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First validated canine behavioral genetics, findings of nine fear, aggression traits in dogs

Anxiety disorders are the most common type of mental illness in the United States. And while much is understood about the biochemistry of anxiety, little is known about the genetic variation associated with it.

Recently published in BMC Genetics, a study led by researchers at Nationwide Children’s Hospital reports that genetic predisposition to aggression toward an owner or a familiar dog is distinct from that for fear and aggression directed at unfamiliar humans and dogs. The researchers identified approximately 12 genes associated with these traits.

“Our strongest focus is on specific genes related to aggression toward unfamiliar humans and dogs, which are associated with highly relevant genes at two genome regions,” said Carlos Alvarez, PhD, principal investigator in the Center for Molecular and Human Genetics in The Research Institute at Nationwide Children’s Hospital. “Those genes are consistent with the core fear and aggression neural pathway known as the amygdala to hypothalamic-pituitary-adrenal axis.”

The findings not only relate to the most important dog behavioral problems but are also likely to be highly relevant to human anxiety disorders, according to Dr. Alvarez.

While the most immediate implications are for veterinary behavioral medicine — genetic testing for risk of specific types of fear and aggression, the long term implications for adults and children with anxiety disorders are encouraging.

Because these risk variants are common across dog breeds, the canine veterinary setting provides an ideal testbed for new therapies targeting those biochemical pathways. Once it is determined which neuronal circuits are affected by the risk variation, this will likely reveal drug targets that could be inhibited or activated to increase or decrease the emotional behavioral effects. Those findings can immediately be tested in pet dog patients under owner consent. And, if those therapies are effective in dogs, they can then be applied to humans with similar conditions. Knowledge of the affected pathways will also provide biomarkers that can be used to identify the patients who are most likely to respond to such treatments.

“This project has only just begun,” said Dr. Alvarez. “We are continuing to identify and validate other genes associated with these traits, including the expansion of dog breeds studied and biological validation of the findings. We are excited about what this work will continue to uncover.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160810180908.htm  Original web page at Science Daily

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* Lions in West and Central Africa apparently unique

Lions in West and Central Africa form a unique group, only distantly related to lions in East and Southern Africa. Biologists at Leiden University confirm this in an article published in Scientific Reports.

In this study, the researchers gathered a genetic dataset of lion populations covering a total of 22 countries. This included samples from each remaining lion population in West and Central Africa, a region where lions and other wildlife are rapidly declining as a consequence of the increasing human population. The researchers managed to gather all the information by teaming up with other people in the field and local conservationists.

Based on the genetic data, it was estimated that the split between the two major groups that can be identified in the lion must have occurred 300,000 years ago. To explain what happened in their evolution, the researchers made a reconstruction of African climatological history. It seems that periodic expansions of the rain forest and the desert drove lions into isolated pockets of suitable habitat, where the different genetic lineages originated that can still be observed today.

This influenced not only the patterns we observe in the lion, but also in other large mammals such as giraffe, buffalo, hartebeest, cheetah and spotted hyena. A general pattern is emerging that shows that many large African savannah mammals show very similar arrangements, with unique lineages in West and Central Africa.

The strong declines in wildlife populations in large parts of West and Central Africa are therefore a reason for major concern. The fact that this region seems to harbour a lot of unique genetic lineages makes conservation in the area extremely important. A delegation from Leiden University will participate in the IUCN World Conservation Congress in September 2016, and will lead a Side Event that aims to establish a Species Action Plan for West and Central Africa. The researchers hope that this will facilitate coordination and funding of projects in the region.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160811120559.htm  Original web page at Science Daily

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How climate change will hurt humanity’s closest cousins

The consequences of climate change are an increasing concern for humans around the world. How will we cope with rising sea levels and climbing temperatures? But it’s not just humans who will be affected by these worldwide shifts — it’s our closest cousins, too: monkeys, apes and lemurs.

A new Concordia study published in the International Journal of Primatology shows that the world’s primate populations may be seriously impacted by climate change.

“Our research shows that climate change may be one of the biggest emerging threats to primates, compounding existing pressures from deforestation, hunting and the exotic pet trade,” says Tanya Graham, the article’s lead author and an MSc student in the Department of Geography, Planning and Environment.

She worked with environment professor Damon Matthews from Concordia and primatology post-doctoral researcher Sarah Turner from McGill to assess the exposure and potential vulnerability of all non-human primate species to projected future temperature and precipitation changes. They found that overall, 419 species of non-human primates — such as various species of lemurs, lorises, tarsiers, monkeys and apes — will experience 10 per cent more warming than the global average, with some primate species experiencing increases of more than 1.5 degrees Celsius in annual average temperature for every degree of global warming.

The researchers also identified several hotspots of primate vulnerability to climate change, based on the combination of the number of species, their endangered status and the severity of climate changes at each location. Overall, the most extreme hotspots, which represent the upper 10 per cent of all hotspot scores, cover a total area of 3,622,012 square kilometres over the ranges of 67 primate species.

The highest hotspot scores occur in Central America, the Amazon and southeastern Brazil, as well as portions of East and Southeast Asia — prime territory for some of the globe’s best-known primates who call these areas home.

The ursine howler monkey, black howler monkey, and barbary macaque are expected to be exposed to the highest magnitude of climate change when both temperature and precipitation are considered. For example, the ursine howler monkey, found in Venezuela, will experience an increase of 1.2 degrees Celsius annually and a 5.3 per cent decline in annual rainfall for each degree of global temperature increase.

“This study highlights the vulnerability of individual species, as well as regions in which primates as a whole may be vulnerable to climate change,” says Matthews, who will present the findings of this study during the Joint Meeting of the International Primatological Society and the American Society of Primatologists in Chicago later this month.

“Our findings can be taken as priorities for ongoing conservation efforts, given that any success in decreasing other current human pressures on endangered species may also increase that species’ ability to withstand the growing pressures of climate changes,” says Graham.

“Primates are often seen as flagship species for entire ecosystems, so conservation can have important ramifications for many other species too. I hope our study will help direct conservation efforts for individual primate species in particular, but also for vulnerable ecosystems in general throughout the tropical regions inhabited by non-human primates,” adds Turner.

This study was funded in part by the Concordia Institute for Water, Energy and Sustainable Systems, the Natural Sciences and Engineering Research Council of Canada and the Fonds de recherche du Québec — Nature et technologies.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160810114052.htm  Original web page at Science Daily

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New insights into how the mind influences the body

Neuroscientists at the University of Pittsburgh have identified the neural networks that connect the cerebral cortex to the adrenal medulla, which is responsible for the body’s rapid response in stressful situations. These findings, reported in the online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS), provide evidence for the neural basis of a mind-body connection.

Specifically, the findings shed new light on how stress, depression and other mental states can alter organ function, and show that there is a real anatomical basis for psychosomatic illness. The research also provides a concrete neural substrate that may help explain why meditation and certain exercises such as yoga and Pilates can be so helpful in modulating the body’s responses to physical, mental and emotional stress.

“Our results turned out to be much more complex and interesting than we imagined before we began this study,” said senior author Peter L. Strick, Ph.D., Thomas Detre Chair of the Department of Neurobiology and scientific director of the University of Pittsburgh Brain Institute.

In their experiments, the scientists traced the neural circuitry that links areas of the cerebral cortex to the adrenal medulla (the inner part of the adrenal gland, which is located above each kidney). The scientific team included lead author Richard P. Dum, Ph.D., research associate professor in the Department of Neurobiology; David J. Levinthal, M.D., Ph.D., assistant professor in the Department of Medicine; and Dr. Strick.

The scientists were surprised by the sheer number of neural networks they uncovered. Other investigators had suspected that one or, perhaps, two cortical areas might be responsible for the control of the adrenal medulla. The actual number and location of the cortical areas were uncertain. In the PNAS study, the Strick laboratory used a unique tracing method that involves rabies virus. This approach is capable of revealing long chains of interconnected neurons. Using this approach, Dr. Strick and his colleagues demonstrated that the control of the adrenal medulla originates from multiple cortical areas. According to the new findings, the biggest influences arise from motor areas of the cerebral cortex and from other cortical areas involved in cognition and affect.

Why does it matter which cortical areas influence the adrenal medulla? Acute responses to stress include a wide variety of changes such as a pounding heart, sweating and dilated pupils. These responses help prepare the body for action and often are characterized as “fight or flight responses.” Many situations in modern life call for a more thought-out reaction than simple “fight or flight,” and it is clear that we have some cognitive control (or what neuroscientists call “top-down” control) over our responses to stress.

“Because we have a cortex, we have options,” said Dr. Strick. “If someone insults you, you don’t have to punch them or flee. You might have a more nuanced response and ignore the insult or make a witty comeback. These options are part of what the cerebral cortex provides.”

Another surprising result was that motor areas in the cerebral cortex, involved in the planning and performance of movement, provide a substantial input to the adrenal medulla. One of these areas is a portion of the primary motor cortex that is concerned with the control of axial body movement and posture. This input to the adrenal medulla may explain why core body exercises are so helpful in modulating responses to stress. Calming practices such as Pilates, yoga, tai chi and even dancing in a small space all require proper skeletal alignment, coordination and flexibility.

The PNAS study also revealed that the areas of the cortex that are active when we sense conflict, or are aware that we have made an error, are a source of influence over the adrenal medulla. “This observation,” said Dr. Strick, “raises the possibility that activity in these cortical areas when you re-imagine an error, or beat yourself up over a mistake, or think about a traumatic event, results in descending signals that influence the adrenal medulla in just the same way as the actual event.” These anatomical findings have relevance for therapies that deal with post-traumatic stress.

Additional links with the adrenal medulla were discovered in cortical areas that are active during mindful mediation and areas that show changes in bipolar familial depression. “One way of summarizing our results is that we may have uncovered the stress and depression connectome,” says Dr. Strick.

Overall, these results indicate that circuits exist to link movement, cognition and affect to the function of the adrenal medulla and the control of stress. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for psychosomatic illness.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160815185555.htm  Original web page at Science Daily

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Cognitive offloading: How the Internet is increasingly taking over human memory

Our increasing reliance on the Internet and the ease of access to the vast resource available online is affecting our thought processes for problem solving, recall and learning. In a new article published in the journal Memory, researchers at the University of California, Santa Cruz and University of Illinois, Urbana Champaign have found that ‘cognitive offloading’, or the tendency to rely on things like the Internet as an aide-mémoire, increases after each use. We might think that memory is something that happens in the head but increasingly it is becoming something that happens with the help of agents outside the head. Benjamin Storm, Sean Stone & Aaron Benjamin conducted experiments to determine our likelihood to reach for a computer or smartphone to answer questions. Participants were first divided into two groups to answer some challenging trivia questions — one group used just their memory, the other used Google. Participants were then given the option of answering subsequent easier questions by the method of their choice.

The results revealed that participants who previously used the Internet to gain information were significantly more likely to revert to Google for subsequent questions than those who relied on memory. Participants also spent less time consulting their own memory before reaching for the Internet; they were not only more likely to do it again, they were likely to do it much more quickly. Remarkably 30% of participants who previously consulted the Internet failed to even attempt to answer a single simple question from memory.

Lead author Dr Benjamin Storm commented, “Memory is changing. Our research shows that as we use the Internet to support and extend our memory we become more reliant on it. Whereas before we might have tried to recall something on our own, now we don’t bother. As more information becomes available via smartphones and other devices, we become progressively more reliant on it in our daily lives.”

