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Goats could increase the risk of a rare lung cancer

Exposure to goats could increase the risk of a certain type of lung cancer, according to French researchers. The study, presented at the European Respiratory Society’s Annual Congress in Amsterdam, has linked a professional exposure to goats with a distinct subset of lung cancer, known as pneumonic-type lung adenocarcinoma (P-ADC). This form of lung cancer has a weak association with tobacco smoking when compared with other types of the disease. In attempting to identify other triggers that may cause the disease, scientists have previously noticed similarities between P-ADC and a viral infection which causes growths in the lungs of sheep. Given these similarities, the researchers have investigated whether a viral agent found in sheep and goats could be easily transferred to people who work with the animals, leading to a partiality for P-ADC. The current epidemiologic study involved 44 patients with P-ADC and 132 controls without the disease. All participants were given a questionnaire assessing a number of risk factors including their smoking status, their personal history of cancer and their exposure to goats.

The results showed that people who had experienced a professional exposure to goats during their lifetime were five times more likely to get P-ADC compared with other types of lung cancer. The findings also showed that P-ADC was significantly associated with females, and people who had never smoked or had any personal history of cancer. Dr Nicolas Girard, from the Louis Pradel Hospital, Hospices Civils de Lyon, said: “Scientists have noticed similarities between P-ADC and a contagious viral infection in sheep before. This led us to explore the possibility that professional exposure to cattle could make humans more susceptible to P-ADC. These findings demonstrate that exposure to goats could be a risk factor for this type of lung cancer, however further studies are needed to assess other potential risk factors for the disease.”

Science Daily
November 1, 2011

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‘Goat Plague’ threat to global food security and economy must be tackled, experts warn

“Goat plague,” or peste des petits ruminants (PPR), is threatening global food security and poverty alleviation in the developing world, say leading veterinarians and animal health experts in this week’s Veterinary Record. They call on the UN Food and Agricultural Organisation (FAO) and the World Organisation for Animal Health (OIE) to turn their attention now to ridding the world of the PPR virus, which carries a very high risk of death among infected animals. The call follows the formal announcement this week by the FAO that a related virus, rinderpest, better known as “cattle plague,” has now been eradicated around the globe. In an editorial, senior vets, all of whom were variously involved in the global rinderpest eradication campaign, say that getting rid of that virus has had far reaching effects. “What is not generally appreciated is that the eradication of rinderpest has yielded benefits that surpass virtually every other development programme in agriculture, and will continue to do so in future,” they write. They cite the case of Chad, where between 1963 and 2002, every dollar spent on rinderpest eradication made a return of at least $US16.

Now the world must focus on achieving the same for PPR, which is endemic in most of sub Saharan Africa “as well as a swathe of countries from Turkey through the Middle East to south Asia,” they say. The virus has also recently been reported in North Africa, central Asia, and China. It’s important to control the infection because it spreads quickly through goat herds and sheep flocks, decimating their numbers, and taking a terrible financial toll on the farmers and families who depend on these animals for their livelihoods, say the authors. And it has also spread to wildlife species, many of which are endangered or threatened. “Because poorer people are more likely to keep small ruminants than cattle, women and children tend to have more access and control over them, PPR control and eradication would be both pro-poor and pro-women and children. It fits many development objectives for nutrition, food security and poverty alleviation,” they write. “We believe that a global programme for the total eradication of PPR should be established as an international undertaking without delay,” they declare. “Given support from governments, international organisations, and funding agencies, we believe that another great success could be achieved within a 10 year time frame with concerted international effort,” they suggest.

In a review published in the same issue, senior international vets, including from the Institute for Animal Health in Pirbright, Surrey, document the history of the infection and explain the scientific basis for eradication of the virus. “Although PPR has not yet been seen in the UK, and is currently absent from most European countries, it is without doubt the fastest growing and potentially the most economically important disease of sheep and goats anywhere in the developing world,” they write. They go on to say that there has been a reluctance to tackle the issue because sheep and goats are considered to be of lesser economic value than cattle, and their shorter working lives mean that it would cost more to eradicate PPR. But they warn: “The ever advancing spread of PPR has made the economic impact of the disease, and consequently the benefits of its eradication, much greater. The imperative for coordinated action is therefore much stronger.”

Science Daily
July 12, 2011

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Experimental oral transmission of atypical scrapie to sheep

To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals’ peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.

Since the discovery of atypical scrapie and its subsequent identification, mostly through active surveillance, in several countries (some with no previous history of transmissible spongiform encephalopathies [TSEs]) such as New Zealand and Australia, scientists have debated whether this form of TSE is in fact spontaneous or acquired rather than contagious. The epidemiologic studies that have been undertaken suggest that atypical scrapie does not appear be transmitted between animals in the field situation. Although the routes by which natural transmission occurs have never been fully established for TSEs, it is widely accepted that ingestion of infective material, i.e., the oral route, is a key component in some TSEs, e.g., kuru, variant Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, and transmissible mink encephalopathy. Within the sheep population, susceptibility to particular strains of TSE has been shown to be heavily affected by polymorphisms of the prion protein gene of the sheep. The successful transmission of atypical scrapie to sheep after intracerebral inoculation has been previously reported for sheep of 1 genotype (A136H154Q171/A136H154Q171), and challenges in other homologous and heterologous genotype combinations are ongoing. However, successful intracerebral transmission of a particular TSE agent in a particular species does not necessarily indicate susceptibility by the oral route.

The tissue distribution of infectivity or disease-specific prion protein (PrPSc) in bovine spongiform encephalopathy in sheep has led to extensive public health control measures based on the known pathogenesis and distribution of PrPSc in edible tissues, and their removal from carcasses of animals over a certain age. Classic scrapie may also show the widespread accumulation of PrPSc in peripheral tissues. Although early studies of atypical scrapie did not show PrPSc or infectivity outside the brain, recent data indicate that peripheral tissues from naturally infected animals can harbor infectivity either in the presence or absence of PrPSc. However, whether this infectivity is established before or after the agent has propagated in the central nervous system is unknown. The first aim of the current study was to examine the distribution of infectivity in peripheral tissues in animals at and beyond the cutoff point for the current meat hygiene regulations of the European Commission (i.e., 12 months of age). The second aim was to investigate the potential for oral transmission of atypical scrapie.

Emerging Infectious Diseases
May 17, 2011

Original web page at Emerging Infectious Diseases

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Novel bluetongue virus serotype from Kuwait

Sheep and goats sampled in Kuwait during February 2010 were seropositive for bluetongue virus (BTV). BTV isolate KUW2010/02, from 1 of only 2 sheep that also tested positive for BTV by real-time reverse transcription–PCR, caused mild clinical signs in sheep. Nucleotide sequencing identified KUW2010/02 as a novel BTV serotype. Bluetongue virus (BTV) infects ruminants, camelids, and occasionally large carnivores. Clinical signs of bluetongue disease (BT) are usually more severe in sheep or white-tailed deer, particularly in populations previously unexposed to the virus; cattle and goats are often asymptomatic. Initial diagnosis of BT based on clinical signs can be confirmed by virus isolation and characterization or identification of viral RNA by reverse transcription PCR. BTV particles contain 3 concentric protein layers surrounding 10 linear double-stranded RNA genome segments, identified as segment-1 to segment-10 (Seg-1 to Seg-10) in order of decreasing size (from 3,954 bp to 822 bp). Twenty-five BTV serotypes have been identified on the basis of the specificity of reactions with neutralizing antibodies generated by their mammalian hosts. Consequently, BTV outer capsid proteins, particularly viral protein (VP) 2 (encoded by Seg-2), show sequence variations that determine virus serotype.

Other BTV proteins, including subcore shell protein VP3(T2) encoded by Seg-3, are more highly conserved. Phylogenetic comparisons of Seg-3 sequences have been used to identify different BTV topotypes and distinguish different Orbivirus species. BTV has been reported in several Middle Eastern countries (Egypt, Jordan, Syria, Turkey, Cyprus, and Iraq) since 1951. In 2008, Egypt reported the absence of BT, and Egypt is the only country in the region to have prohibited BTV vaccination. Iran reported outbreaks of BT in 2008, and Saudi Arabia reported infection without clinical signs, although the serotype(s) were not identified. Multiple serotypes were detected in Israel during 2008 and Oman in 2009. We report characterization of a novel BTV serotype identified in Kuwait in 2010.

Emerging Infectious Diseases
May 17, 2011

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Molecular epidemiology of Coxiella burnetii from ruminants in Q fever outbreak, the Netherlands

Q fever is a zoonosis caused by the bacterium Coxiella burnetii. One of the largest reported outbreaks of Q fever in humans occurred in the Netherlands starting in 2007; epidemiologic investigations identified small ruminants as the source. To determine the genetic background of C. burnetii in domestic ruminants responsible for the human Q fever outbreak, we genotyped 126 C. burnetii–positive samples from ruminants by using a 10-loci multilocus variable-number tandem-repeat analyses panel and compared them with internationally known genotypes. One unique genotype predominated in dairy goat herds and 1 sheep herd in the human Q fever outbreak area in the south of the Netherlands. On the basis of 4 loci, this genotype is similar to a human genotype from the Netherlands. This finding strengthens the probability that this genotype of C. burnetii is responsible for the human Q fever epidemic in the Netherlands.

