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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

Editing crabs and butterflies

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

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

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

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

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

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

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

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


US endangered-species recovery surges to record high

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

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

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

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

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

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

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


* Black bear links real objects to computer images

American black bears may be able to recognize things they know in real life, such as pieces of food or humans, when looking at a photograph of the same thing. This is one of the findings of a study led by Zoe Johnson-Ulrich and Jennifer Vonk of Oakland University in the US, which involved a black bear called Migwan and a computer screen. The findings are published in Springer’s journal Animal Cognition.

The study forms part of a broader research project into the welfare of bears in captivity. It aims to find out how the animals themselves rate the environment in which they are held, and the facilities, food and features provided to them. The goal is to assess this by presenting bears with photographs of objects. To do so, the research team first had to assess whether bears are in fact able to recognize 2-D images of objects and people familiar to them when these are presented to them on a touch screen.

With this in mind, the researchers tested the responses of an American black bear named Migwan. The bear was born in the wild, but was rescued at a very young age and rehabilitated due to injuries. She had previously received several months of training on an unrelated task using photographs of food items from her normal diet. In this study, Migwan was first presented with two sets of objects new to her. Her ability to recognize these later, when presented with photographs including the items she had learned, was then assessed. In a reverse task, she was also trained on the photographs of two different sets of objects and tested on the transfer to real objects.

It was found that Migwan was able to recognize, on a photograph, the visual features of objects or natural stimuli she already knew. It is an ability that bears share with hens, rhesus monkeys, pigeons, tortoises and horses.

“Bears can transfer learning with real objects to photographs of those objects presented on computer screens,” says Johnson-Ulrich.

This means that photographs of items (food, objects, people or other bears) that are familiar to bears can be used to further test their discrimination ability. Johnson-Ulrich therefore believes that the findings have important implications for the use of photographs in computerized studies involving bears, and in ultimately ensuring the welfare of captive bears.

“Because a lot of research with photographic stimuli uses familiar images, for example food or conspecifics, this is useful in suggesting that bears’ responses to these photographs may reflect behaviors towards real items,” Vonk notes.

Johnson-Ulrich and Vonk however caution that the ability of bears to recognize features of real objects within 2D-images does not necessarily mean they understand the representational nature of photographs. It is also still uncertain how well bears are able to recognize tangible objects which they first saw on a photograph before being introduced to the real thing. Further research using other bears is therefore needed to verify if the animals can transfer information from pictures to objects, too.  Science Daily  Original web page at Science Daily


Study shows a new role for B-complex vitamins in promoting stem cell proliferation

The study, published July 11 in Developmental Cell, shows for the first time that an adult stem cell population is controlled by an external factor arising from outside the animal–bacterial folate. In this case, that animal was a small roundworm model organism known as Caenorhabditis elegans. 

“Our study shows that germ stem cells in Caenorhabditis elegans are stimulated to divide by a specific folate that comes from their bacterial diet,” said the study’s co-senior author Edward Kipreos, a professor in UGA’s Franklin College of Arts and Sciences. “Folates are essential B-group vitamins. However, we show that the ability of a specific folate to stimulate germ cells is independent of its role as a vitamin, implying that it acts directly as a signaling molecule.”

Naturally occurring folates exist in many chemical forms; folates are found in food, as well as in metabolically active forms in the human body. Folic acid is the major synthetic form found in fortified foods and vitamin supplements.

“Since its discovery in 1945, folate has been the subject of many studies that resulted in more than 50,000 publications. The finding in this study is the first of its kind because it presents evidence that folate is involved in roles other than those that were known before,” said the study’s co-senior author Jacob Selhub, director of the Vitamin Metabolism Laboratory at Tufts University.

“Grains in the U.S. and a few other countries are currently supplemented with folates,” Kipreos said. “Folate supplementation has been an important contributor in reducing the number of neural tube birth defects. However, a vitamin-independent role of folates may provide a secondary pathway, the nature and biological impact of which for humans are yet to be determined.”

The study describes how a specific folate receptor, FOLR-1, in C. elegans is required for the stimulation of germ stem cell growth.

The research team observed a process in C. elegans in which the action of FOLR-1 is required to promote germ cell tumors that may be similar to the way folate receptors promote the progression of certain cancers in humans. With a few exceptions, folate receptors are not essential for the transport of folates into cells for use as vitamins, but may act to stimulate cell division.

As a part of the published findings, the researchers created the first system that allows C. elegans germ cells to be cultured in vitro.

“This technique provides an important new tool for the study of this major genetic model organism,” Kipreos said. Science Daily Original web page at Science Daily


* Infectious shellfish cancers may jump across species

Transmissible cancers have been found in shellfish, including cockles (Cerastoderma edule) collected in Galicia, Spain. Some clams, mussels and other bivalve molluscs carry infectious cancer cells that can leap between individuals — and that may even have jumped between species.

The discovery, reported on 22 June in Nature, means that transmissible tumours have now been found in six organisms. Two are well known in mammals: a facial tumour that threatens to wipe out Tasmanian devils (Sarcophilus harrisii) and a venereal cancer found in dogs all over the world.

“We thought these things happen now and then in nature, but that this was a fluke. Now, the finding that these seem to be fairly widespread in bivalves changes that outlook,” says Elizabeth Murchison, a molecular biologist at the University of Cambridge, UK, who studies the cancers prevalent in dogs and Tasmanian devils. The further finding that a cancer might have jumped between species is “shocking”, she says.

The latest work is led by virologist Stephen Goff of Columbia University in New York City, whose team last year found the first transmissible cancer among invertebrates — an edible soft-shell clam called Mya arenaria that lives in the tidal mudflats of the Atlantic, ranging from Canada to the southern United States.

Goff, who studies cancers caused by viruses, was looking for the source of a leukaemia common among clams, and discovered that tumours collected from animals in Long Island, Maine and Canada seemed to have the same genome sequence. “We were forced to come to the conclusion that somehow this clone had spread from animal to animal in the oceans up and down the coast,” he says.

After the discovery, Goff’s team reached out to marine biologists to see whether transmissible cancers were prevalent in other molluscs. In mussels (Mytilus trossulus) from British Columbia in Canada, and in cockles (Cerastoderma edule) and golden carpet-shell clams (Polititapes aureus) from the Galician coast in northwest Spain, the team found the same hallmarks of transmissible cancers: tumour cells from different individuals that shared the same genetic markers.

Two different lineages of cancers cells were found in infected cockles, which suggests that transmissible cancers emerged at least twice.

According to genetic analysis of the cancer DNA, the tumours in golden carpet-shell clams seemed to originate from another species of clam that lives in the same sea beds — the pullet shell clam (Venerupis corrugata).

“This is the first time that’s ever been seen,” says Goff. But peculiarly, Goff’s team found no signs of this cancer in the species in which it originated. It could be that the tumour wiped out vulnerable individuals in the original species, Goff suggests, and jumped to another species to find susceptible hosts.

Murchison says that the spreading of cancer between individuals requires the tumour to elude an immune attack, and she expects that the barrier is even higher between species. Clams have more-primitive immune systems than mammals, but Murchison still expects that transmissible tumours must overcome some level of resistance when moving within and between species.

Another mystery is how the cancer cells jump between individuals. Molluscs are voracious filter feeders, and the cancer cells floating around the ocean could make it to their bloodstream to seed new leukaemias. Tumour cells might be released when an animal dies, but Goff notes that the molluscs’ faeces are also full of blood cells. “It may just be that they’re pooping out these cells into the ocean,” he says.

Nature doi:10.1038/nature.2016.20138  Nature  Original web page at Nature


* How prions kill neurons: New culture system shows early toxicity to dendritic spines

Prion diseases are fatal and incurable neurodegenerative conditions of humans and animals. Yet, how prions kill nerve cells (or neurons) remains unclear. A study published on May 26, 2016 in PLOS Pathogens describes a system in which to study the early assault by prions on brain cells of the infected host.

Some of the earliest and potentially most critical changes in prion-infected brains occur at the connections (synapses) between neurons, and specifically at so-called dendritic spines. Dendritic spines are protrusions on the post-synaptic branches of a neuron that receive signals from other neurons. However, to date there has been no experimentally tractable model system in which the early degenerative changes caused by prions can be studied in cell culture.

David Harris, from Boston University School of Medicine, USA, and colleagues have argued that the availability of a neuronal culture system susceptible to the toxic effects of prions is crucial for understanding the underlying mechanisms and for potentially identifying drugs that block neurodegeneration. In this study, they report such a system, which reproduces acute prion neurotoxicity through degeneration of dendritic spines on cultured hippocampal neurons.

The researchers started by culturing neurons isolated from the hippocampus (a brain region involved in learning and memory) of mice. These neurons can be maintained in culture for three weeks, during which time they develop mature dendrites studded with spines, which contain chemical receptors that receive signals from neighboring neurons.

When the cultured neurons were exposed to brain extracts from mice with prion disease (which are known to contain large amounts of infectious prions), they showed rapid and dramatic changes: Within hours, there was severe retraction of spines, reducing their overall density and the size of the remaining ones. These changes in spines occurred without large-scale destruction of the neurons, suggesting that they represented very early events that would affect the functioning of the neurons prior to their actual death. When the researchers used three different kinds of purified prion preparations, they saw similar dendritic spine retraction in the cultures.

It is known that the development of prion disease involves an alteration of the normal cellular prion protein (designated PrPC), such that it assumes an abnormal shape (designated PrPSc). The resulting PrPSc is toxic to neurons, and it can propagate an infection by corrupting the shape of additional molecules of PrPC in a kind of chain-reaction.

To test whether the effects of PrPSc in their cell cultures depended on the neurons’ normal PrPC, the researchers generated cultures of hippocampal neurons from mice that were genetically engineered to lack PrPC. These cultures, they found, were resistant to toxic prion exposure, i.e., they did not show any of the changes in dendritic spines seen in neurons from normal mice containing PrPC.

Finally, the researchers tested neurons from transgenic mice expressing mutant PrPC molecules that were missing a specific region that is thought to interact with toxic prions. And indeed, the researchers found that these neurons–just like neurons without any PrPC–were immune to prion toxicity.

The researchers summarize their results as follows: “We describe a new system that is capable of reproducing acute prion neurotoxicity, based on PrPSc-induced degeneration of dendritic spines on cultured hippocampal neurons.” The system, they state, “provides new insights into the mechanisms responsible for prion neurotoxicity, and it provides a platform for testing potential therapeutic agents.”

Because “dendritic spine loss is a common theme in many neurodegenerative conditions, including Alzheimer’s, Huntington’s, and Parkinson’s diseases, and has been suggested to contribute to clinical symptoms in patients,” the researchers also suggest that their system allows for “direct comparisons between pathogenic mechanisms involved in prion diseases and other neurodegenerative disorders.” Science Daily Original web page at Science Daily


Seeking to rewind mammalian extinction: The effort to save the northern white rhino

In December 2015 an international group of scientists convened in Austria to discuss the imminent extinction of the northern white rhinoceros and the possibility of bringing the species back from brink of extinction. The discussions of this historic meeting appear in the international Journal Zoo Biology. The publication of this work is designed as part of the ongoing effort to raise awareness for the extinction crisis facing rhinos and many other species while also reaching out to the scientific community to share and gather information.