This research suggests that using a certain method for fact finding has a marked influence on the probability of future repeat behaviour. Time will tell if this pattern will have any further reaching impacts on human memory than has our reliance on other information sources. Certainly the Internet is more comprehensive, dependable and on the whole faster than the imperfections of human memory, borne out by the more accurate answers from participants in the internet condition during this research. With a world of information a Google search away on a smartphone, the need to remember trivial facts, figures, and numbers is inevitably becoming less necessary to function in everyday life.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160816085029.htm  Original web page at Science Daily

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Snakes have adapted their vision to hunt their prey day or night

For example, snakes that need good eyesight to hunt during the day have eye lenses that act as sunglasses, filtering out ultraviolet light and sharpening their vision while nocturnal snakes have lenses that allow ultraviolet light through, helping them to see in the dark.

New insights into the relationship between ultraviolet (UV) filters and hunting methods in snakes is one of the findings of the first major study of visual pigment genes and lenses in snakes — published in the advanced online edition of Molecular Biology and Evolution.

The new research was an international collaboration between snake biologists and vision experts led by the David Gower and included fellow Natural History Museum researchers Bruno Simões and Filipa Sampaio. Much of the research, including most of the DNA analyses, was carried out in the Museum’s laboratories.

Scientists have long known that snakes have highly variable sets of rods and cones — the specialised cells in the retina that an animal uses to detect light. But until now, most modern studies of vision in vertebrates (animals with a backbone) have concentrated on mammals, birds and fish.

To see in different colors, animals use visual pigments in their rods and cones that are sensitive to different wavelengths of light. The researchers examined the genes involved in producing the pigments from a broad genomic survey of 69 different species of snakes. What they found was as the genes vary from species to species so does the exact molecular structure of the pigments and the wavelengths of light they absorb.

The new research discovered that most snakes possess three visual pigments and are likely dichromatic in daylight — seeing two primary colours rather than the three that most humans see.

However, it also discovered that snake visual pigment genes have undergone a great amount of adaptation, including many changes to the wavelengths of light that the pigments are sensitive to, in order to suit the diversity of lifestyles that snakes have evolved.

Most snakes examined in the new study are sensitive to UV light, which likely allows them to see well in low light conditions. For light to reach the retina and be absorbed by the pigments, it first travels through the lens of the eye. Snakes with UV-sensitive visual pigments therefore have lenses that let UV light though.

In contrast, the research showed that those snakes that rely on their eyesight to hunt in the daytime, such as the gliding golden tree snake Chrysopelea ornata and the Monypellier snake Malpolon monspessulanus, have lenses that block UV light. As well as perhaps helping to protect their eyes from damage, this likely helps sharpen their sight — in the same way that skiers’ yellow goggles cut out some blue light and improve contrast.

Moreover, these snakes with UV-filtering lenses have tuned the pigments in their retina so that they are no longer sensitive to the short UV light, but absorb longer wavelengths.

All nocturnal species examined (such as N America’s glossy snake Arizona elegans) were found to have lenses that do not filter UV. Some snake species active in daylight also lack a UV-filtering lens, perhaps because they are less reliant on very sharp vision or live in places without very bright light.

By analysing how the pigments have evolved in snakes, the new study concluded also that the most recent ancestor of all living snakes had UV sensitive vision. “The precise nature of the ancestral snake is contentious, but the evidence from vision is consistent with the idea that it was adapted to living in low light conditions on land,” said corresponding author Gower.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160816182620.htm  Original web page at Science Daily

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No blue light, please, I’m tired: Light color determines sleepiness versus arousal in mice

Light affects sleep. A study in mice published in Open Access journal PLOS Biology shows that the actual color of light matters; blue light keeps mice awake longer while green light puts them to sleep easily. An accompanying Primer provides accessible context information and discusses open questions and potential implications for “designing the lighting of the future.”

Light shining into our eyes not only mediates vision but also has critical non-image-forming functions such as the regulation of circadian rhythm, which affects sleep and other physiological processes. As humans, light generally keeps us awake, and dark makes us sleepy. For mice, which are mostly nocturnal, light is a sleep-inducer. Previous studies in mice and humans have shown that non-image-forming light perception occurs in specific photosensitive cells in the eye and involves a light sensor called melanopsin. Mice without melanopsin show a delay in their response to fall asleep when exposed to light, pointing to a critical role for melanopsin in sleep regulation.

Stuart Peirson and Russell Foster, both from Oxford University, UK, alongside colleagues from Oxford and elsewhere, investigated this further by studying sleep induction in mice exposed to colored light, i.e., light of different wave lengths. Based on the physical properties of melanopsin, which is most sensitive to blue light, the researchers predicted that blue light would be the most potent sleep inducer.

To their surprise, that was not the case. Green light, it turns out, puts mice to sleep quickly, whereas blue light actually seems to stimulate the mice, though they did fall asleep eventually. Mice lacking melanopsin were oblivious to light color, demonstrating that the protein is directing the differential response.

Both green and blue light elevated levels of the stress hormone corticosterone in the blood of exposed mice compared with mice kept in the dark, the researchers found. Corticosterone levels in response to blue light, however, were higher than levels in mice exposed to green light. When the researchers gave the mice drugs that block the effects of corticosterone, they were able to mitigate the effects of blue light; drugged mice exposed to blue light went to sleep faster than control mice that had received placebos.

Citing previous results that exposure to blue light — a predominant component of light emitted by computer and smart-phone screens — promotes arousal and wakefulness in humans as well, the researchers suggest that “despite the differences between nocturnal and diurnal species, light may play a similar alerting role in mice as has been shown in humans.” Overall, they say their work “shows the extent to which light affects our physiology and has important implications for the design and use of artificial light sources.”

In the accompanying Primer, Patrice Bourgin, from the University of Strasbourg, France, and Jeffrey Hubbard from the University of Lausanne, Switzerland, say the study “reveals that the role of color [in controlling sleep and alertness] is far more important and complex than previously thought, and is a key parameter to take into account.” The study’s results, they say, “call for a greater understanding of melanopsin-based phototransduction and tell us that color wavelength is another aspect of environmental illumination that we should consider, in addition to photon density, duration of exposure and time of day, as we move forward in designing the lighting of the future, aiming to improve human health and well-being.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160815185816.htm Original web page at Science Daily

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* Pre-Hispanic Mexican civilization may have bred and managed rabbits and hares

Humans living in the pre-Hispanic Mexican city of Teotihuacan may have bred rabbits and hares for food, fur and bone tools, according to a study published August 17, 2016 in the open-access journal PLOS ONE by Andrew Somerville from the University of California San Diego, US, and colleagues.

Human-animal relationships often involve herbivore husbandry and have been key in the development of complex human societies across the globe. However, fewer large mammals suitable for husbandry were available in Mesoamerica. The authors of the present study looked for evidence of small animal husbandry in the pre-Hispanic city of Teotihuacan, which existed northeast of what is now Mexico City from A.D. 1-600. The authors performed stable carbon and oxygen isotope analysis of 134 rabbit and hare bone specimens from the ancient city and 13 modern wild specimens from central Mexico to compare their potential diets and ecology.

Compared to modern wild specimens, the authors found that Teotihuacan rabbit and hare specimens had carbon isotope values indicating higher levels of human-farmed crops, such as maize, in their diet. The specimens with the greatest difference in isotope values came from a Teotihuacan complex that contained traces of animal butchering and a rabbit sculpture.

While the ancient rabbits and hares included in this study could have consumed at least some farmed crops through raiding of fields or wild plants, the authors suggest their findings indicate that Teotihuacan residents may have provisioned, managed, or bred rabbits and hares for food, fur, and bone tools, which could be new evidence of small mammal husbandry in Mesoamerica.

“Because no large mammals such as goats, cows, or horses were available for domestication in pre-Hispanic Mexico, many assume that Native Americans did not have as intensive human-animal relationships as did societies of the Old World,” said Andrew Somerville. “Our results suggest that citizens of the ancient city of Teotihuacan engaged in relationships with smaller and more diverse fauna, such as rabbits and jackrabbits, and that these may have been just as important as relationships with larger animals.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160817142539.htm  Original web page at Science Daily

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Across the animal kingdom there is a strong trend for females to be more caring parents

Using mathematical models, the researchers found that if the only initial difference between the sexes is the size of the sex cells they make (sperm by males and eggs by females), evolution does not favor females becoming more attentive parents.

“Although an egg is a much larger parental investment than a tiny sperm, there is no propensity for females to care more as a result,” said Academy Research Fellow, Dr Lutz Fromhage, from the University of Jyväskylä. But he added, “There is, however, also no evolutionary force favouring equal care by both sexes.” This new finding refutes earlier theories that concluded that equal care by both parents will evolve.

Although females tend to care more than males, there is much variation among species. In many fish, for example, only males guard eggs and defend babies, but in mammals females usually care alone. Dr Fromhage said the study, published in Nature Communications, would lead to a more solid theoretical foundation to understand how male and female parental care evolves.

So why do females provide more care? The researchers propose that another process is important: investment in being sexy, hence mating sooner, might trade-off with the ability to provide care efficiently. Taking this balancing act into account, evolution favors ever more care by the initially more-caring sex. Eventually this sex might end up caring alone. “One factor that could set the ball rolling is an inevitable difference in the certainty of parentage of males and females,” said Prof Michael Jennions from the Australian National University, “with many more sperm than eggs, it is often hard for a male to be sure that he is the father. So males might initially care a little less.”

Many researchers have put forward arguments to explain why females care more than males, but this new study provides formal confirmation based on solid maths.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160818090143.htm Original web page at Science Daily

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Common cold viruses originated in camels, just like MERS

There are four globally endemic human coronaviruses which, together with the better known rhinoviruses, are responsible for causing common colds. Usually, infections with these viruses are harmless to humans. DZIF Professor Christian Drosten, Institute of Virology at the University Hospital of Bonn, and his research team have now found the source of “HCoV-229E,” one of the four common cold coronaviruses — it also originates from camels, just like the dreaded MERS virus.

The Middle East respiratory syndrome (MERS) coronavirus was identified in humans for the first time in 2012. It causes severe respiratory tract infections that are often fatal. Dromedaries were confirmed to be its animal source some time ago.

“In our MERS investigations we examined about 1,000 camels for coronaviruses and were surprised to find pathogens that are related to ‘HCoV-229E’, the human common cold virus, in almost six percent of the cases,” says Drosten. Further comparative molecular genetic analysis of common cold viruses in bats, humans and dromedaries suggests that this common cold virus was actually transmitted from camels to humans. Common cold virus evolution could provide a scenario for MERS emergence

Drosten and his team isolated live camel common cold viruses and discovered that these could principally also enter human cells — via the same receptor used by the common cold virus “HCoV-229E.” However, the human immune system is able to defend itself against the camel viruses, just as it can against common cold viruses. Furthermore, tests with human serum and animal common cold viruses showed that there is no immediate risk of an epidemic in humans, because largest part of the human population already has immunity, owing to the widespread immunity against the common cold virus HCoV-229E.