Q fever is a zoonosis caused by Coxiella burnetii, an intracellular gram-negative bacterium that is prevalent throughout the world. Domestic ruminants are considered the main reservoir for Q fever in humans. However, other animal species, including pet animals, birds, and several species of arthropods, can be infected by C. burnetii and cause human cases of Q fever. The main clinical manifestations of Q fever in goats and sheep are abortion and stillbirth. In cattle, Q fever has been associated with sporadic abortion, subfertility, and metritis. With an abortion, up to 1 billion C. burnetii per gram of placenta can be excreted. Most animal species that carry C. burnetii show no symptoms. Transmission to humans occurs mainly through inhalation of contaminated aerosols.

Recently, 2 DNA-based methods for typing C. burnetii were reported. Multispacer sequence typing is based on DNA sequence variations in 10 short intergenic regions and can be performed on isolated C. burnetii strains or directly on extracted DNA from clinical samples. Multilocus variable-number tandem-repeat analyses (MLVA) is based on variation in repeat number in tandemly repeated DNA elements on multiple loci in the genome of C. burnetii and might be more discriminatory than multispacer sequence typing. MLVA also can be performed on C. burnetii strains or directly on DNA extracted from clinical samples. A total of 17 different minisatellite and microsatellite repeat markers have been described.

Emerging Infectious Diseases
April 19, 2011

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Molecular discrimination of sheep bovine spongiform encephalopathy from scrapie

Sheep CH1641-like transmissible spongiform encephalopathy isolates have shown molecular similarities to bovine spongiform encephalopathy (BSE) isolates. We report that the prion protein PrPSc from sheep BSE is extremely resistant to denaturation. This feature, combined with the N-terminal PrPSc cleavage, allowed differentiation of classical scrapie, including CH1641-like, from natural goat BSE and experimental sheep BSE. Prion diseases, or transmissible spongiform encephalopathies (TSEs), are neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, and bovine spongiform encephalopathy (BSE) in cattle. TSEs are characterized by accumulation of an abnormal isoform of the host-encoded prion protein (PrPC), termed PrPSc.

A novel human prion disease, variant CJD, was reported in 1995 and postulated to be caused by eating beef infected with BSE. Biologic and molecular analyses provided evidence that the same agent was involved in BSE and variant CJD Evidence of sheep and goat susceptibility to BSE and discovery of natural BSE infections in 2 goats prompted the European Commission to increase the search for BSE infections in small ruminants. Although the BSE agent can be recognized by biologic strain typing in conventional mice, large-scale testing of small ruminants required molecular tests able to discriminate BSE from the most common TSEs of small ruminants. Molecular criteria used to discriminate BSE from scrapie are based on the low molecular weight of proteinase K–treated PrPSc (PrPres), a high proportion of the diglycosylated PrPSc, and poor or absent binding with antibodies directed at N-terminal epitopes. This last characteristic was fundamental in developing the discriminatory methods currently approved for surveillance in Europe.

The experimental scrapie isolate CH1641 reportedly shares molecular features with experimental sheep BSE, although lack of transmissibility of CH1641 to conventional mice in comparison to successful transmission of BSE provided evidence that CH1641 and BSE are caused by distinct prion agents. A few natural isolates have been described in sheep, showing molecular and biologic similarities to CH1641, and were named CH1641-like. Subtle pathologic differences were exploited to distinguish these CH1641-like isolates from BSE by immunohistochemical and biochemical analyses by glycoform profiling. However, routine testing by using discriminatory Western blot (WB) methods does not easily distinguish CH1641 and CH1641-like isolates from BSE. We report 2 new CH1641-like isolates; analyze the conformational stability of CH1641-like isolates, BSE, and classical scrapie; and show that a reliable molecular differentiation of these 3 TSE sources is possible by an improved discriminatory WB method.

Emerging Infectious Diseases
April 19, 2011

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The sharpest mind in the farmyard

When we look for examples of intelligent animals, certain species always leap to mind. Ourselves of course, and our close relatives the chimpanzees and other primates. Perhaps the cunning corvids – crows and scrub jays – with their prodigious memories and talent for deception. Dolphins and whales are pretty bright. Many would even agree that there is a sort of intelligence governing the behaviour of social insects like ants. But sheep? Sheep are just thick. Except that they aren’t. Over the past few decades, evidence has quietly built up that sheep are anything but stupid. It now turns out that the humble domestic sheep can pass a psychological test that monkeys struggle with, and which is so sensitive it is used to look for neurological decline in human patients. Laura Avanzo and Jennifer Morton of the University of Cambridge were interested in a new kind of genetically modified sheep. These animals carry a defective gene that in humans causes Huntington’s disease, an inherited disorder that leads to nerve damage and dementia. The hope is that the Huntington’s sheep could be a testing ground for possible treatments.

For that to work, they reasoned, researchers will have to be able to track changes in the cognitive abilities of the Huntington’s sheep. So they decided to find out whether normal sheep could pass some of the challenging tests given to people with Huntington’s. If the sheep passed, that would mean that the Huntington’s sheep could be seen losing the ability as their disease progressed – and maybe regaining it if any treatments worked. So Avanzo and Morton put seven female sheep through a series of increasingly tricky challenges. In one test the sheep walked into a pen that contained two buckets, one blue and the other yellow, with some food in the blue one. Over the course of a few trials they learned what was going on and always went to the blue bucket. When the researchers put the food in the yellow bucket instead, the sheep changed their behaviour accordingly. They also mastered a subtler game in which the food was still in one of the buckets but the clue to its location was the colour of a cone placed nearby, not the colour of the bucket itself.

Next Avanzo and Morton stepped up the intellectual pressure, trying the sheep on intra-dimensional and extra-dimensional set-shifting. These tested the animals’ ability to shift their attention, something that requires a high level of mental control. In intra-dimensional set-shifting, the sheep still had to choose a bucket based on colour, but the set of colours was different: instead of blue and yellow, the choice was purple and green. Humans find this pretty easy. Extra-dimensional shifting is harder, as the sheep had to ignore the colour of the objects and instead focus on their shapes. In a touching piece of scientific understatement, Avanzo and Morton note that their decision to do these tests “was driven more by curiosity than expectation”. Humans and other primates can do set-shifting, but other large animals struggle with it – although researchers have persuaded mice and rats to do it. The task relies on the prefrontal cortex, a part of the brain that is much bigger in humans than other animals.

Impressively, the sheep passed the tests, learning to attend either to different pairs of colours or to the objects’ shapes as necessary. As well as being good news for the study of Huntington’s disease, it’s one more step towards rehabilitating sheep’s reputation. It really is about time we stopped making fun of sheep. They can not only recognise each other’s faces, especially sheep they are socially close to – they can remember significant others for at least two years. They can also discriminate breeds, preferring to look at their own. What’s more, there is evidence that they can group plants by family and memorise the correct route through a maze. They have sophisticated social lives too: rams become long-term buddies and stick up for each other in fights. There are even claims that sheep in the UK have learned to cross cattle grids by rolling across them, but further research may be needed on that point.
Source: PLoS One

New Scientist
February 22, 2011

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Prion disease spreads in sheep via mother’s milk

Transmission of prion brain diseases such as bovine spongiform enecephalopathy (BSE) — also known as mad cow disease — and human variant Creutzfeldt-Jakob disease (vCJD) is generally attributed to the consumption of the brain or organ meat of infected animals but new research demonstrates lambs exposed to milk from prion-infected sheep with inflamed mammary glands can develop prion disease as well. The research, which is published in the January 2011 issue of the Journal of Virology, has major implications for human and livestock health. “Prions cause devastating, ultimately fatal infections in humans,” says corresponding author Christina Sigurdson of the University of California, San Diego School of Medicine. “This study is the first demonstration of prions from an inflamed organ being secreted, and causing clinical symptoms in a natural host for prion disease.”

Recent research had suggested that human-to-human transmission of prions has occurred via blood transfusions, “underscoring the importance of understanding possible transmission routes,” the researchers write. The misfolded prions that cause vCJD in humans, and BSE in cattle — which can be transmitted to humans — commonly accumulate in lymphoid tissues before invading the central nervous system, where they wreak their deadly effects. Inflammation can cause lymphoid follicles to form in other organs, such as liver and kidney, which leads prions to invade organs that normally do not harbor infection. In recent research, this team, led by Ciriaco Ligios of the Istituto Zooprofilattico Sperimentale in Sardinia, Italy and Adriano Agguzi at the University of Zurich, Switzerland, reported sheep with misfolded prions in inflamed mammary glands, also known as mastitis, raising concerns that prions could be secreted into milk. In the new research, the team infected sheep with a common retrovirus that causes mastitis, and misfolded prions. They bred the sheep, in order to stimulate the females to produce milk, which they then collected and fed to lambs that had never been exposed to prions. The lambs developed prion disease after only two years, a speed which surprised the researchers, and “suggested that there was a high level of prion infectivity in milk,” says Sigurdson.

The research raises several disturbing possibilities: •A common virus in a sheep with prion disease can lead to prion contamination of the milk pool and may lead to prion infection of other animals.
•The same virus in a prion-infected sheep could efficiently propagate prion infection within a flock, through transmission of prions to the lambs, via milk. This might be particularly likely on factory farms, where mastitis may be common, and could occur in goats as well as sheep.
•Humans with variant Creutzfeldt-Jakob disease (vCJD) might accumulate prions in inflamed organs, and could also secrete prions.

