“This year doesn’t look like it’s going to be tremendously unusual in terms of overall cases of mosquito-borne diseases,” said Jonathan Day, a professor of medical entomology with the University of Florida’s Institute of Food and Agricultural Sciences. “But transmission of [EEEV] tends to be very focal, and there are some areas that are looking risky.”

EEEV is best known for being deadly in horses, but humans can contract the virus as well.

According to the national Centers for Disease Control and Prevention, the virus can cause a severe infection of the central nervous system in humans, and is fatal for nearly a third of those afflicted.

So far this year, 26 horses have been found to be infected in North Florida, with five more in the state’s Panhandle.

These cases, along with analysis of weather conditions and other indicators, have led UF entomologists to believe that a band of counties beginning at Volusia County and stretching northwest into the Florida Panhandle carry a moderate to high risk of mosquitoes carrying the virus.

For an up-to-date risk map, please visit http://eis.ifas.ufl.edu/eis1.htm.

“July is usually the peak for EEEV transmission,” said Roxanne Connelly, an IFAS professor of medical entomology. “We’ve had the type of weather patterns that can make the problem worse in some areas.”

The disease is spread via mosquitoes that have fed on birds. Humans and horses cannot spread the virus to other humans and horses.

Connelly advises that people in risk areas avoid being outside during peak feeding times for mosquitoes that carry the disease — calm, humid periods from dusk to dawn.

If you are outside during these times, you should cover as much skin as possible. Bare skin should be treated with a repellent that carries DEET or Picaridin.

“There are all sorts of traps and tools out there like bug lights and citronella candles,” Connelly said. “None of them keeps mosquitoes from biting you — only a repellent applied directly on your body can do that.”

Pet birds should be kept inside and, while it is very rare for dogs and cats to contract EEEV, Connelly suggests being aware that pets aren’t immune to pesky mosquito bites.

Spraying dogs and cats with repellents labeled for use on humans can be dangerous because they can lick the repellent while grooming. There are products made for dogs that do not contain DEET, but make sure to read and follow the directions.

Pets are best kept inside away from mosquitoes during peak feeding times. And, any dog that is at risk of being bitten should be on a monthly heartworm prevention treatment. Prevention treatments formulated for cats are also available.

But it turns out that remarkable ability isn’t so mysterious after all — suggesting that researchers could learn how to replicate it in people.

Scientists had long credited the diminutive amphibious creature’s outsized capabilities to “pluripotent” cells that, like human embryonic stem cells, have the uncanny ability to morph into whatever appendage, organ or tissue happens to be needed or due for a replacement.

But in a paper set to appear Thursday in the journal Nature, a team of seven researchers, including a University of Florida zoologist, debunks that notion. Based on experiments on genetically modified axolotl salamanders, the researchers show that cells from the salamander’s different tissues retain the “memory” of those tissues when they regenerate, contributing with few exceptions only to the same type of tissue from whence they came.

Standard mammal stem cells operate the same way, albeit with far less dramatic results — they can heal wounds or knit bone together, but not regenerate a limb or rebuild a spinal cord. What’s exciting about the new findings is they suggest that harnessing the salamander’s regenerative wonders is at least within the realm of possibility for human medical science.

“I think it’s more mammal-like than was ever expected,” said Malcolm Maden, a professor of biology, member of the UF Genetics Institute, and author of the paper. “It gives you more hope for being able to someday regenerate individual tissues in people.”

Also, the salamanders heal perfectly, without any scars whatsoever, another ability people would like to learn how to mimic, Maden said.

Axolotl salamanders, originally native to only one lake in central Mexico, are evolutionary oddities that become sexually reproducing adults while still in their larval stage. They are useful scientific models for studying regeneration because, unlike other salamanders, they can be bred in captivity and have large embryos that are easy to work on.

When an axolotl loses, for example, a leg, a small bump forms over the injury called a blastema. It takes only about three weeks for this blastema to transform into a new, fully functioning replacement leg — not long considering the animals can live 12 or more years.

The cells within the blastema appear embryonic-like and originate from all tissues around the injury, including the cartilage, skin and muscle. As a result, scientists had long believed these cells were pluripotential — meaning they came from a variety of sites and could make a variety of things once functioning in their regenerative mode.

Maden and his colleagues at two German institutions tested that assumption using a tool from the transgenic kit: the GFP protein. When produced by genetically modified cells, GFP proteins have the useful quality of glowing livid green under ultraviolet light. This allows researchers to follow the origin, movement and destination of the genetically modified cells.

The researchers experimented on both adult and embryonic salamanders.

With the embryos, the scientists grafted transgenic tissue onto sites already known to develop into certain body parts, then observed how and where the cells organized themselves as the embryo developed. This approach allowed them to see, literally, what tissues the transgenic tissue made. In perhaps the most vivid result, the researchers grafted GFP-modified nerve cells onto the part of the embryo known to develop into the nervous system. Once the creatures developed, ultraviolet light exams of the adults revealed the GFP cells stretched only along nerve pathways — like glowing green strings throughout the body

With the adults, they took tissue from specific parts or organs from transgenic GFP-producing axolotls, grafted it onto normal axolotls, then cut away a chunk of the grafted tissue to allow regeneration. They could then determine the fate of the grafted green cells in the emerging blastema and replacement tissue.

The researchers’ main conclusion: Only ‘old’ muscle cells make ‘new’ muscle cells, only old skin cells make new skin cells, only old nerve cells make new nerve cells, and so on. The only hint that the axolotl cells could revamp their function came with skin and cartilage cells, which in some circumstances seemed to swap roles, Maden said.

Maden said the findings will help researchers zero in on why salamander cells are capable of such remarkable regeneration. “If you can understand how they regenerate, then you ought to be able to understand why mammals don’t regenerate,” he said.

Maden said UF researchers will soon begin raising and experimenting on transgenic axolotls at UF as part of the The Regeneration Project, an effort to treat human brain and other diseases by examining regeneration in salamanders, newts, starfish and flatworms.

The index components were mixed, with perceptions of personal finances now compared with a year ago up three points to 44 from a revised May reading of 41 but still near historical lows. All others were lower than or the same as last month.

