Culture

MINNEAPOLIS - Tears may hold clues to whether someone has Parkinson's disease, according to a preliminary study released today that will be presented at the American Academy of Neurology's 70th Annual Meeting in Los Angeles, April 21 to 27, 2018.

"We believe our research is the first to show that tears may be a reliable, inexpensive and noninvasive biological marker of Parkinson's disease," said study author Mark Lew, MD, of the Keck School of Medicine of the University of Southern California in Los Angeles and a Fellow of the American Academy of Neurology.

Lew says the research team investigated tears because they contain various proteins produced by the secretory cells of the tear gland, which is stimulated by nerves to secrete these proteins into tears. Because Parkinson's can affect nerve function outside of the brain, the research team hypothesized that any change in nerve function may be seen in the protein levels in tears.

For the study, tear samples from 55 people with Parkinson's were compared to tear samples from 27 people who did not have Parkinson's but who were the same age and gender. Tears were analyzed for the levels of four proteins.

Researchers found differences in the levels of a particular protein, alpha-synuclein, in the tears of people with Parkinson's compared to controls. Additionally, levels of another form of alpha-synuclein, oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson's, were also significantly different compared to controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears.

Total levels of alpha-synuclein were decreased in people with Parkinson's, with an average of 423 picograms of that protein per milligram (pg/mg) compared to 704 pg/mg in people without Parkinson's. But levels of oligomeric alpha-synuclein were increased in people with Parkinson's, with an average of 1.45 nanograms per milligram of tear protein (ng/mg) compared to 0.27 ng/mg in people without the disease. A picogram is 1,000 times smaller than a nanogram.

"Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson's disease and those who don't in a noninvasive manner is exciting," said Lew. "And because the Parkinson's disease process can begin years or decades before symptoms appear, a biological marker like this could be useful in diagnosing, or even treating, the disease earlier."

More research now needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest stages of the disease, before symptoms start.

DURHAM, N.C. -- The fungus that causes athlete's foot and other skin and toenail infections may have lost its ability to sexually reproduce as it adapted to grow on its human hosts.

Scientists analyzed samples of this tenacious organism, called Trichophyton rubrum, and found that nearly all belonged to a single mating type. What's more, when they tried to set the fungi up with members of another mating type, they refused to do the deed, even after the scientists enlisted a variety of seduction schemes -- lowering the lights, cloaking the Petri dishes in plastic, flipping them upside down.

If this fungus can't sexually reproduce, it can't diversify, and if it can't diversify, that may mean its days on this planet are numbered, said Joseph Heitman, MD, PhD, senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine.

But don't expect toenail fungus to appear on the endangered species list anytime soon. "It is commonly thought that if an organism becomes asexual, it is doomed to extinction," Heitman said. "While that may be true, the time frame we are talking about here is probably hundreds of thousands to millions of years."

Though that timeline won't be much help to the nearly 2 billion people who currently suffer from fungal infections of the skin and nails, the discovery that this species may be asexual -- and therefore nearly identical at the genetic level -- does highlight potential vulnerabilities that researchers could exploit in designing more effective antifungal medications. The findings appear online in the journal Genetics.

Fungal infections affect approximately 25 percent of the world's population, and Trichophyton rubrum is usually the species to blame. People can pick up this infection by walking barefoot around swimming pools, showers or locker rooms, or by sharing personal items such as towels or nail clippers. Though there are plenty of over-the-counter powders and ointments along with prescription anti-fungal drugs on the market, most keep the infection at bay but don't clear it. The infection is notoriously difficult to cure, and recent evidence suggests it may often be drug-resistant.

In this study, an international team of researchers decided to take a close look at the genetic makeup and sexual predilections of this fungus. They collected 135 different Trichophyton rubrum samples from around the world and determined their mating type by searching the fungal genome for either the alpha or the HMG domain, which is essentially the molecular equivalent of looking between a dog's legs. The researchers were amazed to find that all but one of the samples were from a single mating type.