However, “This work cannot be directly extrapolated to cattle,” says Sigurdson. She says that BSE prions do not accumulate to detectible levels in lymphoid organs, and thus would not be expected to accumulate with inflammation. “Nonetheless,” she says, “it would be worth testing milk from cattle with mastitis for prions as there may be other cellular sources for prions entry into milk.”

Science Daily
February 8, 2011

Original web page at Science Daily

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Molecular typing of protease-resistant prion protein in transmissible spongiform encephalopathies of small ruminants, France, 2002–2009

The agent that causes bovine spongiform encephalopathy (BSE) may be infecting small ruminants, which could have serious implications for human health. To distinguish BSE from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (PrPres), we used a specifically designed Western blot method to test isolates from 648 sheep and 53 goats. During 2002–2009, classical non-Nor98 transmissible spongiform encephalopathy had been confirmed among ≈1.7 million small ruminants in France. Five sheep and 2 goats that showed a PrPres pattern consistent with BSE, or with the CH1641 experimental scrapie source, were identified. Later, bioassays confirmed infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6 other isolates showed an additional C-terminally cleaved PrPres product, with an unglycosylated band at ≈14 kDa, similar to that found in the CH1641 experimental scrapie isolate and different from the BSE isolate. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases that include scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD) in humans. TSEs are characterized by accumulation in the brain of a disease-associated isoform (PrPd) of a host-encoded cellular prion protein (PrPc). PrPd, in comparison with the normal prion protein PrPc, clearly differs in secondary and tertiary structures and in biochemical characteristics. Proteinase K (PK) digestion destroys PrPc, but in PrPd it generates a protease-resistant fragment known as PrPres. Most TSE diagnostic methods (e.g., ELISA and Western blot tests) are based on detection of PrPres.

The transmissible agent involved in BSE in cattle is known to cause prion diseases in other species under natural conditions. BSE can also be experimentally transmitted to sheep and goats, including after oral challenge to test for transmission. Because BSE-contaminated meat and bone meal may have been fed to small ruminants, BSE may have been transmitted to sheep or goats. Also, the Scientific Steering Committee of the European Commission has hypothesized that the BSE agent might have originated from a scrapie agent in sheep or goats and that these animals may represent a reservoir. In view of these data, the European Commission defined a strategy to investigate the possible presence of BSE in sheep and goats under natural conditions.

The standard for strain typing TSE agents is based on analysis of the phenotypic characteristics of the disease after transmission in laboratory rodents. Biological characterization of the BSE agent in inbred wild-type mice appeared to be reliable, because it showed uniform features in mice. However, this approach is time-consuming and costly. The identification of uniform molecular features of PrPres by Western blot in human variant CJD paved the way to a similar approach for detecting possible BSE in small ruminants. The molecular criteria defined in these studies included electrophoretic mobilities, glycosylation characteristics, and immunolabeling with different monoclonal antibodies. The last criteria enabled mapping of the protease cleavage site of the PrP protein fragment obtained after PK digestion. More recently, the identification of additional C-terminal PrPres products may contribute to discrimination of the different types of CJD or of different scrapie and BSE sources. Discriminant molecular features of the prion protein can also be investigated by immunohistochemical analysis or ELISA. In all of these studies, it was assumed that the strain information was closely associated with the structural features of PrPd.

The Western blot method enabled discrimination of experimental BSE in sheep from most scrapie-affected animals. Nevertheless, discrimination was more difficult with the CH1641 experimental scrapie isolate, which otherwise clearly differs from BSE by its absence of transmissibility to wild-type mice. Similar molecular features to those of CH1641 have been described in a few natural scrapie cases in France and in the United Kingdom. We describe the molecular findings obtained for a large series of TSE infections in France identified in small ruminants by active surveillance during 2002–2009 and for CH1641-like isolates in sheep and in 1 goat.

Emerging Infectious Diseases
January 24, 2011

Original web page at Emerging Infectious Diseases

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Zoonotic cryptosporidiosis from petting farms, England and Wales

Visits to petting farms in England and Wales recently have increased in popularity. Petting farms are commercial operations at which visitors, mainly families and organized groups, are encouraged to have hands-on contact with animals. The ≈1,000 petting farms in the United Kingdom collectively receive >2 million visitors per year, with peak visitor times during school and public holidays. Commercial farms also may host farm visits on single days for group and school visits. The farm attraction business is a substantial part of the rural economy, generating >£12 million annually.

During 1992–2009, a total of 55 outbreaks of infectious intestinal disease associated with petting farms in England and Wales was reported to the Health Protection Agency. Verocytotoxin-producing Escherichia coli O157 (VTEC O157) caused 30 (55%) of these outbreaks (244 persons were affected [range 2–93, mean 8 persons] and 84 were hospitalized); Salmonella enterica serovar Typhimurium definitive phage type 104 caused 2 (3%) of the outbreaks. A total of 23 (42%) petting farm outbreaks were caused by Cryptosporidium spp. (1,078 persons were affected [range 2–541, mean 45 persons] and 29 were hospitalized). We report on these cryptosporidiosis outbreaks as a reminder of the risk to petting farm visitors. Contributory factors reported in the cryptosporidiosis outbreaks included direct contact with preweaned lambs, calves, kids, or animal feces (e.g., diarrhea in lambs, a recognized risk factor for cryptosporidiosis; 11/23 [48%]) and inadequate hand washing facilities (7/23 [30%]). Of outbreaks in which hand washing facilities were inadequate, thumb sucking by children was also noted in 1; in another, alcohol-based hand gels and sanitizers, which are ineffective against Cryptosporidium spp., were used.

Cryptosporidium spp. are coccidian parasites that infect a wide range of farm livestock, including cattle, sheep, goats, pigs, horses, and deer, but are mainly a veterinary problem in neonatal ruminants. C. parvum, for example, is a common agent in the etiology of the neonatal diarrhea syndrome of calves, lambs, and goat kids. Widespread asymptomatic carriage of this parasite exists in livestock in the United Kingdom. In humans, cryptosporidiosis occurs most commonly in children <5 years of age, can be life threatening in immunocompromised persons, and is caused predominantly by C. hominis and C. parvum parasites. Fecal–oral transmission can occur directly from animal to person and from person to person or indirectly through contaminated food or water. Typing of Cryptosporidium spp. has been undertaken by the UK Cryptosporidium Reference Unit since 1999. C. parvum was identified from human feces in 12 (75%) of the 16 petting farm outbreaks since 1999 (feces were not submitted for typing in 4). Additionally, Cryptosporidium spp. oocysts were detected and confirmed as C. parvum from suspected sources (lambs, calves) in 4 (33%) of these 12 outbreaks and linked by GP60 subtype to human cases in 3 outbreaks. Zoonotic risk factors in case–control studies of sporadic cryptosporidiosis cases in England and Wales also have identified an association between C. parvum infection and touching farm animals or visiting a farm.

In petting farm outbreaks, Cryptosporidium spp. displayed a seasonal pattern, as did VTEC O157. Cryptosporidiosis outbreaks occurred more often in springtime (18 vs. 5; p = 0.0001) than did VTEC O157 outbreaks, which occurred more frequently during the summer (25 vs. 5; p<0.00001), especially in August. During spring 2010, two additional C. parvum outbreaks associated with contact with lambs at petting farms were reported in England. Control measures included restricting bottle feeding of lambs and enhancing the supervision of hand washing. The associations with outbreaks of cryptosporidiosis in spring and contact with young farm animals also has been reported in Scotland. Despite the 2 separate seasonal peaks of infection, care should be exercised throughout the year. The importance of careful attention to hygiene and supervision of children visiting farms and the need for appropriate facilities, such as those for hand washing, are covered in the UK Health and Safety Executive standards; operators of petting farms are expected to meet these standards. These guidelines also apply to commercial farms hosting open days. A good practice reminder on managing the risks from VTEC O157 in a petting farm context was published by the Health Protection Agency, Health and Safety Executive, and the Local Government Regulation. Guidance on the control of VTEC O157 infections for farms open to public access applies equally to most gastrointestinal pathogens, including Cryptosporidium spp. The need for a sound approach to managing hygiene control measures at petting farms cannot be overemphasized.

Emerging Infectious Diseases
January 11, 2011

Original web page at Emerging Infectious Diseases

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Wild Scottish sheep could help explain differences in immunity

An 11-year study of a population of wild sheep located on a remote island off the coast of Scotland that gauged the animals’ susceptibility to infection may give new insight into why some people get sicker than others when exposed to the same illness. The answer to this medical puzzle may lie in deep-rooted differences in how animals survive and reproduce in the wild, according to the study, which was led by Princeton ecologist Andrea Graham and published in the Oct. 29 issue of Science. The research revealed that the sheep population over time has maintained a balance of those with weaker and stronger levels of immunity and fertility. “This is a groundbreaking study that to my mind will change our whole understanding of the immunoheterogenity in animal populations,” said Peter Hudson, the Willaman Professor of Biology and director of life sciences at Penn State University. “Graham and colleagues show beautifully the tradeoffs in the immune system as a balance… that maximizes reproductive output.”

