Reverse genetics better vaccines

Cornell-Israel collaboration works backwards to fight virus threatening livestock trade worldwide

European livestock beware: bluetongue virus is coming your way, and it’s deadlier than ever. Once limited to warmer climes, the insect-borne virus’s new highly pathogenic strain has been spreading northward since 2006, reaching farther into Europe than ever before. Bluetongue’s rise threatens ruminants and the industries depending on them. Sheep and deer suffer most, developing dangerously high fevers, swollen mouths, and occasionally the disease’s signature blue tongue. Most infected sheep and deer die; other ruminants (cattle, goats, camels, buffalo, and antelopes) show milder symptoms but can carry the disease, further enabling its spread.

Illnesses, deaths, and international trade restrictions due to bluetongue have cost the world economy billions, including the United States, whose more benign strains still hinder livestock-related exports to bluetongue-free countries. Vaccines work weakly at best: with 25 separate strains each needing yearly updates, the quickly-evolving bluetongue virus seems to defy defense.

In the arms race between virus and victim, human knowledge is catching up. Dr. John Parker, virologist at Cornell University College of Veterinary Medicine’s Baker Institute for Animal Health, has joined Israeli microbiologist Dr. Marcelo Ehrlich of the University of Tel Aviv to learn what makes bluetongue tick, unlocking the inner workings of its deadliest strain with discoveries that could help in designing a lasting universal vaccine.

“No one thought bluetongue would spread this far, and with current vaccines even the most watchful countries can’t protect themselves from it,” said Parker. “Insects carrying bluetongue don’t respect national borders, and climate change has let them expand their range. Meanwhile this new strain is especially virulent: good at bursting through cells to infect new ones. If we can learn how bluetongue kills cells and why this strain is so good at it, we may be able to better control its spread.”

When bluetongue invades a cell it creates a protein called NS3, reproduces, and eventually bursts through the cell. All strains produce NS3, but the more virulent strains produce an altered form. When experiments in Israel suggested NS3 helps degrade cells so the virus can escape, Ehrlich contacted Parker, a former collaborator, who studies cell death.

The pair has created a novel plasmid-based system to discover exactly what NS3 does using reverse genetics. While standard “forward” genetics start with a trait then look for the genes influencing it, recently developed “reverse” genetics systems manipulate specific genes to look for their effects. Parker and Ehrlich are making mutant bluetongue viruses that alter NS3 to see what it does in a cell.

“Reverse genetics has become the gold standard for doing molecular virology,” said Parker. “It’s particularly useful for studying specific proteins. But until recently it was very difficult to develop these systems for reoviruses, the family to which bluetongue belongs.”

In 2006 one of Parker’s collaborators created a new reverse genetics system that uses plasmids, easily copied pieces of bacterial DNA, to insert viral mutants directly into cells, skipping steps that once impeded the study of reoviruses.

“The majority of Cornell’s microbiology labs do this every day: they take plasmid DNA, mutate it, and study the effect on a protein,” said Parker. “It’s much more convenient and makes transferring genetic material between labs easier, enabling better collaboration. In Israel, where virulent bluetongue is common, Marcelo will conduct experiments that for biosecurity reasons could never be conducted in the US, where strains are relatively benign.”

The researchers took an unusual route in constructing the mutant viruses they will study: hiring a company to synthesize them from scratch.

“These days you can make a pathogen by putting in an order,” said Parker. “It was first done for Polio virus, and more and more researchers are taking this approach. It’s cheaper and faster than paying grad students to spend months cloning genes. People used to learn PCR—nowadays my lab staff learn how to place an order, making sure the DNA sequence they ask for is right.”

“Viruses are often seen as mysterious and dangerous things that are hard to control. There’s some truth to that, but we are making significant progress in our abilities to manipulate viruses in ways that help us understand them better in order to develop better vaccines and treatments.”

Their work is supported by the US-Israel Binational Agricultural Research Development (BARD) Fund, which funds collaborative research to solve agricultural problems.

File:Map of molecular epidemiology of bluetongue virus in Europe.gif

The molecular epidemiology of bluetongue virus (BTV) since 1998: routes of introduction of different serotypes and individual virus strains. 

Map Source

‘Scopes Magazine
February 2012

Icelandic horses travel to Cornell

Horses will help unlock immunological mysteries of allergies and herpes

For horses, Iceland is a safe haven from disease. Several pathogens never made it to the island, whose native horses evolved for almost 1,000 years in isolation. Without facing diseases common outside, such as equine herpesvirus type 1 (EHV-1) and insect-induced allergies (called sweet itch or summer eczema), Icelandic horses never had to develop immunity to them. But immunological ignorance comes at a price: When they leave the country, these internationally popular horses are unusually vulnerable.