So is this the all-clear for MERS viruses too? “The MERS virus is a strange pathogen: smaller, regionally restricted outbreaks, for example in hospitals, keep occurring. Fortunately, the virus has not adapted well enough to humans, and has consequently been unable to spread globally up to now,” says Drosten. The results of the current investigations on predecessors of the human HCoV-229E virus in camels depict a situation that is similar to the current situation with MERS. These predecessor viruses are also not optimally adapted to humans.

The global spread of HCoV-229E through human-to-human transmission, which is highly likely to have occurred during a past pandemic, gives rise to concern. “Our current study gives us a warning sign regarding the risk of a MERS pandemic — because MERS could perhaps do what HCoV-229E did.” So there is need for action: DZIF researchers are working intensively on researching a vaccine against MERS; it will go into clinical testing early next year.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160818093438.htm  Original web page at Science Daily

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Canine babesiosis outbreak in UK under control, but needs monitoring

Scientists at the University of Liverpool are using the health records of dogs to monitor the status of a potentially fatal tick-borne disease that appears to have been imported into the UK.

Canine babesiosis is transmitted to dogs by infected ticks, with symptoms including a lack of appetite, fever and jaundice. Although normally only found in mainland Europe, in February 2016 three cases of Babesia were reported at one Essex veterinary practice in dogs that had not travelled abroad.

The outbreak was widely reported in the national media, with concern raised that the disease could soon affect dogs elsewhere in the country.

A team from the Small Animal Veterinary Surveillance Network (SAVSNET), which is as a partnership between the University of Liverpool and the British Small Animal Veterinary Association, used electronic health records and laboratory data to assess the risk of this emerging disease in the UK.

Using data from 2015, they analysed cases of reported tick bites and Babesia in dogs from 392 volunteer veterinary premises across the UK.

Published in the Veterinary Record, the analysis revealed a low background level of Babesia infection in the UK. Based on the sporadic and geographically distributed nature, these cases were most likely linked to overseas travel.

The laboratory data also confirmed a small cluster of eight Babesia cases in the Chelmsford area of Essex, where the reported outbreak was centred. The clustering of these cases was consistent with exposure to a local infected tick population.

Since March this year, SAVSNET has seen no new diagnoses of Babesia in Chelmsford, suggesting that the outbreak may be currently under control.

Dr Alan Radford, SAVSNET academic lead, said: “While this is positive news, we would like to remind vets to keep Babesia in mind, especially in practices close to the outbreak where infected ticks are likely to still be active, and persist in the coming years. Currently this seems to be a rare disease but one that we need to keep an eye on.

“One striking finding from our analysis is that ticks remain active in winter, albeit at presumably low levels. It’s therefore important that we continue to monitor tick activity, and we would encourage vets and nurses across the UK to keep recording information about tick bites they treat.”

Real-time updates of Babesia cases and other important diseases, based on data submitted to SAVSNET, are now available to view as an interactive map on the SAVSNET website.

Dr Fernando Sánchez-Vizcaíno, lead author on the paper concluded: “We’ve shown that health informatics surveillance can help provide real-time local updates on important and emerging pathogens, such as Babesia. This could help monitor the response to outbreaks, and in the future contribute to their early detection.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160818093436.htm  Original web page Science Daily

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Stress bites! Researchers study mosquito/bird interactions

Research shows stressed-out birds more attractive to mosquitoes, raising fears birds exposed to stressors such as road noise, pesticides and light pollution, will be bitten more often and spread more West Nile virus

When researchers from the University of South Florida (USF) and colleagues investigated how the stress hormone, corticosterone, affects how birds cope with West Nile virus, they found that birds with higher levels of stress hormone were twice as likely to be bitten by mosquitoes that transmit the virus. Their studies have implications for the transmission of other viruses such as Eastern Equine Encephalitis, and perhaps even Zika, both known to be carried by the kind of mosquitoes used in this study. A paper describing their research was published in the Proceedings of the Royal Society B.

“Few studies have considered how stress hormone effects on individuals might influence population dynamics,” said study lead author Dr. Stephanie Gervasi, who conducted the studies while carrying out her postdoctoral work at USF and is now at the Monell Chemical Senses Center in Philadelphia. “For vector-borne diseases such as West Nile virus, the presence of corticosterone could influence pathogen spread through effects on contact rates with the mosquitoes that transmit it. In addition, stress hormones have negative effects on animals including immunosuppression and increased susceptibility to infections, which is why we are now also studying how corticosterone affects the birds’ immune response to the virus.”

According to the researchers, mosquitoes use a variety of cues to locate a target, including carbon dioxide output, body size and temperature. They hypothesized that these signals coming from a bird could convey information about stress hormones making the birds more appealing targets for the insects.

With the effects of corticosterone on mosquito feeding choices unknown, in a series of studies the researchers experimentally manipulated songbird stress hormones levels. Then they examined mosquito feeding preferences, feeding success and productivity as well as the defensive behaviors of birds trying to avoid being bitten.

In several phases of the study, zebra finches were treated with a low or high level of corticosterone and their caged light environment was altered to simulate dusk as the birds were made available to mosquitoes for measured periods of time. Bird and mosquito behavior was observed via video and the mosquitoes were later examined to determine if they had fed on the birds. The researchers also investigated the timing of subsequent mosquito egg-laying after the insects fed on the birds.

“Mosquitoes seem to be able to ‘sniff out’ the stress hormone and key in on individual birds,” said the study’s principal investigator Dr. Lynn Martin, associate professor in the USF Department of Integrative Biology. “The birds injected with higher levels of the hormone were twice as likely to be bitten by mosquitoes, even those hormone-treated birds were much more defensive than untreated ones. Corticosterone treatment increased tail flicks, and head shakes, and other defensive behaviors, but the mosquitoes managed to breach those defenses and feed more on stress hormone-treated birds.”

The study’s broader ecological implications suggest that an elevated stress hormone concentration raises the level of host attractiveness, potentially affecting the transmission of mosquito-borne diseases in a number of ways.

“Stress hormones also altered the relationship between the timing of laying and clutch size in mosquitoes,” said co-principal investigator Dr. Thomas Unnasch, chair and Distinguished USF Health Professor in the Department of Global Health, USF College of Public Health.

Mosquitoes that fed on birds with high stress hormone levels tended to lay different sized clutches of eggs at different rates than mosquitoes fed on control birds. These effects of bird stress on mosquito reproduction suggest that mosquito-feeding choice might also affect disease cycles in nature by changing the number of newborn mosquitoes that could be infected later by stressed birds.

The researchers concluded that the corticosterone levels in their test birds were within the range of normal for birds in the wild when exposed to stressors in natural their environments, such as road noise, pesticides and light pollution.

“Much more work is necessary to further understand on the interplay of host corticosterone, vector-feeding behavior, host defenses and mosquito productivity,” the researchers said.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160810084631.htm Original web page at Science Daily

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Insecticide treatment of cattle to kill sand flies and combat leishmaniasis

With an estimated 500,000 human infections and 50,000 deaths annually, visceral leishmaniasis (VL) is the second most prevalent parasitic killer, behind malaria. Leishmania parasites are transmitted through the bite of phlebotomine sand flies. A study published in PLOS Neglected Tropical Diseases makes the case that fighting the insects by treating cattle with the long-lasting insecticide, fipronil, could substantially reduce VL in areas where people and cattle live in close proximity.

Two-thirds of VL cases occur on the Indian subcontinent, and 90% of the Indian VL cases are reported in the densely populated and impoverished state of Bihar. Female sand flies there primarily bite humans and cattle (mostly at night), and after sand fly eggs hatch, the larvae feed on organic matter, the most abundant source being cow patties. At present, control of sand flies in India involves indoor residual spraying with pyrethroid insecticides, but Bihari villagers regularly sleep outdoors during the hot summer months.

Fipronil is an insecticide with a long half-life. The insecticide remains in the system of animals for several weeks to several months, dependent on the concentration administered. Fipronil does not harm mammals at low concentrations, but when fed to cattle at low concentrations in drug form, can kill adult blood-feeding sand flies and sand fly larvae that feed on the cattle feces. Fipronil-based sand fly control could therefore last for several months following a single treatment — and complement the practice of indoor spraying.

David Poché, from Texas A&M University in College Station, USA, and colleagues set out to explore the insecticide’s potential to control sand flies. The researchers developed a mathematical model that describes the effects of fipronil-induced mortality on a sand fly population within a village in Bihar. They describe the model and evaluate its performance based on known parameters. Then they use the model to simulate fipronil-based control schemes with different treatment timing and frequency, and compare their effect on reductions in sand fly populations during spring and summer (June, July, and August are the period of peak human exposure).

Single annual treatments applied in March, May, June, or July noticeably reduced the population peaks that occurred over the 30 to 60 days following treatment, but populations recovered relatively quickly. Treatments applied 3 times per year at 2-month intervals were most effective when initiated in March, reducing the population peaks in April through August by roughly 90% relative compared with no treatment. Treatments applied 6 times per year at 2-month intervals were most effective when initiated in January, reducing population peaks in June through August by over 95%. Monthly treatments resulted in eradication of the sand fly population within 2 years.

Overall, the simulation results suggest that the success of fipronil treatment depends not only on the frequency of applications but also on the timing relative to the sand fly lifecycle. Maintaining high drug levels in cattle feces during the period of high larval abundance seems particularly important.

As the researchers discuss, “while more frequent applications obviously are more efficacious, they also are more expensive and more difficult logistically. Thus, the ability to assess not only efficacy of treatment schemes per se but also their cost-effectiveness and their logistical feasibility is of paramount importance.” In this context, they mention an estimated cost of $1 per cow per treatment, as well as the fact that milk production per cow is estimated to increase by $0.50 per day, thus offering an incentive to villagers to treat their animals.

Further evaluation of sand fly control through the use of fipronil-based drugs in cattle, the researchers say, ideally would involve a field trial in Bihar. Such a trial could provide data on the actual proportion of adult sand flies that obtain their blood meal from cattle and the proportion of eggs laid in organic matter containing cattle feces; numbers that are currently unknown and therefore force the researchers to make assumptions that cause uncertainty in the model predictions.

Suggesting that their model could be adapted to settings where donkeys, dogs, rabbits, or rodents are the main animal targets of blood-thirsty sand flies, the researchers hope that it “will prove useful in the a priori evaluation of the potential role of treatment schemes involving the use of fipronil-based drugs in the control of leishmaniasis on the Indian Subcontinent and beyond.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160818145936.htm  Original web page at Science

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* How norovirus gets inside cells: New clues

Norovirus is the most common viral cause of diarrhea worldwide, but scientists still know little about how it infects people and causes disease because the virus grows poorly in the lab. The discovery, in mice, provides new ways to study a virus notoriously hard to work with and may lead to treatments or a vaccine.

Researchers at Washington University School of Medicine in St. Louis have identified the protein that norovirus — shown here in a colored transmission electron micrograph — uses to invade cells. Norovirus is the most common viral cause of diarrhea worldwide, but scientists still know little about how it infects people and causes disease because the virus grows poorly in the lab. The discovery, in mice, provides new ways to study a virus notoriously hard to work with and may lead to treatments or a vaccine.

Now, researchers at Washington University School of Medicine in St. Louis have identified the protein that norovirus uses to invade cells. The discovery, in mice, provides new ways to study a virus notoriously hard to work with and may lead to treatments or a vaccine.

