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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


US government issues historic $3.5-million fine over animal welfare

Antibody provider Santa Cruz Biotechnology settles with government after complaints about treatment of goats. Santa Cruz Biotech has used goats to produce antibodies.

The US government has fined Santa Cruz Biotechnology, a major antibody provider, US$3.5 million over alleged violations of the US Animal Welfare Act. The penalty from the US Department of Agriculture is the largest in the agency’s history.

The company, which is headquartered in Dallas, Texas, will pay the fine as part of a settlement with the US Department of Agriculture (USDA). The agency had lodged three animal-welfare complaints against Santa Cruz Biotech, after USDA inspectors found evidence that the company mistreated goats at its facility in California.

Santa Cruz Biotech contested the government complaints, and the 19 May settlement agreement says that the company “neither admits nor denies” that it violated US animal-welfare regulations.

The settlement also permanently revokes Santa Cruz Biotech’s government licence to sell, buy, trade or import animals. And it requires the company to cancel its registration to operate as a research facility that uses animals. The company had extracted antibodies for research from animals such as goats and rabbits after injecting the animals with proteins to stimulate antibody production.

Neither Santa Cruz Biotech nor representatives of Covington & Burling, a Washington DC law firm that represents the company, have responded to Nature’s request for comment on the settlement.

Cathy Liss, president of the Animal Welfare Institute, an advocacy group in Washington DC, says that she is shocked by the unprecedented size of the fine on Santa Cruz Biotech. The largest previous fine that the USDA had imposed for animal-welfare complaints was a $270,000 penalty levied in 2011 against Feld Entertainment, which operates the Ringling Brothers and Barnum & Bailey Circus.

The settlement with Santa Cruz Biotech marks the end of a long-running investigation of the company’s animal-welfare practices. The USDA has lodged three animal-welfare complaints against Santa Cruz Biotech since 2007, after agency inspectors reported finding problems such as goats with untreated coyote bites and massive tumours, and rabbits being housed in cruel conditions. USDA inspectors also discovered that Santa Cruz was keeping 841 goats in a hidden facility.

In February, Nature reported that more than 5,000 goats and rabbits had disappeared from Santa Cruz’s facilities before a scheduled hearing on the USDA complaints. Santa Cruz would not confirm whether the animals were killed or sold.

After news of the animals’ disappearance became public, some scientists took to social media to call for a boycott of Santa Cruz’s products. Among them was Stephen Floor, a biologist at the University of California, Berkeley, who says that his lab has since sought out other antibody providers.

Floor says that losing Santa Cruz as an antibody provider will create extra work for researchers. Because the quality and type of antibodies varies widely, individual labs often stick with products from a single company to ensure that their experiments are replicable. “That said, I think any scientist will happily do that work in order to ensure that animal rights are a priority,” he says.

Nature doi:10.1038/nature.2016.19958  Nature  Original web page at Nature


Thousands of goats and rabbits vanish from major biotech lab

Santa Cruz Biotechnology has used goats to make antibodies for research. In July 2015, the major antibody provider Santa Cruz Biotechnology owned 2,471 rabbits and 3,202 goats. Now the animals have vanished, according to a recent federal inspection report from the US Department of Agriculture (USDA).

The company, which is headquartered in Dallas, Texas, is one of the world’s largest providers of antibodies — extracting them from animals such as goats and rabbits by injecting the animals with proteins to stimulate antibody production. Biomedical researchers can then use these antibodies to detect and label the same protein in cell or tissue samples.

But Santa Cruz Biotech is also the subject of three animal-welfare complaints filed by the USDA after its inspectors found evidence that the firm mistreated goats at its facility in California. Discovery of goat facility adds to antibody provider’s woes.

Santa Cruz Biotech has contested the complaints, prompting a hearing in August before a USDA administrative law judge in Washington DC. Four days into the hearing, both parties asked to suspend the proceedings in order to negotiate a settlement. But those negotiations fell through in September.

The USDA hearing is set to resume on 5 April. If Santa Cruz Biotech is found to have violated the US Animal Welfare Act, it could be fined or lose its licence to keep animals for commercial use. The USDA says that the company could face a maximum fine of US$10,000 per violation for each day that a given violation persists. The agency has reported 31 alleged violations by the company.

In the meantime, the company seems to have done away with its entire animal inventory. When the USDA inspected the firm’s California facility on 12 January, it found no animal-welfare violations — and no animals.

The fate of the goats and rabbits is unclear. The company did not respond to questions about the matter, and David Schaefer, director of public relations for the law firm Covington & Burling in Washington DC, which is representing Santa Cruz Biotechnology, declined to comment on the animals’ fate.

As research animals, the goats and rabbits could not be sold for meat, although they could be sold to another business or research entity. Cathy Liss, president of the Animal Welfare Institute, an advocacy group in Washington DC, suspects that the animals were killed. She says that it is unlikely that such a large number of animals bred for such a specific purpose would find a buyer.

David Favre, an expert in animal-welfare law at Michigan State University in East Lansing, argues that the disappearance of the animals should not sway the legal proceedings over whether the company violated the Animal Welfare Act, because the USDA complaints refer to past events. But he says that the court could still take this latest development into account.

Favre is also unhappy with the USDA’s decision to delay action on the complaints. The department’s “whole attitude is ‘we’ll give them time to fix it rather than impose punishment’,” Favre says. “There’s no excuse for a company that size not to be able to comply with the Animal Welfare Act.”

The USDA’s complaints about Santa Cruz Biotech’s operations detail alleged violations of the law since 2007 — among them accounts of goats with untreated coyote bites and massive tumours, and rabbits being housed in cruel conditions. A sick goat died in front of a USDA inspector during one 2012 inspection.

The company also angered the USDA by keeping 841 goats in an unreported facility, which concealed the animals and their living conditions from regulatory scrutiny until 2012. During the August 2015 USDA hearing, former Santa Cruz Biotech veterinarian Robin Parker testified that company president John Stephenson had decided not to tell the USDA inspectors about the second site. She said that she had been told that the regulators tended to “nitpick” the company’s operations.

After leaving Santa Cruz Biotech in 2012, Parker notified the USDA about the unreported facility. When inspectors visited the site, they found animals housed in poor living conditions.

“So much of what was cited involves great animal suffering,” says Liss, whose advocacy group has campaigned for the USDA to take action against the company. “We are hoping that USDA holds out and if there is going to be a settlement, that it includes them permanently losing their licence as a dealer.”

Favre says that the USDA and Santa Cruz Biotech may have already reached some sort of agreement that requires the company to cease keeping animals for commercial use in advance of the 5 April court hearing; that could explain why the company no longer keeps goats or rabbits. But the USDA administrative-law court says that the company has not submitted any exhibits related to animal removal for the upcoming hearing, although its attorneys could petition to add more evidence before the hearing begins.

Were Santa Cruz Biotech to stop producing antibodies, there would still be hundreds of other providers supplying the materials to researchers, says David Rimm, a pathologist at Yale University in New Haven, Connecticut. “I think people might notice, but I don’t think it would impact science at all,” says Rimm.

He speculates that the company may be moving towards making ‘recombinant’ antibodies. These are produced in cells cultured in the lab that are genetically engineered to make specific antibodies. Many companies have switched to this method instead of producing antibodies using animals, Rimm says.

Alice Ra’anan, director of government relations and science policy at the American Physiological Society in Bethesda, Maryland, hopes that the allegations against Santa Cruz Biotechnology will prompt a cultural change among those involved in animal research. The ideal outcome, she says, is “that people will give animal welfare the level of consideration it deserves”.

Nature doi:10.1038/nature.2016.19411  Nature  Original web page at Nature


Sunshine vitamin linked to improved fertility in wild animals

High levels of vitamin D are linked to improved fertility and reproductive success, a study of wild sheep has found. The study, carried out on a remote Hebridean island, adds to growing evidence that vitamin D — known as the sunshine vitamin — is associated with reproductive health.

Experts hope that further studies will help to determine the relevance of the results for other mammals, including people.

Researchers led by the University of Edinburgh measured concentrations of a marker linked to vitamin D in the blood of an unmanaged population of Soay sheep, on St Kilda. Scientists found that sheep with higher levels of vitamin D in their blood at the end of the summer went on to have more lambs in the following spring.

The study offers the first evidence that an animal’s vitamin D status is associated with an evolutionary advantage. Vitamin D is produced in the skin of sheep and other animals, including people, after exposure to sunlight. It can also be found in some foods, including certain types of plants. It is essential for healthy bones and teeth and has been linked to other health benefits.

Many studies in the lab have linked vitamin D to reproductive health in animals and humans. This is the first evidence of the link in wild animals. Scientists carried out the research as part of a long-term study on the evolution of Soay sheep. The animals have lived wild for thousands of years on the islands of St Kilda, a world Heritage site owned and managed by the National Trust for Scotland. The research is published in the journal Scientific Reports. It was funded by the Wellcome Trust and the Natural Environment Research Council.

Dr Richard Mellanby, Head of Small Animal Medicine at the University’s Royal (Dick) School of Veterinary Studies, who led the research, said: “Our study is the first to link vitamin D status and reproductive success in a wild animal population.

“Examining the non-skeletal health benefits of vitamin D in humans is challenging because people are exposed to different amounts of sunlight each day. Studying the relationship between skin and dietary sources of vitamin D — and long term health outcomes — is more straightforward in sheep living on a small island.”  Science Daily  Original web page at Science Daily


Mimicry helps sheep solve a dilemma

Imitation behaviors play a key role in many collective phenomena seen in animals. An analysis of the collective movements of grazing sheep has revealed that sheep alternate slow dispersion phases with very fast regrouping, in which they imitate the behavior of their neighbors. This study, conducted by researchers from the CNRS, CEA, and the Universities of Aberdeen, Nice Sophia Antipolis and Toulouse III — Paul Sabatier, was published on September 28, 2015 in the journal PNAS. It shows that the intensity with which the sheep mimic one another plays a crucial role in the ability of a herd to maximize the grazing area explored while minimizing the time needed to regroup when faced with potential dangers.

Many animal species live in groups, such as shoals of fish and herds of animals. This lifestyle offers many benefits to individuals by increasing protection against predator attacks. It can also sometimes vastly improve the efficiency of foraging for food. In these groups of animals, imitation behaviors are the cornerstone of many collective phenomena. However, individuals do not imitate one another constantly or at the same intensity over time, which has the effect of increasing the complexity of collective behaviors. Group behaviors are determined by the importance with which each animal treats the behavior of its neighbors relative to its own motivations. Knowing how these two types of influences combine to determine the decisions of each individual within a group is crucial for understanding the complex dynamics of many collective phenomena, not only in animals but also in humans.

