable than the relationship towards the solvent, the polymer chains will tend to stay together (associative behaviour).

The balance is a tricky one, because there are all kinds of interactions.“That’s the problem,” says Ruiz.“Polyacids, for example, not only interact with the solvent and other polymers, they also interact with themselves, but some polyamides, for example, prefer to join with other polymers.The same thing happens depending on the quality of the solvent.If the solvent is very good, the polymers tend to join with it.”

 

Most of the solvents used in this work are alcohols, (methanol, ethanol, propanol, etc.) and the effect of their molecule size has been studied.In fact, the size has a lot to do with whether the solvent is good or bad:small alcohols are better solvents that large ones.

Ruiz and her colleagues repeated their solution-based research in the conditions of a surface.They wanted to know what kind of behaviour was displayed by these polymer blends on a surface.They used silicon surfaces covered with a co-polymer layer and added a number of functional groups to that layer.“They end up as if they were strands of hair," says Ruiz.The polymer blends were placed on top and they formed a second layer.These kinds of systems can be manipulated, for example by changing the pH or the temperature, and the chemical and physical properties of the surface change.And in the end, the polymer blend will behave in one way or another according to that.

“We do basic chemistry, but you always have applications in mind.For example, drugs can be inserted between these layers and attached to the hairs of the surface.With the drugas the filling, it would end up like a kind of sandwich.”In that case, by manipulating the pH or temperature, the polymer blend can be dismantled and the drug released at the desired moment.So, one potential application is a capsule that opens at the desired moment.“But that’s still a long way off.We have studied what happens in the solution, and then in a more complex medium, on a surface.When you have studied that, you’ll be able to go one step further.”But the capsule application is still a long way away.The aim of this thesis was to study the behaviour of certain polymers.

Leire Ruiz-Rubio (Bilbao, 1979) graduated in Chemistry at the Faculty of Science and Technology of the UPV/EHU-University of the Basque Country.She did her PhD in the same place under the supervision of the lecturer Maria Teresa Garay-Perez.Today, she works as a researcher in the Department of Physical Chemistry.She also lectures in chemistry at the Faculty of Science and Technology.

 

Breast milk contains more than 700 bacteria

Microbes taken from breast milk by the infant are identified

Spanish researchers have traced the bacterial microbiota map in breast milk, which is the main source of nourishment for newborns. The study has revealed a larger microbial diversity than originally thought: more than 700 species.

The breast milk received from the mother is one of the factors determining how the bacterial flora will develop in the newborn baby. However, the composition and the biological role of these bacteria in infants remain unknown.

A group of Spanish scientists have now used a technique based on massive DNA sequencing to identify the set of bacteria contained within breast milk called microbiome. Thanks to their study, pre- and postnatal variables influencing the micriobial richness of milk can now be determined.

Colostrum is the first secretion of the mammary glands after giving birth. In some of the samples taken of this liquid, more than 700 species of these microorganisms were found, which is more than originally expected by experts. The results have been published in the 'American Journal of Clinical Nutrition'.

"This is one of the first studies to document such diversity using the pyrosequencing technique (a large scale DNA sequencing determination technique) on colostrum samples on the one hand, and breast milk on the other, the latter being collected after one and six months of breastfeeding," explain the coauthors, María Carmen Collado, researcher at the Institute of Agrochemistry and Food Technology (IATA-CSIC) and Alex Mira, researcher at the Higher Public Health Research Centre (CSISP-GVA).

The most common bacterial genera in the colostrum samples were Weissella, Leuconostoc, Staphylococcus, Streptococcus and Lactococcus. In the fluid developed between the first and sixth month of breastfeeding, bacteria typical of the oral cavity were observed, such as Veillonella, Leptotrichia and Prevotella.

"We are not yet able to determine if these bacteria colonise the mouth of the baby or whether oral bacteria of the breast-fed baby enter the breast milk and thus change its composition," outline the authors.

The heavier the mother, the fewer the bacteria

The study also reveals that the milk of overweight mothers or those who put on more weight than recommended during pregnancy contains a lesser diversity of species.

The type of labour also affects the microbiome within the breast milk: that of mothers who underwent a planned caesarean is different and not as rich in microorganisms as that of mothers who had a vaginal birth. However, when the caesarean is unplanned (intrapartum), milk composition is very similar to that of mothers who have a vaginal birth.

These results suggest that the hormonal state of the mother at the time of labour also plays a role: "The lack of signals of physiological stress, as well as hormonal signals specific to labour, could influence the microbial composition and diversity of breast milk," state the authors.

Help for the food industry

Given that the bacteria present in breast milk constitute one of initial instances of contact with microorganisms that colonise the infant's digestive system, the researchers are now working to determine if their role is metabolic (it helps the breast-fed baby to digest the milk) or immune (it helps to distinguish beneficial or foreign organisms).

For the authors, the results have opened up new doors for the design of child nutrition strategies that improve health. "If the breast milk bacteria discovered in this study were important for the development of the immune system, its addition to infant formula could decrease the risk of allergies, asthma and autoimmune diseases," conclude the authors.

 

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References:

Referencia bibliográfica:

Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. "The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery".  American Journal of Clinical Nutrition 96(3):544-551, 2012.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

UCSB researchers perform pioneering research on Type 2 diabetes

		IMAGE:This is Jamey Marth.Click here for more information.

(Santa Barbara, Calif.) –– While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to Type 2 diabetes, autoimmune diseases, and neurodegenerative diseases, among others.

Scientists at UCSB have published groundbreaking results of a study of Type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease.

		IMAGE:This is Frank Doyle.Click here for more information.

The current work is based on a previous major finding by UCSB's Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids. Marth is a professor in the Department of Molecular, Cellular, and Developmental Biology and the Biomolecular Science and Engineering Program; and holds the John Carbon Chair in Biochemistry and Molecular Biology and the Duncan and Suzanne Mellichamp Chair in Systems Biology. He is also a professor with the Sanford-Burnham Medical Research Institute in La Jolla.

"By studying the four types of components that make up the cell, we can, for the first time, begin to understand what causes many of the common grievous diseases that exist in the absence of definable genetic variation, but, instead, are due to environmental and metabolic alterations of our cells," said Marth. UCSB is the only institution studying these four types of molecules in the cells while also using computational modeling to determine their functions in health and disease, according to Marth.

The new study, published in the December 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of Type 2 diabetes.

"Even in the post-genomic era, after the human genome has been sequenced, we're beginning to realize that diseases aren't always in our genes –– that the environment is playing a major role in many of the common diseases," said Marth.

		IMAGE:This image shows four types of macromolecules in cells. The nucleic acids DNA and RNA and proteins are on the left and glycans and lipids are on the right.Click here for more information.

Normally, beta cells in the pancreas sense a rise in blood sugar and then secrete insulin to regulate blood glucose levels. But in Type 2 diabetes, the beta cells fail to execute this important function and blood sugar rises, a trend that can reach life-threatening levels. The researchers identified a "tipping point," or metabolic threshold, that when crossed results in the failure of beta cells to adequately sense glucose in order to properly secrete insulin.

Obesity has long been linked to Type 2 diabetes, but the cellular origin of the disease due to beta cell failure has not been described until now. "In obesity there's a lot of fat in the system," said Marth. "When the cell is exposed to high levels of fat or lipids, this mechanism starts, and that's how environment plays a role, among large segments of the population bearing 'normal' genetic variation. We're trying to understand what actually causes disease, which is defined as cellular dysfunction. Once we understand what causes disease we can make a difference by devising more rational and effective preventative and therapeutic approaches."

The research was based on a unique approach. "This project illustrates the power of systems biology; namely, how a network perspective combined with computational modeling can shed new light on biophysical circuits, such as this beta-cell glucose transport system," said co-author Frank Doyle. "It cannot be done by molecular biology alone, nor computational modeling alone; rather, it requires the uniquely interdisciplinary approach that is second-nature here at UCSB." Doyle is associate dean for research of the College of Engineering; director of UCSB's Institute for Collaborative Biotechnologies; professor of chemical engineering; and the Mellichamp Chair in Process Control.

"We are excited to bring our 20 years of expertise on Type 1 diabetes and systems biology methods to look at the networks responsible for the onset of Type 2 diabetes," said Doyle.

According to the American Diabetes Association, 8.3 percent of the U.S. population has diabetes. The disease can lead to nerve loss, blindness, and death.

The first author of the paper is Camilla Luni, who was a UCSB postdoctoral researcher at the time of the study, and is now with the University of Padova, in Italy. The research was funded by a grant from the U.S. Army Research Office to UCSB's Institute for Collaborative Biotechnologies, and a grant from the U.S. National Institutes of Health.

 

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Shifting the balance between good fat and bad fat> study on p62's role in fat metabolism

by Bruce Lieberman on January 4, 2013  at 10:39 am  | 1 comment

Sanford-Burnham Professors Jorge Moscat, Ph.D., and Maria Diaz-Meco, Ph.D. co-authored a study on p62's role in fat metabolism

Sanford-Burnham researchers show that protein p62 balances metabolism in fat tissue—making it an attractive target for anti-obesity therapies

 In many cases, obesity is caused by more than just overeating and a lack of exercise. Something in the body goes haywire, causing it to store more fat and burn less energy. But what is it? Sanford-Burnham researchers have a new theory—a protein called p62. According to a study the team published December 21 in the Journal of Clinical Investigation, when p62 is missing in fat tissue, the body’s metabolic balance shifts—inhibiting “good” brown fat, while favoring “bad” white fat. These findings indicate that p62 might make a promising target for new therapies aimed at curbing obesity.

“Without p62 you’re making lots of fat but not burning energy, and the body thinks it needs to store energy,” said Jorge Moscat, Ph.D., Sanford-Burnham professor. “It’s a double whammy.” Moscat led the study with collaborators at Helmholtz Zentrum München in Germany and the University of Cincinnati.

p62 and obesity

Moscat’s team had previously produced mice that completely lack the p62 protein everywhere in their bodies. As a result, the animals were obese. They also had metabolic syndrome. In other words, as compared to mice with p62, mice lacking p62 weighed more, expended less energy, had diabetes and had a hyper-inflammatory response that’s characteristic of obesity.

While those results showed that the lack of p62 leads to obesity, “we didn’t know which tissue was responsible for these effects, because p62 was missing in all of them,” Moscat said.

Some researchers believe that muscle tissue, where energy is expended, controls obesity. Others suspect the liver is a key player, or that the brain’s appetite control center is most responsible for obesity.

But then there’s fat itself—both white fat and brown fat. White fat is the type we think of as unwanted body fat. Brown fat, on the other hand, is beneficial because it burns calories. Many researchers now believe that brown fat somehow malfunctions in obesity, but the details are unclear.

p62 shifts the balance between white fat and brown fat

In their latest study, Moscat and colleagues set out to pinpoint the specific tissue responsible for obesity when p62 is missing. They made several different mouse models, each missing p62 in just one specific organ system, such as the central nervous system, the liver, or muscle. In every case, the mice were normal. They weren’t obese like the mice lacking p62 everywhere.

Then they made a mouse model lacking p62 only in their fat tissue. These mice were obese, just like the mice missing p62 in all tissues. Upon further study, the researchers found that p62 blocks the action of an enzyme called ERK while activating another enzyme called p38. When p62 is missing, the enzyme p38 is less active in brown fat, while ERK is more active in white fat. As a result, Moscat said, p62 is “a master regulator” in normal fat metabolism.

According to Moscat, the discovery of p62’s role in brown fat tissue is encouraging, because fat tissue is much more accessible than other parts of the body—the brain, for example—for potential drug therapies. “This makes it easier to think about new strategies to control obesity,” he said.

New methods for preventing or treating obesity, a major epidemic in the United States, are urgently needed. Drug therapies designed to minimize the intake of food have had limited success and also produce considerable side effects.

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This study was funded by the National Institutes of Health -  National Institute of Allergy and Infectious Diseases grant DK088107 and National Cancer Institute grants CA132847 and CA134530.

Original paper:

Müller TD, Lee SJ, Jastroch M, Kabra D, Stemmer K, Aichler M, Abplanalp B, Ananthakrishnan G, Bhardwaj N, Collins S, Divanovic S, Endele M, Finan B, Gao Y, Habegger KM, Hembree J, Heppner KM, Hofmann S, Holland J, Küchler D, Kutschke M, Krishna R, Lehti M, Oelkrug R, Ottaway N, Perez-Tilve D, Raver C, Walch AK, Schriever SC, Speakman J, Tseng YH, Diaz-Meco M, Pfluger PT, Moscat J, & Tschöp MH (2013). p62 Links β-adrenergic input to mitochondrial function and thermogenesis. The Journal of clinical investigation, 123 (1), 469-78 PMID: 23257354

Gene therapy reprograms scar tissue in damaged hearts into healthy heart muscle

 

NEW YORK (Jan. 4, 2013) -- A cocktail of three specific genes can reprogram cells in the scars caused
by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect, said researchers from Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center in a report that appears online in the Journal of the American Heart Association.

"The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting," said Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report's corresponding author. "The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene."

"This experiment is a proof of principle," said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer ingene therapy, who played an important role in the research. "Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts."

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.

Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery,
Rosengart and his colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein.)

The GMT genes alonereduced the amount of scar tissue by half compared to animals that did not
receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart.)

The hearts of the animals that had received both the GMT and the VEGF gene transfers had an
ejection fraction four times greater than that of the animals that had received only the GMT transfer.

Rosengart emphasizes that more work needs to be completed to show that the effect of the VEGF is
real, but it has real promise as part of a new treatment for heart attack that would minimize heart damage.

"We have shown both that GMT can effect change that enhances the activity of the heart and that the VEGF gene is effective in improving heart function even more," said Dr. Crystal.

The idea started with the notion of induced pluripotent stem cells – reprograming mature specialized
cells into stem cells that are immature and can differentiate into different specific cells needed in the body. Dr. Shinya Yamanaka and Sir John B. Gurdon received the Nobel Prize in Medicine and Physiology for their work toward this goal this year.

However, use of induced pluripotent stem cells has the potential to cause tumors. To get around that, researchers in Dallas and San Francisco used the GMT cocktail to reprogram the scar cells into cardiomyocytes (cells that become heart muscle) in the living animals.

Now Rosengart and his colleagues have gone a step farther – encouraging the production of new blood
vessels to provide circulation to the new cells.

###

Others who took part in this work include Megumi Mathison, Ronald Gersch, Ahmed Nasser, Sarit Lilo,
Mallory Korman, Mitchell Fourman, Kenneth Shroyer, Jianchang Yang, Yupo Ma, all
of Stony Brook University Medical
Center and Neil Hackett of Weill Cornell
Medical College.

Funding for this work came from the generosity of James and Lisa Cohen.

Weill Cornell
Medical College

Weill Cornell
Medical College,
Cornell University's
medical school located in New York
  City, is committed to excellence in research,
teaching, patient care and the advancement of the art and science of medicine,
locally, nationally and globally. Physicians and scientists of Weill Cornell
Medical College
are engaged in cutting-edge research from bench to bedside, aimed at unlocking
mysteries of the human body in health and sickness and toward developing new
treatments and prevention strategies. In its commitment to global health and
education, Weill Cornell has a strong presence in places such as Qatar, Tanzania,
Haiti, Brazil, Austria and Turkey.
Through the historic Weill Cornell Medical
College in Qatar,
the Medical College
is the first in the U.S.
to offer its M.D. degree overseas. Weill Cornell is the birthplace of many
medical advances -- including the development of the Pap test for cervical
cancer, the synthesis of penicillin, the first successful embryo-biopsy
pregnancy and birth in the U.S., the first clinical trial of gene therapy for
Parkinson's disease, and most recently, the world's first successful use of
deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell
Medical College
is affiliated with NewYork-Presbyterian
Hospital, where its
faculty provides comprehensive patient care at NewYork-Presbyterian
Hospital/Weill Cornell Medical Center. The Medical
College is also affiliated with the Methodist Hospital
in Houston. For
more information, visit weill.cornell.edu.

Contact:
Lauren Woods

Law2014@med.cornell.edu

646-317-7401

Weill Cornell
Medical College

New findings in the search for genetic clues to insulin production

		IMAGE:This is Karen Mohlke, Ph.D., one of the study’s senior authors and associate professor of genetics at the University of North Carolina School of Medicine. Click here for more information.

(Embargoed) CHAPEL HILL, N.C. – In research published online Dec. 23, 2012 in the journal Nature Genetics, scientists have found three new and relatively rare genetic variants that influence insulin production, offering new clues about the genetic factors behind diabetes..

"Studying genetic variants — even rare ones — helps us learn how genes affect health and disease," said Karen Mohlke, PhD, one of the study's senior authors and associate professor of genetics at the University of North Carolina School of Medicine.  "In this study, we've implicated new genes as playing a role in insulin processing and secretion."

The study is also the first time genetic insights have been reported using exome array genotyping, a new tool that is less costly than genetic sequencing. This analysis allows scientists to quickly screen DNA samples for known variants in specific genes. It is especially helpful for testing variants that are rare.

"The exome array allowed us to test a large number of individuals — in this case, more than 8,000 people — very efficiently," said Mohlke. "We expect that this type of analysis will be useful for finding low-frequency variants associated with many complex traits, including obesity or cancer."

The scientists pulled data from a large health study directed by researchers at the University of Eastern Finland. A research team including postdoctoral scientist Jeroen Huyghe at the University of Michigan, Ann Arbor led the statistical analysis, which integrated genetic data and detailed health records for a sample of 8,229 Finnish males.

Diabetes, which affects more than 25 million people in the United States, results from problems with the body's ability to produce or use insulin. Rather than pinpointing one gene behind the disease, scientists believe there are a whole host of genes that interact with health and lifestyle factors to influence a person's chances of getting the disease.

The study revealed that certain variants of three genes — called TBC1D30, KANK1 and PAM — are associated with abnormal insulin production or processing, even in people without diabetes. The genes may predispose such individuals to developing the disease.

As a next step, the researchers plan to continue to investigate how these genes may lead to diabetes. They also expect the results will inspire other scientists to use exome analysis to look at the genetic factors behind other complex diseases.

###

In addition to Mohlke, the study's co-Principal Investigators included Michael Boehnke, PhD, of the University of Michigan, Ann Arbor and Markku Laakso, MD, of the University of Eastern Finland and Kuopio University Hospital. 

In the U.S., funding for the research came from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Human Genome Research Institute (NHGRI), components of the National Institutes of Health.

Enzyme accelerates malignant stem cell cloning in chronic myeloid leukemia

		IMAGE:This shows chronic myeloid leukemia blood cells.Click here for more information.

An international team, headed by researchers at the University of California, San Diego School of Medicine, has identified a key enzyme in the reprogramming process that promotes malignant stem cell cloning and the growth of chronic myeloid leukemia (CML), a cancer of the blood and marrow that experts say is increasing in prevalence.

The findings are published in the Dec. 24 online early edition of the Proceedings of the National Academy of Sciences (PNAS).

Despite the emergence of new therapies, such as tyrosine kinase inhibitors, CML and other leukemias remain problematic because some cancer stem cells avoid destruction and eventually regenerate themselves, a stem cell process known as self-renewal that can result in a return and spread (metastasis) of the disease.

In the PNAS paper, principal investigator Catriona H. M. Jamieson, MD, PhD, associate professor of medicine at UC San Diego, with colleagues in the United States, Canada and Italy, report that inflammation – long associated with the development of cancer – boosts activity of  an enzyme called adenosine deaminase or ADAR1.

