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Post Traumatic Stress Disorder (PTSD)

#PTSD PTSD is triggered by excess oxidative stress or free radicals which are neutralised by Carbon 60 hydrated fullerenes, the highest natural  antioxidant in the world https://www.academia.edu/11621073/Backgrounder_on_Carbon_60_Hydrated_Fullerenes_V6

PTSD and Oxidative Stress-Connect the DOTS

 

Reference (1)

Coll Antropol. 2011 Dec;35(4):1155-60.

Oxidative stress markers in patients with post-traumatic stress disorder.

Ceprnja M¹, Derek L, Unić A, Blazev M, Fistonić M, Kozarić-Kovacić D, Franić M, Romić Z.

Author information

• ¹University of Zagreb, Dubrava University Hospital, Clinical Department of Laboratory Diagnostics, Zagreb, Croatia. [email protected]

Abstract

Recent study data support the role of oxidative stress in diverse psychiatric disorders. Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. There are numerous studies that indicate that free radicals (FRs) damage neurons, and then play an important role in the pathophysiology of schizophrenia and depression. Active oxygen can cause considerable damage and disrupt the important physiological functions of proteins, lipids, enzymes and DNA. The aim of our study was to investigate the possible differences in the concentration of tromboxane B2, 8-OHdG and protein carbonyls, as significant markers of oxidative damage, and urate, albumin and total protein concentrations as antioxidative molecules in PTSD patients in comparison to the healthy control group. The study included 74 male participants who were active soldiers in the Croatian armed forces from 1991 to 1995. 46 subjects with chronic and current PTSD were recruited from the Department of Psychiatry of Dubrava University Hospital during 2010, 28 healthy subjects were recruited in the same period during the regular medical examination at the Dubrava University Hospital.

Reference (2)

Curr Neuropharmacol. Mar 2014; 12(2): 193–204.

Published online Mar 2014. doi:  10.2174/1570159X11666131120223530

PMCID: PMC3964749

Oxidative Imbalance and Anxiety Disorders

Krolow R,^* Arcego D. M, Noschang C, Weis S. N, and Dalmaz C^*

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil

^* Address correspondence to these authors at the Departamento de Bioquímica, ICBS, UFRGS, Ramiro Barcelos, 2600 (Anexo) Lab. 37. 90035-003 Porto Alegre, RS, Brasil; Tel: 55 51- 3316-5570; Fax: 55 51- 3316-5535; E-mails: rb.moc.oohay@lehcarwolork, Email: rb.moc.oohay@zamladalrac

Abstract

The oxidative imbalance appears to have an important role in anxiety development. Studies in both humans and animals have shown a strong correlation between anxiety and oxidative stress. In humans, for example, the increased malondialdehyde levels and discrepancies in antioxidant enzymes in erythrocytes have been observed. In animals, several studies also show that anxiety-like behavior is related to the oxidative imbalance. Moreover, anxiety-like behavior can be caused by pharmacological-induced oxidative stress. Studies using knockout or overexpression of antioxidant enzymes have shown a relationship between anxiety-like behavior and oxidative stress. Related factors of oxidative stress that could influence anxious behavior are revised, including impaired function of different mitochondrial proteins, inflammatory cytokines, and neurotrophic factors. It has been suggested that a therapy specifically focus in reducing reactive species production may have a beneficial effect in reducing anxiety. However, the neurobiological pathways underlying the effect of oxidative stress on anxiety symptoms are not fully comprehended. The challenge now is to identify the oxidative stress mechanisms likely to be involved in the induction of anxiety symptoms. Understanding these pathways could help to clarify the neurobiology of the anxiety disorder and provide tools for new discovery in therapies and preventive strategies.

Keywords: Antioxidants, anxiety disorders, anxiolytics drugs, genetics, inflammation, mitochondrial, neurotrophic factor, reactive species.