To study these phenomena, the researchers analyzed the collective movement of flocks of a hundred Merino sheep grazing under controlled conditions on the Domaine du Merle at Salon-de-Provence. They demonstrated that these movements have intermittent dynamics: slow dispersion phases alternating with phases of consolidation and very fast movement during which sheep mimic the group already in motion. The analysis of these regroupings, and therefore of the mimicry phase, reveals that they are similar to avalanches: their amplitudes are random and distributed over a range with a very large scale. At the scale of the group, this system appears similar to what is called a “critical” condition.

In addition, by using a mathematical model to reproduce the interactions between sheep and their effect on spontaneous behavior, scientists have shown that the intensity of mimicry plays a critical role in the ability of a herd to maximize the area foraged for grazing while minimizing the time needed to regroup. These studies demonstrate that the intermittent dynamics observed in sheep stem from the need for each individual to balance two conflicting motivations: to explore enough new grazing area to find food but also to stay in contact with other herd members so as to benefit from the protection offered by a compact group.

These results also offer new elements for the current debate on the issue of “criticality” of living systems. Being neither in too much disorder nor too rigidly organized — one of the signatures of critical phenomena in statistical physics — sheep would be able to respond effectively to external disturbances, an advantage that could have been selected by evolution. This study suggests that such behavior could be vital when sheep sense the presence of a predator. It would allow the group to develop a form of “collective intelligence” and circulate information.  Science Daily  Original web page at Science Daily


* New study rewrites genetic history of sheep

At a time when the price of mutton is climbing and wool crashing, a groundbreaking new study has used advanced genetic sequencing technology to rewrite the history of sheep breeding and trading along the ancient Silk Road–insights that can help contemporary herders in developing countries preserve or recover valuable traits crucial to their food and economic security.

The new findings regarding one of the first animals ever domesticated will be published in the October print edition of the journal Molecular Biology and Evolution. They are the product of an unprecedented collaboration involving scientists in China, Iran, Pakistan, Indonesia, Nepal, Finland, and the United Kingdom. The team analyzed the complete mitochondrial DNA of 42 domesticated native sheep breeds from Azerbaijan, Moldova, Serbia, Ukraine, Russia, Kazakhstan, Poland, Finland, China, and the United Kingdom, along with two wild sheep species from Kazakhstan. These data were compared to DNA sequences of 150 breeds from several other countries to complete the most exhaustive maternal genetic analysis of sheep ever undertaken.

The DNA of contemporary sheep can now be read like a historical record, allowing researchers to look back 10,000 years to the time when humans first started herding these animals in the Fertile Crescent of the Middle East.

“What we found is that sheep in Asia are far more genetically diverse than sheep now common in Europe and we can use that diversity to help herders in places like Mongolia and western China who now want to focus on meat rather than wool production,” said Jian-Lin Han, a senior scientist working at the Joint Laboratory on Livestock and Forage Genetic Resources, established in Beijing by the Chinese Academy of Agricultural Sciences (CAAS), and the Nairobi-based International Livestock Research Institute (ILRI). Han and Meng-Hua Li, a molecular geneticist of the Chinese Academy of Sciences (CAS), are the leading corresponding authors of this study.

The scientists found that the rich genetic heritage of Asian sheep is a product of two distinct “migratory waves” of domesticated animals, not one as previously believed. Han said that DNA analysis of thousands of tissue samples of 150 breeds from many countries confirmed previous findings that domesticated sheep first emerged in the Fertile Crescent about 8,000 to 11,000 years ago. And that they then made their way east to what is now China and Mongolia via the Silk Road, a set of trading routes extending some 4,000 miles that has facilitated commerce and human migration between Asia and Europe for thousands of years.

But Han and his colleagues discovered a second migration with evidence that herders in what are now northern China and Mongolia developed their own unique breeds some 5,000 years ago. These animals later made their way back west along the Silk Road, where frequent trading of breeding females, or ewes, allowed them to be mixed in with the progeny of their ancestors to produce yet more distinct breeds. For example, Han said, warriors of the infamous Mongol hordes of Genghis Khan often rode west with live sheep strapped to their horses.

“What this study shows is that the genetic lineages of modern sheep were shaped by thousands of years of trading and breeding moving first west to east and then back, east to west, which created a unique collection of beneficial traits,” said Olivier Hanotte, a livestock geneticist and ILRI collaborator at the University of Nottingham in the United Kingdom. “This is important information for contemporary sheep breeding programs,” he added. “In the world of animal husbandry, to get what you want you first need to know what you have. Until now, we barely knew anything about the genetic makeup of Asian sheep.”

ILRI’s Han said the study lays the foundation for more effective breeding programs that support Asia’s millions of poor livestock herders, many of whom are now seeking breeds of sheep better suited for meat production. Meat animals are now wanted because of a soaring urban demand for meat in developing countries. Mutton prices in China alone have risen more than 40 percent since 2011, presenting new economic opportunities for the country’s poor herding communities. But sheep breeds globally are still dominated by animals developed mainly to produce wool–and prices of wool have dropped steadily since 1996. Furthermore, most breeds raised for meat today are found in Australia and New Zealand, where they dine on relatively expensive feeds and lush pasture grasses.

“The kind of sheep we need in places like Mongolia and western China are animals that are strong and hardy and can cover long distances every day in search of grass,” Han said. “That’s not the kind of animal they’re producing in New Zealand and Australia.

In China today, Han often encounters herders trying on their own to develop more meat-oriented sheep. He said some herders are even experimenting with breeding local sheep with massive wild sheep known as Argali. But that experiment, he says, could bring along undesirable traits as well. New genomic data and genetic markers can guide this effort to enable the inclusion of beneficial traits, he adds.

Han and his colleagues say the next step in their work is to take the information generated from this current study and use it to build a foundation for breeding programs that can efficiently provide herding communities in Asia and sub-Saharan Africa with animals suited to local conditions and preferences.

There have already been strides in the integration of desirable traits in sheep. For example, in Kenya today, ILRI scientists have helped local livestock keepers develop an improved version of an indigenous “hair” sheep long kept by Maasai pastoralists. These red Maasai sheep are among the “climate-smart” solutions being developed to help farmers and herders adapt to climate change in East Africa. The red Maasai sheep better cope with heat stress and disease (they are naturally resistant to intestinal worm infections) and they convert poor forage grasses into meat and milk more efficiently than other breeds.

“In China and many other parts of the world today, a small herd of sheep is a family’s most important asset, providing the family with food, income, clothing, and fertilizer for their crops,” says ILRI’s director general Jimmy Smith. “We need to be doing everything we can to ensure that the animals they raise have the genetic traits that will help the sheep endure and progress and herders benefit from new sources of income, such as the growing mutton market.”

“In coming years and decades, as we face global climate, population, and other changes,” Smith said, “we need to be able to put our hands on the best traits for diverse and changing circumstances. That’s what research like this is giving us. To quote leading genomicist and ILRI collaborator Claire Fraser, ‘Doing biology like this–with knowledge of genomes–is like doing science with the lights turned on.'”  Science Daily  Original web page at Science Daily


Pupil shape linked to animals’ ecological niche

While the eyes may be a window into one’s soul, new research led by scientists at the University of California, Berkeley, suggests that the pupils could also reveal whether one is a hunter or hunted.

An analysis of 214 species of land animals shows that a creature’s ecological niche is a strong predictor of pupil shape. Species with pupils that are vertical slits are more likely to be ambush predators that are active both day and night. In contrast, those with horizontally elongated pupils are extremely likely to be plant-eating prey species with eyes on the sides of their heads. Circular pupils were linked to “active foragers,” or animals that chase down their prey.

The study, led by vision scientist Martin Banks, a UC Berkeley professor of optometry, in collaboration with the United Kingdom’s Durham University, presents a new hypothesis as to why pupils are shaped and oriented the way they are. The findings will be published in the journal Science Advances.

This current research builds upon the foundation set by the late Gordon Walls, a UC Berkeley professor of optometry who published “The Vertebrate Eye and Its Adaptive Radiation” in 1942. The classic text on eye physiology put forward the theory, generally accepted, that slit-shaped pupils allow for different musculature and a greater range in the amount of light entering the eye

For example, the vertical slits of domestic cats and geckos undergo a 135- and 300-fold change in area between constricted and dilated states, while humans’ circular pupils undergo a mere 15-fold change.

“For species that are active both night and day, like domestic cats, slit pupils provide the dynamic range needed to help them see in dim light yet not get blinded by the midday sun,” said Banks. “However, this hypothesis does not explain why slits are either vertical or horizontal. Why don’t we see diagonal slits? This study is the first attempt to explain why orientation matters.”

To explain why horizontally elongated pupils, with few exceptions(are there any explanations for the exceptions?), corresponded to grazing prey animals such as sheep, deer and horses, the researchers turned to computer models to study the effects of different pupil shapes

They found that the horizontal pupils expanded the effective field of view. When stretched horizontally, the pupils are aligned with the ground, getting more light in from the front, back and sides. The orientation also helps limit the amount of dazzling light from the sun above so the animal can see the ground better, the researchers said

“The first key visual requirement for these animals is to detect approaching predators, which usually come from the ground, so they need to see panoramically on the ground with minimal blind spots,” said Banks. “The second critical requirement is that once they do detect a predator, they need to see where they are running. They have to see well enough out of the corner of their eye to run quickly and jump over things.”

But what happens to this orientation when the animal lowers its head to graze? If the pupil follows the pitch of the head, they would become more vertical and the theory falters.

“To check this out, I spent hours at the Oakland Zoo, often surrounded by school kids on field trips, to observe the different animals,” said Banks. “Sure enough, when goats, antelope and other grazing prey animals put their head down to eat, their eyes rotated to maintain the pupils’ horizontal alignment with the ground.

On the other side of the Atlantic, study co-author Gordon Love, a professor of physics at Durham University, found this same pattern when observing sheep and horses at nearby farms. Grazing animals’ eyes can rotate by 50 degrees or more in each eye, a range 10 times greater than human eyes, the researchers said

For ambush predators with vertical-slit pupils, the authors noted the importance of accurately gauging the distance animals would need to pounce on their prey. Researchers identified three cues generally used to gauge distance: stereopsis, or binocular disparity; motion parallax, in which closer objects move farther and faster across our field of vision; and blur, in which objects at different distances are out of focus.