“The effort to save the northern white rhinoceros will need new technologies, new approaches and problem-solving in order to avert its imminent extinction”, said Joseph Saragusty, D.V.M., Ph.D., andrologist from the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, Germany. “The productive engagement of an international multidisciplinary team of experts will be essential to accomplish the ambitious goal of bringing back the northern white rhinoceros from its otherwise certain path to extinction.”

The discussion to save the northern white rhinoceros touches on genetics and cell biology, scientific ethics and the importance of long term strategic thinking and ongoing communications. A key element of these discussions was the need to maintain genetic banks of frozen tissue, spermatozoa and oocytes to use as materials in this fight against extinction.

“Cryobanked genetic resources from this unique form of rhinoceros have been saved in San Diego and in Europe”, said Oliver Ryder, Ph.D., geneticist for San Diego Zoo Global. “The genetic resources in the form of banked viable cell cultures, tissues and spermatozoa, together with the capability to establish induced pluripotent stem cells are the basis for hope that a viable population of northern white rhinoceros can be produced.”

With some genetic tissue from northern white rhinos available the group is looking at advanced reproductive technologies as the hope for the future of the species.

“It was a long way from the idea to the roadmap created in Vienna. I am glad that we found so many competent supporters in the scientific community who believe in the application of advanced cellular and reproductive technologies for the genetic rescue of the northern white rhinoceros. Now we have to demonstrate that this novel strategy can make a difference”, said Thomas Hildebrandt, Prof. Dr., head of the Reproduction Management department at IZW.

The last three northern white rhinoceroses reside in Ol Pejeta Conservancy in Kenya where they were transported from ZOO Dvůr Králové, Czech Republic. “Although we were able to breed the northern white rhinoceroses in our zoo, their health status does not allow them to breed naturally anymore. We are now optimistic that the cutting-edge research outlined in Vienna will give these very last specimens a chance to see an offspring of their own kind”, said Jan Stejskal, Director of International Projects of ZOO Dvůr Králové.

In addition to sharing information about reproductive technologies the group of experts discussed the ethics of spending resources to save one species. The paper voices the hope that the information gathered through this effort would be applied towards other species facing the threat of extinction in the future. Science Daily  Original web page at Science Daily


* Why vultures matter, and what we lose if they’re gone

Researchers highlight ecosystem, human impacts of vulture declines. Cartoon characters in parched deserts often wish them to disappear, since circling vultures are a stereotypical harbinger of death. But, joking aside, vultures in some parts of the world are in danger of disappearing. And according to a new report from University of Utah biologists, such a loss would have serious consequences for ecosystems and human populations alike.

The primary threat to vultures, according to the report published today in Biological Conservation, is the presence of toxins in the carrion they consume. On many continents, vultures are the unfortunate victims of poisoned carcasses — especially impactful because dozens — or even hundreds — of vultures can feast on a single carcass. Populations of most vulture species around the world are now either declining or on the brink of extinction.

Losses of vultures can allow other scavengers to flourish, according to biologists Evan Buechley and Çağan Şekercioğlu. Proliferation of such scavengers could bring bacteria and viruses from carcasses into human cities.

In 2004, Şekercioğlu published a study examining the respective extinction risks of all bird species throughout the world. He noted then that vultures represented the single most threatened group of birds. Now, more than a decade later, Buechley and Şekercioğlu have examined factors affecting the extinction risk of more than 100 bird species, including 22 species of vultures, which eat carrion exclusively, and other scavenging birds that have broader diets.

Their results suggest several inherent ecological traits that likely contribute to vultures’ extinction risk, including their large body masses, slow reproductive rates and highly specialized diets. The greatest external threat to vultures, however, is poisoning.

Poisoning is the greatest extinction risk facing vultures, and impacts 88 percent of threatened vulture species. The poisons come in many forms.

In North America, the California condor, a vulture, experienced sharp declines until only 22 individuals remained by 1982. The leading cause of decline? Toxic lead bullet fragments in the gut piles left behind by hunters after animals had been field-dressed. Intensive conservation efforts helped the species to rebound. The condors now number well over 400, and range over large areas of California, Arizona, Utah and Baja California, Mexico.

In the mid-1990s India experienced a precipitous vulture decline, with more than 95 percent of vultures disappearing by the early 2000s. “That was a massive collapse that led a lot of people to really focus more attention on vultures,” Buechley says. The cause was eventually traced to diclofenac, a veterinary anti-inflammatory drug that relieved pain in cattle, but proved highly toxic to vultures. Hundreds of vultures would flock to each cattle carcass. And if the cow had recently been treated with diclofenac, hundreds of vultures would die. Because of this highly gregarious feeding behavior, less than one percent of cattle carcasses contaminated with diclofenac could account for the steep vulture decline. Fortunately, international cooperation led to a total ban on veterinary diclofenac use. Buechley says the numbers of vultures have stabilized, and are now showing signs of slowly increasing.

Now, the center of the vulture crisis is in sub-Saharan Africa. “In Africa, it’s a lot more challenging,” Buechley says. “It’s a darker story.” Potent newly affordable poisons are used to control predatory pests, such as lions or jackals. The poisons are so toxic that they can cascade through ecosystems: birds, mammals and insects are often found littering the area around these poisoned carcasses. But, as the predominant scavenger, vultures take the brunt of the poisoning and face the largest number of casualties. For example, an elephant carcass poisoned in Namibia in 2007 killed as many as 600 vultures. In other cases, vultures are the victims of poachers who poison carcasses so that vultures do not give away the location of illegally taken animals. “Vultures are taking the hit, indirectly, for a lot of this human-wildlife conflict, as well as the illegal trade in animal parts,” Buechley says. This crisis, unfortunately, is ongoing.

In vultures’ absence, other scavenger populations increase to take advantage of all of the uneaten carrion. By some estimates, in Central America, South America and Africa, vultures eat more meat than all predators combined. Without vultures, animals that eat carrion as a part of their diet (called facultative scavengers, as opposed to vultures, which eat only carrion) proliferate to take advantage of the available nutrients in a dead carcass. “There are a ton of nutrients in carrion that are going to be taken advantage of by something,” Buechley says.

Crows, rats, dogs — any of these species can suddenly become abundant and dominant, to the point of crowding out the remaining vultures. Hundreds of vultures on a carcass can easily frighten away packs of dogs, Şekercioğlu says. But when only a few vultures are left, the dogs can rule.

Such changes in populations of certain animal groups can upset the balance of food webs. “All these facultative scavengers are also predators, and so they also go out and eat other organisms too,” Buechley says. “You have this cascading effect.”

The impact of vultures’ declines are not limited to the realm of ecology, however. Vultures are highly efficient consumers of carrion, sometimes locating and consuming carcasses within an hour, before other forms of decay can set in. And vultures’ stomachs are highly acidic, killing nearly all bacteria or viruses that may be present in carrion. Combined with the fact that vultures rarely come in contact with humans, vultures serve as a barrier to prevent diseases from proliferating in dead animals and spreading to humans. Other facultative scavengers are not so adapted, and could pass along those diseases into human populations, as many are already fixtures in cities.

For example, following the decline of vultures, India experienced a strong uptick in feral dogs — by an estimated seven million. The increase in dogs, potentially feeding on disease-ridden carcasses, is thought to have at least partially caused the rabies outbreak that was estimated to have killed 48,000 people from 1992-2006 in India — deaths that may have been avoided if not for the disappearance of vultures.

Members of the Parsi sect of Zoroastrianism experienced a different impact. For thousands of years, the Parsi people have placed their dead on exposed mountaintops or tall towers for vultures to consume. The practice is called “sky burial.”

But with few vultures and unable to properly handle their dead, the Parsis experienced a crisis within the faith. Some constructed captive vulture aviaries. Others talked about desiccating bodies using focused solar mirrors. The Parsis’ plight exemplifies the vultures’ role in south Asian society — and the various impacts if the vultures aren’t there.

Although the vulture crisis in Africa is ongoing, Buechley and Şekercioğlu can predict what the outcome will be, based on previous experiences in India. Crows, gulls, rats and dogs will boom. And the rabies outbreak in India may just be a prologue, because several sub-Saharan Africa countries already have the highest per-capita rabies infection rates in the world. Rabies is only one of the many potential diseases that vultures had helped regulate.

Buechley notes that the poisoning that is killing vultures is also affecting many other organisms throughout ecosystems. But vultures are the most sensitive canaries in ecological coal mines. The story of the California condor shows that recovery is possible, but at a high cost that countries in the developing world may not be able to pay.

“It’s good news and bad news,” Şekercioğlu says. “It shows that we can bring back these scavengers. But the bad news is that once we get to these numbers, it costs tens of millions of dollars and decades to bring them back. You don’t want to go there. And once you go there, we can afford to save only a few species.”

So, Buechley argues, “the better solution is to invest in vulture conservation here and now, in order to stem incalculable damage from trophic cascades and increased human disease burden in the developing world.”

The study was funded by a National Science Foundation Graduate Research Fellowship and by the University of Utah’s Global Change and Sustainability Center.  Science Daily  Original web page at Science Daily


Study finds vast diversity among viruses that infect bacteria

Viruses that infect bacteria are among the most abundant life forms on Earth. Our oceans and soils, and potentially even our own bodies, would be overrun with bacteria were it not for bacteria-eating viruses–called bacteriophages–that keep the microbial balance in check. Now, a new study suggests that bacteriophages made of RNA — a close chemical cousin of DNA — likely play a much larger role in shaping the bacterial makeup of worldwide habitats than previously recognized. Viruses that infect bacteria are among the most abundant life forms on Earth. Our oceans and soils, and potentially even our own bodies, would be overrun with bacteria were it not for bacteria-eating viruses–called bacteriophages–that keep the microbial balance in check.

Now, a new study at Washington University School of Medicine in St. Louis suggests that bacteriophages made of RNA — a close chemical cousin of DNA — likely play a much larger role in shaping the bacterial makeup of worldwide habitats than previously recognized.

The research, publishing on March 24 in the Open Access journal PLOS Biology, identifies 122 new types of RNA bacteriophages in diverse ecological niches, providing an opportunity to define their contributions to ecology, and potentially to fight bacterial infections, particularly those resistant to antibiotics.

“Lots of DNA bacteriophages have been identified, but there’s an incredible lack of understanding about RNA bacteriophages,” explained senior author David Wang, PhD, associate professor of molecular microbiology. “They have been largely ignored — relatively few were known to exist, and for the most part scientists haven’t bothered to look for them. This study puts RNA bacteriophages on the map and opens many new avenues of exploration.”

Wang estimates that of the more than 1,500 bacteriophages that have been identified, 99 percent of them have DNA genomes. The advent of large-scale genome sequencing has helped scientists identify DNA bacteriophages in the human gut, skin and blood as well as in the environment, but few researchers have looked for RNA bacteriophages in those samples.

