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* Common colon cancer tumor type blocked in mice

A new scientific study has identified why colorectal cancer cells depend on a specific nutrient, and a way to starve them of it. Over one million men and women are living with colorectal cancer in the United States. The National Cancer Institute estimates 4.5% of all men and women will be diagnosed with the cancer during their lifetime, making it the third most common non-skin cancer.

In the study published online in Nature Communications, researchers showed how certain colorectal cancer cells reprogram their metabolism using glutamine, a non-essential amino acid. Many cancer cells rely on glutamine to survive. How they become so dependent on the molecule is hotly debated in the field.

Researchers studied a subset of colorectal cancer cells containing a genetic mutation called PIK3CA. This mutation is located in a gene critical for cell division and movement, and is found in approximately one third of all colorectal cancers. The mutation is also the most commonly identified genetic mutation across all cancers, making the results of the study universally appealing.

Researchers were interested in determining whether or not the common PIK3CA mutation contributes to changes in cancer cell metabolism, such as how nutrients like glutamine are processed. Normally, glutamine is broken down by cancer cells into several other molecules with the help of specific enzymes. This complicated system helps produce adenosine triphosphate, the energy currency of all cells, and other molecules critical for colorectal cancer cell growth.

The researchers found that colorectal cells with the PIK3CA mutation broke down significantly more glutamine than cells without the mutation. The researchers identified several enzymes involved in the process that are more active in the mutant cancer cells than in other cell types, explaining the increased need for glutamine. These enzymes become overactive in the mutant cancer cells due to a cascade of signals led by the protein encoded by mutant PIK3CA gene. This finding represents a novel and important link between the common PIK3CA mutation and altered glutamine metabolism in cancer cells.

Zhenghe John Wang, PhD, professor of genetics and genome sciences and co-leader of the Cancer Genetics Program at Case Western Reserve University School of Medicine helped lead the study. “In layman’s terms, we discovered that colon cancers with PIK3CA oncogenic mutations are addicted to glutamine, a particular nutrient for cancer cells. We also demonstrated that these cancers can be starved to death by depriving glutamine with drugs.”

When the researchers lowered the amount of glutamine available to mutant cancer cells growing in laboratory dishes, the cancer cells died. This discovery led the team to investigate the effects of blocking glutamine availability in mice with colorectal cancer tumors containing the common PIK3CA mutation. Wang and colleagues found that exposing these mice to a compound that blocks glutamine metabolism consistently suppressed tumor growth. They did not observe the same effect on tumors without the mutation. Together, these results provide a promising new therapeutic avenue to suppress growth of colorectal tumors with the PIK3CA mutation. The researchers have filed a patent application based on the unique mechanism of tumor suppression they have identified and the work is available for licensing.

“This study provides the basis for a colon cancer treatment clinical trial that will be started in the summer at the University Hospitals Seidman Cancer Center,” according to Neal Meropol, MD, Dr. Lester E. Coleman, Jr. Professor of Cancer Research and Therapeutics, chief of the division of hematology and oncology, and principal investigator for the trial. The phase I/II study will test the effects of a glutamine metabolism inhibitor in patients with advanced colorectal tumors.

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

https://www.sciencedaily.com/releases/2016/07/160720215322.htm  Original web page at Science Daily

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* Nottingham Dollies prove cloned sheep can live long and healthy lives

Three weeks after the scientific world marked the 20th anniversary of the birth of Dolly the sheep new research, published by The University of Nottingham, in the academic journal Nature Communications has shown that four clones derived from the same cell line — genomic copies of Dolly — reached their 8th birthdays in good health.

Nottingham’s Dollies — Debbie, Denise, Dianna and Daisy — have just celebrated their 9th birthdays and along with nine other clones they are part of a unique flock of cloned sheep under the care of Professor Kevin Sinclair, an expert in developmental biology, in the School of Biosciences.

The research — ‘Healthy ageing of cloned sheep’ — is the first detailed and comprehensive assessment of age-related non-communicable disease in cloned offspring. Published today, Tuesday 26 July 2016, it shows that at between seven to nine years of age (60 to 70 in human years) these cloned sheep were showing no long-term detrimental health effects.

Dolly made history as the first animal to be cloned from an adult cell using a technique known as somatic-cell nuclear transfer (SCNT). The late, Professor Keith Campbell was instrumental in this pioneering work. In 1999 he joined The University of Nottingham where he continued his research in reproductive biology until his death in 2012. The flock of clones are his legacy to the University.

This latest study was led by Professor Kevin Sinclair, a close colleague of Professor Campbell’s.

Professor Sinclair said: “Despite technological advances in recent years’ efficiency of SCNT remains low but there are several groups across the world working on this problem at present and there is reason to be optimistic that there will be significant improvements in future. These improvements will stem from a better understanding of the underlying biology related to the earliest stages of mammalian development. In turn this could lead to the realistic prospect of using SCNT to generate stem cells for therapeutic purposes in humans as well as generating transgenic animals that are healthy, fertile and productive. However, if these biotechnologies are going to be used in future we need to continue to test their safety.”

Nottingham’s oldest clone was born in July 2006. The four Finn-Dorset clones — ‘the Dollies’ — were born in July 2007. A female Lleyn clone was born in August 2007 along with a second clone (breed unknown). In June 2008 six more Lleyn ewes were born.

These animals originated from studies undertaken by Professor Campbell between 2005 and 2007 which sought to improve the efficiency of SCNT. The four Finn Dorsets were derived from the mammary gland cell line that led to the birth of Dolly. The other clones came from fetal fibroblasts.

Longevity and healthy ageing among SCNT clones have long been contentious issues and much was made of Dolly having to undergo treatment for osteoarthritis some time prior to her death in 2003 at six years old.

During 2015 Nottingham’s cloned sheep underwent a series of comprehensive assessments for non-communicable diseases including obesity, hypertension and osteoarthritis — three major comorbidities in aged human populations. The examinations included the use of anaesthesia to carry out x-rays and MRI scans.

The research was carried out under the authority of the United Kingdom Animal (Scientific Procedures) Act 1986 with approval from The University of Nottingham Animal Welfare and Ethical Review Board.

The flock was tested for glucose tolerance and insulin sensitivity. They underwent radio-telemetric assessments to check their heart rate and blood pressure. They had a full musculoskeletal examination carried out by Dr Sandra Corr, a veterinary orthopaedic specialist from the University’s School of Veterinary Medicine and Science and a co-author of this research.

Radiological examinations of all main joints were followed by MRI scans of their knees, the joint most affected by osteoarthritis in Dolly. Their health was compared with a group of naturally bred six-year-old sheep living under similar conditions at the University.

Professor Sinclair said: “Healthy ageing of SCNT clones has never been properly investigated. There have been no detailed studies of their health. One of the concerns in the early days was that cloned offspring were ageing prematurely and Dolly was diagnosed with osteoarthritis at the age of around five, so clearly this was a relevant area to investigate. Following our detailed assessments of glucose tolerance, insulin sensitivity, blood pressure and musculoskeletal investigations we found that our clones, considering their age, were at the time of our research healthy.”

Despite their advanced age the cloned sheep — including the four Dollies — were showing no signs of diabetes, high blood pressure, or clinical degenerative-joint disease. Although some of the animals were showing radiographic evidence of mild, and in Debbie’s case, moderate osteoarthritis none of the animals were lame and none required treatment for osteoarthritis.

There is still a long way to go before SCNT is perfected. However, this research has shown that cloned animals can live long and healthy lives.

Professor Sinclair said: “It is well established that prior to conception and in the early stages of pregnancy during natural or assisted reproduction subtle chemical changes can affect the human genome leading to development and late-onset chronic diseases. Given that SCNT requires the use of assisted reproductive procedures it is important to establish if similar diseases or disorders exist in apparently healthy aged cloned offspring.”

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

https://www.sciencedaily.com/releases/2016/07/160726122958.htm Original web page at Science

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Sexual rivalry may drive frog reproductive behaviors

It may be hard to imagine competing over who gets to kiss a frog, but when it comes to mating, a new study concludes that some frogs have moved out of the pond onto land to make it easier for the male in the pair to give sexual rivals the slip.

Biologists have long thought that some frog species evolved to mate on land — sometimes in unusual places — instead of in open water to better guard eggs and tadpoles from easily being eaten by fish and other predators. But the new research by a team of U.S. and Brazilian frog biologists suggests that mating on land in many species might in part be a strategy that male frogs use to ensure that their own DNA gets passed on, instead of the DNA of their rivals. Sexual selection may trump natural selection in the evolution of these reproductive behaviors, according to the new study, to be published online ahead of print on July 26 in The American Naturalist.

Frogs have a “dizzying array” of reproductive strategies, according to Rayna Camille Bell, a UC Berkeley postdoctoral fellow who contributed to data collection, analyzed and interpreted much of the data, and helped co-author the study, which was led by her doctoral thesis advisor, Kelly Zamudio, a professor at Cornell University.

Mating in frogs typically involves the male wrapping his arms around the female, the female depositing eggs and the male fertilizing the eggs, which will hatch into tadpoles and ultimately develop into froglets. The earliest frogs completed all of these steps in water, but among different frog species there are various strategies for accomplishing these reproductive tasks before a new generation hops or swims off on its own. Frog species vary in where they mate, where they lay eggs, where tadpoles develop and whether and how eggs and tadpoles are tended to by parent frogs. Some species even skip the egg stage, giving birth to live tadpoles or even froglets.

“Biologists noticed an apparent linear progression toward more terrestrial reproduction throughout frog evolution and proposed that frogs avoid putting their eggs and tadpoles in streams or ponds because they would be more vulnerable to aquatic predators,” Bell said. The apparent trend toward increasingly terrestrial reproduction is most evident in tropical frogs, perhaps because more humid environments more easily permit reproduction on land without eggs or tadpoles drying up.

But eggs and tadpoles are still susceptible to predators on land, and biologists haven’t reached a consensus on why so many tropical frog species have terrestrial reproductive modes. If natural selection to minimize aquatic predation on developing eggs and tadpoles was the main driver for evolving terrestrial reproduction, Bell and her collaborators reasoned, there should be equally diverse strategies for placing both eggs and tadpoles out of harm’s way.

But in reviewing datasets built upon the field work of other biologists and their own data on hundreds of species in two different families of tropical frogs, the Hylidae and Leptodactylidae, the researchers found that this was not generally the case.

They found that most of the diversity in reproductive strategies involves the egg stage. Even when eggs are deposited on land, tadpoles often quickly end up in dangerous waters, falling off a leaf into a stream, for instance. This pattern indicates that selection is acting independently on eggs versus tadpoles, Bell said, suggesting that there might be other evolutionary advantages of depositing eggs on land.

“Besides avoiding aquatic predators, the benefit of depositing your eggs on land away from the main body of water — if you are a male frog — is that you get the female away from the breeding frenzy where there are hundreds of males all competing for access to females,” Bell said. “On land, it’s easier to make sure that no other male is moving in on your female and fertilizing her eggs.”

Bell and co-authors found that when mating occurs away from the main body of water, the mating site is often more private and hidden from competing males. Some frog species mate in the water-containing folds of bromeliad leaves, for example, and males in other species even build volcano-shaped mud nests that they may guard while mating.

The researchers hypothesized that if sexual selection is playing a role in the evolution of these mating behaviors, then in species where competition for fertilizing eggs is fierce males should have larger sperm-producing testes, similar to what has been observed in other animals where male competition for mates is intense. Conversely, males in species with private breeding sites should have smaller testes.

Indeed, Bell and colleagues determined that the mass of male testes, which is a proxy for sperm competition, is smaller and less variable in frogs that hide while breeding, indicating they are less vulnerable to other males horning in.