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INTRODUCTION

Anxiety is defined as a state of uneasiness and apprehension. It is a general term that describes a large range of related and commonly experienced subjective mental states which are normally evoked by a wide range of external and internal stressors. Anxiety is a normal emotional response but when it is inappropriate (at in inappropriate time or to an inappropriate degree, and is disruptive to the individual), it then constitutes an anxiety disorder [1, 2]. This condition is implicated in a number of psychiatric disorders, such obsessive compulsive disorder (OCD), panic disorder (PD), social phobias (SP), generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD) [1].

 

Oxidative stress and Cancer Metastasis

Oxidative stress and Cancer Metastasis

Research has shown that 90% of all cancer deaths are due to cancer metastasis. Cancer can only spread in the body when we have an environment of excess free radicals or oxidative stress. An ultra-high, universal, antioxidant like Carbon 60 hydrated fullerenes neutralize free radicals and prevent cancer metastasis.

 

Factsheet #6 Link between Oxidative Stress, Free Radicals and Cancer v4

 

https://www.academia.edu/12211177/Factsheet_6_Link_between_Oxidative_Stress_Free_Radicals_and_Cancer_v4

Longevity and Healthy Aging

Aging Gracefully without Chronic Human Diseases

Time Magazine and National Geographic both recently ran cover stories with a baby on the cover. The tagline reads: This baby could live to be 142 years old. So the question that immediately comes to mind  is: Is this possible  and can everyone age gracefully without chronic human diseases? And can we do it with today’s technology ?

To explore this question we first need to compare the mortality in 1900 versus today. In 1900, half of the deaths were caused by pneumonia, influenza, tuberculosis, gastrointestinal infections.  These diseases were cured largely with antibiotics and antivirals after world war two. Cancer, diabetes, coronary  heart disease, and Alzheimer’s were present but  not near the rates we see today.  Now, the top causes of death today, according to US statistics are heart disease, lung cancer, lung disease (asthma) , stroke, Alzheimer’s,  diabetes  and hypertension. An interesting question to ask would be: Do all these new, twenty first century diseases all have something in common, just like the top causes of death  in 1900 where from bacterial or viral sources?  A review of the medical literature shows two primary causes. In turns out that most chronic human diseases are 1) triggered by excess free radicals or oxidative stress and 2) are the result of a lack of essential minerals and trace minerals and cofactors in our diets.

Oxidative Stress

Free radicals or oxidative stress is the result of our cells metabolizing or breathing oxygen. Free radical are the “waste” products of life, and they are very destructive to cell membranes, proteins and DNA.  Our body has a natural protective system-antioxidant enzymes that neutralize excess free radicals. If this delicate balance is  disrupted,  this then leads to an inflammation response in the body and eventually, chronic diseases could ensue. As we age, our natural antioxidant protective systems decline and we are told to supplement with natural botanical antioxidants, such as blueberries , green tea or cinnamon or antioxidant supplements such as Vitamin E or coenzyme Q10. But then we run into the “antioxidant paradox”. All these food antioxidants  work great as antioxidants in a test tube in the lab, but in human clinical trials, the beneficial effects are either inconclusive or negative. This is because saliva and gut bacteria metabolise many these botanical antioxidants, before they have a chance to act beneficially.

Ukrainian scientists discovered the world’s highest antioxidant called Carbon 60 hydrated fullerenes, which is stable and inert and not metabolised by bacteria. Carbon 60, a natural product,  was discovered in 1985 and a Nobel prize in Chemistry was awarded for this discovery in 1996.  Scientists and doctors were calling it the panacea or silver bullet in medicine, but because it’s not naturally water soluble, just like diamonds, charcoal or activated charcoal, this frustrated scientists. Ukrainian scientist in Kharkiv the first to discovered how to dissolve Carbon 60 in water in 1994. After 20 years of preclinical, safety and clinical studies,  Carbon 60 hydrated fullerenes  were approved as a  “dietary supplement” by the Ukrainian Ministry of Health and has been on the Ukrainian market since 2010. There is now a US patent pending. Scientists are now claiming that most chronic human diseases are triggered by excess free radicals. Just do a search on PUBMED with the key words “oxidative stress” and your own disease and you will find a link. (http://www.ncbi.nlm.nih.gov/pubmed ). Reduce excess free radicals and reduce your disease symptoms. A study at the University of Paris in 2010 showed that rats feed a diet supplemented  with Carbon 60 in olive oil, increased the lifespan of rats by 90% from an average of 25-30 months to over 55 months.