“Our inability to grow the virus in the lab has limited our ability to develop anti-viral agents. If you can’t get the virus to multiply in human cells, how are you going to find compounds that inhibit multiplication?” said Herbert “Skip” Virgin, MD, PhD, the Mallinckrodt Professor and Chair of the Department of Pathology and Immunology and the study’s senior author. “This discovery provides a good basis for our mouse model, which we can then use to understand noroviral pathogenesis and search for treatments in people.” The research is published August 18 in Science.

Norovirus is infamous for causing outbreaks of diarrhea, vomiting and stomach cramps on cruise ships, in military barracks and in other environments where people live in close quarters. For most people, infection leads to an uncomfortable day or two punctuated with frequent trips to the bathroom, but in vulnerable populations such as cancer patients and older people, the disease can be long-lasting and sometimes deadly.

There are many noroviruses, but each is restricted to infecting just one animal species. Human norovirus will not infect any of the species typically used in biomedical research, such as mice, rats or rabbits. Human norovirus won’t grow even in human cells in petri dishes.

“Since human norovirus won’t grow in human cell lines or laboratory animals, you can’t test a drug, you can’t test a vaccine,” Virgin said. “You’d have to do those kinds of studies in people, but it would be better if we can first conduct tests in animal models.”

When mouse norovirus was discovered in 2003, it seemed like a great opportunity to make a mouse model of norovirus infection. The genomes of mouse and human norovirus are very similar, and the viruses even look alike under the electron microscope. Nobody could ever be sure, however, that how mouse norovirus acts in mice is relevant to how human norovirus acts in humans.

Virgin and postdoctoral researchers Craig Wilen, MD, PhD, and Robert Orchard, PhD, thought that if they could identify the reason that mouse norovirus infects only mice and human norovirus infects only humans, they could improve their model of norovirus infection.

The researchers used a genetic tool known as CRISPR-Cas9 to identify mouse genes that are important for mouse noroviral infection. They found that when a gene called CD300lf was knocked down by CRISPR-Cas9, norovirus could not infect the cells. CD300lf codes for a protein on the surface of mouse cells, and the researchers believe the virus latches on to it to get inside the cell.

Furthermore, when the researchers expressed mouse CD300lf protein on the surface of human cells, mouse norovirus was able to infect the human cells and multiply. “Mouse norovirus grew just fine in human cells,” Virgin said. “This tells us that the species restriction is due to the ability to get inside the cells in the first place. Once inside the cells, most likely all the other mechanisms are conserved between human and mouse noroviruses, since the viruses are so similar.”

The researchers also found that mouse norovirus requires a second molecule, or cofactor, to infect cells; CD300lf by itself isn’t enough. But they were unable to nail down the molecule’s identity.

“At this point we know more about what it isn’t than what it is,” said Orchard, a co-lead author on the study. “Every week there’s a new favorite hypothesis. It’s probably a small molecule found in the blood, not a protein.”

It is unusual for a virus to require a cofactor for infection. Their discovery suggests that the lack of a necessary cofactor may be why scientists have had a difficult time growing human norovirus in the lab.

The researchers are working on ways to use human cells with the mouse CD300lf protein to study noroviral infection. One possibility is to use the system to screen drugs to block viral multiplication. Such drugs could be administered prophylactically to people around the epicenter of an outbreak, or as a treatment for immunocompromised individuals.

The discovery of the mouse receptor for norovirus also could lead to a better understanding of how the virus causes disease.

“We still don’t even know if the virus infects epithelial cells or immune cells, and that matters if you want to develop a vaccine,” said Wilen, a co-lead author on the study. “We have developed a knockout mouse that lacks CD300lf, and we are using it to identify the cell types involved. We’re hoping that a better understanding of the pathogenesis will lead to better ways to treat or prevent this very common disease.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160818150000.htm Original web page at Science Daily

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Zika infection may affect adult brain cells

Concerns over the Zika virus have focused on pregnant women due to mounting evidence that it causes brain abnormalities in developing fetuses. However, new research in mice from scientists at The Rockefeller University and La Jolla Institute for Allergy and Immunology suggests that certain adult brain cells may be vulnerable to infection as well. Among these are populations of cells that serve to replace lost or damaged neurons throughout adulthood, and are also thought to be critical to learning and memory.

“This is the first study looking at the effect of Zika infection on the adult brain,” says Joseph Gleeson, adjunct professor at Rockefeller, head of the Laboratory of Pediatric Brain Disease, and Howard Hughes Medical Institute investigator. “Based on our findings, getting infected with Zika as an adult may not be as innocuous as people think.”

Although more research is needed to determine if this damage has long-term biological implications or the potential to affect behavior, the findings suggest the possibility that the Zika virus, which has become widespread in Central and South America over the past eight months, may be more harmful than previously believed. The new findings were published in Cell Stem Cell on August 18.

“Zika can clearly enter the brain of adults and can wreak havoc,” says Sujan Shresta, a professor at the La Jolla Institute of Allergy and Immunology. “But it’s a complex disease — it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle, and now we know what to look for.”

Early in gestation, before our brains have developed into a complex organ with specialized zones, they are comprised entirely of neural progenitor cells. With the capability to replenish the brain’s neurons throughout its lifetime, these are the stem cells of the brain. In healthy individuals, neural progenitor cells eventually become fully formed neurons, and it is thought that at some point along this progression they become resistant to Zika, explaining why adults appear less susceptible to the disease.

But current evidence suggests that Zika targets neural progenitor cells, leading to loss of these cells and to reduced brain volume. This closely mirrors what is seen in microcephaly, a developmental condition linked to Zika infection in developing fetuses that results in a smaller-than-normal head and a wide variety of developmental disabilities.

The mature brain retains niches of these neural progenitor cells that appear to be especially impacted by Zika. These niches — in mice they exist primarily in two regions, the subventricular zone of the anterior forebrain and the subgranular zone of the hippocampus — are vital for learning and memory.

Gleeson and his colleagues suspected that if Zika can infect fetal neural progenitor cells, it wouldn’t be a far stretch for them to also be able to infect these cells in adults. In a mouse model engineered by Shresta and her team to mimic Zika infection in humans, fluorescent biomarkers illuminated to reveal that adult neural progenitor cells could indeed be hijacked by the virus.

“Our results are pretty dramatic — in the parts of the brain that lit up, it was like a Christmas tree,” says Gleeson. “It was very clear that the virus wasn’t affecting the whole brain evenly, like people are seeing in the fetus. In the adult, it’s only these two populations that are very specific to the stem cells that are affected by virus. These cells are special, and somehow very susceptible to the infection.”

The researchers found that infection correlated with evidence of cell death and reduced generation of new neurons in these regions. Integration of new neurons into learning and memory circuits is crucial for neuroplasticity, which allows the brain to change over time. Deficits in this process are associated with cognitive decline and neuropathological conditions, such as depression and Alzheimer’s disease.

Gleeson and colleagues recognize that healthy humans may be able to mount an effective immune response and prevent the virus from attacking. However, they suggest that some people, such as those weakened immune systems, may be vulnerable to the virus is a way that has not yet been recognized.

“In more subtle cases, the virus could theoretically impact long-term memory or risk of depression,” says Gleeson, “but tools do not exist to test the long-term effects of Zika on adult stem cell populations.”

In addition to microcephaly, Zika has been linked to Guillain-Barré syndrome, a rare condition in which the immune system attacks parts of the nervous system, leading to muscle weakness or even paralysis. “The connection has been hard to trace since Guillain-Barré usually develops after the infection has cleared,” says Shresta. “We propose that infection of adult neural progenitor cells could be the mechanism behind this.”

There are still many unanswered questions, including exactly how translatable findings in this mouse model are to humans. Gleeson’s findings in particular raise questions such as: Does the damage inflicted on progenitor cells by the virus have lasting biological consequences, and can this in turn affect learning and memory? Or, do these cells have the capability to recover? Nonetheless, these findings raise the possibility that Zika is not simply a transient infection in adult humans, and that exposure in the adult brain could have long-term effects.

“The virus seems to be traveling quite a bit as people move around the world,” says Gleeson. “Given this study, I think the public health enterprise should consider monitoring for Zika infections in all groups, not just pregnant women.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160818131134.htm Original web page at Science Daily

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Burnout is caused by mismatch between unconscious needs and job demands

New research shows that burnout is caused by a mismatch between a person’s unconscious needs and the opportunities and demands at the workplace. These results have implications for the prevention of jobburnout.

Imagine an accountant who is outgoing and seeks closeness in her social relationships, but whose job offers little scope for contact with colleagues or clients. Now imagine a manager, required to take responsibility for a team, but who does not enjoy taking center-stage or being in a leadership role. For both, there is a mismatch between their individual needs and the opportunities and demands at the workplace. A new study in the open-access journal Frontiers in Psychology shows that such mismatches put employees at risk of burnout.

Burnout is a state of physical, emotional, and mental exhaustion from work, which results in a lack of motivation, low efficiency, and a helpless feeling. Its health effects include anxiety, cardiovascular disease, immune disorders, insomnia, and depression. The financial burden from absenteeism, employee turnover, reduced productivity, and medical, legal, and insurance expenses due to burnout and general work-related stress is staggering: for example, the American Institute of Stress estimates the total cost to American enterprises at 300 billion US$ per year, while a 2012 study commissioned by the Health Programme of the European Union estimates the annual cost to EU enterprises at 272 billion €.

In the new study, researchers from the Universities of Zurich and Leipzig show that the unconscious needs of employees — their so-called “implicit motives” — play an important role in the development of burnout. The researchers focus on two important motives: the power motive, that is, the need to take responsibility for others, maintain discipline, and engage in arguments or negotiation, in order to feel strong and self-efficacious; and the affiliation motive, the need for positive personal relations, in order to feel trust, warmth, and belonging. A mismatch between job characteristics and either implicit motive can cause burnout, the results show. Moreover, a mismatch in either direction is risky: employees can get burned out when they have too much or not enough scope for power or affiliation compared to their individual needs.

“We found that the frustration of unconscious affective needs, caused by a lack of opportunities for motive-driven behavior, is detrimental to psychological and physical well-being. The same is true for goal-striving that doesn’t match a well-developed implicit motive for power or affiliation, because then excessive effort is necessary to achieve that goal. Both forms of mismatch act as ‘hidden stressors’ and can cause burnout,” says the leading author, Veronika Brandstätter, Professor of Psychology at the University of Zurich, Switzerland.

Brandstätter and colleagues recruited 97 women and men between 22 and 62 through the Swiss Burnout website, an information resource and forum for Swiss people suffering from burnout. Participants completed questionnaires about their physical well-being, degree of burnout, and the characteristics of their job, including its opportunities and demands.

To assess implicit motives — whose strength varies from person to person, but which can’t be measured directly through self-reports since they are mostly unconscious — Brandstätter et al. used an inventive method: they asked the participants to write imaginative short stories to describe five pictures, which showed an architect, trapeze artists, women in a laboratory, a boxer, and a nightclub scene. Each story was analyzed by trained coders, who looked for sentences about positive personal relations between persons (thus expressing the affiliation motive) or about persons having impact or influence on others (expressing the power motive). Participants who used many such sentences in their story received a higher score for the corresponding implicit motive.

The greater the mismatch between someone’s affiliation motive and the scope for personal relations at the job, the higher the risk of burnout, show the researchers. Likewise, adverse physical symptoms, such as headache, chest pain, faintness, and shortness of breath, became more common with increasing mismatch between an employee’s power motive and the scope for power in his or her job.