What is special about the tropics?

Most studies of frog mating systems have been in temperate regions. Like this study, new natural history data on mating systems and reproductive modes in both temperate and tropical frog species are likely to challenge preconceived notions of how and why these complex reproductive behaviors evolved, Bell said.

“The tropics have the greatest frog species diversity, as well as the most diversity and complexity in frog reproductive modes,” Bell said, “But we know the least about the biology, behavior and diversity of these tropical species, even though many are threatened, and some are only now being discovered for the first time. Hopefully our study will draw attention to how much we still have to learn about sexual selection and mating system dynamics in frogs.”

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

https://www.sciencedaily.com/releases/2016/07/160726122954.htm Original web page at Science Daily

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Seeing structure that allows brain cells to communicate

For more than a century, neuroscientists have known that nerve cells talk to one another across the small gaps between them, a process known as synaptic transmission (synapses are the connections between neurons). Information is carried from one cell to the other by neurotransmitters such as glutamate, dopamine, and serotonin, which activate receptors on the receiving neuron to convey excitatory or inhibitory messages.

But beyond this basic outline, the details of how this crucial aspect of brain function occurs have remained elusive. Now, new research by scientists at the University of Maryland School of Medicine (UM SOM) has for the first time elucidated details about the architecture of this process. The paper was published today in the journal Nature.

Synapses are very complicated molecular machines. They are also tiny: only a few millionths of an inch across. They have to be incredibly small, since we need a lot of them; the brain has around 100 trillion of them, and each is individually and precisely tuned to convey stronger or weaker signals between cells.

To visualize features on this sub-microscopic scale, the researchers turned to an innovative technology known as single-molecule imaging, which can locate and track the movement of individual protein molecules within the confines of a single synapse, even in living cells. Using this approach, the scientists identified an unexpected and precise pattern in the process of neurotransmission. The researchers looked at cultured rat synapses, which in terms of overall structure are very similar to human synapses.

“We are seeing things that have never been seen before. This is a totally new area of investigation,” said Thomas Blanpied, PhD, Associate Professor in the Department of Physiology, and leader of the group that performed the work. “For many years, we’ve had a list of the many types of molecules that are found at synapses, but that didn’t get us very far in understanding how these molecules fit together, or how the process really works structurally. Now by using single-molecule imaging to map where many of the key proteins are, we have finally been able to reveal the core architectural structure of the synapse.”

In the paper, Blanpied describes an unexpected aspect to this architecture that may explain why synapses are so efficient, but also susceptible to disruption during disease: at each synapse, key proteins are organized very precisely across the gap between cells. “The neurons do a better job than we ever imagined of positioning the release of neurotransmitter molecules near their receptors,” Blanpied says. “The proteins in the two different neurons are aligned with incredible precision, almost forming a column stretching between the two cells.” This proximity optimizes the power of the transmission, and also suggests new ways that this transmission can be modified.

Understanding this architecture will help clarify how communication within the brain works, or, in the case of psychiatric or neurological disease, how it fails to work. Blanpied is also focusing on the activity of “adhesion molecules,” which stretch from one cell to the other and may be important pieces of the “nano-column.” He suspects that if adhesion molecules are not placed correctly at the synapse, synapse architecture will be disrupted, and neurotransmitters

won’t be able to do their jobs. Blanpied hypothesizes that in at least some disorders, the issue may be that even though the brain has the right amount of neurotransmitter, the synapses don’t transmit these molecules efficiently.

Blanpied says that this improved comprehension of synaptic architecture could lead to a better understanding of brain diseases such as depression, schizophrenia and Alzheimer’s disease, and perhaps suggest new ideas for treatments.

Blanpied and his colleagues will next explore whether the synaptic architecture changes in certain disorders: they will begin by looking at a synapses in a mouse model of the pathology in schizophrenia.

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

https://www.sciencedaily.com/releases/2016/07/160727140303.htm  Original web page at Science Daily

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* Warnings of imminent extinction crisis for largest wild animal species

A team of conservation biologists is calling for a worldwide strategy to prevent the unthinkable: the extinction of the world’s largest mammal species.

In a public declaration published in today’s edition of the journal BioScience, a group of more than 40 conservation scientists and other experts are calling for a coordinated global plan to prevent the world’s “megafauna” from sliding into oblivion.

Among the threats cited by the group as drivers of this mass extinction are illegal hunting, deforestation and habitat loss, the expansion of agriculture and livestock into wildlife areas, and the growth of human populations.

“The more I look at the trends facing the world’s largest terrestrial mammals, the more concerned I am we could lose these animals just as science is discovering how important they are to ecosystems and to the services they provide for people,” said Dr. William Ripple, professor of ecology at Oregon State University and lead author of the study.

Ripple worked with other authors on the study to examine population trends of many species, including many of the most well-known, charismatic species such as elephants, rhinos, gorillas, and big cats that are now threatened with extinction.

Approximately 59 percent of the world’s biggest mammalian carnivore species — including the tiger — and 60 percent of the largest herbivores are now listed on the International Union for Conservation of Nature’s Red List of Threatened Species as threatened with extinction.

“Perhaps the biggest threat for many species is direct hunting driven by a demand for meat, pets, and body parts for traditional medicines and ornaments,” Dr. Elizabeth Bennett, WCS’s Vice President of Species Conservation and a co-author on the study. “Only a massive commitment from the international community will stop this rampant destruction of so many animal populations.”

All of these large species play critical roles in their ecosystems. Species at risk include elephants, that provide a suite of vital ecosystem services as ecological engineers, dispersing seeds and nutrients across vast areas. “The loss of elephants in the forests of Central Africa is increasingly damaging the function of the region’s most important ecosystems,” said WCS Conservation Scientist Dr. Fiona Maisels, one of the study’s co-authors. “We’re only beginning to understand how vital these keystone species are to the health of rainforests and other species that inhabit them.”

Human-wildlife conflict is a serious concurrent threat for many species. “With simultaneous loss of wildlife habitat and expansion of human populations and agriculture, negative interactions between people and wildlife are bound to rise,” said WCS India Scientist Dr. Varun R. Goswami, also a co-author on the study. “For wide-ranging megafauna like elephants and tigers, we need landscape-scale conservation strategies, taking into account the increasing interface between wildlife and people.”

Some megafauna face the threat of obscurity. The loss of elephants worldwide to poachers in pursuit of ivory is well-known and is the focus of extensive efforts to shut down this trade, but the study authors point out that many species are at risk from many similar threats but are so poorly known that effective conservation efforts to save them are difficult.

The paper includes a 13-part declaration that highlights the need to acknowledge the threatened status of many large mammals and the vital ecological roles they play. The declaration also cites the importance of integrating the efforts of scientists and funding agencies in developing countries where many species occur; the need for a new global framework to conserve megafauna; and the moral obligation of saving the world’s biggest mammal species.

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

https://www.sciencedaily.com/releases/2016/07/160727172008.htm Original web page at Science Daily

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Should the gray wolf keep its endangered species protection?

Research by UCLA biologists published today in the journal Science Advances presents strong evidence that the scientific reason advanced by the U.S. Fish and Wildlife Service to remove the gray wolf from protection under the Endangered Species Act is incorrect.

A key justification for protection of the gray wolf under the act was that its geographic range included the Great Lakes region and 29 Eastern states, as well as much of North America. The Fish and Wildlife Service published a document in 2014 which asserted that a newly recognized species called the eastern wolf occupied the Great Lakes region and eastern states, not the gray wolf. Therefore, the original listing under the act was invalid, and the service recommended that the species (except for the Mexican gray wolf, which is the most endangered gray wolf in North America) should be removed from protection under the act.

A decision by the U.S. Fish and Wildlife Service to remove the gray wolf from protection under the Endangered Species Act may be made as early as this fall.

In the new study, biologists analyzed the complete genomes of North American wolves — including the gray wolf, eastern wolf and red wolf — and coyotes. The researchers found that both the red wolf and eastern wolf are not distinct species, but instead are mixes of gray wolf and coyote.

“The recently defined eastern wolf is just a gray wolf and coyote mix, with about 75 percent of its genome assigned to the gray wolf,” said senior author Robert Wayne, a UCLA professor of ecology and evolutionary biology. “We found no evidence for an eastern wolf that has a separate evolutionary legacy. The gray wolf should keep its endangered species status and be preserved because the reason for removing it is incorrect. The gray wolf did live in the Great Lakes area and in the 29 eastern states.”

Once common throughout North America and among the world’s most widespread mammals, the gray wolf is now extinct in much of the United States, Mexico and Western Europe, and lives mostly in wilderness and remote areas. Gray wolves still lives in the Great lakes area, but not in the eastern states.

Apparently, the two species first mixed hundreds of years ago in the American South, resulting in a population that has become more coyote-like as gray wolves were slaughtered, Wayne said. The same process occurred more recently in the Great Lakes area, as wolves became rare and coyotes entered the region in the 1920s.

The researchers analyzed the genomes of 12 pure gray wolves (from areas where there are no coyotes), three coyotes (from areas where there are no gray wolves), six eastern wolves (which the researchers call Great Lakes wolves) and three red wolves.

There has been a substantial controversy over whether red wolves and eastern wolves are genetically distinct species. In their study, the researchers did not find a unique ancestry in either that could not be explained by inter-breeding between gray wolves and coyotes.

“If you did this same experiment with humans — human genomes from Eurasia — you would find that one to four percent of the human genome has what looks like strange genomic elements from another species: Neanderthals,” Wayne said. “In red wolves and eastern wolves, we thought it might be at least 10 to 20 percent of the genome that could not be explained by ancestry from gray wolves and coyotes. However, we found just three to four percent, on average — similar to that found in individuals from the same species when compared to our small reference set.”

Pure eastern wolves were thought to reside in Ontario’s Algonquin Provincial Park. The researchers studied two samples from Algonquin Provincial Park and found they were about 50 percent gray wolf, 50 percent coyote.

Biologists mistakenly classified the offspring of gray wolves and coyotes as red wolves or eastern wolves, but the new genomic data suggest they are hybrids. “These gray wolf-coyote hybrids look distinct and were mistaken as a distinct species,” Wayne said.

Eventually, after the extinction of gray wolves in the American south, the red wolves could mate only with one another and coyotes, and became increasingly coyote-like.

Red wolves turn out to be about 25 percent gray wolf and 75 percent coyote, while the eastern wolf’s ancestry is approximately 75 percent gray wolf and 25 percent coyote, Wayne said. (Wayne’s research team published findings in the journal Nature in 1991 suggesting red wolves were a mixture of gray wolves and coyotes.)

Although the red wolf, listed as an endangered species in 1973, is not a distinct species, Wayne believes it is worth conserving; it is the only repository of the gray wolf genes that existed in the American South, he said.

The researchers analyzed SNPs (single nucleotide polymorphisms) — tiny variations in a genetic sequence, and used sophisticated statistical approaches. In the more than two dozen genomes, they found 5.4 million differences in SNPs, a very large number.

Wayne said the Endangered Species Act has been extremely effective. He adds, however, that when it was formulated in the 1970s, biologists thought species tended not to inter-breed with other species, and that if there were hybrids, they were not as fit. The scientific view has changed substantially since then. Inter-breeding in the wild is common and may even be beneficial, he said. The researchers believe the Endangered Species Act should be applied with more flexibility to allow protection of hybrids in some cases (it currently does not), and scientists have made several suggestions about how this might be done without a change in the law, Wayne said.

