Biological and Medical Sciences

Biological and Medical Sciences 27

People who experience job loss, divorce, death of a loved one or any number of life’s upheavals often adopt coping mechanisms to make the situation less traumatic.

While these strategies manifest as behaviors, a Princeton University and National Institutes of Health study suggests that our response to stressful situations originates from structural changes in our brain that allow us to adapt to turmoil.

A study conducted with adult rats showed that the brains of animals faced with disruptions in their social hierarchy produced far fewer new neurons in the hippocampus, the part of the brain responsible for certain types of memory and stress regulation. Rats exhibiting this lack of brain-cell growth, or neurogenesis, reacted to the surrounding upheaval by favoring the company of familiar rats over that of unknown rats, according to a paper published in The Journal of Neuroscience.

The research is among the first to show that adult neurogenesis — or the lack thereof — has an active role in shaping social behavior and adaptation, said first author Maya Opendak, who received her Ph.D. in neuroscience from Princeton in 2015 and conducted the research as a graduate student. The preference for familiar rats may be an adaptive behavior triggered by the reduction in neuron production, she said.

“Adult-born neurons are thought to have a role in responding to novelty, and the hippocampus participates in resolving conflicts between different goals for use in decision-making,” said Opendak, who is now a postdoctoral research fellow of child and adolescent psychology at the New York University School of Medicine.

“Data from this study suggest that the reward of social novelty may be altered,” she said. “Indeed, sticking with a known partner rather than approaching a stranger may be beneficial in some circumstances.”

The findings also show that behavioral responses to instability may be more measured than scientists have come to expect, explained senior author Elizabeth Gould, Princeton’s Dorman T. Warren Professor of Psychology and department chair. Gould and her co-authors were surprised that the disrupted rats did not display any of the stereotypical signs of mental distress such as anxiety or memory loss, she said.

“Even in the face of what appears to be a very disruptive situation, there was not a negative pathological response but a change that could be viewed as adaptive and beneficial,” said Gould, who also is a professor of neuroscience in the Princeton Neuroscience Institute (PNI).

“We thought the animals would be more anxious, but we were making our prediction based on all the bias in the field that social disruption is always negative,” she said. “This research highlights the fact that organisms, including humans, are typically resilient in response to disruption and social instability.”

Co-authors on the paper include: Lily Offit, who received her bachelor’s degree in psychology and neuroscience from Princeton in 2015 and is now a research assistant at Columbia University Medical Center; Patrick Monari, a research specialist in PNI; Timothy Schoenfeld, a postdoctoral researcher at the National Institutes of Health (NIH) who received his Ph.D. in psychology and neuroscience from Princeton in 2012; Anup Sonti, an NIH researcher; and Heather Cameron, an NIH principal investigator of neuroplasticity.

The study is unusual for mimicking the true social structure of rats, Gould said. Rats live in structured societies that contain a single dominant male. The researchers placed rats into several groups consisting of four males and two females in to a large enclosure known as a visible burrow system. They then monitored the groups until the dominant rat in each one emerged and was identified. After a few days, the alpha rats of two communities were swapped, which reignited the contest for dominance in each group.

The rats from disrupted hierarchies displayed their preference for familiar fellows six weeks after those turbulent times, during which time neurogenesis had decreased by 50 percent, Opendak said. (Any neurons generated during the time of instability would take four to six weeks to be incorporated into the hippocampus’ circuitry, she said.)

When the researchers chemically restored adult neurogenesis in these rats, however, the animals’ interest in unknown rats returned to pre-disruption levels. At the same time, the researchers inhibited neuron growth in “naïve” transgenic rats that had not experienced social disruption. They found that the mere cessation of neurogenesis produced the same results as social disruption, particularly a preference for spending time with familiar rats.

“These results show that the reduction in new neurons is directly responsible for social behavior, something that hasn’t been shown before,” Gould said. The exact mechanism behind how lower neuron growth led to the behavior change is not yet clear, she said.

Bruce McEwen, professor of neuroendocrinology at The Rockefeller University, said that the research is a “major step forward” in efforts to explore the role of the dentate gyrus — a part of the hippocampus — in social behavior and antidepressant efficacy.

“The ventral dentate gyrus, where they found these effects, is now implicated in mood-related behaviors and the response to antidepressants,” said McEwen, who is familiar with the research but had no role in it.