Expressed during embryogenesis to help blood cell development, ADAR1 subsequently turns off and is triggered by viral infections where it protects normal hematopoietic stem cells from attack. In leukemia stem cells, however, overexpression of ADAR1 enhances the missplicing of RNA, which leads to greater self-renewal and therapeutic resistance of malignant stem cells.

The findings build upon previous studies by Jamieson and others that elucidate the effects of RNA missplicing and instability. "People normally think about DNA instability in cancer, but in this case, it's how the RNA is edited by enzymes that really matters in terms of cancer stem cell generation and resistance to conventional therapy."

The described RNA editing process, which occurs in the context of human and other primate specific sequences, also underscores the importance of addressing inflammation as "an essential driver of cancer relapse and therapeutic resistance," Jamieson said. It also presents a new target for future therapies.

"ADAR1 is an enzyme that we may be able to specifically target with a small molecule inhibitor, an approach we have already used effectively with other inhibitors," said Jamieson. "If we can block the capacity of leukemia stem cells to use ADAR1, if we can knock down that pathway, maybe we can put stem cells back on the right track and stop malignant cloning."

CML is a cancer initiated by a mutant gene called BCR-ABL in blood forming stem cells that leads to an expansion of white blood cells and their precursors. It is typically slow-growing and often not diagnosed until its later stages when there can be a sudden, dramatic increase in malignant cells, known as blast crisis. Median age of diagnosis is 66 years; incidence of the disease increases with age.  Despite tremendous advances in BCR-ABL tyrosine kinase inhibitor therapies, the majority of patients relapse if therapy is discontinued, in part as a result of dormant cancer stem cell resistance.  This work suggests a novel mechanism for overcoming cancer stem cell resistance to therapy that may prevent relapse and progression.

The estimated prevalence of CML in the United States is 70,000 persons with the disease, projected to steadily increase to approximately 181,000 by 2050. CML is initiated by the mutant BCR-ABL gene, but scientists have not yet identified the cause of the mutation.

 

###

Co-authors are Qingfei Jiang, Leslie A. Crews, Angela C. Court, David J. Goff, Anil Sadarangani and Sheldon R. Morris, Stem Cell Program, UCSD Department of Medicine and UCSD Moores Cancer Center; Christian L. Barrett, UCSD Division of Genome Information Sciences, Departments of Pediatrics; Hye-Jung Chun, Michael Smith Genome Sciences Centre, Vancouver; Jane M. Isquith, Stem Cell Program, UCSD Department of Medicine, UCSD Moores Cancer Center and Department of Animal Science, California Polytechnic State University; Maria A. Zipeto, UCSD Department of Medicine, UCSD Moores Cancer Center and Department of Experimental Medicine, University of Milano-Biocca, Italy; Mark Minden, Princess Margaret Hospital, Toronto, Canada; Jessica M. Rusert and Lawrence S.B. Goldstein, UCSD Department of Cellular and Molecular Medicine and Howard Hughes Medical Institute; Kim-Hien T. Dao, Oregon Health and Science University Knight Cancer Institute; Marco A. Marra, Michael Smith Genome Sciences Centre, Vancouver; and Kelly A. Frazer, UCSD Division of Genome Information Sciences, Departments of Pediatrics.

Funding for this research came, in part, from California Institute for Regenerative Medicine grants RN2-00910-1 and DR1-01430, CIRM training grant TG2-01154, CIRM SEED grant RS1-00228-1, the Government of Canada through Genome Canada and the Ontario Genomics Institute and the Canadian Institute of Health Research and the Ratner family foundation.

 

Gout study offers genetic insight into 'disease of kings' in Genetics

Gout study offers genetic insight into 'disease of kings'
December 23, 2012 in Genetics

Scientists have shed light on why some people are more
susceptible to gout than others. A study has identified 18 new genetic
variations that increase levels of uric acid in the blood, which is the main
cause of the disease. High levels of uric acid form small crystals in joints
and tissues, causing pain and swelling – the main symptoms of the condition
once known as the 'disease of kings'.

Gout is the most common form of inflammatory arthritis,
affecting up to two per cent of the world's population. Understanding how these
common genetic variants increase uric acid levels in the blood may lead to
improvements in the treatment and prevention of the disease. It could also help
research into urate-lowering drugs. The international team of researchers,
including scientists from the University
of Edinburgh and Queen Mary, University of London, say gout is becoming more common
in the developed world. They attribute its rise in part to increasing levels of
obesity and an aging population. This painful joint inflammation affects at
least one in seventy adults in the UK with approximately 900,000
people suffering at least one attack of gout in their lifetime. The work,
published in Nature Genetics, was carried out by analysing the genetic data of
more than 140,000 people, from more than 70 individual studies from Europe, the
U.S., Japan and Australia and represents the
largest study worldwide on this topic. Dr Veronique Vitart, from the Medical
Research Council Human Genetics Unit at the University of Edinburgh,
and one of the lead authors of the study said: "Abnormal levels of uric
acid have been associated with various common diseases and conditions, but
causal relationships are not always clear. Gaining insight into the genetic
components of uric acid levels offers a very useful tool to tackle these issues
and to further our understanding of these conditions." Professor Mark
Caulfield, from the William Harvey Research Institute at Queen Mary, and a lead
author said: "Existing therapies to avoid attacks of gout sometimes cause
side effects. Our findings identify new potential mechanisms for gout and offer
opportunities for new therapies which may improve prevention of this debilitating
condition in the future. Journal reference: Nature Genetics Provided by University of Edinburgh 



Read more at: http://medicalxpress.com/news/2012-12-gout-genetic-insight-disease-kings.html#jCp

Small, Portable Sensors Allow Users to Monitor Exposure to Pollution on Their Smart Phones

  

The CitiSense sensors transmit their air quality readings to smart phones. More pictures of the sensor and its smart phone interface can be found here.

San Diego, Calif., Dec. 18, 2012 -- Computer scientists at the University of California, San Diego have built a small fleet of portable pollution sensors that allow users to monitor air quality in real time on their smart phones. The sensors could be particularly useful to people suffering from chronic conditions, such as asthma, who need to avoid exposure to pollutants.

CitiSense is the only air-quality monitoring system capable of delivering real-time data to users’ cell phones and home computers—at any time. Data from the sensors can also be used to estimate air quality throughout the area where the devices are deployed, providing information to everyone—not just those carrying sensors. 

Just 100 of the sensors deployed in a fairly large area could generate a wealth of data—well beyond what a small number of EPA-mandated air-quality monitoring stations can provide. For example, San Diego County has 3.1 million residents, 4,000 square miles—and only about 10 stations.

“We want to get more data and better data, which we can provide to the public,” said William Griswold, a computer science professor at the Jacobs School of Engineering at UC San Diego and the lead investigator on the project. “We are making the invisible visible.”

The CitiSense sensors detect ozone, nitrogen dioxide and carbon monoxide, the most common pollutants emitted by cars and trucks. The user interface displays the sensor’s readings on a smart phone by using a color-coded scale for air quality based on the EPA’s air quality ratings, from green (good) to purple (hazardous).

Researchers provided the sensors for four weeks to a total of 30 users, including commuters at UC San Diego and faculty, students and staff members in the computer science department at the Jacobs School of Engineering. Computer scientists presented findings from these field tests at the Wireless Health 2012 conference in San Diego earlier this year.

User experiences

A view of the inside of the CitiSense sensor: the three cylindrical components detect ozone, nitrogen dioxide and carbon monoxide.

The sensors turned out to be great educational tools for their users. Many people assume that pollution diffuses equally in the air. But that’s not true. It actually remains concentrated in hot spots, along main roads, at intersections and so on. The sensors made this clear for users. Wendy Chapman, an associate professor at the UC San Diego School of Medicine, was one of them. She often bikes to work and discovered that pollution on her route varies widely. She was exposed to the most pollution when she used the bike path along State Route 56. But when she drove home on that same road, she had virtually no exposure.

“The people who are doing the most to reduce emissions, by biking or taking the bus, were the people who experienced the highest levels of exposure to pollutants,” said Griswold. 

Users discovered that pollution varied not only based on location, but also on the time of the day. When Charles Elkan, a professor in the Department of Computer Science and Engineering, drove into work in mid-morning, the readings on his sensor were low. But when he drove back home in rush hour in the afternoon, readings were sometimes very high. Elkan said being part of the study allowed him to gauge how worried about pollution he should actually be. Air quality in San Diego is fairly good, he added. 

“It’s a valuable study,” Elkan said. “I think it’s going to have a big impact in the future.”

Elkan added that he could envision a day in the near future when the sensors used by CitiSense would be built into smart phones, allowing virtually everyone to keep tabs on the levels of pollution they encounter every day. Of course, that means people might start worrying more about pollution as something they can see and measure.

Many of the users in the study did take action to limit their most severe exposure to pollutants. For example, bicyclists found out that they could avoid a great deal of exposure by simply biking one block away from a busy street. Commuters who took the bus avoided waiting near the vehicle’s tail pipe, where the air quality was poor.  One user convinced his supervisor to install new air filters in the office after registering poor air quality readings on his sensor.

Researchers also noticed that the users were sharing the information they collected, not only with family, friends and colleagues but also with strangers who asked them about the sensors during their commute or in public places. In other words, the sensors turned cell phones into a conversation starter, rather than devices that isolate their users from those around them.

The future of the project

The CitiSense sensor worn on a backpack.

SWhat’s next? Some of the sensors are currently on loan to researchers at San Diego State University who are gauging air quality in San Ysidro, a community right on the border between the United States and Mexico, and one of the most polluted areas in San Diego County.  Researchers hope to secure a grant from the National Institutes of Health to monitor air quality for school-age asthmatic children in that area and to determine what can be done to limit their exposure to pollutants.

 

The ultimate goal of CitiSense is to build and deploy a wireless network in which hundreds of small environmental sensors carried by the public rely on cell phones to shuttle information to central computers where it will be analyzed, anonymized and delivered to individuals, public health agencies and the community at large. The sensors currently cost $1,000 per unit, but could easily be mass-produced at an affordable price. So far, Griswold’s team has built and deployed 20 of them in the field.

Technical challenges

CitiSense would not be possible without the expertise of computer science faculty members and graduate students at the Jacobs School of Engineering. In addition to principal investigator Griswold, the team includes School of Medicine and Calit2 professor Kevin Patrick; computer science professors Ingolf Krueger, Tajana Simunic Rosing, Hovav Shacham and Sanjoy Dasgupta; as well as graduate students and postdoctoral researchers Piero Zappi, Nima Nikzad, Elizabeth Bales, Celal Ziftci, Nichole Quick and Nakul Verma.

A key factor in the project’s success was a breakthrough made by a group led by Dasgupta. Computer scientists used an artificial intelligence method, called Latent Variable Gaussian Regression, to capture high-quality data from the sensors in an uncontrolled environment. The method allowed researchers to remove noise from the data. “Sensors will differ. Sensors will fail,” Griswold explained. “People will breathe on them. We wanted to make sure we got good data in these conditions.”

Technical challenges remain. The data exchanges between smart phones and sensors use up a great deal of the phones’ batteries. During field tests, researchers provided users with two chargers—one for home and one for work—to ensure that their phones were not going to run out of power.

To extend battery life, researchers are experimenting with uploading data from the sensors to the phones every 15 minutes or only when the user wants to retrieve the information. Computer scientists also have developed methods to turn off a phone’s GPS—a huge drain of the devices’ batteries—when the device is immobile.

These innovations to extend battery life were made possible by Krueger’s previous work in service-oriented architecture, which can keep various components—like machine learning, power management and security code—much more separate than in traditional software systems, where functional elements are often so woven into the source code that it is difficult to quickly update any one aspect of the software.

CitiSense is funded by a $1.5 million grant from the National Science Foundation. Qualcomm, Inc. donated funds for the cell phones used for the project

Do palm trees hold the key to immortality?

 

Recent review reveals unique cellular structure and function that may contribute to their long life-span

		IMAGE:Detail of a single vascular bundle from a transverse section of the mature stem, embedded in celloidin and stained with safranin and fast green. It shows the result of sustained... Click here for more information.

For centuries, humans have been exploring, researching, and, in some cases, discovering how to stave off life-threatening diseases, increase life spans, and obtain immortality.  Biologists, doctors, spiritual gurus, and even explorers have pursued these quests—one of the most well-known examples being the legendary search by Ponce de León for the "Fountain of Youth." Yet the key to longevity may not lie in a miraculous essence of water, but rather in the structure and function of cells within a plant—and not a special, mysterious, rare plant, but one that we may think of as being quite commonplace, even ordinary: the palm.  

As an honors botany student at the University of Leeds, P. Barry Tomlinson wrote a prize-winning essay during his final year titled, "The Span of Life."  Fifty years later, Tomlinson (now a Distinguished Professor at The Kampong Garden of the National Tropical Botanical Garden, Miami, FL) teamed up with graduate student Brett Huggett (Harvard University, MA) to write a review paper exploring the idea that palms may be the longest-lived tree, and whether this might be due to genetic underpinnings.  Having retained his essay in his personal files, Tomlinson found that it provided an excellent literature background for working on the question of cell longevity in relation to palms.  Together, Tomlinson and Huggett published their review in the December issue of the American Journal of Botany (http://www.amjbot.org/content/99/12/1891.full.pdf+html).

A component of an organism's life span that biologists have been particularly interested in is whether longevity is genetically determined and adaptive. For botanists, discovering genetic links to increasing crop production and the reproductive lifespan of plants, especially long-lived ones such as trees, would be invaluable. 

In their paper, Tomlinson and Huggett emphasize that in many respects, an organisms' life span, or longevity, is determined by the period of time in which its cells remain functionally metabolically active.  In this respect, plants and animals differ drastically, and it has to do with how they are organized—plants are able to continually develop new organs and tissues, whereas animals have a fixed body plan and are not able to regenerate senescing organs.  Thus, plants can potentially live longer than animals.

"The difference in potential cell longevity in plants versus animals is a significant point," states Tomlinson. "It is important to recognize that plants, which are so often neglected in modern biological research, can be informative of basic cell biological features in a way that impacts human concern at a fundamental level."

The authors focused their review on palm trees because palms have living cells that may be sustained throughout an individual palm's lifetime, and thus, they argue, may have some of the longest living cells in an organism.  As a comparison, in most long-lived trees, or lignophytes, the main part, or trunk, of the tree is almost entirely composed of dead, woody, xylem tissues, and in a sense is essentially a supportive skeleton of the tree with only an inner ring of actively dividing cells.  For example, the skeleton of Pinus longaeva may be up to 3000 years old, but the active living tissues can only live less than a century.

In contrast, the trunks of palms consist of cells that individually live for a long time, indeed for the entire life of an individual.

Which brings up the question of just how long can a palm tree live? The authors point out that palm age is difficult to determine, primarily because palms do not have secondary growth and therefore do not put down annual or seasonal growth rings that can easily be measured.  However, age can be quite accurately assessed based on rate of leaf production and/or visible scars on the trunk from fallen leaves.  Accordingly, the authors found that several species of palm have been estimated to live as long as 100 and even up to 740 years.  The important connection here is that while the "skeleton" of the palm may not be as old as a pine, the individual cells in its trunk lived, or were metabolically active, as long as, or longer than those of the pine's. 

Most plants, in addition to increasing in height as they age, also increase in girth, putting down secondary vascular tissue in layers both on the inner and outer sides of the cambium as they grow.  However, palms do not have secondary growth, and there is no addition of secondary vascular tissue.  Instead, stem tissues are laid down in a series of interconnected vascular bundles—thus, not only is the base of the palm the oldest and the top the youngest, but these tissues from old to young, from base to top, must also remain active in order to provide support and transport water and nutrients throughout the tree. 

		IMAGE:This shows Sabal causiarum, native to Puerto Rico, planted in 1932 at the Montgomery Botanical Center, Coral Gables Florida and in the prime of its long life (estimated height, 20... Click here for more information.

Indeed, the authors illustrate this by reviewing evidence of sustained primary growth in two types of palms, the coconut and the sago palm. These species represent the spectrum in tissue organization from one where cells are relatively uniform and provide both hydraulic and mechanical functions (the coconut) to one where these functions are sharply divided with the inner cells functioning mainly for transporting water and nutrients and the outer ones for mechanical support (the sago palm).  This represents a progression in specialization of the vascular tissues.

Moreover, there is evidence of continued metabolic activity in several types of tissues present in the stems of palms, including vascular tissue, fibers, ground tissue, and starch storage.  Since the vascular tissues in palms are nonrenewable, they must function indefinitely, and Tomlinson and Huggett point out that sieve tubes and their companion cells are remarkable examples of cell longevity as they maintain a long-distance transport function without replacement throughout the life of the stem, which could be for centuries.

Despite several unique characteristics of palms, including the ability to sustain metabolically active cells in the absence of secondary tissues, seemingly indefinitely, unlike conventional trees, in which metabolically active cells are relatively short-lived, the authors do not conclude that the extended life span of palms is genetically determined.

"We are not saying that palms have the secret of eternal youth, and indeed claim no special chemical features which allows cells in certain organisms to retain fully differentiated cells with an indefinite lifespan," states Tomlinson. "Rather, we emphasize the distinctive developmental features of palm stems compared with those in conventional trees."

Tomlinson indicates that this reflects the neglect of the teaching of palm structure in modern biology courses. "This paper raises incompletely understood aspects of the structure and development of palms, emphasizing great diversity in these features," he concludes. "This approach needs elaborating in much greater detail, difficult though the subject is in terms of conventional approaches to plant anatomy."

###

Tomlinson, P. Barry and Brett A. Huggett. 2012. Cell longevity and sustained primary growth in palm stems. American Journal of Botany 99(12): 1891-1902. DOI: 10.3732/ajb.1200089

The full article in the link mentioned is available for no charge for 30 days following the date of this summary at http://www.amjbot.org/content/99/12/1891.full.pdf+html. After this date, reporters may contact Richard Hund at ajb@botany.org for a copy of the article.

The Botanical Society of America (www.botany.org) is a non-profit membership society with a mission to promote botany, the field of basic science dealing with the study and inquiry into the form, function, development, diversity, reproduction, evolution, and uses of plants and their interactions within the biosphere. It has published the American Journal of Botany (www.amjbot.org) for nearly 100 years. In 2009, the Special Libraries Association named the American Journal of Botany one of the Top 10 Most Influential Journals of the Century in the field of Biology and Medicine.

For further information, please contact the AJB staff at ajb@botany.org.

Finding the next leader or For power and status, dominance and skill trump likability

Finding the next Barack Obama or Warren Buffett might be as simple as looking at who attracts the most eyes in a crowd, a new University of British Columbia study finds.

For the study, which used eye-tracking technology, participants who observed groups of strangers were able to accurately predict who would emerge as leader of the group in 120 seconds or less.

According to the study – to appear in the forthcoming Journal of Personality and Social Psychology – two sets of behaviours will accurately predict future leadership and catch people's attention. The first is prestige – the appearance of skill and competency. The second is dominance, which includes the ability to impose ideas on others through bullying and intimidation.

"Our findings suggest there are really two ways to top the social ladder and gain leadership – impressing people with your skills or powering your way through old-fashioned dominance," says lead author Joey Cheng, a PhD candidate in UBC's Dept. of Psychology. "By measuring levels of influence and visual attention, we find that people defer to and readily spot the prestigious and dominant leaders."