Essential minerals and trace minerals.

The National Post ran a story on May 1- “Obese Canadians should be granted legal protection from discrimination, professor says.”  The obesity debate is totally missing the point. Most Doctors are ignoring their own medical research. The cause of the 400% increase in obesity in last 3 decades in Canada and sharp rise in most other chronic human diseases since the 1930’ is due to a chronic lack of essential minerals and trace minerals in our diet (plants, fruits and vegetables) that are needed as co-factors in the body for our biochemical pathways to work efficiently.

The soil minerals concentrations have been dropping  worldwide for the last 100 years, so less and less minerals are  absorbed in fruits, vegetables and other plants. This is due primarily to the fact that  we no longer cook and heat our homes with wood and throw away the ashes (95% minerals) back into the garden to replenish the soil with the 60 essential and trace minerals that our bodies need. Fertilizer only has 3 minerals. Even the nutritional supplements commonly found in most health food stores don't carry the full complement of 90  essential nutrients, which should include 60 essential minerals, 15 essential vitamins, 12 essential amino acids and 3 fatty acids and  the right doses of each and the correct easily absorbable mineral salts.

How do we know that we need 90 essential nutrients? Just talk to any veterinarian. Vets have cured over 600 chronic human diseases in farm animals and in zoo animals by supplementing their food with nutritional pellets. When was the last time you saw a cow with arthritis and a pig with Alzheimer’s?  Vets have to cure an animal after the first time otherwise beef would cost over $500 a pound or eggs $50 a dozen.  Why? Because animals don’t have health insurance. Doctors are quite content to treat your disease symptoms for the rest of your life, billing health insurance and not curing your disease after a few visits. Human  clinical studies in the past 40 years have shown that most chronic human diseases are also caused by essential mineral deficiencies and can be controlled with the proper essential and trace minerals. Diabetes has been controlled with the right amount of chromium and vanadium and other essential cofactors. Arthritis is a lack of proper calcium absorption and cofactors such as Vitamin D and magnesium. Greying hair is a copper deficiency in the diet.

So can we live to be 100 or over without chronic human diseases? Yes by reducing excess oxidative stress or free radicals in our body and ensuring that we get the right daily balance of 90 essential nutrients including 60 minerals and trace minerals.

If you would like more information on the above or a copy of my presentation on Aging Gracefully without Chronic Human Diseases that  I gave at Ukrainian Canadian Social Services last week, send me an email  [email protected] or call (416) 819-9667 or download it from this link  http://bit.ly/1KzZvm8  For Ukrainian listeners,  catch  my Ukrainian radio interview on Radio KONTAKT archives from Saturday April 25, 2015 http://www.kontaktglobal.com/radio-saturday.html

 

Walter Derzko is the president of the startup C60 Water North America

Aging Gracefully without Chronic Human Diseases

I’m adding  a link to a presentation I gave last week to a group of seniors at the Ukrainian Canadian Social Services –Toronto Branch on Aging Gracefully without Chronic Human Diseases.  It’s designed for a non-technical,  layperson audience. You can download it from the link below.

 

https://www.academia.edu/12124838/Aging_Gracefully_without_Chronic_Human_Diseases_v4_UPDATED_

 

Enjoy and Comments Welcomed

 

Walter  Derzko

Toronto

UPDATE on the Carbon[60] Hydrated Fullerenes-The Highest Antioxidant in the World

Scientists  have made a  significant leap in cancer research.