First author Siddharth Krishnamurthy and the team, including Dan Barouch, MD, PhD, Beth Israel Deaconess Medical Center and Harvard Medical School, identified RNA bacteriophages by analyzing data from oceans, sewage, soils, crabs, sponges and barnacles, as well as insects, mice and rhesus macaques.

RNA bacteriophages have been shown to infect gram-negative bacteria, which have become increasingly resistant to antibiotics and are the source of many infections in health care settings. But the researchers also showed for the first time that these bacteriophages may also infect gram-positive bacteria, responsible for strep and staph infections as well as MRSA.

“What we know about RNA bacteriophages in any environment is limited,” Wang said. “But you can think of bacteriophages and bacteria as having a predator-prey relationship. We need to understand the dynamics of that relationship. Eventually, we’d like to manipulate that dynamic to use phages to selectively kill particular bacteria.”  Science Daily  Original web page at Science Daily


Redefining part of 300 year-old classification system for grouping members of the animal kingdom

An international team of biologists has identified the molecular signature of the animal kingdom, providing genetic evidence for an animal classification that has been used for nearly 300 years. Their research, published this week in the journal Nature, offers a historic dataset for the field, serving developmental biologists, evolutionary biologists, and computational biologists alike.

The study was led by Professor Itai Yanai of the Technion-Israel Institute of Technology Department of Biology, in cooperation with research teams in Australia, Germany, the US, and Israel. The research team investigated an extremely diverse set of animal species, applying an extremely powerful technique called CEL-Seq, developed in 2012 by Dr. Tamar Hashimshony in the Yanai lab. CEL-Seq allows for the monitoring of the activity of all genes in individual cells, and the team used it to analyze gene regulation in 70 embryos in each of ten species.

The researchers found a striking pattern of universality across the species. Between phases of similar genes turned ‘on’ at the beginning and the end of development, a mid-developmental transition was discovered. This newly discovered gene regulatory pattern explains how the differences among animals develop and evolve, which allows biology to now have molecular means to define the specific properties of groups of species.

Their work further defines a category of animal life under-defined since 1735 when Swedish botanist Carl Linnaeus, recognized as the father of the biological classification of organisms, proposed a two-name classification system for the world’s plants and also animals classified animals into “families” based on similarities and differences in body “plans.” The work sheds new light on how, at the molecular and genetic levels, animals of different body designs (whether they have a true spinal column (mammals) or just a nerve cord (chordates) have evolved to be different and why.

Nearly eight million different species of animals are thought to inhabit the planet, covering a striking exuberance of diversity. For example, animals span five orders of magnitude of adult body sizes. Prof. Yanai’s team began this research by asking what is common to all animals. To tackle this question, they chose ten of the most different animals one could choose: a fish, a worm, a fly, a water bear, a sponge, and five others, each of a different phylum (a term coined by German naturalist Ernst Haeckel in the 19th century to describe a group of animals with the same body plan). About 35 phyla are typically recognized, however it remains controversial with contention over whether this is a meaningful classification and, if so, what attributes are the same, or different across all animals.

“We selected species representing ten different animal phyla,” said Prof. Yanai. “For each phyla we determined the gene expression profile of all genes from the development of the fertilized egg to the free-living larvae. We found a surprising pattern of gene expression conservation in all species occurring at a pivotal, transitional period in development.”

By studying the molecular programs of development in ten very different animals, the researchers found that all of the animals they studied express two distinct “modules” of genetic expression. (A module is a set of genes — similar across the organisms — that are turned ‘on.’) During the transition between the modules, mechanisms of cell signaling and regulation occur.

With this new knowledge, the researchers proposed a definition for phylum as “a set of species sharing the same signals and transcription factor networks during the mid-developmental transition.” In other words, they clarified the definition by suggesting that those organisms sharing a phylum, formerly by virtue of body design alone, also share a unique and similar genetic and molecular transition that other species do not.

To demonstrate their proposal, the researchers developed an “hourglass model” that captures gene expression differences between species. The inverse hourglass model shows the origin of phyla compared with the hourglass model that demonstrates “within phylum evolution.”

Embryonic development is called the “phylotypic” stage. This is when the embryo begins to assume recognizable features typical of vertebrates. The phylotypic stage represents a general layout on which specialized features — such as the turtle’s shell, the pig’s snout, or your large brain — can be mounted later in development.

The researchers proposed that during the phyletic transition period, properties specific to each phylum are genetically encoded. Their emerging dataset, they said, will be useful in studying the hallmarks of animal body plan formation from the embryonic stage.

As with many scientific discoveries, the researchers suggest that their work “raises more questions than it answers.” For example, “what molecular pathways underlie phyletic transition in each phylum? Why are the phyletic-transition mechanisms so relatively susceptible to change? Is the coupling of the conserved modules universal to all multicellular life?”

“The transition we identified may be a hallmark of development only in animals,” the researchers concluded. “Or, future work may show that this is a general characteristic of development in all multicellular life.”  Science Daily  Original web page at Science Daily


Bees ‘dumb down’ after ingesting tiny doses of the pesticide chlorpyrifos

Honeybees suffer severe learning and memory deficits after ingesting very small doses of the pesticide chlorpyrifos, potentially threatening their success and survival, new research from New Zealand’s University of Otago suggests.

In their study, researchers from the Departments of Zoology and Chemistry collected bees from 51 hives across 17 locations in the province of Otago in Southern New Zealand and measured their chlorpyrifos levels. They detected low levels of pesticide in bees at three of the 17 sites and in six of the 51 hives they examined.

Detecting chlorpyrifos was not a surprise. In 2013, Associate Professor Kim Hageman and her team from Otago’s Department of Chemistry showed that chlorpyrifos was detectable in air, water, and plant samples even in non-sprayed areas of the country, because this pesticide has a high ability to volatilise and travel great distances.

In the laboratory they then fed other bees with similar amounts of the pesticide, which is used around the world to protect food crops against insects and mites, and put them through learning performance tests.

Study lead author Dr Elodie Urlacher says they found that chlorpyrifos-fed bees had worse odour-learning abilities and also recalled odours more poorly later, even though the dose they ingested is considered to be “safe.”

“For example, the dosed bees were less likely to respond specifically to an odour that was previously rewarded. As honeybees rely on such memory mechanisms to target flowers, chlorpyrifos exposure may be stunting their effectiveness as nectar foragers and pollinators,” Dr Urlacher says.

The study identified the threshold dose for sub-lethal effects of chlorpyrifos on odour-learning and recall as 50 picograms of chlorpyrifos ingested per bee, she says.

“This amount is thousands of times lower than the lethal dose of pure chlorpyrifos, which is around 100 billionths of a gram. Also, it is in the low range of the levels we measured in bees in the field.”

The current study is the first to establish the threshold at which a pesticide has an effect on memory specificity in bees while also measuring doses in bee populations in the field, she says.

“Our findings raise some challenging questions about regulating this pesticide’s use. It’s now clear that it is not just the lethal effects on bees that need to be taken into account, but also the serious sub-lethal ones at minute doses,” Dr Urlacher says.  Science Daily  Original web page at Science Daily


New role for motor neurons discovered

A new study presented in the journal Nature could change the view of the role of motor neurons. Motor neurons, which extend from the spinal cord to muscles and other organs, have always been considered passive recipients of signals from interneuronal circuits. Now, however, researchers from Sweden´s Karolinska Institutet have demonstrated a new, direct signalling pathway through which motor neurons influence the locomotor circuits that generate rhythmic movements.

Locomotion is essential to all animals and is based on a carefully balanced interaction between the muscles and the brain. Nerve cells are typically able to both receive and generate electrical impulses, which are then relayed to other nerve cells. The nerve cells that make contact with the muscles are called motor neurons, and for almost a century they have been regarded as passive receivers of the detailed motor programs generated and elaborated by networks of nerve cells in the spinal cord. According to this model, motor neurons relay the signals faithfully and unidirectionally to the muscles.

“We have now uncovered an unforeseen role of motor neurons in the elaboration of the final program for motor behaviour,” says principal investigator Abdel El Manira at Karolinska Institutet’s Department of Neuroscience. “Our unexpected findings demonstrate that motor neurons control locomotor circuit function retrogradely via gap junctions, so that motor neurons will directly influence transmitter release and the recruitment of upstream excitatory interneurons.”

The study was conducted using zebrafish, a common animal model in neurobiological research because they are transparent and relatively easy to manipulate genetically. Through a combination of different methods, the team has shown that there is a direct link via electrical synapses or gap junctions, between motor neurons and the excitatory interneurons that generate rhythmic swimming motions in the fish. These synapses directly connect two neurons, and enable the transfer of electrical signals between these neurons. With the aid of optogenetics, the researchers selectively silenced the activity of motor neurons and showed that they have a strong influence on the locomotor circuit function via gap junctions.

“This study represents a paradigm shift that will lead to a major revision of the long held view of the role of motor neurons,” says Professor El Manira. “Motor neurons can no longer be considered as merely passive recipients of motor commands — they are an integral component of the circuits generating motor behaviour.”  Science Daily  Original web page at Science Daily


Sexuality, not extra chromosomes, benefits animal, biologists find

Most animals, including humans, have two copies of their genome — the full set of instructions needed to make every cell, tissue, and organ in the body.

But some animals carry more than two complete sets of the genome, referred to as polyploidy. Biologists have long wondered whether these extra chromosomes help or hinder those species.

In a study involving multiple generations of a freshwater snail in New Zealand, researchers at the University of Iowa found that polyploidy appears to be neither an asset nor a drawback for females bearing offspring without the help of a male. Instead, it’s the snails’ sexuality that creates an advantage: Asexual females, the study found, grew twice as fast during the late juvenile phase and reached reproductive maturity 30 percent faster than female snails that mated with males.

That in itself raises fundamental biological questions: If asexual females grow faster and bear children much more quickly than sexual females, what’s the purpose of sex, and why is it the dominant method of reproduction in the animal world?

“When we did the study, we thought polyploidy would be bad for asexuals, but we didn’t find any evidence of that,” says Maurine Neiman, associate professor of biology at the UI and corresponding author on the paper, published in the journal Ecology and Evolution. “This is making the role of sex even harder to explain.”

The mud snails, Potamopyrgus antipodarum, live in lakes and streams all over New Zealand. They were also discovered in Idaho in 1987 and have since spread to the Great Lakes and farther east to Chesapeake Bay, according to the U.S. Department of Agriculture, which classifies the animals as an invasive species.

Sexual and asexual females are known to live in the same lakes in New Zealand, although they also exist separately in other lakes. Males will mate with either, but their genes are not passed on in encounters with asexual females. Those factors, and the snails’ abundance, made them a good species in which to test the effects of polyploidy.

The UI team compared sexually reproductive female snails with only two copies of their genome to asexual females carrying three and four copies. Together, they produced enough generations to occupy 1,500 cups — one cup per snail.