Perceptions of personal finances a year from now fell six points to 84, and perceptions of U.S. economic conditions over the next year fell seven points to 65 — it was 51 at this time last year. Perceptions as to whether it is a good time to buy big-ticket items fell nine points to 67. Finally, perceptions of U.S. economic conditions over the next five years remained unchanged at 80.

“In the previous two releases we had suggested the possibility of a small decline in confidence in June, which seems to have been the case,” said Chris McCarty, director of UF’s Survey Research Center at the Bureau of Economic and Business Research. “This is most likely a combination of the fallout from the Florida state budget, which includes several new and increased fees, as well as the bankruptcy of GM.”

Another factor affecting the decline is a sharp increase in Florida’s unemployment rate. A previous unemployment release from the Agency for Workforce Innovation showed a slight decline, but that has since been erased by an increase into double-digit unemployment, he added. Florida’s seasonally adjusted unemployment rate for May 2009 was 10.2 percent, according to the agency.

“Most economists believe unemployment will continue to increase as the economy moves into recovery,” McCarty said.

The economic landscape in Florida remains mixed. On the negative side is high unemployment and continued foreclosures, although the rate of foreclosures in Florida may already have peaked, McCarty said. Gas prices have increased dramatically over the past month, although there are signs that may be reversing.

On the positive side, the Florida Association of Realtors report for May once again showed signs that the median price of existing homes is stabilizing. Since January, the median price has fluctuated in a narrow range and is now up for the year at $144,400. It is increasingly likely that Florida has taken most of its knocks to housing value, even as other states continue to decline, McCarty said.

“Moving forward, we do not expect Florida consumer confidence to decline much more over the next couple of months, barring some unforeseen change here in Florida or nationally,” he said. “There is at least a temporary reaction of the stock market to some recent news, including Iran and dramatic increases in mortgage and credit card delinquencies. So far, this volatility is relatively small and not indicative of a reversal in the economic recovery.”

However, McCarty cautions that everyone should expect the recovery to be long and uneven for some sectors of the economy.

“With the demise of longstanding financial institutions such as Lehman Brothers and manufacturing companies like Chrysler and GM, it is no longer business as usual,” he said. “The U.S. is clearly going to share more of the global economic pie than it has in the past.”

The research center conducts the Florida Consumer Attitude Survey monthly. Respondents are 18 or older and live in households telephoned randomly. The preliminary index for June was conducted from 430 responses. The index is benchmarked to 1966, so a value of 100 represents the same level of confidence for that year.

GAINESVILLE, Fla. — Coffee and tea drinkers, take note — a University of Florida study says a beverage made from a native holly tree might be just the thing to give you a caffeinated kick-start, plus a dose of antioxidants.

Yaupon (YO-ponn) holly is the only U.S. plant that produces substantial amounts of caffeine, said Jack Putz, a botany professor affiliated with UF’s Institute of Food and Agricultural Sciences. A popular ornamental species, yaupon grows wild throughout the Southeast and can be grown in most coastal states.

Centuries ago, American Indians and Spanish settlers steeped yaupon leaves and twigs in hot water to make a stimulating beverage, but that use of the plant is virtually unknown today.

The resulting brew is dark brown and tastes much like green tea. If it makes a comeback, yaupon may spawn a cottage beverage industry, Putz said. And the antioxidants might be useful in nutritional supplements.

“A few years ago we were contacted from a pharmaceutical company in Texas,” he said. “At first, we thought their interest was in caffeine but they said that with all the decaffeinated beverages around, caffeine is cheap. What they were interested in was the antioxidants.”

Nitrogen fertilizer can boost yaupon production and caffeine content, according to a paper Putz co-wrote, published in this month’s issue of the journal Economic Botany. Nitrogen had little effect on antioxidant content.

The researchers focused on a popular ornamental yaupon variety called Nana, said Matt Palumbo, a botany master’s graduate and co-author of the paper. After receiving nitrogen fertilizer, Nana plants yielded 35 percent more leaves; caffeine concentration in the leaves shot up 265 percent.

Nana had about half the antioxidant content of green tea, he said.

“I have found genotypes with antioxidant concentrations at least as high as green tea,” Palumbo said.

Similarly, Nana’s caffeine content was low compared with concentrations reported in previous studies, he said.

Dry, unprocessed yaupon leaves contain between .65 percent and .85 percent caffeine by weight. Coffee beans are about 1.1 percent caffeine by weight and tea leaves about 3.5 percent caffeine.

More research is needed to learn which yaupon varieties have the greatest caffeine and antioxidant content, Palumbo said. Afterward, new cultivars can be developed.

One point seems clear — if U.S. residents begin drinking yaupon tea it could reduce demand for coffee, which may ease ecological pressure on coffee-farming regions of South America, Africa and Southeast Asia, he said.

It’s uncertain whether large-scale yaupon farming would be economically feasible in the U.S., but the antioxidants appear to have commercial potential, he said. And home gardeners might enjoy growing and using yaupon.

One caveat — before making yaupon tea it’s critical to obtain the correct plant, Putz says. There are numerous U.S. holly species, many of them not safe for consumption.

The taste of yaupon tea will be the make-or-break factor for potential users, says Dan Austin, an ethnobotanist based at the Arizona-Sonora Desert Museum in Tucson.

If they don’t like the flavor — something Austin says is quite possible — then they’re unlikely to drink the beverage regardless of the health benefits.

Still, he says, “if the proper spin is put on it, the potential is there.”

And, contrary to popular belief, the guards also show sympathy to the plight of gay men who are targets of sexual assault, said Carrie Cook, who did the research for her doctoral degree in the criminology, law and society department at UF.

“There’s a perception that corrections officers are anti-inmate and not very progressive, but results from my study directly rebut that, perhaps partly because some training programs now incorporate information about HIV and sexually transmitted diseases,” she said

The issue is important because jails and prisons have high incidences of HIV and other sexually transmitted diseases, which are likely to spread into the community, Cook said. More than 90 percent of people who serve time in state and federal prisons are eventually released and jail populations turn over 15 times in one year on average, she said.