Yet in a discrepancy that has long puzzled immunologists, expatriate Icelandic horses give birth to far hardier foals. Born outside Iceland, these foals are up to fifteen times less likely than their parents to develop allergies. In all breeds, foal and adult immune systems work very differently. Learning how and why could help prevent allergies earlier and enable better vaccines protecting foals from early-developing diseases like EHV-1.

Dr. Bettina Wagner, equine immunologist at the College of Veterinary Medicine, works with collaborators at Cornell and in Iceland to unravel the mystery of neonatal immune development with the help of Icelandic horses.

In February 2012, 15 pregnant mares traveled from their native Iceland to Cornell University, meticulously protected from exposure to several common pathogens. With the help of collaborators at the University of Iceland at the Institute for Experimental Pathology Keldur in Reykjavik, Dr. Wagner’s group receives regular samples from the mares’ first brood born in Iceland last Summer. Comparing foals in Iceland to their forthcoming U.S.-born siblings will reveal how separate factors (environmental and maternal) affect immune development.

Clinical collaborators at Cornell assisting with the project include Drs. Gillian Perkins and Dorothy Ainsworth. Dr. Klaus Osterrieder in Berlin, Germany will help in the study of EHV-1 while Dr. Mandi deMestre of the United Kingdom will collaborate on the immune regulations analysis. Cornell professor Dr. Hollis Erb will advise on the statistical analysis of the data.

“We want to know why foals born outside Iceland have better protection than those born in Iceland,” said Dr. Wagner. “It could be due to time of exposure, environment, or some combination of these, but the evidence points more to what the mother passes on.”

Dr. Wagner thinks that protective power may lie in a mare’s milk. Some mammals, including humans, start absorbing antibodies while in the uterus, but horses receive all immunities after birth. To absorb immune protection, newborn foals must quickly drink colostrum, which is packed with immune components.

Mares encountering new allergens may become hypersensitive to the antibodies their systems produce in response. But when they pass these antibodies on through milk, Dr. Wagner thinks that the foals’ budding immune systems may learn to use those same antibodies more constructively.

Dr. Wagner’s group investigates specific antibodies called immunoglobulin-E (IgE), which can go astray in allergic diseases, reacting to harmless stimuli and causing inflammation. Building our understanding of early immune development in horses and humans could help doctors treat allergies and early-striking diseases in both species.

“If we know how allergic diseases start early in life we can interfere before they develop,” said Dr. Wagner. “Horses are a valuable model for human allergies, for which regulatory mechanisms develop very early. It’s difficult to investigate human neonatal immunity, because most maternal immune transfer happens before birth. The horse system is more controllable, especially in Icelandic horses, and can reveal the separate effects of maternal transfer and environmental exposure.”

The study may improve protection from EHV-1, which often strikes before current vaccines designed for adult immune systems can protect foals.

“If we can learn how immune responses in foals differ from those in adults, we can use specific immune reactions that foals can mount early in life to develop better neonatal vaccines for earlier protection from a wide array of infectious diseases.”

This research is funded by the Harry M. Zweig Memorial Fund for Equine Research.

‘Scopes Magazine
February 2012

Cornell China Dairy Institute teaches second crop of food-animal veterinarians from across China

For four weeks this past fall over two dozen dairy veterinarians converged on a private farm in Sanhe City, 37 miles east of Beijing. Here in China’s Heibei province, the Cornell University College of Veterinary Medicine has partnered with Huaxia Dairy as well as local Chinese educational, government, and agricultural institutions to lead an international collaboration that is benefiting animal health and food safety in China and beyond.

Cornell China Dairy Institute has provided hands-on continuing education to approximately 70 Chinese veterinarians and veterinary technicians since its launch in September 2010. During the four-week program, participants from across China attend morning lectures at Sanhe City Vocational Education College followed by afternoon hands-on training at the Huaxia Dairy farm taught by Cornell veterinarians, veterinary students, and lab technicians.

Revenue from the program goes to support the College’s local dairy programs in New York State, including food-animal externships and the highly successful Summer Dairy Institute on which the China program is based.

“This is one of the few international veterinary education programs to offer live hands-on veterinary training as well as lecture-based instruction,” said Dr. Lorin Warnick, associate dean for veterinary education at Cornell. “As agriculture and associated economies become increasingly globalized, the US has a growing interest in international disease management, food safety, and public health. The goals of the program are to advance clinical skills of veterinary staff and improve cattle care and welfare on Chinese dairy farms.  Our faculty and students benefit from seeing the dairy industry firsthand in the world’s most populous country and one in which agricultural practices are changing rapidly.”

