Category Archives: Humans

Ticks untold

Prime suspects in mystery fevers may hold new tick-borne diseases
Suddenly your horse is sick and you don’t know why. She breathes normally but her temperature is rising, her eyes grow yellow with jaundice, she seems depressed, and barely eats. The fever is clear but the cause is not; even the most experienced experts can offer no concrete answers. Eventually the fever fades, but is that the end of whatever caused it or is the source still lurking somewhere inside?

Horse owners across the states are facing this distressing scenario. At the Cornell University Animal Health Diagnostic Center (AHDC), Dr. Linda Mittel fields a growing number of calls about these mysterious fevers of unknown origins (FUOs). Many come from the Northeast, Mid-Atlantic, and Great Lakes areas: the nation’s topmost hotbeds of human tick-borne disease. This pattern led Mittel to suspect that the culprits of the fever caper could be ticks and the difficult-to-diagnose diseases they carry.

“Tick-borne diseases are some of the fastest growing emerging diseases in the United States right now,” said Mittel. “As ticks continue expanding their numbers and geographic range these diseases may affect new areas. We get calls about fevers at broodmare operations, showbarns, and farms where race horses rest or layup, even in areas where they didn’t know they had ticks. But horses moving between states can move ticks with them, and the effects of this movement are starting to show.”

Mittel and colleagues at the AHDC are embarking on a project to find just what diseases ticks in hotbed zones are carrying and whether they are behind the wash of mystery fevers in horses. The study will use samples from horses suffering FUOs to look for bacterial infections known to be transmitted by ticks (Anaplasma, Babesia, Borrelia, Ehrlichia, and Rickettsia) as well as other bacteria known to cause non-respiratory infection in horses (Leptospira, Bartonella, and Neorickettsia.)

These agents are considered emerging infectious diseases in humans, and this will be the first study determining their presence in horses with FUOs. The study will also sample ticks found on or near horses in designated areas to find which pathogens they carry and to potentially discover previously undocumented tick-borne pathogens.

Many tick-borne diseases are sensitive to specific drugs; others are not sensitive to antibiotics at all. Knowing which diseases are at the root of FUOs will help veterinarians treat them effectively. It will also help owners understand how the causes of fevers might impact affected horses’ futures in racing, performance, or showmanship.

“I’m quite excited to start solving the mysteries of these fevers and to possibly uncover new previously unrecognized diseases – in horses and people,” said Mittel. “If these agents are in the horses, humans may also have them without realizing– people who work with these horses might be particularly at risk. Knowing what we’re dealing with here will hopefully solve the mystery of FUOs and help equine and human medicine recognize and address the growing onslaught of tick-borne disease.”

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

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Researchers discover what cancer cells need to travel

Feb. 21, 2012

Cancer cells must prepare for travel before invading new tissues, but new Cornell research has found a possible way to stop these cells from ever hitting the road.

Researchers have identified two key proteins that are needed to get cells moving and have uncovered a new pathway that treatments could block to immobilize mutant cells and keep cancer from spreading, says Richard Cerione, Goldwin Smith Professor of Pharmacology and Chemical Biology at Cornell’s College of Veterinary Medicine.

The study, co-authored by graduate student Lindsey Boroughs, Jared L. Johnson, Ph.D. ‘11, and Marc Antonyak, senior research associate, is published in the Journal of Biological Chemistry (286:37094-37107)

Most adult cells stay stationary, but the ability for some to move helps embryos develop, wounds heal and immune responses mobilize. When migrating cells go astray they can cause developmental disorders, ranging from cardiovascular disease to mental retardation. Metastasis (the spread of cancer from one part of the body to another) also relies on cell migration. How exactly cancer cells migrate
and invade tissues continues to be a mystery. However, Cerione’s lab uncovered a potentially important clue when it noticed that cancer cells gearing up to move would collect a protein called tissue transglutaminase (tTG) into clusters near the cell membrane.

meta“TTG is turning up in many aspects of human cancer research and seems to be contributing to the process that turns cells cancerous,” said Cerione. “Lindsey and Marc discovered that cells must gather tTG into a specific place in their membrane before they can move. But tTG is usually inactive, and we’ve been trying to understand how a cell gets this protein to the exact right place so that it can be activated to stimulate cell migration.”

Observing breast-cancer cells in culture, Cerione’s lab found a missing link in our understanding of cell migration: Cancerous cells become hyperactive invasion vehicles by using tTG together with other proteins like wheels, poking them through the surface to form a “leading edge” that pulls the cell forward. But to get the wheels to the leading edge, it turns out they need another protein to roll them there – a “chaperone” protein called heat-shock-protein-70 (Hsp70).

“We’ve known for years that Hsp70 acts as a chaperone to other proteins, ensuring that they assume the right structure and behave properly when a cell is under stress,” said Cerione. “Heat shock proteins have also been implicated in cancer, although scientists have been trying to understand their exact role in cancer. Our research has uncovered a previously unknown role for these chaperones – helping tTG get to the leading edge. TTG must be in this location for cancer to spread.”

migrating cervical cancer cell

A migrating cervical cancer cell stained for tissue transglutaminase (green). Cells must gather this protein at their leading edge in order to move.

When cells become stressed, Hsp70 influences the behavior of their “client” proteins, ensuring they keep the right shape. Cells need chaperones like Hsp70 to ensure that various proteins work correctly and don’t warp, but these same chaperones can help cancer cells spread by helping move tTG to the membrane surface. Using inhibitors that block the function of chaperones, Cerione and his team paralyzed Hsp70s and stopped breast cancer cells in culture from gathering tTG into a leading edge, effectively immobilizing them.