Though the findings suggested the fungi had become asexual, the scientists wondered if they would mate if given the opportunity. They placed the isolates in petri dishes along with a variety of potentially compatible mating types, under a variety of different conditions, and then waited to see if any magic would happen. After five months, the researchers looked at the petri dishes under a light microscope, scanning for the growth of coiled appendages that might contain spores. They didn't see any.

Curious, the researchers sequenced the genome of the organism. They found that the organism is very clonal, meaning that different isolates (populations) are nearly perfect clones of each other, with little variation from one genome to the next. Any two genomes of Trichophyton rubrum are 99.97 percent identical, which translates to three differences out of every 10,000 genetic letters. Other fungi such as Cryptococcus are only 99.36 percent identical, differing in 64 out of 10,000 letters, making them 21 times more diverse than the toenail fungus.

"Such incredibly high clonality across isolates from around the world is remarkable, and suggests that this organism is very well adapted to humans," said Christina Cuomo, PhD, senior study author and a group leader for the Fungal Genomics Group at the Broad Institute of MIT and Harvard.

But there is a silver lining. Because the fungus is so clonal and could also be asexual, its ability to adapt further may be more limited than some other fungi. Thus, any new strategies that researchers could develop against this species may have a higher chance of success than those targeting sexual species, which are more capable of mutating or amplifying drug-resistance genes.

Researchers who analyzed gene expression in synovial tissue samples from rheumatoid arthritis patients' joints identified different patterns that may be clinically meaningful. The findings, which are published in Arthritis & Rheumatology, indicate that the mechanisms of pain differ in patients with different synovial subtypes of rheumatoid arthritis, and they may help guide clinicians as they develop optimal treatment strategies for patients.

"We were surprised to find that some patients had high pain, tenderness, and even swollen joint counts while exhibiting minimal inflammation in their tissue or blood. This suggests that some patients can have high disease activity scores with little inflammation," said lead author Dr. Dana Orange, of The Rockefeller University. "It stands to reason that patients with minimal tissue inflammation may not respond to our usual immune-targeting drugs."

Prior studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) may be linked with higher cardiovascular risks, but few have assessed potential different cardiovascular risk between NSAID classes or across individual NSAIDs.

A British Journal of Clinical Pharmacology study including 55,629 patients with hypertension in a Taiwanese database did not observe different cardiovascular risks in patients who received cyclooxygenase-2 enzyme selective NSAIDs or nonselective NSAIDs during 4 weeks of follow-up.

The study also found no apparent difference in cardiovascular risk when comparing celecoxib with diclofenac, ibuprofen, or naproxen, although a significantly increased risk was observed when comparing celeocxib with mefenamic acid.

"Our results provide important information about the comparative safety of alternative NSAID use in patients with hypertension in real-world settings. Under low-to-moderate daily dose and a short-term treatment period, most commonly used NSAIDs have similar cardiovascular safety profiles," said co-author Dr. Chia-Hsuin Chang, of the National Taiwan University Hospital.

AUGUSTA, Ga. (Feb. 22, 2018) - A portable ultrasound can help nephrologists better detect fluid in the lungs of patients with end-stage kidney disease, according to a study by physicians at the Medical College of Georgia at Augusta University.

Patients with the disease, characterized by the kidneys' inability to work well enough to meet your body's basic needs, can accumulate fluid all over their bodies, and commonly in the lungs says second-year nephrology fellow Dr. Omar Saleem.

The trick is knowing where the fluid is and how much needs to be removed, Saleem says, and accumulation in the lungs can lead to complications like heart failure and high blood pressure.

Saleem, and other faculty and students from MCG, will present their research at the Southern Regional Meetings of the American Federation for Medical Research this week in New Orleans.

When it comes to diagnosing "wet lungs," the standard has been listening for chest crackling sounds with a stethoscope and measuring blood pressure - more fluid on the lungs prevents oxygen from being absorbed into the bloodstream. "But that's quite subjective," he says. "For instance, sometimes you can't hear the crackling. That's why the ultrasound adds to the physical exam."