Surprisingly, the study finds that one's likeability – long considered essential for modern leaders – does not consistently predict the attainment of greater status. While participants preferred leaders with prestige, they were surprisingly likely to choose dominant leaders. They were also more forgiving of dominant behaviour than outside observers, the researchers say.

The findings might explain the ongoing prevalence of aggressive leaders in business and politics, such as Donald Trump or Toronto mayor Rob Ford. According to the researchers, today's dominant behaviour has evolved from resource and power battles from our evolutionary past. Prestige's viability as means of attaining status, has increased with the rise of meritocracy in society.

Backgrounder

The study had two parts. First, 200 participants completed a problem-solving task in small groups while being videotaped. Group members rated participants' dominance, prestige and influence during the task, including their own. Participants who were more dominant or prestigious had a greater influence on the task and were perceived as more influential by group members.

In the second part of the study, 60 additional participants watched a total of 120 seconds of short videos of the initial group interactions while wearing an eye-tracking device. These participants paid significantly greater attention to individuals in the clips who appeared more dominant or prestigious, indicating their higher levels of influence.

 

###

Study co-authors include Jessica Tracy, Alan Kingstone, Joseph Henrich (UBC psychology) and Tom Foulsham (formerly UBC, now University of Essex).

 

NTU study finds ways to prevent muscle loss, obesity and diabetes

		IMAGE:This shows Associate Professor Ravi Kambadur from Nanyang Technological University who discovered the myostatin link in muscle loss during extreme situations like starvation or chronic disease.Click here for more information.

A research study from Nanyang Technological University (NTU) has yielded important breakthroughs on how the body loses muscle, paving the way for new treatments for aging, obesity and diabetes.

The study found that by inhibiting a particular molecule produced naturally in the body, muscle loss due to aging or illnesses can be prevented. Blocking the same molecule will also trigger the body to go into a 'fat-burning mode' which will fight obesity and also treat the common form of diabetes.

The exciting discoveries have led NTU scientists to embark on joint clinical research with local hospitals to further validate their findings which were previously carried out on animals.

Their research on how humans lose muscle during extreme conditions such as chronic diseases or starvation was published last month in Cell Metabolism, a prestigious journal known for publishing biological breakthroughs.

Associate Professor Ravi Kambadur and his team from the NTU School of Biological Sciences found that a protein called Myostatin, which controls muscle cell growth, is responsible for initiating muscle loss.

When excess levels of Myostatin is bound to a muscle cell, it induces heavy loss of mitochondria (the part of the cell responsible for energy production that keeps a cell alive), which in turn causes the muscle cell to waste or lose muscle tissue (atrophy) due to the 'lack of energy'.

		IMAGE:This is Nanyang Technological University Associate Professor Ravi Kambadur who discovered the myostatin link in muscle loss during extreme situations like starvation and chronic diseasesClick here for more information.

Under normal healthy conditions, small loss of Mitochondria is needed for the regeneration of new cells, but when a patient is suffering from chronic diseases or is bedridden (and muscles are not used often), this process is disrupted due to high levels of myostatin which results in increased mitochondrial loss and muscle atrophy.

Prof Kambadur said recent studies have shown that extreme muscle wasting can lead to death.

"For example, about 30 per cent of cancer patients die not because of cancer, but because of muscle loss also known as cachexia," said Prof Kambadur.

"When someone is suffering from a chronic disease and doesn't eat enough, the body starts to generate energy by breaking down muscle proteins and that is the reason we see a lot of muscle wasting under chronic disease conditions."

"Over the years, our research has revealed that this type of muscle wasting is initiated by excess levels of myostatin in the body. If we block myostatin from binding to cells, then muscles won't waste away and we can then mitigate the effects of aging and chronic diseases."

Apart from regulating the growth and loss of muscle, myostatin also regulates whether the body will burn fat or carbohydrates during fasting and meal times.

Blocking myostatin keeps the body in "fat-burning mode" and promotes muscle growth at the same time - which could potentially make obesity a thing of the past.

Because obesity is one of the main causes of the most common form of diabetes, Type 2 diabetes, blocking myostatin could also treat diabetes. In the US, 90 to 95 per cent of diabetes cases are Type 2, as reported by the Centers for Disease Control and Prevention.

According to Singapore's Health Promotion Board, diabetes is among the top ten causes of death locally. In 2010, it was reported by Ministry of Health that 11.3 per cent of the Singaporean adults aged 18 to 69 years are affected by diabetes while 10.8 percent were obese.

"In near future, myostatin blockers could increase fat utilisation in the body and give you the benefits of exercise, without actually doing intense physical activity," Prof Kambadur explained.

"This would be a good alternative treatment for people who are unable to exercise, such as those who are bed-ridden or are in cancer treatment, who are most at risk of massive muscle loss."

Prof Kambadur added that while blocking myostatin sounds like a good idea, there is a need to study the long term effects, as the molecule is needed to regulate cell growth for normal body operation.

Other studies on myostatin conducted by Prof Kambadur's group have also yielded interesting results.

For instance, people who exercise regularly have been found to have lower levels of myostatin as compared to those who do not.  Studies have also found that older people have more myostatin and this can explain why when one ages, muscles become weaker.

Prof Kambadur's research projects on myostatin are funded by Ministry of Education, Biomedical Research Council and the National Research Foundation's (NRF) Competitive Research Programme (CRP). The research on myostatin is conducted in collaboration with Associate Professor Mridula Sharma from the National University of Singapore.  The husband-and-wife team have collaborated on various research projects in the area of skeletal muscle for many years.

###

Media contact:

 

Lester Kok
Assistant Manager
Corporate Communications Office
Nanyang Technological University
Tel: 6790 6804
Email: lesterkok@ntu.edu.sg

About Nanyang Technological University

A research-intensive public university, Nanyang Technological University (NTU) has 33,500 undergraduate and postgraduate students in the colleges of Engineering, Business, Science, and Humanities, Arts, & Social Sciences. In 2013, NTU will enrol the first batch of students at its new medical school, the Lee Kong Chian School of Medicine, which is set up jointly with Imperial College London.

NTU is also home to four world-class autonomous institutes – the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre on Environmental Life Sciences Engineering – and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI), Energy Research Institute @ NTU (ERI@N) and Institute on Asian Consumer Insight (ACI).

A fast-growing university with an international outlook, NTU is putting its global stamp on Five Peaks of Excellence: Sustainable Earth, Future Healthcare, New Media, New Silk Road, and Innovation Asia.

Besides the main Yunnan Garden campus, NTU also has a satellite campus in Singapore's science and tech hub, one-north and is setting up a third campus in Novena, Singapore's medical district. For more information, visit www.ntu.edu.sg

 

Assessing the effects of cell phone radiation on brain tissue

Assessing the effects of cell phone radiation on brain tissue
December 17, 2012 by Sunanda Creagh in Medical research

 

Researchers have found a novel, non-invasive technique for measuring brain hot spots caused by electromagnetic radiation from mobile phones, according to a study published today.

However, the scientists noted their model measured a "worst case scenario" level of heat and that in reality, the body's natural self-cooling mechanisms would reduce the amount of heat rise in the
brain caused by a mobile phone. The World Health Organisation's cancer agency,
the International Agency for Research on Cancer (IARC), classed mobile phones
as Group 2B or "possibly carcinogenic" in a report released last
year. That puts them in the same IARC category as coffee, napthalene and
pickled vegetables. To test how much electromagnetic energy from cell phone
radiation was absorbed into a brain, US researchers David H. Gultekin and
Lothar Moeller used nuclear magnetic resonance (NMR) techniques on a brain that
had been removed from a cow. The scientists rigged up an antenna system to help
create 3D images of the hot spots without allowing the strong magnetic fields
of the NMR to interfere with the results. The results were checked against heat
measurements taken with fibre optic temperature sensors and showed that the NMR
method delivered accurate findings. The researchers concluded that "NMR
thermometry offers sufficient spatial and temporal resolution to characterise
the hot spots from absorbed cell phone radiation in… biological tissues."
However, the researchers said that a biological process called perfusion—in
which blood is directed to overheated body parts to help cool them down—would
mean that the amount of heat rise caused by a mobile phone in a living brain would
be less in real life than what was studied in this experiment. Ads by Google
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www.SinoBiological.com "This study essentially presents the worst case
scenario in terms of radiation-heated brain tissue. The temperature rise in the
in vivo brain tissue is expected to be smaller because of perfusion," the
study said. The study was published in the journal Proceedings of the National
Academy of Sciences. Their technique was an improvement on existing methods to
test for hot spots, which currently involve inserting a probe into a gel
designed to mimic the way a brain would conduct heat. "They are invasive
and they can not measure the thermal fields in ex-vivo or in-vivo tissues. NMR
method is non-invasive and can measure the thermal fields in ex-vivo and
in-vivo including the perfusion effects," said one of the scientists who
conducted the research, Dr David Gultekin from the Memorial Sloan-Kettering
Cancer Centre in New York.
Another author of the paper, Dr Lothar Moeller of Bell Labs, said "our
method has the advantages that it can be applied to measure remotely temperature
enhancement caused by cell phone radiation inside in-vivo brain. No other
existing method can do this." Professor Rodney Croft, Professor of Health
Physiology at the University
of Wollongong and a
researcher of mobile phone radiation said the research was interesting
proof-of-concept study but "I don't think it has much relevance to the
mobile phone debate." "What they are talking about at the moment is a
non-realistic model using biological material without thermoregulation,"
meaning natural mechanisms that help cool down overheated body parts, said Dr
Croft. "We can be exposed to quite a lot of changes in temperature and our
body can deal with it. If we get mobile phone exposure, because it's such a
small amount of heat, the thermoregulation can deal with that without any
difficulty." Dr Croft said there still was no research suggesting major
health problems caused by mobile phone use. "It really doesn't represent
much of a risk. We are talking about a conclusion that it remains a possibility
[that they may cause cancer] but there is no evidence it is a problem."
More information: "NMR imaging of cell phone radiation absorption in brain
tissue," by David H. Gultekin and Lothar Moeller: www.pnas.org/conte…
0/1205598109 Journal reference: Proceedings of the National Academy of Sciences
Provided by The Conversation This story is published courtesy of the The
Conversation (under Creative Commons-Attribution/No derivatives)



Read more at: http://medicalxpress.com/news/2012-12-effects-cell-brain-tissue.html#jCp

How to get fossil fuels from ice cream and soap

December 17, 2012 Scientists at the University of Manchester
have identified a biocatalyst which could produce chemicals found in ice-cream
and household items such as soap and shampoo – possibly leading to the
long-term replacement of chemicals derived from fossil fuels.

Writing in PNAS, the researchers have shown that the emerging
field of synthetic biology can be used to manipulate hydrocarbon chemicals,
found in soaps and shampoos, in cells. This development, discovered with
colleagues at the University of Turku in Finland, could mean fuel for cars
or household power supplies could be created from naturally-occurring fatty
acids. The researchers, led by Professor Nick Turner from The University of
Manchester, used synthetic biology to hijack the naturally-existing fatty acids
and direct those fatty molecules towards the production of ready-to-use fuel
and household chemicals. Hydrocarbon chemicals are everywhere in our daily
lives; as fragrance in soap, thickener in shampoo and fuel in the car. Their
number of carbons and whether they are acid, aldehyde, alcohol or alkane are
important parameters that influence how toxic they are to biological organisms,
the potential for fuel and their olfactory perception as aroma compounds. The
breakthrough allows researchers to further explore how to create renewable
energy from sustainable sources, and the advance could lead to more innovative
ways of sourcing fuel from natural resources. Synthetic biology is an area of
biological research and technology that combines science and engineering for
the benefit of society. Significant advances have been made in this field in
recent years. Professor Turner said: "In our laboratories in Manchester we currently
work with many different biocatalysts that catalyse a range of chemical
reactions – the key is to match up the correct biocatalyst with the specific
product you are trying to make. "Biocatalysts recognise molecules in the
way that a lock recognises a key – they have to fit perfectly together to work.
Sometime we redesign the lock so that if can accept a slightly different key
allowing us to make even more interesting products. "In this example we
need to make sure that the fatty acid starting materials would be a perfect
match for the biocatalysts that we discovered and developed in our
laboratories. "As with many leading areas of science today, in order to
make major breakthroughs it is necessary for two or more laboratories around
the world to come together to solve challenging problems." More
information: Carboxylic acid reductase is a versatile enzyme for the conversion
of fatty acids into fuels and chemical commodities, by M. Kalim Akhtar,
Nicholas J. Turner, and Patrik R. Jones, PNAS, 2012. Journal reference:
Proceedings of the National Academy of Sciences Provided by University of Manchester 



Read more at: http://phys.org/news/2012-12-fossil-fuels-ice-cream-soap.html#jCp

New nano technology may enable earlier cancer diagnosis

Nanoparticles amplify tumor signals, making them much easier to detect in the urine.

Anne Trafton, MIT News Office

December 14, 2012

                                                                                                                                                           These nanoparticles created by MIT engineers can act as synthetic biomarkers for disease. The particles (brown) are coated with peptides (blue) that are cleaved by enzymes (green) found at the disease site. The peptides then accumulate in the urine, where they can be detected using mass spectrometry.                                                                           
Image: Justin H. Lo

December 16, 2012

Finding ways to diagnose cancer earlier could greatly improve the chances of survival for many patients. One way to do this is to look for specific proteins secreted by cancer cells, which circulate in the bloodstream. However, the quantity of these biomarkers is so low that detecting them has proven difficult.

A new technology developed at MIT may help to make biomarker detection much easier. The researchers, led by Sangeeta Bhatia, have developed nanoparticles that can home to a tumor and interact with cancer proteins to produce thousands of biomarkers, which can then be easily detected in the patient’s urine.

This biomarker amplification system could also be used to monitor disease progression and track how tumors respond to treatment, says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT.

“There’s a desperate search for biomarkers, for early detection or disease prognosis, or looking at how the body responds to therapy,” says Bhatia, who is also a member of MIT’s David H. Koch Institute for Integrative Cancer Research. She adds that the search has been complicated because genomic studies have revealed that many cancers, such as breast cancer, are actually groups of several diseases with different genetic signatures.

The MIT team, working with researchers from Beth Israel Deaconess Medical Center, described the new technology in a paper appearing in Nature Biotechnology on Dec. 16. Lead author of the paper is Gabriel Kwong, a postdoc in MIT’s Institute for Medical Engineering and Science and the Koch Institute.

Amplifying cancer signals

Cancer cells produce many proteins not found in healthy cells. However, these proteins are often so diluted in the bloodstream that they are nearly impossible to identify. A recent study from Stanford University researchers found that even using the best existing biomarkers for ovarian cancer, and the best technology to detect them, an ovarian tumor would not be found until eight to 10 years after it formed.

“The cell is making biomarkers, but it has limited production capacity,” Bhatia says. “That’s when we had this ‘aha’ moment: What if you could deliver something that could amplify that signal?”

Serendipitously, Bhatia’s lab was already working on nanoparticles that could be put to use detecting cancer biomarkers. Originally intended as imaging agents for tumors, the particles interact with enzymes known as proteases, which cleave proteins into smaller fragments.

Cancer cells often produce large quantities of proteases known as MMPs. These proteases help cancer cells escape their original locations and spread uncontrollably by cutting through proteins of the extracellular matrix, which normally holds cells in place.

The researchers coated their nanoparticles with peptides (short protein fragments) targeted by several of the MMP proteases. The treated nanoparticles accumulate at tumor sites, making their way through the leaky blood vessels that typically surround tumors. There, the proteases cleave hundreds of peptides from the nanoparticles, releasing them into the bloodstream.

The peptides rapidly accumulate in the kidneys and are excreted in the urine, where they can be detected using mass spectrometry.

This new system is an exciting approach to overcoming the problem of biomarker scarcity in the body, says Sanjiv Gambhir, chairman of the Department of Radiology at Stanford University School of Medicine. “Instead of being dependent on the body to naturally shed biomarkers, you’re sampling the site of interest and causing biomarkers that you engineered to be released,” says Gambhir, who was not part of the research team.

Distinctive signatures

To make the biomarker readings as precise as possible, the researchers designed their particles to express 10 different peptides, each of which is cleaved by a different one of the dozens of MMP proteases. Each of these peptides is a different size, making it possible to distinguish them with mass spectrometry. This should allow researchers to identify distinct signatures associated with different types of tumors.

In this study, the researchers tested their nanoparticles’ ability to detect the early stages of colorectal cancer in mice, and to monitor the progression of liver fibrosis.

Liver fibrosis is an accumulation of scarring in response to liver injury or chronic liver disease. Patients with this condition have to be regularly monitored by biopsy, which is expensive and invasive, to make sure they are getting the right treatment. In mice, the researchers found that the nanoparticles could offer much more rapid feedback than biopsies.

They also found that the nanoparticles could accurately reveal the early formation of colorectal tumors. In ongoing studies, the team is studying the particles’ ability to measure tumor response to chemotherapy and to detect metastasis.

The research was funded by the National Institutes of Health and the Kathy and Curt Marble Cancer Research Fund.

Nanofibers clean sulfur from fuel

 

       

---

Nanofibers of metal oxide provide lots of highly reactive surface area for scrubbing sulfur compounds from fuel. Sulfur has to be removed because it emits toxic gasses and corrodes catalysts.

CHAMPAIGN, Ill. —     Sulfur compounds in petroleum fuels have met their nano-structured match.

University of Illinois researchers developed mats of metal oxide nanofibers that scrub sulfur from petroleum-based fuels much more effectively than traditional materials.  Such efficiency could lower costs and improve performance for fuel-based catalysis, advanced energy applications and toxic gas removal.

          Co-led by Mark Shannon, a professor of mechanical science and engineering at the U. of I. until his death this fall, and chemistry professor Prashant Jain, the researchers demonstrated their material in the journal Nature Nanotechnology.

          Sulfur compounds in fuels cause problems on two fronts: They release toxic gases during combustion, and they damage metals and catalysts in engines and fuel cells. They usually are removed using a liquid treatment that adsorbs the sulfur from the fuel, but the process is cumbersome and requires that the fuel be cooled and reheated, making the fuel less energy efficient.

          To solve these problems, researchers have turned to solid metal oxide adsorbents, but those have their own sets of challenges. While they work at high temperatures, eliminating the need to cool and re-heat the fuel, their performance is limited by stability issues. They lose their activity after only a few cycles of use.

          Previous studies found that sulfur adsorption works best at the surface of solid metal oxides, so graduate student Mayank Behl, from Jain’s group, and Junghoon Yeom, then a postdoctoral researcher in Shannon’s group, set out to create a material with maximum surface area. The solution: tiny grains of zinc titanate spun into nanofibers, uniting high surface area, high reactivity and structural integrity in a high-performance sulfur adsorbent.

          The nanofiber material is more reactive than the same material in bulk form, enabling complete sulfur removal with less material, allowing for a smaller reactor. The material stays stable and active after several cycles. Furthermore, the fibrous structure grants the material immunity from the problem of sintering, or clumping, that plagues other nano-structured catalysts.

“Our nanostructured fibers do not sinter,” Jain said. “The fibrous structure accommodates any thermophysical changes without resulting in any degradation of the material. In fact, under operating conditions, nanobranches grow from the parent fibers, enhancing the surface area during operation.”

Jain’s group will continue to investigate the enhanced properties of nanofiber structures, hoping to gain an atomic-level understanding of what makes the material so effective.