The researchers ruled out motion parallax as a factor since using that cue would require head movement that could reveal the predator’s position. The remaining two cues, binocular disparity and blur, work together with vertically elongated pupils and front-facing eyes, the researchers said.

Binocular vision works better at judging differences when contours are vertical and objects are at a distance, while blur comes into play for horizontal contours and near-field targets. Vertical-slit pupils maximize both cues, the researchers said. Vertical pupils are not equally distributed among ambush predators, however.

“A surprising thing we noticed from this study is that the slit pupils were linked to predators that were close to the ground,” said William Sprague, a postdoctoral researcher in Banks’ lab. “So domestic cats have vertical slits, but bigger cats, like tigers and lions, don’t. Their pupils are round, like humans and dogs.

Among the 65 frontal-eyed, ambush predators in this study, 44 had vertical pupils, and 82 percent of them had shoulder heights that were less than 42 centimeters (16.5 inches). Vertical pupils appear to maximize the ability of small animals to judge distances of prey.

The authors explained this by calculating that depth-of-field cues based upon blur are more effective for estimating distances for short animals than tall ones.

“We are learning all the time just how remarkable the eye and vision are,” said Love. “This work is another piece in the jigsaw puzzle of understanding how eyes work.” The authors noted that this research focused on terrestrial species. They expect to examine associations of aquatic, aerial and arboreal life on eye position and pupil shape in

future studies.  Science Daily  Original web page at Science Daily


* Race to stamp out animal plague begins

Goats and sheep are sold frequently, which could challenge the vaccination effort against peste des petits ruminants. Humanity wiped out smallpox in 1980 and the cattle virus rinderpest in 2011. Polio stands on the brink of eradication, with just 21 cases recorded this year worldwide. Now, health officials have launched a global effort to vanquish yet another disease — a sheep- and goat-killer that is little known in rich countries, but creates economic ruin for the world’s poorest people. A conference hosted by the United Nations in Abidjan, Côte d’Ivoire, from 31 March to 2 April, marked the roll out of a global campaign to eradicate by 2030 the sheep and goat virus, which is known as PPR — an abbreviation of its French name, peste des petits ruminants. PPR eradication is technically feasible, say animal-health specialists, but it is uncertain where the effort’s organization and billions of dollars of necessary funding will come from. “This is an exercise in persuading the world community and funders that this work could and should be done,” says Jeffrey Mariner, an epidemiologist at Tufts University veterinary school in North Grafton, Massachusetts, who attended the meeting.

PPR is related to measles and rinderpest, which once threatened the livelihoods of cattle herders, especially those in Africa. Causing high fever, diarrhoea and lesions in the mouths of sheep and goats, PPR is highly infectious and kills 30–70% of the animals it infects. It is endemic across northern, central and west Africa and south Asia, and it has more recently taken hold in China and Turkey. The UN puts the economic costs of PPR at between US$1.5 billion and $2.1 billion per year, a burden borne by some of the world’s poorest people, who rely on sheep and goats for food and income. “Sheep and goats are the cattle of the poor, and they are the bank for the poor,” says Bernard Vallat, director-general of World Organisation for Animal Health (OIE) in Paris, which co-hosted the meeting. Nature Original web page at Nature


* Close relationship of ruminant pestiviruses and classical swine fever virus

To determine why serum from small ruminants infected with ruminant pestiviruses reacted positively to classical swine fever virus (CSFV)–specific diagnostic tests, we analyzed 2 pestiviruses from Turkey. They differed genetically and antigenically from known Pestivirus species and were closely related to CSFV. Cross-reactions would interfere with classical swine fever diagnosis in pigs.

Pestiviruses are enveloped viruses within the family Flaviviridae that have a highly variable single-stranded positive-sense RNA genome of ≈12.3 kb. The genus Pestivirus comprises the established species bovine viral diarrhea virus (BVDV)–1, BVDV-2, border disease virus (BDV), and classical swine fever virus (CSFV), as well as a growing number of additional tentative Pestivirus species. CSFV is the causative agent for classical swine fever, which is notifiable to the World Organisation of Animal Health because it is highly contagious and can cause great loss of pigs. For a given country, CSFV-positive status severely diminishes international trade of pigs and pig products. Accordingly, because of cross-reacting antibodies, infections of pigs (nonruminants) with ruminant pestiviruses, which occasionally occur under natural conditions, can cause serious problems with regard to serologic diagnosis of classical swine fever.

In Turkey, 2 pestiviruses, Aydin/04 and Burdur/05, have been isolated from a sheep and a goat with clinical signs of border disease. A detailed genetic and antigenic characterization revealed that these 2 isolates must be regarded as representatives of a new Pestivirus species that is closely related to CSFV and can cause serious diagnostic problems in established CSFV serology. During 2004–2007, serum samples from 1,036 sheep and goats in Turkey were serologically screened for infection with pestiviruses of small ruminants. Of these, 11 serum samples from 7 sheep herds gave positive or doubtful reactions in the CSFV antibody–specific ELISA (HerdChek, IDEXX) and were subjected to commonly used virus neutralization testing (VNT). VNT against the 2 established CSFV strains Alfort187 (genotype 1.1) and Diepholz (genotype 2.3) and against the BDV strains Moredun (genotype 1) and Gifhorn (genotype 3) revealed higher BDV titers in only 3 serum samples. Equal or slightly higher titers against the CSFV reference strains became evident in 8 of the 11 serum samples, which came from 5 regions of Turkey. Further VNT analyses with the 2 previously obtained isolates, Aydin/04 and Burdur/05, demonstrated neutralizing antibody titers that were equal or higher than those against BDV and CSFV test strains. To elucidate the reason for strong serologic reactivity in CSFV assays, we genetically and antigenically characterized pestiviruses Aydin/04 and Burdur/05.

The complete genome sequence of Aydin/04 was determined as reported previously. The genome sequence of Burdur/05 was determined by next-generation sequencing on an Illumina MiSeq platform (2 × 250-bp paired end run, 593,328 reads) as recently described. Template total cellular RNA was extracted from supernatant of sheep fetal thymus cells. Of all reads, 73.9% were found to be of host origin. Of the nonhost reads, 89.9% assembled into a single sequence contig encompassing the entire pestivirus Burdur/05 genome (coverage 196-fold).

Read more:  Emerging Infectious Diseases  Original web page at Emerging Infectious Diseases


Developing vaccines for insect-borne viruses

Vaccines developed using proteins rather than live viruses can help protect animals and subsequently humans from insect-borne viruses, according to Alan Young, chief scientific officer for Medgene Labs, an animal health company that develops therapeutics and diagnostics, including vaccines. “Platform technologies — that is where our niche is,” said Young, who is also a veterinary science professor at South Dakota State University. Medgene uses advances in molecular biology and technologies licensed from the university.

The company’s initial vaccine formulation targets Rift Valley Fever, found in Africa and the Arabian Peninsula. The viral disease is particularly devastating to sheep, with a mortality rate of 90 percent in lambs and 10 percent in adult sheep. The virus affects cattle, camels and goats similarly, but to a lesser extent. It can be spread to humans in the same manner as animals — through the bite of an infected mosquito. Of the vaccines available, the one produced from a live virus can result in spontaneous abortions in pregnant ewes and the one from an inactivated virus does not provide long-term immunity, according to the Centers for Disease Control and Prevention. Medgene is developing a vaccine to alleviate both problems. Four ewes in an experimental group lambed after being vaccinated, according to director of lab operations, Jessica Zweibahmer. The next step will be to test the lambs for antibodies to see if the immunity crossed over from mother to fetus. Young explained that using proteins rather than live agents to produce an immune reaction significantly reduces the chance of side effects. That makes Medgene’s vaccines both safe and effective.

“We approach vaccine targets from a virus family perspective,” Young said. For instance, what works for Rift Valley Fever can then be applied to Heartland virus, which is in the same family, and a vaccine for Porcine Epidemic Diarrhea virus can be expanded to Porcine Delta Coronavirus. Recent changes in the way regulatory agencies license vaccines could reduce the path to licensing a vaccine to as little as 12 months, according to Young. “We have a well-developed expression technology to produce these proteins,” Young said. “Inserting a different section in the sequence will allow us to produce a new vaccine more quickly.” Young credits company co-founder South Dakota Innovation Partners for providing the support his business needs. Partnership agreements secured by SDIP provide a pathway for worldwide distribution. Science Daily Original web page at Science Daily


* Scrapie could breach the species barrier

INRA scientists have shown for the first time that the pathogens responsible for scrapie in small ruminants (prions) have the potential to convert the human prion protein from a healthy state to a pathological state. In mice models reproducing the human species barrier, this prion induces a disease similar to Creutzfeldt-Jakob disease. These primary results published in Nature Communications on 16 December 2014, stress the necessity to reassess the transmission of this disease to humans. Scrapie is a neurodegenerative disease that has been known for centuries and which affects sheep and goats. Similar to Bovine Spongiform Encephalopathy (BSE) or mad cow disease, scrapie is caused by a transmissible pathogen protein called prion. However, and contrary to BSE, epidemiological studies have never been able to establish a link between this disease and the occurrence of prion diseases in humans. “Risks of transmitting scrapie to humans (zoonose) were hitherto considered negligible because of the species barrier that naturally prevents prion propagation between species,” said Olivier Andreoletti, INRA scientist who led the present study. Researchers at INRA studied the permeability of the human transmission barrier to pathogens responsible for scrapie, using animal models specifically developed for this purpose. This approach previously allowed the confirmation of the zoonotic nature of prions responsible for BSE in cows and of the variant of Creutzfeldt-Jakob disease in humans (vCJD). Unexpectedly, in these rodent models, certain pathogens responsible for scrapie were able to cross the transmission barrier. Moreover, the pathogens that propagated through this barrier were undistinguishable from the prions causing the sporadic form of Creutzfeldt-Jakob disease (sCJD). This data suggest a potential link between the occurrence of certain sCJD and these animal prions. “Since CJD is scarce, about 1 case per million and per year, and incubation periods are usually long -several decades- it is extremely difficult for epidemiological studies to try and make this link,” explains Olivier Andreoletti. In their conclusions, the authors stress the fact that CJD cases are rare though scrapie has been circulating for centuries in small ruminants for which we eat the meat. Even if in future studies scrapie is finally confirmed to have a zoonotic potential, the authors consider that this disease does not constitute a new major risk for public health.  Science Daily  Original web page at Science Daily


