HIV testing yields diagnoses in Kenya but few seek care

A sweeping effort in a rural region of Kenya to test all adults for HIV discovered 1,300 new infections, but few of the newly diagnosed people pursued treatment, a study in the journal Lancet HIV reports.
PROVIDENCE, R.I. [Brown University] — Between December 2009 and February 2011, health workers with the AMPATH Consortium sought to test and counsel every adult resident in the Bunyala subcounty of Kenya for HIV. A study in the journal Lancet HIV reports that the campaign yielded more than 1,300 new positive diagnoses, but few of those new patients sought health care.

“Home-based counseling and testing (HBCT) provided a diagnosis to nearly 40 percent of people living with HIV in this subcounty who otherwise most likely would not have gone for HIV testing,” said study lead author Becky Genberg, assistant professor (research) of health services, policy and practice in the Brown University School of Public Health. “They therefore would not have known about their HIV infection and not had the opportunity to change their behavior to protect others.”

AMPATH’s HBCT program is part of a strategy to identify all individuals living with HIV in the catchment area, start them on antiretroviral medication as soon as possible, and help them stay on their medications. Antiretroviral medication not only suppresses HIV infections for most patients but also reduces their ability to transmit the virus.

Genberg with co-author Edwin Sang “We are working on a variety of studies, all designed to understand the barriers facing the newly diagnosed, and to implement and evaluate strategies to increase their engagement and retention in HIV care over time.”

In Bunyala, home to about 66,000 people, the HBCT program tested about 32,000 adults. Among them, 3,482 had HIV. Of those, 2,122 already knew they were infected, but 1,360 did not know it yet.

A major finding of the study is that three years later only 15 percent of the newly diagnosed people had engaged in care for their infection. A likely reason why, Genberg said, is that newly diagnosed people typically don’t yet feel sick.

“That so few linked to care following HBCT is a call for innovative and creative strategies to work alongside HBCT to support the mostly healthy, asymptomatic newly diagnosed to engage with care in a way that is meaningful for them,” Genberg said.

In an editorial in the journal, Rashida Ferrand of the London School of Hygiene and Tropical Medicine said the study sounds a warning that home-based testing must be paired with effective ways to convince newly diagnosed patients to seek help.

“Unless paired with interventions targeted at hard-to-reach populations, the diagnosing of undiagnosed individuals in many settings will not be cost-effective and will have little effect on individual and population viral suppression,” she and colleagues wrote.

Genberg, who has been in Kenya this winter, said she is working with Kenyan collaborators on developing the needed interventions: “Right now we are working on a variety of studies, all designed to understand the barriers facing the newly diagnosed, and to implement and evaluate strategies to increase their engagement and retention in HIV care over time.”

In addition to Genberg the study’s authors are Joseph Hogan and Corey Duefield of Brown; Violet Naanyu, Juddy Wachira, and Samson Ndege of Moi University in Kenya; Edwin Sang, Monicah Nyambura, and Michael Odawa of AMPATH; and corresponding author Paula Braitstein of the University of Toronto.

The President’s Emergency Plan for AIDS Relief funded the study though USAID (grant AID-623-A-12-0001). Additional support came from the National Institutes of Health (K01MH099966) and the Bill and Melinda Gates Foundation.

Source: Brown University

Diagnosis targets in primary care are misleading, unethical, UK experts say

Last month, there was public outcry at the news that GPs in England would be paid £55 for each case of dementia diagnosed.

Now come targets for six other conditions, including diabetes coronary heart disease, asthma and depression, writes Dr Martin Brunet, a GP in Surrey. "But the data on which they are based are flawed, and the approach incentivises potentially harmful overdiagnosis," he argues.

Every practice in England has been told its diagnosis rate for each condition, estimated from practice data and the expected prevalence, he explains. The intention is to exert pressure on general practitioners to increase diagnosis rates, but he believes the principles behind such a policy need to be questioned.

Brunet argues that applying error prone national prevalence data to an individual practice is problematic. Although attempts are made to account for local demographics, practices may be under pressure to "improve" diagnosis rates that are far better than the data would suggest, he warns.