“We are interested in finding out the atomic sites on the surface of the material where the hydrogen sulfide adsorbs,” said Jain, who is also affiliated with the Beckman Institute for Advanced Science and Technology at the U. of I. “If we can know the identity of these sites, we could engineer an even more efficient adsorbent material. The atomic or nanoscale insight we gain from this material system could be useful to design other catalysts in renewable energy and toxic gas removal applications.”

This work was supported by the National Science Foundation, the department of chemistry and the Frederick Seitz Materials Research Laboratory at the U. of I.

      Editor's note: To contact Prashant Jain, call 217-333-3417; email jain@illinois.edu.
The paper, “A regenerable oxide-based H2S adsorbent with nanofibrous morphology,” is available online.

Using light to remotely trigger biochemical reactions

Light-Triggered Biocatalysis Using Thermophilic Enzyme–Gold Nanoparticle Complexes

Matthew D. Blankschien †‡, Lori A. Pretzer §, Ryan Huschka §, Naomi J. Halas ‡§#, Ramon Gonzalez †‡#*, and Michael S. Wong †‡§*

^†Department of Chemical and Biomolecular Engineering,^‡Richard E. Smalley Institute for Nanoscale Science and Technology, ^§Department of Chemistry, Department of Electrical and Computer Engineering, Department of Physics and Astronomy, ^#Department of Bioengineering,Laboratory for Nanophotonics and the Rice Quantum Institute, Department of Civil and Environmental Engineering, Rice University, 6100 Main Street, Houston, Texas 77005-1892, United States

ACS Nano, Article ASAP

DOI: 10.1021/nn3048445

Publication Date (Web): December 13, 2012

Copyright © 2012 American Chemical Society

*Address correspondence to ramon.gonzalez@rice.edu;mswong@rice.edu.

¶ Author Contributions

These authors contributed equally to this study.

Abstract

The use of plasmonic nanoparticle complexes for biomedical applications such as imaging, gene therapy, and cancer treatment is a rapidly emerging field expected to significantly improve conventional medical practices. In contrast, the use of these types of nanoparticles to noninvasively trigger biochemical pathways has been largely unexplored. Here we report the light-induced activation of the thermophilic enzyme Aeropyrum pernix glucokinase, a key enzyme for the decomposition of glucose via the glycolysis pathway, increasing its rate of reaction 60% with light by conjugating the enzyme onto Au nanorods. The observed increase in enzyme activity corresponded to a local temperature increase within a calcium alginate encapsulate of 20 °C when compared to the bulk medium maintained at standard, nonthermophilic temperatures. The encapsulated nanocomplexes were reusable and stable for several days, making them potentially useful in industrial applications. This approach could significantly improve how biochemical pathways are controlled for in vitro and, quite possibly, in vivo use.

Keywords: 

nanorod; thermophilic enzyme; alginate; 

Do-it-yourself viruses: How viruses self assemble

Do-it-yourself viruses: How viruses self assemble

		IMAGE:The capsid enveloping a virus is essential for protection and propagation of the viral genome. Many viruses have evolved a self-assembly method which is so successful that the viral capsid...Click here for more information.

A new model of the how the protein coat (capsid) of viruses assembles, published in BioMed Central's open access journal BMC Biophysics,  shows that the construction  of intermediate structures prior to final capsid production (hierarchical assembly) can be more efficient than constructing the capsid protein by protein (direct assembly). The capsid enveloping a virus is essential for protection and propagation of the viral genome. Many viruses have evolved a self-assembly method which is so successful that the viral capsid can self assemble even when removed from its host cell.

The construction of large protein structures has been observed experimentally but the mechanism behind this is not well understood. Even the 'simple' icosahedral protein coat of the T1 virus requires integration of 60 protein components. Computational models of the physical interactions of component proteins are used to investigate the dynamics and physical constraints that regulate whether the components assemble correctly.

Using computer simulations a team from the Institute for Theoretical Physics and the Center for Quantitative Biology (BioQuant), University of Heidelberg, has compared direct and hierarchical assembly methods for T1 and T3 viruses. The  team led by Ulrich S Schwarz, realised that direct assembly often led to the formation of unfavorable intermediates, especially when the dissociation rate was low, which hindered further assembly, causing the process to stall. In contrast, for many conditions hierarchical assembly was more reliable, especially if the bonds involved had a low dissociation rate.

Discussing the practical applications of these results, Dr Schwarz commented, "Hierarchical assembly has not been systematically investigated before. Theoretical models and computer simulations, like ours, can be used to understand the mechanism behind assembly of complex viruses and give an indication of how other large protein complexes assemble."

He continued, " With our computer simulations, we are now in a position to investigate systems which are too large to be studied by molecular resolution. This rational approach might have many applications not only in biomedicine, but also in materials science, where many researchers strive to learn from nature how to assembly complex structures."

 

###

Media Contact

Dr Hilary Glover
Scientific Press Officer, BioMed Central
Tel:  +44 (0) 20 3192 2370
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Email: hilary.glover@biomedcentral.com

Notes

1. Stochastic Dynamics of Virus Capsid Formation: Direct versus Hierarchical Self-Assembly Johanna E Baschek, Heinrich CR Klein and Ulrich S SchwarzBMC Biophysics (Section: Computational and theoretical biophysics) (in press)

Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BioMed Central's open access policy.

Article citation and URL available on request on the day of publication.

Please credit images to Johanna E Baschek, Heinrich CR Klein and Ulrich S Schwarz. More images and videos are available on request.

2. BMC Biophysics is an open access journal publishing original peer-reviewed research articles in experimental and theoretical aspects of biological processes from the microscopic to macroscopic level, including thermodynamics, structural stability and dynamics, molecular biophysics, signalling, novel biophysical methods and computational biophysics.

3. BioMed Central is an STM (Science, Technology and Medicine) publisher which has pioneered the open access publishing model. All peer-reviewed research articles published by BioMed Central are made immediately and freely accessible online, and are licensed to allow redistribution and reuse. BioMed Central is part of Springer Science+Business Media, a leading global publisher in the STM sector. @BioMedCentral

 

 

 

Toward a new model of the cell

Everything you always wanted to know about genes

		IMAGE:This image shows the hierarchical ontology of genes, cellular components and processes derived from large genomic datasets.Click here for more information.

Turning vast amounts of genomic data into meaningful information about the cell is the great challenge of bioinformatics, with major implications for human biology and medicine. Researchers at the University of California, San Diego School of Medicine and colleagues have proposed a new method that creates a computational model of the cell from large networks of gene and protein interactions, discovering how genes and proteins connect to form higher-level cellular machinery.

The findings are published in the December 16 advance online publication of Nature Biotechnology.

"Our method creates ontology, or a specification of all the major players in the cell and the relationships between them," said first author Janusz Dutkowski, PhD, postdoctoral researcher in the UC San Diego Department of Medicine. It uses knowledge about how genes and proteins interact with each other and automatically organizes this information to form a comprehensive catalog of gene functions, cellular components, and processes.

"What's new about our ontology is that it is created automatically from large datasets. In this way, we see not only what is already known, but also potentially new biological components and processes – the bases for new hypotheses," said Dutkowski.

Originally devised by philosophers attempting to explain the nature of existence, ontologies are now broadly used to encapsulate everything known about a subject in a hierarchy of terms and relationships. Intelligent information systems, such as iPhone's Siri, are built on ontologies to enable reasoning about the real world. Ontologies are also used by scientists to structure knowledge about subjects like taxonomy, anatomy and development, bioactive compounds, disease and clinical diagnosis.

A Gene Ontology (GO) exists as well, constructed over the last decade through a joint effort of hundreds of scientists. It is considered the gold standard for understanding cell structure and gene function, containing 34,765 terms and 64,635 hierarchical relations annotating genes from more than 80 species.

"GO is very influential in biology and bioinformatics, but it is also incomplete and hard to update based on new data," said senior author Trey Ideker, PhD, chief of the Division of Genetics in the School of Medicine and professor of bioengineering in UC San Diego's Jacobs School of Engineering.

"This is expert knowledge based upon the work of many people over many, many years," said Ideker, who is also principal investigator of the National Resource for Network Biology, based at UC San Diego. "A fundamental problem is consistency. People do things in different ways, and that impacts what findings are incorporated into GO and how they relate to other findings. The approach we have proposed is a more objective way to determine what's known and uncover what's new."

In their paper, Dutkowski, Ideker and colleagues capitalized upon the growing power and utility of new technologies like high-throughput assays and bioinformatics to create elaborately detailed datasets describing complex biological networks. To test the approach, the scientists pulled together multiple such datasets, applied their method, and then compared the resulting "network-extracted ontology" to the existing GO.

They found that their ontology captured the majority of known cellular components, plus many additional terms and relationships, which subsequently triggered updates of the existing GO.

Neither Ideker nor Dutkowski say the new approach is intended to replace the current GO. Rather, they envision it as complementary high-tech model that identifies both known and uncharacterized biological components derived directly from data, something the current GO does not do well. Moreover, they note a network-extracted ontology can be continuously updated and refined with every new dataset, moving scientists closer to the complete model of the cell.

 

###

 

Co-authors are Michael Kramer, UCSD Departments of Medicine and Bioengineering; Michal A. Surma, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany and UCSF Department of Cellular and Molecular Pharmacology; Rama Balakrishnan and J. Michael Cherry, Department of Genetics, Stanford University; and Nevan J. Krogan, UCSF Department of Cellular and Molecular Pharmacology and J. David Gladstone Institutes, San Francisco.

Funding for this research came, in part, from National Institutes of Health grants (P41-GM103504, P50-GM085764, R01-GM084448 and P50-GM081879).

 

 

Better Tools for Saving Water and Keeping Peaches Healthy

By Dennis  O'Brien December 13, 2012 Peach growers in California may soon have better tools for saving water because of work by U.S. Department of Agriculture (USDA) scientists in Parlier, Calif Agricultural Research Service (ARS) scientist Dong Wang is evaluating whether infrared sensors and thermal technology can help peach growers decide precisely when to irrigate in California's San Joaquin Valley. ARS is USDA's principal intramural scientific research agency, and the research supports the USDA priority of promoting international food security. Irrigation is the primary source of water for agriculture in the valley  during the summer, and wells have been forced to reach deeper to bring up enough  water to meet increasing demands. Peaches also require much of their water from June through September, when temperatures and demands for water are at their highest. Wang and Jim Gartung, an ARS  agricultural engineer, installed 12 infrared temperature sensors in peach  orchards at the San Joaquin  Valley Agricultural Sciences Center in Parlier and gave trees one of four  irrigation treatments: applying furrow or subsurface drip irrigation, with or  without postharvest water stress. They also measured crop yields and assessed the quality of the fruit to  compare the output of trees grown under deficit irrigation with trees grown  under normal conditions. Deficit irrigation has been used to produce some  varieties of grapes and has been studied for its potential in fruit tree and row  crop production. But it has yet to be widely adopted, in part because growers  need better tools to strike a balance between saving water and keeping crops  viable and healthy, according to Wang. They used the sensors to measure temperatures in the tree canopies, and  calculated a "crop water stress index" based on the differences between tree  canopy temperatures and the surrounding air temperatures. Higher index numbers indicated more stressed trees. The researchers found that midday canopy-to-air temperature differences in  trees that were water-stressed postharvest were in the 10- to 15-degree  Fahrenheit range, consistently higher than the 3- to 4-degree Fahrenheit range  in the trees that were not water-stressed. For comparison purposes, the researchers placed leaves from stressed and non-stressed trees in a pressure chamber and measured the pressure required to squeeze water out of them. When the trees are water-stressed, it takes more pressure to squeeze moisture from them. The results, published in Agricultural Water Management, show that the pressure chamber results were  consistent with data collected by the infrared sensors, which means the sensors may be an effective tool for managing water use in peach orchards. Read more about this research in the November/December 2012 issue of Agricultural Research magazine.

Brain cells activated, reactivated in learning and memory

University of California, Davis

December 13, 2012

 

Memories are made of this, the song  says. Now neuroscientists have for the first time shown individual mouse brain cells being switched on during learning and later reactivated during memory
recall. The results are published Dec. 13 in the journal Current Biology.

 

We store episodic memories about events in our lives in a part of a brain called the hippocampus, said Brian Wiltgen, now an assistant professor at the Center for Neuroscience and
Department of Psychology at the University of California, Davis. (Most of the work was conducted while Wiltgen was working at the University of Virginia.) In animals,
the hippocampus is important for navigation and storing memories about places.

 

"The exciting part is that we
are now in a position to answer a fundamental question about memory,"
Wiltgen said. "It's been assumed for a long time that the hippocampus is
essential for memory because it drives reactivation of neurons (nerve cells) in
the cortex. The reason you can remember an event from your life is because the
hippocampus is able to recreate the pattern of cortical activity that was there
at the time."

 

According to this model, patients
with damage to the hippocampus lose their memories because they can't recreate
the activity in the cortex from when the memory was made. Wiltgen's mouse
experiment makes it possible to test this model for the first time.

 

"We can now do a nice test of
hippocampal function," Wiltgen said.

 

Current thinking is that learning
activates a group of neurons that undergo changes, making new connections with
each other to store the memory. Retrieving the memory reactivates the network.

 

Researchers working with human
subjects, at UC Davis and elsewhere, use imaging techniques such as functional
magnetic resonance imaging to see which areas of the brain are switched on and
off in learning and retrieval. But fMRI cannot pick out an object as small as a
single cell.

 

Wiltgen and University of Virginia
graduate student Kaycie Tayler used a genetically modified mouse that carries a
gene for a modified green fluorescent protein. When nerve cells in the mouse
are activated, they produce a long-lived green fluorescence that persists for
weeks, as well as a short-lived red fluorescence that decays in a few hours.

 

However, the whole system can be
suppressed by dosing the mouse with the antibiotic doxycycline, so Tayler and
Wiltgen could manipulate the point at which they started tagging activated
cells.

 

The mice were put into a new cage
with an unfamiliar odor and given a few minutes to explore. Then they were
given a mild electrical shock through the cage floor. When returned to the cage
a couple of days later, the mice would remember the shock and stay frozen in
one place.

 

When they examined the brains of the
mice, the researchers could see which cells had been activated initially to
form the memory and which were reactivated later to recall it.

 

About 40 percent of the cells in the
hippocampus that were tagged during initial memory formation were reactivated,
Wiltgen said. There was also reactivation of cells in parts of the brain cortex
associated with place learning and in the amygdala, which is important for
emotional memory.

 

There was no evidence of
reactivation when the mice were tested in a new environment that they did not
remember, Wiltgen said.

 

The researchers also looked at
whether reactivation changed as memories got older. Over several weeks,
reactivation in the cortex and parts of the hippocampus remained stable, but it
decreased in other brain regions like the amygdala.

 

In future work, Wiltgen's team plans
to examine the role of the hippocampus and other brain regions in forming memories
and explore new ways to activate or block memories.

 

Other authors of the paper are
Kazumasa Tanaka at the University of Virginia
and Leon Reijmers at Tufts University School of Medicine.

The work was supported by the
McKnight Foundation, the National Science Foundation and the Nakajima
Foundation.

 

About UC Davis

 

For more than 100 years, UC Davis
has engaged in teaching, research and public service that matter to California and transform
the world.

Located close to the state capital,
UC Davis has more than 33,000 students, more than 2,500 faculty and more than
21,000 staff, an annual research budget of nearly $750 million, a comprehensive
health system and 13 specialized research centers. The university offers
interdisciplinary graduate study and more than 100 undergraduate majors in four
colleges -- Agricultural and Environmental Sciences, Biological Sciences,
Engineering, and Letters and Science. It also houses six professional schools
-- Education, Law, Management, Medicine, Veterinary Medicine and the Betty
Irene Moore School of Nursing.

 

Media contact(s):

* Brian Wiltgen, Center for
Neuroscience, (530) 754-9137, bjwiltgen@ucdavis.edu

* Andy Fell, UC Davis News Service,
(530) 752-4533, ahfell@ucdavis.edu

 

View this story on the Web at

<http://news.ucdavis.edu/search/news_detail.lasso?id=10437>

Scientists induce, relieve depression symptoms in mice with light

December 12, 2012 in Neuroscience

http://medicalxpress.com/news/2012-12-scientists-relieve-depression-symptoms-mice.html#nwlt

Among  those who suffer from depression, the dual inabilities to experience enjoyment
in things once pleasurable and to physically motivate oneself—to meet
challenges, or even to get out of bed in the morning—have been documented for
decades, though it has been mysterious why these very different kinds of
symptoms show up together, and also disappear together when depression is
successfully treated. It has been suspected that the brain chemical dopamine
could be a key player in the illness. And yet, in the long history of the study
of depression, no one has been able to clearly tie these key concepts together,
until now.

Researchers at Stanford  University have successfully induced and relieved depression-like deficiencies in both pleasure and motivation in mice by controlling just a single area of the brain known as
the ventral tegmental area. It is the first time that well-defined types of
neurons within a specific brain region have been directly tied to the control of
myriad symptoms of major depressive illness. In the paper to be published in
Nature on Dec. 12, Stanford bioengineer Karl Deisseroth, MD, PhD, and a team
including postdoctoral scholars Kay Tye, PhD, and Melissa Warden, PhD, and
research assistant Julie Mirzabekov have used a technique known as optogenetics
to pinpoint a specific brain location that produces multiple depression-like
symptoms. The region in question is the ventral tegmental area, or VTA, a source
of dopamine and a central player in the brain's internal motivation and reward
systems. "We have for the first time directly tied dopamine neurons in the VTA
to controlling and relieving these very different and diverse symptoms," said
Deisseroth, the study's senior author and a professor of bioengineering and of
psychiatry and behavioral sciences. "While depression is a complex disease with
still many unknowns, this knowledge may help launch new kinds of investigation
into the pathways of depression in the brain, and develop concepts to help
people suffering from depression." Deisseroth's team was able to both induce and
relieve multiple depression-like symptoms in laboratory mice by genetically
modifying the dopamine neurons in the VTA to be sensitive to light. Using fiber
optic cables inserted in rodents' brains, they could then instantaneously
produce and inhibit the depression-like symptoms by turning the light on and
off. This research technique, developed by Deisseroth at Stanford in 2005, is
known as optogenetics.