“When we began, we thought the project would take six to nine months,” says Katelyn Larkin, who earned her bachelor’s and master’s degrees in biology at the UI and has worked in Neiman’s lab since she was a sophomore. “Instead, it took more than three years. We learned that these snails grow at a snail’s pace.”

The asexual females, regardless of the number of genomic copies they possessed, grew faster and reached reproductive maturity quicker than the sexual females, the researchers discovered. In human terms, it’d be as if the asexual females could produce children at 13 years of age, whereas the sexual females wouldn’t reach reproductive age until age 18. Couple that with the fact that asexual females produce only female offspring, and you wonder why sexual female snails still exist.

“It’s not only that (the asexuals) are not making males. The asexual daughters are growing up faster too,” Neiman notes.

Before her study, Neiman thought the asexual females would bear extra costs for each additional genome because they would be chock full of metabolically expensive ingredients like RNA and proteins. Such is the case with plants, like wheat. But there was no difference in growth rate, shell length, or time to reproductive maturity between asexual females with three genomic copies and those with four, ruling out that theory.

Instead, the surprise lay in the fact the asexual females didn’t seem to pay any price whatsoever for having those extra genomes. In fact, there was no discernible disadvantage at all.

So, why do sexual female snails exist, and how do they survive when they’re co-existing and competing with asexual females?

The answer may lie in part to a parasitic worm that preys upon the snails. The asexual females are more vulnerable because their offspring’s genomes are exact replicas of their own, making them easier to target and wipe out. The sexual females, because they mate, inherit a separate, distinct genomic set that diversifies the gene pool and thus makes them better able to withstand parasitic attacks.

Still, sexual females have been found alongside asexuals in lakes without the parasitic worms, which muddies the whole idea that genetic diversity is the sole reason why sexual snails persist. Neiman seems to like it that way.

“You could argue that our genome is the most important thing we have, yet we don’t know why humans have two copies when a lot of organisms do fine with one, or three, or more,” she says. “This research speaks to that question.”  Science Daily  Original web page at Science Daily


The power of touch: Sex-changing snails switch sooner when together

Many animals change sex at some point in their lives, often after reaching a certain size. Snails called slipper limpets begin life as males, and become female as they grow. A new Smithsonian study shows that when two males are kept together and can touch one another, the larger one changes to female sooner, and the smaller one later. Contact, rather than chemicals released into the water, is necessary for the effect.

“I was blown away by this result,” said co-author Rachel Collin, staff scientist at the Smithsonian Tropical Research Institute (STRI). “I fully expected that the snails would use waterborne cues to see their world.”

The article, co-authored by former STRI intern Allan Carrillo-Baltodano, now a pre-doctoral student at Clark University, was published in The Biological Bulletin.

Tropical slipper limpets, Crepidula cf. marginalis, live under rocks in intertidal areas along the shore, obtaining food by filtering plankton and other particles from the water. Their thin, flattened shells have a built-in shelf. When flipped over, they resemble men’s house slippers. Often found in clusters, they occur alone or as pairs or trios consisting of a large female with one or two smaller males riding piggyback on her shell.

A male limpet has a comparatively enormous penis–sometimes as long as his entire body–which rather incongruously emerges from the right side of his head. This elongated apparatus is necessary to extend around and under the female’s shell in order to reach her genital opening. When a snail changes sex, the penis gradually shrinks and then disappears at the same time that female organs develop. It is thought that this kind of sex change is advantageous because large animals are able to produce larger numbers of eggs as females, while small males can still produce plenty of sperm (which require much less energy to make than eggs).

In experiments, two males differing slightly in size were kept in small cups containing seawater. In some cups they were allowed to be in contact with one another, while in others a mesh barrier kept them apart while allowing water to pass through. The larger snails in the pairs in direct contact with their partners grew more quickly and changed into females sooner than those kept apart. Conversely, the smaller member of a pair that was in contact delayed sex change compared to ones separated by mesh.

In sex-changing coral-reef fishes, visual, behavioral and chemical cues may all influence switching by individuals that associate with each other. Slipper limpets, which are sedentary and have poor vision, were initially expected to depend more on waterborne chemical cues, already known to affect other aspects of their behavior. Surprisingly, slipper limpets turned out to be like fishes in showing a greater response to behavioral interactions or perhaps contact-based chemical cues, than waterborne signals. Slipper snails don’t move around much, so you don’t really think of them having complex reactions to each other,” Collin said. “But this study shows that there is more going on there than we thought.”  Science Daily  Original web page at Science Daily


DNA repair enzyme identified as a potential brain cancer drug target

Rapidly dividing cells rely on an enzyme called Dicer to help them repair the DNA damage that occurs as they make mistakes in copying their genetic material over and over for new cells. UNC Lineberger Comprehensive Cancer Center researchers have built on the discovery of Dicer’s role in fixing DNA damage to uncover a new potential strategy to kill rapidly dividing, cancerous cells in the brain.

In the journal Cell Reports, researchers report that when they removed Dicer from preclinical models of medulloblastoma, a common type of brain cancer in children, they found high levels of DNA damage in the cancer cells, leading to the cells’ death. The tumor cells were smaller, and also more sensitive to chemotherapy.

“This is the first time that the specific function of Dicer for DNA damage has been looked at in the context of the developing brain or even in brain tumors, despite that the fact that the protein has been extensively studied,” said Mohanish Deshmukh, PhD, a UNC Lineberger member and professor in the UNC School of Medicine Department of Cell Biology and Physiology and also the Neuroscience Center. “We have found that targeting Dicer could be an effective therapy to either prevent cancer development or to actually sensitize tumors to chemotherapy.”

Scientists have understood for more than a decade that Dicer plays an important role in the cell for processing microRNAs, which regulate the expression of genes in cells. But Deshmukh said it was in 2012 that scientists discovered a direct role of Dicer in repairing DNA damage. And that function, he said, is of importance for cancer research. That’s because rapidly dividing cells — such as cancer cells — incur DNA damage as they divide. And chemotherapy and radiation treatments often work by damaging the cells’ DNA, leading to cell death. Removing a key enzyme that repairs DNA in cancerous cells could help prevent DNA repair.

“We found that cancerous cells upregulate Dicer,” said Vijay Swahari, MBBS, MS, a postdoctoral fellow at the UNC Neuroscience Center and the first author of this study. “We think tumors upregulate Dicer because its function is to repair DNA.”

In their study, Deshmukh and his team studied the effect of deleting Dicer in several types of rapidly dividing cells, including of preclinical brain cancer models. They deleted Dicer in the normal, rapidly dividing developing brain cells in the cerebellum of animal models, finding spontaneous DNA damage in the brain cells, leading to severe degeneration of the cerebellum. They also tested whether Dicer had a similar effect on rapidly dividing cells outside of the brain. Upon deleting Dicer from embryonic stem cells, the authors found a similar effect.

To test whether they could exploit the role of Dicer to kill cancerous cells, Swahari and his collaborators also deleted Dicer in medulloblastoma models, and found that these cells also had high DNA damage levels and degeneration. The tumor load was lower, and the cells were more sensitive to chemotherapy.

“We found that when you delete Dicer, these tumors are more sensitive to DNA damage,” Swahari said. “We also took the next step by injecting chemotherapy into models where Dicer was deleted, finding that not only are the tumors smaller, but the tumors are also more sensitive to chemotherapy.”

Based on their findings, the researchers believe that Dicer could be investigated as a potential drug target for medulloblastoma and other types of brain cancer. “We are excited about these results because of the implication that Dicer inhibitors could be developed as a potential therapy for treating rapidly-dividing tumors like medulloblastoma,” Deshmukh said. Science Daily  Original web page at Science Daily


China’s bold push into genetically customized animals

New kinds of dogs, goats, monkeys and pigs are being made quickly, though scientists voice worries about ethics.

China’s western Shaanxi Province is known for rugged windswept terrain and its coal and wool, but not necessarily its science. Yet at the Shaanxi Provincial Engineering and Technology Research Center for Shaanbei Cashmere Goats, scientists have just created a new kind of goat, with bigger muscles and longer hair than normal. The goats were made not by breeding but by directly manipulating animal DNA—a sign of how rapidly China has embraced a global gene-changing revolution.

Geneticist Lei Qu wants to increase goatherd incomes by boosting how much meat and wool each animal produces. For years research projects at his lab in Yulin, a former garrison town along the Great Wall, stumbled along, Qu’s colleagues say. “The results were not so obvious, although we had worked so many years,” his research assistant, Haijing Zhu, wrote in an e-mail.

That changed when the researchers adopted the new gene-customizing technology called CRISPR–Cas9, a technique developed in the U.S. about three years ago. CRISPR uses enzymes to precisely locate and snip out segments of DNA, much like a word-processor finding and deleting a given phrase—a process known as “gene-editing.” Although it is not the first tool scientists have used to tweak DNA, it is by far more precise and cheaper than past technologies. The apparent ease of this powerful method now raises both tantalizing possibilities and pressing ethical questions.

Once the goat team began to deploy CRISPR, their progress was rapid. In September Qu and 25 other collaborating scientists in China published the details of their research in Nature’s Scientific Reports. In early-stage goat embryos they had successfully deleted two genes that suppressed both hair and muscle growth. The result was 10 goat kids exhibiting both larger muscles and longer fur—designer livestock—that, so far, show no other abnormalities. “We believed gene-modified livestock will be commercialized after we demonstrate that it is safe,” predicts Qu, who envisions this work as a simple way to boost the sale of goat meat and cashmere sweaters from Shaanxi.

The research is just one of a recent flurry of papers by Chinese scientists that describe CRISPR-modified goats, sheep, pigs, monkeys and dogs, among other mammals. In October, for instance, researchers from the country discussed their work to create unusually muscled beagles in the Journal of Molecular Cell Biology. Such research has been supported via grants from the National Natural Science Foundation of China, Ministry of Agriculture, Ministry of Science and Technology as well as provincial governments.

Dozens, if not hundreds, of Chinese institutions in both research hubs like Beijing and far-flung provincial outposts have enthusiastically deployed CRISPR. “It’s a priority area for the Chinese Academy of Sciences,” says Minhua Hu, a geneticist at the Guangzhou General Pharmaceutical Research Institute and one of the beagle researchers. A colleague, Liangxue Lai of the Guangzhou Institutes of Biomedicine and Health, adds that “China’s government has allocated a lot of financial support in genetically modified animals in both the agriculture field and the biomedicine field.

This is raising a number of ethical worries about making new life forms. Unlike past gene therapies, changes made using CRISPR to zygotes or embryos can become “permanent”—that is, they are made to the DNA that will be passed onto future generations. For each zygote or embryo that scientists successfully transform, typically dozens, if not hundreds, of others do not work. But the technology is rapidly improving. “What is different about CRISPR is that the technology is vastly more efficient and so the possibility of it being practiced widely is that much more real,” says George Daley, a stem-cell biologist at Harvard Medical School. Past efforts to manipulate the genetic code of life have been slower, more cumbersome and more unpredictable. “The ethical concerns are now upon us because the technology is real,” he adds.