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

https://www.sciencedaily.com/releases/2016/07/160727150802.htm  Original web page at Science Daily

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Songbirds’ epic migrations connected to a small cluster of genes

Scientists from the University of British Columbia have shown that there is a genetic basis to the migratory routes flown by songbirds, and have narrowed in on a relatively small cluster of genes that may govern the behaviour.

“It’s amazing that the routes and timing of such complex behaviour could be genetically determined and associated with a very small portion of the genome,” said researcher Kira Delmore, lead author of the paper published in Current Biology.

“What’s even more amazing is that differences in this behaviour could be helping to maintain the huge diversity of songbirds we see in the natural world.”

Seasonal migration is one of the most remarkable biological phenomena in the world, with routes spanning thousands of kilometres and involving billions of animals. Songbirds travel up to 15,000 kilometres, despite often weighing under ten grams. They undertake these journeys alone at night and return to the same locations year after year.

Delmore and her colleagues used coin-sized light-level geolocators to track songbirds’ migrations, and next-generation sequencing techniques to get an in-depth view of their genomes. They applied these two recently-developed techniques to two closely related groups of Swainson’s thrushes in B.C., and their hybrids.

While the groups are evolutionarily and genetically related, they take different routes on migration each year. A coastal group migrates down the west coast, southward to Mexico and Central America, while an inland group near Kamloops migrates southeastward to the southeastern USA and then South America. The groups interbreed northeast of Vancouver, in the coastal mountains.

Previous work conducted by the team showed that birds from the hybrid population take intermediary migration routes, which cross deserts and mountainous regions. These inferior routes likely cause hybrids to have lower reproductive success, resulting in less gene flow between the groups and more differentiation between them.

By linking the migratory behavior of hybrids to their genetic makeup, these researchers pinpointed a single cluster of roughly 60 genes on one chromosome that largely accounts for the difference in migration patterns.

The genes play an important role in the birds’ circadian, nervous and cell signalling systems. They are also located in regions of the genome that have reduced movement of genes from one population of thrushes to the other.

“Smaller scale studies have associated some genes in this region with migratory behavior in organisms as diverse as butterflies, fish and other birds,” said UBC zoologist Darren Irwin, senior author of the study. “These results provide even stronger evidence that evolution of this genetic cluster can cause different migratory routes, facilitating the evolution of two species from one.”

Delmore conducted the research while at UBC and is now with the Max Planck Institute for Evolutionary Biology, where she will continue to winnow down the set of genes responsible for migration, and use the same cutting edge techniques to investigate other populations of birds.

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

https://www.sciencedaily.com/releases/2016/07/160728143251.htm Original web page at Science Daily

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Why brain neurons in Parkinson’s disease stop benefiting from levodopa

Though the drug levodopa can dramatically improve Parkinson’s disease symptoms, within five years one-half of the patients using L-DOPA develop an irreversible condition — involuntary repetitive, rapid and jerky movements. This abnormal motor behavior appears only while taking L-DOPA, and it stops if the drug is stopped. However, if L-DOPA is taken again, even many months later, it quickly re-emerges.

In research to prevent this side effect and extend the usefulness of L-DOPA — which is the most effective drug treatment for Parkinson’s disease — University of Alabama at Birmingham researchers have uncovered an essential mechanism of this long-term memory for L-DOPA-induced-dyskinesia, or LID.

They report a widespread reorganization of DNA methylation — a process in which the function of DNA is modified — in brain cells caused by L-DOPA. They also found that treatments that increase or decrease DNA methylation can alter dyskinesia symptoms in an animal model.

Thus, modification of DNA methylation may be a novel therapeutic target to prevent or reverse LID behavior.

“L-DOPA is a very valuable treatment for Parkinson’s, but in many patients its use is limited by dyskinesia,” said David Standaert, M.D., Ph.D., the John N. Whitaker Professor and chair of the Department of Neurology at UAB. “Better means of preventing or reversing LID could greatly extend the use of L-DOPA without inducing intolerable side effects. The treatments we have used here, methionine supplementation or RG-108, are not practical for human use; but they point to the opportunity to develop methylation-based epigenetic therapeutics in Parkinson’s disease.”

The research by David Figge, Karen Eskow Jaunarajs, Ph.D., and corresponding author David Standaert, Center for Neurodegeneration and Experimental Therapeutics, UAB Department of Neurology, was recently published in The Journal of Neuroscience.

Although studies of LID in animal models have shown changes in gene expression and cell signaling, a key unanswered question still remained: Why is the neural sensitization seen in LID persistent when delivery of L-DOPA is transient?

The UAB researchers suspected DNA methylation changes — the attachment of a methyl group onto nucleotides in DNA — because methylation is known to stably alter gene expression in cells as they grow and differentiate. Furthermore, methylation changes in neurons have been shown to be involved during the formation of place memory and the development of addictive behavior after cocaine use.

In general, increased DNA methylation has a silencing effect on nearby gene expression, while removal of the methyl groups enhances gene expression.

Figge and colleagues found that:

L-DOPA treatment of parkinsonian rodents enhanced the expression of two DNA demethylases.

Cells in the dorsal striatum in the LID model showed extensive, location-specific changes in DNA methylation, mostly seen as demethylation.The changes in DNA methylation were near many genes with established functional importance in LID.

Modulating global DNA methylation — either by injecting methionine to increase methylation or applying RG-108, an inhibitor of methylation, to the striatum — modified the dyskinetic behavior of LID, down or up, respectively.

“Together,” the researchers wrote, “these findings demonstrate that L-DOPA induces widespread changes to striatal DNA methylation and that these modifications are required for the development and maintenance of LID.”

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

https://www.sciencedaily.com/releases/2016/07/160728143608.htm  Original web page at Science Daily

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Tooth wear sheds light on the feeding habits of ancient elephant relatives

How can we ever know what ancient animals ate? For the first time, the changing diets of elephants in the last two million years in China have been reconstructed, using a technique based on analysis of the surface textures of their teeth.

The work was carried out by a University of Bristol student, working with an international team of researchers. The research was published online in Quaternary International.

Today, elephants live only in remote, tropical parts of Africa and southern Asia, but before the Ice Ages they were widespread.

As his undergraduate research project, Zhang Hanwen, MSci Palaeontology and Evolution graduate and now PhD student at the University of Bristol, undertook cutting-edge analysis of fossilised elephant teeth from China.

In a collaboration with the University of Leicester, and the Institute of Vertebrate Paleontology and Paleoanthropology in Beijing, where the fossilised teeth are curated, Hanwen sampled 27 teeth for tiny wear patterns called microwear.

“We are talking huge, brick-sized molars here — the largest of any animal,” said Hanwen, “but the signs of tooth wear are tiny, down to thousandths of a millimetre. However, these microscopic surface textures can tell us whether they were eating grass or leaves.”

Hanwen took peels of the fossilised teeth in China, using high-grade dental moulding materials, and captured the 3D surface textures under a digital microscope at the University of Leicester. The textures were quantified and analysed to identify what the elephants were eating in the days and weeks before they died.

By comparing the results with information from modern ruminants (deer, antelopes and oxen) of known diet, the study concluded two extinct elephants from Southern China — Sinomastodon and Stegodon — were primarily browsing on leaves. The third, Elephas, which includes the modern Asian elephants, shows much more catholic feeding habit, incorporating both grazing and browsing.

“It’s wonderful that we can identify diets of any fossil mammal with confidence now,” said Professor Christine Janis, from the University of Bristol, one of Hanwen’s PhD supervisors and a leading expert on the evolution of herbivorous mammals.

“This is based on the fact that the microwear textures produced by different kinds of plant material are comparable across unrelated animals.”

“This method for identifying diet relies on high-quality 3D surface data and analysis,” said Professor Mark Purnell, of the University of Leicester, another co-supervisor of Hanwen’s.

“It removes the subjectivity of trying to quantify microwear textures by identifying and counting scratches and pits in 2D microscopic images.”

Sinomastodon and Stegodon coexisted in Southern China between 2.6 and one million years ago, but Sinomastodon then became extinct and left Stegodon to become the dominant elephant of Southern China for the remainder of the Pleistocene, the time of the great Ice Ages.

“The fossil pollen record, and recently-excavated mammal fossil assemblages from various karst cave sites near the Chinese-Vietnamese border, suggest a prolonged, fluctuating period of environmental deterioration around this time,” Hanwen explained.

He added: “Forests were on the decline, alongside many of the more archaic mammal species that inhabited them. The highly evolved molars of Stegodon, with multiple enamel ridges, might have allowed it to browse on its preferred foliage in a more efficient way, thus outcompeting Sinomastodon, which preferred the same diet, but had less sophisticated molars consisting of large, blunt, conical cusps.”

On the other hand, the new study also suggests that Stegodon and Elephas subsequently coexisted for long periods in Southern China by eating different things. Stegodon remained a specialist foliage feeder whereas Elephas was more of a generalist, consuming a wider variety of vegetation.

Stegodon became extinct at around 11,000 years ago, at the end of the Pleistocene, coinciding with the worldwide disappearance of large mammal species at this time, including the iconic woolly mammoths, giant deers and sabretoothed cats. The Asian elephant survived in Southern China into historical times.

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

https://www.sciencedaily.com/releases/2016/07/160728101924.htm Original web page at Science Daily

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* Scientists warn about health of English bulldog

According to new research it could be difficult to improve the health of the English bulldog, one of the world’s unhealthiest dog breeds, from within its existing gene pool. The findings will be published in the open access journal Canine Genetics and Epidemiology.

The English bulldog’s limited genetic diversity could minimize the ability of breeders to recreate healthy phenotypes from the existing genetic stock, which were created by human-directed selection for specific desired physical traits.

Many large regions of the bulldog’s genome have been altered to attain the extreme changes in its outward appearance. This includes significant loss of genetic diversity in the region of the genome that contains many of the genes that regulate normal immune responses. Despite this, the English bulldog is one of the most popular dog breeds, particularly in the US, where the bulldog was the fourth most popular pure breed in 2015.

Lead author, Niels Pedersen from Center for Companion Animal Health, University of California, US, said: “The English bulldog has reached the point where popularity can no longer excuse the health problems that the average bulldog endures in its often brief lifetime. More people seemed to be enamoured with its appearance than concerned about its health. Improving health through genetic manipulations presumes that enough diversity still exists to improve the breed from within, and if not, to add diversity by outcrossing to other breeds. We found that little genetic ‘wiggle room’ still exists in the breed to make additional genetic changes.”

Pedersen adds: “These changes have occurred over hundreds of years but have become particularly rapid over the last few decades. Breeders are managing the little diversity that still exists in the best possible manner, but there are still many individuals sired from highly inbred parents. Unfortunately eliminating all the mutations may not solve the problem as this would further reduce genetic diversity. We would also question whether further modifications, such as rapidly introducing new rare coat colors, making the body smaller and more compact and adding more wrinkles in the coat, could improve the bulldog’s already fragile genetic diversity.”

This is the first broad-based assessment of genetic diversity in the English bulldog using DNA analysis rather than pedigrees. DNA analysis is needed to measure, monitor and maintain genetic diversity. This has been done in several other breeds including Standard and Miniature Poodles, American Golden Retrievers, and American and European Italian Greyhound.

The researchers sought to identify whether there is enough genetic diversity still existing within the breed to undertake significant improvements from within the existing gene pool. The researchers examined 102 English bulldogs, 87 dogs from the US and 15 dogs from other countries. These were genetically compared with an additional 37 English bulldogs presented to the US Davis Veterinary Clinical Services for health problems, to determine that the genetic problems of the English bulldogs were not the fault of commercial breeders or puppy mills.