 

The  team examined mice in a depressed-like, low-motivation state induced by mild
stressors whose VTA neurons had been optogenetically modified. "When given light
stimulation to the VTA dopamine neurons, these mice showed a robust increase in
escape-related behavior. They immediately tried harder to get out of challenging
situations—reversing back to normal levels of effort from the depressed-like
state they were in," explained Deisseroth. Similarly, he said, when offered the
choice of sugar water over plain, the mice that had been in a depressed-like
state chose the sugar water with much greater frequency when their VTA dopamine
neurons were stimulated by illumination. They opted to experience pleasure—back
to normal levels. Finally, and remarkably, Deisseroth noted, optogenetically
inhibiting the VTA dopamine neurons instead of stimulating them caused, rather
than corrected, both kinds of depression symptoms—instantaneously and
reversibly. "These results directly implicated a single class of neuron in a
single brain region—ventral tegmental dopamine neurons—in both producing and
relieving very different depression-related symptoms, addressing a mystery in
disease pathophysiology," said Deisseroth. And yet, another key question still
remained: What are the VTA dopamine neurons doing to downstream circuits? In
other words, how are the depression-related control signals read out? To answer
these questions, the researchers next took the work a step further by mapping
the effects of dopamine neuron activity in the VTA on the nucleus accumbens, a
brain center thought to influence diverse functions of pleasure, and likely the
site of action for addictive drugs as well as natural rewards. Seeing a change
in the nucleus accumbens would provide information on the mechanism for how VTA
dopamine neuron effects are manifested in the brain. "Indeed, we established
that electrophysiological representation of action in the nucleus accumbens is
in fact fundamentally altered by VTA dopamine neuron activation. If we activate
the VTA dopamine neurons, it influences the nucleus accumbens' encoding of
physical, motivated action," emphasized Deisseroth. Together, these results
represented a long-sought circuit-level insight into the causes and nature of
depression-related behavior. While the results are significant, Deisseroth, who
is also a practicing psychiatrist, cautioned that depression and other mental
illnesses are complex, multidimensional and vary from patient to patient. The
symptoms of depression are certainly influenced by many neural circuits, he
said. "Nonetheless, the VTA dopamine circuitry we studied is very similar in
both rodents and humans. And we have shown that the neurons in this circuit
specifically cause, correct and encode diverse symptoms of depression. This is a
significant advance in our understanding of the biological underpinnings of
depression and related behaviors, with promising implications for future
research," said Deisseroth. More information: DOI: 10.1038/nature11740 Related:
DOI: 10.1038/nature11713 Journal reference: Nature Provided by Stanford University Medical Center
http://medicalxpress.com/news/2012-12-scientists-relieve-depression-symptoms-mice.html#nwlt

 

Need to move soon? Don't trust your emotions

Consumers are more likely to make emotional instead of objective assessments when the outcomes are closer to the present time than when they are further away in the future, according to a new study in the Journal of Consumer Research.

"The proximity of a decision's outcome increases consumer reliance on feelings when making decisions. Feelings are relied upon more when the outcome is closer in time because these feelings appear to be more informative in such situations," write authors Hannah H. Chang (Singapore Management University) and Michel Tuan Pham (Columbia University).

From which snack to buy to which apartment to rent, we base many of our decisions on either feelings or objective assessment. The option that appeals more to our feelings is often not the one that "makes more sense." When do consumers rely more on their feelings than objective assessments? And how does the proximity of the decision outcome influence consumer decision-making? For example, when looking for an apartment to rent, some consumers may decide which apartment to rent only a week before moving in, while others may decide several months in advance.

In one study, college students were asked to imagine that they were about to graduate, had found a well-paying job, and were looking for an apartment to rent after graduation. They were then given a choice between an apartment that appeals more to their feelings (a smaller, prettier apartment with better views) and an option that is objectively better (a bigger, more conveniently located apartment). Compared to college juniors and those who imagined graduating a year later, college seniors and those who imagined graduating and moving into an apartment next month were more likely to choose the former option.

"Companies should consider the time between consumer decision-making and consumption. When consumers will be deciding immediately prior to consumption (choosing an entrée at a restaurant or a mobile phone plan), companies should focus on messages that appeal to consumers' feelings. When they will be deciding well in advance (choosing a retirement plan or booking flights), companies should focus less on emotional appeals and instead emphasize messages that appeal to objective assessments," the authors conclude.

 

###

Hannah H. Chang and Michel Tuan Pham. "Affect as a Decision-Making System of the Present." Journal of Consumer Research: June 2013. For more information, contact Hannah H. Chang (hannahchang@smu.edu.sg) or visit http://ejcr.org/.

 

The dark side of kerosene lamps: High black carbon emissions

The dark side of kerosene lamps: High black carbon
emissions

 

CHAMPAIGN, Ill. — The small kerosene lamps that light millions of homes in developing countries have a dark side: black carbon – fine particles of soot released into the atmosphere.

Simple kerosene lamps, a common source of light in the developing world, emit
high levels of black carbon – 20 times more than previously thought, according
to a new study. | Photo
by Tami Bond

New measurements show that
kerosene wick lamps release 20 times more black carbon than previously thought,
say researchers at the University of Illinois and the University of
California, Berkeley. The group published its findings in the
journal Environmental Science and Technology.



Black carbon is a hazard for human health and the environment, affecting air
quality both indoors and out. It has a major impact on climate as it absorbs
heat and sunlight, warming the air. Although it only lingers in the atmosphere
for about two weeks, one kilogram of black carbon can cause as much warming in
that short time as 700 kilograms of carbon dioxide circulating in the
atmosphere for 100 years, according to study leader Tami Bond,
a professor of civil and
environmental engineering at the U. of I.



“There’s a lot of interest right now in reducing black carbon as a quick way to
reduce climate warming – a way to reduce warming in the immediate future,
although not a full solution to long-term climate change,” Bond said. “In its
short lifetime of two weeks, it adds a lot of energy to the atmosphere. It’s
immediate warming now, which is why people are talking about reducing it.”



Previously, emissions researchers did not consider kerosene lamps a large
source of black carbon because of the relatively small amount of fuel used in a
lamp verses other particle-emitting sources, such as cookstoves or diesel
engines. However, the new measurements from the field show that 7 to 9 percent
of fuel burned is converted to black carbon – a very high emission factor,
making such lamps a major source of black carbon. In addition, unlike the
cocktail of aerosol particles released by cookstoves and cooking fires, the
dark curls rising from a kerosene lamp are nearly pure black carbon.



The good news is that there are inexpensive, easy alternatives that could curb
black carbon emissions from lamps. For example, LED lamps charged by solar
panels are becoming more popular. But an even easier fix would be to place a
glass shield around the lamp, which reduces – though does not eliminate – the
amount of black carbon particles that escape.



“Unlike cooking stoves, which also are very important health hazards but
challenging to replace, people actually like to replace the kerosene lamps,”
Bond said. “When it comes to lamps, nobody says, ‘I really like this tin can
that I filled with kerosene.’ It’s a plausible, inexpensive way to reduce
climate warming immediately, which is something we haven’t really had in the
black carbon field before.”



The study authors hope that, with the new data in hand, agencies working in
developing countries will implement lamp-replacement initiatives to develop and
distribute affordable alternatives.



"Getting rid of kerosene lamps may seem like a small, inconsequential step
to take,” said study lead author Nicholas Lam, a UC Berkeley graduate student,
“but when considering the collective impact of hundreds of millions of
households, it's a simple move that affects the planet."



The Centers for Disease Control and Prevention, the National Institute of
Environmental Health Sciences, the U.S. Agency for International Development
and the Environmental Protection Agency supported this research.

Editor's
note: To reach Tami Bond, call 217-244-5277; email yark@illinois.edu. The paper, “Household Light
Makes Global Heat: High Black Carbon Emissions From Kerosene Wick Lamps,” is
available online.

 

In vitro study finds digested formula, but not breast milk, is toxic to cells

In vitro study finds digested formula, but not breast milk, is toxic to cells Findings may help explain development of fatal condition in premature infants IMAGE:This microscopic image of cells shows the effects of breast milk vs. infant formula digestion. Cells are alive and healthy after the digestion of breast milk (top row) with only... Click here for more information. Free fatty acids created during the digestion of infant formula cause cellular death that may contribute to necrotizing enterocolitis, a severe intestinal condition that is often fatal and occurs most commonly in premature infants, according to a study by University of California, San Diego bioengineers. Their report, which was based on in vitro tests comparing the digestion of fresh human breast milk and nine different infant formulas, was published online in the journal Pediatric Research. Scientists have long known that premature infants fed formula are more likely to develop necrotizing enterocolitis than those fed breast milk. The condition is the leading cause of death from gastrointestinal diseases in premature infants, but the underlying mechanism has not been understood. Alexander Penn, a research scientist working in the Microcirculation Laboratory of bioengineering Professor Geert Schmid-Schönbein from the UC San Diego Jacobs School of Engineering, believes they have come closer to an answer. Penn and others had previously determined that the partially digested food in a mature, adult intestine is capable of killing cells, due to the presence of free fatty acids which have a "detergent" capacity that damages cell membranes. The intestines of healthy adults and older children have a mature mucosal barrier that may prevent damage due to free fatty acids. However, the intestine is leakier at birth, particularly for preterm infants, which could be why they are more susceptible to necrotizing enterocolitis. Therefore, the researchers wanted to know what happens to breast milk as compared to infant formula when they are exposed to digestive enzymes. They "digested," in vitro, infant formulas marketed for full term and preterm infants as well as fresh human breast milk using pancreatic enzymes or fluid from an intestine. They then tested the formula and milk for levels of free fatty acids. They also tested whether these fatty acids killed off three types of cells involved in necrotizing enterocolitis: epithelial cells that line the intestine, endothelial cells that line blood vessels, and neutrophils, a type of white blood cell that is a kind of "first responder" to inflammation caused by trauma in the body. IMAGE:This chart shows the high concentration of unbound (cytotoxic) free fatty acids (FFAs) (shown in white) created by the digestion of infant formula compared to the relatively small presence of... Click here for more information. Overwhelmingly, the digestion of formula led to cellular death, or cytotoxicity – in less than 5 minutes in some cases – while breast milk did not. For example, digestion of formula caused death in 47 percent to 99 percent of neutrophils while only 6 percent of them died as a result of milk digestion. The study found that breast milk appears to have a built-in mechanism to prevent cytotoxicity. The research team believes most food, like formula, releases high levels of free fatty acids during digestion, but that breast milk is digested in a slower, more controlled, process. Currently, many neonatal intensive care units are moving towards formula-free environments, but breastfeeding a premature infant can be challenging or physically impossible and supplies of donor breast milk are limited. To meet the demand if insufficient breast milk is available, less cytotoxic milk replacements will need to be designed in the future that pose less risk for cell damage and for necrotizing enterocolitis, the researchers concluded. This may be of benefit not only to premature infants, but also to full-term infants at higher risk for disorders that are associated with gastrointestinal problems and more leaky intestines, such as autism spectrum disorder. Dr. Sharon Taylor, a professor of pediatric medicine at UC San Diego School of Medicine and a pediatric gastroenterologist at Rady Children's Hospital, San Diego, said the study offers more support to an already ongoing push by hospitals, including neonatal intensive care units, to encourage breastfeeding even in more challenging circumstances in the NICU. For patients who are too premature or frail to nurse, Dr. Taylor said hospital staff should provide consultation and resources to help mothers pump breast milk that can be fed to the baby through a tube. The research was carried out in collaboration with Dr. Taylor, Karen Dobkins of the Department of Psychology, and Angelina Altshuler and James Small of the Department of Bioengineering at UC San Diego and was funded by the National Institutes of Health (NS071580 and GM85072). The researchers conclude that breast milk has a significant ability to reduce cytotoxicity that formula does not have. One next step is to determine whether these results are replicated in animal studies and whether intervention can prevent free fatty acids from causing intestinal damage or death from necrotizing enterocolitis. ###

Do we live in a computer simulation? UW researchers say idea can be tested

Is this supported by the fact the Voyager 1 found an unexpected band of magnetic energy at the edge of the solar system?  Voyager  1 finds a surprise at the edge of the solar system..NASA's  Voyager 1, which is headed for interstellar space, runs into an unexpected
'magnetic highway.'

Do we live in a computer simulation? UW researchers say idea can be tested

By Vince
Stricherz

News and Information

Posted under: News Releases, Research, Science

A decade ago, a British philosopher put forth the notion that the universe we live in might in fact be a computer simulation run by our descendants. While that seems far-fetched, perhaps even
incomprehensible, a team of physicists at the University of Washington has come up with a potential test to see if the idea holds water.

The concept that current humanity could possibly be living in a computer simulation comes from a 2003 paper published in Philosophical Quarterly by Nick Bostrom, a philosophy professor at
the University of Oxford. In the paper, he
argued that at least one of three possibilities is true:

• The human species is likely to go
  extinct before reaching a “posthuman” stage.
• Any posthuman civilization is very
  unlikely to run a significant number of simulations of its evolutionary
  history.
• We are almost certainly living in a
  computer simulation.

He also held that “the belief that there is a significant chance that we
will one day become posthumans who run ancestor simulations is false, unless we
are currently living in a simulation.”

The conical (red) surface shows the relationship between energy and momentum in special relativity, a fundamental theory concerning space and time developed by Albert Einstein, and is the
expected result if our universe is not a simulation. The flat (blue) surface
illustrates the relationship between energy and momentum that would be expected
if the universe is a simulation with an underlying cubic lattice

With current limitations and trends in computing, it will be decades
before researchers will be able to run even primitive simulations of the
universe. But the UW team has suggested tests that can be performed now, or in
the near future, that are sensitive to constraints imposed on future
simulations by limited resources.

Currently, supercomputers using a technique called lattice quantum
chromodynamics and starting from the fundamental physical laws that govern the
universe can simulate only a very small portion of the universe, on the scale
of one 100-trillionth of a meter, a little larger than the nucleus of an atom,
said Martin Savage,
a UW physics professor.

Eventually, more powerful simulations will be able to model on the scale
of a molecule, then a cell and even a human being. But it will take many
generations of growth in computing power to be able to simulate a large enough
chunk of the universe to understand the constraints on physical processes that
would indicate we are living in a computer model.

However, Savage said, there are signatures of resource constraints in
present-day simulations that are likely to exist as well in simulations in the
distant future, including the imprint of an underlying lattice if one is used
to model the space-time continuum.

The supercomputers performing lattice quantum chromodynamics
calculations essentially divide space-time into a four-dimensional grid. That
allows researchers to examine what is called the strong force, one of the four
fundamental forces of nature and the one that binds subatomic particles called
quarks and gluons together into neutrons and protons at the core of atoms.

“If you make the simulations big enough, something like our universe
should emerge,” Savage said. Then it would be a matter of looking for a
“signature” in our universe that has an analog in the current small-scale
simulations.

Savage and colleagues Silas
Beane of the University
of New Hampshire, who
collaborated while at the UW’s Institute
for Nuclear Theory, and Zohreh Davoudi, a UW physics graduate student,
suggest that the signature could show up as a limitation in the energy of
cosmic rays.

In a paper they have posted on arXiv, an online archive for preprints of scientific papers in a number of fields, including physics, they say that the highest-energy cosmic rays would
not travel along the edges of the lattice in the model but would travel
diagonally, and they would not interact equally in all directions as they
otherwise would be expected to do.

“This is the first testable signature of such an idea,” Savage said.

If such a concept turned out to be reality, it would raise other
possibilities as well. For example, Davoudi suggests that if our universe is a
simulation, then those running it could be running other simulations as well,
essentially creating other universes parallel to our own.

“Then the question is, ‘Can you communicate with those other universes
if they are running on the same platform?’” she said.

###

For more information, contact Savage at 206-543-7481 or mjs5@uw.edu; or Davoudi at 206-543-9310 or davoudi@uw.edu.

 

Brain study shows why some people are more in tune with what they want

Brain study shows why some people are more in tune with what
they want

 

December 9, 2012 in Neuroscience

 

Wellcome Trust researchers have discovered how the brain
assesses confidence in its decisions. The findings explain why some people have
better insight into their choices than others.

 

 

Throughout life, we're constantly evaluating our options and
making decisions based on the information we have available. How confident we
are in those decisions has clear consequences. For example, investment bankers
have to be confident that they're making the right choice when deciding where
to put their clients' money. Researchers at the Wellcome Trust Centre for
Neuroimaging at UCL led by Professor Ray Dolan have pinpointed the specific
areas of the brain that interact to compute both the value of the choices we
have in front of us and our confidence in those choices, giving us the ability
to know what we want. The team used functional magnetic resonance imaging
(fMRI) to measure activity in the brains of twenty hungry volunteers while they
made choices between food items that they would later eat. To determine the
subjective value of the snack options, the participants were asked to indicate
how much they would be willing to pay for each snack. Then after making their
choice, they were asked to report how confident they were that they had made
the right decision and selected the best snack. It has previously been shown
that a region at the front of the brain, the ventromedial prefrontal cortex, is
important for working out the value of decision options. The new findings
reveal that the level of activity in this area is also linked to the level of
confidence participants placed on choosing the best option. The study also
shows that the interaction between this area of the brain and an adjacent area
reflects participants' ability to access and report their level of confidence
in their choices. Dr Steve Fleming, a Sir Henry Wellcome Postdoctoral Fellow
now based at New York
University, explains:
"We found that people's confidence varied from decision to decision. While
we knew where to look for signals of value computation, it was very interesting
to also observe neural signals of confidence in the same brain region." Dr
Benedetto De Martino, a Sir Henry Wellcome Postdoctoral Fellow at UCL, added:
"Overall, we think our results provide an initial account both of how
people make choices, and also their insight into the decision process."
The findings are published online in the journal Nature Neuroscience. Journal
reference: Nature Neuroscience Provided by Wellcome Trust 



Read more at: http://medicalxpress.com/news/2012-12-brain-people-tune.html#jCp

Antibiotic-eating bug unearthed in soil

American Society of Agronomy
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www.agronomy.org
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NEWS RELEASE
Contact: Madeline Fisher, Science Communications Manager, 608-268-3973, mfisher@sciencesocieties.org

Antibiotic-eating bug unearthed in soil

A newly discovered bacterium degrades an antibiotic both to protect itself and get nutrition

Dec. 6, 2012 -- It’s well known how bacteria exposed to antibiotics for long periods will find ways to resist the drugs—by quickly pumping them out of their cells, for instance, or modifying the compounds so they’re no longer toxic.

Now new research has uncovered another possible mechanism of antibiotic “resistance” in soil. In a paper published on Dec. 6 in the Journal of Environmental Quality, a group of Canadian and French scientists report on a soil bacterium that breaks down the common veterinary antibiotic, sulfamethazine, and uses it for growth.

Certain soil bacteria are already known to live off, or “eat,” agricultural pesticides and herbicides, says the study’s leader, Ed Topp, a soil microbiologist with Agriculture and Agri-Food Canada in London, Ontario. In fact, the microbes’ presence in farm fields can cause these agrichemicals to fail.

But to Topp’s knowledge, this is the first report of a soil microorganism that degrades an antibiotic both to protect itself and get nutrition.

“I think it’s kind of a game changer in terms of how we think about our environment and antibiotic resistance,” he says.

Concerns about widespread antibiotic resistance are what led Topp and his collaborators to set up an experiment 14 years ago, in which they dosed soils annually with environmentally relevant concentrations of three veterinary antibiotics: sulfamethazine, tylosin, and chlortetracycline. Commonly fed to pigs and other livestock, antibiotics are thought to keep animals healthier. But they’re also excreted in manure, which is then spread once a year as fertilizer in countless North American farm fields.

The researchers first wanted to know whether these yearly applications were promoting higher levels of antibiotic resistance in soil bacteria. But a few years ago, they also decided to compare the persistence of the drugs in soil plots that had been repeatedly dosed, versus fresh soils where antibiotics were never applied.

They did this experiment, Topp explains, because of previous work indicating that pesticides often break down more quickly in soils with a long history of exposure, indicating that pesticide-degrading microbes have been selected for over time.

Still, it came as a surprise when they saw antibiotics also degrading much faster in long-term, treated plots than in fresh, control soils, he says. In particular, sulfamethazine—a member of the antibiotic class called sulfonamides—disappeared up to five times faster.

The researchers subsequently cultured from the treated plots a new strain of Microbacterium, an actinomycete that uses sulfamethazine as a nitrogen and carbon source. Extremely common in soil, actinomycete bacteria are known to degrade a wide range of organic compounds. And now at least two other sulfanomide-degrading Microbacterium strains have been reported, Topp says: one from soil and another from a sewage treatment plant.

Taken together, the findings suggest that the capability to break down sulfanomides could be widespread. And if it’s indeed true that “the microbiology in the environment is learning to break these drugs down more rapidly when exposed to them, this would effectively reduce the amount of time that the environment is exposed to these drugs and therefore possibly attenuate the impacts,” Topp says.