Tailored to meet the current needs of the veterinary community in China, content integrates topics such as how to care for sick or injured cows, calf health and heifer-raising, dairy reproduction, and techniques for ensuring high quality milk production.

“The China dairy program is part of the College’s global efforts and will help to transform animal health training in this region of the world,” said Dean Michael Kotlikoff. “The global community is connected in ways that are critical to the health and well-being of animals, people, and the environment everywhere. Cornell is positioned well to help influence the direction veterinary medicine takes, in the United States and around the world.”

The timing is right for this type of initiative, according to Charles Shao, CEO of Huaxia Dairy Farm, who explained that China’s dairy industry is presently in a growth phase.

“There is an intense desire to improve efficiency and production in China and to be able to support increased consumer demand for high quality milk and dairy products,” said Shao. “This collaboration has the potential to have a strong impact on the delivery of veterinary services to dairy farms in China.”

The program also supports goals outlined in the College’s strategic plan, including finding opportunities to influence the standards for veterinary practice followed around the world and providing teaching opportunities for Cornell veterinary students who may be interested in a career in academia.

Josh Boyden ’12 spent two weeks in China as a teaching assistant in October 2011.

“While faculty lectured in the mornings, employees would present us with cases and questions on the farm that demanded immediate attention,” said Boyden, who plans to go into large-animal practice in the Northeast after graduation. “The chance to interact with enthusiastic employees and promote good on-farm practices helped reinforce the importance of basics and offered great perspective and personal satisfaction.”

This year’s teaching team also included teaching assistant Karen James ’12; PhD student Dr. Soon Hon Cheong; alum Dr. Mark Thomas ’97; and Drs. Lorin Warnick, Charles Guard, Daryl Nydam, Robert Gilbert, Rodrigo Bicalho, Gary Bennett, and Michael Zurakowski.

“As the program grows, so do the College’s opportunities for international engagement,” said Warnick. “Most participants are dairy farm staff, but we have also begun to see graduate students attending from the Chinese Agriculture University in Beijing. Feedback has been very positive about the value of the course material.”

Support for the Cornell China Dairy Institute comes from student tuition, Huaxia Dairy, Pfizer Animal Health, the U.S. Grains Council, Alta Genetics, Land O’ Lakes, Sanhe City Vocational Education College, and the Sanhe City government.

‘Scopes Magazine
February 2012

How unchecked alarms can spark autoimmune disease

November 29, 2011

A white blood cell engulfs an invading Bacillus anthracis
A neutrophil (yellow), the most abundant white blood cell type and the first line of defense against invading microbes, engulfs Bacillus anthracis (orange), the agent of anthrax. The bacteria break down, releasing DNA that triggers an immune response.

One in five Americans suffers from autoimmune disease, in which the immune system goes off-track and attacks the body’s own cells. Cornell researchers have identified a signaling mechanism in immune-system cells that may contribute to this mistake, opening the door for possible new therapies for autoimmune diseases such as lupus and arthritis.

Cynthia Leifer, assistant professor of microbiology and immunology in the College of Veterinary Medicine, and colleagues described the mechanism in the August issue of the European Journal of Immunology. The problem lies in what are called innate immune cells, the first responders to infection.

“Innate immune cells have internal watchdogs called TLR-9 receptors that set off alarms whenever they encounter invaders,” said Leifer. “They look for general classifying patterns [in DNA] to determine whether something is a virus, bacterium, protozoan, or part of self.”

However, some of these patterns exist both in invading organisms and the body’s own cells, so mistakes can arise.

Cynthia Leifer

Leifer

“We are mapping the critical regulatory mechanisms that keep these receptors from responding to self-DNA so that we can know if and how they predispose people to autoimmune disorders when they fail,” Leifer said.

Innate immune cells engulf things that look dangerous, tear them open, and release their components, including DNA. When TLR-9 receptors see DNA that identifies microbes, they send a signal to fire up more immune-system activity, including inflammation and the creation of antibodies. But before a receptor can work, enzymes in the cell must prepare it by chopping off part of the receptor molecule and leaving a part that can bind to microbe DNA.

From there, Leifer believes it’s a numbers game. If too many receptors are prepared, they may respond to the small amount of self-DNA that makes its way into immune cells, triggering an autoimmune response. So the immune cell has a regulatory mechanism, an enzyme pathway that cuts prepared receptors in a second place.