Although research has looked at sexual assaults in prisons, little has been done in jails where Cook did her study. Jails have 17 times as many inmates admitted as prisons and they are released more quickly into the community — jail time rarely exceeds a year — with those inmates who are infected bringing an increased risk to community health.

“We rarely lock up somebody and keep them there forever, so what happens to people in that environment is not going to stay there,” she said.

University of South Dakota psychology professor Cindy Struckman-Johnson, an expert on issues related to prison rape, said Cook’s study “suggests that there may be a sea change in how security officers perceive and respond to the problem of inmate rape.” Surveys conducted by the Bureau of Justice Statistics for the Prison Rape Elimination Act of 2003 indicated that sexual abuse of inmates was a serious problem in prisons and jails, and research from the 1990s shows many correctional officers in state prisons questioned the credibility of inmates who reported being raped in prison, particularly those who were gay or bisexual, she said.

The strongest point of agreement among the officers surveyed was that 96 percent said they should do everything in their power to protect their wards against sexual assault, and 95 percent say they should encourage inmates to report these crimes.

The study also found that corrections officers consider gay men or those with feminine qualities less responsible for rape than inmates who previously consented to sex or those who take money or cigarettes in exchange for sex, Cook said.

Eighty-eight percent disagreed or strongly disagreed with the statement that homosexual inmates get what they deserve if they are raped in jail. Otherwise, the proportion of those disagreeing or strongly disagreeing was 76 percent for inmates who had taken money or cigarettes in exchange for consensual sex and 74 percent who had previously consented to sex in jail.

“That officers find inmates who are homosexual or who act feminine most credible indicates they almost expect these people to be targeted in a correctional setting,” she said.

The lowest response from officers concerned whether the officers should talk with inmates about the risks of being sexually assaulted, Cook said. Only 59 percent said they thought it was their place to do so, suggesting they believe it is a more appropriate role for counselors, she said.

“It shows they’re more likely to blame inmates for what they do in jail than who they are,” Cook said.

In many ways, perceptions of inmate credibility mirror attitudes about female rape victims in the community at large, Cook said. Women who are known to have had previous relationships with their perpetrators, for example, are often seen as less believable, she said.

“I think that many scholars, including myself, would argue that it’s very difficult to call any sexual acts consensual in a correctional environment,” she said. “An inmate may agree to have sex with an inmate who offers physical protection from other inmates, or there could be other underlying circumstances.”

No reliable statistics are available for the number of rapes in prisons and jails because inmates — particularly men — are reluctant to report it, she said.

“Sexual assault really targets inmates for further attacks,” she said. “Typically in a correctional environment, there are the powerful and the weak. Once someone is preyed upon, they become a successful target and it opens the door for others to prey upon them.”

GAINESVILLE, Fla. — “What brings you in to see me today?”

“Part of my left breast has been painful for awhile.”

“Can you lie down so that I can examine you?”

It sounds like a snippet of conversation between doctor and patient. But the doctor, in this recent exchange at the University of Florida campus, was actually an engineering doctoral student — and the patient a “mixed reality human” composed of a life-sized computer avatar on a flat screen and a mannequin with a prosthetic breast.

Intimate procedures such as breast exams, while a routine and critical part of medical care, are notoriously tough to teach. Medical students practice on disembodied prosthetics but have limited opportunities to practice exams on real people — especially patients who have an abnormality. In a collaboration with the Augusta, Ga.-based Medical College of Georgia and three other universities, UF engineers have crafted a solution: a hybrid computer/mannequin that helps train students not only how to correctly perform a breast exam — but also how to talk to, and glean information from, the patient during the procedure.

The project is important because correct examinations and good doctor-patient communication are critical to successful medical treatment, said Benjamin Lok, a UF assistant professor of computer and information sciences and engineering who heads the effort.

“Studies have shown that communication skills are actually a better predictor of outcome than medical skills,” Lok said. With the virtual patient, “all of a sudden, students have to not only practice their technique, but they also have to work on their empathy.”

The mixed reality human, named Amanda Jones, “talks” to students, and they respond via a computer speech and voice recognition system tailored by doctoral student Aaron Kotranza, Lok and others on the team. Her physical form — a mannequin — is immobile, but her virtual representation, created by the engineers, moves and speaks from a large flat screen above her physical body. Students can also view Jones through a head-mounted display.

The interaction is unscripted, but it follows a typical pattern for a woman’s visit and examination — with both verbal and tactile challenges for the medical students.

The student must tease out Jones’ medical history, listen to her concerns and respond to her questions. Just as in a real exam, this interaction occurs simultaneously with the physical examination. For that, the student must use the correct palpitating technique and apply the proper pressure. Sensors within the prosthetic breast — developed by Dr. Carla Pugh at Northwestern University — provide pressure information depicted by colors on the virtual breast, guiding students in the exams. The engineers can program the system to include or exclude an abnormality — and the attendant conversation.

It sounds awkward, and to be sure, the speech recognition element has its hiccups.

But especially for students reared in an era of sophisticated three-dimensional video games, the system turns out to be surprisingly convincing. The researchers have tested it on about 100 medical students so far, all from the Medical College of Georgia, where co-principal investigator Dr. D. Scott Lind is based. One of their most consistent and prominent findings: Students do not hesitate to express empathy to Jones.

“We have found that they will try to comfort the virtual human,” Kotranza said. “They’ll often touch the mannequin in order to comfort her.”

A pilot study has concluded that students who practiced with a mixed realty human improved their communication skills and their technical abilities, but more trials are needed to determine whether those skills persist once the students examine real patients.

That said, it seems obvious that more practice students get, the better off they will be. Lok said the mixed reality patient is not intended to replace real volunteers - far from it. But students typically have only a handful of opportunities with those volunteers before graduating. The mixed reality patient can add to their training while making it easier for teachers to help students with both their conversational and medical techniques.

“What happens if you find something in a woman’s breast? How do you talk to the patient?” Lok asked. “Students have to somehow build their database of experience.”

While the breast exam research continues, the team also intends to explore other intimate exams. Next in line: prostate exams. Lok and the students already have prosthetics they intend to couple with a virtual male patient similar to the breast exam patient.