You never change things by fighting the existing reality. To change something, build a new model that makes the existing model obsolete.

R. Buckminster Fuller

90% of all cancer deaths come from cancer spreading in the body from one organ to another, called metastasis. Stop metastasis, stop many unnecessary premature cancer deaths.

Belgium researches in 2014 determined that cancer metastasis  can only occur if there are excess free radicals in the body. Specifically they conclude: “under certain conditions, the mitochondria produce more free radicals known as superoxide ions (O2.-). It is this overproduction of superoxide that leads to the formation of metastasis and, consequently, the growth of a tumor. “ See “A world first: Researchers identify a treatment that prevents tumor metastasis (Université catholique de Louvain)”  http://www.eurekalert.org/pub_releases/2014-07/ucdl-awf072414.php

So, logically, if you can reduce excess oxidative stress and free radical levels in the body back to  normal levels, theoretically, you  should be able to prevent metastasis and reduce the risk of cancer  growth and eliminate most cancer deaths. 

This not only applies to cancer, but many other chronic human diseases, which appear to be triggered by excess free radicals too.

Just do a search on PUBMED using the term “oxidative stress” the name of any chronic human disease and you will see a connection/link  to free radicals and most diseases. See http://www.ncbi.nlm.nih.gov/pubmed

In fact, researcher in Ukraine have already reduced oxidative stress  in cancer  cases and many other chronic human diseases with a safe, natural, organic molecule, called Carbon [60] or specifically the water-soluble version, called Carbon 60 Hydrated Fullerenes, C60HYFNs. It was approved by the Ukrainian Ministry of Health in 2010, as a dietary supplement and antioxidant, after 20 years of preclinical and clinical studies.  It’s the world’s highest antioxidant and free radical scavenger,  neutralizing excess free radicals. It was discovered in 1985 and a Nobel prize in Chemistry was awarded for the discover in 1996. Two years before that,  Ukrainian researched discovered how to make Carbon[60] water-soluble, since most Carbon allotropes do not dissolve  in water.

 (see  the medical and biological properties in Carbon 60 Hydrated Fullerenes   http://www.ipacom.com/index.php/en/fullerenes-and-water-left/74 )

Most recently (Dec. 2014), Ukrainian researchers showed that C60HYFNs combined with traditional chemotherapy (Doxorubicin) , eliminates tumors in animal models without the toxic effects seen with traditional chemo. They showed that this combination: “resulted in tumor growth inhibition, prolongation of life, metastasis inhibition, and increased number of apoptotic tumor cells and was more effective than the corresponding course of Dox treatment alone.”

See C60 fullerene as synergistic agent in tumor-inhibitory Doxorubicin treatment. http://www.ncbi.nlm.nih.gov/pubmed/25504158

Carbon 60, a radiation protector,  also reduces the negative effects of traditional radiation therapy. See  Peculiarities of the antioxidant and radioprotective effects of hydrated C60 fullerene nanostuctures in vitro and in vivo.  http://www.ncbi.nlm.nih.gov/pubmed/19539750

The molecule C60 HYFNs is now US patent pending (March 2014). http://www.freepatentsonline.com/y2014/0079746.html

We are in the process of submitting the clinical studies to the FDA to get a GRAS designation to sell C60HYFNs as an antioxidant  dietary supplement in the USA, Canada and Mexico.

Walter Derzko

President

C60 Water North America

416-819-9667

Belgian Researchers Discover Way to Block Cancer Metastasis

 

Free Radicals and Cancer Metastasis

KEY QUOTE:  The Belgian team led by Sonveaux has found the mechanism by which cells can control changes caused at least in part by free radicals. The free radical involved in the metastacism of tumor cells is superoxide. Tests in mice on melanoma and breast cancer cells showed that administering an antioxidant stopped the production of superoxide. That, in turn, prevented cell changes that would lead to metastasis.