He examined 24 ESKD patients at Augusta University Health. As part of the normal physical exam, he placed the ultrasound probe on the patients' chests to get a good view of the lungs. If there was fluid, he would see B-lines, which are actually reflections of the water in the lungs that appear as long, vertical white lines on an ultrasound. The higher the number of B-lines and the more intense, or bright, they were, the more fluid was present.

"This is an objective marker of lung water, the accumulation of which can lead to serious complications for already fragile patients. We're right at the edge here and we're trying to keep people from tipping over into heart failure," says Dr. Stanley Nahman, MCG nephrologist and director of the Department of Medicine's Translational Research Program. "This will change the way we manage these people with dialysis."

Physicians can then better target dialysis treatments. "I can set the fluid removal goal at a higher point during dialysis," Saleem says. "Where I might normally take off two liters of fluid, I might take three or four in someone who has water in their lungs"

"Our kidneys take all the fluid that comes from normal intake through diet and drinking and they filter the waste products, which we excrete in urine," says "But these patients rarely urinate. They count on dialysis to keep their fluid in balance." The kidneys also help the body reabsorb essential nutrients into the bloodstream.

Hemodialysis uses a special filter called a dialyzer - or an artificial kidney - to filter waste, balance electrolytes and remove extra fluid. End-stage kidney disease (ESKD) patients are typically receiving dialysis three times each week.

Also presenting is Dr. Elizabeth Chu, a second-year internal medicine resident and 2016 MCG graduate, who proposes a new way to manage the way former inmates with ESKD re-enter society.

The Georgia Department of Corrections is one of the largest state correctional systems in the country, supervising nearly 52,000 inmates - many of them have ESKD and are on three-times weekly dialysis at Augusta State Medical Prison. But there is currently no plan to help them figure out how to navigate treatment when they get out of prison, Chu says.

"We were finding that nephrologists were frequently called to the emergency room to provide dialysis to former inmates with ESKD and nowhere else to go," she says. "When we consulted Augusta State Medical Prison regarding discharge of these patients, we found that most did not have active Medicare, which pays for dialysis. When they were released, inmates were given copies of their dialysis run sheets, documenting their treatments, the address of the nearest Social Security Office with instructions to 'go sign up for Medicare' and instructions to go to the ER for their dialysis until they got Medicare."

With an average 12-week waiting period for Medicare, these former inmates were not eligible to enroll at private dialysis treatment centers, instead heading to their local emergency rooms for up to 36 treatments before they received insurance through Medicare.

"Not only was the funding gap resulting in erratic and inadequate care, but it also generated unnecessary costs borne by society," Chu says.

A year of dialysis (150 treatments) in an outpatient facility costs about $89,000; one dialysis treatment in the Augusta University Medical Center Emergency Department is around $25,000. For a patient, receiving three treatments a week over 12 weeks costs could add up to around $900,000. The lack of regular medical care can also result in complications and unnecessary hospitalizations, which are also costly.

To define the scope of the problem, Chu reviewed the records of all ESKD patients at Augusta State Medical Prison from 2014-16, looking for demographic information and anticipated re-entry years. She also made comparisons to a national cohort.

Over the three-year study period, the prison had 180 dialysis patients. From this group, 73, or 41 percent, were discharged from the prison, which is an average of 24 patients per year - comparable to numbers for prison systems outside of Georgia.

"Assuming 24 re-entry patients per year at an ER dialysis cost of $900,000 per patient, the state could save around $21 million annually," Chu said.

She proposes a Comprehensive Disease Management Program instead. Chu says hiring a re-entry navigator with a background in corrections social work and case management who initiates applications for Medicare four to six months before inmates are released would be a huge help. This navigator would also contact dialysis centers, hospitals and parole officers in the area where the inmate intended to live, and could have post-release visits at least monthly for two years, to make sure patients were following through with treatment plans.