Importantly, these results immediately suggest that interventions that prevent or repair such mismatches could increase well-being at work and reduce the risk of burnout.

“A starting point could be to select job applicants in such a way that their implicit motives match the characteristics of the open position. Another strategy could be so-called “job crafting,” where employees proactively try to enrich their job in order to meet their individual needs. For example, an employee with a strong affiliation motive might handle her duties in a more collaborative way and try to find ways to do more teamwork,” says Brandstätter.

“A motivated workforce it the key to success in today’s globalized economy. Here, we need innovative approaches that go beyond providing attractive working conditions. Matching employees’ motivational needs to their daily activities at work might be the way forward. This may also help to address growing concerns about employee mental health, since burnout is essentially an erosion of motivation. To do so, we must increasingly take account of motivational patterns in the context of occupational stress research, and study person-environment-fit across entire organizations and industries,” says Beate Schulze, a Senior Researcher at the Department of Social and Occupational Medicine of the University of Leipzig and Vice-President of the Swiss Expert Network on Burnout.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160811171643.htm  Original web page at Science Daily

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* Gene therapy treats all muscles in the body in muscular dystrophy dogs

Muscular dystrophy, which affects approximately 250,000 people in the U.S., occurs when damaged muscle tissue is replaced with fibrous, fatty or bony tissue and loses function. For years, scientists have searched for a way to successfully treat the most common form of the disease, Duchenne Muscular Dystrophy (DMD), which primarily affects boys. Now, a team of University of Missouri researchers have successfully treated dogs with DMD and say that human clinical trials are being planned in the next few years.

“This is the most common muscle disease in boys, and there is currently no effective therapy,” said Dongsheng Duan, the study leader and the Margaret Proctor Mulligan Professor in Medical Research at the MU School of Medicine. “This discovery took our research team more than 10 years, but we believe we are on the cusp of having a treatment for the disease.”

Patients with Duchenne muscular dystrophy have a gene mutation that disrupts the production of a protein known as “dystrophin.” Absence of dystrophin starts a chain reaction that eventually leads to muscle cell degeneration and death. Affected boys lose their ability to walk and breathe as they get older. This places significant limitations on individuals afflicted with the disease. Dystrophin also is one of the largest genes in the human body.

“Due to its size, it is impossible to deliver the entire gene with a gene therapy vector, which is the vehicle that carries the therapeutic gene to the correct site in the body,” Duan said. “Through previous research, we were able to develop a miniature version of this gene called a microgene. This minimized dystrophin protected all muscles in the body of diseased mice.”

However, it took the team more than 10 years to develop a strategy that can safely send the micro-dystrophin to every muscle in a dog that is afflicted by the disease. The dog has a body size similar to that of an affected boy. Success in the dog will set the foundation for human tests.

In this latest study, the MU team demonstrated for the first time that a common virus can deliver the microgene to all muscles in the body of a diseased dog. The dogs were injected with the virus when they were two to three months old and just starting to show signs of DMD. The dogs are now six to seven months old and continue to develop normally

“The virus we are using is one of the most common viruses; it is also a virus that produces no symptoms in the human body, making this a safe way to spread the dystrophin gene throughout the body,” Duan said. “These dogs develop DMD naturally in a similar manner as humans. It’s important to treat DMD early before the disease does a lot of damage as this therapy has the greatest impact at the early stages in life.”

https://www.sciencedaily.com/  Science  Daily

https://www.sciencedaily.com/releases/2015/10/151022141722.htm  Original web page at Science Daily

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UK government gives Brexit science funding guarantee

Philip Hammond, the UK’s chancellor of the exchequer, has promised to underwrite EU research projects after Brexit.

British scientists say they’re relieved by a government promise to guarantee them funding for existing EU research projects, even after the country leaves the European Union. But the reassurance only partly allays concerns about Brexit’s effect on UK science.

The United Kingdom receives billions of euros for research from the European Union, mostly from its €74.8-billion (US$83.6-billion) Horizon 2020 (H2020) programme. June’s referendum vote for the nation to leave the EU left British scientists worried that funding for existing multi-year projects could be yanked away. And the uncertainty led to reports of EU collaborators deciding to drop UK scientists from future grant applications — even though the United Kingdom is still a full member of the EU. Tell Nature: Big or small, we want to hear how Brexit is affecting you

But on 13 August, the government announced that it will step in to pay UK contributions to EU H2020 projects after Brexit, provided that the projects were bid for before the day that the UK leaves the EU (a date which has not yet been fixed). “By underwriting Horizon 2020 funding in this way today, we are again demonstrating the importance we place on maintaining the world leading research that takes place in the UK,” said UK science minister, Jo Johnson.

Other types of EU project were given lesser guarantees. UK recipients of EU ‘structural funds’ (some of which are spent on research infrastructure) are to be assured funding only if they bid for them before an annual address on the nation’s finances known as the ‘Autumn Statement’ — an event that typically takes place in November or December. Still, the promise ensures that, for example, the UK’s University of Manchester can expect to receive £5 million (US$6.4 million) from EU funds for a planned Graphene Engineering Innovation Centre.

“Since the referendum vote, the research community has been struggling with the uncertainty. This provides huge reassurance,” says Sarah Main, director of the Campaign for Science and Engineering (CaSE) in London. The move will also reassure European collaborators, she says.

“This is encouraging news that provides much-needed stability for British universities during the transition period as the UK exits the EU, and provides an important signal to European researchers that they can continue to collaborate with their UK colleagues as they have before,” said Alistair Jarvis, deputy chief executive of the higher-education umbrella group Universities UK in London.

But the campaign group Scientists for EU issued a statement calling the announcement “decidedly underwhelming” and “a confirmation of the bare essentials, but nothing more”. After Brexit, UK scientists may lose the ability to apply for H2020 funding, depending on the terms of the split. And the government has not committed to shoring up those potential lost funds with domestic grants, Scientists for EU pointed out.

“This guarantee alleviates some of the uncertainties about existing and imminent H2020 grants, but does nothing to dispel fears about mobility between the UK and the rest of the EU following Brexit, which is integral to many H2020 schemes, nor does it address longer-term funding issues,” says Paul Crowther, who heads the physics and astronomy department at the University of Sheffield, UK.

Main says that she is still encouraged by the government’s continued support for science. She cites another example of political positive intentions: a letter from UK Prime Minister Theresa May in July to the director of London’s Francis Crick Institute, Paul Nurse, saying that the government was committed to ensuring a positive outcome for UK science. “To be honest, I’m feeling positive,” she says.

Nature doi:10.1038/nature.2016.20434

http://www.nature.com/news/index.html Nature

http://www.nature.com/news/uk-government-gives-brexit-science-funding-guarantee-1.20434 Original web page at Nature

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More evidence that ‘healthy obesity’ may be a myth

The term “healthy obesity” has gained traction over the past 15 years, but scientists have recently questioned its very existence. A study published August 18 in Cell Reports provides further evidence against the notion of a healthy obese state, revealing that white fat tissue samples from obese individuals classified as either metabolically healthy or unhealthy actually show nearly identical, abnormal changes in gene expression in response to insulin stimulation.

“The findings suggest that vigorous health interventions may be necessary for all obese individuals, even those previously considered to be metabolically healthy,” says first author Mikael Rydén of the Karolinska Institutet. “Since obesity is the major driver altering gene expression in fat tissue, we should continue to focus on preventing obesity.”

Obesity has reached epidemic proportions globally, affecting approximately 600 million people worldwide and significantly increasing the risk of heart disease, stroke, cancer, and type 2 diabetes. Since the 1940s, evidence supporting the link between obesity and metabolic and cardiovascular diseases has been steadily growing. But in the 1970s and 80s, experts began to question the extent to which obesity increases the risk for these disorders. Subsequent studies in the late 90s and early 2000s showed that some obese individuals display a relatively healthy metabolic and cardiovascular profile.

Recent estimates suggest that up to 30% of obese individuals are metabolically healthy and therefore may need less vigorous interventions to prevent obesity-related complications. A hallmark of metabolically healthy obesity is high sensitivity to the hormone insulin, which promotes the uptake of blood glucose into cells to be used for energy. However, there are currently no accepted criteria for identifying metabolically healthy obesity, and whether or not such a thing exists is now up for debate.

To address this controversy, Rydén, Carsten Daub, and Peter Arner of the Karolinska Institutet assessed responses to insulin in 15 healthy, never-obese participants and 50 obese subjects enrolled in a clinical study of gastric bypass surgery. The researchers took biopsies of abdominal white fat tissue before and at the end of a two-hour period of intravenous infusion of insulin and glucose. Based on the glucose uptake rate, the researchers classified 21 obese subjects as insulin sensitive and 29 as insulin resistant.

Surprisingly, mRNA sequencing of white fat tissue samples revealed a clear distinction between never-obese participants and both groups of obese individuals. White fat tissue from insulin-sensitive and insulin-resistant obese individuals showed nearly identical patterns of gene expression in response to insulin stimulation. These abnormal gene expression patterns were not influenced by cardiovascular or metabolic risk factors such as waist-to-hip ratio, heart rate, or blood pressure. The findings show that obesity rather than other common risk factors is likely the primary factor determining metabolic health.

“Our study suggests that the notion of metabolically healthy obesity may be more complicated than previously thought, at least in subcutaneous adipose tissue,” Rydén says. “There doesn’t appear to be a clear transcriptomic fingerprint that differentiates obese subjects with high or low insulin sensitivity, indicating that obesity per se is the major driver explaining the changes in gene expression.”

One limitation of the study is that it examined gene expression profiles only in subcutaneous white fat tissue, not other types of fat tissue or other organs. Moreover, all of the obese subjects were scheduled to undergo bariatric surgery, so the findings may only apply to individuals with severe obesity.

In future research, Rydén and his collaborators will track the study participants after bariatric surgery to determine whether weight loss normalizes gene expression responses to insulin. They will also look for specific genes linked to improved metabolic health in these individuals.

In the meantime, the study has an important take-home message. “Insulin-sensitive obese individuals may not be as metabolically healthy as previously believed,” Rydén says. “Therefore, more vigorous interventions may be necessary in these individuals to prevent cardiovascular and metabolic complications.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160818131127.htm  Original web page web page at Science Daily

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Novel compounds arrested epilepsy development in mice

A team led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans’ Neuroscience Center of Excellence, has developed neuroprotective compounds that may prevent the development of epilepsy. The findings will be published online in Scientific Reports, a Nature journal, on July 22, 2016.

In this study in an experimental model of epilepsy in mice, the compounds prevented seizures and their damaging effects on dendritic spines, specialized structures that allow brain cells to communicate. In epilepsy, these structures are damaged and rewire incorrectly, creating brain circuits that are hyper-connected and prone to seizures, an important example of pathological plasticity.

“In the current study, preservation of dendritic spines and subsequent protection from seizures, were observed up to 100 days post-treatment, suggesting the process of epilepsy development has been arrested,” notes Dr. Nicolas Bazan, Director of the LSU Health New Orleans Neuroscience Center of Excellence.

Dr. Bazan and Professor Julio Alvarez-Builla Gomez, a medicinal chemist from the University of Alcala in Spain, discovered and patented the LAU compounds, named for the inventors in Louisiana and the Spanish university. A number of LAU compounds were studied in this research, which blocked a neuroinflammatory signaling receptor, protecting dendritic spines and lessening seizure susceptibility and onset, as well as hyper-excitability.