Many Swiss breeders have started to outcross the breed with the Olde English Bulldogge (an American breed) to create the Continental Bulldog, hoping to improve the breed’s health. Although outcrossing the English bulldog could improve its health, many breeders feel that any deviations from the original standard will no longer be an English bulldog.

The breed started from a relatively small genetic base with a founder population of 68 individuals after 1835 and has undergone a number of human created artificial bottlenecks (drastic reductions in population size). These could also have greatly diminished genetic diversity.

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

https://www.sciencedaily.com/releases/2016/07/160729092534.htm  Original web page at Science Daily

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Scientists grow mini human brains

Scientists in Singapore have made a big leap on research on the ‘mini-brain’. These advanced mini versions of the human midbrain will help researchers develop treatments and conduct other studies into Parkinson’s Disease (PD) and aging-related brain diseases.

These mini midbrain versions are three-dimensional miniature tissues that are grown in the laboratory and they have certain properties of specific parts of the human brains. This is the first time that the black pigment neuromelanin has been detected in an organoid model. The study also revealed functionally active dopaminergic neurons.

The human midbrain, which is the information superhighway, controls auditory, eye movements, vision and body movements. It contains special dopaminergic neurons that produce dopamine — which carries out significant roles in executive functions, motor control, motivation, reinforcement, and reward. High levels of dopamine elevate motor activity and impulsive behaviour, whereas low levels of dopamine lead to slowed reactions and disorders like PD, which is characterised by stiffness and difficulties in initiating movements.

Also causing PD is the dramatic reduction in neuromelanin production, leading to the degenerative condition of patients, which includes tremors and impaired motor skills. This creation is a key breakthrough for studies in PD, which affects an estimated seven to 10 million people worldwide. Furthermore, there are people who are affected by other causes of parkinsonism. Researchers now have access to the material that is affected in the disease itself, and different types of studies can be conducted in the laboratory instead of through simulations or on animals. Using stem cells, scientists have grown pieces of tissue, known as brain organoids, measuring about 2 to 3 mm long. These organoids contain the necessary hallmarks of the human midbrain, which are dopaminergic neurons and neuromelanin.

Jointly led by Prof Ng Huck Hui from A*STAR’s Genome Institute of Singapore (GIS) and Assistant Prof Shawn Je from Duke-NUS Medical School, this collaborative research between GIS, Duke-NUS, and the National Neuroscience Institute (NNI) is funded by the National Medical Research Council’s Translational Clinical Research (TCR) Programme In Parkinson’s disease (PD) and A*STAR. Other collaborators are from the Lieber Institute for Brain Development, the Johns Hopkins University School of Medicine, and the Nanyang Technological University.

Assistant Prof Shawn Je from Duke-NUS Medical School’s Neuroscience & Behavioural Disorders Programme said, “It is remarkable that our midbrain organoids mimic human midbrain development. The cells divide, cluster together in layers, and become electrically and chemically active in three-dimensional environment like our brain. Now we can really test how these mini brains react to existing or newly developed drugs before treating patients, which will be a game changer for drug development.”

Prof Tan Eng King, Research Director and Senior Consultant, Department of Neurology at NNI and Lead PI of the TCR Programme in PD, remarked, “The human brain is arguably the most complex organ and chronic brain diseases pose considerable challenges to doctors and patients. This achievement by our Singapore team represents an initial but momentous scientific landmark as we continue to strive for better therapies for our patients.”

GIS Executive Director Prof Ng Huck Hui said, “Considering one of the biggest challenges we face in PD research is the lack of accessibility to the human brains, we have achieved a significant step forward. The midbrain organoids display great potential in replacing animals’ brains which are currently used in research; we can now use these midbrains in culture instead to advance our understanding and future studies for the disease, and perhaps even other related diseases.”

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

https://www.sciencedaily.com/releases/2016/07/160730154504.htm Original web page at Science Daily

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Scientists identify immunological profiles of people who make powerful HIV antibodies

People living with HIV who naturally produce broadly neutralizing antibodies (bNAbs) that may help suppress the virus have different immunological profiles than people who do not, researchers report. While bNAbs cannot completely clear HIV infections in people who have already acquired the virus, many scientists believe a successful preventive HIV vaccine must induce bNAbs. The new findings indicate that bNAb production may be associated with specific variations in individual immune functions that may be triggered by unchecked HIV infection. Defining how to safely replicate these attributes in HIV-uninfected vaccine recipients may lead to better designed experimental vaccines to protect against HIV. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Researchers led by a team at Duke University identified these immunologic variations by studying blood samples collected from people living with HIV by the NIAID-supported Center for HIV/AIDS Vaccine Immunology (CHAVI). The team compared blood samples from the 51 individuals with the highest level of bNAbs with samples taken from 51 individuals with few or no bNAbs present. The analysis performed revealed that many variations in immune cell function triggered by chronic HIV infection are associated with high levels of bNAbs. The specific changes included a higher frequency of antibodies that attack one’s own cells, called autoantibodies; fewer immune regulatory T cells, which were also less active in these individuals; and a higher frequency of memory T follicular helper immune cells.

With this immune system configuration, the activity of antibody-producing immune cells called B cells may be less restricted because they are supported by T follicular helper cells and may be hindered by regulatory T cells. This, in turn, could lead to more efficient production of protective bNAbs against HIV. These findings support approaches to developing an HIV vaccine that involve modifying an individual’s immune system to mimic these conditions through the addition of vaccine boosters called adjuvants or other means.

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

https://www.sciencedaily.com/releases/2016/07/160729143030.htm Original web page at Science Daily

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Financial cycles of acquisition and ‘buybacks’ threaten public access to breakthrough drugs

New research on the financial practices surrounding a ‘wonder drug’ with a more than 90% cure rate for hepatitis C — a blood-borne infection that damages the liver over many years — shows how this medical breakthrough, developed with the help of public funding, was acquired by a major pharmaceutical company following a late-stage bidding war.

The research shows how that company more than doubled the drug’s price over original pricing estimates, calculating “how much health systems could bear” according to researchers, and channelled billions of dollars in profits into buying its own shares rather than funding further research.

In this way, the company, Gilead Sciences, passed significant rewards on to shareholders while charging public health services in the US up to $86k per patient, and NHS England almost £35k per patient, for a three month course of the drug.

The high prices have contributed to a rationing effect: many public systems across the US and Europe treat only the sickest patients with the new drug, despite its extraordinary cure rate, and the fact that earlier treatment of an infectious disease gives it less opportunity to spread.

Gilead’s strategy of acquisitions and buybacks is an example of an industry-wide pattern, say the researchers. Many big pharmaceutical companies now rely on innovation emerging from public institutes, universities, and venture-capital supported start-ups — acquiring the most promising drug compounds once there is a level of “certainty,” rather than investing in their own internal research and development.

The researchers, from Cambridge University’s Department of Sociology, say this effectively leaves the public “paying twice”: firstly for the initial research, and then for patent-protected high priced medications. A summary of their research has been commissioned by the British Medical Journal (BMJ) and is published today.

“Large pharmaceutical companies rarely take a drug from early stage research all the way to patients. They often operate as regulatory and acquisition specialists, returning most of the subsequent profits to shareholders and keeping some to make further acquisitions,” said lead researcher Victor Roy, a Cambridge Gates Scholar.

The study’s senior author, Prof Lawrence King, said: “Drug research involves trial and error, and can take years to bear fruit — too long for companies that need to show the promise of annual growth to investors, so acquisitions are often the best way to generate this growth.”

There are an estimated 150 million people worldwide chronically infected with hepatitis C. It disproportionately affects vulnerable groups such as drug users and HIV sufferers, and can ultimately lead to liver failure through cirrhosis if left untreated.

Roy and King’s article tells the story of the curative drug Sofosbuvir. The compound was developed by a start-up that emerged from an Emory-based laboratory that received funding from the US National Institutes of Health and the US Veterans Administration.

The start-up, Pharmasset, eventually raised private funding to develop sofosbuvir. When Phase II trials proved more promising than Gilead’s in-house hepatitis C prospects, it acquired Pharmasset for $11bn following a bidding war — the final weeks of which saw Pharmasset’s valuation rocket by nearly 40%.

“The cost of this late stage arms race for revenues has become part of the industry justification for high drug prices,” write Roy and King.

Once Sofosbuvir was market-ready in 2013, Gilead set a price of $84k. A US Senate investigation later revealed that Pharmasset had initially considered a price of $36k.

By the first quarter of 2016, Gilead had accumulated over $35bn in revenue from hepatitis C medicines in a little over two years — nearly 40 times Gilead and Pharmasset’s combined reported costs for developing the medicines.

Last year, Gilead announced that a lion’s share of those profits — some $27bn — will go towards ‘share buybacks’: purchasing its own shares to increase the value of the remaining ones for shareholders. By contrast, between 2013 and 2015 Gilead increased research investment by $0.9bn to $3bn total.

“Share buybacks are a financial manoeuvre that emerged during the early 1980s due to a change in rules for corporations by the Reagan administration. The financial community now expects companies to reward shareholders with buybacks, but directing profit into buybacks can mean cannibalising innovation,” said Roy.

A further example they cite is that of Merck, who spent $8.4bn in 2014 to acquire a drug developer specialising in staph infections. The next year they closed the developer’s early stage research unit, laying off 120 staff. Three weeks after that, Merck announced an extra $10bn in share buybacks.

In the BMJ article, the researchers set out a number of suggestions to counter the consequences of the current financial model. These include giving health systems greater bargaining power to negotiate deals for breakthrough treatments, and limiting share buybacks.

Roy and King also highlight a possible future model that uses a mix of grants and major milestone prizes to “push” and “pull” promising therapies into wider application, and, crucially, uncouples drug prices from supposed development costs, including those added by shareholder expectations. They write that this approach may be attempted for areas of major public health concern.

“The treatments for Hepatitis C may portend a future of expensive therapies for Alzheimer’s to many cancers to HIV/AIDS. Health systems and patients could face growing financial challenges,” said King.

“We need to recognise what current business models around drug development might mean for this future.”

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

https://www.sciencedaily.com/releases/2016/07/160727194358.htm  Original web page at Science Daily

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Hybrid treatment hunts down and kills leukemia cells

Researchers at UC Davis and Ionis Pharmaceuticals have developed a hybrid treatment that harnesses a monoclonal antibody to deliver antisense DNA to acute lymphoblastic leukemia (ALL) cells and that may lead to less toxic treatments for the disease.

The study, published in the journal Molecular Medicine, demonstrated that once delivered, the therapeutic DNA reduced levels of MXD3, a protein that helps cancer cells survive. This novel conjugate therapy showed great promise in animal models, destroying ALL cells while limiting other damage.

“We’ve shown, for the first time, that anti-CD22 antibody-antisense conjugates are a potential therapeutic agent for ALL,” said Noriko Satake, associate professor in the Department of Pediatrics at UC Davis. “This could be a new type of treatment that kills leukemia cells with few side effects.”

ALL is the most common type of childhood cancer. It is a disease in which the bone marrow makes too many immature lymphocytes, a type of white blood cell. While most children survive ALL, many patients suffer late or long-term side effects from treatment, which may include heart problems, growth and development delays, secondary cancers and infertility.

Antisense oligonucleotides are single strands of DNA that can bind to messenger RNA, preventing it from making a protein. While antisense technology has long shown therapeutic potential, getting the genetic material inside target cells has been a problem.

In the study, researchers attached antisense DNA that inhibits the MXD3 protein to an antibody that binds to CD22, a protein receptor expressed almost exclusively in ALL cells and normal B cells.