Graham, an assistant professor of ecology and evolutionary biology at Princeton who also is on the faculty of the University of Edinburgh, led the study of wild Soay sheep on the remote island of Hirta in the St. Kilda archipelago, about 100 miles west of the Scottish mainland. The scientists tested the animals for levels of antibodies, natural molecules produced by the sheep’s immune systems to fend off infections such as influenza or those caused by parasitic worms. The sheep whose blood contained the most antibodies lived the longest, the researchers found. These animals also were most likely to survive harsh winters. However, they failed to produce as many offspring each spring as other sheep. Sheep with lower levels of antibodies tended to die earlier, they found, but also gave birth to more lambs each year. Viewed in terms of breeding and, ultimately, evolutionary success, the differing groups of sheep were equally successful in that the longer-lived but less fertile sheep and the shorter-lived but more fertile sheep produced about the same number of progeny over the course of their lives. The overall balance, the researchers said, could help explain why immunity varies so much among individuals. The tendency to form either strong or weak responses to infection ran in families in the sheep, the researchers also found. “This genetic basis means that natural selection has the chance to shape the trait,” Graham said. If differing responses to infection still result in equal long-term reproductive success, she said, this means “selection seems actually to be maintaining this genetic variation in immunity.”

Such a balance could help explain why vaccines seem to protect some people better than others or why some people get sicker than others when exposed to the same infection. “We have long suspected that strong immune responses should prolong life in the face of infections, but might also be costly to reproduction,” Graham said. “To find evidence for such tradeoff may clarify why animals vary so much in the strength of their immune responses, and even in their predisposition to infection or autoimmunity. The technique used to study immunology in the wild was vital to the importance of the study, according to Lynn Martin, an assistant professor in the department of integrative biology at the University of South Florida. “For so long, the field of immunology has been based on studies of domesticated animals in clean lab environments where animals are given all the food they want, shelter from the elements and few to no challenges with parasites,” Martin said. “These conditions are great to get at the details of how hosts are dealing with parasites at the molecular and cellular level, but they’re not representative of natural conditions and may bias our understanding of immune functions.”

The study also touches on autoimmunity, when the body exhibits such a strong immune response that it attacks its own tissues. The study suggests that autoimmunity, seen in such human diseases as lupus and rheumatoid arthritis, might also occur in the wild. This aspect of the study needs to be further explored, Graham said. The study is significant, according to Andrew Read, a professor of biology and entomology, also at Penn State, because it shows that immunity can both increase and decrease evolutionary success, depending on the circumstances. “This is a really excellent example of the power of long-term ecological studies,” said Read, an expert in the evolutionary genetics of infectious disease.

PhysOrg.com
November 9, 2010

Original web page at PhysOrg.com

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Eye test for neurological diseases in livestock developed

The eyes of sheep infected with scrapie — a neurological disorder similar to mad cow disease — return an intense, almost-white glow when they’re hit with blue excitation light, according to a research project led by Iowa State University’s Jacob Petrich. The findings suggest technologies and techniques can be developed to quickly and noninvasively test for transmissible spongiform encephalopathies, progressive and fatal neurological diseases such as mad cow disease in cattle and Creutzfeldt-Jakob disease in humans. Petrich, in fact, is working to develop a testing device. The findings were published earlier this year in the journal Analytical Chemistry. The project was supported by a grant from the U.S. Department of Defense. The research is the result of an accidental discovery while Petrich and his collaborators were developing a fluorescence spectroscopy device that’s now used in slaughterhouses to test livestock carcasses for feces and possible E. coli contamination. “One day we were testing the apparatus by shining light on the carcass and we saw the spinal cord glow — it fluoresced,” said Petrich, professor and chair of Iowa State’s chemistry department. “We saw the spinal cord through the skin. The light was pretty intense. It was an amazing result.”

That sparked some new thinking: Maybe fluorescence technology could be used to test animals for transmissible spongiform encephalopathies such as bovine spongiform encephalopathy — what’s often called mad cow disease. To reduce the risk of human exposure to the diseases, the brains and spinal cords of animals are removed during slaughter and processing. But there is no quick test to identify animals with the diseases. And so Petrich and a team of researchers began studying the feasibility of a fluorescence test. The researchers collected 140 eyeballs from 73 sheep. Thirty five of those sheep were infected with scrapie; 38 were not. The researchers took fluorescence readings from various parts of the eyes of all the sheep. “The bottom line is the scrapie-positive retinas fluoresced like crazy,” Petrich said. “And the scrapie-negative ones did not.” A previous study published in the journal Veterinary Pathology reported that the function and structure of retinas are altered in cattle infected with transmissible mink encephalopathy. Members of that study team included Iowa State researchers M. Heather West Greenlee, an associate professor of biomedical sciences in the College of Veterinary Medicine; Justin Greenlee, a collaborator assistant professor of biomedical sciences; and Juergen Richt, a collaborator associate professor of veterinary microbiology and preventive medicine. Other studies have reported that lipofuscin, an intracellular fluorescent pigment, accumulates in the eyes of animals infected with the neurological diseases. Petrich and his team attribute the glow from scrapie-positive retinas to the elevated levels of lipofuscin.

Whatever the cause, Petrich said it’s clear there are distinct differences in the fluorescence and spectroscopic signatures of retinas from sheep that were naturally infected with scrapie and those that were not. And so he and his research team think there’s great promise for a diagnostic test based on that discovery. That has Petrich starting to develop a device (he likes to call it a “gizmo”) that could be used in meat plants to test the retinas of animals for signs of neurological diseases. He expects it will take several years to develop, build and test a useful device. “What I like about this is it’s really simple,” Petrich said. “It’s light in and light out.”

Science Daily
November 9, 2010

Original web page at Science Daily

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Severe pneumonia outbreak kills bighorn sheep

Wildlife officials worry an unusually aggressive pneumonia outbreak will result in stagnation in affected bighorn sheep populations. Wildlife officials say an outbreak of bacterial pneumonia killing bighorn sheep herds in five Western states is without precedent. Every year, a small number of bighorn sheep succumb to pneumonia, but this winter Montana, Washington, Utah, Wyoming, and Nevada all have reported unusually high incidences of sickness and death among their wild sheep populations. The outbreak’s toll is difficult to determine, since bighorn sheep roam remote locations, but officials estimate 1,000 sheep in nine wild herds had died as of early April. Some 300 of those deaths represented sick animals that were culled—a measure adopted by three states to prevent the disease from infecting other herds. “I’ve been doing wild sheep work for 30-plus years, and I cannot recall a period of time when there were so many bighorn die-offs going on at once,” said Kevin Hurley, the bighorn sheep coordinator with the Wyoming Game and Fish Department. “A bad year is when you’ve got two or three (pneumonia-related deaths in a herd), and here you’ve got (many) times that,” added Hurley, who chairs the Western Association of Fish and Wildlife Agencies’ Wild Sheep Working Group.

The outbreak is expected to abate in the spring when herds migrate from their winter grazing lands, yet concerns about the long-term impact of the die-offs are mounting. Dr. Peregrine L. Wolff, the Nevada state wildlife veterinarian, says after pneumonia sweeps through an adult sheep population, it then kills off the lambs, and the cycle can repeat itself for several years, leading to herd stagnation. “The population increases by ones and twos instead of 30s and 40s,” Dr. Wolff explained. The lamb die-off is the most worrisome aspect of the outbreak, according to Dr. Kristin G. Mansfield, the Washington state wildlife veterinarian. “We are really going to be monitoring our lamb survival for the next several years to see what kind of impact this disease has had and try to determine whether our interventions are having any effect,” she said. Each state is handling the outbreak differently. In Nevada, government biologists and veterinarians have been tagging herds and using radio collars to monitor them and track die-off. Additionally, more than 60 ill sheep have been darted with doses of tulathromycin, which is more commonly used to treat pneumonia in cattle.

Why this pneumonia outbreak is so widespread is hard to know. A summary of the die-offs through mid-March compiled by the Western Association of Fish and Wildlife Agencies documents instances of confirmed and probable contact between wild and domestic sheep and goats in some of the areas with the highest numbers of bighorn die-offs. Domestic sheep and goats harbor diseases to which they’re immune but which are capable of causing disease in wild sheep. While this interaction between wild and domestic animals may be the cause in some instances of bighorn sickness and death, it doesn’t necessarily explain outbreaks in Washington, Utah, and Wyoming, where no such contact is documented to have occurred. Weather and nutritional stress may also be contributing factors. “Everybody’s looking for one common denominator, one silver bullet answer to what’s going on. Unfortunately, we don’t have it,” Hurley said. This June, in Oregon, the Northern Wild Sheep and Goat Council will host a workshop for affected states and others to share their latest data and the effectiveness of their response protocols so far. Long-term strategies for managing bighorn sheep populations will also be discussed.

JAVMA
May 11, 2010

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New test may help address costly parasite in sheep industry

Researchers at Oregon State University and the University of Georgia have developed an improved, more efficient method to test for the most serious of the parasitic worms in sheep, a problem that causes hundreds of millions of dollars in losses every year to the global sheep and wool industry. This technology is now available, and will allow a faster, easier and less expensive way to test for the presence and quantity of Haemonchus contortus, or “barber pole” worms, a species that is very pathogenic to sheep, goats and llamas. This will help sheep ranchers deal with this problem more quickly and effectively, optimize their management practices, and sometimes avoid costly therapies. Findings about the new test were just published in Veterinary Parasitology, a professional journal. “This particular parasite is much more pathogenic in sheep than other worms, and previous methods to detect it were very labor intensive and often not commercially practical,” said Michael Kent, an OSU professor of microbiology. “Now ranchers and veterinarians can test for this problem and target their management or treatment strategies much more effectively.”