Wild sheep show benefits of putting up with parasites

In the first evidence that natural selection favors an individual’s infection tolerance, researchers from PrincetonUniversity and the University of Edinburgh have found that an animal’s ability to endure an internal parasite strongly influences its reproductive success. Reported in the journal PLoS Biology, the finding could provide the groundwork for boosting the resilience of humans and livestock to infection. The researchers used 25 years of data on a population of wild sheep living on an island in northwest Scotland to assess the evolutionary importance of infection tolerance. They first examined the relationship between each sheep’s body weight and its level of infection with nematodes, tiny parasitic worms that thrive in the gastrointestinal tract of sheep. The level of infection was determined by the number of nematode eggs per gram of the animal’s feces. While all of the animals lost weight as a result of nematode infection, the degree of weight loss varied widely: an adult female sheep with the maximum egg count of 2,000 eggs per gram of feces might lose as little as 2 percent or as much as 20 percent of her body weight. The researchers then tracked the number of offspring produced by each of nearly 2,500 sheep and found that sheep with the highest tolerance to nematode infection produced the most offspring, while sheep with lower parasite tolerance left fewer descendants. To measure individual differences in parasite tolerance, the researchers used statistical methods that could be extended to studies of disease epidemiology in humans, said senior author Andrea Graham, an assistant professor of ecology and evolutionary biology at Princeton. Medical researchers have long understood that people with similar levels of parasite infection can experience very different symptoms. But biologists are just beginning to appreciate the evolutionary importance of this individual variation. “For a long time, people assumed that if you knew an individual’s parasite burden, you could perfectly predict its health and survival prospects,” Graham said. “More recently, evolutionary biologists have come to realize that’s not the case, and so have developed statistical tools to measure variation among hosts in the fitness consequences of infection.”

Graham and her colleagues used the wealth of information collected over many years on the Soay sheep living on the island of Hirta, about 100 miles west of the Scottish mainland. These sheep provide a unique opportunity to study the effects of parasites, weather, vegetation changes and other factors on a population of wild animals. Brought to the island by people about 4,000 years ago, the sheep have run wild since the last permanent human inhabitants left Hirta in 1930. By keeping a detailed pedigree, the researchers of the St Kilda Soay Sheep Project can trace any individual’s ancestry back to the beginning of the project in 1985, and, conversely, can count the number of descendants left by each individual. Nematodes puncture an animal’s gut and can impede the absorption of nutrients. Therefore, tolerance to nematode infection could result from an ability to make up for the lost nutrition, or from the ability to repair damage the parasites cause to the gut, Graham said. “This island is way out in the North Atlantic, where the sun doesn’t shine much,” she said. “So tolerant individuals might be the ones who are better able to compete for food or better able to assimilate protein and other useful nutrients from the limited forage.” Tolerant animals might invest energy in gut repair, but would then be expected to incur costs. Graham and her colleagues identified a similar evolutionary tradeoff in a 2010 study that compared immune-response levels and reproductive success in female Soay sheep. They found that animals with strong antibody responses produced fewer offspring each year, but also lived longer. The team has not yet been able to detect costs of parasite tolerance in the sheep, but such costs could help explain variation in tolerance if the most tolerant animals were at a disadvantage under particular conditions. While the PLoS Biology findings provide strong evidence that natural selection favors infection tolerance, they do raise questions, such as how the tolerance is generated, and why variation might persist from one generation to the next despite the reproductive advantage of tolerance, Graham said. The data in this study did not permit the researchers to detect a genetic component to tolerance. If genetics do play a role, she suspects multiple genes may interact with environmental factors to determine tolerance; ongoing research will help to tease apart these possibilities. Understanding the genetic underpinnings of nematode tolerance could someday guide efforts to boost tolerance in livestock by identifying and selectively breeding those animals that exhibit a heightened parasite tolerance, said David Schneider, an associate professor of microbiology and immunology at Stanford University.

“This study shows that parasite tolerance can have a profound effect on animal health and breeding success,” said Schneider, who is familiar with the work but was not involved in it. “In the long term, this suggests that it could be profitable to invest in breeding tolerant livestock.” In humans and domesticated animals, intestinal parasites are becoming increasingly resistant to the drugs used to treat infections, Graham said. If the availability of nutrients, even just during the first few months of life, impacts lifelong parasite tolerance, simple nutritional supplements could be an effective way to promote tolerance in people. About 2 billion people are persistently infected with intestinal nematode parasites worldwide, mostly in developing nations. Children are especially vulnerable to the worms’ effects, which include anemia, stunted growth and cognitive difficulties. “Ideally, we would clear the worms from the bellies of the kids who have those heavy burdens,” Graham said. “But if we could also understand how to ameliorate the health consequences and thus promote tolerance of nematodes, that could be a very powerful tool.”  Science Daily  Original web page at Science Daily


* Gene study shows how sheep first separated from goats

Scientists have cracked the genetic code of sheep to reveal how they became a distinct species from goats around four million years ago. The study is the first to pinpoint the genetic differences that make sheep different from other animals. The findings could aid the development of DNA testing to speed-up selective breeding programmes, helping farmers to improve their stocks. The research identifies the genes that give sheep their fleece and uncovers features of their digestive system, which makes them so well-suited to a diet of low quality grass and other plants. It also builds the most complete picture yet of sheep’s complex biology. Further studies using this resource could reveal new insights to diseases that affect sheep. Researchers from the University of Edinburgh’s Roslin Institute, which receives strategic funding from the Biotechnology and Biological Sciences Research Council, were part of a global team that has decoded the genome sequence — the entire genetic make-up — of domestic sheep for the first time. This team — the International Sheep Genomics Consortium — compared the sheep’s genes with those of other animals — including humans, cattle, goats and pigs. The analysis identifies several genes that are associated with wool production. It also reveals genes that underpin the evolution of the rumen — a specialised chamber of the stomach that breaks down plant material to make it ready for digestion. This collaborative study, involving 26 research institutions in eight different countries, was led by researchers from the Commonwealth Scientific and Industrial Research Organisation, Australia; BGI and the Kunming Institute of Zoology, China; Utah State University and Baylor College of Medicine in the US; and The Roslin Institute. The BBSRC-funded ARK-Genomics facility — which is part of Edinburgh Genomics at the University of Edinburgh — provided a substantial body of sequence data, including information on which genes are expressed in a spectrum of 40 different tissues. The study is published today in the journal Science.  Science Daily

July 8, 2014  Original web page at Science Daily



Goats are far more clever than previously thought, and have an excellent memory

This sequence shows how the goats needed to learn how to retrieve food from a box. They used a linked sequence of steps; first by pulling a lever with their mouths and then by lifting it to release the reward. Goats learn how to solve complicated tasks quickly and can recall how to perform them for at least 10 months, which might explain their remarkable ability to adapt to harsh environments, say researchers at Queen Mary University of London. Writing in the journal Frontiers in Zoology (26 March), the scientists trained a group of goats to retrieve food from a box using a linked sequence of steps; first by pulling a lever with their mouths and then by lifting it to release the reward. The goats’ ability to remember the task was tested after one month and again at 10 months. They learned the task within 12 trials and took less than two minutes to remember the challenge. “The speed at which the goats completed the task at 10 months compared to how long it took them to learn indicates excellent long-term memory,” said co-author Dr Elodie Briefer, now based at ETH Zurich. Before each learning session, some of the goats had the opportunity to watch another goat to demonstrate the task. Dr Briefer added: “We found that those without a demonstrator were just as fast at learning as those that had seen demonstrations. This shows that goats prefer to learn on their own rather than by watching others.” This is the first time that scientists have investigated how goats learn complex physical cognition tasks, which could explain why they are so adaptable to harsh environments and good at foraging for plants in the wild, for example.  Science Daily

April 15, 2014  Original web page at Science Daily


Male scent stimulates female goats’ fertility

The distinctive aroma of goats does more than just make barnyards extra fragrant. Male goats can use their heady scent to make female goats ovulate simply by being near them. Researchers had ascribed this ‘male effect’ to chemicals known as primer pheromones — a chemical signal that can cause long-lasting physiological responses in the recipient. Examples of primer pheromones are rare in mammals; the male effect in goats and sheep, and a similar effect in mice and rats, where the presence of males can speed up puberty in females, are the only known cases. But exactly what substances are at work and how has remained a mystery. Now, reproductive biologist Yukari Takeuchi from the University of Tokyo and her colleagues have identified a single molecule, known as 4-ethyloctanal, in the cocktail of male goat pheromones that activates the neural pathway that regulates reproduction in females. ”It has long been thought that pheromones have pivotal roles in reproductive success in mammals, but the mechanisms are scarcely known,” says Takeuchi. The researchers found that male goat pheromones are generally synthesized in the animal’s head skin, so they designed a hat containing a material that captured their odorous molecules and placed them on the goats for a week to collect the scent.

Analysis of the gases collected identified a range of compounds, many of which were unknown and were not present in castrated males. When exposed to a cocktail of 18 of these chemicals, the brains of female goats showed a sudden increase in the activity of the gonadotropin-releasing hormone (GnRH) pulse generator — the neural regulator of reproduction. But one molecule stood out: 4-ethyloctanal, a chemical not previously found in nature and that has an orangy, floral odour. When presented to the female goats on its own, the chemical elicited a similar, albeit weaker, response, and the cocktail showed less of an effect when that ingredient was removed. None of the other chemicals appeared to have a statistically significant effect. The work is published today in Current Biology. Peter Brennan, a physiologist at the University of Bristol, UK, says that the work will be useful in husbandry in goats and other ruminants, such as sheep, but he is not sure that the whole effect can be ascribed to the pheromones alone. “How much of this effect is innate and how much is learned?” he asks. Takeuchi admits that she cannot be sure, but she thinks it is an innate reaction, because it was seen irrespective of the mating experience of the female goats. The main benefit of the work, says Takeuchi, is that it could be used to develop new, more-natural technologies that improve the efficiency of breeding and to treat reproductive disorders. “To control reproductive problems, it is important to regulate not only inhibitory factors such as infection or stress, but also accelerative factors such as pheromones,” she says. The group is now looking to find similar pheromones and pathways in other economically important livestock animals, such as sheep and cows.  Nature

March 18, 2014  Original web page at Nature


New vaccine against lung diseases in goats and sheep

An intranasal spray was developed using local isolated bacterium in Malaysia and it was found to provide better protection against infections by Mannheimia haemolytica bacterium than imported vaccines. Universiti Putra Malaysia has launched a new vaccine against lung or pneumonic diseases in goats and sheep that was developed and patented by its scientists. The soft launch of “STVac7,” the first intranasal spray vaccine for goats and sheep, was officiated by the Deputy Minister of Science, Technology and Innovation, Datuk Dr Abu Bakar Mohamad Diah, in a brief ceremony on 24 Oct., 2013. The vaccine was developed and tested from 1998 to 2005 by UPM scientists led by Prof Dr Mohd Zamri Saad of the Faculty of Veterinary Medicine. The other scientist involved is Dr Md. Sabri Mohd Yusoff. The patent for the STVac7 vaccine has been commercialised to Fed Tech Sdn Bhd, for RM4 million and the company has appointed Bio-Angle Vacs Sdn Bhd to manage the production and marketing of the vaccine, said the Vice Chancellor of UPM, Prof Datuk Dr Mohd Fauzi Hj Ramlan, when speaking at the ceremony. He said he is confident that the vaccine could penetrate the local and foreign market, since in Malaysia alone, there were more than 600,000 goats and sheep at present and the figure is expected to increase to 1 million by 2015, a growth rate of 12.1% as projected by the Veterinary Services Department.