It is difficult to distinguish males from females among King Penguins, but a new Ibis study reveals that King Penguins can be sexed with an accuracy of 100% based on the sex-specific syllable pattern of their vocalisations. Using the beak length, King Penguin individuals can be sexed with an accuracy of 79%.

The new findings may help investigators understand how King Penguins choose mates, and they offer a cost- effective, non-invasive technique for researchers to sex King Penguins in the field.

"The sex-specific syllable pattern in King Penguin calls is a very interesting finding, both from an evolutionary perspective as it is rare in non-passerine species, but also because it allows researchers with very little training to reliably identify the gender of King Penguins without handling the individuals," said lead author Hannah Kriesell, of the Centre Scientifique de Monaco and the University of Strasbourg.

ROCHESTER, Minn. -- When people are suffering from a chronic medical condition, they may place their hope on treatments in clinical trials that show early positive results. However, these results may be grossly exaggerated in more than 1 in 3 early clinical trials, reports a new study led by Mayo Clinic and published today in Mayo Clinic Proceedings.

"This phenomenon of exaggerated early results was present in a whopping 37 percent of the studies we reviewed," says Fares Alahdab, M.D., lead author of the study and a research fellow in Mayo Clinic's Evidence-Based Practice Center. "Physicians and patients should be cautious about new or early clinical trial evidence. Exaggerated results could lead to false hope as well as possibly harmful effects."

Dr. Alahdab and the team of researchers led by the center's director, M. Hassan Murad, M.D., reviewed thousands of research articles from the top 10 general medical journals using impact factors. (Impact factors are an internationally accepted ranking system for scientific journals). They collected 70 meta-analysis articles published during an 8½-year period (Jan. 1, 2007, to June 23, 2015) that included the results of 930 clinical trials.

They discovered that the first or second studies (in terms of publication year) reported an effect that was 2.67 times larger than what eventually was shown when subsequent trials were published. The team focused its research on clinical trials evaluating drugs or devices for use in treating chronic conditions -- those conditions that generally persist over time, including cancer, stroke, heart disease, diabetes and kidney disease.

"Often, patients are living with more than one chronic condition, and they and their doctors watch for research about new treatments," says Dr. Murad. "They need to be aware that the effect seen in earlier trials may not bear out over time and may be much more modest."

"Some people may think this is an anti-innovation message," Dr. Murad says. "To the contrary, we welcome new treatments. We just want people to know that the benefit seen in real practice, when treatments are given to people with various comorbidities and in different settings, may be smaller than what was seen in the earliest clinical trials."

When publishing early clinical trial results, the research team also hopes their research colleagues will consider the possibility of the Proteus effect -- a name often given to the phenomenon of early exaggeration followed by moderation over time. The research team hopes their colleagues will temper their language to avoid providing false optimism.

Researchers have long wondered how glial cells, which help provide nutrition and maintain the immediate environment around nerve cells, modulate the activity of nerve cells.

Researchers led by Robert Paul Malchow, associate professor of biological sciences at the University of Illinois at Chicago, have discovered that glial cells may modulate the release of neurotransmitters -- chemicals that relay signals between nerve cells -- by increasing the acidity of the extracellular environment. Their findings are reported in the online journal PLOS ONE.

Neurons communicate with one another both electrically - through action potentials that result in changes in cell membrane permeability -- and chemically through the release of neurotransmitters, such as serotonin and dopamine. Adenosine triphosphate, or ATP, is best known for its role in metabolism where it helps cells use energy, but is also a common neurotransmitter. Previous research has suggested that ATP might play a role in signaling between glial cells and nerve cells.

When the researchers applied ATP to retinal glial cells, they saw an immediate and massive release of acid from the cells. "We decided to further investigate ATP and glial cells because of this really strong response that raised acid levels in the environment right next to the glial cells more than 1000 percent," said Malchow.

In living organisms, ATP is released by neurons into the space between nerve cells called the synapse, when a nerve cell becomes excited. In other words, when the nerve cell is actively relaying a message to its neighbors.