“The connection to social behavior shown here is an important addition because social withdrawal is a key aspect of depression in humans, and the anterior hippocampus in humans is the homolog of the ventral hippocampus in rodents,” McEwen said. “Although there is no ‘animal model’ of human depression, the individual behaviors such as social avoidance, and brain changes such as neurogenesis, have been very useful in elucidating brain mechanisms in human depression.”

At this point, the extent to which the exact mechanism and behavioral changes the researchers observed in the rats would apply to humans is unknown, Gould and Opendak said. The study’s overall conclusion, however, that social disruption and instability lead to neurological changes that help us to better cope is likely universal, they said.

“Most people do experience some disruption in their lives, and resilience is the most typical response,” Gould said. “After all, if organisms always responded to stress with depression and anxiety, it’s unlikely early humans would have made it because life in the wild is very stressful.”

“For people who are exposed to social disruption frequently, our animal model suggests that these life events may be accompanied by long-term changes in brain function and social behavior,” Opendak said. “Although we hope that our findings may guide research on the mechanisms of resilience in humans, it is important as always to exercise caution when extrapolating these data across species.”

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The consumption of LSD, short for lysergic acid diethylamide, can produce altered states of consciousness. This can lead to a loss of boundaries between the self and the environment, as might occur in certain psychiatric illnesses. David Nutt, professor of Neuropsychopharmacology at Imperial College, leads a team of researchers who study how this psychedelic substance works in the brain.

In this study, Dr. Neiloufar Family, post-doc from the University of Kaiserslautern, investigates how LSD can affect speech and language. She asked ten participants to name a sequence of pictures both under placebo and under the effects of LSD, one week apart.

“Results showed that while LSD does not affect reaction times,” explains lead author Neiloufar Family, “people under LSD made more mistakes that were similar in meaning to the pictures they saw.” For example, when people saw a picture of a car, they would accidentally say ‘bus’ or ‘train’ more often under LSD than under placebo. This indicates that LSD seems to effect the mind’s semantic networks, or how words and concepts are stored in relation to each other. When LSD makes the network activation stronger, more words from the same family of meanings come to mind.

The results from this experiment can lead to a better understanding of the neurobiological basis of semantic network activation. Neiloufar Family explains further implication: “These findings are relevant for the renewed exploration of psychedelic psychotherapy, which are being developed for depression and other mental illnesses. The effects of LSD on language can result in a cascade of associations that allow quicker access to far away concepts stored in the mind.”

The many potential uses of this class of substances are under scientific debate. “Inducing a hyper-associative state may have implications for the enhancement of creativity,” Family adds. The increase in activation of semantic networks can lead distant or even subconscious thoughts and concepts to come to the surface.

 

SOURCE


Cell-to-cell communication in the brain

mercredi, 02 novembre 2016 21:18 Written by

Neuroscientists have long known that brain cells communicate with each other through the release of tiny bubbles packed with neurotransmitters—a fleet of vessels docked along neuronal ends ready to launch when a trigger arrives.

Now, a study conducted in mice by neurobiologists at Harvard Medical School reveals that dismantling the docking stations that house these signal-carrying vessels does not fully disrupt signal transmission between cells.

The team’s experiments, described Aug. 17 in the journal Neuron, suggest the presence of mechanisms that help maintain partial communication despite serious structural aberrations.

“Our results not only address one of the most fundamental questions about neuronal activity and the way cells in the brain communicate with each other but uncover a few surprises too,” said Pascal Kaeser, senior author on the study and assistant professor of neurobiology at HMS.

“Our findings point to a fascinating underlying resilience in the nervous system.”

Ultrafast signal transmission between neurons is vital for normal neurologic and cognitive function. In the brain, cell-to-cell communication occurs at the junction that connects two neurons—a structure known as a synapse.

At any given moment, neurotransmitter-carrying vesicles are on standby at designated docking stations, called active zones, each awaiting a trigger to release its load across the synaptic cleft and deliver it to the next neuron.

Signal strength and speed are determined by the number of vesicles ready and capable of releasing their cargo to the next neuron.

Neuroscientists have thus far surmised that destroying the docking stations that house neurotransmitter-loaded bubbles would cause all cell-to-cell communication to cease. The HMS team’s findings suggest otherwise.

To examine the relationship between docking stations and signal transmission, researchers analyzed brain cells from mice genetically altered to lack two key building proteins, the absence of which led to the dismantling of the entire docking station.