The company’s collaboration with UPM would ensure that it would produce the STVac7 vaccines under Good Manufacturing Practices (GMP) since it would be using the facilities at FTU.GMP@Biotech (or FTU), a service centre under the Faculty of Biotechnology and Biomolecular Science of UPM. Dr Fauzi said FTU which was established in 1999 is now equipped with the facilities for upstream and downstream production of biotechnological products, including packaging and bottling. The FTU services centre which cost RM14 million to develop, is now serving a horde of local companies like Malaysia Agriculture HighTech, Stella Gen, Johor BioMicrobe, Pascal Biotech, MVP, One Biotech for the development and production of their biotechnology products. He said Bio-Angle Vacs Sdn Bhd and FTU were currently developing the standard operating procedure (SOP) for the mass production of the STVAC 7 vaccine using the GMP facilities of the service centre as well as product registration before marketing. “Actual production for the commercialisation of the product with the GMP certification will begin in July 2014 using the Original Equipment Concept,” Dr Fauzi said.

Meanwhile, replying to questions, Prof Dr Zamri said the STVac7 is a vaccine against mannheimiosis or respiratory diseases of goats and sheep caused by bacteria. It was developed and produced using sophisticated recombinant technology which, unlike the imported vaccines, has been demonstrated to provide protection against bacterium infection in the small ruminants like goats and sheep. “The current available vaccines against this disease are imported vaccines prepared using foreign strains. They are given via intramuscular injections. The vaccines were found to be ineffective and expensive. “Therefore, STVac7 was developed using local isolated bacterium that was found to be able to provide protection against infections by Mannheimia haemolytica bacterium A2, A7 and A9. This was proven to be better protection,” said Prof Zamri who graduated with his Doctor of Veterinary Medicine degree from UPM before obtaining his PhD from Liverpool. “The product is cheap and effective. If used according to the suggested protocol, it can reduce mortality due to this disease by more than 90%,” he added. Prof Zamri said the pneumonic diseases brought about by the bacterium usually caused a mortality rate of 30% during the rainy season and the goats and sheep farmers could benefit from the STVac7. “The product itself is ready for the market since laboratory and field tests have been completed,” he said, adding that they started their research in 1998 which ended in 2005.

Science Daily
December 10, 2013

Original web page at Science Daily


Ticks kill sheep

In some lamb herds, a mortality rate of 30 percent has been recorded, albeit, no predators have been involved in these losses. The situation is so serious that the sheep industry could be under threat. It is therefore crucial to identify the causes and implement preventative measures. The answer may be found somewhere within the genetics of the sheep and the course of the disease, assessment and control of tick populations and biological control of ticks. Tick-bites in sheep may result in the disease tick-borne fever (TBF), induced by the bacterium Anaplasma phagocytophilum ( TBF causes high fever and weakens the immune system. “It is estimated that approximately 300,000 lambs are exposed to this bacteria each year. However, they do not necessarily die from the infection,” says tick researcher Lise Grøva at Bioforsk Organic at Tingvoll in Norway. The disease itself is not fatal, but makes sheep more susceptible to secondary infections.” Arthritis is the most common disease that can arise. Illness normally occurs 10-14 days after grazing starts. Blood tests show that almost all the lambs are infected during the season in tick infested areas.”

The direct cause of death due to TBF is often an acute Pasteurella infection — a bacterial disease which can cause acute blood poisoning with inflammation of the heart sac, heart, lungs or digestive organs. It is therefore recommended to vaccinate sheep against Pastuerella in areas where tick-borne fever is prevalent. Disinfection of the umbilical cord in lambs immediately after birth has also been effective. It prevents new bacteria from entering the bloodstream. Bacteria can survive in the body for a long time and can attack and cause disease if the immune system is weakened. There are no exact figures as to how many lives ticks take compared to predators. There have been attempts to uncover this by using radio transmitters to monitor the sheep. However, in practice, it has proved difficult to find the mortalities in order to say anything about the cause of death with this type of monitoring. Work is currently in progress to develop measures that may help sheep tolerate tick bites better. Breeding resistant animals is one important research area. “We know that individuals respond differently to infection. Some lambs experience a shorter period of fever and a shorter period with poor immune system after an infection than others. We are also looking at whether some individuals have more ticks than others, and whether this has an influence on the growth in lambs,” says Grøva.

She emphasizes that having robust animals with good immune systems is a prerequisite for sheep husbandry in tick areas. There is also an on-going study that looks at the effects of long acting acaricides against ticks. “The usage of acaricides against ticks is widespread, but we question whether it is right to utilise them as it is seems that lambs are infected despite the use of such remedies.” The bacteria can also infect humans through tick bites. However, there is little knowledge of the occurrence and the consequences of this. “It is presumed that the infection can cause flu-like conditions. In people with impaired immune systems an infection can cause pneumonia, but as far as we know nobody has died from this,” says Grøva. Sick sheep are not slaughtered. Some sheep can be healthy carriers, where the meat is considered safe. The bacterium is not absorbed through the gut, and it will not survive freezing treatment or boiling. Grøva says it is possible that the research on sheep and ticks could benefit humans. Bioforsk is also attempting to determine if fungal spores can have impact on tick populations. “This could contribute in helping us control tick populations, for example in restricted areas such as spring pasture for sheep. This could also be of interest as far as recreational areas are concerned.”

Science Daily
November 26, 2013

Original web page at Science Daily


Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein

Public and animal health controls to limit human exposure to animal prions are focused on bovine spongiform encephalopathy (BSE), but other prion strains in ruminants may also have zoonotic potential. One example is atypical/Nor98 scrapie, which evaded statutory diagnostic methods worldwide until the early 2000s. To investigate whether sheep infected with scrapie prions could be another source of infection, we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of classical and atypical scrapie, sheep with experimental BSE, and cattle with BSE. We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods when mice were inoculated with classical or atypical scrapie prions. These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to naturally occurring prions of sheep than after exposure to epizootic BSE prions of ruminants.

Emerging Infectious Diseases
November 12, 2013

Original web page at Emerging Infectious Diseases


Big horns clash with longevity in sheep

Gene for small horns lowers sexual fitness but boosts lifespan. Soay sheep have greatest sexual fitness when they have two versions of a gene that determines horn size Red 78 — a ram with horns like elephant tusks — sired 95 lambs before he died at the ripe (for a ram) old age of nine. A gene with a role in horn growth explains his fertility and his longevity, finds a study of sheep on a remote Scottish isle. The work also explains how variation can persist in traits that offer big reproductive boosts. Ample horns are a ram’s ticket to reproductive success. During the breeding season, males fight for access to females, and those with the largest horns win. But if big horns are a sexual asset, the genes underlying the trait should have become ubiquitous, says Susan Johnston, an evolutionary biologist at the University of Edinburgh, UK, who led the research. Yet some male sheep have short horns or none at all. “From an evolutionary perspective, it doesn’t really make sense,” Johnston says. Johnston’s team turned to the sheep living on Hirta, an island 160 kilometres west of the Scottish mainland. The animals, a primitive breed called Soay (Ovis aries), are known for their diminutive size and their agility on cliffs. Two years ago, Johnston’s group reported that a single gene, RXFP2, explains horn variability in the sheep (S. E. Johnston et al. Mol. Ecol. 20, 2555–2566; 2011). One version of the gene, Ho+, is linked to large horns; another allele, HoP, is associated with small ones.

In the latest study, published in Nature, Johnston’s team related the RXFP2 genes of 1,750 sheep to three factors: horn size, reproductive success and lifespan (S. E. Johnston et al. Nature; 2013). Males with one or two copies of the Ho+ allele had the biggest horns. They fathered twice as many lambs as those with two copies of the short-horned allele, averaging 3 (versus 1.6) each year, says Johnston. But where lifespan was concerned, rams with two copies of HoP had an edge, she says, with a 75% chance per year of surviving the harsh Hirta winter, compared with a 61% chance for those with two long-horned alleles. The scientists found that rams with one version of each allele (heterozygotes) had the best of everything: they were big-horned, fecund and long-lived. And this explains why short-horned rams persist. “I’m just impressed by the simple elegance of this story,” says Hopi Hoekstra, an evolutionary geneticist at Harvard University in Cambridge, Massachusetts. Johnston says that to learn more, scientists will need to study the gene: in humans and mice, it is involved in sexual development and bone density. She adds that heterozygotes such as Alpha Red 78 end up with more offspring largely because they outlive homozygous big-horned males, which tend to die young.

September 3, 2013

Original web page at Nature


Schmallenberg virus among female lambs, Belgium, 2012

Reemergence of Schmallenberg virus (SBV) occurred among lambs (n = 50) in a sheep flock in Belgium between mid-July and mid-October 2012. Bimonthly assessment by quantitative reverse transcription PCR and seroneutralization demonstrated that 100% of lambs were infected. Viremia duration may be longer in naturally infected than in experimentally infected animals. During late summer and fall 2011, a nonspecific febrile syndrome characterized by hyperthermia, decreased milk production, and diarrhea occurred among lactating cows in Germany. A new virus, named Schmallenberg virus (SBV), was identified as the cause. This arbovirus of the genus Orthobunyavirus, family Bunyaviridae, affects domestic and wild ruminants and has been documented in Western European countries since 2011. The most notable consequences of this new pathogen are caused by its ability to cross the placental barrier. Depending on the gestational age of the offspring, abortion, stillbirth, or severe congenital malformations, including arthrogryposis and defects of central nervous system, might occur. Transplacental infection of offspring that occurred during 2011 led to economic losses in animal husbandry of sheep, goats, and cattle during birthing periods occurring during November 2011 through spring 2012.