 

N.B. This is confirmation why Carbon 60 Hydrated Fullerenes stops cancer metastasis, by scavanging free radicals that cause cancer. Ukrainian scientists have known this for over ten years!!--Walter Derzko

September 18, 2014

12:28 AM                

WASHINGTON—

Cancer remains one of the deadliest diseases, despite many new methods to combat it. Modern medicine has treatments to prevent the growth of primary tumor cells. But most cancer deaths are caused by metastasis, when primary tumor cells change and move to other parts of the body. A team of Belgian scientists says it has found a way to prevent that process.

Metastasis occurs as primary tumor cells leave the tumor, get into the blood stream, pass through the circulatory system, and then find new tissue to colonize.

Belgian scientists at a research institute of the Université Catholique de Louvain say they have discovered a way to prevent the metastasis of primary tumors from breast and melanomic cancer cells in mice.

"When you have few metastases, this is still manageable for therapy. But when you have a lot of metastases all around your body, you are good for palliative care, it's sad to say so. So what we've found is a treatment able to prevent metastases. Of course, this offers a high hope for patients which are at risk for metastases," said Professor Pierre Sonveaux of the Université Catholique de Louvain.

Cancer specialists say metastasis is a complicated process about which much is still unknown.

"For instance, cells have to change their shapes in order to metastasize, and we don't understand basic questions about how cells can change their shape," said the Institute of Cancer Research’s Chris Bakal.

The Belgian team led by Sonveaux has found the mechanism by which cells can control changes caused at least in part by free radicals. The free radical involved in the metastacism of tumor cells is superoxide. Tests in mice on melanoma and breast cancer cells showed that administering an antioxidant stopped the production of superoxide. That, in turn, prevented cell changes that would lead to metastasis.

"In some of these models, we found 100 percent response. It means that we prevented by 100 percent the dissemination of metastases. When you are a scientist and when you find this, you just fall on the ground. This is a very nice result," said Sonveaux.

The research, published in the journal Cell Reports, has drawn praise from other scientists. Bakal said the findings could lead to the development of a therapy to prevent the spread of metastatic cancer cells by blocking pathways to free radicals.

"What it suggests is that by targeting these pathways, these free radical pathways, it could represent a way, a therapeutic avenue, by which to inhibit metastasis, which we weren't necessarily clear of before. So if we lower the amount of free radicals in metastatic cells, it suggests we could prevent metastasis," said Bakal.

Belgian researchers say they now want to find out if this strategy can be applied to prevent metastasis of other tumors, such as colon cancer, lung cancer and prostate cancer. The next step would be developing the necessary drugs and starting clinical trials on cancer patients.

New non-invasive technique could revolutionize the imaging of metastatic cancer

 

 

		IMAGE:   This is Paul Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of... Click here for more information.

Bioluminescence, nanoparticles, gene manipulation – these sound like the ideas of a science fiction writer, but, in fact, they are components of an exciting new approach to imaging local and metastatic tumors. In preclinical animal models of metastatic prostate cancer, scientists at Virginia Commonwealth University Massey Cancer Center, VCU Institute of Molecular Medicine and Johns Hopkins Medical Institutions have provided proof-of-principle of a new molecular imaging approach that could revolutionize doctors' ability to see tumors that have metastasized to other sites in the body, including the bones.

Recently published in the OnlineFirst edition of the journal Cancer Research, a journal of the American Association for Cancer Research, this multiple institution study is the first to develop in vivo (in animal models) a systemically administered, non-invasive, molecular-genetic technique to image bone metastases resulting from prostate cancer. The new method relies on the detection of a gene known as AEG-1, which was originally discovered by the study's co-lead investigator Paul B. Fisher, M.Ph., Ph.D., and has been shown to be expressed in the majority of cancers but not in normal, healthy cells. In preclinical studies, the researchers were able to image bone metastases with greater accuracy than any clinically approved imaging method.