According to the National Institutes of Health, the epilepsies are a spectrum of brain disorders ranging from severe, life-threatening and disabling, to ones that are much more benign. In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing strange sensations, emotions, and behavior or sometimes convulsions, muscle spasms, and loss of consciousness. It is not uncommon for people with epilepsy, especially children, to develop behavioral and emotional problems in conjunction with seizures. Issues may also arise as a result of the stigma attached to having epilepsy, which can lead to embarrassment and frustration or bullying, teasing, or avoidance in school and other social settings. For many people with epilepsy, the risk of seizures restricts their independence (some states refuse drivers licenses to people with epilepsy) and recreational activities. Epilepsy can be a life-threatening condition. Some people with epilepsy are at special risk for abnormally prolonged seizures or sudden unexplained death in epilepsy. There is currently no cure.

The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health. “Future clinical studies would evaluate the potential application of the compounds that we have developed and/or the mechanisms that we have discovered that are targeted by these compounds in the development of epilepsy,” concludes Dr. Bazan. “Most of the anti-epileptic drugs currently available treat the symptom – seizures- not the disease itself. Understanding the potential therapeutic usefulness of compounds that may interrupt the development process may pave the way for disease-modifying treatments for patients at risk for epilepsy.”

The research is part of an ongoing effort in Dr. Bazan laboratory to understand the critical role of brain plasticity which underlies many aspects of health and disease, from developmental disorders like dyslexia to aging, retinal degeneration, neurotrauma (concussions, TBI), stroke, Parkinson’s and Alzheimer’s disease.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/07/160722092930.htm Original web page at Science Daily

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Modifying a living genome with genetic equivalent of ‘search and replace’

Researchers including George Church have made further progress on the path to fully rewriting the genome of living bacteria. Such a recoded organism, once available, could feature functionality not seen in nature. It could also make the bacteria cultivated in pharmaceutical and other industries immune to viruses, saving billions of dollars of losses due to viral contamination.

Finally, the altered genetic information in such an organism wouldn’t be able to contaminate natural cells because of the code’s limitations outside the lab, researchers say, so its creation could stop laboratory engineered organisms from genetically contaminating wildlife. In the DNA of living organisms, the same amino acid can be encoded by multiple codons — DNA “words” of three nucleotide letters.

Here, building on previous work that demonstrated it was possible to use the genetic equivalent of “search and replace” in Escherichia coli to substitute a single codon with an alternative, Nili Ostrov, Church and colleagues explored the feasibility of replacing multiple codons, genome-wide.

The researchers attempted to reduce the number of codons in the E. coli code from 64 to 57 by exploring how to eradicate more than 60,000 instances of seven different codons. They systematically replaced all 62,214 instances of these seven codons with alternatives. In the recoded E.coli segments that the researchers assembled and tested, 63% of all instances of the seven codons were replaced, the researchers say, and most of the genes impacted by underlying amino acid changes were expressed normally.

Though they did not achieve a fully operational 57-codon E. coli, “a functionally altered genome of this scale has not yet been explored,” the authors write. Their results provide critical insights into the next step in the genome rewriting arena — creating a fully recoded organism.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/08/160818145954.htm  Original web page at Science Daily

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* Scientists test nanoparticle drug delivery in dogs with osteosarcoma

At the University of Illinois, an engineer teamed up with a veterinarian to test a bone cancer drug delivery system in animals bigger than the standard animal model, the mouse. They chose dogs — mammals closer in size and biology to humans — with naturally occurring bone cancers, which also are a lot like human bone tumors.

In clinical trials, the dogs tolerated the highest planned doses of cancer-drug-laden nanoparticles with no signs of toxicity. As in mice, the particles homed in on tumor sites, thanks to a coating of the drug pamidronate, which preferentially binds to degraded sites in bone. The nanoparticles also showed anti-cancer activity in mice and dogs.

The researchers report their results in the Proceedings of the National Academy of Sciences.

These findings are a proof-of-concept that nanoparticles can be used to target bone cancers in large mammals, the researchers said. The approach may one day be used to treat metastatic skeletal cancers, they said.

The dogs were companion animals with bone cancer that were submitted for the research trials by their owners, said U. of I. veterinary clinical medicine professor Dr. Timothy Fan, who led the study with materials science and engineering professor Jianjun Cheng. All of the dogs were 40 to 60 kilograms (88 to 132 pounds) in weight, he said.

“We wanted to see if we could evaluate these drug-delivery strategies, not only in a mouse model, but also at a scale that would mimic what a person would get,” Fan said. “The amount of nanoparticle that we ended up giving to these dogs was a thousand-fold greater in quantity than what we would typically give a mouse.”

Using nanoparticles with payloads of drugs to target specific tissues in the body is nothing new, Cheng said. Countless studies test such approaches in mice, and dozens of “nanopharmaceuticals” are approved for use in humans. But the drug-development pipeline is long, and the leap from mouse models to humans is problematic, he said.

“Human bone tumors are much bigger than those of mice,” Cheng said. “Nanoparticles must penetrate more deeply into larger tumors to be effective. That is why we must find animal models that are closer in scale to those of humans.”

Mice used in cancer research have other limitations. Researchers usually inject human or other tumor cells into their bodies to mimic human cancers, Fan said. They also are bred to have compromised immune systems, to prevent them from rejecting the tumors.

“That is one of the very clear drawbacks of using a mouse model,” Fan said. “it doesn’t recapitulate the normal immune system that we deal with every day in the person or in a dog.”

There also are limitations to working with dogs, he said. Dogs diagnosed with bone cancer often arrive at the clinic at a very advanced stage of the disease, whereas in humans, bone cancer is usually detected early because people complain about the pain and have it investigated.

“On the flip side of that, I would say that if you are able to demonstrate anti-cancer activity in a dog with very advanced disease, then it would be likely that you would have equivalent or better activity in people with a less advanced stage of the disease,” Fan said.

Many more years of work remain before this or a similar drug-delivery system can be tested in humans with inoperable bone cancer, the researchers said.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/07/160725192351.htm Original web page at Science Daily

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* First public collection of bacteria from the intestine of mice

Mouse models are extensively used in pharmaceutical and medical research, and it is known that the communities of microbes in their intestine can have a significant impact on the research output. However, there is still insufficient information available about many bacteria inhabiting the intestine of mice. For the first time, a collection of cultured bacterial strains provides comprehensive information on the mouse gut microbiota: Scientists at the Technical University of Munich were able to isolate, characterize, and archive a hundred strains, including 15 hitherto unknown taxa.

They are microscopically small and live both on humans and animals. They can help with recovery from an illness or literally make you sick: Billions of micro-organisms, most of which are found in the intestines, as well as on the skin and other regions of the body, living in symbiosis with the host. These tiny beings are of central importance, and experts refer to them as intestinal microbiota or the microbiome. Decoding its characteristics and obtaining a better understanding of it is what scientists at the Central Institute for Nutrition and Food Research (ZIEL) at the Technical University of Munich (TUM) are working on.

76 cultured bacterial species from the mouse microbiome identified and archived

One key to obtaining information about the interactions between gut bacteria and their host are mouse models. However only a handful of mouse intestinal bacteria have been made publicly available and fully characterized so far. This is a highly limiting factor for research, because it complicates the annotation of data obtained by molecular techniques, and because it has been shown that gut microbiomes are to some extent specific to their host, and researchers have been using strains of other origin in mouse models. Dr. habil. Thomas Clavel from ZIEL and colleagues describe a new resource in “Nature Microbiology” which, for the first time, contains a hundred cultured bacterial strains from the mouse gut microbiome. For this study, 1500 cultures were examined, and 76 different species were identified and archived.

“The goal of our work was to take a big initial step towards decoding the cultured fraction of gut bacterial communities in mice. There is still a lot left to do. We will be making our work available to scientists around the world and hope that others will also help to find the pieces to complete the puzzle,” said Clavel, who has been researching various bacteria in gut microbiomes at the TU Munich for ten years. Although the mouse gut microbiome presents a number of similarities with the human microbiome, the work showed that around 20 percent of the strains in the collection prefer colonizing the intestines of mice.

In order to better understand colonization processes in the intestine, bacteria first need to be identified and characterized in detail. “Because mouse models are indispensable for preclinical studies, the resource now made available shall contribute to a better understanding of microbe-host interactions and to a higher degree of standardization,” said Clavel.

For the first time, the researchers were able to characterize new bacteria with important functional properties: For example Flintibacter butyricum produces the short-chain fatty acid butyrate from both sugars and proteins — a rare property in the realm of intestinal bacteria. Butyrate is a main product of fermentation in the intestine, and has been shown to have anti-inflammatory and positive effects against metabolic diseases in numerous studies.

“We still have a lot of gaps in our knowledge about gut microbiomes, but with the publicly available database of cultured mouse gut bacteria and their genetic material, we are now a little closer to our goal,” Thomas Clavel from the TUM stated enthusiastically.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160812103715.htm Original web page at Science Daily

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Heart muscle made from stem cells aid precision cardiovascular medicine, study shows

Heart muscle cells made from induced pluripotent stem cells faithfully mirror the expression patterns of key genes in the donor’s native heart tissue, according to researchers at the Stanford University School of Medicine. As a result, the cells can be used as a proxy to predict whether a patient is likely to experience drug-related heart damage.

The discovery validates the use of such cells to test the potential cardiotoxicity of certain drugs and to devise new therapies for conditions like cardiomyopathy. Pinpointing people who are likely to suffer heart damage before these people undergo treatment could increase the safety profile of many medications, the researchers believe.

“Thirty percent of drugs in clinical trials are eventually withdrawn due to safety concerns, which often involve adverse cardiac effects,” said Joseph Wu, MD, PhD, director of Stanford’s Cardiovascular Institute and professor of cardiovascular medicine and of radiology. “This study shows that these cells serve as a functional readout to predict how a patient’s heart might respond to particular drug treatments and identify those who should avoid certain treatments.”

Wu is the senior author of the study, which will be published online Aug. 18 in Cell Stem Cell. Cardiovascular medicine instructor Elena Matsa, PhD, is the lead author of the research.

The ability to create stem cells from easily obtained skin or blood samples has revolutionized the concept of personalized medicine and made it possible to create many types of human tissue for use in the clinic. Researchers have wondered, however, whether the process of creating stem cells, and subsequently coaxing those stem cells to become other tissues, might affect the patterns of gene expression and even the ways the specialized cells function. If so, these changes could limit their clinical usefulness.

Matsa, Wu and their colleagues created heart muscle cells, or cardiomyocytes, from iPS cells from seven people not known to have genetic predisposition to cardiac problems. They sequenced the RNA molecules made by the heart muscle cells to learn which proteins the cells were making, and how much. They then compared the results within individuals — looking at the gene expression patterns of cardiomyocytes derived from several batches of iPS cells from each person — as well as among all seven study subjects.

They also investigated how the cardiomyocytes from each person responded to increasing amounts of two drugs, one called rosiglitazone that is sometimes used to treat Type 2 diabetes and another called tacrolimus that serves as an immunosuppressant to inhibit the rejection of transplanted organs. Each of the two drugs has been associated with adverse cardiac effects in some people, but it has not been possible to predict which patients will experience heart damage.