This applies to CRISPR experiments to “edit” the DNA of all plants and animals—as well as in the future, perhaps, humans, if scientists like Qu further hone the technique. Unlike past gene therapies, changes made using CRISPR to zygotes or embryos become “permanent”; that is, they enter the germ line and will be passed onto future generations. “As with any intervention, there’s always a trade-off in issues between human welfare and animal welfare and gauging the environmental impacts,” says Daley, referring the quest for “improved” livestock, a current focus of China’s gene-editing research. And on the even more complicated topic of potential CRISPR experiments involving human DNA, he wonders, “Can we draw a clear line between what might be allowable for medical research or applications and what we must strictly prohibit?” Finding an answer that the whole world can agree on is geneticists’ and ethicists’ next big task.

China is not the birthplace of CRISPR (currently there’s an ongoing patent battle between scientists at Massachusetts Institute of Technology and the University of California, Berkeley, for that claim). China, however, has been an extremely rapid adopter, aided by a fast-growing research budget and the sheer scale of China’s science establishment, which is largely state-affiliated. Between 2008 and 2012 China’s research and development spending fully doubled, according to the Organization for Economic Cooperation and Development’s Science, Technology and Industry Outlook 2014. (Now second in the world, China’s research budget may surpass the U.S. by 2019, the report projects.) Yet despite its strengths, “China is a relative newcomer to international scientific community and doesn’t have the same institutional-review traditions in place,” says Daley, adding that scientists in the U.S. and Europe are now keenly watching how Chinese scientists will deploy such powerful tools.

The level and sophistication of work in China using CRISPR is already “about the same” as in Europe and the U.S., where the technology was codeveloped, says George Church, a professor of genetics at Harvard Medical School. An analysis by Thomson Innovation, a division of London-based Thomson Reuters, found that more than 50 Chinese research institutions have filed gene-editing patents.

Some experiments in China, as in the U.S. and U.K., are aimed at potential biomedical applications. For instance, scientists at Yunnan Key Laboratory of Primate Biomedical Research have used CRISPR to augment the neurological development of monkeys in an effort to test the feasibility of creating primate disease models for better understanding human conditions like autism, schizophrenia and Alzheimer’s disease. Many experiments, like the one on cashmere goats and a similar experiment that deleted the gene-inhibiting muscle growth in sheep, are aimed at transforming animal husbandry—more muscled livestock could help satiate China’s fast-growing middle-class appetite for meat.

But what first brought widespread global attention, or infamy, to China’s ambitions was a recent published experiment on human embryos, the first in the world. In April China became a lightning rod for criticism and anxiety when a team of Chinese scientists published a paper online in the journal Protein & Cell detailing attempts to use CRISPR to modify nonviable human embryos, obtained with consent from a fertility clinic. Their aim had been to delete a gene linked to a blood disorder called beta-thalassemia without creating other mutations, but the experiment failed on 85 attempted embryos.

The research was legal within China, which bans experiments on human embryos more than 14 days old, and was supported in part by government grants. (Such research is not banned in most U.S. states but is probably ineligible for federal funding.)

Many international observers reacted with sharp rebuke, attributing nefarious intentions to the Chinese scientists. “No researcher has the moral warrant to flout the globally widespread policy agreement against altering the human germ line,” Marcy Darnovsky, executive director of the California-based Center for Genetics and Society, a nonprofit advocacy group, wrote in a statement reacting to the report. Respected news organizations ran ominous headlines: “Chinese Scientists Edit Genes of Human Embryos, Raising Concerns” appeared in The New York Times and “Editing Humanity” in The Economist.

Because China is new to global scientific stage, its institutional standards for approving research projects are not fully transparent to the world, Daley says. Moreover, the researchers involved were not the heads of well-known global institutions, like the Broad Institute of M.I.T. and Harvard University or the Francis Crick Institute in London, whom global research community knows well and understands their motivations. Daley adds that now China’s scientific establishment is “responsibly stepping up to discussion.”

The controversy may have been a bit overblown. The Chinese scientists say they were not trying to edit human germ line or develop clinical uses. Junjiu Huang, co-author of the paper and a geneticist at Sun Yat-sen University in Guangzhou, wrote in an e-mail to Scientific American that “It is forbidden to do germ-line editing in clinic.” Yet he defended the potential to learn about human diseases through future CRISPR experiments. “Using CRISPR–Cas9 technology, scientists could learn more about what are the real functions of key genes in the human preimplantation period. … We can also figure out the mechanism of gene repairing, which could lead to a new understanding of how genetic diseases occur during early development.

Later appraisals credit the carefulness of their method, including the choice to deliberately use nonviable embryos that could never become babies, Harvard’s Church says. But the flap itself pointed to both the seriousness of the stakes and concern over whether Chinese scientists will accept same ethical principles as Westerners.

In early December scientists from the U.S., U.K. and China will meet at the U.S. National Academy of Sciences in Washington, D.C., in an effort to codify international consensus on editing DNA, focusing on the human germ line. Church, who has participated in preliminary meetings with Chinese and U.S. counterparts, says that the important takeaway from these debates may not be that China is an ethical outlier but rather that public discussion and clarification of guidelines, especially regarding the human germ line, is dearly needed. “I think China is behaving just as responsibly as others. I would not characterize China as being problematic in any way. Chinese scientists worked well within the legal system of most countries but I think there might have been some misunderstandings about consensus at that time,” he says. “I think it’s important to talk about it. I think many people want every opportunity to discuss this issue—sometimes you need an event to make it newsworthy.

Although scientists today offer a range of views on what is acceptable, the essential divide may not be between East and West. In September a researcher at the London-based Francis Crick Institute, Kathy Niakan, filed an application with U.K. regulators “to use new [CRISPR] ‘genome editing’ techniques on human embryos,” according to an institution statement. “The work carried out at the Crick will be for research purposes and will not have a clinical application. However, the knowledge acquired from the research will be very important for understanding how a healthy human embryo develops.

Meanwhile Chinese scientists point out that the country is having its own internal debates about the ethics of editing DNA.

Whatever the discussions in Washington yield, Yaofeng Zhao at the State Key Laboratory of Agrobiotechnology, a geneticist working on sheep, says that China is also grappling with its own internal ethical and safety debates about moving CRISPR experiments, for agriculture and biomedicine, beyond the lab. “I think there are different viewpoints on gene modification. Even in China there are different viewpoints on this issue. Some people in the general public, they are scared. But for most academics, I think most scientists support this kind of research—we need to do something for the future,” he says. In contrast to Qu, the cashmere-goat specialist, Zhao doesn’t think designer meat will be soon be on dinner plates. “If you want to use modified animals in agriculture, you must consider the public opinion—Can they accept this? Even if the technology is quite safe, it depends on many factors if you want to commercialize this kind of animal in agriculture.” There is already precedent for the Chinese government spending heavily on GMO crop research, including improved corn, wheat and rice, but delaying commercialization due to fierce public resistance.

In areas where science advances faster than regulation it may be possible for individual scientists or labs—in China or any country—to act outside of national consensus. At the Shenzhen International Biotech Leaders Summit on September 23, the private genomics firm BGI–Shenzhen, a maverick in the field, announced that it would begin selling gene-edited micro pigs as pets; the smaller pigs were originally created with the intention of biomedical research. Yong Li, technical director of BGI’s animal science platform, who turned down an interview request about the pigs for Scientific American, previously told Nature that he wanted to “evaluate the market.” (Pets are less regulated than agriculture, and do not supply national markets.) Some Chinese researchers clearly disapprove. Lai, co-author of the beagle paper, says he believes scientists should “not use CRISPR technique to create pets with special traits to satisfy some pet owner’s special favor.”

Lai’s own work does not involve human embryos but he offered his opinion on the larger ongoing debate: If safety and efficacy issues can first be addressed, he is open to the future possibility of therapeutic uses, but not to eugenics. “In human beings CRISPR could be used to correct the mutation, which cause genetic human diseases, and it should not be used to generate any particular traits which some people may favor.” Other Chinese scientists working with CRISPR expressed similar views but none purported to predict the future—in China or elsewhere. Huang notes, “The gene-editing technology is very hot all over the world.”

Public debate over any powerful new technology reflects preexisting public hopes and fears, Church says. In the case of CRISPR that includes the desire to eliminate hereditary diseases as well as concerns about the commodification of parenting, the privileges of rich over poor and, newly, the rise of China.

Nature doi:10.1038/nature.2015.18826 Nature  Original web page at Nature


* ‘Gene drive’ mosquitoes engineered to fight malaria

The Anopheles stephensi mosquito can spread the malaria parasite to humans. Mutant mosquitoes engineered to resist the parasite that causes malaria could wipe out the disease in some regions — for good. Humans contract malaria from mosquitoes that are infected by parasites from the genus Plasmodium. Previous work had shown that mosquitoes could be engineered to rebuff the parasite P. falciparum, but researchers lacked a way to ensure that the resistance genes would spread rapidly through a wild population.

In work published on 23 November in the Proceedings of the National Academy of Sciences, researchers used a controversial method called ‘gene drive’ to ensure that an engineered mosquito would pass on its new resistance genes to nearly all of its offspring — not just half, as would normally be the case. The result: a gene that could spread through a wild population like wildfire.  For Anthony James, a molecular biologist at the University of California, Irvine, and an author of the paper, such a release would spell the end of a 30-year quest to use mozzie genetics to squash malaria.

James and his laboratory have painstakingly built up the molecular tools to reach this goal. They have worked out techniques for creating transgenic mosquitoes — a notoriously challenging endeavour — and isolated genes that could confer resistance to P. falciparum. But James lacked a way to ensure that those genes would take hold in a wild population.

The concept of engineering a gene drive has been around for about a decade, and James’s laboratory had tried to produce them in the past. The process was agonizingly slow.

Then, in January, developmental biologists Ethan Bier and Valentino Gantz at the University of California, San Diego, contacted James with a stunning finding: they had engineered a gene drive in fruit flies, and wondered whether the same system might work in mosquitoes. James jumped at the opportunity to find out. Bier and Gantz had used a gene-editing system called CRISPR–Cas9 to engineer a gene drive. They inserted genes encoding the components of the system that were designed to insert a specific mutation in their fruit flies. The CRISPR-Cas9 system then copied that mutation from one chromosome to the other. James used that system in mosquitoes to introduce two genes that his past work showed would cause resistance to the malaria pathogen.

The resulting mosquitoes passed on the modified genes to more than 99% of their offspring. Although the researchers stopped short of confirming that all the insects were resistant to the parasite, they did show that the offspring expressed the genes

“It’s a very significant development,” says Kenneth Oye, a political scientist who studies emerging technologies at the Massachusetts Institute of Technology in Cambridge. “Things are moving rapidly in this field.”

Other teams are developing gene drives that could control malaria. A team at Imperial College London has developed a CRISPR-based gene drive in A. gambiae, the mosquito species that transmits malaria in sub-Saharan Africa. The group’s gene drive inactivates genes involved in egg production in female mosquitoes, which could be used to reduce mosquito populations, according to team member  Austin Burt, an evolutionary geneticist. Their results will be published in Nature Biotechnology next month, Burt says.