He also questions the ethical implications for individual patients of unnecessary tests and treatments that "could do more harm than good" and divert resources away from people with symptoms.

Targets in healthcare always threaten to undermine trust in the doctor-patient relationship, says Brunet. "For this reason patients need to trust that the doctor will act solely in their best interests, unencumbered by competing interests."

"NHS England needs to hear the clear message from doctors and patients that setting targets for diagnosis is problematic, unscientific, and unethical," he argues. "Instead, it needs to trust doctors and their patients to know when to seek a diagnosis."

Source: BMJ-British Medical Journal

Cone snail venom holds promise for medical treatments for cancer, addiction

Professor Frank Marí in the Charles E. Schmidt College of Science at Florida Atlantic University holds a live Conus regius, a particular species of cone snail collected by the Marí group at the Florida Keys. Credit: Professor Anton Oleinik

While considered a delicacy in some parts of the world, snails have found a more intriguing use to scientists and the medical profession offering a plethora of research possibilities. Cone snails are marine mollusks, just as conch, octopi and squid, but they capture their prey using venom. The venom of these marine critters provides leads for detection and possible treatment of some cancers and addictions.

Frank Marí, Ph.D., professor in the Department of Chemistry and Biochemistry in FAU's Charles E. Schmidt College of Science at Florida Atlantic University, has focused his research on cone snail venom and has published a study in the current issue of the Journal of Biological Chemistry.

"The venom produced by these animals immobilizes prey, which can be worms, other snails and fish," said Marí. "The venom is an extraordinary complex mixture of compounds with medicinal properties."

The venom components selectively target cells in the body and make them valuable drug leads and powerful molecular tools for understanding the human body's processes. One class of venom components is the alpha-conotoxins, named so because they target nicotinic receptors that are central to a range of diseases such as Alzheimer's disease, schizophrenia, tobacco addiction and lung cancer.

The venom of a particular species of cone snail, Conus regius, collected by the Marí group at the Florida Keys, is particularly rich in alpha conotoxins. Aldo Franco, Ph.D., who worked in Marí's lab, described more than ten new alpha-conotoxins in his Ph.D. dissertation at FAU. 

Among these, they found RegIIA, a compound that potently blocked the alpha3beta4 nicotinic receptor. This particular receptor when activated can be associated with lung cancer and nicotine addiction.

"We investigated in detail how RegIIA interacts with the alpha3beta4 nicotinic receptors and embarked on engineering new compounds that were more specific toward alpha3beta4 receptors and not other nicotinic receptors," said Marí. "Our aim is to open new avenues for cancer and addiction research inspired on compounds from marine animals."

Cone snails can be found throughout the Florida coast at different depths. Marí and his team regularly collect these animals using SCUBA and sometimes using deep-water submarines.

Source: Florida Atlantic University

Lost memories might be able to be restored, suggests research into marine snail

New UCLA research indicates that lost memories can be restored. The findings offer some hope for patients in the early stages of Alzheimer's disease.

New UCLA research indicates that lost memories can be restored. The findings offer some hope for patients in the early stages of Alzheimer's disease.

For decades, most neuroscientists have believed that memories are stored at the synapses -- the connections between brain cells, or neurons -- which are destroyed by Alzheimer's disease. The new study provides evidence contradicting the idea that long-term memory is stored at synapses.

"Long-term memory is not stored at the synapse," said David Glanzman, a senior author of the study, and a UCLA professor of integrative biology and physiology and of neurobiology. 

"That's a radical idea, but that's where the evidence leads. The nervous system appears to be able to regenerate lost synaptic connections. If you can restore the synaptic connections, the memory will come back. It won't be easy, but I believe it's possible."

The findings were published recently in eLife.

Glanzman's research team studies a type of marine snail called Aplysia to understand the animal's learning and memory. The Aplysia displays a defensive response to protect its gill from potential harm, and the researchers are especially interested in its withdrawal reflex and the sensory and motor neurons that produce it.