“We found that the gene expression patterns of the iPS cell-derived cardiomyocytes from each individual patient correlated very well,” said Matsa. “But there was marked variability among the seven people, particularly in genes involved in metabolism and stress responses. In fact, one of our subjects exhibited a very abnormal expression of genes in a key metabolic pathway.”

Heart muscle cells from this person, the researchers found, responded differently than the others to exposure to rosiglitazone. Concerns about its effect on cardiac function have caused the drug to be withdrawn from the market in Europe and have strictly limited its use in the United States.

“This person’s cells produced abnormal amounts of reactive oxygen species, were unable to regenerate their mitochondria and contracted much more weakly when exposed to rosiglitazone than cells derived from the other subjects,” said Matsa.

Although the researchers were unable to identify a specific genetic mutation likely to cause such an outcome, they were able to pinpoint an important metabolic pathway involved in the response to the drug by comparing the subject’s gene expression profile with that of the others whose cells were unaffected. They were also able to correct the defect by using a genome editing technique to boost the expression of a gene in the pathway and restore normal function.

Finally, although the researchers showed that meaningful variability exists in the gene expression patterns of the seven individuals, they couldn’t yet be certain that the iPS-derived cardiomyocytes faithfully replicated each person’s native heart tissue. To investigate, they created iPS cells from another three people who had undergone either heart biopsies or transplants. They then compared the iPS-derived cardiomyocytes with the matching native heart tissue and confirmed that the gene expression patterns correlated in many significant ways — particularly for genes involved in metabolic pathways critical to cardiac function.

“Many people talk about precision medicine or precision health, but there are only few examples of how to carry it out in a clinically meaningful way,” said Wu. “I think the patient-derived iPS cell platform gives us a surrogate window into the body and allows us to not only predict the body’s function but also to learn more about key disease-associated pathways.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160818131132.htm  Original web page at Science Daily

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* Brain’s chemical signals seen in real time

Neuroscientists have invented a way to watch the ebb and flow of the brain’s chemical messengers in real time. They were able to see the surge of neurotransmitters as mice were conditioned — similarly to Pavlov’s famous dogs — to salivate in response to a sound.

The study, presented at the American Chemical Society’s meeting in Philadelphia, Pennyslvania, on 22 August, uses a technique that could help to disentangle the complex language of neurotransmitters. Ultimately, it could lead to a better understanding of brain circuitry.

The brain’s electrical surges are easy to track. But detecting the chemicals that drive this activity — the neurotransmitters that travel between brain cells and lead them to fire — is much harder. “There’s a hidden signalling network in the brain, and we need tools to uncover it,” says Michael Strano, a chemical engineer at the Massachusetts Institute of Technology in Cambridge.

In many parts of the brain, neurotransmitters can exist at undetectably low levels. Typically, researchers monitor them by sucking fluid out from between neurons and analysing the contents in the lab. But that technique cannot measure activity in real time. Another option is to insert a metal probe into the space between neurons to measure how neurotransmitters react chemically when they touch metal. But the probe is unable to distinguish between structurally similar molecules, such as dopamine, which is involved in pleasure and reward, and noradrenaline which is involved in alertness.

Enter neuroscientist Paul Slesinger of the Icahn School of Medicine at Mount Sinai in New York City and neurophysicist David Kleinfeld of the University of California, San Diego. In May, they reported a method for making genetically modified human cells that produce artificial receptors for neurotransmitters. These receptors are also linked to fluorescent molecules so that when a particular neurotransmitter binds to its receptor, the cell lights up.

The researchers injected these cells, known as CNiFERs (cell-based neurotransmitter fluorescent engineered reporters) into the brains of 13 mice. Then, they cut a window into each mouse’s skull to expose its brain and put a transparent cover over the hole so that they could watch the cells light up in real time through a microscope.

Over the course of five days, the researchers trained the mice by playing a sound before giving them a sugar treat. The mice soon learned to salivate in anticipation as soon as they heard the sound. Each day, the researchers recorded light from the animals’ brains, enabling them to determine the exact moment at which neurotransmitters were released. For the first time, they could see a surge of dopamine — the pleasure molecule that drives salivation — after the sound that occurred more rapidly as the association became stronger.

Noradrenaline, a molecule involved in alertness, is also thought to surge in this type of learning, but researchers have never been able to distinguish it from dopamine in real time. But by engineering CNiFERs specific to each neurotransmitter, Slesinger and Kleinfeld showed, also for the first time, that the noradrenaline spike occured at variable times following the tone and did not change with training. This suggests that the neurotransmitter could be responding to some other factor or behavioural reaction.

The ability to use separate CNiFERs for the two neurotransmitters might eventually reveal whether noradrenalin has a role in learning and addiction, and whether drugs that target it are likely to change behaviour.

Strano says that the technique is an improvement on current methods because it quantifies neurotransmitters directly instead of calculating them through their effects. “It’s one of the purest tests you can do,” he says.

But he worries that genetically modified cells might not act the same way as natural cells. His lab is working on a set of nanotubes that cross the blood–brain barrier and emit light when they encounter a neurotransmitter in the brain.

But Lin Tian, a neuroscientist at the University of California, Davis, thinks that the technique is of limited use. The CNiFERs show whether the total amount of a molecule such as dopamine is increasing or decreasing, but they do not reveal which neuron is sending or receiving the signal — making it hard to map tangled brain circuits.

Instead, Tian and her colleagues are modifying bacterial proteins so that they bind neurotransmitters and emit light. This technique is precise enough to detect the signalling molecule glutamate in a single gap between two neurons, thus revealing the exact cells involved.

Tian says that CNiFERs might be more useful for amino-acid-based neuropeptides, such as orexin, which is involved in sleep and drug-seeking behaviours. These larger molecules are more difficult to detect with chemical techniques. Slesinger says that he and his collaborators are working on CNiFERs for this and other neuropeptides.

All of the researchers are trying to expand the repertoire of neurotransmitters that can be detected. Kleinfeld says that CNiFERS are unlikely to be used in humans any time soon because implanting cells into the brain could be dangerous. But they might be used to detect whether drugs are working in mice, and they are sensitive enough to reveal, perhaps, more subtle ways in which the brain malfunctions.

Nature doi:10.1038/nature.2016.20458

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/brain-s-chemical-signals-seen-in-real-time-1.20458 Original web at Nature

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Citrus fruits could help prevent obesity-related heart disease, liver disease, diabetes

Oranges and other citrus fruits are good for you — they contain plenty of vitamins and substances, such as antioxidants, that can help keep you healthy. Now a group of researchers reports that these fruits also help prevent harmful effects of obesity in mice fed a Western-style, high-fat diet.

The researchers are presenting their work today at the 252nd National Meeting & Exposition of the American Chemical Society (ACS).

“Our results indicate that in the future we can use citrus flavanones, a class of antioxidants, to prevent or delay chronic diseases caused by obesity in humans,” says Paula S. Ferreira, a graduate student with the research team.

More than one-third of all adults in the U.S. are obese, according to the U.S. Centers for Disease Control and Prevention. Being obese increases the risk of developing heart disease, liver disease and diabetes, most likely because of oxidative stress and inflammation, Ferreira says. When humans consume a high-fat diet, they accumulate fat in their bodies. Fat cells produce excessive reactive oxygen species, which can damage cells in a process called oxidative stress. The body can usually fight off the molecules with antioxidants. But obese patients have very enlarged fat cells, which can lead to even higher levels of reactive oxygen species that overwhelm the body’s ability to counteract them.

Citrus fruits contain large amounts of antioxidants, a class of which are called flavanones. Previous studies linked citrus flavanones to lowering oxidative stress in vitro and in animal models. These researchers wanted to observe the effects of citrus flavanones for the first time on mice with no genetic modifications and that were fed a high-fat diet.

The team, at Universidade Estadual Paulista (UNESP) in Brazil, conducted an experiment with 50 mice, treating them with flavanones found in oranges, limes and lemons. The flavanones they focused on were hesperidin, eriocitrin and eriodictyol. For one month, researchers gave groups either a standard diet, a high-fat diet, a high-fat diet plus hesperidin, a high-fat diet plus eriocitrin or a high-fat diet plus eriodictyol.

The high-fat diet without the flavanones increased the levels of cell-damage markers called thiobarbituric acid reactive substances (TBARS) by 80 percent in the blood and 57 percent in the liver compared to mice on a standard diet. But hesperidin, eriocitrin and eriodictyol decreased the TBARS levels in the liver by 50 percent, 57 percent and 64 percent, respectively, compared with mice fed a high-fat diet but not given flavanones. Eriocitrin and eriodictyol also reduced TBARS levels in the blood by 48 percent and 47 percent, respectively, in these mice. In addition, mice treated with hesperidin and eriodictyol had reduced fat accumulation and damage in the liver.

“Our studies did not show any weight loss due to the citrus flavanones,” says Thais B. Cesar, Ph.D., who leads the team. “However, even without helping the mice lose weight, they made them healthier with lower oxidative stress, less liver damage, lower blood lipids and lower blood glucose.”

Ferreira adds, “This study also suggests that consuming citrus fruits probably could have beneficial effects for people who are not obese, but have diets rich in fats, putting them at risk of developing cardiovascular disease, insulin resistance and abdominal obesity.”

Next, the team will explore how best to administer these flavanones, whether in citrus juice, by consuming the fruit or developing a pill with these antioxidants. In addition, the team plans to conduct studies involving humans, Cesar says.

Cesar acknowledges funding from the Support Program for Scientific Development of the School of Pharmaceutical Sciences at UNESP and by Citrosuco, an orange juice production company in Matão, Sao Paulo, Brazil.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160821093054.htm  Original web page at Science Daily

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CRISPR’s hopeful monsters: gene-editing storms evo-devo labs

A model and fossil of Tiktaalik roseae, a transitional fossil that illustrates how fish began to develop limbs.

Most summers since 1893, young developmental and evolutionary biologists have flocked to Woods Hole, Massachusetts, to master the tricks of their trade. At the world-famous Marine Biological Laboratory there, students in its annual embryology course dissect sea urchins and comb jellies, and graft cells together from different animals. But for the last three years, the keen apprentices have been learning something new: gene editing.

The precise, efficient CRISPR–Cas9 gene-editing technique has already taken life-sciences labs by storm. Now it is sweeping through evo-devo, the field that seeks to explain the developmental changes underlying evolutionary adaptations.

Rather than simply infer what caused historic transitions, such as how fish developed limbs, scientists can check their hypotheses directly with CRISPR. The idea is simple: cut out the fish genes thought to be involved in making fins, and see whether the fish start to form something resembling feet.

That is exactly what researchers report today in Nature, using CRISPR to help explain how fish developed feet and started walking. Others have wielded the technique to determine how butterflies evolved exquisite colour vision, and how crustaceans acquired claws.

“CRISPR is a revolution all across biology, but for evo-devo it’s transformative,” says Arnaud Martin, an evolutionary developmental biologist at George Washington University in Washington DC. “We can do things we were not able to do before.”

Neil Shubin, a palaeontologist and developmental biologist at the University of Chicago in Illinois, has used gene-editing to examine how the tips of fish fins, or rays, were replaced by feet and digits in four-legged land vertebrates, or tetrapods.