"Currently, we do not have a sensitive and specific non-invasive technique to detect bone metastases, so we are very encouraged by the results of this study" says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at the VCU School of Medicine and director of the VCU Institute of Molecular Medicine. "Additionally, because AEG-1 is expressed in the majority of cancers, this research could potentially lead to earlier detection and treatment of metastases originating from a variety of cancer types."

Imaging the expression of a gene in real time is not an easy task. To do it, the scientists used a promoter called AEG-Prom. A promoter is a set of chemical instructions coded in DNA that initiates activity in a gene. The team combined AEG-Prom with imaging agents consisting of a gene that produces firefly luciferase, the bioluminescent substance that makes fireflies glow, and a gene called HSV1tk, which initiates a chemical reaction when specific radioactive compounds are administered. The team then inserted the combination into tiny nanoparticles that are injected intravenously. When exposed to specific proteins that activate the AEG-Prom, including the c-MYC protein that is elevated in many cancer cells, the AEG-Prom initiates activity in the imaging agent, and the location of cancer cells expressing the imaging agent are made visible using sensitive imaging devices.

"The imaging agents and nanoparticle used in this study have already been tested in unrelated clinical trials. Moving this concept into the clinic to image metastasis in patients is the next logical step in the evolution of this research," says co-lead author Martin G. Pomper, M.D., Ph.D., William R. Brody Professor of Radiology at Johns Hopkins Medical Institutions. "My colleagues and I are working toward this goal, and we look forward to opening a study to deploy this technology as soon as possible."

Fisher and Pomper are pioneering the use of cancer-specific and cancer-selective gene promoters to image cancer. Previous studies in melanoma and breast cancer leveraged another gene originally discovered by Fisher called progression elevated gene-3 (PEG-3) using a promoter known as PEG-Prom. In addition to imaging, this approach could also be used to deliver therapeutic agents, such as targeted therapies, directly to local and distant tumors sites and allow physicians to monitor drug delivery in real time. Separate studies are currently under way to examine the therapeutic potential of this strategy.

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Fisher and Pomper collaborated on this research with Siddik Sarkar, Ph.D., postdoctoral research scientist in the Department of Human and Molecular Genetics at the VCU School of Medicine, as well as Akrita Bhatnagar, Ph.D., Yuchuan Wang, Ph.D., Ronnie C. Mease, Ph.D., Matthew Gabrielson, M.D., Polina Sysa, M.D., lL Minn, Ph.D., Gilbert Green, Brian Simmons, Ph.D., and Kathleen Gabrielson, D.V.M., Ph.D., all from Johns Hopkins Medical Institutions.

This study was supported by National Cancer Institute grant CA151838, the Prostate Cancer Foundation, the Patrick C. Walsh Foundation, the National Foundation for Cancer Research and, in part, by VCU Massey Cancer Center's NIH-NCI Cancer Center Support Grant P30 CA016059.

The full manuscript of this study is available online at: http://cancerres.aacrjournals.org/content/early/2014/08/21/0008-5472.CAN-14-0018.full.pdf

 

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Space: The final frontier… open to the public

 

UTMB research shows average people healthy enough for commercial space travel

Historically, spaceflight has been reserved for the very healthy. Astronauts are selected for their ability to meet the highest physical and psychological standards to prepare them for any unknown challenges. However, with the advent of commercial spaceflight, average people can now fly for enjoyment. The aerospace medicine community has had very little information about what medical conditions or diseases should be considered particularly risky in the spaceflight environment, as most medical conditions have never been studied for risk in space — until now.

The aerospace medicine group at the University of Texas Medical Branch at Galveston recently studied how average people with common medical problems — high blood pressure, heart disease, diabetes, lung diseases like asthma or emphysema and back and neck injuries, surgeries or disorders — would be able to tolerate the stresses of commercial spaceflight. Overall, they found that nearly everyone with well-controlled medical conditions who participated in this project tolerated simulated flight without problems. The study can be found in the journal Aviation, Space and Environmental Medicine.