Not that negative impacts aren’t still occurring, he cautions. In particular, long-term exposure to antibiotics puts significant pressure on soil bacteria to evolve resistance, which they typically do by giving and receiving genes that let them detoxify drugs, or keep the compounds out of their cells.

What the new research suggests, though, is that soil bacteria could be swapping genes for breaking down antibiotics at the same time.

“My guess is that’s probably what’s happening, but it remains to be determined,” Topp says. “It’s actually extremely fascinating.”

The work was funded by Agriculture and Agri-Food Canada.

Topp can be reached at 519-457-1470 e.235; ed.topp@agr.gc.ca

# # #

The full article is available for no charge for 30 days following the date of this summary. View the abstract at https://dl.sciencesocieties.org/publications/jeq/abstracts/0/0/jeq2012.0162.

 

The Journal of Environmental Quality is a peer-reviewed, international journal of environmental quality in natural and agricultural ecosystems published six times a year by the American Society of Agronomy (ASA), Crop Science Society of America (CSSA), and the Soil Science Society of America (SSSA). The Journal of Environmental Quality covers various aspects of anthropogenic impacts on the environment, including terrestrial, atmospheric, and aquatic systems.

 

The American Society of Agronomy (ASA) www.agronomy.org, is a scientific society helping its 8,000+ members advance the disciplines and practices of agronomy by supporting professional growth and science policy initiatives, and by providing quality, research-based publications and a variety of member services.

How the common 'cat parasite' gets into the brain

[PRESS RELEASE, 7 December 2012] Toxoplasma is a common 'cat parasite', and has previously been in the spotlight owing to its observed effect on risk-taking and other human behaviours. To some extent, it has also been associated with mental illness. A study led by researchers from Karolinska Institutet now demonstrates for the first time how the parasite enters the brain to influence its host.

A dendritic cell infected by
the Toxoplasma gondii (in red).

"We believe that this knowledge may be important for the further understanding of complex interactions in some major public health issues, that modern science still hasnt been able to explain fully", says Antonio Barragan, researcher at the Center for Infectious Medicine at Karolinska Institutet and the Swedish Institute for Communicable Disease Control. "At the same time, it's important to emphasize that humans have lived with this parasite for many millennia, so today's carriers of Toxoplasma need not be particularly worried."

 

The current study, which is published in the scientific journal PLoS Pathogens, was led by Dr Barragan and conducted together with researchers at Uppsala University

 

Toxoplasmosis is caused by the extremely common Toxoplasma gondii parasite. Between 30 and 50 per cent of the global population is thought to be infected, and an estimated twenty per cent or so of people in Sweden. The infection is also found in animals, especially domestic cats. People contract the parasite mostly by eating the poorly cooked flesh of infected animals or through contact with cat faeces. The infection causes mild flu-like symptoms in adults and otherwise healthy people before entering a chronic and dormant phase, which has previously been regarded as symptom-free. It is, however, known that toxoplasmosis in the brain can be fatal in people with depleted immune defence and in fetuses, which can be infected through the mother. Because of this risk, pregnant women are recommended to avoid contact with cat litter trays.

 

A number of studies have been presented in recent years showing that the toxoplasmosis parasite affects its host even during the dormant phase. It has, for example, already been observed that rats become unafraid of cats and even attracted by their scent, which makes them easy prey. This has been interpreted as the parasite assuring its survival and propagation, since the consumed rat then infects the cat, which through its faces can infect the food that other rats might then proceed to eat. A number of studies also confirm that mental diseases like schizophrenia, depression and anxiety syndrome are more common in people with toxoplasmosis, while others suggest that toxoplasmosis can influence how extroverted, aggressive or risk-inclined an individual's behaviour is.

 

"We've not looked at behavioural changes in people infected with toxoplasma, as that's been dealt with by previous studies," says Dr Barragan. "Instead, we've shown for the first time how the parasite behaves in the body of its host, by which I mean how it enters the brain and manipulates the host by taking over one of the brain's neurotransmitters."

 

In one laboratory experiment, human dendritic cells were infected with toxoplasma. After infection, the cells, which are a key component of the immune defence, started secreting the signal substance GABA. In another experiment on live mice, the team was able to trace the movement of infected dendritic cells in the body after introducing the parasite into the brain, from where it spread and continued to affect the GABA system.

 

GABA is a signal substance that, amongst other effects, inhibits the sensation of fear and anxiety. Disturbances of the GABA system are seen in people with depression, schizophrenia, bipolar diseases, anxiety syndrome and other mental diseases.

 

"For toxoplasma to make cells in the immune defence secrete GABA was as surprising as it was unexpected, and is very clever of the parasite," says Dr Barragan. "It would now be worth studying the links that exist between toxoplasmosis, the GABA systems and major public health threats."

 

The study was financed with a grant from the Swedish Research Council.

Publication:

      Jonas M. Fuks, Romanico B. G. Arrighi, Jessica M. Weidner, Suresh Kumar Mendu, Zhe Jin, Robert P. A. Wallin, Bence Rethi, Bryndis Birnir and Antonio Barragan        

GABAergic signaling is linked to a hypermigratory phenotype in dendritic cells infected by Toxoplasma gondii

            PLoS Pathogens, online 6 December 2012, open access        

•         Journal website

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•         Department of Medicine, Huddinge

Research Suggests a New Strategy to Prevent or Halt Periodontal Disease

December 7, 2012

PHILADELPHIA — Periodontitis, a form of chronic gum disease that affects nearly half of
the U.S.
adult population, results when the bacterial community in the mouth becomes
unbalanced, leading to inflammation and eventually bone loss. In its most
severe form, which affects 8.5 percent of U.S. adults, periodontitis can
impact systemic health.

By blocking a molecular
receptor that bacteria normally target to cause the disease, scientists from
the University of Pennsylvania have now
demonstrated an ability in a mouse model to both prevent periodontitis from
developing and halt the progression of the disease once it has already
developed.

The study, published in
the Journal of
Immunology, was led by Toshiharu Abe, a postdoctoral researcher in the Department
of Microbiology in Penn’s School of
Dental Medicine. Abe works in the lab of George
Hajishengallis, a professor in the department who was a senior author on
the paper. The co-senior author was John D.
Lambris, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in
the Department of Pathology and
Laboratory Medicine in Penn’s Perelman
School of Medicine. Kavita B. Hosur and Evlambia
Hajishengallis from Penn Dental Medicine also contributed to the research,
as did Penn Medicine’s Edimara S. Reis
and Daniel
Ricklin.

In previous research,
Hajishengallis, Lambris and colleagues showed that Porphyromonas gingivalis,
the bacterium responsible for many cases of periodontitis, acts to “hijack”
a receptor on white blood cells called C5aR. The receptor is part of the
complement system, a component of the immune system that helps clear infection
but can trigger damaging inflammation if improperly controlled.

By hijacking C5aR, P.
gingivalis subverts the complement system and handicaps immune cells, rendering
them less able to clear infection from the gum tissue. As a result, numbers of
P. gingivalis and other microbes rise and create severe inflammation. According
to a study
published last year by the Penn researchers, mice bred to lack C5aR did not
develop periodontitis.

Meanwhile, other studies
by the Penn group and others have shown that Toll-like receptors, or TLRs — a
set of proteins that also activate immune cell responses — may act in concert
with the complement system. In addition, mice lacking one form of TLR called
TLR2 do not develop bone loss associated with periodontitis, just like the
C5aR-deficient mice.

In the new study, the
Penn team wanted to determine if the synergism seen by other scientists between
the complement system and TLRs was also at play in this inflammatory gum
disease.

To find out, they
injected two types of molecules, one that activated C5aR and another that
activated TLR2, into the gums of mice. When only one type of molecule was
administered, a moderate inflammatory response was apparent a day later, but
when both were injected together, inflammatory molecules increased dramatically
— soaring to levels higher than would have been expected if the effect of
activating both receptors was merely additive.

This finding suggested to
the scientists that the Toll-like receptor signaling was somehow involved in
“crosstalk” with the complement system, serving to augment the inflammatory
response. Turning that implication on its head, they wondered whether blocking
just one of these receptors could effectively halt the inflammation that allows
P. gingivalis and other bacteria to thrive and cause disease.

Testing this hypothesis,
the researchers synthesized and administered a molecule that blocks the
activity of C5aR, to see if it could prevent periodontitis from developing.
They gave this receptor “antagonist,” known as C5aRA, to mice that were then
infected with P. gingivalis. The C5aRA injections were able to stave off
inflammation to a large extent, reducing inflammatory molecules by 80 percent
compared to a control, and completely stopping bone loss.

And when the mice were
given the antagonist two weeks after being infected with P. gingivalis, the
treatment was still effective, reducing signs of inflammation by 70 percent and
inhibiting nearly 70 percent of periodontal bone loss.

“Regardless of whether we
administered the C5a receptor antagonist before the development of the disease
or after it was already in progress, our results showed that we could inhibit
the disease either in a preventive or a therapeutic mode,” Hajishengallis said.


This is significant for extending these findings to a potential human
treatment, as treatments would most likely be offered to those patients already
suffering from gum disease.

Because not all cases of
periodontitis are caused by P. gingivalis, the research team also wanted to see
whether C5aRA could effectively prevent or treat the disease when it arose due
to other factors. To do so, they placed a silk ligature around a single molar
tooth in a group of mice. The obstruction not only blocked the natural cleaning
action of saliva, but also enabled bacteria to stick to the ligature itself,
resulting in a massive accumulation of bacteria. This microbial build-up
rapidly leads to periodontitis and bone loss, within just five days in the
mice.

The researchers then
injected the gum tissue adjacent to the ligated molar tooth with C5aRA in some
of the mice, and gave the other mice a control.

“These mice that got the
C5a receptor antagonist developed at least 50 percent less inflammation and
bone loss compared to an analog of C5a receptor antagonist which is not
active,” Hajishengallis said.

This result gives the
researchers greater confidence that the C5aRA treatment could be effective
against periodontitis in general, not just those cases caused by P. gingivalis
bacteria.

The team is now working
to replicate their success in mice in other animal models, an important step
toward extending this kind of treatment to humans with gum disease.

“Our ultimate goal is to
bring complement therapeutics to the clinic to treat periodontal diseases,”
Lambris said. “The complement inhibitors, some of which are in clinical trials,
developed by my group are now tested in various periodontal disease animal
models and we hope soon to initiate clinical trials in human patients.”

The study was supported
by the National Institutes of Health.

 

International Team of Green Scientists Propose Safety Testing System for Development of New Chemicals

 

Process Can Help To Ensure That Consumer Products Are Free of Harmful Endocrine Disruptors

PITTSBURGH—A group of scientists from North America and Europe, including Carnegie Mellon University’s Terry Collins, has developed a five-tiered testing system that manufacturers can use to ensure that the chemicals and consumer products they produce are free of harmful endocrine disrupting chemicals like BPA or DDT. Their study, “Designing Endocrine Disruption Out of the Next Generation of Chemicals,” will be published in the January 2013 issue of the Royal Society of Chemistry journal Green Chemistry, and is currently available online.

Endocrine disrupting chemicals, which are commonly used in consumer products, can mimic hormones and lead to a host of modern-day health epidemics including cancers, learning disabilities and immune system disorders. The new testing system can help manufacturers avoid creating products that contain the harmful chemicals.

“Endocrine disrupting chemicals are a clear and present danger to the welfare of all living species,” said Collins, the Teresa Heinz Professor in Green Chemistry and director of the Institute for Green Science at CMU. “It is important for people everywhere and especially for future generations that we strive to design chemicals that are not endocrine disruptors themselves and materials that are inherently free of endocrine disruptors.”

Historically, chemists have endeavored to create products that are both effective and economical, but rarely have they been asked to consider the product’s potential toxicity, particularly developmental toxicity. This has led to consumer products that unintentionally contain harmful chemicals like endocrine disruptors, and to the subsequent replacement of these products. One of the most recent examples is the discovery of BPA in popular baby products.

The 23 authors of the current study, who are chemists, biologists and environmental health scientists, say that recent product recalls and bans indicate that product manufacturers do not have adequate tools for avoiding the introduction of endocrine disrupting chemicals into their products. Furthermore, they feel that governments have not come up with adequate methods for regulating against endocrine disrupting chemicals. The researchers concluded that as the understanding of the threat of these chemicals to human health has grown, the need for an effective testing strategy for endocrine disrupting chemicals has become imperative.  According to Collins, effective testing will help to protect health and the environment and will safeguard chemical manufacturers while reducing the need for future regulatory interventions.

The researchers used 20 years of research on endocrine disruptors to create a five-tiered testing system called the Tiered Protocol for Endocrine Disruption (TiPED). Manufacturers can use any of the tiers to test their products based on their needs. Each tier increases with complexity and cost, as well as with the reliability of results. As a proof of concept, the researchers tested six known endocrine disruptors using all five tests. Each disruptor was identified as being “endocrine active” by one or more of the tests.

The researchers hope that chemists and companies will incorporate these tests at the early stages of product development, allowing them to detect and avoid endocrine disrupting chemicals early on. By using the tests, manufacturers can create safer products and provide their consumers with peace of mind in knowing that the products  tested are safe from endocrine disruption to the highest standards of science at any given time. The researchers plan to update the tests as new research on endocrine disruptors becomes available.

For more information on TiPED, visit: www.tipedinfo.com. A full list of authors can be found by accessing the paper on the Green Chemistry website: http://pubs.rsc.org/en/content/articlelanding/2013/gc/c2gc35055f.

This research was funded by the National Institute of Environmental Health Sciences, the Cedar Tree Foundation, the Johnson Family Foundation, the Kendeda Fund, the Marisla Foundation, the John Merck Fund and the Passport Foundation.

By: Jocelyn Duffy, jhduffy@andrew.cmu.edu, 412-268-9982

Researchers develop novel 3-D culture system for inflammatory breast cancer

SAN ANTONIO, TX (December 8, 2012)—Inflammatory breast cancer (IBC) is a very rare and aggressive disease that progresses rapidly and is associated with a very low survival rate. To understand how this type of cancer spreads, it's crucial to characterize the interactions between cancer cells and their 3D environment. Researchers at Fox Chase Cancer Center have developed a novel, 3D culture system that mimics the environment surrounding these cancer cells. This model could be used to test new anticancer drugs capable of inhibiting the spread of IBC tumors.

"The tumor microenvironment plays a pivotal role in tumor development and progression, and it also plays a big role in restricting tumorigenesis," says senior study co-investigator Edna Cukierman, PhD, Associate Professor of Cancer Biology at Fox Chase. "So understanding the interactions between the tumor and the environment will help us to come up with new ways to target the tumor." K Alpaugh, a co-author in this collaborative work, will present the study findings at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium on Saturday, December 8, 2012.

For the study, Cukierman, a tumor microenvironment expert, and her colleagues in the lab of Massimo Cristofanilli, MD, Professor at Fox Chase and a leading expert in inflammatory breast cancer, used tumor-associated stromal cells from patients with advanced IBC to build a 3D structure consisting of cell-derived extracellular matrix—scaffold that provides structural and biochemical support to cells.

After culturing a plethora of established and patient-derived cancer cells in the stromal 3D system, the researchers categorized them into two groups. While some cells showed a significant increase in proliferation and resembled those seen in aggressive tumors, others were more similar to cells in less-aggressive tumors. These two types of cells modified the extracellular matrix in distinct ways, indicating that there is a dynamic interplay between cancer cells and the microenvironment.

Moreover, exposure to the matrix caused all of the cancer cells to increase their expression of the protein epithelial cadherin (i.e., E-Cadherin), whose levels are often elevated in IBC tumors. These findings suggest that the microenvironment may promote the proliferation, growth and invasion of IBC tumors.

"Our system could be used to predict the in vivo behavior of cells and to study the signaling mechanisms that are responsible for tumor-microenvironment interactions in IBC cancer," Cukierman says. "We have some gene candidates that we believe are responsible for the degree of aggressiveness we observe in the 3D model, so we would like to manipulate these genetically using mutants or pharmacologically using inhibitors to block the proteins that we believe are responsible. If that reverses the aggressiveness, it could give us a good hint of what types of targets we could perhaps try to develop and bring to the clinic in the future."

 

###

Co-investigators on this study include Xiaoshen Dong, Janusz Franco-Barraza, Zhaomei Mu, R. Katherine Alpaugh and Massimo Cristofanilli from Fox Chase.

Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet status for excellence three consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach.  For more information, visit Fox Chase's Web site at www.foxchase.org or call 1-888-FOX CHASE or (1-888-369-2427).

 

Studies assess genetics, modified treatment to improve outcomes, reduce toxicity

(ATLANTA, December 8, 2012) – Research identifying genetic factors that affect survival of patients with blood cancers and evaluating the effectiveness of modified treatment strategies to improve outcomes while reducing toxicity will be presented today at the 54th Annual Meeting of the American Society of Hematology (ASH).

While the cancer research community has seen many significant therapeutic advances over the last decade, only recently have investigators identified how patients' individual genetic makeup influences their short- and long-term response to therapy, demonstrating that while the disease may respond positively to therapy, the patient may not. Current studies take these insights a step further, examining specific patient subpopulations to determine their risk for negative outcomes and whether early preventive interventions or treatment adjustments may help avoid treatment-related toxicity.

"Data presented today offer important insights into how and why patients respond to blood cancer treatment," said William G. Woods, MD, moderator of the press conference, Pediatric Hematology/Oncology Director, and the Daniel P. Amos Children's Chair of the Aflac Cancer Center and Blood Disorders Service at Children's Healthcare of Atlanta. "Findings from these studies help further support the notion of one day personalizing cancer treatment to the individual, rather than to the disease, to improve survival and reduce toxicity."

This press conference will take place on Saturday, December 8, 2012, at 10:00 a.m. EST.

WT1 SNP rs16754 Genotype Predicts Treatment Related Mortality (TRM) in African-American and Asian Pediatric AML Patients: A Report From the Children's Oncology Group[Abstract 1385]

New research suggests that the presence of a specific genetic marker, known as WT1 SNP rs16754, may be associated with reduced toxicity from chemotherapy in African-American and Asian children with acute myeloid leukemia (AML).

AML, the second most common form of leukemia in children, is a blood cancer in which the bone marrow makes a large number of abnormal white blood cells that crowd out other healthy blood cells over time, leading to infection, anemia, or excessive bleeding. Although 60 to 70 percent of children with AML achieve long-term remission after treatment with multi-agent chemotherapy, the treatment-related mortality (TRM) associated with this intensive treatment regimen remains a major concern for this patient population. Recently, researchers have developed models that use sophisticated genome sequencing techniques to better understand how patients' genetic makeup may influence their risk of TRM.

The WT1 gene, a tumor suppressor that regulates cell growth, can be subject to "loss-of-function" mutations that lead to the development of AML. Unlike genetic mutations, single-nucleotide polymorphisms (SNPs, naturally occurring variations in the DNA that determine an individual's unique genetic makeup) are not typically thought to play a role in leukemia development or treatment response. However, researchers recently discovered that the presence of SNP rs16754 in the WT1 gene is correlated with improved outcomes in pediatric patients with AML. Based on the fact that the frequency of SNP rs16754 varies by race, researchers assessed the effect of this SNP on outcomes in specific ethnic patient groups.