When researchers measured signal strength in neurons with missing docking stations, they observed that those cells emitted much weaker signals when demand to transmit information was low. However, when stronger triggers were present, these cells transmitted remarkably robust signals, the researchers noticed.

“We would have guessed that signal transmission would cease altogether but it didn’t,” said Shan Shan Wang, a neuroscience graduate student in Kaeser’s lab and a co-first author of the study. “Neurons appear to retain some residual communication even with a key piece of their communication apparatus missing.”

Elimination of one active zone building block, a protein called RIM, led to a three-quarter reduction in the pool of vesicles ready for release. Disruption of another key structural protein, ELKS, resulted in one-third fewer ready-to-deploy vesicles. When both proteins were missing, however, the total reduction in the number of releasable vesicles was far less than expected. More than 40 percent of a neuron’s vesicles remained in a “ready to launch” state even with the entire docking station broken down and vesicles failing to dock.

The finding suggests that not all launch-ready vesicles need to be docked in the active zone when a trigger arrives. Neurons, the researchers say, appear to form a remote critical reserve of vesicles that can be quickly marshaled in times of high demand.

“In the absence of a docking sites, we observed that vesicles could be quickly recruited from afar when the need arises,” said Richard Held, an HMS graduate student in neuroscience and co-first author on the paper.

The team cautions that any clinical implications remain far off, but say that their observations may help explain how defects in genes responsible for making neuronal docking stations may be implicated in a range of neurodevelopmental disorders.


On managing academic stress

lundi, 24 octobre 2016 22:16 Written by

Most of us have probably heard at some point in our lives that stress is not entirely a bad thing. Acute stress, such as having an upcoming deadline or being about to take a test, can boost your motivation  to rise to the challenge and “get it done”. However, chronic stress (often times characteristic of “the grad school experience”) can have adverse (and enduring) effects if not managed properly. As someone who has an (undiagnosed) impulse control disorder that is exacerbated stress and who was diagnosed with IBS during my third year of grad school, I know this all too well. It wasn’t until I started having IRL conversations with other academics that I realized that academic stress is both real and commonplace. 

Apparently, I wasn’t the only one with IBS, waking up in the middle of the night feeling like I was having a heart attack (if you haven’t experienced this, count yourself lucky), and reaching those times of feeling overwhelmed/burnt out. It also didn’t help that there’s this notion that stress just comes with academia (i.e. it is something to be expected and handled) and nobody really feels comfortable talking about openly. It’s almost as though to admit that you are feeling stressed out is equivalent to being weak. Before I proceed, allow me to try to convince you that this notion is antiquated and incorrect. Academia is stressful for pretty much everyone who is human and academic stress comes in many flavors throughout an academic career. Some examples include: first year stress (esp. if you did not major in neuroscience or psychology), stress of picking lab and becoming a new member, grant-writing stress, project trouble-shooting stress, oral presentation stress, comp/qualifying exam stress, lab drama stress, publishing stress, thesis-writing and defense stress, finding a job stress, tenure-track stress, out of funding stress and the list goes on. Furthermore, some would say that the “academic climate” now is more competitive and cut throat that it used to be (way back when in the 80s, 90s). So there. More stress. 

The first step is to identify stress for what it is and to determine your specific triggers so that you can better develop coping strategies. Also, try to be specific as to what aspect of the stressor throws you over the edge. Is it timing? Lack of controllability? Working with others? Not feeling the sense of mastery you want? Poor lifestyle? You get the picture. 

Below are a set of points that have been helpful to me. This list is by no means all-inclusive, so feel free to customize it. This list is more about providing a starting point of ideas as to how to manage your stress (and preserve your sanity).

1. Take care of yourself: Eat, sleep, and be active. Also, cut down on your vices or substitute for less harmful ones. Sure, sounds easy enough. But not really. During my PhD, I worked outside the city and my workday was from 9:00AM (all aboard the NKI shuttle at 8AM though) until 6:00PM. This means that I started to get ready around 7AM and was back home around 7:30PM. Every day. For years. To make matters worse, I was going to bed at 1-2AM. BAD IDEA. Now I make it a priority to get at least 6 hours but usually aim for 7-9 (yes, 9!). If you are getting less than 6 hours in regularly, you are likely not sleeping enough. Also, I’m sure many of you are familiar (i.e. guilty of) being so busy you forget to eat. Don’t. Give yourself options: bring snacks to lab, have food delivery numbers handy in a pinch or even buy back-up tie over meals to keep in the break room (i.e. yogurts, a loaf of bread, cheese, cold cuts, frozen dinners, etc.). Also, try sneaking in a little exercise into your life by walking to work, picking up a training/workout class, getting into intramural sports (more likely if you work somewhere that has an undergrad campus), or even just dancing by yourself in the comfort of your own house. Basically, find something that helps you work up a sweat. If you’re at a school w/ an undergrad campus, chances are you have a wealth of activities available to you at little or no cost (i.e. access to pools, gym facilities, fitness classes, etc.). 