They enhanced the snail's withdrawal reflex by giving it several mild electrical shocks on its tail. The enhancement lasts for days after a series of electrical shocks, which indicates the snail's long-term memory. Glanzman explained that the shock causes the hormone serotonin to be released in the snail's central nervous system.

Long-term memory is a function of the growth of new synaptic connections caused by the serotonin, said Glanzman, a member of UCLA's Brain Research Institute. As long-term memories are formed, the brain creates new proteins that are involved in making new synapses. If that process is disrupted -- for example by a concussion or other injury -- the proteins may not be synthesized and long-term memories cannot form. (This is why people cannot remember what happened moments before a concussion.)

"If you train an animal on a task, inhibit its ability to produce proteins immediately after training, and then test it 24 hours later, the animal doesn't remember the training," 

Glanzman said. "However, if you train an animal, wait 24 hours, and then inject a protein synthesis inhibitor in its brain, the animal shows perfectly good memory 24 hours later. In other words, once memories are formed, if you temporarily disrupt protein synthesis, it doesn't affect long-term memory. That's true in the Aplysia and in human's brains." (This explains why people's older memories typically survive following a concussion.)

Glanzman's team found the same mechanism held true when studying the snail's neurons in a Petri dish. The researchers placed the sensory and motor neurons that mediate the snail's withdrawal reflex in a Petri dish, where the neurons re-formed the synaptic connections that existed when the neurons were inside the snail's body. When serotonin was added to the dish, new synaptic connections formed between the sensory and motor neurons. But if the addition of serotonin was immediately followed by the addition of a substance that inhibits protein synthesis, the new synaptic growth was blocked; long-term memory could not be formed.

The researchers also wanted to understand whether synapses disappeared when memories did. To find out, they counted the number of synapses in the dish and then, 24 hours later, added a protein synthesis inhibitor. One day later, they re-counted the synapses.

What they found was that new synapses had grown and the synaptic connections between the neurons had been strengthened; late treatment with the protein synthesis inhibitor did not disrupt the long-term memory. The phenomenon is extremely similar to what happens in the snail's nervous system during this type of simple learning, Glanzman said.

Next, the scientists added serotonin to a Petri dish containing a sensory neuron and motor neuron, waited 24 hours, and then added another brief pulse of serotonin -- which served to remind the neurons of the original training -- and immediately afterward add the protein synthesis inhibitor. This time, they found that synaptic growth and memory were erased. When they re-counted the synapses, they found that the number had reset to the number before the training, Glanzman said. This suggests that the "reminder" pulse of serotonin triggered a new round of memory consolidation, and that inhibiting protein synthesis during this "reconsolidation" erased the memory in the neurons.

If the prevailing wisdom were true -- that memories are stored in the synapses -- the researchers should have found that the lost synapses were the same ones that had grown in response to the serotonin. But that's not what happened: Instead, they found that some of the new synapses were still present and some were gone, and that some of the original ones were gone, too.

Glanzman said there was no obvious pattern to which synapses stayed and which disappeared, which implied that memory is not stored in synapses.

When the scientists repeated the experiment in the snail, and then gave the animal a modest number of tail shocks -- which do not produce long-term memory in a naive snail -- the memory they thought had been completely erased returned. This implies that synaptic connections that were lost were apparently restored.

"That suggests that the memory is not in the synapses but somewhere else," Glanzman said. 

"We think it's in the nucleus of the neurons. We haven't proved that, though."

Glanzman said the research could have significant implications for people with Alzheimer's disease. Specifically, just because the disease is known to destroy synapses in the brain doesn't mean that memories are destroyed.

"As long as the neurons are still alive, the memory will still be there, which means you may be able to recover some of the lost memories in the early stages of Alzheimer's," he said.

Glanzman added that in the later stages of the disease, neurons die, which likely means that the memories cannot be recovered.

The cellular and molecular processes seem to be very similar between the marine snail and humans, even though the snail has approximately 20,000 neurons and humans have about 1 trillion. Neurons each have several thousand synapses.