The researchers determined that a rise in ATP outside the nerve cells causes adjacent glial cells to release hydrogen ions, which raise the acidity of the immediate extracellular environment. The hydrogen ions, in turn, bind to calcium channels in the nerve cell membranes, closing these channels off. The calcium channels, when open, allow for the release of neurotransmitters.

"Increases in acidity in the extracellular environment produced by the glial cells forms a feedback loop which prevents the release of too much neurotransmitter," said Malchow.

The researchers used ultrasensitive pH sensors developed at the Marine Biological Laboratory to measure the changes in pH levels around isolated retinal glial cells from a variety of organisms, including humans.

The researchers hypothesize that acid released by glial cells decreases the release of neurotransmitters from nerve cells. This is because the acid binds to and inhibits neuronal calcium channels, which control the release of neurotransmitters.

"We believe that this ATP-mediated release of protons by glial cells acts as an essential feedback mechanism throughout the nervous system to limit over-excitability of neurons," Malchow explained.

DURHAM, N.C. -- Researchers at Duke University have created a framework for helping bioengineers determine when to use multiple lines of cells to manufacture a product. The work could help a variety of industries that use bacteria to produce chemicals ranging from pharmaceuticals to fragrances.

The research was published online the week of February 19, 2018 in the Proceedings of the National Academy of Sciences.

Every cell in the world is constantly absorbing nutrients and raw materials and transforming them into something more useful. Often the process provides the cells with energy or some other vital vitamin or mineral, while leaving behind byproducts that can be beneficial for other cells. This is especially true in complex multicellular organisms and ecosystems, where several different types or species of cells can work together to generate a single complex final product.

Scientists have been harnessing these abilities since the 1970s to produce useful substances like human growth hormone, pharmaceuticals, fragrances and biofuels. Most of the time they rely on a single type of cell for such endeavors for the sake of simplicity. But sometimes the process becomes too complicated.

"Typically when people are modifying cells to produce something they use a single population, but when you only use one type of cell to do everything, there's an upper limit on what it can handle, which becomes a limitation to how sophisticated a compound you can ask the cell to make," said Ryan Tsoi, a graduate student studying biomedical engineering at Duke and first author of the paper. "Having multiple cell types dividing the labor has been explored, but only on a case-by-case basis. This is the first systematic look into what circumstances make multiple cell lines better than one."

In the study, Tsoi and his advisor, Lingchong You, the Paul Ruffin Scarborough Associate Professor of Engineering at Duke, put together a system of equations to model how important variables interact in these types of systems. For example, they can model the strain that complex tasks put on a single cell's growth rate or the inefficiencies introduced when cells must pass signals, enzymes and proteins back and forth in a division-of-labor scheme.

They put together more than 20 different variations of how these systems could be built and how they might interact. When they ran the simulations, they discovered that every trial boiled down to how the variables affected two factors -- how fast the cells are able to grow and how much efficiency is lost when two types of cells share resources while transporting molecules between them.

"It's comparable to when researchers are working together on a grant proposal or a paper," said You. "It's a balance between how easy it is to do by yourself, how efficient it will be in working with other collaborators, and how big of a payoff the collaboration will be at the end of the day."

Moving forward, Tsoi plans on using the new framework to develop the new bioengineered systems he is planning to study. He hopes others will do the same.

"All of these parameters are measurable and quantifiable," said Tsoi. "The idea is that for any system, you could obtain all of these parameters either through basic experiments or textbooks, throw them into this mathematical model, and not only obtain a basic answer of whether or not to use division of labor, but a measure of how much it would benefit your project."

Scientists at Tokyo Institute of Technology (Tokyo Tech) developed a motility-reactivation method to help determine how light-responsive changes in flagellar waveform in Volvox rousseletii, a multicellular spheroidal alga, are regulated. These results advance current understanding of how flagellar motility increased in complexity as single-celled organisms evolved into multicellular forms.