Working with cells in culture, Leifer identified this second chopping event, which cuts TLR-9 at a different site. This produces a molecule that binds to DNA, blocking it from reaching the prepared receptors, and does not send a signal.

“People without autoimmune diseases have the right balance of these two chopping events,” Leifer said. “Our studies suggest that people with a propensity for these diseases might have a defect in this pathway that allows more prepared receptors to signal for immune responses. This may be a potential target for therapies designed to help quiet those alarms.”

A second but interrelated problem Leifer has tackled involves how TLR-9 moves through an immune cell from the placewhere it is created to its working site. In earlier work she described the protein sequences in TLR-9 that act as address labels guiding where the receptor travels.

“We think they’re interrelated because if you don’t travel properly you don’t get chopped properly,” she said. “If TLR-9 ends up in the wrong place at the wrong time, it can sound a false alarm.

Leifer’s research is supported by the National Institutes of Health.

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

—–

Original Press Release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/leifer.cfm

 

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Nov11/LeiferDNA.html

Medical Xpress (PhysOrg)

http://medicalxpress.com/news/2011-11-unchecked-alarms-autoimmune-disease.html

MyScience

http://www.myscience.us/wire/how_unchecked_alarms_can_spark_autoimmune_disease-2011-cornell

Bionity

http://www.bionity.com/en/news/135431/how-unchecked-alarms-can-spark-autoimmune-disease.html

R&D Mag

http://www.rdmag.com/News/Feeds/2011/11/general-sciences-how-unchecked-alarms-can-spark-autoimmune-disease/

ECN

http://www.ecnmag.com/News/Feeds/2011/11/blogs-the-cutting-edge-how-unchecked-alarms-can-spark-autoimmune-disease/

Futurity

http://www.futurity.org/top-stories/false-alarm-can-spark-autoimmune-disease/

Study shows drinking ‘raw’ milk puts farmworkers, babies, and others at higher disease risk

Nov. 8, 2011

By Carly Hodes

Will a fresh glass of “raw” milk nourish or poison you? Pasteurization almost always provides protection from contamination. Unpasteurized “raw” milk, on the other hand, provides a potential breeding ground for disease-causing bacteria such as E. coli, Listeria, Campylobacter and Salmonella, all of which have caused outbreaks spread by raw milk in the past year, said Ynte Schukken, professor of epidemiology and herd health at Cornell’s College of Veterinary Medicine.

researcher Ynte Schukken with dairy cows
Dr. Ynte Schukken, professor of epidemiology and herd health, with livestock.

He has co-authored a paper in the August issue of the Journal of Food Production quantifying the risk of contracting Listeria monocytogenes from raw milk. In collaboration with the U.S. Department of Agriculture’s Agriculture Research Service and the New York State Department of Agriculture and Markets, the four-year project of graduate student Alejandra Latorre produced a comprehensive map showing which populations were most at risk when buying from various sources.

“Listeria is one of the most virulent and deadly foodborne pathogens,” said Schukken. “Our study demonstrates the relative risk various populations face when ingesting raw milk, including farmworkers, pregnant women, young babies and the elderly. Compared to intermediate-aged adults, these last three groups were particularly susceptible.”

The researchers analyzed risk across various purchasing methods including buying from a farm’s on-site store, directly from its bulk tank or from a third-party retailer. “Raw milk from retailers proved most dangerous by far. But when it comes to milk, the safest purchasing decision you can make is to buy it pasteurized,” Schukken said.

Despite its dangers, 28 states permit the sale of raw milk. Enthusiasts claim health benefits from nutritious compounds supposedly destroyed by pasteurization.

“These claims are not backed by scientific evidence, and several studies have shown them to be myths,” said Schukken. “Pasteurization helped revolutionize health, effectively ending diseases such as tuberculosis and Q fever. Bypassing this safety measure could have serious consequences for public health, dramatically increasing bacterial infection and outbreaks.”

Other tips to minimize risk, says Schukken: “Make sure the farm is a legal raw milk farm participating in a testing program. Only buy what you can finish in a week, keep it cold in your fridge, and use it quickly.”