2. Plan, organize, and prioritize. These are all related to time management skills. Unfortunately, there is no grad school class on time management so most grad students have to adopt a trial and error approach. Others, like myself, had a gracious PhD mentor that taught them how to timeline/schedule experiments. (Side note: I did my PhD in a developmental behavioral neuroscience lab so scheduling was a must.)There is really something to be said for putting down what you need to do on paper. I know it’s stressful to see your to-do list (which usually seems never-ending) but it helps keep important stuff in mind and it feels really good to cross things off :) Let your to-do list motivate you, not paralyze you! Also, keep in mind the order of importance of things as you work on the list. Ex. I use iCal to schedule experiments, meeting, events, etc. My phone does this thing where it synchronizes Facebook events, Google calendar, and iCal so that when I look at a day, I see EVERYTHING that is happening each day and when/where. I also keep a Post-It note stuck on the right side of my laptop (I bring it to lab) with things that need to happen ASAP. On the wall above my desk I keep a handwritten list of things that need to be done in lab over the next couple of weeks (on a continuous basis or for a specific cohort of animals, etc). Developing time management skills is important because it’s easy to forget to do something you have not made time for! By this I mean that what doesn’t get scheduled, typically doesn’t get done :/ The responsibility is yours. Also, if you are stressing about a specific aspect of a project or getting a particular data-set, ask your PI what they think your priority should be (this may be something they need for a grant, talk, etc.). 

3. Create a social support network and maintain healthy social relationships. You know, people you can talk to (and let your guard down with).  These may be friends, family, significant other, colleagues, lab mates, conference buddies, neighbors, etc. It is often beneficial to have a mix of people (i.e. the have been there forever, the school/lab ones, outside academia). Swap stories with lab mates, peers, colleagues you trust instead of bottling up everything. I think it gives a sense of solidarity since a lot of the stress lab/academic situations are commonplace. Keep in mind that school/work struggles are not exclusive to academia and you can often gain meaningful insights and a different perspective from people outside academia. One last thing on this: don’t neglect your own role when the time to buffer someone else comes! You can’t take all the support but not give any. 

4. Learn how to say no (know your limits). One of the easiest ways to bring in paramount stress levels into your life during grad school/postdoc is to say yes to more than you can handle. In academia ideas and projects are constantly being formed/pursued and it is not unnatural for students/postdocs to have more than one project. This is ok but avoid spreading yourself too thin. I, like many, have been guilty of this. Some things I’ve gotten done and some I’m still trying to push out. Oh well. If you’re feeling stressed out, (see #2 and note below). 

Reminder: PIs know that you’re working on project X. But they usually don’t factor in all the little details that go into making project X happen, such as breeding, habituation, surgeries, post-op rec periods, time in b/w tests, etc. It is your job to remind them! 

Note: Doing #2 will help you tell your PI exactly how your time in the lab is spent. It’s WAY easier to postpone starting something or reduce your role if you have PROOF that you have no time for it. If it’s really important, compromises will be made (hurray!). 

5. Make time for hobbies. Even better, cultivate new ones. Working really hard does not mean that all you do is work. Try to become really good at something other than science :) Find a variety of interesting, fun and/or enjoyable things to do outside of lab. It helps to have hobbies of varying intensities (some active, some passive) so that you have options if you come back too tired or what not. Have more low-key ones (ex. cooking*, singing, drawing/painting, knitting, becoming an expert at ______, delve into a decade, explore a music genre, start a collection) and active (i.e. martial arts, yoga, train for a marathon, pick up a new dance, teach your body how to do something new or just walk around). 

*Learning how to cook gives you a head up on #1. 