Oye notes that such technological advances are outpacing the regulatory and policy discussions that surround the use of gene drive to engineer wild populations. Gene drives are controversial because of the potential that they hold for altering entire ecosystems.

Before testing gene drive in the field, Oye hopes that researchers will study the long-term consequences of the changes, such as their stability and potential to spread to other species, as well as methods to control them. “I’m less worried about malevolence than getting something wrong,” he says.

Esvelt says that the US-based researchers made a wise decision in selecting a non-native mosquito species for their experiments. (The team worked with Anopheles stephensi, which is native to the Indian subcontinent.) “Even if they escaped the lab, there’d be no one to mate with and spread the drive,” Esvelt says.

James predicts that it will take his team less than a year to prepare mosquitoes that would be suitable for field tests, but he is in no rush to release them. “It’s not going to go anywhere until the social science advances to the point where we can handle it,” he says. “We’re not about to do anything foolish.”

Nature doi:10.1038/nature.2015.18858   Nature  Original web page at Nature


Preventing dental implant infections

One million dental implants are inserted every year in Germany, and often they need to be replaced due to issues such as tissue infections caused by bacteria. In the future, these infections will be prevented thanks to a new plasma implant coating that kills pathogens using silver ions.

Bacterial infection of a dental implant is a dreaded complication, as it carries with it a high risk of jawbone degeneration. Implanting an artificial dental root sets off a race between infectious pathogens and the body’s own cellular defenses. If the bacteria win, they form a biological film over the titanium to protect themselves from antibiotics. Once the implant is colonized by germs, the result is an inflammatory reaction, which can result in bone atrophy.

To lower the risk of infection and improve the long-term effectiveness of the implant, researchers at the Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Bremen have developed a new type of implant coating in cooperation with industry partners. The DentaPlas coating helps prevent the growth of bacteria, thus allowing the implant to properly take hold and thereby form a faster and more permanent bond with the jawbone. The trick to this lies in combining surface materials that feature physical as well as chemical properties. “We have given the DentaPlas coating a rough texture, which promotes cellular growth, in addition to combining it with a hydrophilic plasma polymer coating, which attracts moisture,” says Dr. Ingo Grunwald, project manager at the IFAM. Researchers have integrated silver nanoparticles into the thin plasma polymer coating, which is up to just 100 nanometers thick. The silver nanoparticles dissolve over a period of several weeks, and during that time they continuously release small quantities of anti-microbial silver ions, which kill bacteria.

“The DentaPlas system consists of three layers, with two plasma polymer layers surrounding a center layer of silver. Within this structure a biocide reservoir is formed, and the outermost layer releases the ions. This is beneficial because it prevents direct contact between the tissue and the silver particles, which can be toxic when exposed,” says developer Dr. Dirk Salz. Researchers can tailor the silver concentration as well as the thickness of the layers and their porosity. This allows the silver ions to penetrate the outermost plasma polymer layer over a set period of time deemed necessary to properly integrate the implant. When the silver reservoir is exhausted, no more silver ions are released, thus avoiding any long-term toxic effects.

In trials using finished implants and titanium test samples, the IFAM researchers demonstrated that the DentaPlas coating is not only anti-microbial but also fully biocompatible and sterilizable. The test samples were coated using a plasma polymerization facility at the IFAM in Bremen. Researchers confirmed the mechanical stability and robustness of the DentaPlas coating in trials using the lower jawbones of pigs taken from butcher shops. Here, they subjected the DentaPlas coated implants to the rigors of being screwed into place using the instruments found in modern dental practices. The DentaPlas coating passed this stress test with flying colors. Project partner and Fraunhofer spinoff Bio Gate AG successfully transferred the processes of coating the test samples and titanium screws to its own production facilities. The medical technology company is also the manufacturer of the DentaPlas three-layer coating system.

A demonstration unit of the plasma polymer coating is currently available. Researchers will be presenting a dental implant featuring the DentaPlas coating at the MEDICA trade fair in Düsseldorf from November 16 -19 at the joint Fraunhofer booth.  Science Daily  Original web page at Science Daily


* Climate change threatens survival of common lizards

While there is no doubt that climate change is affecting many organisms, some species might be more sensitive than others. Reptiles, whose body temperature depends directly on environmental temperature, may be particularly vulnerable. Scientists have now shown experimentally that lizards cope very poorly with the climate predicted for the year 2100.

In a new study, publishing in the Open Access journal PLOS Biology on October 26th, Elvire Bestion, Julien Cote and colleagues examined the consequences of a 2°C warmer climate on the persistence of populations of common lizards (Zootoca vivipara), a widespread European reptile. Their results show that many common lizard populations could disappear rapidly as a consequence of such warmer temperatures.

“Breed fast and die young” seems to be the new mantra of common lizards in the face of climate change; it is also the conclusion reached by researchers from the Station d’écologie expérimentale du CNRS à Moulis (SEEM) and the Laboratoire Evolution et Diversité Biologique (EDB, CNRS/Université Toulouse 3 Paul Sabatier/ENFA) who studied this small European reptile species.

The team used the Metatron — a system of semi-natural enclosures in which temperature can be manipulated — to create two distinct climates: one similar to the present climate and another 2 °C warmer, corresponding to the predicted climate for the end of the century. Eighteen populations of common lizards were put into Metatron enclosures over two years in the “present” or “warmed” climate. Populations were surveyed for one year, allowing the team to determine the impact of warmer climates on demographic parameters such as growth rate, reproduction and survival.

“While a two-degrees warmer climate might seem beneficial at first, as it leads to faster growth of juvenile lizards and earlier access to reproduction, it also leads to lower survival in adult individuals, which should endanger population survival,” says Elvire Bestion, co-lead author of the study and currently working at Exeter University (United Kingdom). A model of population dynamics showed that the increased adult mortality would lead to decreased population growth rates, and ultimately to rapid population extinctions in around 20 years.

“Although these results might seem dramatic, we do not predict extinction of common lizards at the scale of the species, but we suggest that populations at the southern edge of their range of distribution might particularly suffer from warmer climates,” adds Julien Cote, biologist at the Laboratoire Evolution et Diversité Biologique (France) and co-lead author of the study. Indeed, comparisons of experimental conditions to climatic conditions encountered by European populations of common lizards show that warmer climates might threaten between 14 and 30 % of European populations depending on the carbon emission scenario.

“Anecdotally, we also showed that warmer climates led some adult females to engage into a second reproduction event during the summer, while these lizards normally reproduce only once a year during the spring. Combined with the earlier juvenile reproduction and the higher adult survival, these results suggest a shift of demographic strategy from a relatively long life and low reproductive output to a faster life, higher reproductive investment. We can wonder whether this strategy shift may help adaptation of populations to warmer climates over time,” concludes Elvire Bestion, adding a positive note to overall pessimistic results. Science Daily  Original web page at Science Daily


Medication dose needed for general anesthesia varies widely: Some patients may require less anesthesia

The amount of anesthetic required for general anesthesia during surgery varies widely from patient to patient and some may be able to receive a lower dose than typically administered, suggests a study being presented at the ANESTHESIOLOGY® 2015 annual meeting.

“Providing general anesthesia is a delicate balance, ensuring the patient receives enough, but not more than needed,” said Ana Ferreira, M.D., lead author of the study and a medical researcher in the Anesthesiology Department at Centro Hospitalar do Porto, Portugal. “Our research shows that there is no way to predict how much a patient will need. Administering the correct amount of anesthetic requires a physician anesthesiologist who has extensive knowledge of anesthesia and how to use it safely and effectively, understands the body, monitors vital functions closely and can instantly react to changes taking place. This expertise drives better outcomes and more personalized care.”

Physician anesthesiologists use a combination of anesthesia medications for surgery, including one — most commonly propofol — to render the patient unconscious. In the study, researchers determined that the amount of propofol required to produce unconsciousness varied widely between patients and was independent of age, gender, weight or height. Close monitoring of the patient’s neurological signs and brainwaves was used to determine when the correct dosage was achieved.

For the study, 126 patients were given propofol in a constant slow rate of infusion, enabling researchers to continuously monitor patient response and precisely determine when loss of consciousness occurred (e.g. not answering to name, not opening the eyes, etc.), as well as identify the exact amount of propofol required. Researchers found that there was a variation of 300 percent in the amount of propofol required to induce loss of consciousness and that more than two-thirds of the patients required less than the initial dose recommended by drug package inserts. The time needed to induce loss of consciousness varied from one minute and 22 seconds to nearly four minutes, researchers said. They also found significantly less propofol was required if pain medication (remifentanil) was given to the patient before propofol was provided, rather than after.

“We need to replace the recommendation of administering a specific amount of propofol based on a patient’s weight and age with a technique that allows individualization of a patient’s needs. That means administering propofol slowly at induction and monitoring the patient’s response every 10 seconds to precisely identify the moment loss of consciousness occurs, identifying the amount of propofol each patient requires and then using that information to guide the infusion rate of propofol required to maintain an adequate level of anesthesia,” said Pedro Amorim, M.D., co-author of the study, chief of staff of the Anesthesiology Department at Centro Hospitalar do Porto. “The time required for induction, using this method, is longer than if propofol is given based on the patient’s weight and age, but less than four minutes to induce loss of consciousness is acceptable and ensures safe and effective care.”  Science Daily  Original web page at Science Daily


Mapping the genes that increase lifespan

Following an exhaustive, ten-year effort, scientists at the Buck Institute for Research on Aging and the University of Washington have identified 238 genes that, when removed, increase the replicative lifespan of S. cerevisiae yeast cells. This is the first time 189 of these genes have been linked to aging. These results provide new genomic targets that could eventually be used to improve human health. The research was published online on October 8th in the journal Cell Metabolism.

“This study looks at aging in the context of the whole genome and gives us a more complete picture of what aging is,” said Brian Kennedy, PhD, lead author and the Buck Institute’s president and CEO. “It also sets up a framework to define the entire network that influences aging in this organism.”

The Kennedy lab collaborated closely with Matt Kaeberlein, PhD, a professor in the Department of Pathology at the University of Washington, and his team. The two groups began the painstaking process of examining 4,698 yeast strains, each with a single gene deletion. To determine which strains yielded increased lifespan, the researchers counted yeast cells, logging how many daughter cells a mother produced before it stopped dividing.

“We had a small needle attached to a microscope, and we used that needle to tease out the daughter cells away from the mother every time it divided and then count how many times the mother cells divides,” said Dr. Kennedy. “We had several microscopes running all the time.”

These efforts produced a wealth of information about how different genes, and their associated pathways, modulate aging in yeast. Deleting a gene called LOS1 produced particularly stunning results. LOS1 helps relocate transfer RNA (tRNA), which bring amino acids to ribosomes to build proteins. LOS1 is influenced by mTOR, a genetic master switch long associated with caloric restriction and increased lifespan. In turn, LOS1 influences Gcn4, a gene that helps govern DNA damage control.