Once the antibody binds to CD22, the conjugate is drawn inside the leukemia cell, allowing the antisense molecule to prevent MXD3 production. Without this anti-apoptotic protein, ALL cells are more prone to cell death.

The hybrid treatment was effective against ALL cell lines in vitro and primary (patient-derived) ALL cells in a xenograft mouse model. Animals that received the hybrid therapy survived significantly longer than those in the control group.

Designed to be selective, the treatment only targets cells that express CD22. While it does attack healthy B cells, the therapy is expected to leave blood stem cells and other tissues unscathed.

“You really don’t want to destroy hematopoietic stem cells because then you have to do a stem cell transplant, which is an extremely intensive therapy,” noted Satake. “Our novel conjugate is designed so that it does not harm hair, eyes, heart, kidneys or other types of cells.”

While the study shows the conjugate knocked down MXD3, researchers still have to figure out how this was accomplished. In addition, they will investigate combining this treatment with other therapies. Because it hastens cell death, the conjugate could make traditional chemotherapy drugs more effective. In addition, the approach might work against other cancers.

“You can see this as proof of principle,” Satake said. “You could switch the target and substitute the antibody, which could be used to treat other cancers or even other diseases.”

Access the full report at: http://static.smallworldlabs.com/molmedcommunity/content/pdfstore/15_210_Satake.pdf

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https://www.sciencedaily.com/releases/2016/07/160728155631.htm  Original web page at Science Daily

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Parasitic infection may have spoiled zebrafish experiments

A common parasite that infects laboratory zebrafish may have been confounding the results of years of behavioural experiments, researchers say – but critics say the case isn’t proven.

Like the rat, the zebrafish (Danio rerio) is used in labs worldwide to study everything from the effects of drugs, to genetic diseases and disorders such as schizophrenia and autism. Since both zebrafish and people are highly social, researchers think that zebrafish may be a better lab model for some human behaviours than rodents.

Zebrafish demonstrate their preference for each other by clustering into shoals – a social behaviour that researchers measure when they want to test how drugs affect zebrafish stress and anxiety levels, as a proxy for potential human responses. But this behaviour can change when fish are infected with a neural parasite called Pseudoloma neurophilia, scientists from Oregon State University in Corvallis report in a paper published on 11 July in the Journal of Fish Diseases.

The team say that individual fish infected with P. neurophilia swim closer to each other than do non-infected fish, a behaviour that is also associated with increased stress and anxiety. The finding casts doubt on results from previous experiments, says lead study author Sean Spagnoli, a veterinary surgeon – since the infection may have scrambled researchers’ interpretations of shoaling behaviour.

Spagnoli first heard that a parasite was infecting many laboratory zebrafish when he was working at the Zebrafish International Resource Center (ZIRC) in Eugene, Oregon – a central repository which sends out zebrafish strains to researchers and also tests zebrafish health. P. neurophilia settles in the brain, spinal cord and nerves of zebrafish.

“The paper is great, as it raises some doubts about the way behaviour may be used to study brain function in zebrafish,” says Robert Gerlai, a behavioural geneticist from the University of Toronto Mississauga in Canada. But he advises not jumping to conclusions on the basis of one study. Gerlai has concerns about the work; in particular, he says, Spagnoli’s team relied on a low-tech method to measure their fish shoals, taking screen snapshots and measuring the distance between each fish rather than more precise continuous tracking. And the researchers didn’t check what else might have been affecting the zebrafish, he adds.

Elena Dreosti, a geneticist at University College London, says that the paper’s data are weak and the effects it shows are small. “Considerable additional work is needed to know if this is likely to have a significant impact on the type of behaviour research that is done by the community working with zebrafish,” she says.

But Spagnoli says that his low-tech method is all that’s needed to raise the red flag that infection can influence behaviours such as shoaling. He agrees that he hasn’t proven that the P. neurophilia is directly responsible for the changed behaviour – but says that his study suggests that shoaling changes when the parasite is present.

As many as half of all laboratory facilities may be using some infected zebrafish, according to ZIRC data from 2015 – although only 28 facilities submitted their zebrafish to the centre for health checks that year. Within a facility, infection rates hover around 7-10%; some tanks may have no infected zebrafish, but others have many, Spagnoli says.

Nuno Pereira, a zebrafish veterinarian at the Gulbenkian Science Institute in Oeiras, Portugal, says that most researchers are already aware of the importance of testing for the parasite – and Spagnoli agrees that labs have drastically improved their screening protocols.

But Spagnoli thinks that many labs may still have a significant number of fish that are infected. “I haven’t seen a single paper that stated that ‘fish used were certified pathogen-free for P. neurophilia’,” he says. The team will continue to study the parasite’s effects, he says, and is also looking at the potential influence of another common contaminant, Mycobacterium chelonae, on shoaling behaviour.

Nature doi:10.1038/nature.2016.20308

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

http://www.nature.com/news/parasitic-infection-may-have-spoiled-zebrafish-experiments-1.20308  Original web page at Nature 

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* Human nose holds novel antibiotic effective against multiresistant pathogens

A potential lifesaver lies unrecognized in the human body: Scientists at the University of Tübingen and the German Center for Infection Research (DZIF) have discovered that Staphylococcus lugdunensis which colonizes in the human nose produces a previously unknown antibiotic. As tests on mice have shown, the substance which has been named Lugdunin is able to combat multiresistant pathogens, where many classic antibiotics have become ineffective. The research results will be published on 27 July in the scientific journal Nature.

Infections caused by antibiotic-resistant bacteria — like the pathogen Staphylococcus aureus (MRSA) which colonizes on human skin — are among the leading causes of death worldwide. The natural habitat of harmful Staphylococcus bacteria is the human nasal cavity. In their experiments, Dr. Bernhard Krismer, Alexander Zipperer and Professor Andreas Peschel from the Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT) observed that Staphylococcus aureus is rarely found when Staphylococcus lugdunensis is present in the nose.

“Normally antibiotics are formed only by soil bacteria and fungi,” says Professor Andreas Peschel. “The notion that human microflora may also be a source of antimicrobial agents is a new discovery.” In future studies, scientists will examine whether Lugdunin could actually be used in therapy. One potential use is introducing harmless Lugdunin-forming bacteria to patients at risk from MRSA as a preventative measure.

Researchers from the Institute of Organic Chemistry at the University of Tübingen closely examined the structure of Lugdunin and discovered that it consists of a previously unknown ring structure of protein blocks and thus establishes a new class of materials.

Antibiotic resistance is a growing problem for physicians. “There are estimates which suggests that more people will die from resistant bacteria in the coming decades than cancer,” says Dr. Bernhard Krismer. “The improper use of antibiotics strengthens this alarming development” he continues. As many of the pathogens are part of human microflora on skin and mucous membranes, they cannot be avoided. Particularly for patients with serious underlying illnesses and weakened immune systems they represent a high risk — these patients are easy prey for the pathogens. Now the findings made by scientists at the University of Tübingen open up new ways to develop sustainable strategies for infection prevention and to find new antibiotics — also in the human body.

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

https://www.sciencedaily.com/releases/2016/07/160729093039.htm  Original web page at  Science Daily

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Labrador study offers vets clues on why dogs’ tails lose their wag

A painful condition that affects dogs’ tails may be more common than previously thought, a study suggests.

The research offers clues to potential causes of the illness — known as limber tail — which mostly affects larger working dog breeds, such as Labrador Retrievers.

Researchers say their findings are the first step towards preventing the distressing condition, which causes the tail to become limp and painful.

The team at the University of Edinburgh compared 38 cases of limber tail that were identified from owners’ reports about their dogs’ health with 86 dogs that had no tail symptoms.

Their goal was to gain insight into habits and lifestyle factors that might explain why some dogs are affected and not others.

The majority of dogs in the study were pets but those affected by limber tail were more likely to be working dogs, they found.

Swimming has previously been thought to be a risk factor for limber tail, which is sometimes known as ‘swimmers’ tail’. Some but not all of the affected dogs had been swimming prior to the onset of symptoms, the study found.

Dogs with the condition were more likely to live in northern areas, lending support to anecdotal reports that limber tail is associated with exposure to the cold.

Labradors that had suffered limber tail were more likely to be related to each other than unaffected dogs, which may indicate an underlying genetic risk.

Experts hope that further studies will identify genes associated with the condition, which could one day help breeders to identify animals that are likely to be affected. Over time, this could help to reduce the disease prevalence.

The symptoms usually resolve within a few days or weeks so many cases are not reported to vets. This may be why it has been so underestimated in the past. However, owners report that it can be very painful and distressing for the animals.

The study is the first large-scale investigation of limber tail and was conducted as part of the Dogslife project, which follows the health and wellbeing of more than 6000 Labradors from across the UK.

Dr Carys Pugh, who led the study at the University’s Roslin Institute and Royal (Dick) School of Veterinary Studies, said: “We were surprised by how many owners were reporting limber tail to us but it meant we had the chance to do a detailed investigation.

“We have been able to add evidence to a lot of internet speculation about risk factors and the new findings relating to geographical region and family links give us avenues to pursue in understanding and avoiding the condition.”

The study, published in the Veterinary Record, was funded by the Kennel Club Charitable Trust. The Roslin Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council.

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

https://www.sciencedaily.com/releases/2016/08/160801110205.htm Original web page at Science Daily

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How birds soar to great heights

Migratory birds often use warm, rising atmospheric currents to gain height with little energy expenditure when flying over long distances.

It’s a behavior known as thermal soaring that requires complex decision-making within the turbulent environment of a rising column of warm air from the sun baked surface of the earth.

But exactly how birds navigate within this ever-changing environment to optimize their thermal soaring was unknown until a team of physicists and biologists at the University of California San Diego took an exacting computational look at the problem.

In this week’s online version of the journal Proceedings of the National Academy of Sciences, the scientists demonstrated with mathematical models how glider pilots might be able to soar more efficiently by adopting the learning strategies that birds use to navigate their way through thermals.

“Relatively little is known about the navigation strategies used by birds to cope with these challenging conditions, mainly because past computational research examined soaring in unrealistically simplified situations,” explained Massimo Vergassola, a professor of physics at UC San Diego.

To tackle the problem, he and his colleagues, including Terrence Sejnowski, a professor of neurobiology at the Salk Institute and UC San Diego, combined numerical simulations of atmospheric flow with “reinforcement learning algorithms” — equations originally developed to model the behavior and improved performance of animals learning a new task. Those algorithms were developed in a manner that trained a glider to navigate complex turbulent environments based on feedback on the glider’s soaring performance.

According to Sejnowski, the “reinforcement learning architecture” was the same as that used by Google’s DeepMind AlphaGo program, which made headlines in 2016 after beating the human professional Go player Lee Sedol.

When applying it to soaring performance, the researchers took into account the bank angle and the angle of attack of the glider’s wings as well as how the temperature variations within the thermal impacted vertical velocity.

“By sensing two environmental cues — vertical wind acceleration and torque — the glider is able to climb and stay within the thermal core, where the lift is typically the largest, resulting in improved soaring performance, even in the presence of strong turbulent fluctuations,” said Vergassola. “As turbulent levels rise, the glider can avoid losing height by adopting increasingly conservative, risk-averse flight strategies, such as continuing along the same path rather than turning.”

The researchers write in their paper that, based on their study, “torque and vertical accelerations” appear to be the sensorimotor cues that most effectively guide the most efficient soaring path of birds through thermals, rather than differences in temperature.

“Temperature was specifically shown to yield minor gains,” they write adding that “a sensor of temperature could then be safely spared in the instrumentation for autonomous flying vehicles.”