The other institutions participating in the project are the University of Central Florida, the University of Georgia and Northwestern University. The research, part of a larger effort involving a number of different virtual patient projects, is supported by grants of about $2.8 million primarily from the National Science Foundation and the National Institutes of Health.

The analysis of a well-preserved skull from 54 million years ago contradicts some common assumptions about brain structure and evolution in the first primates. The study also narrows the possibilities for what caused primates to evolve larger brain sizes. The study is scheduled to appear online the week of June 22 in the Proceedings of the National Academy of Sciences.

The skull belongs to a group of primitive primates known as Plesiadapiforms, which evolved in the 10 million years between the extinction of the dinosaurs and the first traceable ancestors of modern primates. The 1.5-inch-long skull was found fully intact, allowing researchers to make the first virtual mold of a primitive primate brain.

“Most explanations on the evolution of primate brains are based on data from living primates,” said lead author Mary Silcox, an anthropologist at the University of Winnipeg and research associate at UF’s Florida Museum of Natural History. “There have been all these inferences about what the brains of the earliest primates would look like, and it turns out that most of those inferences are wrong.”

Researchers used CT scans to take more than 1,200 cross-sectional X-ray images of the skull, which were combined into a 3-D model of the brain.

“A large and complex brain has long been regarded as one of the major steps that sets primates apart from the rest of mammals,” said Florida Museum vertebrate paleontologist and study co-author Jonathan Bloch. “At our very humble beginnings, we weren’t so special. That happened over tens of millions of years.”

The animal, Ignacius graybullianus, represents a side branch on the primate tree of life, Bloch
said. “You can think of it as a cousin of the main line lineage that would have given rise ultimately to us.”

In previous research, Bloch and Silcox established that Plesiadapiforms were transitional species. Ignacius was similar to modern primates in terms of its diet and tree-dwelling but did not leap from tree to tree like modern fast-moving primates.

In many ways, the early primate behaved like living primates but with a brain that was one-half to two-thirds the size of the smallest modern primates. This means that factors such as tree-dwelling and fruit-eating can be eliminated as potential causes for primates evolving larger brain sizes, Silcox said, because “the smaller brained Ignacius was already doing those things.”

The mold suggests a “startling combination” of features in the early primate that requires a rethinking of primate brain evolution, said Florida State University anthropologist Dean Falk, who was not involved in the study.

“Hypotheses about early primate brain evolution often link keen smell with nocturnal insect-eating, and a more recently evolved increase in visual processing with fruit-eating in arboreal habitats,” Falk said.

The move to larger brain size occurred during an evolutionary burst that happened 10 million years after the extinction of the dinosaurs. At that point, visual features in the brain became much more prominent while the olfactory bulbs became proportionately smaller.

More than likely, Bloch said, this change in brain structure and size was related to primates living in closed canopy forests that brought trees closer together and allowed for more leaping. But answering that will require the discovery and analysis of new fossils.

Changes in brain size and brain structure in the early stages of primate evolution have generated enormous debates for decades. But until now, fossil evidence has been lacking.

Many models of the ancestral primate brain are based on tree shrews, which come from southeast Asia and are distantly related to humans. But with some 70 million years of evolution between them and humans, “it turns out tree shrew brains are not a good model,” Silcox said.

The team headed by Eric Ford, an assistant professor of astronomy, used the Canary Islands-based GTC to observe a known star and its Jupiter-sized orbiting planet as part of an effort aimed in part at learning how planets contract in size as their stars age. With analysis of the data from the observations now under way, the team also hoped to glean insights about how to tune the GTC’s capabilities to study not only huge, gaseous Jupiter-size planets but also Neptune-sized or “super-Earth”-sized planets that could be closer in composition to Earth.

“The excellent site and large size of the GTC plus the unique filtering capabilities of its detectors will allow astronomers to minimize the effects of Earth’s atmosphere,” Ford said. “By repeatedly measuring the color of exoplanets’ host stars, astronomers can study the atmospheres of exoplanets — and distinguish small planets from other phenomena such as large star spots or binary stars.”

The UF team’s late-May observations were among several announced earlier this week by the Instituto de Astrofisica de Canarias that marked the long-awaited scientific debut of the GTC, first launched in 2000 on the island of La Palma, and only recently completed. UF contributed $5 million to the roughly $180 million telescope and owns a 5 percent share – the only U.S. institution with an ownership stake in the telescope. The Spanish government owns 90 percent, with Mexico owning the remaining 5 percent.

The GTC’s unique 34.1-foot primary mirror, composed of 36 hexagonal segments, gives it unparalleled abilities to see deep into the universe and examine distant objects in great detail. The telescope is equally notable for the ultra-precise computer control of its mirror segments — control that makes possible more finely detailed images than achievable with other telescopes. Its size and controllability makes the GTC powerful enough to detect an ordinary candle from 20,000 miles away — and resolve the width of its flame from six miles away.

UF astronomers say they will use the telescope to learn more about what occurred in the earliest years of the universe, how stars, planets and galaxies come into being, and to discover and learn more about planets outside our solar system.

“We made this investment because we want our excellent faculty and students to have as much opportunity as possible for top-class research,” said Stan Dermott, chairman of the astronomy department. “In astronomy, that requires access to the best facilities.”

Ford, graduate student Knicole Colón, and postdoctoral associates Brian Lee and Suvrath Mahadven, tapped a Spanish-built astronomical instrument, OSIRIS, to gather the data on the extrasolar star, HAT-P-3, and its planet, HAT-P-3b.

However, A UF-designed and built instrument, CanariCam, is anticipated to be the second instrument installed on the GTC. Among other goals, CanariCam will explore origins and early evolution of planetary systems by imaging the protoplanetary disks where planets are born. UF astronomers also made significant contributions to a third instrument expected to be installed on the GTC known as FRIDA.

“The University of Florida is a partner not just in the observing sense,” Dermott said. “We are also a partner in the sense of being the major builder of instruments for the telescope.”

The GTC’s first, ceremonial observations occurred in 2007, before the telescope’s mirror was complete. A formal inauguration is planned for July 24 on the island of La Palma. King Juan Carlos I and Queen Sofia of Spain will preside over the ceremony.