Several vectors of SBV have been identified. Biting midges, small flying insects of the species Culicoides, were vectors for serotype 8 of bluetongue virus that emerged during 2006 in Europe, and they seem to play a key role in spreading SBV. Similar to distribution of serotype 8 of bluetongue virus in 2007, SBV circulation occurred during 2012 in regions where viral circulation was limited or not yet detected in 2011. However, few investigations of acute viral circulation in regions where most of the ruminant livestock were infected during 2011 have been performed. The high in-flock seroprevalence ranging from 70–100% in regions documenting SBV outbreaks (i.e., North Rhine-Westphalia in Germany, the Eastern part of Belgium, and the southern part of the Netherlands) is believed to limit reemergence of SBV. The objective of this study was to assess whether SBV reemergence occurred in a sheep flock that had experienced an SBV infection outbreak during autumn 2011 and reached a seroconversion rate of 99.5%. Female lambs born in late autumn 2011 or early winter 2012 were followed bimonthly to assess natural SBV primary infection by using quantitative reverse transcription PCR (RT-qPCR) and seroneutralization (SN).

Emerging Infectious Diseases
July 9, 2013

Original web page
at Emerging Infectious Diseases


Potential new target to thwart antibiotic resistance: Viruses in gut confer antibiotic resistance to bacteria

Bacteria in the gut that are under attack by antibiotics have allies no one had anticipated, a team of Wyss Institute scientists has found. Gut viruses that usually commandeer the bacteria, it turns out, enable them to survive the antibiotic onslaught, most likely by handing them genes that help them withstand the drug. What’s more, the gut viruses, called bacteriophage or simply phage, deliver genes that help the bacteria to survive not just the antibiotic they’ve been exposed to, but other types of antibiotics as well, the scientists reported online June 9 in Nature. That suggests that phages in the gut may be partly responsible for the emergence of dangerous superbugs that withstand multiple antibiotics, and that drug targeting of phages could offer a potential new path to mitigate development of antibiotic resistance. “The results mean that the antibiotic-resistance situation is even more troubling than we thought,” said senior author Jim Collins, Ph.D., a pioneer of synthetic biology and Core Faculty member at the Wyss Institute for Biologically Inspired Engineering, who is also the William F. Warren Distinguished Professor at Boston University, where he leads the Center of Synthetic Biology.

Today disease-causing bacteria have adapted to antibiotics faster than scientists can generate new drugs to kill them, creating a serious global public-health threat. Patients who are hospitalized with serious bacterial infections tend to have longer, more expensive hospital stays, and they are twice as likely to die as those infected with antibiotic-susceptible bacteria, according to the World Health Organization. In addition, because first-line drugs fail more often than before, more expensive therapies must be used, raising health-care costs. In the past, Collins and other scientists have probed the ways gut bacteria adapt to antibiotics, but they’ve focused on the bacteria themselves. But Collins and Sheetal Modi, Ph.D., the lead author of the study and a postdoctoral fellow in Collins’ laboratory and at the Wyss Institute, knew that phage were also abundant in the gut, and that they were adept at ferrying genes from one bacterium to another. The researchers wondered whether treating mice with antibiotics led phage in the gut to pick up more drug-resistance genes, and if so, whether that made gut bacteria stronger. They gave mice either ciprofloxacin or ampicillin — two commonly prescribed antibiotics. After eight weeks, they harvested all the viruses in the mice’s feces, and identified the viral genes present by comparing them with a large database of known genes. They found that the phages from antibiotic-treated mice carried significantly higher numbers of bacterial drug-resistance genes than they would have carried by chance. What’s more, phage from ampicillin-treated mice carried more genes that help bacteria fight off ampicillin and related penicillin-like drugs, while phage from ciprofloxacin-treated mice carried more genes that help them fight off ciprofloxacin and related drugs. “When we treat mice with certain classes of drugs, we see enrichment of resistance genes to those drug classes,” Modi said. The phage did more than harbor drug-resistance genes. They could also transfer them back to gut bacteria — a necessary step in conferring drug resistance. The researchers demonstrated this by isolating phage from either antibiotic-treated mice or untreated mice, then adding those phage to gut bacteria from untreated mice.

Phage from ampicillin-treated mice tripled the amount of ampicillin resistance, while phage from ciprofloxacin-treated mice doubled the amount of ciprofloxacin resistance. That was bad enough, but the scientists also found signs that the phage could do yet more to foster antibiotic resistance. That’s because gut phage from mice treated with one drug carried high levels of genes that confer resistance to different drugs, which means that the phage could serve as backup when bacteria must find ways to withstand a variety of antibiotics. “With antibiotic treatment, the microbiome has a means to protect itself by expanding the antibiotic resistance reservoir, enabling bugs to come back to be potentially stronger and more resistant than before,” Collins said. “Antibiotic resistance is as pressing a global health problem as they come, and to fight it, it’s critical to understand it,” said Don Ingber, M.D., Ph.D., Wyss Institute Founding Director. “Jim’s novel findings offer a previously unknown way to approach this problem — by targeting the phage that live in our intestine, rather than the pathogens themselves.”

Science Daily
June 25, 2013

Original web page at Science Daily


Schmallenberg virus genome engineered to understand how to reduce disease caused by the virus

Scientists engineer the Schmallenberg virus genome to understand how to reduce disease caused by the virus. Researchers from the MRC Centre for Virus Research at the University of Glasgow in Scotland have developed methods to synthesize and change the genome of Schmallenberg virus (SBV). SBV is a recently discovered pathogen of livestock such as cattle, sheep and goats. The researchers have laid bare important ways by which this virus causes disease. The full report about the study publishes on January 10 in the Open Access journal, PLOS Pathogens. SBV is of great concern because it causes stillbirths, abortions and fetal defects in pregnant cows and ewes. It has spread rapidly throughout Europe since its discovery in Germany less than eighteen months ago (in October 2011).

The new study describes researchers’ use of molecular biological methods to design and assemble the viral “genome” completely in a test tube in a form that can be easily introduced and replicated in cultured cells. From these cells the researchers recovered virus with identical infection properties to the “natural” SBV. This approach, known as ‘reverse genetics’, allowed them to control the viral genome and identify a gene (called NSs) involved in protecting the virus against the immune response of infected animals. The researchers made viruses missing the NSs gene and found they made mice in the laboratory less sick than viruses containing the NSs gene. The researchers also discovered that SBV rapidly grows in the brain and spinal cord of aborted lambs and calves. The virus prefers to infect cells called neurons, which explains why it infects and damages the brain. This also results in muscular defects such as abnormally flexed legs often seen in stillborn animals when virus is transmitted from an SBV infected mother to the calves or lambs in the uterus during pregnancy. Scottish researchers, led by Massimo Palmarini and Alain Kohl, suggest that the ability to engineer and control the SBV genome will allow the future development of new vaccines for this virus that is of great concern to European farmers.

Science Daily
February 5, 2013

Original web page at Science Daily


First goat genome sets a good example for facilitating de novo assembly of large genomes

In a collaborative study published online today in Nature Biotechnology, researchers from Kunming Institute of Zoology, Chinese Academy of Sciences, BGI, and other institutes, have completed the first genome sequence of domestic goat by a robust approach integrated with next-generation sequencing (NGS) and whole-genome mapping (WGM) technologies. The goat genome is the first reference genome for small ruminant animals and may help to advance the understanding of distinct ruminants’ genomic features from non-ruminant species. This work also yields a valuable experience for facilitating the de novo assemblies of large, complex genomes in the future. Goats are recognized as an important member of the world livestock industry, and with many unique biological features. They are an important economic resource in many developing countries around the world, especially in China and India. However, despite their agricultural and biological importance, breeding and genetic studies of goats have been hampered by the lack of a high quality reference genome sequence. The goat genome sequence will be useful for facilitating the identification of SNP markers for marker-assisted breeding, and improving the utility of the goat as a biomedical model and bioreactor. With the availability of next-generation sequencing (NGS), draft assemblies are easy to generate nowadays. However, to finish a sequence to the chromosome level remains a hard nut to crack. In this study, the results show that a single NGS platform, when combined with whole-genome mapping technology, could produce a finished assembly much faster and with high quality than other currently available mapping strategies such as BACs or FISH. Through this integrated approach, researchers obtained the ~2.66 Gb goat reference genome from a female Yunnan black goat.

Transposable elements (TEs) are major components of mammalian genomes and contribute to gene and/or genome evolution. The TEs in goat genome are similar to those of cattle, and contain large numbers of ruminant-specific repeats, such as SINE-tRNA and SINE-BovA. It is reported that SINE-BovA repeat expanded primarily in the cattle genome. However, in this study, researchers found the SINE-tRNA repeat expanded specifically in the goat genome. Through constructing a phylogenetic tree among goats, cattle, horses, dogs, opossums and humans, researchers found the goat shared a common ancestor with cattle about 23 million years ago. Further comparison analysis revealed 44 rapidly evolving genes under positive selection, seven of which are immune-related genes and three are pituitary hormone or related genes. The immune-related genes identified also exist in cattle. The findings suggest that the rapid evolution of pituitary hormones may be related to the different features between goat and cattle in milk production, development rates of the fetus and/or hair variation. The major histocompatibility complex (MHC) plays an important role in the immune system. In this study, the goat MHC was found to be located on chromosome 23 and contains two regions with length of 2.25 Mb and 360 kb, respectively. With the high quality genome assembly, further understanding of the goat MHC will be useful for immunological studies and vaccine development.