“Our findings shed light on the decision-making processes that birds might use to successfully navigate thermals in turbulent environments,” said Vergassola. “This information could guide the design of simple mechanical instrumentation that would allow autonomous gliders to travel long distances with minimal energy consumption.”

“The high levels of soaring performance demonstrated in simulated turbulence could lead to the development of energy efficient autonomous gliders,” said Sejnowski, who is also a Howard Hughes Medical Institute Investigator.

Other members of the research team were Gautam Reddy, a physicist at UC San Diego and the first author of the paper, and Antonio Celani of the Abdus Salam International Center for Theoretical Physics in Trieste, Italy. The study was supported by a grant from the Simons Foundation.

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

https://www.sciencedaily.com/releases/2016/08/160801163844.htm  Original web page at Science Daily

 

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Why is cocaine so addictive? Study using animal model provides clues

Scientists at Wake Forest Baptist Medical Center are one step closer to understanding what causes cocaine to be so addictive. The research findings are published in the current issue of the Journal of Neuroscience.

Cocaine addiction is a debilitating neurological disorder that affects more than 700,000 people in the United States alone, according to the Substance Abuse and Mental Health Services Administration. With repeated use, tolerance may develop, meaning more of the drug is required to achieve the same euphoric effect. Cocaine addiction can be characterized by repeated attempts at abstinence that often end in relapse.

“Scientists have known for years that cocaine affects the dopamine system and dopamine transporters, so we designed our study to gain a better understanding of how tolerance to cocaine develops via the dopamine transporters,” said Sara R. Jones, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist and lead author of the study.

“Currently there isn’t any effective treatment available for cocaine addiction so understanding the underlying mechanism is essential for targeting potential new treatments.”

Using an animal model, the research team replicated cocaine addiction by allowing rats to self-administer as much cocaine as they wanted (up to 40 doses) during a six-hour period. Six-hour-a-day access is long enough to cause escalation of intake and tip animals over from having controlled intake to more uncontrolled, binge-like behavior, Jones said.

Following the five-day experiment, the animals were not allowed cocaine for 14 or 60 days. After the periods of abstinence, the researchers looked at the animals’ dopamine transporters and they appeared normal, just like those in the control animals that had only received saline.

However, a single self-administered infusion of cocaine at the end of abstinence, even after 60 days, fully reinstated tolerance to cocaine’s effects in the animals that had binged. In the control animals that had never received cocaine, a single dose did not have the same effect.

These data demonstrate that cocaine leaves a long-lasting imprint on the dopamine system that is activated by re-exposure to cocaine, Jones said. This ‘priming effect,’ which may be permanent, may contribute to the severity of relapse episodes in cocaine addicts.

“Even after 60 days of abstinence, which is roughly equivalent to four years in humans, it only took a single dose of cocaine to put the rats back to square one with regard to its’ dopamine system and tolerance levels, and increased the likelihood of binging again,” Jones said. “It’s that terrible cycle of addiction.”

Jones added that hope is on the horizon through preclinical trials that are testing several amphetamine-like drugs for effectiveness in treating cocaine addiction.

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

https://www.sciencedaily.com/releases/2016/08/160801163906.htm Original web page at Science Daily

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What can a sea-lion teach us about musicality?

Ronan the sea lion can keep the beat better than any other animal, a study published in Frontiers in Neuroscience found out more.

Whether it is Mozart, Hendrix, Miles Davis, or tribal drumming, few activities feel as uniquely human as music. And, indeed, for a long time, most scientists believed that Homo sapiens was the only species capable of creating and responding to rhythm and melody.

This view, however, was challenged profoundly in 2009, when a cockatoo called Snowball was shown to be an able dancer.

Snowball bopping along to pop songs clearly demonstrated that non-human species had the neurobiological apparatus required to process rhythmic stimuli and move in time them.

And now — following investigations that have shown that chimps, bonobos, parrots and budgerigars have similar capabilities — a study of a head-bobbing Californian sea lion called Ronan has provided data that may aid scientists in their quest to understand the biological roots of musicality.

Ronan was placed in captivity when she was about a year old after failing to thrive in the wild. Her new team of keepers had previously explored the cognitive abilities of sea lions, and in what was originally a side-project explored at weekends, Peter Cook and Andrew Rouse decided to see if Ronan could keep a beat.

Rewarding her with fish treats every time she successfully nodded along to a click track, Cook and Rouse eventually found that Ronan could beat-keep better than any other non-human animal. Later, she learnt to dance to pop songs too; her favourite is Earth, Wind and Fire’s Boogie Wonderland.

They published an initial report in 2013 documenting this skill, which included numerous control experiments that confirmed that she was truly responding to the rhythmic input. And now in a paper in Frontiers in Neuroscience, Rouse and the team take their analysis a step further.

“A lot of the work that has been done on beat-keeping in general — to show whether a person or an animal is entrained — has used an observational approach, which looks at how close the animal is to each individual beat,” explains Rouse. But such studies “don’t reveal any underlying cause.”

To probe the brain mechanisms responsible for beat-keeping, Rouse says you must, “get a person or animal moving to the beat, then change the rhythm suddenly and look at how they adapt to the change, how they find the beat again.”

This is what they did. After shifting either the tempo or phase of the click track that Ronan was bobbing her head to, the researchers carefully charted how her movements were recalibrated. Something they also did by playing Boogie Wonderland at different speeds. And then they tested if a simple mathematical equation could account for the data.

The equation they used was from the physics of coupled oscillators — which can be as stripped down as two swinging pendulums. Applying this to the brain, the theory behind the experiment is that to move in time to music, the neural activity in auditory brain centres first oscillates in synchrony with the rhythmic input and then this oscillation entrains an oscillation in the neurons of the motor centres that drive movement.

This idea lies at the core of the neural resonance theory of music. And previous studies in people had shown that the equation describes well human beat-keeping. Rouse says that they asked, “Does Ronan’s behaviour fit this proposed model? And we found that it does.”

One thing that is important about Ronan is that sea lions are not “vocal mimics.” All the previous animals that had been shown to have beat-keeping abilities had been of species that have vocal flexibility.

This suggested that perhaps the skill was dependent on specialised neural circuits that are required for vocal flexibility. Ronan’s achievements and their accordance with an equation that simply describes two oscillating entities (in this case, oscillating populations of active neurons) suggest that the neural underpinnings of beat-keeping may be more ancient and widespread than previously thought.

Here, though, Rouse is cautious, he says the work doesn’t specifically distinguish between theories of musicality. He says we need to look further at all theories but that this opens up “a new avenue of exploration.”

Discussing why it took so long to appreciate the beat-keeping ability of non-human creatures, and the possibility that it is a skill lying dormant in many animals, Rouse discusses just how much practice humans get; how deeply and widely music is embedded in human culture. From a very early age babies are bounced on their mothers’ knees, they are exposed to nursery rhymes and music is all around them. “This coupling between auditory and motor regions, we have kind of beaten into us from day one,” he says, “Other animals don’t.”

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

https://www.sciencedaily.com/releases/2016/08/160802125610.htm Original web page at Science Daily

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Shorter telomeres reveal stress in migratory birds

The stress of birds’ continent-spanning annual migrations, it appears, leads to faster aging and a potentially earlier death. A new study in The Auk: Ornithological Advances reveals that telomeres, structures on the ends of chromosomes that shorten with age, are shorter in migratory birds than in their non-migratory counterparts.

Migration lets birds take advantage of abundant food resources at high latitudes during the breeding season while escaping the region’s harsh winters. However, it’s also an enormous undertaking, and the benefits that birds gain from it come with a cost. Carolyn Bauer of North Dakota State University and her colleagues compared the telomeres — bits of non-coding DNA that shorten during cell division and stress — of migratory and resident birds from the same species, the Dark-eyed Junco. They found that the migrants had significantly shorter telomeres than birds that stayed put year-round, suggesting that the migratory birds were aging at a faster rate and that the stress of a migratory lifestyle may actually shorten birds’ lifespans.

“Whenever our cells divide, we lose a little bit of DNA on the ends of our chromosomes, and telomeres are simply non-coding regions that act as ‘protective caps,” explains Bauer. Once they reach a certain threshold of shortness, the cell dies. Importantly, exposure to stress can also make telomeres shorten faster. For their study, Bauer and her colleagues collected blood samples from 11 migratory and 21 resident juncos in Virginia, using only first-year birds to ensure that any telomere differences were not simply due to age. “I’ve been interested in measuring telomeres since I was undergraduate at the University of Washington,” says Bauer. “I remember my introductory biology professor lecturing about telomeres and how environmental stress could cause them to shorten.”

If migrating is so stressful, why keep doing it? Bauer and her colleagues believe that the costs of migration must be balanced out by the reproductive boost birds get from nesting in resource-rich northern habitats. They hope that future studies will determine whether shorter telomeres reflect the stress of migration itself or if they’re the result of decreased self-maintenance, as well as whether telomere length is negatively correlated with migratory distance.

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https://www.sciencedaily.com/releases/2016/08/160803072812.htm Original web page at Science Daily

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DNA’s dynamic nature makes it well-suited to serve as the blueprint of life

A new study could explain why DNA and not RNA, its older chemical cousin, is the main repository of genetic information. The DNA double helix is a more forgiving molecule that can contort itself into different shapes to absorb chemical damage to the basic building blocks — A, G, C and T — of genetic code. In contrast, when RNA is in the form of a double helix it is so rigid and unyielding that rather than accommodating damaged bases, it falls apart completely.

The research, published August 1, 2016 in the journal Nature Structural and Molecular Biology, underscores the dynamic nature of the DNA double helix, which is central to maintaining the stability of the genome and warding off ailments like cancer and aging. The finding will likely rewrite textbook coverage of the difference between the two purveyors of genetic information, DNA and RNA.

“There is an amazing complexity built into these simple beautiful structures, whole new layers or dimensions that we have been blinded to because we didn’t have the tools to see them, until now,” said Hashim M. Al-Hashimi, Ph.D., senior author of the study and professor of biochemistry at Duke University School of Medicine.

DNA’s famous double helix is often depicted as a spiral staircase, with two long strands twisted around each other and steps composed of four chemical building blocks called bases. Each of these bases contain rings of carbon, along with various configurations of nitrogen, oxygen, and hydrogen. The arrangement of these atoms allow G to pair with C and A to pair with T, like interlocking gears in an elegant machine.

When Watson and Crick published their model of the DNA double helix in 1953, they predicted exactly how these pairs would fit together. Yet other researchers struggled to provide evidence of these so-called Watson-Crick base pairs. Then in 1959, a biochemist named Karst Hoogsteen took a picture of an A-T base pair that had a slightly skewed geometry, with one base rotated 180 degrees relative to the other. Since then, both Watson-Crick and Hoogsteen base pairs have been observed in still images of DNA.

Five years ago, Al-Hashimi and his team showed that base pairs constantly morph back and forth between Watson-Crick and the Hoogsteen configurations in the DNA double helix. Al-Hashimi says that Hoogsteen base pairs typically show up when DNA is bound up by a protein or damaged by chemical insults. The DNA goes back to its more straightforward pairing when it is released from the protein or has repaired the damage to its bases.

“DNA seems to use these Hoogsteen base pairs to add another dimension to its structure, morphing into different shapes to achieve added functionality inside the cell,” said Al-Hashimi.

Al-Hashimi and his team wanted to know if the same phenomenon might also be occurring when RNA, the middleman between DNA and proteins, formed a double helix. Because these shifts in base pairing involve the movement of molecules at an atomic level, they are difficult to detect by conventional methods. Therefore, Al-Hashimi’s graduate student Huiqing Zhou used a sophisticated imaging technique known as NMR relaxation dispersion to visualize these tiny changes. First, she designed two model double helices — one made of DNA and one made of RNA. Then, she used the NMR technique to track the flipping of individual G and A bases that make up the spiraling steps, pairing up according to Watson-Crick or Hoogsteen rules.