Two University of Florida scientists are part of the multicenter team of researchers that made the discovery, which could pave the way for better treatments that target the disease, according to findings published Wednesday in the journal Nature.

“What makes our study so important is that although neuroblastoma accounts for 7 percent of childhood cancers, it is responsible for 15 percent of deaths in children with cancer,” said Wendy London, a research associate professor of epidemiology, biostatistics and health policy research at the UF College of Medicine and a member of the UF Shands Cancer Center. “This paper adds yet another gene in the pathway that could lead to tumorigenesis (tumor formation) of neuroblastoma.”

Neuroblastoma forms in developing nerve cells, with tumors most often found on a child’s adrenal gland. It’s the most common form of cancer in babies and the third most common childhood cancer, according to the American Cancer Society.

Led by Dr. John J. Maris, director of the Cancer Center at The Children’s Hospital of Philadelphia, researchers performed what’s known as a genome-wide association study to uncover errors in DNA that could be associated with neuroblastoma.

To do this, researchers analyzed the genetic makeup of 846 patients with neuroblastoma, whose samples were derived from the Children’s Oncology Group Neuroblastoma Tumor Bank, and 803 healthy patients in a control group.

On the basis of their initial findings, the researchers performed a second validation analysis, pinpointing that a glitch called a “copy number variation” in a single chromosome is associated with neuroblastoma. Copy number variation has to do with the gain, loss or duplication of snippets of DNA.

“This is part of series of papers that creates the bigger picture, an understanding of the genetic mechanisms that lead to neuroblastoma,” said London, the principal investigator for the Children’s Oncology Group Statistics and Data Center at UF. “We are searching for genetic targets to treat with therapy.”

The researchers reported additional genetic links in Nature Genetics in May. The team discovered that on the gene called BARD1, six single-nucleotide polymorphisms — variations in tiny pieces of DNA — were also associated with neuroblastoma.

“Only two years ago we had very little idea of what causes neuroblastoma,” said Maris, who led both studies. “Now we have unlocked a lot of the mystery of why neuroblastoma arises in some children and not in others.”

Although neuroblastoma is one of the more common childhood cancers, it is relatively rare overall when compared with more common adult cancers, which has proved to be a challenge for researchers trying to uncover its causes, said Dr. Peter Zage, an assistant professor of pediatrics at the Children’s Cancer Hospital at the University of Texas M.D. Anderson Cancer Center.

“Dr. Maris’ group has been able to collect a relatively large number of cases for a neuroblastoma study and so has been able to identify these genetic variations and specific genes to provide us with some new avenues for therapy that we probably would not have been able to identify looking at the smaller cohorts of patients we each see at our individual institutions. In that sense, it’s certainly an amazing leap forward in our understanding of the disease.”

The discovery does hold promise for developing treatments, but London cautions that these potential “targeted therapies” won’t work on all neuroblastoma patients. Not all neuroblastoma patients have this particular genetic anomaly, and not all children with this anomaly will develop neuroblastoma. Development of neuroblastoma is complicated and can occur because of multiple reasons, arising after a complex chain of events, London said.

“What’s amazing is there are so many different ways for tumorigenesis to occur,” London said. “That’s the reason it is so hard to treat and cure cancer, or even to understand why it happens and how it happens.”

All the researchers involved in the study are members of the Children’s Oncology Group, the only National Institutes of Health/National Cancer Institute pediatric cancer cooperative group. The group performs clinical trials, collects specimens and performs statistical analysis related to pediatric cancers. UF is one of three institutions with a COG Statistics and Data Center, where study design, data collection and statistical analysis for COG research occurs.

Wait times to receive a deceased donor kidney transplant have increased over the years, but this study is the first to define and quantify what this wait time means for older patients. Researchers suggest that some candidates should consider live-donor options rather than wait for deceased-donor organs to become available.

The findings give firm data that can guide patients in making decisions, and policymakers in allocating donated organs.

“If someone knows that they have a 10 percent chance of dying before transplantation, they might consider it differently than if they know they have an 80 or 90 percent chance,” said Jesse Schold, an assistant professor of medicine and first author of the paper published today (June 18) in the Clinical Journal of the American Society of Nephrology. “Understanding what these survival estimates are may provide a more objective and useful basis for evaluating donor options for this population.”

The researchers suggest that some patients need to ask their doctors about their chances of surviving to receive a transplant, and, once they decide, to speed through the steps necessary to get on the waiting list. It can take several months for patients to go from primary care provider referral to a transplant center and through the medical tests and additional steps involved in getting their name on the list.

“Older patients must be referred for transplantation sooner than they are now, and they need to be guided through the process of pursuing live donor kidney transplantation,” said Harvard transplant psychologist Jim Rodrigue, director of behavioral health services and research in the Transplant Institute at Beth Israel Deaconess Medical Center. “The older population is least likely to pursue a live donor transplant and is less likely to have healthy living donors available.”

That’s because the older people get, the older their siblings and peer network become, with potentially more medical problems than when they were younger. And older patients tend to say they do not want to burden their adult children, other relatives or friends by asking them to be live donors.

About 50 percent of the more than half a million people in the United States who have end-stage renal disease are older than 60. In medically eligible patients, kidney transplantation gives a better survival chance than dialysis.

The UF team examined data from the national Scientific Registry of Transplant Recipients for almost 55,000 candidates older than 60 who were listed for a single-kidney deceased-donor transplant from 1995 through 2007. They used statistical models to estimate the time to receive a transplant and time to death after getting on the list.

Although overall about half of the over-60 group was projected to die before transplant, different subgroups had even higher likelihood of dying before a transplant.

Long-standing racial disparities are borne out by the data, with black patients having a higher probability than white patients of dying before a transplant: Sixty-two percent of black patients older than 60 will likely die before getting a transplant.

“That is an important finding because African-Americans are substantially less likely than whites to receive a live donor transplant, regardless of age,” Rodrigue said. “For those who are over 60, this is simply more bad news.”

Another notable disparity is that people’s survival chances vary greatly — from 8 percent to 81 percent — depending on where in the country they happen to live.