“Calorie restriction has been known to extend lifespan for a long time.” said Dr. Kennedy. “The DNA damage response is linked to aging as well. LOS1 may be connecting these different processes.”

A number of the age-extending genes the team identified are also found in C. elegans roundworms, indicating these mechanisms are conserved in higher organisms. In fact, many of the anti-aging pathways associated with yeast genes are maintained all the way to humans.

The research produced another positive result: exposing emerging scientists to advanced lab techniques, many for the first time.

“This project has been a great way to get new researchers into the field,” said Dr. Kennedy. “We did a lot of the work by recruiting undergraduates, teaching them how to do experiments and how dedicated you have to be to get results. After a year of dissecting yeast cells, we move them into other projects.”

Though quite extensive, this research is only part of a larger process to map the relationships between all the gene pathways that govern aging, illuminating this critical process in yeast, worms and mammals. The researchers hope that, ultimately, these efforts will produce new therapies.

“Almost half of the genes we found that affect aging are conserved in mammals,” said Dr. Kennedy. “In theory, any of these factors could be therapeutic targets to extend healthspan. What we have to do now is figure out which ones are amenable to targeting.”  Science Daily  Original web page at Science


King crabs threaten Antarctic ecosystem due to warming ocean

King crabs may soon become high-level predators in Antarctic marine ecosystems where they haven’t played a role in tens of millions of years, according to a new study led by Florida Institute of Technology. “No Barrier to Emergence of Bathyal King Crabs on the Antarctic Shelf,” published online in the Proceedings of the National Academy of Sciences, ties the reappearance of these crabs to global warming.

Lead author Richard Aronson, professor and head of Florida Tech’s Department of Biological Sciences, said the rising temperature of the ocean west of the Antarctic Peninsula — one of the most rapidly warming places on the planet — should make it possible for king crab populations to move to the shallow continental shelf from their current deep-sea habitat within the next several decades.

Researchers found no barriers, such as salinity levels, types of sediments on the sea floor, or food resources, to prevent the predatory crustaceans from arriving if the water became warm enough.

“Because other creatures on the continental shelf have evolved without shell-crushing predators, if the crabs moved in they could radically restructure the ecosystem,” Aronson said.

The study provides initial data and does not by itself prove that crab populations will expand into shallower waters. “The only way to test the hypothesis that the crabs are expanding their depth-range is to track their movements through long-term monitoring,” said James McClintock of the University of Alabama at Birmingham (UAB), another author of the study.

In the 2010-11 Antarctic summer, in research funded by the National Science Foundation (NSF), the team used an underwater camera sled to document a reproductive population of the crabs for the first time on the continental slope off Marguerite Bay on the western Antarctic Peninsula. That area is only a few hundred meters deeper than the continental shelf where the delicate ecosystem flourishes.

The overall effect of the migration of king crabs to shallower waters, explained postdoctoral scientist and study co-author Kathryn Smith of Florida Institute of Technology, would be to make the unique Antarctic ecosystem much more like ecosystems in other areas of the globe, a process ecologists call biotic homogenization. Such changes, the researchers conclude, would fundamentally alter the Antarctic sea-floor ecosystem and diminish the diversity of marine ecosystems globally.

The data used in the paper were collected during an expedition to Antarctica run jointly by NSF, the Swedish Polar Research Secretariat and the Swedish Research Council. The expedition included scientists from Florida Tech, UAB, the Woods Hole Oceanographic Institution, the University of Gothenburg in Sweden and the University of Southampton in the United Kingdom.   Science Daily  Original web page at Science Daily


* Dramatic rise seen in antibiotic use

Antibiotic use is growing steadily worldwide, driven mainly by rising demand in low- and middle-income countries, according to a report released on 17 September. The research presents the clearest picture yet of how and where the drugs are used, and the prevalence of different types of antibiotic resistance.

The Center for Disease Dynamics, Economics and Policy (CDDEP), a non-profit group headquartered in Washington DC, based the analysis on data from scientific literature and national and regional surveillance systems. The organization used this to calculate and map the rate of antibiotic resistance for 12 types of bacteria in 39 countries, and trends in antibiotic use in 69 countries over the past 10 years or longer.

Global antibiotic consumption grew by 30% between 2000 and 2010. This growth is driven mostly by countries such as South Africa and India, where antibiotics are widely available over the counter and sanitation in some areas is poor.

In India, for instance, the number of Klebsiella pneumoniae infections that are resistant to a class of powerful antibiotics called carbapenems doubled from 29% in 2008 to 57% in 2014. By contrast, fewer than 10% of K. pneumoniae infections in the United States and Europe are carbapenem resistant.

The report also found that the use of antibiotics in livestock is growing worldwide. The problem is particularly acute in China, which used about 15,000 tons of antibiotics for this purpose in 2010; the country is projected to double its consumption by 2030.

Most high-income countries, by contrast, have begun instituting regulations on antibiotic use, and these are starting to pay off. According to the report, the number of methicillin-resistant Staphylococcus aureus (MRSA) infections, for example, has dropped precipitously in many areas, such as the United Kingdom, over the past eight years.

“I think it’s a very thorough and thought-provoking report,” says Daniel Sahm, chief scientific officer at International Health Management Associates in Schaumburg, Illinois. Because it is so difficult to gather data from developing countries, he says, the information used in the new analysis might contain holes: an argument for more-aggressive surveillance.

The report lists six steps for preventing antibiotic resistance in countries that do not yet have good policies. Some of those measures, such as improving sanitation, are obvious, whereas policies that restrict antibiotic use in agriculture and hospitals might be more difficult or controversial to implement.

But Timothy Walsh, a medical microbiologist at Cardiff University, UK, says that, although the suggestions offered are worthwhile, international cooperation in setting up a global surveillance network and regulations is necessary to limit the overuse of antibiotics. “We can pour as much money and sentiment and goodwill into the front end of the problem as we want,” he says. “But unless we start to have international action and accountability, we’re going to just keep on making the same mistakes over and over again.”

Nature doi:10.1038/nature.2015.18383  Nature  Original web page at Nature


* Global burden of leptospirosis is greater than thought, and growing

The global burden of a tropical disease known as leptospirosis is far greater than previously estimated, resulting in more than 1 million new infections and nearly 59,000 deaths annually, a new international study led by the Yale School of Public Health has found.

Professor Albert Ko, M.D., and colleagues conducted a systematic review of published morbidity and mortality studies and databases, and for the first time developed a disease model to generate a worldwide estimate of leptospirosis’ human toll. The results were published Sept. 17 in PLOS Neglected Tropical Diseases.

While leptospirosis is relatively unknown in the developed world, it is a growing scourge in resource-poor settings throughout Latin America, Africa, Asia, and island nations. The spirochetal bacteria that causes the disease is shed in the urine of rats and other mammals. The pathogen survives in water and soil and infects humans upon contact through abrasions in the skin.

The finding shows leptospirosis is one of the leading zoonotic (diseases passed between animals and humans) causes of morbidity and mortality in the world and is a call to action, said Ko, chair of the Department of Epidemiology (microbial disease) at Yale School of Public Health.

“The study identified an important health burden caused by this life-threatening disease, which has been long neglected because it occurs in the poorest segments of the world’s population,” said Ko, who has studied the disease for years in Brazil’s urban slum communities, or favelas. “At present, there are no effective control measures for leptospirosis. The study provides national and international decision-makers with the evidence to invest in initiatives aimed at preventing the disease, such as development of new vaccines, as well as targeting the underlying environmental and social conditions, rooted in social inequity, that lead to its transmission.”

The researchers said that the incidence of the disease has the potential to grow even further in the coming decades due to global climate change and rapid urbanization. The disease is particularly prevalent in urban slums where inadequate sewerage and sanitation, combined with extreme climatic events and heavy seasonal rainfall, enhance contact with contaminated environments, causing epidemics. It is estimated that the world’s slum population will double to 2 billion people by 2030.

Leptospirosis results in severe illness and has emerged as an important cause of pulmonary hemorrhage and acute renal failure in developing countries, where death occurs in 10% of patients, and hemorrhaging occurs in up to 70%.

It is likely that the latest numbers still underestimate the problem, the researchers noted, as leptospirosis patients are frequently misdiagnosed with malaria, dengue, or other illnesses. There is also not an adequate diagnostic test for the disease.

Prior inconclusive estimates of the leptospirosis burden have contributed to its status as a neglected tropical disease and hampered efforts to develop effective prevention and control measures, the researchers said.  Science Daily  Original web page at Science Daily


The mending tissue: Cellular instructions for tissue repair

The epithelial tissue, or the epithelium, is one of four major types of tissue that lines the surfaces of all organs and hollow spaces in our body. The epithelium protects the organs from damage and maintains the body in a state of balance by allowing a selective in-and-out passage of substances. Proper function of the epithelium requires an intact layer of epithelial cells.

During the lifetime of an organism, gaps or holes of different sizes and shapes are introduced into this intact epithelium. They may appear as a consequence of natural biological processes such as embryo development when cells move around and rearrange to establish body patterns, or during cell turnover in adult tissues, when dead cells are cleared away by neighbouring healthy cells. In addition, injury or disease may also lead to wounds or ulcers in the tissue. In either case, any gap in the tissue needs to be sealed so that the normal functioning of the tissue is restored.

In the likelihood of an open wound or gap causing complications such as infections, inflammation or even cancer, our body has developed two major repair mechanisms whereby cells surrounding the gap collectively move in and seal the open spaces completely.

To do so, cells either put forth finger-like protrusions called lamellipodia to crawl along the underlying surface or form an interconnecting belt or cable of actin filaments and myosin proteins. When this cable contracts, it pulls the cells closer in a coordinated fashion, similar to the action of drawing a purse-string. However, the extent to which either mechanism contributes to tissue repair is known to depend on several factors such as the gap geometry, gap size or the presence or absence of an underlying supporting surface.

To determine the impact of tissue geometry on gap closure, the international research team studied the effects of gap shapes on gap closure mechanisms.

By using microfabrication techniques to grow epithelial cells around stencils made of an inert polymer, they created gaps of desired shapes within the cell culture. The boundaries of the gap were either protruding inwards (concave edges) or were extending away (convex edges).

Interestingly, the researchers noted that the speed at which cells along the gap edge moved depended on the local curvature. Specifically, they found that cells at the convex edge moved in faster than those at the concave edges. To test the relevance of their findings in a living system, the researchers studied wound repair in flies and found a similar association between wound shape and wound repair.

The current study has identified a universal mechanism that explains how the geometrical properties of tissue regulate forces and guide cellular movement during physiological processes such as cell turnover, embryo development and wound healing. Cells essentially receive the instructions on how to close a gap by sensing and measuring the shape of the gap itself. Further understanding of how cells do this will help researchers know how to treat chronic medical conditions involving wounds or unsealed gaps as well as designing new substrates to optimise tissue regeneration.  Science Daily  Original web page at Science Daily


* Researchers discover surprisingly wide variation across species in genetic systems that influence aging

A new study focusing on insulin signaling uncovered surprising genetic diversity across reptiles, birds and mammals. Scientists previously assumed the process remained much the same throughout the animal kingdom, but the new research shows that the genetic pathways in reptiles evolved to include protein forms not observed in mammals. A new Iowa State University study focusing on insulin signaling uncovered surprising genetic diversity across reptiles, birds and mammals.