As a photosynthetic alga, the spheroid Volvox rousseletii must move in a light-sensitive way to survive. It achieves this by beating numerous flagella toward its posterior end for swimming forward and turning via changing the direction of flagellar motion from back to front if it perceives light. Exactly how this movement is regulated remains unclear, and existing techniques for studying the mechanism underlying flagellar motility are more suitable for single-celled organisms. Drs. Ueki and Wakabayashi at Tokyo Tech modified them for use with V. rousseletii and developed a powerful method of removing cell membranes with a detergent. The scientists call the demembranated V. rousseletii "Detergent-Extracted Volvox (DEV)" or simply "Zombie Volvox". The motility of Zombie Volvox can be induced (reactivated) through the addition of an ATP buffer. Adding other substances can then allow the observation of their effects on motility.

Because calcium ions are a common modulator of flagella beating, the scientists tested its influence on Zombie Volvox. These "dead" organisms proceeded to move as if they were alive and photostimulated (i.e. stimulated owing to sudden change in light intensity); flagella beat toward the anterior direction, and swimming speeds decreased. In contrast, reactivation with ATP only (no calcium addition) caused flagellar beating toward the posterior end and faster swimming speeds, as is the case for live V. rousseletii under continuous light (i.e., no sudden change in light intensity).

Additionally, the effects of calcium addition were stronger on flagella on the anterior region of the spheroid compared with flagella on the posterior end, indicating that the anterior part of V. rousseletii is more sensitive to calcium ions than the posterior part. The sensitivity gradient is critical for appropriate movement in response to light; when light is illuminated from the side, beating direction changes of all flagella will cause the organism to spin instead of orienting toward/away from the light. It is possible that the gradient also allows more fine-tuned, efficient light-responsive motility than what is possible in unicellular photosynthetic organisms.

The researchers highlight how differences in the anterior and posterior hemispheres in V. rousseletii affect the photobehavior of spheroids. Their findings contribute to understanding the evolution of multicellular organisms, specifically changes in their size which require division of labor for effective movement.

Key repeating moments in the film give viewers the information they need to understand the storyline. The scenes cause identical reactions in the viewer's brain. The results deepen our understanding of how the brain functions, how narratives work in film, and memory mechanisms impaired by conditions such as Alzheimer's disease.

In an Aalto University film study combining art and neuroscience, viewers were shown Christopher Nolan's early classic Memento (2000). The protagonist suffers from long-term memory loss and is unable to retain new memories for no longer than a few minutes. The events unfold in reversed chronological order. To provide the viewer means to piece together and understand the storyline, key scenes repeat at certain intervals throughout the film. These scenes work as clues: they give new information needed to understand the plot.

Every time they appear, the key moments make the same regions of the brain react in an identical fashion. Even the brains of different viewers show similar activity during the same vital scenes.

'Normally people make sense of a film's plot in their own individual ways. So far it has been difficult to capture indications of simultaneous understanding in the brains of several viewers with brain imaging methods. We have now, however, managed to identify brain activity connected to the story being reconstructed in the viewer's mind. The repeating key moments in Memento provide an opportunity to pinpoint viewers' cognitive activities: they react in a similar way to the information they get from the key moments', explains Professor Pia Tikka of Tallinn University, who leads the NeuroCine research group initially formed in Aalto University.

The research made use of functional magnetic resonance imaging (fMRI) - which measures changes in the blood oxygen levels in the brain - and also multivariate analysis when comparing the brain activity of different viewers. The brain was divided into three-dimensional data points called voxels. Using multivariate analysis, the researchers studied the activation patterns of the voxels. The key moments in the film triggered similar and repeating patterns the researchers say are close to being "neural fingerprints".

'There is a total of 15 key moments in Memento that give the viewer opportunities to better understand the story - sort of "The Butler Did It"-types of revelations. While the activation of the voxels varies randomly during other parts of the film, at each of the 15 key moments certain voxels are in the same position for each viewer and form an identical fingerprint pattern,' describes Iiro Jääskeläinen, Aalto University professor in systems neuroscience.