Exactly how Hsp70 gets tTG going remains unknown, but Cerione believes other proteins are involved.

“If we can better understand how Hsp70 influences tTG, we can figure out ways to modulate that interaction to immobilize cancer cells and keep them from becoming invasive,” said Cerione. “We suspect Hsp70 is using a third kind of protein to move tTG, and that’s what we’re trying to figure out now. Finding the next link in this chain of events could have important consequences for preventing cancer migration and metastasis.”

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

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Original Press Release:

Cornell University College of Veterinary Medicine news

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

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Feb12/CancerMovers.html

Ithaca Journal

http://www.theithacajournal.com/article/20120222/LIFE/202220336/Cornell-scientists-find-cancer-cells-need-travel?odyssey=mod|newswell|text|Life|s

PhysOrg

http://www.physorg.com/news/2012-02-cancer-cells.html

ECNMag

http://www.ecnmag.com/News/Feeds/2012/02/blogs-the-cutting-edge-researchers-discover-what-cancer-cells-need-to-tra/

Zeit News

http://www.zeitnews.org/biotechnology/researchers-discover-what-cancer-cells-need-to-travel.html

My Science

http://www.myscience.cc/news/2012/what_cancer_cells_need_to_travel-2012-cornell

Reddit

http://www.reddit.com/r/science/comments/q0swt/cancer_cells_must_prepare_for_travel_before/

Laboratory Equipment

http://www.laboratoryequipment.com/news-Proteins-Key-to-Stopping-Cancer-from-Spreading-022312.aspx

Viral quality controls could halt herpes’ spread

Sept. 13, 2011

Herpesviruses are thrifty reproducers — they only send off their most infectious progeny to invade new cells. Two Cornell virologists recently have discovered how these viruses determine which progeny to release.

herpes simplex virion

Recently enveloped herpes simplex virion in the perinuclear space of an infected cell.

The College of Veterinary Medicine researchers report in the Aug. 23 (108:34) issue I of the Proceedings of the National Academy of Sciences on the mechanisms of this quality-control system, which helps streamline viral reproduction to optimize its spreading.

The virologists identified proteins in the nuclear membranes of infected cells that control which viral products exit. This map could be used to identify new targets for future drugs that would hamper viral reproduction by clogging inspection pathways to trap viruses in the cells they first infect.

“When a herpesvirus hijacks a cell, it turns the nucleus into a viral production factory,” said Joel Baines, the James Law Professor of Virology, who co-authored the study with postdoctoral research associate Kui Yang. “It makes protein shells called capsids, stuffs them with viral DNA and ships them out of the nuclear membrane to infect new cells. But errors in the assembly line leave some capsids empty, without DNA, and shipping these is a waste of resources.”

When capsids bud from the nuclear membrane, they take pieces of it with them, forming protective lipid envelopes that let them move to new cells. Empty capsids can’t reproduce, so the virus only allows capsids with DNA through. How the membrane could determine whether the capsid had DNA or not was a mystery until Yang and Baines mapped its method.

Joel Baines

Joel Baines

“We found clamplike proteins on the surface of herpesvirus capsids that hold them together and keep them from bursting when they’re stuffed full of DNA,” said Baines. “Those with DNA have far more of these than empty capsids. We also found a protein complex living in the host cell’s nuclear membrane that binds to these structural support proteins, selecting DNA-filled capsids to pull through the membrane. Thus the virus releases only its most infectious particles.”

This streamlining process has helped herpesvirus species spread prevalently and permanently across all animal species. Eight of the 25 known viruses in the herpes family regularly infect humans, posing a leading cause of human viral infection.

Once in a body, herpesvirus stays for life. It can flare up at any time, causing symptoms and diseases, ranging from infected sores to brain inflammation, birth defects and cancers of the nose, throat and lymphatic system. Though usually not fatal, herpes can prove dangerous to patients with weak immune systems, such as those with HIV/AIDS or infants who contract HIV/AIDS from their mothers.

Various species of Herpesvirus

Various species of Herpesvirus

There is no cure for herpes, but Baines’ map illustrates a viral reproduction system that can be subverted.

“Take away either component, the capsid’s clamplike proteins or the membrane’s inspector proteins, and nothing escapes the host cell,” said Baines. “This opens the door to developing drugs that could block the interactions between these protein complexes, covering the binding sites to clog the system so that no viral particles get through. This would significantly slow or even stop the virus’s spread between cells. Our lab is now working on even more detailed maps of these proteins’ exact interaction sites that will help drug developers pinpoint precise targets to thwart viral reproduction.”

The research was supported, in part, by the National Institutes of Health.

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

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Original press release:

Cornell University College of Veterinary Medicine news
http://www.vet.cornell.edu/news/herpes.cfm

Media hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Sept11/HerpesMap.html

MyScience

http://www.myscience.cc/wire/discovery_could_lead_to_ways_to_halt_spread_of_herpesvirus-2011-cornell

Bionity

http://www.bionity.com/en/news/134351/study-uncovers-how-herpesvirus-spreads.html?WT.mc_id=ca0067

MedicalXPress (PhysOrg)

http://medicalxpress.com/news/2011-09-discovery-ways-herpes.html

Electronic Component News

http://www.ecnmag.com/News/Feeds/2011/09/blogs-the-cutting-edge-discovery-could-lead-ways-to-prevent-herpes-spread/

Futurity

http://www.futurity.org/health-medicine/how-to-stop-herpes-from-going-viral/

Herpes Pain Relief

http://www.herpespainrelief.info/4349/cornell-chronicle-study-uncovers-how-herpesvirus-spreads/