“It seems inherently unjust that we have such significant geographic disparity in survival on the waiting list based on where you live,” Rodrigue said.

It is true that some regions are better than others at recovering organs and have better donor rates. But based on the study’s results, one thing for policymakers to consider might be redrawing geographical boundaries of designated transplant regions so that more people have a better shot at getting an organ.

“We like to promote equity and policies that give a fair chance,” Schold said.

While the study findings support broad conclusions about patients’ survival chances, they might not apply to individual patients.

Still, Rodrigue said, they will change the doctor-patient conversations at his institute, for one. In the past, the underlying assumption was that patients will eventually get a deceased donor organ.

“Now we’ll have a more directed conversation with patients about the risk of death,” he said. “It’s not just how long you wait.”

GAINESVILLE — For most parents, soothing a child’s anxiety is just part of the job. But for a parent whose child has obsessive-compulsive disorder, soothing anxiety and helping with behaviors linked to the disease could lead to more severe symptoms, University of Florida researchers say.

Often, parents of children with OCD will help their children complete rituals related to their obsessions and compulsions, such as excessive bathing or checking things like door locks, according to findings recently published in the Journal of Consulting and Clinical Psychology. These accommodations can be anything that makes the symptoms of OCD less impairing, from reassuring a child that his hands are clean and his baby brother is OK to even doing his homework for him or buying objects that make the child feel safe.

“Parents do that because that is what a parent whose child doesn’t have OCD would do,” said Lisa Merlo, a UF assistant professor of psychiatry and the lead author of the study. “If your child is upset, you try to comfort them. But what we know is, for patients with OCD, if they get an accommodation, that reinforces the OCD to them.

“It’s validating the OCD in the kid’s mind, and that’s what you don’t want to do.”

About one in 200 children and teenagers in the United States have OCD, according to the American Academy of Child & Adolescent Psychiatry.

The study included 49 children between 6 and 18 with OCD and their families who came to UF for a type of treatment called cognitive-behavioral therapy. This form of therapy involves exposing children to their fears and teaching them better ways to respond and cope. During the sessions, therapists teach parents how they should deal with their child’s OCD, too.

Prior to the start of the 14-session therapy, the researchers gauged how severe each child’s condition was and compared it to how many accommodating behaviors parents reported. They found that the more severe the child’s OCD, the more the child’s family seemed to accommodate OCD behaviors.

“You would think if parents are helping, the kids would be less impaired,” Merlo said. “But what we are seeing is that it snowballs and makes it worse and worse.”

After the treatment, researchers noticed a significant decrease in how often families were assisting children with OCD behaviors and rituals. Children whose families had the biggest decrease in these accommodations also had the biggest improvement in their OCD symptoms, Merlo said.

What researchers don’t yet know is if a family’s “help” causes a child’s OCD to worsen or if the severity of the disease causes parents to try to do more to help their children.

Some children, including many who come to UF’s clinic, have symptoms so severe it prevents them from playing with friends or even going to school, Merlo said. In these instances, parents often feel they have to do whatever they can to help their children function, from doing their homework for them to buying specific items they feel like they need.

“If a kid is struggling a lot, parents feel like they have to do a lot to get through the day,” Merlo said. “But if the child is not experiencing the natural consequences of the OCD symptoms, then they don’t have any motivation to stop.”

This phenomenon isn’t exclusive to children and parents, said Jonathan S. Abramowitz, an associate professor and associate chairman of psychology at the University of North Carolina at Chapel Hill.

“We see it with adults’ spouses and partners, too. In trying to be helpful to the person with OCD, they end up making the problem worse.”

Although therapists have noticed this phenomenon anecdotally, there has so far been little research evidence to prove it. UF’s study will help therapists and scientists address the problem, he said.

“It is very nice to have research data to back up these clinical observations,” he said.

Researchers with the McKnight Brain Institute of the University of Florida, in collaboration with scientists at the University of Frankfurt, Germany, discovered that inflammation of microglia — an abundant cell type that plays an important supporting role in the brain — does not appear to be associated with dementia in Alzheimer’s disease.

The finding supports recent clinical trial results that indicate anti-inflammatory drugs are not effective at fighting dementia in patients with Alzheimer’s disease, which affects about 5.3 million Americans.

“For almost 20 years now, it’s been claimed that brain inflammation contributes to the development of Alzheimer’s disease dementia, and based on that claim, numerous clinical trials with anti-inflammatory drugs have been conducted. They have been unsuccessful,” said Wolfgang Streit, a professor of neuroscience at the College of Medicine. “In the current paper we have shown that the brain’s immune system, made up of microglia, is not activated in the brains of Alzheimer’s patients, as would be the case if there were inflammation. Instead, microglia are degenerating. We claim that a loss of microglial cells contributes to the loss of neurons, and thus to the development of dementia.”

Microglial cells are a subset of a very large population of brain cells known as glial cells. Neurons are the workhorse cells of the brain, enabling thought and movement, but glia are their faithful sidekicks, providing physical and nutritional support.

Glial cells, which outnumber neurons 10-to-1, are at the heart of a popular explanation for Alzheimer’s disease that suggests protein fragments called beta amyloid — Abeta for short — clump together in the spaces between brain cells, causing memory loss and dementia. Inflammation theories suggest that microglia become “activated” and mount an immune response to these protein clumps, and instead of being helpful, a toxic release of chemicals occurs, worsening the disease effects.

However, Streit’s high-resolution observations did not find evidence that Abeta activates, or inflames, human microglia cells. Nor did researchers find evidence that inflammation is to blame for brain cell death.

“This paper potentially represents a paradigm shift in the way we look at Alzheimer’s disease,” said Mark A. Smith, a professor of pathology at Case Western Reserve University and editor-in-chief of the Journal of Alzheimer’s Disease. “The study goes against the very popular idea of neuro-inflammation; instead, the idea that microglia are senescent is consistent with a number of features of the disease.

“The research makes a very good case that these cells are subject to aging,” said Smith, who did not participate in the study. “These cells were thought to be activated (against Alzheimer’s), but this paper makes a strong case that they are not. The study has taken a novel approach that has led to a novel insight.”