—–

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Nov11/RawMilk.html

Medical Xpress (PhysOrg)

http://medicalxpress.com/news/2011-11-raw-poses-groups.html

MyScience

http://www.myscience.us/wire/drinking_raw_milk_puts_farmworkers_babies_and_others_at_higher_disease_risk-2011-cornell

Minnesota Ag Connection

http://www.minnesotaagconnection.com/story-national.php?Id=2396&yr=2011

UPI

http://www.upi.com/Health_News/2011/11/19/Raw-milk-puts-babies-farm-workers-at-risk/UPI-75531321743525/?spt=hs&or=hn

Western Farm Press

http://westernfarmpress.com/management/running-risks-raw-milk-food-safety-blunder

Real Raw Milk Facts

http://www.realrawmilkfacts.com/raw-milk-news/story/cornell-drinking-raw-milk-puts-farmworkers-babies-and-others-at-higher-dise/

Public Opinion Online

http://www.publicopiniononline.com/living/ci_19445503

Bites

http://bites.ksu.edu/news/151355/11/11/09/us-running-risks-raw-milk-food-safety-blunder

Southwest Farm Press

http://southwestfarmpress.com/livestock/running-risks-raw-milk-food-safety-blunder

Oct. 26, 2011

By Carly Hodes

maned wolf
The maned wolf, native to southeast South America, a near-threatened species, is one of the kinds of animals that students in the new Cornell-Smithsonian joint graduate program may address as they learn to become wildlife conservation scientists.

At a time when extinction threatens nearly one-quarter of all known vertebrate species, Cornell and the Smithsonian Conservation Biology Institute (SCBI) have teamed up to offer a new shared doctoral program that will train the next generation of wildlife conservation scientists.

The Cornell-Smithsonian Joint Graduate Training Program (JGTP) began accepting applications this month to train students who will leverage basic research at Cornell with conservation initiatives pioneered by one of the nation’s pre-eminent wildlife research institutes. Using the facilities, resources and expertise at both institutions, students will learn to become independent investigators equipped to study and preserve some of the rarest species on the planet.

“We are in the midst of Earth’s sixth mass extinction, and this crisis is manmade,” said Alex Travis, director of the Cornell Center for Wildlife Conservation, who helped organize the program. “Although we must continue to take every effort to preserve natural ecosystems, numbers of more and more species have dropped so low that they require focused conservation efforts. We want to train top students in a setting in which they will be able to apply basic scientific approaches and cutting-edge techniques to the preservation of biodiversity. The knowledge these collaborations generate will then help solve real conservation problems around the world.”

Students in the five-year program benefit from the dual mentorship of a Cornell faculty member and an SCBI staff scientist. Collaborative research projects will utilize resources in Ithaca and SCBI campuses (in Front Royal, Va., and Washington, D.C.), allowing students the opportunity to work with advanced biomedical facilities at Cornell and endangered species populations such as cheetahs, clouded leopards, cranes and oryx at SCBI.

Jen Nagashima
Jennifer Nagashima, the first student admitted in the Cornell-Smithsonian Joint Graduate Training Program during last year's pilot phase, studies canine reproduction.

Jennifer Nagashima, the first JGTP student admitted during last year’s pilot phase, for example, works on canine reproduction. She studies aspects of female reproduction at SCBI, where she works on in-vitro egg maturation and fertility synchronization. In the Travis lab, she is learning new technologies to preserve genetic resources of male animals using spermatogonial stem cells. She’s also synthesizing both lines of training in studies on assisted reproduction techniques such as in-vitro fertilization and embryo transfer. She has rounded out her studies by delving into how hormones control the canine reproductive cycle with Ned Place, a reproductive endocrinologist at Cornell.

“These topics are highly complementary, and Jennifer’s study benefits tremendously from her work in these three labs,” said Travis. “Bringing these skills together could help manage captive populations of endangered canids such as the African wild hog and South America’s maned wolf. Interestingly, these same approaches could help dog breeders filter diseases out of domestic populations while also helping humans. There are over 400 human diseases having similarity to diseases in dogs. Identifying genetic causes of disease can then benefit everyone.”

Carly Hodes is a writer at the College of Veterinary Medicine.

—–

Original press release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/doctoralprogram.cfm

 

Media hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Oct11/SmithsonianVet.html

US Ag Net

http://www.usagnet.com/state_headlines/state_story.php?tble=NY2011&ID=994

News from Planet Earth

http://www.newsfromplanetearth.com/60749/cornell-smithsonian-to-train-new-generation-of-wildlife-scientists/

High Beam Research

http://www.highbeam.com/doc/1G1-270907727.html

Media Newswire

http://media-newswire.com/release_1161547.html

Classroom innovation prepares students for clinics and professional life

Whatever their background, most new veterinary students share one desire: to work with animals as soon as possible. Continuous modifications and improvements to the curriculum—in response to input from faculty, students, alumni, and employers— have resulted in a history of  classroom adaptations in Cornell’s veterinary curriculum that continually bring students closer to the action sooner.