Glanzman used to believe that traumatic memories could be erased but he has changed his mind. He now believes that, because memories are stored in the nucleus, it may be much more difficult to modify them. He will continue to study how the marine snail's memories are restored and how synapses re-grow.

Co-authors of the study include Shanping Chen, Diancai Cai and Kaycey Pearce, research associates in Glanzman's laboratory.

The research was funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health and the National Science Foundation.

Almost all the processes that are involved in memory in the snail also have been shown to be involved in memory in the brains of mammals, Glanzman said.

In a 1997 study published in the journal Science, Glanzman and colleagues identified a cellular mechanism in the Aplysia that plays an important role in learning and memory. A protein called N-methyl D-aspartate, or NMDA, receptor enhances the strength of synaptic connections in the nervous system and plays a vital role in memory and in certain kinds of learning in the mammalian brain as well. Glanzman's demonstration that the NMDA receptor plays a critical role in learning in a simple animal like the marine snail was entirely unexpected at the time.

Source: University of California, Los Angeles

Weigh-in once a week or you'll gain weight

The researchers found that weight loss was related to how often individuals weighed themselves. Credit: Image courtesy of Cornell Food & Brand Lab

Stepping on the scale is common among dieters but how does the frequency of weigh-ins impact weight? A new study in PLOS ONE showed that the more frequently dieters weighed themselves the more weight they lost, and if participants went more than a week without weighing themselves, they gained weight.

The researchers analyzed 2,838 weight measurements (up to a years' worth of weigh-ins) from 40 overweight individuals (with a body mass index of 25 and over) who indicated that weight loss was a personal goal or concern. The researchers found that weight loss was related to how often individuals weighed themselves. "The more often you weigh yourself the more weight you lose," says to lead author Elina Helander from Tempere Univeristy of Technology in Finland. This observational study cannot prove causation -- it may be that less serious dieters weight themselves less or that dieters who stop losing weight stop weighting themselves. The average time that participants could go between weighting without gaining weight was 5.8 days or about a weekly weigh-in.

Previous Findings by the Research Team

Weigh yourself at least once a week if you wish to lose weight, and weighing yourself everyday may help you stay on track. A previous study by the same research team found that your weight naturally fluctuates throughout the week and that most people weigh the least on Wednesday. To summarize both studies Brian Wansink, PhD, Director of the Cornell Food and Brand Lab and author of Slim by Design: Mind Eating Solutions for Everyday Life advises, "The bottom line is: If you want to lose weight, it's best to weigh yourself every day. But if you weigh yourself only once a week, do it on Wednesday because that will give you the most accurate reading."

Source: Cornell Food & Brand Lab

When you lose weight, where does the fat go? Most of the mass is breathed out as carbon dioxide, study shows

Despite a worldwide obsession with diets and fitness regimes, many health professionals cannot correctly answer the question of where body fat goes when people lose weight.
Credit: © Lovrencg / Fotolia

Despite a worldwide obsession with diets and fitness regimes, many health professionals cannot correctly answer the question of where body fat goes when people lose weight, a UNSW Australia study shows.

The most common misconception among doctors, dieticians and personal trainers is that the missing mass has been converted into energy or heat.

"There is surprising ignorance and confusion about the metabolic process of weight loss," says Professor Andrew Brown, head of the UNSW School of Biotechnology and Biomolecular Sciences.

"The correct answer is that most of the mass is breathed out as carbon dioxide. It goes into thin air," says the study's lead author, Ruben Meerman, a physicist and Australian TV science presenter.

In their paper, published in the British Medical Journal today, the authors show that losing 10 kilograms of fat requires 29 kilograms of oxygen to be inhaled and that this metabolic process produces 28 kilograms of carbon dioxide and 11 kilograms of water.

Mr Meerman became interested in the biochemistry of weight loss through personal experience.

"I lost 15 kilograms in 2013 and simply wanted to know where those kilograms were going. After a self-directed, crash course in biochemistry, I stumbled onto this amazing result," he says.

"With a worldwide obesity crisis occurring, we should all know the answer to the simple question of where the fat goes. The fact that almost nobody could answer it took me by surprise, but it was only when I showed Andrew my calculations that we both realised how poorly this topic is being taught."