One of the distinguishing characteristics of mammals is the protective growth known as hair. It is produced by hair follicles within the skin, which could provide either protection (guard hairs) or insulation (underfur). The two major hair follicles include the primary hair follicle that produces only coat hair in all mammals, and the secondary hair follicle that can produce the cashmere or “fine hair” in certain mammals, including goats and antelopes. Despite a 2,500-year history and the extent of raw cashmere production, people are lack of understanding of the molecular mechanisms of cashmere formation and development. Researchers conducted transcriptomic analysis on the primary and secondary follicles of a cashmere goat, revealing 51 genes that are differentially expressed between the two types of hair follicles. Keratin and keratin-associated proteins are the main structural proteins of hair fibers, determining the quality of fiber together. In the study, 29 keratin genes and 30 keratin-associated protein genes were detected in both types of follicles. Interestingly, they found two keratin genes and ten keratin-associated protein genes were consistently differentially expressed between primary and secondary hair follicles, suggesting that the keratin-associated protein genes may be more important in determining the structure of cashmere fibers. In addition to the keratin genes and keratin-associated protein genes, researchers also found several enzymes of amino acid biosynthesis, with implications in regulating primary hair growth and hair cycle. Xun Xu, Deputy Director of BGI, said, “The goat reference genome is an important stepping stone in the molecular breeding of cashmere goats, and will help to advance the comparative studies on ruminants. The transcriptomic analysis on the primary and secondary follicles will open a new way for better improving the quality cashmere wool.”

Science Daily
January 22, 2013

Original web page at Science Daily


Resistant parasites in sheep in Norway

Sheep in the Norwegian counties of Rogaland and Hordaland have an increased risk of hosting gastrointestinal parasites which cannot be efficiently treated with benzimidazole — the most frequently used deworming agent for sheep in Norway. A national monitoring programme, increased focus on good treatment procedures and reducing excessive treatment are measures that can prevent the spreading of resistant parasites to other parts of the country. A well-functioning and sustainable small ruminants industry in Norway depends on the effective control of gastrointestinal parasites in these animals. Atle V. Meling Domke’s doctoral research has charted the distribution of resistant parasites in Norwegian sheep and goat herds, studied treatment procedures and revealed which gastrointestinal parasites are present in small ruminants in Norway. His work shows that sheep excrete more parasite eggs in their faeces than goats and that there are higher numbers of eggs in animals in the Southwest of the country than in inland regions or in Northern Norway. The low occurrence of parasites in goats can be due to the fact that the adult goats do not share pastures with the kids, as is the case with sheep and lambs. The most frequently occurring gastrointestinal parasite found in small ruminants in Norway was Teladorsagia circumcincta. The blood-sucking parasite Haemonchus contortus was found in sheep as far north as the Lofoten Islands.

Domke’s research project also included a survey about treating parasites in small ruminants. The results of this survey showed that 90% of the farmers were at risk of administering the wrong amount of medicine. The study also revealed that lambs in Southwest Norway were treated more often than animals in inland regions and in Northern Norway. For goats, the treatment was most usually given during the suckling period. Antiparasitic drugs (anthelmintics) based on the active ingredient benzimidazole were the most frequently used on sheep, while both benzimidazole and macrocyclic lactones were common treatments for goats. 28 flocks of sheep and 28 herds of goats from all over the country were tested in order to chart the occurrence of resistant gastrointestinal parasites. In addition, tests were carried out on 32 flocks of sheep which were thought to have an increased risk of developing resistance to medication. The criteria for an increased risk were a high treatment rate, high animal density or treatment combined with a change of pasture. No resistant parasites were found in goats. In 10.5% of the randomly selected flocks of sheep, the effect of the active ingredient benzimidazole was found to be unsatisfactory. It was also shown to have a poor effect on 31% of the high-risk flocks. The resistant flocks were mainly located in the South West — mostly in the county of Rogaland — but also to some extent in the county of Hordaland. The parasites that had developed resistance to benzimidazole were Teladorsagia circumcincta and Haemonchus contortus.

Science Daily
November 27, 2012

Original web page at Science Daily


Selfish sheep seek the center

To escape a hungry wolf, a sheep doesn’t have to outrun the wolf, just the other sheep in its flock. Many researchers think that such selfish behavior, not cooperation for the benefit of the whole crowd, shapes the movements of groups of animals. But the decades-old “selfish herd theory” has been hard to back up with data. Now, a detailed analysis of how a flock of sheep moves to avoid a sheepdog has found that the theory holds true. Each sheep heads to safety in the center of the flock, rather than running directly away from the dog, Current Biology, 22 (2012). “It’s really difficult to measure 2D spatial information on large animals in the wild,” says biologist Theodore Stankowich of the University of Massachusetts, Amherst, who was not involved in the new work. “They’ve taken advantage of a unique opportunity to work with the sheep to answer these types of questions in a controlled environment.” Studies on seals, crabs, and pigeons have shown that those animals seem to herd for selfish reasons, but the data have often been crude. Biologist Andrew King and colleagues at the Royal Veterinary College of the University of London attached GPS backpacks to 46 sheep and to a trained Australian Kelpie dog. When they released the dog to herd the sheep, they recorded the location of each animal every second. Then, they analyzed the data to determine what factors influenced each sheep’s path. The movements of the sheep, the researchers reveal today online in Current Biology, could be best predicted by the center of the flock. Rather than run in a line away from the dog, scatter in all directions, or follow their nearest neighbors, the sheep all hurried toward the flock’s center. The sheep began to converge when the dog was 70 meters away. Even as the flock as a whole moved, each sheep continuously competed to be as near the middle as possible.

“The fact that they’re running toward the center reduces the chances of their being on the edge and being picked off by a predator,” says King. It’s a selfish behavior since each sheep puts the animals at the fringes of the flock at risk in order to save itself. The new observation helps back up hypotheses on the evolutionary pressures that have encouraged animals to group. In addition, further work could reveal how herding behaviors change when sheep are infected with neurodegenerative diseases such as scrapie, which kills sheep and can quickly spread throughout a flock if infected animals aren’t quarantined. The results could lead to ways to detect infections earlier through behavioral monitoring, says King. “These methods are an advance on previous efforts,” says Stankowich. “I’d like to see the same technique applied to other large mammals.” Even if sheep herd for selfish protection, the findings don’t necessarily hold true for all animals. And trained sheepdogs may not be the best mimic of a dangerous predator, King acknowledges. “It could be a downgraded level of threat, because it’s something the sheep have experienced before,” he says. The animals’ response to a wolf, for example, could be different.

August 7, 2012

Original web page at ScienceNow


Vaccine for deadly sheep virus is on its way

A deadly, previously unknown virus that triggers abortions in sheep, goats and cattle, is spreading around Europe, causing more trouble for the beleaguered livestock industry. But farmers may have a vaccine to fight it with by next year. Virologists are meeting in Lelystad, the Netherlands, this week to discuss Schmallenberg virus, which belongs to a virus family never seen in Europe before. Three companies are already testing candidate vaccines. Normally these would take years to come to market but faster approval could stop the virus taking hold. Since Schmallenberg was identified in Germany last November, it has caused a wave of sheep abortions across northern Europe and the UK and has now spread to Italy. The subgroup of the family to which the virus belongs includes Oropouche virus, which infects humans and is the second-most common cause of fever in tropical South America after dengue. Schmallenberg’s closest relatives, such as Akabane virus found in Japan, Australia and Israel, only infect ruminants, however, so it is thought unlikely to infect humans. The last animal virus to take Europe by surprise was bluetongue, which like Schmallenberg is spread by biting midges and exploded in the same regions of Germany, the Netherlands and Belgium in 2007. Accelerated approval for a vaccine cleared bluetongue from Europe by 2010.

A sense of urgency might also stop Schmallenberg settling in. “All the tests required for licensing a vaccine would take two years,” says Peter Mertens, head of insect-borne viruses at the Institute for Animal Health in Pirbright, UK. If governments lift the more onerous testing requirements, vaccines might be permitted after being given to animals and observed for long enough to see if they are safe, induce effective antibodies and prevent infection. In Lelystad, however, researchers will focus on better ways to detect antibodies to the virus, says Martin Beer of the Friedrich Loeffler Institute in Insel Riems, Germany, which first isolated the virus and proved its link to disease. Antibodies reveal which animals have been infected. Rapid tests in time for when midges return in spring will show where the virus spreads. An antibody test can also tell researchers when the virus has caused a fetus to be malformed, says Beer. Right now, that is not clear because the virus itself has cleared by the time the animal is delivered. The tests will also prove which animals are safe for export.

New Scientist
March 20, 2012

Original web page at New Scientist


Goat kids can develop accents

The ability to change vocal sounds (vocal plasticity) and develop an accent is potentially far more widespread in mammals than previously believed, according to new research on goats from Queen Mary, University of London. Vocal plasticity is the ability of an individual to modify the sound of their voice according to their social environment. Humans benefit from an extreme form of vocal plasticity which allows us to produce a wide range of sounds and accents, but in most other mammals (except, for example, bats and whales) vocalisations were thought to be genetically determined, with very limited flexibility and ability to learn. Dr Elodie Briefer and Dr Alan McElligott from Queen Mary’s School of Biological and Chemical Sciences investigated genetic and social effects on goat kid calls. The team studied four groups of pygmy goats, who were all full or half siblings. They were recorded during two socially and ecologically distinct periods: at one week old, when they typically stay hidden from predators with their siblings; and at five weeks old, when they form social groups with animals of the same age, known as ‘crèches’. Writing in the journal Animal Behaviour, the team report that despite their limited vocal repertoire, the calls of goat half-siblings became more similar when they were raised in the same social group together.

Dr Briefer explains: “We found that genetically related kids produced similar calls, which is not that surprising. But the calls of kids raised in the same social groups were also similar to each other, and became more similar as the kids grew older. This suggests that goat kids modify their calls according their social surroundings, developing similar ‘accents’.” The existence of vocal plasticity in mammals such as goats reveals a possible early pathway in the evolution of vocal communication, which eventually led to human language and speech. Dr McElligott explains: “The research also highlights the important cognitive abilities that some of our domestic animals possess, and which have remained undetected until now. Improved knowledge of their behaviour and cognition provides essential information for improving animal welfare.”
March 6, 2012

Original web page at


Discovery uses ‘fracture putty’ to repair broken bone in days

Broken bones in humans and animals are painful and often take months to heal. Studies conducted in part by University of Georgia Regenerative Bioscience Center researchers show promise to significantly shorten the healing time and revolutionize the course of fracture treatment. “Complex fractures are a major cause of amputation of limbs for U.S. military men and women,” said Steve Stice, a Georgia Research Alliance Eminent Scholar, animal and dairy scientist in the UGA College of Agricultural and Environmental Sciences and director of the UGA Regenerative Bioscience Center. “For many young soldiers, their mental health becomes a real issue when they are confined to a bed for three to six months after an injury,” he said. “This discovery may allow them to be up and moving as fast as days afterward.” Stice is working with Dr. John Peroni to develop a fast bone healing process. “This process addresses both human and veterinary orthopedic needs,” said Peroni, an associate professor of large animal surgery in the UGA College of Veterinary Medicine and a member of the RBC. Peroni and Stice are leading a large animal research project funded by the U.S. Department of Defense (DOD) The project includes scientists and surgeons from the Baylor University College of Medicine, Rice University and the University of Texas, who conducted the early studies.