Prior studies indicated that at any given time, one percent of the bases in the DNA double helix were morphing into Hoogsteen base pairs. But when Zhou looked at the corresponding RNA double helix, she found absolutely no detectable movement; the base pairs were all frozen in place, stuck in the Watson-Crick configuration.

The researchers wondered if their model of RNA was an unusual exception or anomaly, so they designed a wide range of RNA molecules and tested them under a wide variety of conditions, but still none appeared to contort into the Hoogsteen configuration. They were concerned that the RNA might actually be forming Hoogsteen base pairs, but that they were happening so quickly that they weren’t able to catch them in the act. Zhou added a chemical known as a methyl group to a specific spot on the bases to block Watson-Crick base pairing, so the RNA would be trapped in the Hoogsteen configuration. She was surprised to find that rather than connecting through Hoogsteen base pairs, the two strands of RNA came apart near the damage site.

“In DNA this modification is a form of damage, and it can readily be absorbed by flipping the base and forming a Hoogsteen base pair. In contrast, the same modification severely disrupts the double helical structure of RNA,” said Zhou, who is lead author of the study.

The team believes that RNA doesn’t form Hoogsteen base pairs because its double helical structure (known as A-form) is more compressed than DNA’s (B-form) structure. As a result, RNA can’t flip one base without hitting another, or without moving around atoms, which would tear apart the helix.

“For something as fundamental as the double helix, it is amazing that we are discovering these basic properties so late in the game,” said Al-Hashimi. “We need to continue to zoom in to obtain a deeper understanding regarding these basic molecules of life.”

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https://www.sciencedaily.com/releases/2016/08/160801113823.htm Original web page at Science Daily

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* Desert elephants pass on knowledge — not mutations — to survive

Despite reported differences in appearance and behavior, DNA evidence finds that Namibian desert elephants share the same DNA as African savanna elephants. However, Namibian desert-dwelling elephants should be protected so they can continue to pass on their unique knowledge and survival skills to future generations.

“The ability of species such as elephants to learn and change their behavior means that genetic changes are not critical for them to adapt to a new environment,” said lead author Alfred Roca, a professor of animal sciences and member of the Carl R. Woese Institute for Genomic Biology at the University of Illinois. “The behavioral changes can allow species to expand their range to novel marginal habitats that differ sharply from the core habitat.”

Namibian desert-dwelling elephants have figured out how to prevent overheating in triple-digit temperatures by covering their bodies with sand wetted by their urine or regurgitated water from a specialized pouch beneath their tongue that holds many gallons of water. They also remember the location of scarce water and food resources across their home ranges, which are unusually large compared to those of other elephants. They play a critical role in this arid ecosystem by creating paths and digging watering holes.

Published in Ecology and Evolution, this study evaluated the nuclear DNA and mitochondrial DNA (mtDNA) of both desert-dwelling and non-desert-dwelling elephant populations throughout Namibia. Researchers found the desert-dwelling elephant DNA was not significantly different from the DNA of other savanna elephant populations in Namibia, except from those of the Caprivi Strip.

Female elephants live in tight-knit matrilineal family groups so mutations in mtDNA, which is passed from mothers to offspring, are closely tied to geographic populations. Not surprisingly, mitochondrial DNA from savanna elephants in Namibia’s Caprivi Strip — a small region analogous to Oklahoma’s panhandle — was more similar to mitochondrial DNA of elephants in Botswana and Zimbabwe, which border the Caprivi Strip.

“Our results and the historical record suggest that a high learning capacity and long distance migrations enabled Namibian elephants to shift their ranges to survive against high variability in climate and in hunting pressure,” said first author Yasuko Ishida, a research scientist in animal sciences at Illinois.

The lack of genetic differentiation (aside from the Caprivi Strip) is consistent with historical evidence of elephant movements during the Namibian War of Independence, which increased hunting pressures. Using mtDNA, the researchers identified other Namibian elephant migration patterns; for example, elephants from the Ugab River catchment shared mtDNA with elephants from the Huab River catchment, from where they are said to have migrated.

The lack of genetic differences in Namibian elephants could also be attributed to their long distance migrations; large home ranges; recent increases in population size and range; or gene flow provided by male elephants breeding with different groups of female elephants.

“Regardless, these elephants should be conserved,” said Roca. “Their knowledge of how to live in the desert is crucial to the survival of future generations of elephants in the arid habitat, and pressure from hunting and climate change may only increase in the coming decades.

“The desert elephants are also rumored to be larger, which may put them at greater risk for trophy game hunting,” he added. “Animals that live in these marginal environments are vulnerable, and their numbers do not bounce back very quickly. ”

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https://www.sciencedaily.com/releases/2016/08/160803161607.htm  Original web page at Science Daily

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* Can you teach koalas new tricks?

In a paper titled Using complementary remote detection methods for retrofitted eco-passages: a case study for monitoring individual koalas in south-east Queensland published by the CSIRO on Tuesday (July 26), the Environmental Futures Research Institute team verified 130 crossings by koalas involving a retrofitted structure or a road surface over a 30-month period.

Professor Darryl Jones said nobody knew whether the structures would actually keep koalas safe from being hit by cars or if they would work. “We expected the animals to take a while to get used to them,” he said.

“To our great surprise they were using them three weeks into it. Can you teach koalas new tricks? You can, that’s the point. I was the first sceptical person to say they’re not that smart.”

The team used a range of technologies that allowed them to not just generically monitor whether koalas passed through the crossing but pinpointed individual koalas and the exact time they entered and left the tunnel.

Using camera traps, audio radio transmitters and RFID tags that are similar to microchips in pets, they gathered more information than any researcher ever has or would be necessary to monitor koala movements and habits.

“This is all about trying to make absolutely sure that koalas are using some of the structures we’ve put out for them to get safely under roads,” Professor Jones said.

“Knowing how they do that is really difficult. You can get photos but you don’t know if it’s the same animal each time.

“The essence of this you can get really import information using a range of technologies at the same time. That’s a world first. Nobody has done that so comprehensively before.

“We really wanted to know what individual koalas were doing, whether they crossed at the same time each day. We wanted more information than most people ever need and we did that using this range of technologies.”

Professor Jones said most people living in suburban Brisbane or parts of the Gold Coast did not realise koalas lived all around them and that these structures were keeping them safe in their backyards and off the roads.

The research was supported by funding from the Queensland Department of Transport and Main Roads, which was responsible for the structures.

“The tunnels were an experiment,” Professor Jones said.

“Nobody knew whether they would work or not. We really wanted to know what the local koala was doing so we got ridiculous amount of details of these animals.

“We needed to be clear on whether they were successful because the structures were so innovative and risky that we tried really hard to prove it. That’s why it was worth it.

“Although we don’t want the koalas to be disturbed, all over the place on the Gold Coast and in Brisbane there are special koala specific tunnels and ledges that’s allowing them to cross. Those animals are not going to be hit anymore so that’s good news.

The crossings studied in Brisbane were within the jurisdictions of Brisbane City, Redland City and Moreton Bay Regional Council.

Traffic volumes for this region are predicted to increase by 19 per cent, or 2.8 million trips per day between 2006 and 2031.

The paper states: “The continuous clearing of koala habitat for development has placed a great deal of pressure on local koala populations and the risk of vehicle strike is recognised as a key threatening process for ongoing koala persistence in this region.

“The focus must shift from studies that simply assess how many species pass through an eco-passage (i.e. presence), to those that assess the utilisation level by individuals.

“Such information will represent a powerful step forward in providing road authorities with recommendations in relation to the design and placement of crossing structures, and ensuring that the costs equal the ecological benefit.”

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https://www.sciencedaily.com/releases/2016/08/160804101628.htm Original web page at Science Daily

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A study led by researchers at The University of Nottingham has discovered that the fertility of dogs may have suffered a sharp decline over the past three decades

The research, published in the academic journal Scientific Reports, found that sperm quality in a population of stud dogs studied over a 26-year period had fallen significantly.

The work has highlighted a potential link to environmental contaminants, after they were able to demonstrate that chemicals found in the sperm and testes of adult dogs — and in some commercially available pet foods — had a detrimental effect on sperm function at the concentrations detected.

As ‘man’s best friend’ and closest companion animal, the researchers believe that the latest results may offer a new piece of the puzzle over the reported significant decline in human semen quality — a controversial subject which scientists continue to debate.

Dr Richard Lea, Reader in Reproductive Biology in the University’s School of Veterinary Medicine and Science, who led the research said: “This is the first time that such a decline in male fertility has been reported in the dog and we believe this is due to environmental contaminants, some of which we have detected in dog food and in the sperm and testes of the animals themselves.

“While further research is needed to conclusively demonstrate a link, the dog may indeed be a sentinel for humans — it shares the same environment, exhibits the same range of diseases, many with the same frequency and responds in a similar way to therapies.”

The study centred on samples taken from stud dogs at an assistance dogs breeding centre over the course of 26 years. Professor Gary England, Foundation Dean of the School of Veterinary Medicine and Science and Professor of Comparative Veterinary Reproduction, who oversaw the collection of semen said: “The strength of the study is that all samples were processed and analysed by the same laboratory using the same protocols during that time and consequently the data generated is robust.”

The work centred on five specific breeds of dogs — Labrador retriever, golden retriever, curly coat retriever, border collie and German shepherd — with between 42 and 97 dogs studied every year.

Semen was collected from the dogs and analysed to assess the percentage of sperm that showed a normal forward progressive pattern of motility and that appeared normal under a microscope (morphology).

Over the 26 years of the study, they found a striking decrease in the percentage of normal motile sperm. Between 1988 and 1998, sperm motility declined by 2.5 per cent per year and following a short period when stud dogs of compromised fertility were retired from the study, sperm motility from 2002 to 2014 continued to decline at a rate of 1.2% per year.

In addition, the team discovered that the male pups generated from the stud dogs with declining semen quality, had an increased incidence of cryptorchidism, a condition in which the testes of pups fail to correctly descend into the scrotum.

Sperm collected from the same breeding population of dogs, and testes recovered from dogs undergoing routine castration, were found to contain environmental contaminants at concentrations able to disrupt sperm motility and viability when tested.

The same chemicals that disrupted sperm quality, were also discovered in a range of commercially available dog foods — including brands specifically marketed for puppies.

Dr Lea added: “We looked at other factors which may also play a part, for example, some genetic conditions do have an impact on fertility. However, we discounted that because 26 years is simply too rapid a decline to be associated with a genetic problem.”

Over the past 70 years, studies have suggested a significant decline in human semen quality and a cluster of issues called ‘testicular dysgenesis syndrome’ that impact on male fertility which also include increased incidence of testicular cancer, the birth defect hypospadias and undescended testes.

However, declining human semen quality remains a controversial issue — many have criticised the variability of the data of the studies on the basis of changes in laboratory methods, training of laboratory personnel and improved quality control over the years.

Dr Lea added: “The Nottingham study presents a unique set of reliable data from a controlled population which is free from these factors. This raises the tantalising prospect that the decline in canine semen quality has an environmental cause and begs the question whether a similar effect could also be observed in human male fertility.”

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https://www.sciencedaily.com/releases/2016/08/160809095138.htm  Original web page at Science Daily

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An hour of moderate exercise a day enough to counter health risks from prolonged sitting

The health risks associated with sitting for eight or more hours a day — whether at work, home or commuting — can be eliminated with an hour or more of physical activity a day, according to a study from an international team of researchers.