6. Find your ground. This one is really open-ended as it means different things to different people, but it’s important because it helps you keep connected to yourself. It may include (but is not limited to): talking to your relatives (especially the older ones) regularly, keeping in touch with your cultural roots through organizations/clubs/meetups, volunteering, going to church, meditating, developing your spiritual life, introspection, etc. 

7. Stay positive. Avoid falling down the black hole of discouragement and despair. Way easier to get sucked in than it is to claw out. If you let yourself go you will need to be aggressive about obtaining new outlook. And possibly outside help. Remember that misery loves company and protect your positivity. Being positive despite adversity is a choice. You have the power to decide. More on the value of thinking happy thoughts here.

8. Give yourself a reality check. From an intellectual standpoint, there is some sort of a re-wiring that happens when you’ve been in academia for a while. It’s hard to describe because it constitutes different things by career stage and by people. In my experience, this transformation happened towards the end of grad school. It’s around this time that people often ask themselves: WHY AM I DOING THIS? WHAT IS THIS FOR? WHAT DOES IT ALL MEAN?  For me, the result of pondering these things resulted in a personal epiphany that all of this (i.e. science, academia, my thesis) was bigger than myself and only a limited part of the world. It does not define who I am as a person, and it will be pretty much irrelevant if the world goes to shit a la Walking Dead or Revolution. Heck, there’s people in the world right now worrying about whether or not they will live to see tomorrow. It was a weird mix of  learning how to stop sweating the small stuff and focusing on moving towards the big picture, feeling privileged to be able to pursue doing research, while also understanding that there are things beyond your control and that sometimes you can only control the way you handle a situation and what you do to remedy it. 

9. Go on vacation. This one’s self-explanatory. Try to avoid the compulsion to check your work e-mail :) If you opt for a stay-cation, make it a point to disconnect. 

 

SOURCE


New understanding of how cytomegalovirus interacts with host cells provides potential therapeutic target

Viruses hijack the molecular machinery in human cells to survive and replicate, often damaging those host cells in the process. Researchers at the University of California San Diego School of Medicine discovered that, for cytomegalovirus (CMV), this process relies on a human protein called CPEB1. The study, published October 24 in Nature Structural and Molecular Biology, provides a potential new target for the development of CMV therapies.

“We found that CPEB1, one of a family of hundreds of RNA-binding proteins in the human genome, is important for establishing productive cytomegalovirus infections,” said senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine.

CMV is a virus that infects more than half of all adults by age 40, and stays for life. Most infected people are not aware that they have CMV because it rarely causes symptoms. However, CMV can cause serious health problems for people with compromised immune systems, or babies infected with the virus before birth. There are currently no treatments or vaccines for CMV.

 

(Source: health.ucsd.edu)


One of the physicists who helped find the Higgs boson, Elina Berglund, has spent the past three years working on something completely different - a fertility app that tells women when they're fertile or not.

It's not the first fertility app out there, but Berglund's app works so well that it's been shown to help women avoid pregnancy with 99.5 percent reliability - an efficacy that puts it right up there with the pill and condoms.

Best of all, the app doesn't have any side effects, and just requires women to input their temperature daily to map their fertility throughout the month.

Back in 2012, Berglund was working at CERN on the Large Hadron Collider experiment to find the famous Higgs boson. But after the discovery of the particle, she felt it was time to work on something completely different. 

"I wanted to give my body a break from the pill," she told Daniela Walker fromWired, "but I couldn't find any good forms of natural birth control, so I wrote an algorithm for myself."

The resulting app is called Natural Cycles, and so far, it's had pretty promising results.

Using a woman's natural fertility cycle to help her avoid getting pregnant isn't a new idea - it stems from something called the rhythm method, which is a form of contraceptive that claims to work just by having women avoid unprotected sex on fertile days each month.

In theory, that should work quite well. After all, there's only a roughly nine-day window during which a woman can get pregnant each month. But the rhythm method is pretty unreliable, seeing as all women have slightly different cycles, and in real life, it only has a success rate of around 75 percent.

But Berglund's algorithm is different - it uses the same advanced statistical methods she used at CERN, and is based on a woman's daily temperature rather than simply the day of her cycle.

That's because after ovulation, women see a spike in progesterone, which makes their bodies up to 0.45 degrees Celsius warmer.

So by entering your temperature in the app daily, and comparing the results with a broader dataset, the app lets you know when you can have unprotected sex (a green day) and when to use contraception, such as condoms (a red day).