The authors met when Mr Meerman interviewed Professor Brown in a story about the science of weight loss for the Catalyst science program on ABC TV in March this year.

"Ruben's novel approach to the biochemistry of weight loss was to trace every atom in the fat being lost and, as far as I am aware, his results are completely new to the field," says Professor Brown.

"He has also exposed a completely unexpected black hole in the understanding of weight loss amongst the general public and health professionals alike."

If you follow the atoms in 10 kilograms of fat as they are 'lost', 8.4 of those kilograms are exhaled as carbon dioxide through the lungs. The remaining 1.6 kilograms becomes water, which may be excreted in urine, faeces, sweat, breath, tears and other bodily fluids, the authors report.

"None of this is obvious to people because the carbon dioxide gas we exhale is invisible," says Mr Meerman.

More than 50 per cent of the 150 doctors, dieticians and personal trainers who were surveyed thought the fat was converted to energy or heat.

"This violates the Law of Conservation of Mass. We suspect this misconception is caused by the energy in/energy out mantra surrounding weight loss," says Mr Meerman.

Some respondents thought the metabolites of fat were excreted in faeces or converted to muscle.

"The misconceptions we have encountered reveal surprising unfamiliarity about basic aspects of how the human body works," the authors say.

One of the most frequently asked questions the authors have encountered is whether simply breathing more can cause weight loss. The answer is no. Breathing more than required by a person's metabolic rate leads to hyperventilation, which can result in dizziness, palpitations and loss of consciousness.

The second most frequently asked question is whether weight loss can cause global warming.

"This reveals troubling misconceptions about global warming which is caused by unlocking the ancient carbon atoms trapped underground in fossilised organisms. The carbon atoms human beings exhale are returning to the atmosphere after just a few months or years trapped in food that was made by a plant," says Mr Meerman, who also presents the science of climate change in high schools around Australia.

Mr Meerman and Professor Brown recommend that these basic concepts be included in secondary school curricula and university biochemistry courses to correct widespread misconceptions about weight loss among lay people and health professionals.

Source: University of New South Wales

Infectious prion protein discovered in urine of patients with variant Creutzfeldt-Jakob disease

Claudio Soto, Ph.D., in one of his labs at The University of Texas Health Science Center at Houston (UTHealth). Credit: Image courtesy of University of Texas Health Science Center at Houston

The misfolded and infectious prion protein that is a marker for variant Creutzfeldt-Jakob disease – linked to the consumption of infected cattle meat – has been detected in the urine of patients with the disease by researchers at The University of Texas Health Science Center at Houston (UTHealth) Medical School.

The results of the international study, led by Claudio Soto, Ph.D., professor of neurology at the UTHealth Medical School, will be published in the Aug. 7 issue of the New England Journal of Medicine.

Variant Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in animals – also known as Mad Cow disease – are fatal neurodegenerative disorders. There are currently no noninvasive tools available to diagnose the disease and there are no treatments.

Sporadic Creutzfeldt-Jakob disease occurs worldwide at a rate of around 1 new case per million people per year. The variant form is a new disease occurring in people who either ate the beef of cows with bovine spongiform encephalopathy or, in the case of three patients in the United Kingdom, received blood transfusions from asymptomatic infected donors.

The international team of researchers analyzed urine samples from 68 patients with sporadic Creutzfeldt-Jakob disease, 14 patients with variant Creutzfeldt-Jakob disease, four patients with genetic prion diseases, 50 patients with other neurodegenerative diseases, 50 patients with nondegenerative neurologic diseases and 52 healthy persons.

Soto’s laboratory used a protein misfolding cyclic amplification assay, invented in the lab, which mimics the prion replication process in vitro that occurs in prion disease. The misfolded prion proteins were detected in the urine of 13 of 14 patients with variant Creutzfeldt-Jakob disease. The single patient whose urine was negative had been receiving an experimental treatment of pentosan polysulfate directly into the brain. No misfolded prion proteins were detected in the urine of any the other study subjects, including the patients who had sporadic Creutzfeldt-Jakob disease.