While researchers know that ancient fish developed limbs – Shubin led the team that in 2004 discovered a 375-million-year-old fossil that seemed to catch that transition in the act – they also thought that the foot was an evolutionary novelty without an equivalent in fish, because rays and feet are made of different kinds of bone.

But Shubin says gene-editing has changed his mind. His team used CRISPR to engineer zebrafish lacking various combinations of the several hox13 genes they possess – genes that researchers already thought played an important role in laying down fin rays.

None of the mutants grew fully fledged feet, Shubin notes, but some possessed “fingery fins” made of the same kind of bone that builds fingers and toes in tetrapods. “As a palaeontologist I studied and trained thinking these are two different kinds of bones that are completely unrelated developmentally or evolutionarily,” says Shubin. “These results challenge that assumption.”

The zebrafish is a popular model organism, whose genome is regularly manipulated in the lab. But CRISPR vastly sped up the experiments performed by Shubin’s team. One next step will be to knock out hox13 genes in fish species that more closely resemble the ancient fish that gained limbs, say Aditya Saxena and Kimberly Cooper, evolutionary developmental biologists at the University of California, San Diego. Those experiments are now conceivable thanks to CRISPR, they note in a commentary that accompanies Shubin’s article.

Editing crabs and butterflies

There is little reason to think the technique will not work on other, more esoteric species, too. “CRISPR seems to be universally working in any organism,” says Martin, who has successfully applied the technique to a marine crustacean called Parhyale hawaiensis, which is gaining popularity in evo-devo.

In a January Current Biology paper, he and colleague Nipam Patel, at the University of California, Berkeley, found that inactivating different Hox genes in the species messes with the development of specialized appendages such as antennae and claws. If scientists can successfully rear an animal in the lab so they can gain access to its eggs, they should be able to use CRISPR, Martin says.

Such flexibility is important for evo-devo researchers, says Claude Desplan, a developmental neurobiologist at New York University, whose team applied CRISPR to yellow swallowtail butterflies in a Nature paper published last month, to test a theory about how photoreceptors in their eyes detect a broader spectrum of colours than insects such as fruit flies. On-going experiments in his lab have applied gene-editing to wasps and ants.

So far, evo-devo researchers have focused on using CRISPR to eliminate a gene’s activity or to introduce genes, such as the one encoding green fluorescent protein, that make it possible to better track an animal’s development. But Martin expects researchers will soon begin using the tool to precisely alter DNA sequences in animals to test ideas about specific genetic changes. Those could include changes to regulatory DNA sequences that influence where and when a gene is active, which may have contributed to adaptations such as tetrapod limbs.

Researchers could also make an educated guess at the DNA sequences of ancient transitional creatures and insert those into living animals using CRISPR, says Bhart-Anjan Bhullar, a palaeontologist at Yale University in New Haven, Connecticut. Last year, his team used chemicals to modify development pathways in chickens that they thought helped to mould the snouts of theropod dinosaurs into modern birds’ beaks. He hopes to now be able to do such experiments with CRISPR.

Bhullar, who attended last month’s embryology course at Woods Hole, says he’s impressed by the success of gene-editing trials by students there, where scientists had the chance to use CRISPR editing on zebrafish, the crustacean P. hawaiensis, frogs, slipper snails and sea squirts.

With CRISPR, “stuff just works”, Bhullar says. “This is rapidly going to become the standard in evolutionary developmental biology.”

Nature doi:10.1038/nature.2016.20449 Read the related News & Views article, “Fin to limb within our grasp”.

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/crispr-s-hopeful-monsters-gene-editing-storms-evo-devo-labs-1.20449  Original web page at Nature

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US endangered-species recovery surges to record high

The Santa Cruz Island Fox is one of three subspecies of fox removed from the Endangered Species Act list this month.

More species protected by the US Endangered Species Act (ESA) have recovered during President Barack Obama’s administration than under all other presidents combined, the US Department of Interior announced on 11 August. And 2016 marks a record high for species recovery, with six so far officially ‘delisted’ from ESA’s roster.

The ESA, passed in 1973 to assist the recovery and protection of imperilled species and ecosystems, is widely seen as a landmark piece of environmental legislation. During Obama’s presidency, 19 species have now recovered and been delisted; this compares to seven such removals under George W. Bush, six during Bill Clinton’s administration and five under Ronald Reagan. Source: US Dept. Interior/US Fish & Wildlife Service.

That may simply be a result of the 43-year-old ESA legislation finally starting to pay dividends, says Noah Greenwald, director of endangered species at the Center for Biological Diversity, a non-profit conservation group headquartered in Tucson, Arizona. “It also reflects the fact that the Obama administration has been putting more resources into processing delistings for recovered species, in an effort to counter attacks from Republicans in Congress who say the law has a poor success rate,” he adds.

The latest delistings are of three subspecies of fox native to California’s Channel Islands (Urocyon littoralis ssp.). The Department of Interior says that the foxes, listed in 2004, represent the “fastest successful recovery” of any ESA mammal, crediting efforts including a captive-breeding programme and a vaccination campaign against a canine virus.

But the ESA process does not move as quickly as it should when it comes to listing species for protection in the first place, according to research by Greenwald and his colleagues. In a report published last month, they calculate that it takes a species on average 12 years to be listed after first consideration — much more than the two years that the law says it should.

Nature doi:10.1038/nature.2016.20448 Read a previous Trend Watch: ‘US grants for zebrafish studies on the rise’

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/us-endangered-species-recovery-surges-to-record-high-1.20448 Original web page at Nature

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Human ‘super predator’ more terrifying than bears, wolves and Human ‘super predator’ more terrifying than bears, wolves and dogs

Bears, wolves and other large carnivores are frightening beasts but the fear they inspire in their prey pales in comparison to that caused by the human ‘super predator.’

A new study by Western University demonstrates that smaller carnivores, like European badgers, that may be prey to large carnivores, actually perceive humans as far more frightening. Globally, humans now kill smaller carnivores at much higher rates than large carnivores do, and these results indicate that smaller carnivores have learned to fear the human ‘super predator’ far more than they fear their traditional enemies.

These findings by Liana Zanette and Michael Clinchy from Western’s Faculty of Science, in collaboration with celebrated British biologist David Macdonald from University of Oxford’s Wildlife Conservation Research Unit (WildCRU) and others, were published this week in Behavioral Ecology.

Zanette, a professor in Western’s Department of Biology, and her colleagues experimentally demonstrated that smaller carnivores, like badgers, foxes and raccoons, that may appear to be habituated to humans because they live among us, are actually experiencing elevated levels of fear — living in fear of the human ‘super predator’ in human-dominated landscapes.

“Our previous research has shown that the fear large carnivores inspire can itself shape ecosystems. These new results indicate that the fear of humans, being greater, likely has even greater impacts on the environment, meaning humans may be distorting ecosystem processes even more than previously imagined,” explains Zanette, a wildlife ecologist. “These results have important implications for conservation, wildlife management and public policy.”

By frightening their prey, large carnivores help maintain healthy ecosystems by preventing smaller carnivores from eating everything in sight, and the loss of this ‘landscape of fear’ adds to conservation concerns regarding the worldwide loss of large carnivores. Fear of humans has been proposed to act as a substitute, but these new results demonstrate that the fear of humans is qualitatively different and cannot be expected to fulfill the same ecosystem function.

The team conducted the study on Europeans badgers in Wytham Woods, just outside of Oxford (UK). To experimentally compare their relative fearfulness, the team played badgers the sounds of bears, wolves, dogs and humans in their natural habitat and filmed their responses, using hidden automated speakers and cameras. Whereas hearing bears and dogs had some effect, simply hearing the sound of people speaking, in conversation, or reading passages from books, prevented most badgers from feeding entirely, and dramatically reduced the time spent feeding by those few badgers that were brave enough to venture forth — while hearing the sound of the human ‘super predator.’

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/07/160725135357.htm Original web page at Science Daily

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Antibiotics weaken Alzheimer’s disease progression through changes in the gut microbiome

Long-term treatment with broad spectrum antibiotics decreased levels of amyloid plaques, a hallmark of Alzheimer’s disease, and activated inflammatory microglial cells in the brains of mice in a new study by neuroscientists from the University of Chicago.

The study, published July 21, 2016, in Scientific Reports, also showed significant changes in the gut microbiome after antibiotic treatment, suggesting the composition and diversity of bacteria in the gut play an important role in regulating immune system activity that impacts progression of Alzheimer’s disease.

“We’re exploring very new territory in how the gut influences brain health,” said Sangram Sisodia, PhD, Thomas Reynolds Sr. Family Professor of Neurosciences at the University of Chicago and senior author of the study. “This is an area that people who work with neurodegenerative diseases are going to be increasingly interested in, because it could have an influence down the road on treatments.”

Two of the key features of Alzheimer’s disease are the development of amyloidosis, accumulation of amyloid-ß (Aß) peptides in the brain, and inflammation of the microglia, brain cells that perform immune system functions in the central nervous system. Buildup of Aß into plaques plays a central role in the onset of Alzheimer’s, while the severity of neuro-inflammation is believed to influence the rate of cognitive decline from the disease.

For this study, Sisodia and his team administered high doses of broad-spectrum antibiotics to mice over five to six months. At the end of this period, genetic analysis of gut bacteria from the antibiotic-treated mice showed that while the total mass of microbes present was roughly the same as in controls, the diversity of the community changed dramatically. The antibiotic-treated mice also showed more than a two-fold decrease in Aß plaques compared to controls, and a significant elevation in the inflammatory state of microglia in the brain. Levels of important signaling chemicals circulating in the blood were also elevated in the treated mice.

While the mechanisms linking these changes is unclear, the study points to the potential in further research on the gut microbiome’s influence on the brain and nervous system.

“We don’t propose that a long-term course of antibiotics is going to be a treatment — that’s just absurd for a whole number of reasons,” said Myles Minter, PhD, a postdoctoral scholar in the Department of Neurobiology at UChicago and lead author of the study. “But what this study does is allow us to explore further, now that we’re clearly changing the gut microbial population and have new bugs that are more prevalent in mice with altered amyloid deposition after antibiotics.”

The study is the result of one the first collaborations from the Microbiome Center, a joint effort by the University of Chicago, the Marine Biological Laboratory and Argonne National Laboratory to support scientists at all three institutions who are developing new applications and tools to understand and harness the capabilities of microbial systems across different fields. Sisodia, Minter and their team worked with Eugene B. Chang, Martin Boyer Professor of Medicine at UChicago, and Vanessa Leone, PhD, a postdoctoral scholar in Chang’s lab, to analyze the gut microbes of the mice in this study.

Minter said the collaboration was enabling, and highlighted the cross-disciplinary thinking necessary to tackle a seemingly intractable disease like Alzheimer’s. “Once you put ideas together from different fields that have largely long been believed to be segregated from one another, the possibilities are really amazing,” he said.

Sisodia cautioned that while the current study opens new possibilities for understanding the role of the gut microbiome in Alzheimer’s disease, it’s just a beginning step.

“There’s probably not going to be a cure for Alzheimer’s disease for several generations, because we know there are changes occurring in the brain and central nervous system 15 to 20 years before clinical onset,” he said. “We have to find ways to intervene when a patient starts showing clinical signs, and if we learn how changes in gut bacteria affect onset or progression, or how the molecules they produce interact with the nervous system, we could use that to create a new kind of personalized medicine.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160721072559.htm  Original web page at Science Daily