There have been two trials so far, and the second one analysed data on more than 4,000 women aged 20 to 35 using the app.

Over the course of one year, there were 143 unplanned pregnancies in the cohort, 10 of which were conceived on green days, giving the app a 99.5 percent reliability rating. (The rest of the unplanned pregnancies were the result of women not using the app properly.)

To put that into perspective, condoms are 98 percent effective, and IUD devices are 99 percent reliable, as is the pill, when taken at the same time every day.

The latest trial was published in the European Journal of Contraceptive and Reproductive Healthcare.

Of course, Natural Cycles can't protect against STIs, so it isn't recommended for everyone. But for people who are having sex with a regular and trusted partner, the results so far suggest that it can work as well as more traditional types of birth control.

The app can also help women plan pregnancies, by taking the guesswork out of finding the best day to have sex.

But the real aim for Berglund now is to have the app classified as a contraceptive, not just a fertility monitor. "We are a natural alternative to the pill - with no side effects," she told Walker.

Not everyone is so convinced, though. In the latest trial, more than 1,000 women dropped out and stopped using the app over the course of the year, which shows that it can be hard to maintain. And women also have to be highly motivated and organised to record their temperatures at the same time every single day. 

"It’s not a clinical trial but shows real-life performance," one of the researchers in the study, Kristina Gemzell Danielsson, from the Karolinska Intitutet in Sweden,told Wired. "True, motivation is key. For many women this is not the best method. However for motivated women it can be an alternative."

"Natural Cycles is not recommended to those who are very young or very keen to avoid a pregnancy, since there are other more effective methods," she added.

Those more effective methods are ones that don't require people to remember to take a pill, put on a condom, or record their temperature daily, such asintrauterine contraception or implants.

That's because human error can mess with things quite a lot. In fact, the UK'sNational Health Service (NHS) explained that when the app was used perfectly all the time, only five out of every 1,000 women would fall pregnant every year - a rate slightly better than the pill.

But for "typical use" - where the app isn't used entirely correctly every day - it's more likely that seven out of every 100 women would experience accidental pregnancies, which is around 93 percent efficiency.

They also reminded women that an app will never protect against diseases.

"However effective an application may be, it will not protect you against sexually transmitted infections, unlike the low-tech - but very reliable - condom," the NHS Choices blog explains.

Still, Berglund is working on improving the reliability constantly. The app now has 100,000 users paying £6.99 per month, and in June, the company receivedUS$6 million in funding.

She's now hired another particle physicist from CERN to help analyse the data from the app and make it more reliable and personalised for each woman.  

"It can be very scary, especially when it has to do with your body and your health," she told Wired. "We know we are dealing with women’s lives here and we take that very seriously."

But with women still waiting for the male contraceptive pill to be rolled out, and many experiencing negative side effects such as depression from other types of hormonal contraceptive, it's nice to know that some of the great minds in science are working on new options for us. 

SOURCE


The existence of microbial life on Mars remains highly controversial, but recent evidence of water, complex organic molecules, and methane in the Martian environment, combined with findings from the 1976 Viking mission, have led to the conclusion that existing life on Mars is a possibility that must be considered, as presented in an article in Astrobiology. 

 
In “The Case for Extant Life on Mars and Its Possible Detection by the Viking Labeled Release Experiment,” coauthors Gilbert V. Levin, Arizona State University, Tempe, and Patricia Ann Straat, National Institutes of Health, Bethesda, MD (retired), clearly outline the evidence to support the “biological hypothesis,” which argues that the results of the 1976 Viking Labeled Release experiment were positive for extant microbial life on the surface of Mars. 
 
Further, Drs. Levin and Straat evaluate the “non­biological hypotheses” to explain the Viking results, which many scientists support, but the authors conclude that the experimental evidence supports a biological explanation and the likelihood that microorganisms were able to evolve and adapt to be able to survive in the harsh conditions of the Martian environment. “Even if one is not convinced that the Viking LR results give strong evidence for life on Mars, this paper clearly shows that the possibility must be considered,” says Chris McKay, PhD, Senior Editor of Astrobiology and an astrobiologist with NASA Ames Research Center, Moffett Field, CA. “We cannot rule out the biological explanation. This has implications for plans for sample return from Mars and for future human missions.” 
 