To determine if the presence of SNP rs16754 affected survival, remission, relapse risk, and TRM in pediatric AML patients of different ethnicities, a team of investigators analyzed the DNA of 492 children with AML enrolled in the CCG-2961 protocol, a Phase III Children's Cancer Group trial. The intensive treatment regimen delivered to patients during CCG-2961 allowed researchers to study the effects of ethnicity on patient outcome, while minimizing non-biological influences such as access to care or oral medication compliance. Of the 492 patients, 138 (28%) had the SNP rs16754 (SNP+). After stratifying the patients by ethnicity, the investigators found that the presence of SNP rs16754 varied by race, with 53 percent of Asians, 34 percent of Hispanics, 25 percent of Caucasians, and 21 percent of African Americans carrying the genetic variation. The SNP+ patients had higher five-year overall survival rates than those without the variation (SNP-) (61% vs. 44%). Within each racial subgroup, the five-year overall survival rate was higher in the SNP+ patients.

Although survival improvements in leukemia clinical trials are often attributed to increased remission rates or decreased relapse, remission and relapse rates did not differ significantly between SNP+ and SNP- patients in this study. The investigators examined whether the SNP had any association with TRM and found that TRM rates did not differ by SNP rs16754 genotype when all ethnicities were considered together. However, TRM rates in SNP+ African-American and Asian patients, when taken together, were significantly lower than in SNP- patients of those two ethnicities. African-American and Asian patients without SNP rs16754 had significantly higher rates of treatment-related toxic death compared to SNP+ patients (African-American: 25% vs. 0%; Asian: 43% vs. 0%). These results suggest that the protective effect of the presence of SNP rs16754 in reducing chemotherapy-related toxicity in pediatric AML patients is more pronounced in those of African-American and Asian descent.

"Identifying the patient-specific factors that can affect responses to treatment in different patients with the same disease brings us closer to our goal of designing personalized treatments that provide the most therapeutic benefit with the least amount of toxicity to these children," said Phoenix Ho, MD, lead author and Attending Physician at Seattle Children's Hospital in the Division of Pediatric Hematology/Oncology at the University of Washington School of Medicine and Research Associate at the Fred Hutchinson Cancer Research Center in Seattle. "Our analysis was conducted on a trial completed in 2002, and treatment protocols for pediatric AML have evolved since that time. Our next step is to validate our findings by studying this same association in contemporary trials. We are also designing studies to uncover the mechanism behind the association between the SNP and reduced toxicity, with the hope of translating these findings into improved treatments for pediatric AML."

Dr. Ho will present this study in a poster presentation on Saturday, December 8, at 5:30 p.m. EST at the Georgia World Congress Center in Hall B1-B2, Level 1, Building B.

Genetic Susceptibility to Anthracycline-Related Congestive Heart Failure (CHF) in Survivors of Hematopoietic Cell Transplantation (HCT)[Abstract 589]

Researchers have identified specific genetic factors that are associated with heart failure in patients who have undergone hematopoietic stem cell transplantation (HCT) for blood cancer.

The transplantation of blood-forming stem cells from the bone marrow, circulating blood, or umbilical cord blood is the primary treatment option for many patients with blood cancer who relapse after receiving standard front-line therapies. During the transplant, healthy stem cells replace damaged cells that caused the illness, effectively curing patients of their disease. Advances in transplant strategies have led to a growing number of long-term survivors of HCT. However, this growing population of survivors is at risk for developing life-threatening complications such as congestive heart failure, due in large part to their exposure to pre-HCT treatments with a class of chemotherapy drugs called anthracyclines. Transplant survivors tend to develop heart failure earlier than the general population, and the overall survival rate following diagnosis is less than 50 percent.

By analyzing transplant patient demographics such as age and gender, treatment strategy (i.e., pre-HCT chemotherapy and chest radiation), and presence of cardiovascular risk factors such as high blood pressure, diabetes, and high cholesterol, researchers have been able to create a clinical profile to determine which patients are likely to develop heart failure after transplant. However, this current profile is limiting, as it fails to accurately explain the wide variability in the risk of heart failure between individual patients. Importantly, it does not account for how individuals' genetic makeup can exacerbate their risk of developing heart failure.

Seeking additional insight into how genetics can influence the risk for developing heart failure later in life, researchers conducted a case-control study to identify the genetic pathways that may make certain transplant survivors more sensitive to the toxicities of pre-transplant chemotherapy and subsequently increase their risk of heart failure. In this study, the investigators evaluated specific genes responsible for the breakdown of anthracyclines into toxic byproducts (CBR1, CBR3, NQO1, MRP1, and MRP2), defense from oxidative stress, a condition that causes damage to healthy heart cells (NCF4, RAC2, CYBA, SOD), iron overload (HFE), and blood pressure and heart rate regulation (AGT, AGTR1, ACE and ADRB1, ADRB2) in 77 patients with leukemia, lymphoma, and myeloma who underwent a transplant at City of Hope between 1988 and 2007 and later developed congestive heart failure. Investigators matched the survivors with 178 controls (transplant survivors who did not experience heart failure).

After comparing the genetic makeup of the transplant survivors who developed heart failure to their controls, researchers found that patients who had variations in the MRP2, RAC2, and HFE genes had up to a three-fold higher risk of developing heart failure after transplant; these genes are responsible for key proteins that regulate the metabolism of anthracyclines and defense against oxidative stress. Females with two or more genetic variations were at the highest risk of developing the conditions when compared to males with one or none of these variations. The discovery of these genetic variations supplements previously identified clinical variables known to affect a transplant survivor's heart health.

"Following this study we now have a much better profile of those transplant survivors who are likely to develop heart failure," said Saro Armenian, DO, MPH, lead author and Assistant Professor in the Division of Outcomes Research and Medical Director of the Pediatric Survivorship Clinic in the Childhood Cancer Survivorship Program at City of Hope in Duarte, Calif. "Armed with these insights, we can now create better screening measures and perhaps even tailor intervention strategies based on a patients' genetic makeup, minimizing long-term transplant-related toxicity and making a tremendous difference in the long-term health of these patients."

Dr. Armenian will present this study in an oral presentation on Monday, December 10, at 2:45 p.m. EST at the Georgia World Congress Center in Room C108-C109, Level 1, Building C.

Daunorubicin or Not During the Induction Treatment of Childhood Standard-Risk B-Cell Precursor Acute Lymphoblastic Leukemia (SR-BCP-ALL): The Randomized Fralle 2000-A Protocol[Abstract 135]

New data demonstrate that omitting the chemotherapy drug daunorubicin from an initial treatment regimen for children with standard-risk acute lymphocytic leukemia (ALL) does not reduce survival outcomes, suggesting that these children may be able to achieve positive outcomes without having to endure a treatment associated with both short- and long-term toxicities.

ALL, the most common form of leukemia in children, is a fast-growing cancer of the white blood cells in which the bone marrow makes a large number of abnormal white blood cells that are unable to develop and fight infection. Important developments over the past 20 years have led to seminal insights about ALL in children, and today nearly 90 percent of children diagnosed with standard-risk ALL are cured. Some treatment regimens for standard-risk ALL include initial infusions of daunorubicin, a type of anthracycline. While effective, continual use of this therapy is associated with potential long-term heart damage, leading researchers to assess whether eliminating or reducing the dosage of daunorubicin during the initial one-month induction therapy period might provide the same level of efficacy as the standard treatment protocol with reduced long-term risk.

In order to assess the efficacy of ALL treatment without daunorubicin during induction therapy, a team of researchers from 20 centers across France and one center in Belgium initiated a multicenter Phase III clinical trial in which 1,128 pediatric patients with standard-risk B-cell ALL were randomized into two treatment arms. Arm A included 560 patients who received a standard dose of daunorubicin during induction therapy, while Arm B included 568 patients who did not receive initial therapy with daunorubicin. Both groups received doxorubicin during  delayed intensification (last treatment phase before reaching maintenance) and a standard protocol of 24-month maintenance therapy from December 2000 to June 2010, during which five-year event-free survival (EFS) and overall survival (OS) were assessed.

For those patients treated with daunorubicin, the five-year EFS rate was 92.9 percent, compared to 93.3 percent in the non-daunorubicin arm. Overall survival rates were 97.2 percent and 98.2 percent in the daunorubicin and non-daunorubicin arms, respectively. Measurements of minimal residual disease, in which a small number of leukemic cells remain during treatment, were also equivalent in the two study arms. These results demonstrate similar efficacy rates of treatment strategies for standard-risk ALL that do or do not include induction treatment with daunorubicin.

"Our study data have the potential to benefit children with ALL in two important ways," said Andre Baruchel, MD, lead author and Head of the Department of Pediatric Hematology at the Robert Debré University Hospital (Assistance Publique Hôpitaux de Paris) in Paris. "First, we now have strong evidence that reducing the amount of chemotherapy initially administered to these children, who constitute the majority of ALL patients, does not negatively affect their immediate outcome. Perhaps more importantly, we know and anticipate that removing harmful chemotherapy from their treatment can help minimize their risk of experiencing heart damage later in life."

Dr. Baruchel will present this study in an oral presentation on Sunday, December 9, at 5:00 p.m. EST at the Georgia World Congress Center in Room A103, Level 1, Building A.

ATRA and Arsenic Trioxide (ATO) Versus ATRA and Idarubicin (AIDA) for Newly Diagnosed, Non High-Risk Acute Promyelocytic Leukemia (APL): Results of the Phase III, Prospective, Randomized, Intergroup APL0406 Study by the Italian-German Cooperative Groups Gimema-SAL-AMLSG [Abstract 6]

New research demonstrates the efficacy of the first curative treatment for acute promyelocytic leukemia (APL) that does not include chemotherapy, marking an important step toward front-line use of targeted therapies for acute leukemia.

APL is an uncommon, yet aggressive, subtype of acute myeloid leukemia (AML) in which there are too many immature white blood cells in the bone marrow, leading to a shortage of normal white and red blood cells and platelets in the blood, which is associated with clotting defects that can cause serious bleeding. Without prompt diagnosis and treatment, APL can be fatal in a matter of hours or days.

Early treatment regimens for APL relied heavily on anthracycline-based chemotherapy with daunorubicin or idarubicin. In the early 1990s, research supported the addition of a non-chemotherapeutic agent, all-trans-retinoic acid (ATRA, a vitamin A derivative developed from ancient Chinese herbal medicine), to standard regimens. ATRA causes cancer cells to develop fully into mature blood cells, which progress through full differentiation and eventually die (unlike leukemia cells that are unable to fully mature). The combination regimen of chemotherapy and ATRA dramatically improved the survival outlook for those with APL and made the disease curable in up to 80 percent of patients. More recently, another natural compound, arsenic trioxide (ATO), was integrated into APL treatment, showing higher efficacy and better tolerability when compared with conventional chemotherapy. Today, as investigators continue to report the success of targeted cancer therapies (best exemplified by imatinib for chronic myeloid leukemia), researchers have questioned whether traditional toxic chemotherapy is still necessary to achieve high cure rates for patients with APL.

To investigate whether a combination of ATO+ATRA could provide the same therapeutic benefit as conventional treatment including chemotherapy, researchers from the Italian-German cooperative teams Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), Study Alliance Leukemia (SAL) group, and German-Austrian AML Study Group (AMSLG) designed a multicenter, international Phase III trial in which 162 patients with standard-risk APL were divided into two treatment arms. Patients in Arm A received a regimen of ATO+ATRA, while patients in Arm B received the standard ATRA+idarubicin (AIDA) treatment regimen. The primary study objective was event-free survival (EFS) at two years, with secondary objectives including overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) rates, molecular response, and safety.

Results suggest that the targeted ATO+ATRA therapy strategy might offer similar efficacy to the chemotherapy-based regimen. In the 154 patients who were evaluable for response, complete remission was achieved in all patients (100%) in the ATO+ATRA arm and 95 percent in the AIDA arm. EFS was observed in 97 percent in the ATO+ATRA arm, with one death and two relapses, compared to 86.7 percent in the AIDA arm, in which seven deaths and four relapses were observed. Overall survival, DFS, and CIR rates were 98.7 percent, 97 percent, and 1.6 percent, respectively, in the ATO+ATRA arm, versus 91.1 percent, 91.6 percent, and 4.3 percent, respectively, in the AIDA arm. Additionally, fewer side effects (fever, low neutrophil and platelet counts) were observed in the ATO+ATRA arm.

"This is one of the first times that we can report the success of a treatment strategy for an acute leukemia that relies solely on targeted molecular therapy," said Francesco Lo-Coco, MD, lead author and Chairman of the APL subcommittee of the Italian GIMEMA group and Professor of Hematology at University Tor Vergata in Rome, Italy. "Our results are an important step toward the further utilization of targeted therapies for other types of leukemia, as we begin to focus on improving the overall treatment experience for patients by offering new strategies that deliver the same efficacy as traditional options with considerably lower toxicity."

Dr. Lo-Coco will present this study during the Plenary Scientific Session on Sunday, December 9, at 3:45 p.m. EST at the Georgia World Congress Center in Hall B5, Level 1, Building B.

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American Society of Hematology 54th Annual Meeting

The study authors and moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on new targeted treatment for chronic lymphocytic leukemia (CLL) and hard-to-treat blood disorders, strategies to increase the efficacy and safety of treatments for clotting disorders, and advances in stem cell technology and transplant strategies. For the complete annual meeting program and abstracts, visit www.hematology.org/2012abstracts. Follow ASH (@ASH_hematology) on Twitter (use the hashtag #ASH12 when posting tweets about the meeting) and on Facebook at www.facebook.com/AmericanSocietyofHematology for the most up-to-date information about the 2012 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 50 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. The official journal of ASH is Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, which is available weekly in print and online.

Flexible silicon solar-cell fabrics may soon become possible

		IMAGE:For the first time, a silicon-based optical fiber with solar-cell capabilities has been developed that is capable of being scaled up to many meters in length. The research, led by...Click here for more information.

For the first time, a silicon-based optical fiber with solar-cell capabilities has been developed that has been shown to be scalable to many meters in length. The research opens the door to the possibility of weaving together solar-cell silicon wires to create flexible, curved, or twisted solar fabrics. The findings by an international team of chemists, physicists, and engineers, led by John Badding, a professor of chemistry at Penn State University, will be posted by the journal Advanced Materials in an early online edition on 6 December 2012 and will be published on a future date in the journal's print edition.

The team's new findings build on earlier work addressing the challenge of merging optical fibers with electronic chips -- silicon-based integrated circuits that serve as the building blocks for most semiconductor electronic devices such as solar cells, computers, and cell phones. Rather than merge a flat chip with a round optical fiber, the team found a way to build a new kind of optical fiber -- which is thinner than the width of a human hair -- with its own integrated electronic component, thereby bypassing the need to integrate fiber-optics with chips. To do this, they used high-pressure chemistry techniques to deposit semiconducting materials directly, layer by layer, into tiny holes in optical fibers.

		IMAGE:For the first time, a silicon-based optical fiber with solar-cell capabilities has been developed that is capable of being scaled up to many meters in length. The research, led by...Click here for more information.

Now, in their new research, the team members have used the same high-pressure chemistry techniques to make a fiber out of crystalline silicon semiconductor materials that can function as a solar cell -- a photovoltaic device that can generate electrical power by converting solar radiation into direct-current electricity. "Our goal is to extend high-performance electronic and solar-cell function to longer lengths and to more flexible forms. We already have made meters-long fibers but, in principle, our team's new method could be used to create bendable silicon solar-cell fibers of over 10 meters in length," Badding said. "Long, fiber-based solar cells give us the potential to do something we couldn't really do before: We can take the silicon fibers and weave them together into a fabric with a wide range of applications such as power generation, battery charging, chemical sensing, and biomedical devices."

Badding explained that one of the major limitations of portable electronics such as smart phones and iPads is short battery life. Solar-boosted batteries could help solve this problem. "A solar cell is usually made from a glass or plastic substrate onto which hydrogenated amorphous silicon has been grown," Badding explained. "Such a solar cell is created using an expensive piece of equipment called a PECVD reactor and the end result is something flat with little flexibility. But woven, fiber-based solar cells would be lightweight, flexible configurations that are portable, foldable, and even wearable." This material could then be connected to electronic devices to power them and charge their batteries. "The military especially is interested in designing wearable power sources for soldiers in the field," Badding added.

The team members believe that another advantage of flexibility in solar-cell materials is the possibility of collecting light energy at various angles. "A typical solar cell has only one flat surface," Badding said. "But a flexible, curved solar-cell fabric would not be as dependent upon where the light is coming from or where the sun is in the horizon and the time of day."

Pier J. A. Sazio of the University of Southampton in the United Kingdom and one of the team's leaders added, "Another intriguing property of these silicon-fiber devices is that as they are so compact, they can have a very fast response to visible laser light. In fact, we fabricated fiber-based photodetectors with a bandwidth of over 1.8 GHz."

###

In addition to Badding and Sazio, other researchers who contributed to this study include lead author Rongrui He, Todd D. Day, Mahesh Krishnamurthi, Justin R. Sparks, and Venkatraman Gopalan from Penn State.

The research was funded by the National Science Foundation, Penn State's Materials Research Institute Nano Fabrication Network, and the United Kingdom's Engineering and Physical Sciences Research Council (EPSRC).

[ Katrina Voss ]

CONTACTS

 

John Badding:  814-777-3054 (mobile), jbadding@pearl.chem.psu.edu

Pier J. A. Sazio:  44-23-8059-3144, pjas@orc.soton.ac.uk

Barbara Kennedy (PIO): 814-863-4682, science@psu.edu

IMAGES

 

High-resolution images associated with this research are online at http://www.science.psu.edu/news-and-events/2012-news/Badding12-2012.

CAPTIONS

 

1. A cross-sectional image of the new silicon-based optical fiber with solar-cell capabilities. Shown are the layers -- labeled n+, i, and p+ -- that have been deposited inside the pore of the fiber.

2. A coiled strand of a meter-long solar-cell junction fiber, thinner than the width of a human hair, which has been created by a team of chemists, physicists, and engineers led by John Badding at Penn State University.

CREDIT

 

Badding lab, Penn State University

GRANT NUMBERS

 

Engineering and Physical Sciences Research Council (EP/G028273/1 and EP/I035307/1), National Science Foundation (DMR-0806860 and DMR-1107894), and the Penn State Materials Research Science and Engineering Center (NSF DMR-0820404)

 

 

 

 

 

 

 

New evidence for epigenetic effects of diet in healthy ageing

6 December, 2012

New research in human volunteers has shown that molecular changes to our genes, known as epigenetic marks, are driven mainly by ageing but are also affected by what we eat.

The study showed that whilst age had the biggest effects on these molecular changes, selenium and vitamin D status reduced the accumulation of epigenetic changes, and high blood folate and obesity increased them. These findings support the idea that healthy ageing is affected by what we eat.

Dr Nigel Belshaw

Researchers from the Institute of Food Research led by Dr Nigel Belshaw, working with Prof John Mathers and colleagues from Newcastle University, examined the cells lining the gut wall from volunteers attending colonoscopy clinic. The Institute of Food Research is strategically funded the Biotechnology and Biological Sciences Research Council and this study was also funded by the Food Standards Agency.

The study volunteers were free from cancer or inflammatory bowel disease and consumed their usual diet without any supplements. The researchers looked for specific epigenetic modifications of the volunteers’ genes that have been associated with the earliest signs of the onset of bowel cancer – an age-related disease. These epigenetic marks, known as DNA methylation, do not alter the genetic code but affect whether the genes are turned on or off. These methylation marks are transmitted when cells divide, and some have been associated with the development of cancer.