Ever since a study back in 1953 discovered that London bus drivers were at greater risk of heart disease compared to bus conductors, scientists have found increasing evidence that lack of physical activity is a major risk factor for several diseases and for risk of early death. Recent estimates suggest that more than 5 million people die globally each year as a result of failing to meet recommended daily activity levels.

Studies in high-income countries have suggested that adults spend the majority of their waking hours sitting down. A typical day for many people is driving to work, sitting in an office, driving home and watching TV. Current physical activity guidelines recommend that adults do at least 150 minutes of moderate intensity exercise per week.

In an analysis published today in The Lancet that draws together a number of existing studies, an international team of researchers asked the question: if an individual is active enough, can this reduce, or even eliminate, the increased risk of early death associated with sitting down?

In total the researchers analysed 16 studies, which included data from more than one million men and women. The team grouped individuals into four quartiles depending on their level of moderate intensity physical activity, ranging from less than 5 minutes per day in the bottom group to over 60 minutes in the top. Moderate intensity exercise was defined as equating to walking at 3.5 miles/hour or cycling at 10 miles/hour, for example.

The researchers found that 60 to 75 minutes of moderate intensity exercise per day were sufficient to eliminate the increased risk of early death associated with sitting for over eight hours per day. However, as many as three out of four people in the study failed to reach this level of daily activity.

The greatest risk of early death was for those individuals who were physically inactive, regardless of the amount of time sitting — they were between 28% and 59% more likely to die early compared with those who were in the most active quartile — a similar risk to that associated with smoking and obesity. In other words, lack of physical activity is a greater health risk than prolonged sitting.

“There has been a lot of concern about the health risks associated with today’s more sedentary lifestyles,” says Professor Ulf Ekelund from the Medical Research Council Epidemiology Unit at the University of Cambridge. “Our message is a positive one: it is possible to reduce — or even eliminate — these risks if we are active enough, even without having to take up sports or go to the gym.

“For many people who commute to work and have office-based jobs, there is no way to escape sitting for prolonged periods of time. For these people in particular, we cannot stress enough the importance of getting exercise, whether it’s getting out for a walk at lunchtime, going for a run in the morning or cycling to work. An hour of physical activity per day is the ideal, but if this is unmanageable, then at least doing some exercise each day can help reduce the risk.”

The researchers acknowledge that there are limitations to the data analysed, which mainly came from participants aged 45 years and older and living in western Europe, the US and Australia. However, they believe that the strengths of the analysis outweigh these limitations. Most importantly, the researchers asked all included studies to reanalyse their data in a harmonized manner, an approach that has never before been adopted for a study of this size and therefore also provides much more robust effect estimates compared with previous studies.

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How birds unlock their super-sense, ultraviolet vision

The ability of finches, sparrows, and many other birds to see a visual world hidden to us is explained in a study published in the journal eLife.

Birds can be divided into those that can see ultraviolet (UV) light and those that cannot. Those that can live in a sensory world apart, able to transmit and receive signals between each other in a way that is invisible to many other species. How they unlock this extra dimension to their sight is revealed in new findings from the Washington University School of Medicine in St. Louis.

The study reveals two essential adaptions that enable birds to expand their vision into the UV range: chemical changes in light-filtering pigments called carotenoids and the tuning of light-sensitive proteins called opsins.

Birds acquire carotenoids through their diets and process them in a variety of ways to shift their light absorption toward longer or shorter wavelengths. The researchers characterized the carotenoid pigments from birds with violet vision and from those with UV vision and used computational models to see how the pigments affect the number of colors they can see.

“There are two types of light-sensitive cells, called photoreceptors, in the eye: rods and cones. Cone photoreceptors are responsible for color vision. While humans have blue, green, and red-sensitive cones only, birds have a fourth cone type which is either violet or UV-sensitive, depending on the species,” says senior author Joseph Corbo, MD, PhD, Associate Professor of Pathology and Immunology.

“Our approach showed that blue-cone sensitivity is fine-tuned through a change in the chemical structure of carotenoid pigments within the photoreceptor, allowing both violet and UV-sighted birds to maximize how many colors they can see.”

The study also revealed that sensitivity of the violet/UV cone and the blue cone in birds must move in sync to allow for optimum vision. Among bird species, there is a strong relationship between the light sensitivity of opsins within the violet/UV cone and mechanisms within the blue cone, which coordinate to ensure even UV vision.

Taken together, these results suggest that both blue and violet cone cells have adapted during evolution to enhance color vision in birds.

“The majority of bird species rely on vision as their primary sense, and color discrimination plays a crucial role in their essential behaviors, such as choosing mates and foraging for food. This explains why birds have evolved one of the most richly endowed color vision systems among vertebrates,” says first author Matthew Toomey, a postdoctoral fellow at the Washington University School of Medicine.

“The precise coordination of sensitivity and filtering in the visual system may, for example, help female birds discriminate very fine differences in the elaborate coloration of their suitors and choose the fittest mates. This refinement of visual sensitivity could also facilitate the search for hidden seeds, fruits, and other food items in the environment.”

The team now plans to investigate the underlying molecular mechanisms that help modify the carotenoid pigments and light-sensitive protein tuning in a wide range of bird species, to gather further insights into the evolution of UV vision.

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

https://www.sciencedaily.com/releases/2016/07/160712093355.htm  Original web page at Science Daily

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Scavenger crows provide public service, research shows

Crows are performing a useful function and keeping our environment free from rotting carcasses, research carried out at the University of Exeter in Cornwall has discovered.

Using motion activated cameras in and around Falmouth and the University’s Penryn Campus, Cornwall, ecologists observed what happened to experimental rat carcasses which they placed under view.

The researchers found that most of the carcass removal ecosystem service — which has been well studied in more natural and exotic habitats, such as vultures in Africa — is being carried out by crows, with a little help from foxes, magpies, badgers and herring gulls.

Dr Richard Inger, a researcher attached to the Environmental and Sustainability Institute at Penryn Campus, said: “If you consider all the wildlife that lives in the habitats in our towns and countryside, it might seem odd that we rarely see dead animals, apart from roadkill. This is because other animals act as scavengers and eat them.

“It’s a bit grizzly but crows and other scavengers, which are often perceived as pests and generally fairly unloved species, are performing a very valuable service. Without these scavengers dead animals would be scattered around our environment rotting and causing a hygiene hazard.”

The researchers observed and filmed 17 vertebrate species eating rat carcasses which they placed at 12 study sites between May and September 2015. Seven species including the Carrion Crow, the Common Buzzard, European Magpie, Herring Gull, Fox and Badger were recorded eating the carcasses, with 98 per cent of the activity carried out by the Crows.

Dr Inger highlighted the importance of the scavenger role and added: “We know what can happen when natural scavengers are removed as this was the case with the vulture populations of India, which plummeted massively in the 1990s. Vultures were fatally poisoned by a veterinary drug given to cattle, meaning that carcasses were not eaten by vultures but instead by feral dogs, which grew in numbers and caused a huge increase in cases of rabies.”

Professor Kevin J.Gaston, Director of the Environment and Sustainability Institute, and co-author on the paper, said: “It is vital that we understand the different ecological functions and services that organisms provide, if we are to value and manage them most appropriately. Sometimes, as in this case, it will be individual species that are especially important. In others it will be the diversity of species. In both cases, the level of function and service depends on having sufficient individuals thriving in the landscape.”

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https://www.sciencedaily.com/releases/2016/07/160712110430.htm Original web page at Science Daily

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Scientists move closer to developing therapeutic window to the brain

Researchers at the University of California, Riverside are bringing their idea for a ‘Window to the Brain’ transparent skull implant closer to reality through the findings of two studies that are forthcoming in the journals Lasers in Surgery and Medicine and Nanomedicine: Nanotechnology, Biology and Medicine.

The implant under development, which literally provides a ‘window to the brain,’ will allow doctors to deliver minimally invasive, laser-based treatments to patients with life-threatening neurological disorders, such as brain cancers, traumatic brain injuries, neurodegenerative diseases and stroke. The recent studies highlight both the biocompatibility of the implant material and its ability to endure bacterial infections.

The Window to the Brain project is a multi-institution, interdisciplinary partnership led by Guillermo Aguilar, professor of mechanical engineering in UCR’s Bourns College of Engineering, and Santiago Camacho-López, from the Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE) in Mexico.

The project began when Aguilar and his team developed a transparent version of the material yttria-stabilized zirconia (YSZ) — the same ceramic product used in hip implants and dental crowns. By using this as a window-like implant, the team hopes doctors will be able to aim laser-based treatments into patients’ brains on demand and without having to perform repeated craniotomies, which are highly invasive procedures used to access the brain.

The internal toughness of YSZ, which is more impact resistant than glass-based materials developed by other researchers, also makes it the only transparent skull implant that could conceivably be used in humans. The two recent studies further support YSZ as a promising alternative for currently available cranial implants.

Published July 8 in Lasers in Surgery and Medicine, the most recent study demonstrates how the use of transparent YSZ may allow doctors to combat bacterial infections, which are a leading reason for cranial implant failure. In lab studies, the researchers treated E-Coli infections by aiming laser light through the implant without having to remove it and without damaging the surrounding tissues.

“This was an important finding because it showed that the combination of our transparent implant and laser-based therapies enables us to treat not only brain disorders, but also to tackle bacterial infections that are common after cranial implants. These infections are especially challenging to treat because many antibiotics do not penetrate the blood brain barrier,” said Devin Binder, M.D., a neurosurgeon and neuroscientist in UCR’s School of Medicine and a collaborator on the project.

Another recent study, published in the journal Nanomedicine: Nanotechnology, Biology and Medicine, explored the biocompatibility of YSZ in an animal model, where it integrated into the host tissue without causing an immune response or other adverse effects.

“The YSZ was actually found to be more biocompatible than currently available materials, such as titanium or thermo-plastic polymers, so this was another piece of good news in our development of transparent YSZ as the material of choice for cranial implants,” Aguilar said.

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

https://www.sciencedaily.com/releases/2016/07/160712133916.htm Original web page at Science Daily

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Ravens learn best from their affiliates

Transmission of information from one individual to another forms the basis of long-term traditions and culture, and is critical in adjusting to changing environmental conditions. Animals frequently observe each other to learn about food, predators and their social environment. The study fills an important gap in our understanding of how different types of social connections affect animals’ ability to learn from the behavior of others.

Social connections range from aggressive interactions to the affiliative behaviors that are critical in forming strong social bonds. Human social behavior is frequently analyzed as social networks to capture its extent and complexity. By adopting a similar approach for ravens and analyzing their social networks, Christine Schwab and Thomas Bugnyar found that not all social connections are equally effective at influencing observation and learning. In particular, networks based on affiliative behaviors (sitting close to and preening each other, sharing food and objects) played a major role in influencing how information was transmitted in the group. Some of the most frequent affiliative behaviors were between siblings, thus emphasizing the importance of family ties in learning.

Previous studies have shown that physical proximity between individuals can facilitate learning. However, until now, hardly anything was known about the role of different social connections in observation and learning. To mimic the presence of novel information, the researchers gave raven groups a task with which they were unfamiliar. The task included a food reward to motivate ravens to solve it. Ravens only observed others’ interactions with the task if they had strong social bonds to those group members. Presence of strong social bonds increases tolerance among individuals, allowing them to observe each other from a close distance. Birds with strong bonds to the group members who had already solved the task were able to observe them from a close distance, and as a result, gained this new information sooner than those who were not connected.

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

https://www.sciencedaily.com/releases/2016/07/160713101619.htm  Original web page at Science Daily