This parasite causes significant production losses, and in some cases it’s the limiting factor to sheep production on pasture lands. The nematodes can cause internal bleeding, which in turn can lead to anemia, poor food conversion and growth, low protein levels, reduced lamb production and wool yield, and in some cases death. Known as the barber pole or wire worm, Haemonchus contortus is a blood-sucking parasite that pierces the lining of the sheep’s stomach. It’s a prolific egg producer, releasing up to 10,000 eggs per day, and often causes problems in warmer climates or during the summer. Once an infection is demonstrated, expensive treatments or complex management strategies are often needed to address it. The new lectin staining test is based on a peanut agglutinin that binds to eggs of the parasite and can be easily visualized with a microscope using ultraviolet light. It’s an improved version of previous technology developed by scientists in Australia that was slower, less effective, more expensive and required more advanced training to perform, researchers say.

The relatively inexpensive test was developed by microbiologists and veterinary doctors at OSU and UGA, and is now available through those institutions. Its use should continue to expand and become more readily available around the world, Kent said. The test may also be of special value to ranchers interested in organic production of sheep, goats and llamas, who try to avoid use of chemical treatments in maintaining the health of their animals. “One of the current testing tools commonly used by sheep and goat farmers in dealing with H. contortus is the FAMACHA© method, in which the farmer compares the animal’s lower eyelid color to swatches on a card to determine the animal’s anemia status,” said Bob Storey, a UGA researcher who co-developed the lectin staining test. “This method only works in situations where H. contortus is the primary parasite in a given herd’s worm population. The new lectin staining test allows for a faster and less expensive method of determining the predominance of H. contortus in a herd worm population, thereby making it easier for producers to determine if FAMACHA© can be a useful tool for them. Additionally, for the veterinarian dealing with an anemic animal and a heavy parasite burden, the lectin staining test provides quick feedback as to whether the anemia is parasite-based or may be due to another cause.” The test requires only a small amount of feces, and results are available in as little as two days. Anyone interested in obtaining the test can get information on sampling, test results and fees from the Veterinary Diagnostic Laboratory at OSU (http://oregonstate.edu/vetmed/diagnostic or 541/752-5501), or Bob Storey (Dept. of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Ga., 30602 or 706/542-0195). As with any animal health concerns, results should be reviewed with a veterinarian so that proper treatment programs can be put in place, researchers said.

Science Daily
January 26, 2010

Original web page at Science Daily

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Genetic characterization of foot-and-mouth disease viruses, Ethiopia, 1981–2007

Foot-and-mouth disease (FMD) is endemic to sub-Saharan Africa. To further understand its complex epidemiology, which involves multiple virus serotypes and host species, we characterized the viruses recovered from FMD outbreaks in Ethiopia during 1981–2007. We detected 5 of the 7 FMDV serotypes (O, A, C, Southern African Territories [SAT] 1, and SAT 2). Serotype O predominated, followed by serotype A; type C was not recognized after 1983. Phylogenetic analysis of virus protein 1 sequences indicated emergence of a new topotype within serotype O, East Africa 4. In 2007, serotype SAT 1 was detected in Ethiopia and formed a new distinct topotype (IX), and serotype SAT 2 reappeared after an apparent gap of 16 years. The diversity of viruses highlights the role of this region as a reservoir for FMD virus, and their continuing emergence in Ethiopia will greatly affect spread and consequent control strategy of the disease on this continent. Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious and economically devastating disease of cloven-hooved domestic and wild animals. It can cause a high number of deaths among young animals and production losses in adults and is the single most limiting constraint to international trade of live animals and animal products. FMDV belongs to the genus Aphthovirus in the family Picornaviridae and possesses a single strand of positive-sense RNA genome. It has a high mutation rate because the viral RNA–dependent RNA polymerase lacks proofreading ability, resulting in 7 immunogenically distinct serotypes (O, A, C, Southern African Territories [SAT] 1, SAT 2, SAT 3, and Asia 1) and numerous and constantly evolving variants showing a spectrum of antigenic diversity. Vaccination is an effective way to control FMD; however, the protection conferred by vaccination or infection is usually serotype specific and sometimes incomplete within a serotype. Emergence of these viruses in Ethiopia will greatly affect spread and consequent control strategy of the disease on this continent because restriction of animal movement between many African countries is limited.

Emerging Infectious Diseases
September 22, 2009

Original web page at Emerging Infectious Diseases

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Mary had a lot of lambs: Researchers identify way to accelerate sheep breeding

Mary had a little lamb, but only once a year. However, Cornell Sheep Program researchers have discovered an unusual form of a gene that prompts ewes to breed out of season as well as conceive at younger ages and more frequently. They conducted a simple genetic test to identify the presence of the unusual form of the gene, the so-called M allele that other researchers had suspected might be correlated with out-of-season fertility, in their test flock and then validated the gene’s relationship with aseasonal breeding by observing that trait in the flock. The finding, published in the August issue of the Journal of Animal Science (Vol. 87, No. 8), may be a boon for the sheep industry worldwide, especially when combined with the Sheep Program’s STAR system – a method to manage ewes to lamb five times in three years rather than once a year. “The primary biological limit for sheep production worldwide is the seasonality of breeding, but the market for high-quality lamb is a 52-week thing,” said Doug Hogue, professor emeritus of animal science in the College of Agriculture and Life Sciences. His Cornell colleague Mike Thonney and former Cornell postdoctoral researcher Raluca Mateescu, now at Oklahoma State University co-authored the paper with Andrea Lunsford, a graduate student at OSU.

Although the presence of the M allele has been definitively correlated with the ability to breed out of season, the researchers caution that it may only be a marker for the gene actually responsible for the trait. “Breeding out of season is a complex trait,” Mateescu said, “so there are a lot of genes controlling it.” Mateescu observed the phenotype – the physical expression of the gene – in the researchers’ flock during a postdoctoral fellowship at Cornell. “In this case, we’re talking about a receptor gene for melatonin,” Thonney explained. Melatonin is a naturally produced hormone commonly found in many animals. The change in the DNA sequence of the M allele does not change the amino acid sequence of the protein. This means that it may be an accurate indicator for the phenotype of breeding out of season, though it’s uncertain whether the gene actually impacts how the sheep’s body reacts to melatonin. And there may be a risk of losing the association over generations, the researchers said, as recombination could occur between the marker and the functional gene. Thus, the researchers stress that it will be very important to validate the gene’s ability to indicate for aseasonal breeding each time the allele is bred into a new sheep population.

“I think it’s very exciting … we only have one gene, but it’s definitely a tool that farmers can use,” said Mateescu, who is now focusing on placing markers across the sheep’s entire genome to more accurately determine which gene or genes directly affect the trait of aseasonal reproduction. The allele is particularly useful for management under the STAR system, developed by Hogue and Cornell sheep farm manager Brian Magee in the early 1980s, which uses nutrition and conventional breeding techniques to reduce the time between heats. “If a ewe doesn’t get pregnant when she is supposed to, instead of a year, it’s only 73 days [using the STAR system] until she has another opportunity,” Thonney said. While the STAR system requires better nutrition and more farm labor to manage the lambing, each lambing event involves fewer ewes than traditional yearly lambing. The researchers hope that the discovery of the M allele may help the STAR system adapt to consistently high levels of production without any additional risk to flock health.

Science Daily
August 25, 2009

Original web page at Science Daily

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Secret of Scotland’s shrinking sheep solved

Call it the case of the shrinking sheep. On the remote Scottish island of Hirta, sheep have been getting smaller, shrinking an average of 5% over the last 24 years. Don’t blame evolution, though. Researchers say climate change is the real culprit. The Hirta sheep belong to a breed known as Soay, after the remote Scottish island where they arose. One of the most primitive forms of domestic sheep, Soays first came to Hirta in 1932. Because Hirta is a remote island, its sheep have remained genetically isolated, and no other sheep have been brought in for breeding. That’s made Hirta’s Soays ideal subjects for scientific study. In 2007, scientists first reported that the sheep were smaller than they had been in the past. This prompted biologist Arpat Ozgul of Imperial College London and colleagues to analyze body weight data going back 24 years. The researchers confirmed that the Soays had indeed been getting smaller. And, as they report online today in Science, the reason appears to be climate change.

In the past, Hirta’s sheep gorged on grass during their first summer, the team notes, piling on the weight in order to make it through the island’s typically harsh winters. But over the past quarter-century, Hirta has had unusually short and mild winters. As a result, Ozgul and colleagues propose, grass has become available for more months of the year, meaning the Soay sheep do not have to bulk up as much. In addition, Hirta’s harsh winters used to kill small ewes born to young mothers. But now these small ewes survive–and because of their low birth weight, they never get as big as normal sheep. That drives down the average size of the entire population, the team reports. Further mathematical modeling allowed the researchers to propose that natural selection has played little–if any–role in the shrinkage of the Hirta sheep. Malcolm Gordon, an ecologist and evolutionary biologist at the University of California, Los Angeles, praises the study. But he says that other mechanisms may be at work. “Changing environmental conditions on the island … may have led to changes in the chemical composition and nutritional value of the plant foods the sheep eat,” he says, and that may have shrunk the sheep. Though at the end of the day, he says, climate change could still be the root cause.