The investigators studied the relationship between the occurrence of these epigenetic marks at genes known to be affected in cancer, and factors including the volunteers’ age, sex, body size and the levels of some nutrients in the volunteers’ blood. The biggest influence on gene methylation was age. This fits with the fact that the biggest risk factor for bowel cancer is age, with risk increasing exponentially over 50 years old.

The findings, published in the journal Aging Cell, showed that men tended to have a higher frequency of these epigenetic changes than women, which is consistent with men being at a greater risk of bowel cancer. Volunteers with higher vitamin D status tended to show lower levels of methylation, and a similar effect was observed for selenium status. Again, this is consistent with the known links between higher vitamin D and selenium and reduced bowel cancer risk.

The B vitamin folate is essential for health, but in this study, high folate status was associated with increased levels of epigenetic changes linked with bowel cancer.   These findings are consistent with some epidemiological studies suggesting that excessive folate intakes may increase risk in some people.  The results of this study showing an association between folate status and epigenetic changes linked to cancer, together with those from another recent study by Nigel Belshaw’s group showing that, in cells grown in the laboratory, they could be induced by exposure to high levels of folic acid, emphasise the need for further research on optimal folate status in humans.  The researchers intend to investigate the mechanism for the effect of folate on DNA methylation in a follow-up study.

Obesity is also a risk factor for bowel cancer. This study found relationships between body size (height, weight and waist circumference) and epigenetic changes. How excess body weight induces these epigenetic changes, and the consequences for gut health, are currently being investigated at IFR and in Newcastle University.

In summary, the results of this study support the hypothesis that ageing affects the epigenetic status of some genes and that these effects can be modulated by diet and body fatness.

Reference:

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa, Aging Cell, doi: 10.1111/acel.12030

For more information on this, please see the article written by Nigel Belshaw and Ian Johnson on the Gut Health and Food Safety blog.

For more information on cancer and epigenetics, see:

Johnson IT, Belshaw NJ  (2008) Environment, diet and CpG island methylation: epigenetic signals in gastrointestinal neoplasia. Food Chem Toxicol. 2008 Apr;46(4):1346-59. Epub 2007 PMID:17976883

Baylin SB, Jones PA: (2011) A decade of exploring the cancer epigenome – biological and translational implications. Nat Rev Cancer 11, 726-34

Contacts:

IFR Press Office:

Andrew Chapple, 01603 251490, andrew.chapple@ifr.ac.uk

My microbes Our gut bacteria’s collection of genomes is unique, and remains stable over time

My microbes

• PR_05Dec12_My_microbes
• PR05Dec12_Mikroben_ganz_persönlich

In a nutshell :

• The gut metagenome is the collection of all the genomes of all the microbes in the
  human intestinal tract : it is specific to each human, like a second genetic
  signature
• At least in healthy humans, this personal metagenome is stable over time
• The gut metagenome is very large and complex: scientists developed innovative,
  state-of-the-art, computational tools to analyse it with a high resolution

We all have E.coli
bacteria in our gut but each of us carries a version that is genetically
slightly different. The same can be said of most gut microbes: our own gut
metagenome, that is the sum of all the genomes of all our gut microbes, appears
to be really specific to each of us, and to remain stable over time. For the
first time, researchers from the European Molecular Biology Laboratory (EMBL)
have studied this metagenome at such a high resolution that individual
mutations in the various strains could be analysed. Their findings, published
today in Nature, could have widespread consequences in medicine: gut
microbes are known to be essential for functions as vital as digesting food or
providing vitamins, but can also be involved in diseases if they carry certain
mutations.

The scientists analysed the gut metagenome
of 207 individuals from Europe and the USA, matching more than 7 billion
pieces of DNA (of 100 lettres each) to the genomes of our most abundant gut
microbial species. “This large scale analysis showed that, at least when
healthy, we carry a unique set of bacterial strains and their mutations in our
gut, over a long time,” explains Peer Bork who led the study at EMBL. “It is
like a second genetic signature, but one that probably does not come from our
parents but that we acquire from the environment in early childhood.”

When comparing the specific
mutations from the same individual over time, the researchers found that the
metagenome remains stable for at least one year, and probably much longer when
the individuals are healthy. Results also show that there is only little
geographic difference when comparing metagenomes of European with
North-American individuals. This indicates that gradual adaptation is possible.

For each individual,
approximately 6 billion DNA letters of their gut metagenome have been analysed,
many more than the 3.3 billion DNA letters of human DNA that we inherit from
each of our parents. These 6 billion DNA letters belong to hundreds of
microbes, each with thousands of different strains or variants: mapping each
DNA fragment of the metagenome to its right place, in the right bacterial
genome, is extremely complex. To achieve this breakthrough and carry the
analysis down to the single DNA letter, scientists had to develop various new
computational methods. In the current study more than 10 million mutations have
been detected in the 207 individuals.

All these detailed data is now
stored in public databases, such as dbSNP, freely available to the scientific
community. These findings could lead to the development of new approaches in
the identification of gut diseases, pathogens, or antibiotic resistance. On the
longer term, they may also open new avenues for personalised therapies.

Further information:

More
information on the research projects of the Bork group

Previous research on the gut microbiome by Peer Bork

My Microbes project - discover your gut type

Source Article

Genomic variation landscape of
the human gut microbiome

Siegfried Schloissnig,
Manimozhiyan Arumugam, Shinichi Sunagawa, Makedonka Mitreva, Julien Tap, Ana
Zhu, Alison Waller, Daniel R. Mende, Jens Roat Kultima, John Martin, Karthik
Kota, Shamil R. Sunyaev, George M. Weinstock and Peer Bork. Nature, Advanced online Publication: 5 December, 2012

Article Abstract

While large-scale efforts have
rapidly advanced the understanding and practical impact of human genomic
variation, the latter is largely unexplored in the human microbiome. We
therefore developed a framework for metagenomic variation analysis and applied
it to 252 fecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101
reference species, we detected 10.3 million single nucleotide polymorphisms
(SNPs), 107,991 short indels, and 1,051 structural variants. The average ratio
of non-synonymous to synonymous polymorphism rates of 0.11 was more variable
between gut microbial species than across human hosts. Subjects sampled at
varying time intervals exhibited individuality and temporal stability of SNP
variation patterns, despite considerable composition changes of their gut
microbiota. This implies that individual-specific strains are not easily
replaced and that an individual might have a unique metagenomic genotype, which
may be exploitable for personalized diet or drug intake.

Press Contact

Isabelle Kling,
Communications Officer

EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany

Tel:	+49 6221 387-8355
E-mail:	isabelle.kling@embl.de

Lena Raditsch, Head of Communications

EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany

Tel:	+49 6221 387-8125
E-mail:	lena.raditsch@embl.de

http://www.embl.de/aboutus/communication_outreach/media_relations/2012/121205_Heidelberg/

Feeling Disgust May Enhance Our Ability to Detect Impurities

 

Related Topics: Emotions,
Individual
Differences, Perception,
Psychological
Science, Visual
Perception

Disgust – it’s an emotion we experience when we encounter things that are
dirty, impure, or otherwise contaminated. From an evolutionary standpoint,
experiencing the intense, visceral sense of revulsion that comes with disgust
presumably helps us to avoid contaminants that can make us sick or even kill
us. But new research suggests that disgust not only helps us to avoid
impurities, it may also make us better able to see them.

If something looks dirty and disgusting, we typically assume it’s
contaminated in some way; when something is white, however, we are more likely
to assume that it’s clean and pure. Research has shown that people from many
different cultures hold this association between lightness and purity, which
may explain why we prefer white teeth, white operating rooms, and white
porcelain bathroom fixtures.

“In the psychology of purity, even the slightest deviation from a pure state
(i.e., whiteness) is an unacceptable blemish,” observe psychological scientist
Gary Sherman and his co-authors.

They hypothesized that if feeling disgust motivates people to create or
protect pure environments, it may also lead them to prioritize the light end of
the visual spectrum. For people trying to preserve cleanliness and purity, the
ability to distinguish even slight deviations from a light shade like white may
become particularly important.

Sherman, who is now at Harvard
University’s Kennedy
School of Government, and his co-authors investigated this hypothesis in three
studies, in which they tested participants’ ability to make subtle gray-scale
discriminations in both ends of the light spectrum. Their findings are
published in Psychological Science, a journal of the Association for
Psychological Science.

In their first study, 123 college students were presented with sets of
rectangles. In each set of four rectangles, one rectangle was either slightly
darker or slightly lighter than the others. The participants were asked to
indicate which of the four rectangles in each set was different from the other
three. After completing the discrimination task, they completed a survey that
measured their overall sensitivity to disgust.

In general, the students were better at identifying the rectangle that stood
out when the rectangles were presented on the dark end of the visual spectrum.
But the researchers observed a significant relationship between participants’
performance on the light end of the spectrum and their levels of trait disgust
– people who showed higher sensitivity to disgust also showed better
performance on the light end of the spectrum relative to the dark end.
Importantly, this effect was specific to disgust, as there was no such
relationship between participants’ levels of trait fear and their
discrimination performance.

These findings were confirmed in a second study, showing that students who
reported greater disgust sensitivity were better at distinguishing a faint
number set against a background of a nearly identical shade presented on the
light end of the visual spectrum relative to the dark end.

Based on these findings, Sherman
and his co-authors wondered whether disgust might actively influence what
people perceive. Based on the idea of perceptual tuning, they hypothesized that
inducing disgust would actually “tune” participants’ visual perception,
enhancing their ability to discriminate among small deviations in lightness.

In the third study, participants were presented with a slide show of
emotional images designed to elicit either disgust (i.e., images of
cockroaches, trash) or fear (i.e., images of a handgun, an angry face). They
then completed another perceptual discrimination task.

Just as in the first two studies, greater trait disgust predicted better
performance on light-end trials relative to performance on dark-end trials. But
the emotional images had different effects depending on the participants’
disgust sensitivity. For participants who were low on trait disgust, viewing
disgusting images seemed to have no effect on their discrimination performance
on either end of the spectrum. For participants who were highly sensitive to
disgust, however, viewing disgusting images significantly enhanced their
performance on light-end trials.

“Research on the experience-altering nature of emotion has typically focused
on nonperceptual experience, such as changes in cognitive appraisals. It is
clear, however, that these influences extend to perception,” the researchers
conclude.

Together, the three studies provide evidence for an interactive relationship
between disgust sensitivity and perceptual sensitivity that may ultimately help
us detect and avoid the germs, toxins, and other contaminants around us.

This research was co-authored by Gerald Clore of the University of Virginia
and Jonathan Haidt, who is now at the New York University Stern School of
Business.

 
 
 
 
 
 
 
 
 
 
 
 

###

For more information about this study, please contact: Gary D. Sherman at gary_sherman@hks.harvard.edu.

The APS journal Psychological Science is the
highest ranked empirical journal in psychology. For a copy of the article
"The Faintest Speck of Dirt: Disgust Enhances the Detection of
Impurity" and access to other Psychological Science research
findings, please contact Anna Mikulak at 202-293-9300 or amikulak@psychologicalscience.org.

Related Topics: Emotions,
Individual
Differences, Perception,
Psychological
Science, Visual
Perception

 

For Immediate Release

Contact: Anna
Mikulak

Association for Psychological Science

202.293.9300

amikulak@psychologicalscience.org

 

US Tests EMP Bomb

Game changer


Video: Doomsday for Iran? US Tests EMP Bomb

http://www.youtube.com/watch?feature=player_embedded&v=fhZLkmQ0jUE#!


Boeing has successfully tested an EMP missile that could be doomsday for Iran; media
have largely ignored the development.


By Tzvi Ben Gedalyahu


December 05, 2012 "Israel National News"
-- Boeing has successful tested an electro-magnetic pulse (EMP) missile that turns “science fiction into science fact” and could be the doomsday weapon against Iran, but media have largely
ignored the development.

The U.S. Air Force and Boeing demonstrated the device more than two months ago over a military site in the Utah desert, reported the VR-Zone technology website.

Boeing did not keep the test a secret, but most mainstream media and technology sites overlooked the report.

The test was codenamed CHAMP --Counter-Electronics High Power Advanced Missile Project and was the first time a real EMP missile has been tested with positive real world results.

One of the most startling developments in the research and test
is that the missile system does not use any explosives, thereby limiting damage
to its intended goal of directing microwave energy that can cause instant
blackouts.

Keith Coleman, who serves as Boeing’s CHAMP program manager in their Phantom Works division, stated that video camera showed “images of numerous desktop computers running, and then
suddenly all of them go out quickly followed by the camera going to black,”
VR-Zone reported.

“We hit every target we wanted to... Today we made science fiction, science fact,” said Coleman.

An Arutz Sheva opinion article in August mentioned Israel's  possible use of an EMP bomb against Iran. The report triggered a chain reaction, allegedly influencing U.S. intelligence sources who have since been quoted in several publications with doubtful assumptions that the article reflected Israel government thinking.

The London Times subsequently reported that an EMP bomb could cripple Iran by shutting down its electronics and sending the Islamic Republic “back to the Stone Age.”

EMP causes non-lethal gamma energy to react with the magnetic field and produces a powerful electromagnetic shock wave that can destroy electronic devices, especially those used in Iran’s nuclear plants.

The shock wave would knock out Iran’s power grid and communications systems for transport and financial services, leading to economic collapse.


Boeing has successfully tested an EMP missile that could be doomsday for Iran;
media have largely ignored the development.

http://www.informationclearinghouse.info/article33238.htm

 

Salk Scientists Develop Faster, Safer Method for Producing Stem Cells

Salk Scientists Develop Faster, Safer Method for Producing Stem Cells

Released: 12/3/2012 6:00 PM EST 
Source: Salk Institute for Biological Studies

 http://www.newswise.com/articles/view/596822/?sc=dwhn

The new method boosts cell yields and increases safety, helping to get another step closer to regenerative medicine

Newswise — LA JOLLA, CA---- A new method for generating stem cells from mature cells promises to boost stem cell production in the laboratory, helping to remove a barrier to regenerative medicine therapies that would replace damaged or unhealthy body tissues.

The technique, developed by researchers at the Salk Institute for Biological Studies, allows for the unlimited production of stem cells and their derivatives as well as reduces production time by more than half, from nearly two months to two weeks.

"One of the barriers that needs to be overcome before stem cell therapies can be widely adopted is the difficulty of producing enough cells quickly enough for acute clinical application," says Ignacio Sancho-Martinez, one of the first authors of the paper and a postdoctoral researcher in the laboratory of Juan Carlos Izpisua Belmonte, the Roger Guillemin Chair at the Salk Institute.

They and their colleagues, including Fred H. Gage, professor in Salk's Laboratory of Genetics, have published a new method for converting cells in this week's Nature Methods.

Stem cells are valued for their "pluripotency," the ability to become nearly any cell in the body. Stem cells for research and clinical uses are derived in two ways, either directly from cells young enough to still be pluripotent, or from mature cells that have been "reprogrammed" to be pluripotent.

The first kind are called "embryonic stem cells," (ESCs) even though the term is a misnomer. They are actually taken from blastocysts, the hollow bundle of cells approximately the size of a tip of a pin that is formed by a fertilized egg after five days of cell division. After a blastocyst implants in the uterus, the embryo stage begins.

Aside from the well-known ethical controversies, ESCs have a less discussed problem: Tissues grown from ESCs may trigger immune reactions when they are transplanted into patients.

In order to overcome both ethical and medical concerns, scientists learned how to coax mature cells (called "somatic cells") that had differentiated into particular types of tissue back to their pluripotent state. These so-called "induced pluripotent stem cells," or iPSCs, set off whole new rounds of research, including a third way to get desired cell types.

As it turns out, iPSCs have their own problems. They take a long time to create in the lab, in a highly inefficient process that can take up to two months to complete. First, somatic cells must be reprogrammed to iPSCs, which takes considerable time and effort. Then, the iPSCs have to be differentiated into specific cell lineages prior to therapeutic application. Far worse, they can sometimes develop into tumors, called teratomas, which can be cancerous.

Knowing this, scientists wondered if it might not be necessary to go all the way back to the blank slate of a pluripotent stem cell. Key to this idea is that pluripotent stem cells do not immediately grow into particular cells. They go through intermediate progenitor phases where they become "multipotent," and can only develop into cell types within a certain cellular lineage. While a pluripotent cell can become nearly any cell in the body, a multipotent blood cell, for example, can become red or white blood cells or platelets, but not distant lineages such as neurons.

Thus, in order to avoid the potential problems of working with iPSCs, scientists developed the technique of "direct lineage conversion." Unlike the familiar scenario, in which a pluripotent cell would divide and generate all different cell types of an adult individual, in direct lineage conversion one somatic cell is turned into just one other cell type, thus, for example, one skin cell becomes one muscle cell, but nothing else.

While this technique is effective, the Salk team and their colleagues wondered if there might be a modification that could be both more efficient and safer.

"Beyond the obvious issue of safety, the biggest consideration when thinking about stem cells for clinical use is productivity," says Salk post doctoral researcher Leo Kurian, a first co-author on the paper.

The team developed a new technique, which they dubbed "indirect lineage conversion" (ILC). In ILC, as explained in detail in Nature Methods, somatic cells are pushed back to an earlier state suitable for further specification into progenitor cells.

ILC has the potential to generate multiple lineages once cells are transferred to the team's specially developed chemical environment. Most importantly, ILC saves time and reduces the risk of teratomas by not requiring iPSC generation. Instead, somatic cells are directed to become the progenitor cells of particular lineages. "We don't push them to zero, we just push them a bit back," Sancho-Martinez says.

Using ILC, the group reprogrammed human fibroblasts (skin cells) to become angioblast-like cells, the progenitors of vascular cells. These new cells could not only proliferate, but also further differentiate into endothelial and smooth muscle vascular lineages. When implanted in mice, these cells integrated into the animals' existing vasculature.

"One of the long-term hopes for stem cell research is exemplified by this study, where stem cells would self-assemble into 3D structures and then integrate into existing tissues," says Juan Carlos Izpisua Belmonte.

While such clinical use may be years away, this new method has several advantages over current techniques, he explains. It is safer, since it does not seem to produce tumors or other undesirable genetic changes, and results in much greater yield than other methods. Most important, it is faster, and this is part of what makes it not only more productive, but less risky.

"Generally it can take up to two months to create iPSCs and their differentiated derivatives, which increases the chances for mutations to take place," says Emmanuel Nivet, the third of the first co-authors. "Our method takes only 15 days, so we've substantially decreased the chances for spontaneous mutations to take place."

Other researchers on the study were: Aitor Aguirre, Krystal Moon, Caroline Pendaries, Cecile Volle-Challier, Francoise Bono, Jean-Marc Herbert, Julian Pulecio, Yun Xia, Mo Li, Nuria Montserrat, Sergio Ruiz, Ilir Dubova, Concepcion Rodriguez, Ahmet M. Denli, Francesca S. Boscolo, Rathi D. Thiagarajan, Jeanne F. Loring and Louise C. Laurent.

The work was supported by: the California Institute for Regenerative Medicine; the F.M. Kirby Foundation; National Institutes of Health; the Hartwell Foundation; the Millipore Foundation; the Esther O'Keeffe Charitable Trust Foundation; Fundacion Cellex; the G. Harold and Leila Y. Mathers Charitable Foundation; The Leona M. and Harry B. Helmsley Charitable Trust, Sanofi; and the Ministerio de Economia y Competitividad.

About the Salk Institute for Biological Studies:

The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.