"Physiological stresses of flight include increased acceleration forces, or 'G-forces,' during launch and re-entry, as well as the microgravity period," said lead author Dr. Rebecca Blue. "Our goal was to see how average people with common medical problems, who aren't necessarily as fit as a career astronaut, would be able to tolerate these stresses of an anticipated commercial spaceflight."

Some medical conditions are of particular interest within the commercial spaceflight industry, either because of the high rate of occurrence or because of the potential to cause sudden, serious medical events. The researchers studied how people with these common conditions performed when put through centrifuge simulations of spaceflight launch and re-entry.

The centrifuge allows researchers to mimic the acceleration of a rocket launch or of a spacecraft re-entering through the atmosphere. Astronauts regularly use centrifuges to train for their own spaceflights.  The acceleration forces expected in a commercial spaceflight profile are tolerable, but can be uncomfortable, for healthy individuals. The researchers wanted to see if they were equally tolerable for individuals with complex medical histories or whether there were certain conditions that would make it more difficult for them to handle the flight.

"This study further supports the belief that, despite significant chronic medical conditions, the dream of spaceflight is one that most people can achieve," said Blue.

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Other authors of this paper include James Pattarini, David Reyes, Robert Mulcahy, Charles Mathers, Johnené Vardiman, Tarah Castleberry and James Vanderploeg of UTMB and Alejandro Garbino of Baylor College of Medicine.

This research was supported by the Federal Aviation Administration's Center of Excellence for Commercial Space Transportation, which has designated UTMB's aerospace medicine group as a leader in research for the commercial spaceflight industry. The goal of the UTMB group is to identify the knowledge gaps regarding commercial spaceflight and to address these gaps with research to allow for science-based decision-making within the field. The team also had support from the National Space Biomedical Research Institute to complete this work.

How stress tears us apart

A team from the EPFL Brain Mind Institute has discovered an important synaptic mechanism: the activation of a cleaving enzyme, leading to behavioral problems connected to chronic stress.

		IMAGE:   Carmen Sandi's team at EPFL discovered an important synaptic mechanism in the effects of chronic stress. It causes the massive release of glutamate which acts on NMDA receptors, essential for... Click here for more information.

Why is it that when people are too stressed they are often grouchy, grumpy, nasty, distracted or forgetful? Researchers from the Brain Mind Institute (BMI) at EPFL have just highlighted a fundamental synaptic mechanism that explains the relationship between chronic stress and the loss of social skills and cognitive impairment. When triggered by stress, an enzyme attacks a synaptic regulatory molecule in the brain. This was revealed by a work published in Nature Communications.

Carmen Sandi's team went to look for answers in a region of the hippocampus known for its involvement in behavior and cognitive skills. In there, scientists were interested in a molecule, the nectin-3 cell adhesion protein, whose role is to ensure adherence, at the synaptic level, between two neurons. Positioned in the postsynaptic part, these proteins bind to the molecules of the presynaptic portion, thus ensuring the synaptic function. However, the researchers found that on rat models affected by chronic stress, nectin-3 molecules were significantly reduced in number.

The investigations conducted by the researchers led them to an enzyme involved in the process of protein degradation: MMP-9. It was already known that chronic stress causes a massive release of glutamate, a molecule that acts on NMDA receptors, which are essential for synaptic plasticity and thus for memory. What these researchers found now is that these receptors activated the MMP-9 enzymes which, like scissors, literally cut the nectin-3 cell adhesion proteins. "When this happens, nectin-3 becomes unable to perform its role as a modulator of synaptic plasticity" explained Carmen Sandi. In turn, these effects lead subjects to lose their sociability, avoid interactions with their peers and have impaired memory or understanding.