ScienceNow
July 28, 2009

Original web page at ScienceNow

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Possible basis of memories for different smells uncovered

Ben W. Strowbridge, Ph.D, associate professor of Neuroscience and Physiology/Biophysics, and Yuan Gao, a Ph.D. student in the neurosciences program at Case Western Reserve University School of Medicine, are the first to discover a form of synaptic memory in the olfactory bulb, the part of the brain that processes the sense of smell. Their study, entitled “Long-term plasticity of excitatory inputs to granule cells in the rat olfactory bulb” will be published in the June 2009 issue of Nature Neuroscience and is currently available online. In the 1970s, scientists discovered that elemental connections between brain cells, called synapses, could change their strength following brief periods of activity. This process, called long-term potentiation (LTP), is the leading candidate to explain how we store information about specific places, names and events. While laboratories around the world have found LTP in nearly every part of the mammalian brain there was one glaring exception: the part of the brain that first processes the sense of smell, the olfactory bulb.

Gao, a fourth-year graduate student, had learned that damaging olfactory sensory pathways prevents sheep from forming selective bonds with her own lambs, causing them to adopt lambs from other mothers. This cued her curiosity as to how a mother ewe forms such a selective bond with her lamb within several hours of parturition, a bond that is primarily dependent on olfactory sensory recognition. Using an innovative home-built laser microscope, Strowbridge and Gao were able to determine that the olfactory bulb does in fact have LTP. This specialized microscope used an advanced imaging technique called “2-photon excitation” which enabled the researchers to see entire brain cells and then test whether different types of inputs to the cell could mediate olfactory memory. “The real surprise in the study was the specific brain connection that changed following experience. It was a rarely-studied brain projection from the cortex back to the olfactory bulb” said Strowbridge.

Neuroscientists commonly believe that the way the brain processes information is similar to climbing a pyramid—starting from the bottom and working up to the top. All of the sensory systems have a large number of low-level cells that do very simple things (forming the base of the pyramid), and then they feed their results to brain areas higher up the pyramid. The brain cells in these “higher” regions begin to reflect abstract concepts, such as the shape of human faces, in the visual system or melodies in the auditory system. The brain areas related to our conscious perception of the world are presumably at the top of pyramid. However, the Case Western Reserve University researchers found that the brain circuit had the ability to change with experience was unexpectedly a connection from high in the pyramid (the olfactory cortex) back to a lower level (the olfactory bulb).

One of the implications of Strowbridge and Gao’s work is that the brain may learn about different smells by having higher brain areas first make a prediction about which scent it might be, and then test that prediction against the actual sensory data coming into the brain. “Our work suggests that there is much more talking back-and-forth between higher and lower brain areas during olfactory learning,” continued Strowbridge. “We are just beginning to explore the function of the feedback circuits that inform low-level parts of the brain, like the olfactory bulb, about predictions made by higher-order brain regions. The 2-photon microscope used in this study is an ideal tool to ask what these different brain circuits are actually doing.” Previous studies had suggested that the circuit changes associated with olfactory learning, such as sheep learning to recognize their own lambs though their characteristic scents, involved changes in the olfactory bulb. Strowbridge and Gao discovered that certain olfactory brain circuits can change with experience. This discovery provides a possible explanation for how animals can form memories of particular scents.

EurekAlert! Medicine
May 19, 2009

Original web page at EurekAlert! Medicine

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Closing in on goat scrapie

Goats are tough, spirited animals, but they’re no match for scrapie, a form of transmissible spongiform encephalopathy. Now, with a “helping hand” from science, the animals’ plight could take a turn for the better. Toward that end, Agricultural Research Service (ARS) scientists and their collaborators have developed a live-animal test to detect scrapie in goats. Called the rectal mucosa biopsy test (RMBT) or rectal biopsy, the new method involves snipping a tiny piece of lymphoid tissue from the lining of an afflicted animal’s rectum. A dab of local anesthetic eases the animal’s discomfort, notes microbiologist Katherine O’Rourke with the ARS Animal Diseases Research Unit in Pullman, Wash. Lymphoid tissue is used because it collects malformed proteins called prions, which are thought to cause scrapie, adds O’Rourke. She’s a member of a scrapie research team that includes Washington State University, Colorado State University, the Animal and Plant Health Inspection Service (APHIS), the National Park Service and the Canadian Food Inspection Agency.

On a related front, ARS Pullman geneticist Stephen White is leading studies to characterize the prion protein gene of goats and identify differences between individual animals and breeds harboring the gene. His team has so far examined the sequences and distribution of alleles—alternative forms of genes—from 446 goats representing 10 breeds, including Alpine, Angora, Boer and Nubian. The ARS Pullman lab also is collaborating with APHIS to formulate a strategy aimed at helping the U.S. goat industry eliminate scrapie from its herd, which numbers four million head. Hardships imposed by scrapie on America’s goat and sheep producers include the physical loss of animals, costs of disposal of carcasses and offal, trade restrictions and diminished domestic and international markets for breeding stock, semen and embryos.

Science Daily
May 4, 2009

Original web page at Science Daily

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FDA planning to ban cattle brains, spinal cords from all animal feed

Federal authorities (USA) are accepting comments on a planned regulation that would prohibit use of some cattle tissues in all animal feeds by late April. The regulation published by the Food and Drug Administration is intended to reduce the risk of transmission of bovine spongiform encephalopathy by prohibiting use of brains and spinal cords from cattle 30 months and older in all animal feed. The materials are already prohibited from use in feed for ruminants, including cattle, sheep, and goats. “The added measure of excluding high-risk materials from all animal feeds addresses risks associated with accidental feeding of such material to cattle, which could occur through cross-contamination of ruminant feed with non-ruminant feed or feed ingredients during manufacture and transport or through misfeeding of non-ruminant feed to ruminants on the farm,” states a Nov. 25, 2008 update from the FDA.

The regulation would also ban from animal feed the entire carcasses of all BSE test-positive cattle, the entire carcass of any cow 30 months or older that is not inspected and passed for human consumption and from which the brain and spinal cord is not removed, tallow derived from the prohibited materials that contain more than 0.15 percent insoluble impurities, and mechanically separated beef derived from the prohibited materials, according to information from the FDA. The FDA also released in late November a report indicating that, of 7,876 firms that handle materials prohibited from use in ruminant feed, none had violations of the Ruminant Feed Ban that warranted regulatory sanctions during their most recent inspections, and 121 required voluntary corrective action. The firms examined by state and federal inspectors include renderers, feed mills, protein blenders, ruminant feeders, on-farm mixers, pet food manufacturers, animal feed salvagers, distributors, retailers, and animal feed transporters.

JAVMA
January 13, 2009

Original web page at JAVMA

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Old sheep raising the population growth

Populations of wild animals face the challenge of surviving in a changing climate. Researchers at Imperial College London and Université Claude Bernard Lyon have shown how a sheep population on a remote island off the west coast of Scotland responds to two consequences of climate change: altered food availability and the unpredictability of winter storms. Dr. Thomas Ezard, lead author of the study, revealed, “When times are good and food is plentiful, lambs contribute almost twice as much to changes in population size than when times are hard. On the flip side, the oldest sheep contribute most to population growth when conditions are harsh.” The work, published in the September issue of The American Naturalist, suggests that the dynamics of populations are influenced not only by the weather but also by the ability of individuals to respond to it. New mathematical breakthroughs have made it possible to show how environmental change affects populations, like these sheep. The key is appreciating (1) how weather affects individual sheep and (2) how the weather changes from one year to the next. If consecutive years have similar weather, the dynamics of the population will be very different than if conditions are unrelated from one year to the next. Professor Tim Coulson concluded, “A thorough understanding of the likely effects of climate change on the ecology of wild populations requires linking populations to their environment. This demands application of innovative mathematical methods, as used here.”

EurekAlert! Medicine
September 16, 2008

Original web page at Eurek Alert! Medicine

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Resistant prions: Can they be transmitted by environment as well as direct contact?

Prions, the pathogens that cause scrapie in sheep, can survive in the ground for several years, as researchers have discovered. Animals can become infected via contaminated pastures. It is not yet known whether the pathogens that cause BSE and CWD are equally resistant. A flock of sheep at pasture – a seemingly idyllic scene. But appearances can be deceptive: If the animals are suffering from scrapie, entire flocks may perish. Scrapie is an infectious disease in which prions destroy the animal’s brain, rather like BSE. The brain becomes porous, the sheep lose their orientation, they suffer from strong itching sensations and scrape off their fleece. Eventually, the infected animals die.