“Healing of critical-size defects is a major challenge to the orthopedic research community,” Peroni said. “Large-bone defects must be stabilized and necessitate technologies that induce rapid bone formation in order to replace the missing tissue and allow the individual to return to rapid function. To date, no single material can suffice.” The group they lead is a multidiscipline and multi-institutional group actively working on bone tissue engineering. “Our group has been working productively together on numerous projects through the last several years,” Stice said, “So, a collegial relationship and successful collaborative working relationship is already established.” Between 2009 and 2011, the collaborations received a $1.4 million grant from the DOD for the use of stem cells in fracture healing to be tested in sheep.

“In our experiences with large animal models, following the guidelines established by our animal care and use committee,” Stice said, “we have been successful in formulating a product that contains mesenchymal stem cells and allows them to survive in the environment of the fracture long enough to elicit the rapid formation of new bone.” This year, the group showed bone can be generated in sheep in less than four weeks. The speed in which bone is formed is one of the truly unique features of this study. To start the bone regeneration process, the RBC used adult stem cells that produce a protein involved in bone healing and generation. They then incorporated them into a gel, combining the healing properties into something Stice calls “fracture putty.” With Peroni’s assistance, the Houston-based team used a stabilizing device and inserted putty into fractures in rats. Video of the healed animals at two weeks shows the rats running around and standing on their hind legs with no evidence of injury. The RBC researchers are testing the material in pigs and sheep, too.

“The small-animal work has progressed, and we are making good progress in large animals,” he said. More work is needed to get to human medical trials, but the threat of losing federal funding for biomedical work through the DOD means they will have to find new ways to fund the project. “The next step is to show that we can rapidly and consistently heal fractures in a large animal,” Peroni said, “then to convert it to clinical cases in the UGA [College of Veterinary Medicine] clinics where clinicians treat animals with complex fractures all the time.” Once they have something that works for animals, it will be passed over to the DOD for human use. Peroni, who is chairman of the North American Veterinary Regenerative Medicine Association, is hopeful this material will be promoted to the veterinary and human medical fields through the educational efforts of NAVRMA and the RBC. However, the RBC isn’t the only group working on a faster fix for broken bones. “Our approach is biological with the putty,” Stice said. “Other groups are looking at polymers and engineering approaches like implants and replacements which may eventually be combined with our approach. We are looking at other applications, too, using this gel, or putty, to improve spinal fusion outcomes.” One of the best hopes for the fracture putty is in possible facial cranial replacements, an injury often seen on the battlefield. The project ends in mid-2012. “By then we are to deliver the system to the DOD,” Stice said.

Science Daily
February 21, 2012

Original web page at Science Daily


New animal virus takes northern Europe by surprise

Scientists in northern Europe are scrambling to learn more about a new virus that causes fetal malformations and stillbirths in cattle, sheep, and goats. For now, they don’t have a clue about the virus’s origins or why it’s suddenly causing an outbreak; in order to speed up the process, they want to share the virus and protocols for detecting it with anyone interested in studying the disease or developing diagnostic tools and vaccines. The virus, provisionally named “Schmallenberg virus” after the German town from which the first positive samples came, was detected in November in dairy cows that had shown signs of infection with fever and a drastic reduction in milk production. Now it has also been detected in sheep and goats, and it has shown up at dozens of farms in neighboring Netherlands and in Belgium as well. According to the European Commission’s Standing Committee on the Food Chain and Animal Health, cases have been detected on 20 farms in Germany, 52 in the Netherlands, and 14 in Belgium. Many more suspected cases are being investigated. “A lot of lambs are stillborn or have serious malformations,” Wim van der Poel of the Dutch Central Veterinary Institute in Lelystad says. “This is a serious threat to animal health in Europe.”

“We are taking this very, very seriously,” adds Thomas Mettenleiter, head of the Friedrich-Loeffler-Institute (FLI), the German federal animal health lab located on the island of Riems. The virus appears to be transmitted by midges (Culicoides spp.), and infections likely occurred in summer and autumn of last year, but fetuses that were exposed to the virus in the womb are only now being born. The first cases of lambs with congenital malformations such as hydranencephaly—where parts of the brain are replaced by sacs filled with fluid—and scoliosis (a curved spine) appeared before Christmas. “Now, in some herds 20% to 50% of lambs show such malformations,” Mettenleiter says. “And most of these animals are born dead.” Scientists are bracing for many more cases to appear, especially in cattle, because bovine fetuses infected in summer 2011 would be expected to be born in February and March.

Virologists have made some headway since they first announced the detection of the Schmallenberg virus in November. They have been able to isolate the virus and to culture it in insect and hamster cells. Evidence that it’s responsible for the observed symptoms has become stronger with its isolation from brain tissue of affected lambs. “The characteristic malformations, together with the frequent virus detection in brains of malformed animals, clearly support a causal link,” FLI’s Martin Beer says. In a first animal experiment, scientists at FLI also infected three cows with the virus and showed that the virus replicated in them; one developed fever and diarrhea. FLI researchers have already sequenced the genome of the new pathogen. Comparisons indicate it is a member of a group called the orthobunyaviruses. These viruses consist of three segments called S (short), M (middle), and L (long) and are mainly transmitted by mosquitoes and midges. Although the viruses are best known from Asia, some have been circulating in Europe for decades. Initially, scientists said the virus most closely resembled the Akabane virus, a pathogen that has been found in cattle, buffalo, sheep, camels, dogs, and other species, leading them to call it an “Akabane-like virus.”

Now they say that at least the S segment of Schmallenberg’s genome is most closely related to sequences of a different orthobunyavirus called Shamonda virus. Both Akabane and Shamonda virus belong to the so-called Simbu serogroup and are known to infect ruminants and to be transmitted by midges. But there are few orthobunyavirus sequences available with which to compare the new virus, so scientists are starting to sequence more members of the family. “Orthobunyaviruses have been neglected for a long time, and we just don’t know a lot about them,” says Jonas Schmidt-Chanasit of the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany. A host of questions remains unanswered. Which vector species is transmitting the disease? Can animals infect each other directly? And of course, where did the virus come from? “The problem with orthobunyaviruses is that their segmented genome makes the emergence of new combinations very easy, just like with influenza viruses,” Schmidt-Chanasit says. He points to a recent outbreak of a new orthobunyavirus in Peru. The pathogen, named Iquitos virus, turned out to have combined S and L segments of a known virus called Oropouche and the M segment of a new virus.

Whether the Schmallenberg virus could sicken humans is unknown. At least 30 orthobunyaviruses have been associated with human disease; the Oropouche virus, also a member of the Simbu serogroup, causes a febrile disease often associated with headaches, dizziness, skin rash, and malaise, whereas the Iquitos virus can cause diarrhea, vomiting, and nausea. But these viruses seem to be dependent on midges to infect humans and are not known to be directly transmitted from infected farm animals. Midges are less likely to bite humans than mosquitoes, and there have been no reports of unusual human illnesses from farmers whose livestock is infected. A risk assessment by the European Centre for Disease Prevention and Control in Stockholm, issued just before Christmas, concluded that “it is unlikely that this new orthobunyavirus can cause disease in humans, but it cannot be excluded at this stage.” But the experts recommended closely monitoring the health of farmers and vets.

January 24, 2012

Original web page at ScienceNow


Gene therapy shows promise as hemophilia treatment in animal studies

For the first time, researchers have combined gene therapy and stem cell transplantation to successfully reverse the severe, crippling bleeding disorder hemophilia A in large animals, opening the door to the development of new therapies for human patients. Researchers at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine, collaborating with other institutions, report in Experimental Hematology that a single injection of genetically-modified adult stem cells in two sheep converted the severe disorder to a milder form. The journal is a publication of the Society for Hematology and Stem Cells. “A new approach to treating severe hemophilia is desperately needed,” said lead author Christopher D. Porada, Ph.D., associate professor of regenerative medicine at Wake Forest Baptist. “About 75 percent of the world doesn’t have access to the current treatment – therapy to replace missing clotting factors. This puts patients in most of the world at risk of severe and permanent disabilities.” Porada cautioned that challenges will need to be overcome before the treatment can be applied to humans, including that the sheep developed an immune response to the therapy that could decrease its effectiveness and duration.

There is currently no cure for the rare bleeding disorder hemophilia. People with this genetic disorder lack a protein, known as a clotting factor, needed for normal blood clotting. As a result, they may bleed for a longer time than others after an injury, as well as bleed internally, especially in joints such as the knees, ankles, and elbows. This bleeding can damage the organs and tissues and be life threatening. Even when life-threatening bleeds are prevented with replacement therapy, it doesn’t prevent smaller bleeds within the joints that can cause pain and decreased mobility. People with hemophilia A, the most common type, are missing clotting factor VIII. For the study, the researchers used a combined stem cell/gene therapy approach to increase levels of factor VIII produced by the animals. The scientists first inserted a gene for factor VIII into engineered mesenchymal stem cells, a type of adult stem cell. The cells – acting as a carrier for the gene – were then injected into the abdominal cavity of the sheep. The scientists selected mesenchymal stem cells to carry the gene because they have the ability to migrate to sites of injury or inflammation. In the treated animals, the cells migrated to the joints and stopped ongoing bleeding. In addition, all spontaneous bleeding events ceased, and the existing joint damage was completely reversed, restoring normal posture and gait to these crippled animals, and enabling them to resume a normal activity level.

However, a paradox of the treatment was that while the symptoms were eliminated, the sheep developed an immune response to factor VIII, suggesting that the treatment’s effects would be reduced or shorter in duration. The scientists are currently working to learn why the immune response occurred and to develop strategies to prevent it. “While preliminary, these findings could pave the way for a new therapy for hemophilia patients who experience debilitating bleeding in their joints,” Porada said.

EurekAlert! Medicine
November 15, 2011

Original web page at EurekAlert! Medicine