The researchers, in conjunction with Polish neuroscientists, were able to confirm this mechanism in rodents both in vitro and in vivo. By means of external treatments that either activated nectin-3 or inhibited MMP-9, they showed that stressed subjectscould regain their sociability and normal cognitive skills. "The identification of this mechanism is important because it suggests potential treatments for neuropsychiatric disorders related to chronic stress, particularly depression," said Carmen Sandi, member of the NCCR-Synapsy, which studies the neurobiological roots of psychiatric disorders.

Interestingly, MMP-9 expression is also involved in other pathologies, such as neurodegenerative diseases, including ALS or epilepsy. "This result opens new research avenues on the still unknown consequences of chronic stress," concluded Carmen Sandi, the BMI's director.

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Scientists pioneer microscopy technique that yields fresh data on muscular dystrophy

18-Sep-2014

New imaging tech lets scientists 'paint' a target in a living subject and watch it work -- with unprecedented sensitivity and precision

		IMAGE:   A new single-molecule imaging technique developed at USC provides new insights into the role of dystrophin proteins for muscle function in Caenorhabditis elegans worm models of Duchenne muscular dystrophy. Click here for more information.

Scientists at USC have developed a new microscopy technology that allows them to view single molecules in living animals at higher-than-ever resolution.

Dubbed "Complementation Activated Light Microscopy" (CALM), the new technology allows imaging resolutions that are an order of magnitude finer than conventional optical microscopy, providing new insights into the behavior of biomolecules at the nanometer scale.

In a paper published on Sept. 18 by Nature Communications, the researchers behind CALM used it to study dystrophin – a key structural protein of muscle cells – in Caenorhabditis elegans worms used to model Duchenne muscular dystrophy.

Duchenne muscular dystrophy is the most severe and most common form of the degenerative disease.

The researchers showed that dystrophin was responsible for regulating tiny molecular fluctuations in calcium channels while muscles are in use. The discovery suggests that a lack of functional dystrophin alters the dynamics of ion channels – helping to cause the defective mechanical responses and the calcium imbalance that impair normal muscle activity in patients with muscular dystrophy.

Ten Times the Precision of Optical Microscopy

CALM works by splitting a green fluorescent protein from a jellyfish into two fragments that fit together like puzzle pieces. One fragment is engineered to be expressed in an animal test subject while the other fragment is injected into the animal's circulatory system.

When they meet, the fragments unite and start emitting fluorescent light that can be detected with incredible accuracy, offering imaging precisions of around 20 nanometers. Conventional optical microscopy of living tissues can only achieve a 200 nanometer resolution at best. For scale, a sheet of paper is 100,000 nanometers thick.

"Now, for the first time, we can explore the basic principles of homeostatic controls and the molecular basis of diseases at the nanometer scale directly in intact animal models," said Fabien Pinaud, assistant professor at the USC Dornsife College of Letters, Arts and Sciences and lead researcher on the project.

Pinaud collaborated with scientists from the University Claude Bernard Lyon in France and the University of Würzburg in Germany.

Building the Tools for Tomorrow's Research

The new technology lies at the heart of the convergence of science and engineering at USC, where researchers from both fields collaborate to create the tools that make scientific and medical breakthroughs possible.

"There are trillions of proteins at work on an infinitely small scale at every moment in an animal's body. The ability to detect individual protein copies in their native tissue environment allows us to reveal their functional organization and their nanoscale molecular behaviors despite this astronomical complexity," Pinaud said.

Next, Pinaud and his colleagues will focus on engineering other colors of split-fluorescent proteins to image the dynamics of individual ion channels at neuromuscular synapses within live worms.

"It so happens that the same calcium channels we studied in muscles also associate with nanometer-sized membrane domains at synapses where they modulate neuronal transmissions in both normal and disease conditions," Pinaud said. Using multi-color CALM, his team and collaborators will probe how these tiny active zones of neurons are assembled and how they influence the function of calcium channels during neuron activation.

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This research was funded by USC startup funds and the computational work was supported by the USC Center for High-Performance Computing and Communications.