It is difficult to contain the disease – all too often, scrapie will break out again on the same farm several months or years after it has apparently been eradicated. Are the prions transmitted not only by direct contact, but also by the environment – perhaps by the pastures? How long do prions that get into the pasture via the saliva and excrements of the sick animals, persist in the ground? Together with fellow-scientists from the Robert Koch Institute in Berlin and the Friedrich Loeffler Institute (Federal Research Institute for Animal Health) on the island of Riems, research scientists from the Fraunhofer Institute for Molecular Biology and Applied Ecology IME in Schmallenberg investigated these questions on behalf of the German Ministry for Environment, Nature Conservation and Nuclear Safety BMU. “We mixed soil samples with scrapie pathogens to find out how long the pathogens would survive,” says Dr. Björn Seidel, who headed the investigations at IME. “Even after 29 months, in other words more than two years, we were still able to detect prions in the soil.”

But are these prions still infectious? “The soil actually seems to increase the infectiousness of the pathogens. The incubation period – the time it takes for the disease to break out – is exceedingly short even after the prions have persisted in the soil for 29 months. All of the animals that were given contaminated soil became sick within a very short time. These results indicate that fresh incidences of scrapie among sheep are due to contaminated pastures,” says Seidel in summary. The results of the study reveal that sheep may even become infected from the surface water, though the risk of infection is much lower in this case. There is no danger to humans, however: scrapie pathogens seem unable to affect them. Another cause for concern is chronic wasting disease (CWD). Like BSE and scrapie, this is caused by prions, but it mainly affects deer. The numbers of infected animals in North America are rising steeply. How long do BSE and CWD prions survive in the ground? “To find this out, we urgently need to carry out further tests. The appropriate research applications have already been submitted,” says Seidel.

Science Daily
September 2, 2008

Original web page at Science Daily

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Bluetongue spreads despite vaccinations

Bluetongue is back. It has survived another winter in northern Europe, and now farmers are vaccinating livestock in a race against the biting midges that carry the virus. The first cases of the disease, which affects ruminants, began to surface this month, with France so far reporting 260. Most are located along the front line of last year’s outbreaks, suggesting that the epidemic is spreading into new territory despite France’s compulsory vaccination policy. In England, voluntary vaccination has been rolled out across the country from the south-east, where bluetongue arrived last year. The vaccination “front” has now reached Yorkshire in northern England, alarmingly close to the country’s main sheep areas. The disease kills sheep but only makes cattle ill.

Sheep just outside the vaccinated zone are at high risk, being close to potential infection, but are unlikely to be vaccinated till autumn. Much depends on whether enough farmers south of the line have vaccinated their livestock to slow the spread of the virus. The number of cases to date in France, though, suggests that it may be hard to stop.

New Scientist
August 19, 2008

Original web page at New Scientist

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Genetic basis for the black sheep of the family

Coat color of wild and domestic animals is a critical trait that has significant biological and economic impact. Researchers have now identified the genetic basis for black coat color, and white, in a breed of domestic sheep. In the wild, mammalian coat color is essential for camouflage and plays a role in social behavior. Coat color also strongly influences the animals we choose to breed both as livestock and as pets. Understanding the genetic determinants of coat color in livestock species such as sheep, specifically bred for their coat color, is critical for improving efficient selection of the desired trait. Classical genetics has associated alternative forms, or alleles, of the agouti signaling protein gene (ASIP) with coat color variation in a number of mammals including mice, rats, dogs, cats, pigs, and sheep. However, most research has been focused on the mouse, with little understood about the genetic basis for coat color in economically important livestock species such as sheep.

The wild-type coat color of sheep is typically dark-bodied with a pale belly, however sheep raisers have strongly selected for a uniformly white coat domestic sheep. A problem for the sheep industry is a recessive black “non-agouti” allele of the ASIP gene carried by white sheep that cannot be distinguished within the flock, resulting in black coat color at a low, but persistent frequency. Determining the exact genetic differences at the ASIP locus could assist in efficient selection for white coat color. Scientists at the CSIRO Queensland Bioscience Precinct in Australia have now taken this step and identified the molecular mechanisms underlying white and black coat color in domestic sheep. The researchers investigated the genetic architecture of the ASIP gene in several sheep breeds by sequencing the ASIP locus and measuring gene expression. “Surprisingly what we found was in fact that the genetic cause of domestic white and black sheep involves a novel tandem duplication affecting the ovine agouti gene and two other neighboring genes, AHCY and ITCH,” explains Dr. Belinda Norris, lead author of the study.

“We discovered a novel mechanism in which the dominant white sheep is caused by the ubiquitous expression of a duplicated agouti coding sequence located immediately downstream of a duplicated ITCH gene promoter region.” It was found that recessive black sheep harbor only poorly expressed non-duplicated agouti alleles, likely a result of a defective single-copy ancestral agouti gene promoter. The researchers also studied the ASIP locus in Barbary sheep, an ancient species exhibiting a tan body and pale belly. They confirmed in this ancient sheep that expression of a single-copy agouti gene determines coat color patterning, similarly to findings previously described in mice and pigs. Norris notes that this work will aid in the development of gene copy number detection and analysis methods in the mapping and association of heritable traits in livestock animals. For sheep raisers, this could ultimately mean a genetic test that would identify carriers of the black non-agouti allele. Furthermore, these findings will help to unravel the events leading to the domestication of sheep, and future work may be able to pinpoint when the dominant Agouti mutation occurred, and whether it occurred as single or multiple events.

Science Daily
July 22, 2008

Original web page at Science Daily

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Sheep’s sex determined by diet prior to pregnancy

Maternal diet influences the chances of having male or female offspring. New research has demonstrated that ewes fed a diet enriched with polyunsaturated fats for one month prior to conception have a significantly higher chance of giving birth to male offspring. This study was carried out by a team of researchers from the Division of Animal Sciences at the University of Missouri and led by R. Michael Roberts. Roberts explains how diet at the time of conception is the most important factor when it comes to influencing the sex of the offspring: “Our study ruled out body condition, ewe weight, previous births, time of breeding, and likely dominance as reasons for the gender skewing. Rather, it was the composition of the diet consumed in the time period around conception that was responsible for this sex-ratio effect.”

Polyunsaturated fats are essential nutrients. It is believed that the dietary ratio between omega-3 and omega-6 fats has important biological effects, especially in terms of inflammation, immunity and central nervous system signalling. The omega-6 fats used in this study were protected from digestion by naturally occurring rumen bacteria to ensure that they would be absorbed through the intestines of the sheep. In animal social groups where a small number of dominant males mate with a large number of females, it has been theorised that having male offspring would be of genetic advantage to a very healthy, well fed female, while females consuming a poorer diet would have greater genetic success by giving birth to female offspring. According to Roberts: “Although this theory is attractive, former observations have often been contradictory, leading some to dismiss its relevance. This is the first experimental study in controlled conditions showing that supplementing maternal diet, in this case by increasing omega-6 polyunsaturated fatty acid intake, can skew the sex ratio towards males in a farm species.” These findings will be important to the livestock industry. As Roberts points out, “Increasing the amount of fat in feed during the breeding period could provide a means of controlling the sex ratio of offspring born to a herd or flock.”

Science Daily
June 24, 2008

Original web page at Science Daily

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Secret of Scottish sheep evolution discovered

Researchers from the University of Sheffield, as part of an international team, have discovered the secret of why dark sheep on a remote Scottish Island are mysteriously declining, seemingly contradicting Darwin’s evolutionary theory. Dr Jacob Gratten and Dr Jon Slate, from the University’s Department of Animal and Plant Sciences, led the team, which found that the gene responsible for dark coat colour is linked to other genes that reduce an animal’s fitness. The researchers looked at coat colour in a feral population of Soay sheep on Hirta in the St Kilda Archipelago. On Hirta about three quarters of sheep have dark brown coats, while the remaining quarter have light sandy coats. However, despite the fact that the dark-coated Soay sheep are larger, which is usually linked to survival and reproductive success, the frequency of light-coated sheep has increased over the last 20 years.

Darwin’s theory would have predicted that because dark-coated sheep appear fitter that they would do better than light-coated sheep, until only dark-coated sheep remained in the population. However, this study shows that the process of evolution by natural selection in Soay sheep, although still evident, is actually more complex than this. Dr Gratten and colleagues used a statistical genetics approach similar to that used by medical geneticists, when trying to map genes for human disease such as heart disease or diabetes. They found that the dark coat trait is usually co-inherited with a set of genes that increase size but decrease reproductive success. The light coat trait is usually co-inherited with a set of genes that decrease size but increase reproductive success.

This discovery means that sheep with one copy of the dark gene and one copy of the light gene are quite large and also have quite high reproductive success. Sheep with two copies of the dark gene are larger still, but have poor reproductive success. Sheep with two copies of the light gene are small, but still have quite high reproductive success. This means that the two types of dark sheep although indistinguishable visually, vary in Darwinian fitness. The study was based on over 20 years of field data, and involved researchers from the University of Edinburgh and the Queensland Institute of Medical Research in Brisbane, as well as members of the University of Sheffield. Dr Jacob Gratten said: “The aim of this study was to improve understanding of how evolution by natural selection operates. The study addresses an important problem in evolutionary biology. It shows that predicting the evolutionary response to selection is difficult without knowledge of which genes are in close proximity to each other. It also highlights that an understanding of the underlying genetic basis of a highly visible trait was necessary in order to understand its evolution.”