“We want to give students the tools they’ll need as veterinarians as early as possible so they can refine them over the time they’re with us,” said McDaniel. “Last Fall we introduced a new set of labs in which first-years perform basic procedures on all major species. After spending mornings learning anatomy while dissecting cadavers in Block I they look at the same structures in live animals in the afternoon. It gives these young people a wonderful sense of accomplishment and they can practice these skills during their summer experiences.”

Teaching skills to students sooner, the Clinical Procedures module now precedes the Public Health module, helping students gain comfort with one of medicine’s most infamously difficult endeavors: surgery.

“Surgical skills are hard for students; there’s a steep learning curve for handling instruments,” said McDaniel. “Past students got their first surgery experience in their third year. Now incoming first-years learn correct instrument handling from real surgeons and more advanced techniques and suture patterns in the spring.”

In response to student suggestions in course evaluations instructors introduced discussion sections to the Ethics and Animal Care module.  Small groups of students discuss ethically charged scenarios and share perspectives. The module’s latter portion now includes new lectures and discussions on animal nutrition.

The Community Practice Service (CPS) began offering underclassmen new opportunities to observe appointments run by fourth-year students and to practice communicating with clients by conducting brief patient-history interviews on camera. Peers and faculty use the recording to offer students constructive feedback on communication skills. Meanwhile, third-year students in the Communication Skills module must navigate new simulated client interactions involving actors playing clients with varied temperaments.

These classroom innovations aim to build solid foundations of competence and confidence they will need in their next stage of training and professional life.

“We meet students when they first walk in the door and begin equipping them with skills they’ll need in the clinics and beyond,” said Dr. Carolyn McDaniels, veterinary curriculum instructor and current director of Course VII. “This kind of course never existed when I was in school.”

Course VII, or “Block VII”, revolutionized veterinary learning at Cornell nearly twenty years ago. A foundation course, its six sequential sections span students’ first 2.5 years. Former course director Dr. John Ludders, professor emeritus of anesthesiology, has seen it through its multifaceted evolution.

“Back when we were designing the ‘new curriculum’ we realized students would miss basics such as examination skills, ethics, and public health,” recalled Ludders.  “So Dr. John Saidla designed a course called ‘Block VII’ to fill curricular gaps. The students really appreciated the course. When he left around 1999 several clinical faculty stepped up to help lead and refine the course.

“Students seemed inadequately prepared for clinic rotations. They could not perform some basic tests or properly restrain patients, and had problems understanding basic public health issues. So we revised Block VII to strengthen physical examination skills, teaching students to milk dairy cattle, perform diagnostic procedures in cadavers, complete governmental health certificates for patients, and use basic clinical equipment.”

Course VII became a catch-all repository for essential material not covered in the other six blocks. Last year, with the help of several faculty and former course directors, Dr. McDaniel led the course through its most recent innovations.

“In teaching I often ask myself and my students what makes someone a great veterinarian,” said Dr. McDaniel. “There has to be a knowledge base, but they also most have technical hand skills and the ability to communicate effectively. The first six blocks in the curriculum build the knowledge base. We cover the rest. That’s two thirds of a veterinarian’s most important learning.  I love watching students become veterinarians over the three years we see them in this course.”

‘Scopes Magazine
October 2011

Weighing in on weighing less

Nutrition research reveals paths to weight loss and the secret life of fat

Americans are getting fatter and so are their pets. Following rising trends in human obesity, nearly half of pet dogs and cats weigh too much, and it’s taking heavy tolls on their health. Cancer, diabetes, arthritis, and other bone and joint problems disproportionately plague overweight animals. Nutrition clinicians at Cornell’s Companion Animal Hospital are helping downsize this growing problem by creating knowledge and solutions that could help humans and pets reach healthy weights.

“Obesity is the number one preventable health problem in veterinary medicine today,” said Dr. Joseph Wakshlag, head of Cornell’s nutrition and obesity management services. “Food equals love; people give treats, pets get fatter. Education and prevention are the only real tools against obesity.”

Dr. Wakshlag’s team of two resident trainees and one nutrition technician offers personalized nutritional support and weight-management planning for pets. Their clinical research has attracted sponsorship from Nestle Purina, a pet-food manufacturer that values new nutrition knowledge, resulting in three papers this year and several studies in progress.

The first proved pedometers attached to bungee cord collars can accurately count a dog’s steps and used the technique to show that dogs that walk more stay fitter. The second paper used their pedometer methodology to demonstrate for the first time that exercising dogs could help them lose weight, and determined how many calories dogs can eat per 1,000 steps of walking while still trimming down.  Dr. Wakshlag uses his findings to develop intervention plans based on dog walking to prevent canine obesity.