Using a commercially available antibody, Streit for the first time created a marker for microglial cells in human brain specimens that had been in chemical storage. The specimens were from 19 people with varying degrees of Alzheimer’s, ranging from severe to none at all. Two of the samples were from Down syndrome patients, who are known to develop Alzheimer’s pathology in middle age.

When researchers examined these cells alongside neurons under a high-resolution microscope, they found that — unless an infection had occurred elsewhere in the body — microglial cells from Alzheimer’s patients were not distinctly larger or unusually shaped, which would have been the case had they been inflamed.

“What I expected to see is activated microglia right next to dying neurons,” Streit said. “That is what I did not find. What I propose is glia are dying, and the neurons lose support. We now need to find out what caused glia to degenerate. Rather than trying to find ways to inhibit microglia with anti-inflammatory drugs, we need to find ways to keep them alive and strong. It’s a whole new field.”

The microglial cells had a tangled, fragmented appearance, similar to neurons in the throes of Alzheimer’s disease or — old age.

“These cells are breaking into pieces,” said Streit, who collaborated with Alzheimer’s researcher Dr. Heiko Braak, of the Institute for Clinical Neuroanatomy in Frankfurt. “They are on their way out. For the first time, we are proving that microglial cells are subject to aging and may undergo degeneration, and that the loss of these cells precedes the loss of neurons. Research has been so focused on finding activated microglia, no one considered that these cells were degenerating and neurons lost support.”

The work was supported by the National Institutes of Health, the German Research Council and the Evelyn F. and William L. McKnight Brain Institute.

Alzheimer’s disease is the sixth leading cause of death in the United States and the fifth leading cause of death for Americans 65 and older, according to the Alzheimer’s Association. The association estimates Alzheimer’s and other dementias cost Medicare, Medicaid and businesses a total of $148 billion annually.

In mice implanted with human colorectal cancer cells, tumor volume decreased 53 percent and cancer cell growth slowed by 49 percent in those treated with a gene that encodes for the artificial protein, compared with those that were untreated.

The research team, led by Dr. Bradley S. Fletcher, an assistant professor of pharmacology and therapeutics in the College of Medicine, created the so-called fusion protein to target another protein called tumor endothelial marker 8, or TEM8, which was recently found to be preferentially expressed in the inner lining of tumor vessels. Such differences in protein expression enable delivery of drug molecules to the cells that harbor these proteins.

“The protein we created did a very good job of homing to the tumor and binding,” said Stephen Fernando, who recently completed his doctoral studies. “By targeting TEM8, we can potentially create a therapy against cancer.”

The Fletcher group is the first to target cancer cells through protein binding to TEM8. The findings, now available online, are featured on the cover of the June 15 edition of Cancer Research.

“If you can cut off the blood supply, then you can inhibit the tumor from growing — there have been many attempts,” said Brad St. Croix, director of the National Cancer Institute’s Tumor Angiogenesis Section, whose group first identified the TEM genes that over-express in tumor endothelial cells. “The concept of targeting tumor blood vessels has been around for many years, but it’s good that we’re finally getting around to the stage where we can see the vessels being targeted therapeutically — it’s pretty exciting, I think.”

St. Croix was not part of the current research team, but donated some experimental materials.

The UF group created a “fusion protein” — part of which binds to TEM8, and the other which promotes thrombosis, or blood clotting — and delivered genes that encode for it to the lungs of mice. The delivery vehicle was a transposon called Sleeping Beauty, a piece of DNA that can insert new genes stably and efficiently into a cell’s genome.

The lungs then functioned as a factory to produce the protein that later found its way to the target cells in the tumor vessels.

“We felt that TEM8 was an ideal target because it was inside the vessel, preferentially expressed there and unique,” Fletcher said.

In addition to promoting blood clots, the strategy also resulted in reduced tumor vessel density, possibly by interfering with TEM8 function.

Fletcher’s group previously applied the Sleeping Beauty transposon gene delivery method to the treatment of hemophilia and pulmonary hypertension and the prevention of lung transplant rejection in animal studies. After developing those three successful models, they looked for disease applications in which poor outcomes would be worth the risk associated with gene therapy.

“We felt that cancer was potentially a target,” Fletcher said. “Gene therapy has a lot of risk associated with it, so you don’t want to do it for diseases that are not life-threatening.”

The group plans to come up with a method to increase the amounts of the thrombosis-inducing protein produced in the body, and test whether higher dosing leads to unintended blood clots.

They are also looking into ways to deliver the protein directly to the sites of interest, rather than through genes that later produce the protein, and apply the method in other areas such as prostate cancer. Other work will include the use of coated nanoparticles to detect tumors and deliver drugs or radiate heat to destroy cancer cells when bombarded by radio waves.

The work was supported by a grant from the James and Esther King Foundation, and a travel grant for Fernando from the American Society of Gene Therapy.

Initial research suggested that enlargement and abnormalities of axillary sentinel lymph nodes — located in the armpit area near the breast — were predictive of cancer. But a University of Florida Shands Cancer Center researcher says it’s not the size of the node or enhancement, but the loss of a key part of a normal node’s structure called the fatty hilum that more accurately signals the spread of disease. The findings are available online in the Journal of Magnetic Resonance Imaging.

In addition to changing ideas about what doctors should look for while evaluating lymph nodes, the finding reinforces the value of using MRI to determine the extent of breast cancer prior to surgery.

“We found that the loss of fatty hilum in an axillary lymph node on MRI correlated with finding the spread of breast cancer in axillary nodes at the time of surgery,” said Dr. Stephen Grobmyer, an assistant professor of surgical oncology and endocrine surgery at the UF College of Medicine, who noted that not all nodes without fatty hilum necessarily had cancer.

The UF study retrospectively examined 56 female patients ranging in age from 30 to 82. All women had a sentinel lymph node biopsy. Fifteen women had cancer in the nodes that required complete removal. Four of eight patients in whom a loss of fatty hilum was seen in an axillary node on MRI were found to have cancerous lymph nodes at the time of their breast surgery. By comparison, only 11 out of 48 patients, or 23 percent, with all fatty hilum in place had cancer.