Source:
 
Gilbert V. Levin, Patricia Ann Straat. The Case for Extant Life on Mars and Its Possible Detection by the Viking Labeled Release Experiment. Astrobiology, 2016; 16 (10): 798 DOI:10.1089/ast.2015.1464 

When prion proteins mutate, they trigger mad cow and Creutzfeldt-Jakob disease. Although they are found in virtually every organism, the function of these proteins remained unclear. Researchers from the University of Zurich and the University Hospital Zurich now demonstrate that prion proteins, coupled with a particular receptor, are responsible for nerve health. The discovery could yield novel treatments for chronic nerve diseases.

Ever since the prion gene was discovered in 1985, its role and biological impact on the neurons has remained a mystery. “Finally, we can ascribe a clear-cut function to prion proteins and reveal that, combined with particular receptor, they are responsible for the long-term integrity of the nerves,” says Professor Adriano Aguzzi from the Neuropathological Institute at the University of Zurich and University Hospital Zurich. The present study therefore clears up a question that researchers have been puzzling over for 30 years, but ultimately went unanswered.

Prions are dangerous pathogens that trigger fatal brain degeneration in humans and animals. In the 1990s, they were responsible for the BSE epidemic more commonly known as mad cow disease. In humans, they cause Creutzfeldt-Jakob disease and other neurological disorders that are fatal and untreatable. Meanwhile, we know that infectious prions consist of a defectively folded form of a normal prion protein called PrPC located in the neuron membrane. The infectious prions multiply by kidnapping PrPand converting it into other infectious prions.

Absent prion proteins cause nerve diseases

For a long time, it remained unclear why we humans – like most other organisms – have a protein in our neurons that does not perform any obvious function, yet can be extremely dangerous. Aguzzi has spent decades researching this issue and examining the theory that animals without the PrPC gene are resistant to prion diseases. But what are the repercussions for the organism if the prion protein is deactivated?

A few years ago, Aguzzi and his team discovered that mice without the PrPCgene suffer from a chronic disease of the peripheral nervous system. The reason: The so-called Schwann cells around the sensitive nerve fibers no longer form an insulating layer to protect the nerves. Due to this insulating myelin deficit, the peripheral nerves become diseased, potentially resulting in motoric disorders in the motion tract and paralysis.

The researchers have now gone one step further in the lab: In a new study, Alexander Küffer and Asvin Lakkaraju clarify exactly why the peripheral nerves become damaged in the absence of the prion protein PrPC. They discovered how the PrPC produced by the neurons docks onto the Schwann cells: namely via a receptor called Gpr126. If the prion protein and the receptor work together, a particular messenger substance (cAMP) which regulates the chemical interaction in the cells and is essential for the integrity of the nerve’s protective sheath increases. Gpr126 belongs to the large family of “G-protein-coupled receptors”, which are involved in many physiological processes and diseases.

30-year-old research question finally answered

This discovery solves a key question that has long puzzled neuroscientists and points towards future applications in hospitals. “If you want to deactivate the prion protein PrPC fully for potential Creutzfeld-Jakob disease treatments, you need to know the potential side effects on the nerves in the future,” explains Aguzzi. Moreover, the present results on the effect of PrPC at molecular level could yield a new approach for peripheral neuropathy. Currently, there are only extremely limited therapeutic options for these chronic debilitating diseases of the nervous system.


Serendipity yields new neuron type in mouse retina

dimanche, 23 octobre 2016 15:20 Written by

In the retina of mice, a new type of neuron that falls outside century-old classifications has been discovered.

Neurons are nerve cell involved in receiving or sending signals. The new cell, which the UW Medicine researchers conducting the research named GluMI (pronounced “gloomy”) acts like one class of neurons, but anatomically resembles another.

The discovery is bound to excite vision researchers, said Luca Della Santina, one of the study’s co-lead authors and a former postdoctoral student in the University of  Washington Department of Biological Structure.

“This cell represents not just a new kind of neuron but a new way to convey information within the retina,” he said.

The researchers detailed their findings in a paper, “Glutamatergic monopolar interneurons provide a novel pathway of excitation in the mouse retina,” published  Aug. 8, in Current Biology.

The scientists didn’t expect to find a new type of cell, Della Santina said. This part of the retina has been well-mapped. For the past 100 or so years scientists have placed retinal interneurons squarely into one of two boxes.