“What could be less invasive than detecting this disease in urine? The fact that we were able to detect just the variant Creutzfeldt-Jakob disease form in the urine is very important. This could lead to the development of commercial technology for diagnosis as well as to determine the safety of donated blood and urinary products,” said Soto, who is the director of The George and Cynthia Mitchell Center for Research in Alzheimer’s disease and Related Brain Disorders, and founder of Amprion Inc, a biotech company developing the cyclic amplification technology for commercial application.

According to the World Health Organization (WHO), variant Creutzfeldt-Jakob disease affects younger patients, who have a median age of 28 at death, compared to sporadic Creutzfeldt-Jakob disease with a median age of 68. Most patients, after diagnosis of either form, live less than a year before death.

As of June 2, 2014, 177 of 229 people in the world with Creutzfeldt-Jakob disease were from the United Kingdom. A 2013 study published in the British Medical Journal has estimated that approximately 30,000 people in the United Kingdom might be carriers of the variant form of the disease.

“This study reports, for the first time, the detection of the abnormal prion protein in the urine from patients with variant Creutzfeldt-Jakob disease using the protein misfolding amplification technique pioneered by Dr. Claudio Soto,” said co-author James W. Ironside, FMedSci, FRSE, professor of clinical neuropathology at the National CJD Research and Surveillance Unit at the University of Edinburgh. “This has great potential to allow the development of a highly sensitive and specific non-invasive test that can be used for the diagnosis of variant Creutzfeldt-Jakob disease, and potentially as a screening tool for variant Creutzfeldt-Jakob disease infection in asymptomatic individuals, which is a topic of current interest in the United Kingdom.”

Source: University of Texas Health Science Center at Houston

Tree diseases can help forests

A healthy seedling of the tree Castilla elastica is on the left, while a dying seedling, attacked by a plant pathogen, is on the right. A study in the Journal of Ecology by University of Utah biologists shows that such tree diseases, while killing individual seedlings, can increase forest biodiversity. Credit: Erin Spear, University of Utah.

Plant diseases attack trees and crops and can hurt lumber and food production, but University of Utah biologists found that pathogens that kill tree seedlings actually can make forests more diverse.

While low rainfall has been blamed for a lack of drought-sensitive trees near the Pacific side of the Panama Canal, the new study answers a mystery about what keeps drought-tolerant trees from that area from living along the wetter Caribbean side of the canal. The answer: disease-causing plant pathogens, the researchers report in their study, published online Wednesday, Nov. 12 by the Journal of Ecology.

"Because seedlings of disease-sensitive tree species can't survive in the wetter forests and drought-sensitive tree species cannot survive in the drier forests, different tree species inhabit the wetter and drier forests even though they are only 30 miles apart" in Panama, says Phyllis Coley, a senior author of the study and a distinguished professor of biology.
In other words, tree pathogens contribute to the staggering diversity of trees in Panama's tropical forests, she adds.

The study's first author, biology doctoral student Erin Spear, says that is important because "conservation planning and predictions about how tree species distributions may shift with climate change require an understanding of the factors currently influencing where species can and cannot survive."

That is particularly important in tropical forests and other forests that are under elevated threat of deforestation.

Funding for the study came from Sigma Xi -- The Scientific Research Society, the Smithsonian Institution and the National Science Foundation.

Of Forests and Pathogens

Tropical forests are threatened, and dry tropical forests are even more threatened because sunnier, drier climates are better for growing crops and are favored by people. Some 90 percent of Panama's residents live on the nation's drier Pacific slope.

Forests are essential for feeding and sheltering animals, providing important medicines, storing carbon and water, and reducing erosion by holding soil in place. These functions are influenced by different species inhabiting a forest, so it is essential to understand why certain tree species can survive in certain areas but not others.

Panama's forests also are important economically because tree roots limit how much soil erodes into the Panama Canal, ensuring that huge container ships can pass. Researchers also believe the forests help maintain water levels in the canal because forest soil stores water, slowly releasing it into streams feeding the canal during the dry season.