The research sets the stage for an improved understanding of metabolism, growth and aging and may have implications for medicine and human health, said Anne Bronikowski, an associate professor of ecology, evolution and organismal biology and a lead author of the study.

Insulin signaling is a critical biological process that governs the rate at which cells grow and divide and ultimately regulates aging. Scientists previously assumed the process remained much the same throughout the animal kingdom. But the new research shows that the genetic pathways in reptiles evolved to include protein forms not observed in mammals, a finding that suggestions these proteins carry out new or additional functions in reptiles.

The researchers looked at a molecular network known as the insulin/insulin-like signaling and target of rapamycin network (IIS/TOR). Because the IIS/TOR network regulates critical aspects of animal biology, scientists have long speculated that the network would work more or less the same in most animal species.

Bronikowski and Fred Janzen, a professor of ecology, evolution and organismal biology, completed the study along with former and current members of their labs. The research team compared the genomes of mammals and birds with 17 reptile species. The team found an abundance of variation in the hormones and receptors of the network, which bucks the conventional wisdom and indicates that hormones delivered through insulin likely undertake additional functions in reptiles.

“The study provides a critical step toward understanding how the IIS/TOR network may regulate variation in metabolism, modes of reproduction and rates of aging,” Bronikowski said. “It highlights genetic variants that occur in nature that may be useful in a human health context. It therefore lays the groundwork for future research to identify natural genetic variants that may work together to alter the function of this network, which may lend insight into metabolic and aging diseases and treatments.”

Previous studies of insulin signaling have focused on species commonly used as laboratory models, such as mice, fruit flies and nematodes. The new study compared 66 species, including 17 reptile species for which the research group had to generate transcriptome data — or the set of all RNA molecules in a particular genome — because the data didn’t exist previously. The team was able to sequence the reptile data with the help of support from the ISU Center for Integrated Animal Genomics.

The wide range of variation discovered by the study may suggest that the insulin signaling network could be targeted by new medical therapies to treat conditions associated with aging, Bronikowski said. “The variation indicates that there might be some flexibility in how these genes work,” she said. “The next step might be to look at how we can influence the genes to produce better medical outcomes.”  Science Daily  Original web page at Science Daily


*Injured spinal cord: Regeneration possible with epothilone?

Damage to the spinal cord rarely heals because the injured nerve cells fail to regenerate. The regrowth of their long nerve fibers is hindered by scar tissue and molecular processes inside the nerves. An international team of researchers led by DZNE scientists in Bonn now reports in Science that help might be on the way from an unexpected quarter: in animal studies, the cancer drug epothilone reduced the formation of scar tissue in injuries to the spinal cord and stimulated growth in damaged nerve cells. Both promoted neuronal regeneration and improved the animals’ motor skills.

Nerve cells are wire-like conductors that transmit and receive signals in the form of electrical impulses. This function can be impaired by accidents or disease. Whether or not the affected nerves can recover largely depends on their location: for instance nerve cells in the limbs, torso and nose can regenerate to some degree and regain some or all of their function. In contrast, the neurons in the brain and spinal cord do not have this ability. If they are damaged by accident or disease, the patient is likely to suffer long-term paralysis or other disabilities. But why is regeneration of these neurons and their long nerve fibers impeded? It is already known that inhibiting factors in newly formed scar tissue and other cellular processes block axon regrowth.

“The ideal treatment for promoting axon regeneration after spinal cord injury would inhibit the formation of scar tissue,” says Professor Frank Bradke, who leads a working group at the DZNE’s site in Bonn and who conducted the study. “However, it is also important that the growth-inhibiting factors are neutralized while reactivating the poor axons’ regenerative potential.” A feasible administration of a potential treatment is also essential for clinical application. In cooperation with international researchers, Bradke and his team have now managed to take another step towards the development of a future treatment. From their previous research, it was already known that stabilizing microtubules would reduce the formation of scar tissue and promote axonal growth. Microtubules are long, tubular filaments inside the cell that can grow and shrink dynamically. They are part of the cell’s supportive skeleton, which also controls cell growth and movement.

The substance epothilone can stabilize microtubules and is already licensed on the American market — as a cancer treatment. “It all depends on the dose,” says Dr. Jörg Ruschel, the study’s lead author. “In higher doses, epothilone inhibits the growth of cancer cells, while low doses have been shown to stimulate axonal growth in animals without the severe side-effects of cancer treatment.” Epothilone is superior to other cancer drugs with a similar effect because it can penetrate the blood-brain barrier into the central nervous system, thus reaching the damaged axons directly. Experiments have shown epothilone works on several levels. Epothilone reduces the growth of scar tissue by inhibiting the formation of microtubules in the cells that form the scar tissue. Therefore they cannot migrate to the spinal cord lesion and cause wound scarring. At the same time, epothilone promotes growth and regeneration in the nerve cells by causing microtubules to grow into the damaged axon tips.

In short: through the same effect, namely microtubule stabilization, epothilone is able to inhibit directional movement in scar-forming cells while stimulating active growth in nerve cell axons. The animals treated with epothilone after spinal cord injury walked better than those that received no treatment, due to improved balance and coordination. The next goal of Bradke and his team is to test the effect of epothilone on various types of lesion.  Science Daily  Original web page at Science Daily


* UK funders demand strong statistics for animal studies

Experiments that use only a small number of animals are common, but might not give meaningful results. Replace, refine, reduce: the 3 Rs of ethical animal research are widely accepted around the world. But now the message from UK funding agencies is that some experiments use too few animals, a problem that leads to wastage and low-quality results.

On 15 April, the research councils responsible for channelling government funding to scientists, and their umbrella group Research Councils UK, announced changes to their guidelines for animal experiments. Funding applicants must now show that their work will provide statistically robust results — not just explain how it is justified and set out the ethical implications — or risk having their grant application rejected. The move aims to improve the quality of medical research, and will help to address widespread concerns that animals — mostly mice and rats — are being squandered in tiny studies that lack statistical power

“If the study is underpowered your results are not going to be reliable,” says Nathalie Percie du Sert, who works on experimental design at the National Centre for the Replacement, Refinement and Reduction (NC3Rs) of Animals in Research in London. “These animals are going to be wasted.” Researchers say that sample size is sometimes decided through historical precedent rather than solid statistics. There is also a lack of clarity: last year, an analysis of selected papers published in Nature or Public Library of Science journals describing animal experiments revealed that few reported the use of statistical tests to determine sample size, even though both publishing groups had endorsed guidelines to improve reporting standards (D. Baker et al. PLoS Biol. 12, e1001756; 2014).

Animals feature in a wide range of experiments, many of which are designed to test drugs before trials are done in people. The effects that researchers are looking for in these preclinical studies are often subtle, and ‘power calculations’ are needed to reveal the number of animals needed to show an effect. But an international academic partnership called the CAMARADES project (Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies), has shown that many animal studies are underpowered: studies in stroke, for example, are typically powered at between 30% and 50%, meaning that there is just a 30–50% chance of detecting a biological effect if it exists. Malcolm Macleod, a neuroscientist at the University of Edinburgh, UK, blames, among other things, a lack of training and support in experimental design, as well as limited funds: animals are expensive to work with.

Some say that the pressure to ‘reduce’ may be one of the reasons for small experiments, but others counter that this is a misinterpretation of the 3 Rs because small experiments are ethically problematic if they have low statistical power. The problem is not limited to Britain: last year, Francis Collins, director of the US National Institutes of Health (NIH), and Lawrence Tabak, NIH deputy director, warned about a lack of reproducibility in preclinical research and mentioned a dearth of sample-size calculations as one of the problems. The situation infuriates animal-welfare proponents. “It’s completely unethical to use animals in studies that aren’t properly designed,” says Penny Hawkins, head of the research-animals department at the Royal Society for the Prevention of Cruelty to Animals in Southwater, UK.

Boosting the number of animals in specific experiments need not mean more animals are used overall because multiple small experiments can often be replaced by fewer, larger ones “One potential implication is we need to ask for money to do larger studies,” says Marcus Munafò, a psychologist at the University of Bristol, UK. Another way to increase sample sizes would be to link up researchers working on similar topics. Munafò notes that this is what geneticists now do for studies that require scanning a large number of genomes. “That template already exists,” he says. “The question is, how do you initiate that cultural change?” More immediately, du Sert is developing an online tool for the NC3Rs that will help researchers to design robust studies. “We’re not blaming anyone for the way they were doing things before,” she adds. “That was the practice at the time.”

Nature 520, 271–272 (16 April 2015) doi:10.1038/520271a  Nature  Original web page at Nature


Fruit fly studies shed light on adaptability of nerve cells

An international team of researchers at German Center for Neurodegenerative Diseases (DZNE) and Tokyo Institute of Technology (Tokyo Tech) have revealed in a collaborative study — published today in NEURON, that neurons in the eye change on the molecular level when they are exposed to prolonged light. The researchers could identify that a feedback signalling mechanism is responsible for these changes. The innate neuronal property might be utilized to protect neurons from degeneration or cell death in the future. Changes in the functional connections between neurons — ‘synapses’ — contribute to our ability to adapt to environmental changes. However until now, little was known about the signalling underlying such ‘synaptic plasticity’. Now, investigations of fruit flies by researchers at the German Center for Neurodegenerative Diseases (DZNE), Tokyo Tech, the National Institute of Genetics in Japan, and the European Neuroscience Institute in Germany reveal details of the mechanisms behind synaptic plasticity.

“The synaptic changes that we have identified might reflect an innate neuronal property that leads to protection from excessive stimuli,” explains Dr. Atsushi Sugie, the study’s lead author and Postdoc at DZNE. “By enhancing this property, we might be able to protect neurons from degeneration or cell death.” Recent studies have suggested that changes in a region at the presynaptic membrane, described as the active zone, control synapse function. The research teams based in Germany and Japan exposed living fruit flies — the commonly studied Drosophila  — to different light regimes and then compared the active zones in the photoreceptors. T-shaped structures at the presynaptic membrane tether synaptic vesicles and control the release of neurotransmitters to the postsynaptic neuron. By tagging proteins that are crucial to these T-shaped structures the researchers revealed a drop in a subset of active zone proteins, while others remained unchanged. Further, they found that corresponding to the loss of structural proteins, the number of T-shaped structures was also reduced.

The researchers were also able to identify that a feedback mechanism was responsible for these changes and that it relied on the signalling protein Wnt. The results contribute to a better understanding of the molecular mechanisms underlying brain functions such as learning and memory. Future work may investigate how modifying the Wnt signal can be used to manipulate synaptic plasticity, with possible therapeutic applications for neurodegenerative or mental diseases.  Science Daily  Original web page at Science Daily