Bipolar neurons relay information from the retina’s photoreceptors, which capture light, to the specialized cells that process those signals into vision for the brain, called ganglion cells. Monopolar neurons, on the other hand, typically aren’t contacted directly by photoreceptors. They also provide inhibition, meaning they hit the brakes to keep nerve cell signaling traffic in check. 

But the GluMI cell is an oddity. Its structure clearly is monopolar, yet it functions like a bipolar cell by exciting the ganglion cells.

Della Santina first noticed the GluMIs in 2010, while studying the retina of transgenic mice. These animals were engineered to manufacture a fluorescent protein to help illuminate different cells in different colors. He observed a cell type that looked monopolar but, puzzlingly, didn’t have any of the markers of an inhibitory retinal cell.

He set his finding aside while he finished his original research. A team at UW Medicine, including Rachel Wong, Sidney Kuo, Takeshi Yoshimatsu, and Fred Rieke, as well as a researcher at the University of Tokyo, then got together to solve the cellular conundrum.

They turned first to its appearance. Under a microscope the GluMI cells seemed to have synaptic ribbons—a hallmark of bipolar cells. Yet the researchers weren’t 100 percent certain. They got a helping hand from a relatively new imaging method called serial block-face electron microscopy, which is a way to generate high-resolution, 3-dimensional images from biological samples. This powerful microscope zooms in to reveal a cell’s ultrastructure at nanometer resolution. A nanometer is very roughly about one million times smaller than the circumference of a ballpoint pen tip. The 3-D images they created confirmed that GluMI had synaptic ribbons.

Once they understood the structure, the researchers turned to function. Sid Kuo, a postdoctoral fellow with Fred Rieke, confirmed that the cell was relaying light information and showed that its light responses differed from those of bipolar cells. But since the cell wasn’t contacted by the photoreceptors, the source of these light responses was a mystery. It still is.

After debating what to call their new cell, they decided to name it a glutamatergic monopolar interneuron, or GluMI. The “gloomy” cell was not named after the Seattle weather, quipped Wong, a UW professor of biological structure.

Although they didn’t intend to find it, the UW team looks forward to exploring the role of the GluMI cell in visual function, in conjunction with their research colleagues around the world, she added. 


Neurobiological Factors for Schizophrenia

dimanche, 23 octobre 2016 15:18 Written by

It is impossible to predict the onset of schizophrenic psychosis. If factors linked to a risk of psychosis can be identified, however, these may yield significant insights into its underlying mechanisms. Basel-based scientists have now established a link between particular genes and the size of important brain structures in individuals with an elevated risk of psychosis. The results of the study appear in the latest edition of the scientific journalTranslational Psychiatry

Schizophrenic psychoses are a frequently occurring group of psychiatric disorders caused by a combination of biological, social and environmental factors. These disorders are associated with changes to the brain structure: for example, the hippocampus in the temporal lobe is usually smaller in affected individuals than in healthy ones. It is not yet known whether these changes to the brain structure are a result of the disorders and their accompanying medications, or whether they are already present before the onset of symptoms.

Together with a research group from the University of Basel, Fabienne Harrisberger and Stefan Borgwardt examined the brain structures of individuals exhibiting an elevated risk of psychosis, and those of individuals experiencing the onset of psychotic symptoms for the first time. Initially, scientists from the Adult Psychiatric Clinic of the University Psychiatric Clinics (UPK) and the Transfaculty Research Platform Molecular and Cognitive Neurosciences (MCN) observed no appreciable difference between the hippocampi of individuals at high risk and those of patients.

Next, together with scientists from the Transfaculty Research Platform, they investigated whether any known schizophrenia risk genes are associated with the hippocampus. This appears to be the case: the greater the number of risk genes a person possessed, the smaller the volume of their hippocampus – regardless of whether they were a high-risk study participant or a patient. This means that a group of risk genes is connected with a reduction in the size of a critical region of the brain before the disorder manifests itself.

Potential for differentiated therapy

This result is significant for the understanding of neurobiological factors contributing to schizophrenia. It is well-known that none of the wider risk factors (e.g. genes, environment, unfavorable social situation) can be used to predict the onset of psychosis in a specific individual. However, the discovery may be of use for the treatment of schizophrenia.

“It is quite possible that individuals with smaller hippocampi will react differently to therapy compared to those with normally developed hippocampi,” explains Prof. Stefan Borgwardt of the Neuropsychiatry and Brain Imaging Unit. Further studies to ascertain the therapeutic potential of this research are planned.


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