Diversity is high in tropical forests. A 930-square-mile area bordering the Panama Canal has more than 800 tree species. By comparison, about half the state of Rhode Island -- or some 610 square miles -- is forested, and that area has only 51 tree species.

Part of the reason Panama's forests have more species is because the Pacific end of the canal receives less annual rainfall -- about 5.9 feet -- than the Caribbean end, where 9.8 feet of rain falls annually.

"While there is considerable evidence that less rain in the drier, Pacific forests means that drought-sensitive tree species can't survive there, it has been unclear what prevents the drought-tolerant species of the drier forests from living in the wetter forests," says University of Utah biology professor Tom Kursar, the study's other senior author. "Our study tackled that unanswered question."

So Spear braved mud, rain, insects and snakes to monitor seedlings of a variety of tree species in the wetter and drier forests of central Panama for pathogen-caused damage and death. Plant pathogens that make plants sick include bacteria, viruses and fungi.

Spear says the researchers' findings suggest that "all seedlings are at a greater risk of being injured and killed by pathogens in the wetter forests than in the drier forests." This could be because the damp environment of the wetter forests helps pathogens survive, and more rainfall helps pathogens move from one seedling to another.

But that's only half the story. Coley says that their study indicates "pathogens are implicated in the absence of the dry-forest tree species from the wetter forests, where they might otherwise be able to live. That is because dry-forest tree species are more likely to die from pathogen attack than wet-forest species."

Diagnosing Sick Seedlings

Spear collected the seeds for the study by hiking for miles, kayaking in the canal to collect fruit from overhanging branches, and even riding a crane-carried gondola more than 100 feet upward into the forest canopy.

She conducted the study at two forest sites in central Panama: one at the large Metropolitan Natural Park in Panama City on the drier Pacific side, and one on private property in the Santa Rita Ridge area on the wetter Caribbean side. She planted "gardens" of tree seeds -- including species typical of wetter and drier forests -- in 30 locations at each site. More than 1,000 seeds were planted; 725 of them sprouted.

Once the seeds were planted, the researchers covered them with wire mesh to protect the seeds and seedlings from being crushed by tree branches or eaten by animals.

Spear visited both sites weekly and took notes on the 725 seedlings. Weekly visits were essential because, diseased seedlings can be dead and decomposing within days.

"We monitored when the seeds germinated, the occurrence of and date when symptoms of pathogen attack were observed, if and when a seedling died, and we ascribed a cause of death," Spear says. Pathogen symptoms included patches of black, dead tissue in the leaves or stem. "In some cases, we could actually see the pathogen growing on the seedling," she says.

Of the 725 seedlings that germinated, 38 percent suffered pathogen-caused damage, including 11 percent of seedlings killed by pathogens.

Compared with seedlings in the drier forest, seedlings in the wetter forest were 74 percent more likely to suffer pathogen-caused damage and 65 percent more likely to be killed by pathogens.

"But what was really striking was that pathogen-caused damage was five times more likely to be lethal for seedlings of dry-forest species than for wet-forest species," suggesting dry- and wet-forest species differ in their ability to halt or slow infection, Spear says.

The researchers next plan to identify specific fungi, bacteria and other pathogens and whether they differ in wetter and drier forests.

During her study at the drier park site in Panama City, Spear discussed her research with tourists and other park visitors.

"I'd emerge from the tangles of vines sweaty, muddy and generally disheveled and people couldn't help but ask what I was doing," Spear recalls. "It was heartening to hear how the forest had touched these very different people."

A brief time-lapse video of a seedling dying from pathogen attack during a period of several days can be seen at: http://vimeo.com/58026978 Video by Erin Spear, University of Utah.


Source: University of Utah

Study may help slow the spread of flu

A false color image of an influenza virus particle, or “virion.” Credit: Centers for Disease Control/Cynthia Goldsmith

An important study conducted in part at the Department of Energy's SLAC National Accelerator Laboratory may lead to new, more effective vaccines and medicines by revealing detailed information about how a flu antibody binds to a wide variety of flu viruses.