The hospital’s nutrition residents are expanding on Dr. Wakshlag’s third study addressing a new finding that is changing the way veterinarians and human doctors look at fat.

“Historically people saw fat tissue as inert energy deposits,” said Dr. Jason Gagne ’09, second-year resident in the nutrition service. “Recently we’ve realized it acts more like endocrine tissue, releasing proteins called adipokines that activate the immune system and cause chronic inflammation. This can exacerbate many disease processes and lower insulin resistance, leading to diabetes. We’re trying to learn which cells in fat tissue produce adipokines.”

First-year resident Dr. Renee Streeter studies how heavy hounds handle hidden health hazards from pro-inflammatory proteins. Her research compares dogs’ adipokine levels to their body conditions and the levels of anti-inflammatory omega three fatty acids in their blood. While most adipokines increase with body score (higher is fatter) and harm the body, one kind does the opposite.

“Adiponectin is the single beneficial thing released from fat,” said Dr. Wakshlag. “Unlike other adipokines, it’s an anti-inflammatory insulin sensitizer. An injection of adiponectin will make your insulin work better. When you’re lean, you release a lot of it, when you’re fat, you release a lot less. That’s why you have to lose weight to become more sensitive to insulin.”

In the nutrition team’s clinical trials, inflammatory responses decreased due to lowering levels of bad adipokines after dogs lost weight.

“While most adipokines fell, we were surprised to find that canine adiponectin levels stayed the same. Dogs have much more adiponectin than cats or humans, no matter if they’re fat or thin. This may be one reason why dogs are less prone to Type-II diabetes than other species.”

Cornell’s headway on the obesity battlefront owes its success largely to corporate sponsors investing in the future of healthy pets.

“Nestle Purina has been phenomenally generous,” said Dr. Wakshlag. “They funded our pedometer-based weight-loss studies, Renee’s study, and Jason’s entire two-year residency. Proctor and Gamble, who makes Natura Products, IAMS, and Eukanuba, recently stepped up to fund Renee’s 3 year residency program, with plans to make this a continual position for the Cornell University Hospital for Animals.

“These partnerships meet the rising demand for nutrition knowledge in the private and corporate sectors. Two Cornell veterinary alumni– Dr. Kurt Venator ‘03 of Nestle Purina and Dr. Susan Giovengo ‘91 of Proctor and Gamble – helped make our residencies possible.  These pet food companies know the value of having nutrition experts in hospitals and hope to help fight the obesity epidemic these future clinicians will face.”

‘Scopes Magazine
October 2011

Reining in Roaring


Earlier detection and new treatments for horse racing’s number-one performance problem


It’s a big day at the track. Years of training and thousands of dollars are at
stake. The gates open and your horse lunges forward. But his breath comes
in gasps. It looks as if he’s wearing a heavy mask that is blocking his access to
air. Worn nerves signal sluggishly to weakened muscles that barely respond
enough to open his airway. He slows and falls to the back of the pack.

This career-limiting problem affects nearly 8 percent of race horses and a higher percentage of sport horses. Oficially called “recurrent laryngeal neuropathy,” the common equine disease is better known as “roaring” for the strained sounds affected horses make when they try to run. It shares similarities with human vocal cord paralysis, a neurological condition
causing difi culty breathing and loss of speech and requiring tracheostomy and intensive surgery. Roaring starts early and
unseen, slowly wearing down the nerves that stimulate the muscle responsible for opening the larynx.

“Upper airway problems cause poor performance in many race horses,” said Dr. Jonathan Cheetham, an equine surgeon and sports medicine practitioner at Cornell’s Equine Hospital. “Symptoms often show in a horse’s second to fourth year, when a trainer has already invested thousands in its athletic career. The standard treatment, surgery called a laryngeal tie-back together with a ‘lazer hobday’ procedure to remove the vocal cords, returns 65-70 percent of treated horses to racing. But that’s after six weeks of recovery and another six weeks to regain fitness. It takes a toll on the horses, their trainers, and the racing economy.”

Taking roaring by the reigns, Dr. Cheetham and the Equine Performance Clinic team are helping to change how veterinarians look at and treat the disease. The team running the Clinic’s indoor treadmill offers good client service while researching new methods to diagnose disease earlier and improve treatments.