Grobmyer said these findings provide surgeons with another tool to help personalize medicine and evaluate factors that could indicate whether cancer has spread prior to surgery.

“I think this is another step to understanding how we can use MRI to improve care of breast cancer patients,” said Grobmyer, medical director of the UF Comprehensive Breast Center. “We are just suggesting that there may be information that people have not yet paid attention to that may impact our understanding of the staging of a patient’s disease. With this technology, if you look and see there is a node or several nodes with no fatty hilum, one would be very suspicious that there might be metastatic disease present. Instead of doing an invasive sentinel node biopsy, one could do a less invasive image-guided biopsy to obtain important staging information.”

He added it is also important that we now understand that MRI features that suggest cancer in the breast do not apply for evaluating disease in axillary lymph nodes. Currently, there is no standard MRI criterion for determining if cancer is in the nodes.

Although not routinely administered to all breast cancer patients, magnetic resonance imaging, or MRI, can offer a detailed picture of the breast, providing precise details about breast cancer locations and size. The scan is augmented through a technique known as contrast enhancement, which makes it easier to discern between cancerous and healthy tissue. The standard scan includes the axillary lymph nodes, the most common first site of spread for breast cancer.

Dr. Steven E. Harms, a radiologist with the Breast Center of Northwest Arkansas, said the accurate diagnosis of lymph node metastases is critical for patients with breast cancer, and the ability to determine their presence before the initial surgery could spare many patients the need for more than one operation.

“Over-treatment with a full axillary node removal is associated with a high incidence of lymphedema, a lifelong and often debilitating condition resulting from the disruption of lymph channels,” said Harms, who, in 2007, helped to draft the American Cancer Society breast cancer screening guidelines which recommend breast MRI screening for high risk patients.

Grobmyer said he hopes studies of a larger number of patients will further validate these findings so they can be broadly applied. He said the great advantage of an MRI is its ability to pick up more than 95 percent of invasive breast cancers.

In late 2007, UF researchers presented findings about the diagnostic value of MRI in influencing treatment plans for women, citing that it can find previously undetected cancerous areas, including cancer in the opposite breast. MRI also helps to better determine tumor size and assess an individual’s response to chemotherapy, making it useful for planning surgical procedures, UF surgeons say.

Of more than 100 possible mutations of a single gene inherited by people with familial ALS, the mutations most inclined to produce clumps of problematic cellular debris known as “protein aggregates” appear to be associated with quicker progress of the disease, according to researchers with the University of Florida’s McKnight Brain Institute writing online this week in Human Molecular Genetics.

Meanwhile, in a separate study recently online in the Proceedings of the National Academy of Sciences, scientists describe how these protein clumps — long considered a defining characteristic of ALS — do not cause the disease, but appear later on, increasing in number between onset of weakness and paralysis in patients.

Together, these findings suggest that the deadly course of the disease is linked to the formation of these protein clumps, even though the sickness may have been well under way.

“Blocking aggregation of these proteins could be a therapeutic target for individuals with this genetic mutation,” said David Borchelt, a professor of neuroscience and director of the SantaFe HealthCare Alzheimer’s Disease Research Center at UF’s McKnight Brain Institute. “Right now, there is little that can be done to help these patients.”

ALS involves the death of nerve cells that stretch from the brain to the spinal cord, and from the spinal cord to muscles. It strikes people between the ages of 40 and 70, according to the ALS Association. An estimated 30,000 Americans have the disease at any given time.

Patients usually have a life expectancy of two to five years, with some notable exceptions, such as Cambridge University scientist and author Stephen Hawking, who has survived for more than 40 years since his diagnosis.

The cause of ALS is unknown in about 80 percent of cases, but 10 percent to 20 percent of ALS cases can be traced to an inherited genetic defect. No matter the cause, scientists believe that a basic cellular process in which amino acids are folded into proteins goes wrong in ALS. The misfolded proteins cannot perform their intended function. Instead, they form the troublesome protein aggregates.

UF’s research centered around one gene that produces an enzyme called superoxide dismutase 1, or SOD1. Although SOD1 performs an important role in cell maintenance by warding off dangerous molecules known as free radicals, 146 different mutations in the SOD1 gene have been identified in patients with inherited ALS.

UF scientists, including doctoral student Mercedes Prudencio with Dr. Peter Andersen of Umea University in Sweden, analyzed data from ALS patients to correlate the disease features with more than 30 different variants of SOD1. They found that the mutations most associated with protein aggregation are generally predictive of a more rapid disease progression.

In the PNAS study, UF researchers with investigators from the University of Texas Health Science Center in San Antonio pinpointed when the protein clumping begins and how long the disease has been at work before symptoms actually appear.

By studying SOD1 in mice genetically engineered with a form of ALS, UF doctoral student Celeste Karch demonstrated that the protein clumps appear in spinal cord tissues later in the disease, about the same time that symptoms appear, but well after cell damage occurs from nerve loss and the formation of fluid-filled pockets called vacuoles.

The finding suggests the aggregated proteins may elude normal cellular “housecleaning” methods, or their formation is heightened by stress conditions in the cell.

“As the disease enters the symptomatic stage in mice, the buildup of protein is rapid and dramatic,” Borchelt said. “However, the formation of these aggregates is not the whole story. It is well established that significant damage to the nervous system occurs well before the symptoms appear. The uncontrolled misfolding of SOD1 seems to be confined to the late stage of disease, which is when symptoms first appear, giving hope that treatments targeting this process could be beneficial.”

Furthermore, the findings suggest that there is a larger therapeutic window to treat ALS, if scientists can find a way to diagnose the disease before the hallmark protein clumping begins.

“Many scientists had accepted that protein aggregation was tied to the causation of ALS,” said Joan Selverstone Valentine, a UCLA professor of chemistry and biochemistry who did not participate in the study. “But this research shows these aggregates form during disease progression, not initiation. It is important to know what to look for as an early cause of the disease and what causes it to get more severe. That means we have to look for something upstream of aggregation as a cause, as well as understand the steps in the progress. If you can prevent or halt the aggregation, you can stop the disease in its tracks. That’s as good as a cure if it can be done early enough.”

-30-