The flu virus infects millions of people each year. While for most this results in an unproductive and uncomfortable week or two, the flu also contributes to many deaths in the average flu season. And while vaccines are effective in preventing the flu, they require almost yearly reformulation to keep up with the constantly changing virus.

At SSRL and APS, a team of researchers from The Scripps Research Institute, Fujita Health University and Osaka University studied both samples of flu virus components and an anti-flu antibody. The antibody, called F045-092, was already known to neutralize the flu by connecting to the region of the flu virus that binds to host cells, so it can no longer bind to its target and cause infection.

"There are patches of the virus that are more hypervariable than others," said Peter Lee, a postdoctoral research associate at The Scripps Research Institute and first author of the paper. "But the flu always binds to host cells within the same region, and so that binding site needs to be functionally conserved. That makes it a site of vulnerability."

The team used the X-ray beams at SLAC's Stanford Synchrotron Radiation Lightsource (SSRL) and Argonne National Laboratory's Advanced Photon Source (APS), both DOE Office of Science User Facilities, to view the structure of the antibody bound to one subtype of the flu virus called H3N2. They discovered that the antibody inserts a loop into the binding site of the virus, which would otherwise attach to a receptor in a host cell. Additional experimental data showed that F045-092 binds a wide variety of strains and subtypes, including all H3 avian and human viruses from 1963 to 2011 that were tested.

This understanding of the antibody's structural details and binding modes offers new insight for future structure-based drug discovery and novel avenues for designing future vaccines.
But the only way to achieve those goals is for many groups of scientists to work together, Lee said. "Our lab is very focused on the structure of the virus and antibodies, while there are lots of other labs focused on everything from small protein design to vaccine design," he said. "Hopefully we can use this structural information and join together as one big team to tackle the flu."

Source: SLAC National Accelerator Laboratory

Natural substance in red wine has an anti-inflammatory effect in cardiovascular diseases

Researchers see great therapeutic potential in the natural substance resveratrol, particularly in connection with prevention of the synthesis of inflammatory factors in cardiovascular diseases. Credit: photo/©: Peter Pulkowski, Mainz University Medical Center

A natural substance present in red wine, resveratrol, inhibits the formation of inflammatory factors that trigger cardiovascular diseases. This has been established by a research team at the Department of Pharmacology of the University Medical Center of Johannes Gutenberg University of Mainz (JGU) working in collaboration with researchers of the Friedrich Schiller University in Jena and the University of Vienna. Their results have recently been published in the scientific journal Nucleic Acids Research.

Despite the fact that they eat more fatty foods, the French tend to less frequently develop cardiac diseases than Germans. This so-called French Paradox is attributed to the higher consumption of red wine in France and it has already been the subject of various studies in the past. A number of research projects have actually demonstrated that the natural product resveratrol, present in red wine, has a protective effect against cardiovascular diseases. But what exactly is the reason for this? It seems that at least part of the protective effect can be explained by the fact that resveratrol inhibits the formation of inflammatory factors, a conclusion reached by the research team of Junior Professor Andrea Pautz and Professor Hartmut Kleinert of the Mainz University Medical Center following collaboration in a joint project with Professor Oliver Werz of the Friedrich Schiller University in Jena and Professor Verena Dirsch of the University of Vienna. In fact, the researchers discovered that the natural substance binds to the regulator protein KSRP and activates it. KSRP reduces the stability of messenger RNA (mRNA) in connection with a number of inflammatory mediators and thus inhibits their synthesis.

"We now know more precisely how resveratrol inhibits the formation of the inflammatory factors that trigger cardiovascular diseases. This is an important finding in view of the fact that more recent research has shown that cardiovascular diseases are significantly promoted by inflammatory processes in the body," said Pautz. Cardiovascular disorders, such as myocardial infarction and strokes, frequently occur in association with chronic inflammatory diseases, such as arthritis. The natural substance resveratrol thus has major therapeutic potential, particularly when it comes to the treatment of inflammatory diseases that can cause serious damage to the cardiovascular system.

Source: Universität Mainz