According to Cheetham, the horse is a useful preclinical model of human airway disease. Much of what he is learning and working out at Cornell could help restore function in human patients with laryngeal disease. The Equine Performance Clinic pioneered techniques using a trans-esophageal ultrasound to evaluate airway muscles in horses.  Developed at Cornell with support from the Harry M. Zweig Memorial Fund, these techniques could give human doctors a new view of deteriorating laryngeal muscles and let them follow progress after treatment.

The team is developing a novel treatment for roaring using a laryngeal pacemaker to electronically stimulate the muscle and maintain its function: another technology applicable to humans with vocal paralysis.

Cheetham has spent the past year developing new ways of detecting neurological disease earlier, thanks to a grant from the Grayson Jockey-Club Foundation.

“Motor nerves need insulation from myelin sheathes to carry signals quickly,” said Dr. Cheetham. “Laryngeal neuropathy works by breaking down myelin in the two major meter-long nerves controlling the horse’s airway muscles, slowing their conduction velocity and cutting off the muscles from adequate stimulation. If we can use nerve conduction velocity to detect early myelin breakdown we may be able to catch the disease before the muscle starts shrinking.”

Placing tiny needles into the nerves, Dr. Cheetham measured conduction speeds across their length to see how speeds vary across the nerves. Next he will validate a technique that does not use needles and look at how nerve conduction velocity at the weanling stage affects performance of 2-year-old horses with the hope of confirming it as a viable diagnostic and predictive tool. Validating such a test would expand the window of detection and open doors to earlier prevention and treatments, and aid understanding of the disease mechanisms that produce ‘roaring’ in horses.

“We have also been developing ways of enhancing nerve grafting using tissue engineering techniques,” said Dr. Cheetham. “If we can pick up problems early, we might be able to treat without invasive surgery or a permanent implant. It could be safer, cheaper, and faster, and may improve the success of recovery from airway diseases in both horses and humans.”

Discuss this work with Dr. Cheetham on Facebook
https://www.facebook.com/CornellEquine
Visit the Equine Performance Center website
http://www.vet.cornell.edu/labs/eptc/intro.htm

‘Scopes Magazine
October 2011

Life-saving surgery inspires gift to help the hospital see inside ailing wildlife

When their dog, Buzz, faced a life-threatening condition in October 2009, Richard and Stacy Hoffman drove their Scottish terrier six hours from Maryland to Cornell University Hospital for Animals, where a timely surgery saved his life.

Their experience inspired several donations to the Companion Animal Hospital, and as strong supporters of animal welfare they were keen to learn more about the College’s commitment to animal care. The Hoffmans oversee a family foundation that funds projects supporting otherwise overlooked wildlife. When they took a tour of Cornell’s Janet L. Swanson Wildlife Health Center, which provides hospitalization and medical care to sick or injured wild animals brought in by the public with the goal of releasing them back to their original habitat, they knew they had found a match.

“Some wildlife species get a lot of attention while others that might not be quite as ‘sexy’ fall under the radar,” said Richard Hoffman. “It’s important to us and to Earth’s ecosystems that species don’t dwindle because no one noticed or cared. We took a tour of the Center and saw the work they do helping local wildlife and training students who could someday translate that experience to a greater scale, and we wanted to give something tangible to help.”

Through a gift from their foundation, the Hoffmans helped the Center purchase four pieces of imaging equipment that will provide invaluable diagnosis and treatment options for the animals treated at the Center while simultaneously building a multimedia library usable for teaching and research in wildlife medicine.

“The biggest new piece is an endogo®HD, a totally portable, wireless, high-definition endoscopic imaging platform that can record, store, and play back images and videos taken from inside an animal’s body, making it particularly useful for diagnosis and teaching,” said Dr. George Kollias, Jay Hyman Professor of Wildlife Medicine and Chief of the Center. “We also purchased a small-diameter rigid endoscope for birds and small mammals that allows veterinarians to use surgical instruments to take biopsies, retrieve ingested foreign bodies, and conduct minimally invasive surgeries.”

For their tiniest patients, the Center purchased a fully functional miniature endoscope. Finally, all endoscopes were updated with new, more powerful light sources.

“We use this technology to help diagnose and treat wildlife when laboratory tests and other diagnostics don’t provide definitive answers,” said Kollias. “It lets us use minimally invasive techniques to visualize the organ surfaces and to take tissue samples if organs or tissues safely. The equipment is also particularly useful in species for which there is little or no published clinical laboratory data or disease description.”

The Hoffmans hope their gift will help veterinarians, students, and researchers find ways to prevent future problems in wildlife and promote research to help wildlife.

‘Scopes Magazine
February 2012