Science Daily
February 5, 2008

Original web page at Science Daily

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Vaginal insemination for ewe

The effect of different thawing procedures for ram semen frozen in mini tubes and mini straws on the fertility of sheep was tested in a field trial. Altogether, 719 Norwegian Crossbred ewes, aged between six months and six-and-a-half years from 8 farms, were inseminated vaginally in natural oestrus with frozen-thawed semen. Mini tubes were thawed at 70 °C for 8 sec (T70) and mini straws either at 50 °C for 9 sec (S50) or at 35 °C for 12 sec. Vaginal insemination with 200 x 106 spermatozoa resulted in 25-days non-return rates of 63.2, 59.6, and 62.5 % (overall 61.8 %), respectively, and lambing rates of 56.8, 55.0, and 59.2 % (overall 57.0 %), respectively. No significant effect on fertility (as 25-days non-return- or lambing rate) was seen for straw type/thawing temperature (P=0.5/0.5), but semen filled in mini straws and thawed at 35 °C resulted numerically in the highest lambing rate (59.2 %). A significant effect was, however, seen for farmer (P=>0.0001/>0.0001) and ram (P=0.009/0.002). Moreover, age of the ewes had a significant effect on the NR rate (0.007), but not on lambing rate (P=0.2). A vaginal deposition of frozen ram semen containing approximately 200 x 106 spermatozoa, filled in mini straws and thawed at 35 °C is a simplified technique that under field conditions and used on a do-it-yourself regime gives acceptable lambing rates in Norway.

BioMed Central
October 16, 2007

Original web page at Acta Veterinaria Scandinavica

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New strategy to create genetically-modified large animals

Researchers at the University of Pennsylvania School of Veterinary Medicine have demonstrated the potential of a new strategy for genetic modification of large animals. The method employs a harmless gene therapy virus that transfers a genetic modification to male reproductive cells, which is then passed naturally on to offspring. Ina Dobrinski, associate professor and director of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet, and her colleagues introduced adeno-associated virus, AAV, to male germline stem cells in both goats and mice. The study showed that AAV stably transduced male germ line stem cells and led to transgene transmission through the male germ line. The findings, available online in The FASEB Journal and in the February 2008 print edition, are the first report of transgenesis via germ cell transplantation in a non-rodent species, a promising approach to germ line genetic modification. It also demonstrates that germline transduction and germ cell transplantation in large animals provides an approach that is potentially less costly than microinjection and cloning, the traditional methods used to generate transgenic large animal models for biomedical research.

Researchers used mouse germ cells harvested from experimentally induced cryptorchid donor testes that were then exposed in vitro to AAV vectors carrying a green fluorescent protein transgene and transplanted to germ cell-depleted recipient testes, resulting in colonization of the recipient testes by transgenic donor cells. When researchers mated these recipient males with wild-type females, 10 percent of offspring carried the gene originally introduced into the transplanted germ cells, meaning the genetic modification had been passed on. To broaden the approach to non-rodent species, AAV-transduced germ cells from goats were transplanted to recipient males in which endogenous germ cells had been depleted by fractionated testicular irradiation. Transgenic germ cells colonized recipient testes and produced transgenic sperm. When semen was used for in vitro fertilization, 10 percent of embryos were transgenic.

“Initially, the team used the established germ cell transplantation model in the mouse to investigate whether AAV-mediated transduction of germ cells was possible and could result in transgene transmission,” Dobrinski said. “To broaden the applicability of the results for different mammalian species, the approach was then applied to a large animal species in which germ cell transplantation-mediated transgenesis would provide an important alternate approach to the generation of transgenic animal models for biomedical research.” Currently, somatic cell nuclear transfer or pronuclear injection is used to generate transgenic animals. These inefficient and difficult methods also carry a risk of producing offspring with developmental abnormalities. The use of retroviral or lentiviral vectors has been reported in rodents, but it requires that animals be handled and maintained under higher biosafety precautions that render this approach less practical for transgenesis in large animal species. In contrast, animals exposed to AAV can be maintained under standard husbandry conditions. AAV is a dependent virus that carries no disease and causes only a very mild response from the immune system. Because AAV can infect both dividing and non-dividing cells and passes its genome, it is considered an excellent candidate for use in gene therapy.

Science Daily
October 2, 2007

Original web page at Science Daily

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Calls for vaccination against bluetongue disease

A vaccine is available for the deadly animal virus that has been rampaging across northern Europe, and was reported for the first time in the UK last week. On Wednesday, agriculture ministers from the Netherlands, Belgium, France and Germany will ask the EU to approve widespread vaccination. But to stop a bigger outbreak next year, animals must be vaccinated in spring before infected, biting flies which spread the disease start swarming. And the vaccine may not be ready, because the plant in the UK that makes it has been shut following safety concerns. Bluetongue is common in livestock in warm countries, and is carried by tiny biting midges of the genus Culicoides. Symptoms are often mild in cattle, but it can kill up to 80% of infected sheep. Cold winters previously kept the disease out of temperate countries by killing off any infected midges.

As climate has warmed, however, bluetongue has spread into countries such as Spain and Italy. In July 2006, it broke out for the first time in the Netherlands, and quickly spread to Belgium, Germany, France and Luxembourg.In August 2007, it hit those countries again, showing the infection can now persist through Europe’s winters. It has also spread – this year has seen nearly 5000 outbreaks. With infected animals near the Belgian coast experts predicted that infected midges, which can be blown 300 kilometres and carried in vehicles, would reach the UK. Two cows with bluetongue have now been confirmed on a farm near Ipswich, UK, since 22 September. Because of previous outbreaks in southern Europe, the French-owned vaccine manufacturer Merial started developing vaccines three years ago, with initial money from the European Commission. Spanish and Italian farmers have been using them successfully for several years, says Philip Connolly, a Merial spokesman.

There are 24 immunologically distinct “serotypes” of bluetongue virus – vaccine against one does not work against another. European farmers vaccinate against serotypes 2 and 4. The UK and northern Europe have been hit by serotype 8, apparently from Sub-Saharan Africa. But there is a vaccine to that too. “We decided last January to start serotype 8 vaccine development,” says Connolly. “The vaccines to 2 and 4 work well, so we are confident this will be just as effective.” He likens the switch in serotype to the changes in each year’s flu vaccine, which do not require separate testing. “We had every intention of having the vaccine ready for early 2008,” Connolly told New Scientist. “But our factory isn’t allowed to touch live virus.” The vaccine is made from killed bluetongue virus. The plant at Pirbright where Merial manufactures it was implicated in an escape of foot and mouth disease virus in August, and the plant has shut down all work with live viruses since. “We would have to be back up and running by late October to do it in time,” says Connolly. Another vaccine company, Intervet, has developed a serotype 8 vaccine, but will not have an approved plant in time.

New Scientist
October 2, 2007

Original web page at New Scientist

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Manganese levels increase in scrapie-infected sheep before clinical symptoms develop

Sheep infected with scrapie and cows infected with BSE have elevated levels of manganese in their blood before clinical symptoms appear, according to new research. The findings, published in the Journal of Animal Science, also show that scrapie-resistant sheep produce elevated levels of the metal when “challenged” with the disease. This suggests that elevated manganese levels in the blood and central nervous system are caused by the animal’s initial response to the disease. The findings raise the possibility of using manganese levels in the blood as a potential diagnostic marker for prion infection. At present, only post-mortem examination of the brain tissue gives a certain diagnosis. Scrapie, Bovine Spongiform Encephalopathy (BSE) and Creutzfeldt-Jakob Disease (CJD) are neurodegenerative diseases that affect the brain and nervous system of sheep, cows and humans respectively.

They are transmitted by mis-formed prion proteins which cause tiny loss of brain cell in different regions of the brain, leading to impairment of brain function, including memory changes, personality changes and problems with movement that worsen over time. “Definite diagnosis of prion disease is currently only possible post-mortem,” said Professor David Brown from the University of Bath who led the study with colleagues from the universities of Hull and Edinburgh. “These findings suggest that elevated blood manganese could be used as a robust diagnostic marker for prion infection, even before the onset of apparent clinical disease. “In practice, however, it would be difficult implement a widespread screening programme, given that the mass spectrometry we use to measure levels is expensive and labour intensive.” The research builds on the 2002 discovery that mice infected with scrapie have higher levels of manganese. This is the first time that tissue from farm animals infected with prion diseases have been studied in this way.

One of the most interesting findings from this study came from the analysis of blood samples from scrapie-resistant sheep. When challenged with the disease, these sheep showed similar levels of manganese as non-resistant sheep challenged in the same way. “Elevated levels of manganese in scrapie-resistant sheep imply that the change in blood manganese is a result of the scrapie challenge and not a consequence of scrapie pathology,” said Professor Brown, from the University of Bath’s Department of Biology & Biochemistry. “Although these sheep are considered to be resistant to scrapie, they do show some indications that scrapie challenge results in similar metabolic changes as occur in non-resistant sheep.” Another interesting finding was that although levels of manganese were elevated, there were differences in the blood levels of selenium and molybdenum in experimental and field cases of BSE in cows. This suggests that the way a cow acquires the disease affects the metabolic processes involved. “The origin of the increased manganese in the brains and blood of infected animals remains unknown,” said Professor Brown. “The three possibilities are that there is decreased secretion of manganese from the body, release of manganese from other tissues or increased absorption of manganese from the environment. “Currently there is insufficient evidence to favour any of these three theories.”

Science Daily
August 7, 2007

Original web page at Science Daily