The researchers observed the fingerprint patterns across large regions of the brain, especially in the prefrontal lobe and parietal lobe.

'What is astounding is that the change in the viewer's brain, and especially in the visual cortex, starts to occur already seconds before the key scene even begins. Clearly there are some kinds of clues in the film communicating to the brain that something worth noting is about to happen. This speaks of the brain's ability to anticipate and predict,' Jääskeläinen adds.

Viewers in the control group were shown the film's events in chronological order, where the key moments were not repeated. No fingerprint patterns emerged, and there was no anticipatory activity either.

Unprecedented in the setup was that the test subjects freely viewed a feature-length, 105-minute film in its entirety in the brain scanner.

'In brain research, it is more common to show test subjects short sections of the same film or from different films and seek answers for strictly predefined questions. Such a setup, however, does not allow the film's dramaturgy and characters' development to properly play out. We have taken a step forward in understanding both the functioning of the brain and the process of understanding film narratives, says professor Tikka, also a filmmaker herself.

The results help comprehend how the brain remembers things based on received or obtained clues.

'Memento simulates what it feels like to be a person who has suffered damage to the hippocampus that has obliterated the formation of long-term memories. Even short-term memories last only for a couple of minutes before they are gone. The hippocampus also gets damaged - albeit to a lesser extent - in cases of severe and protracted stress as stress hormones gnaw the brain. Our work also sheds more light on the neural basis of memory which is of great help when we wish to understand dementias such as Alzheimer's disease,' Jääskeläinen believes.

A bone marrow transplant is often the only therapy available to save leukaemia patients, but the risk of complications is high. In spite of devoting considerable time and effort to finding a suitable donor, nearly half of all patients experience an unwanted reaction of their immune system, which often attacks their skin and liver and in up to 50% of cases the intestines. Researchers at FAU (Friedrich-Alexander-Universität Erlangen-Nürnberg) have succeeded in deciphering what causes this in some instances life-threatening inflammation of the intestines, possibly opening up new approaches for treatment. They have published the results of their research in the Journal of Clinical Investigation (DOI: 10.1172/JCI89242).

The severe immune reaction is triggered by a special form of the donor's immune cells. These so-called T-lymphocytes recognise that the recipient's cells are foreign and attack them. Researchers at FAU were able to show that this particular form of T-lymphocytes are controlled by a protein named BATF ('basic leucin zipper ATF-like transcription factor'). 'The BATF protein acts as a central switch in the donor's T-lymphocytes,' explains Prof. Dr. Kai Hildner from the Department of Medicine 1 - Gastroentrology, Pneumology and Endocrinology. 'If the protein is turned on, it can lead to highly aggressive immune cells being developed, which massively increase inflammatory processes, interacting with other immune cells to cause extensive damage in the intestines after a stem cell transplant.'

The group led by Professor Hildner in cooperation with the Department of Medicine 5 and working groups from Frankfurt, Regensburg and Würzburg were also able to demonstrate another connection: T-lymphocytes from the donor which migrate into the intestines release a messenger substance (GM-CSF - granulocyte-macrophage colony-stimulating factor) which triggers the inflammatory reaction in the intestines. When researchers used medication to prevent these specialised T-lymphocytes from developing and functioning, the inflammation in the intestines disappeared.

The scientists hope that the discovery of this molecular mechanism will lead to new therapies being developed to influence inflammation in the intestines after transplants, further increasing patients' chances of survival after a stem cell transplant.

The enzyme that produces DNA building blocks plays an important role when cells divide. In a new study, researchers have discovered for the first time that the so-called master switch of the enzyme can change locations - while still performing the same task.

Regardless of whether you are human, a worm or a bacterium, all beings need to create new cells in order to grow or to replace old cells. But before a cell can divide, it must copy its entire genome, that is, its DNA. This is where the enzyme in question comes into play.

The enzyme, RNR, produces the building blocks required for DNA replication. When copying DNA, it is important to have precisely the right amount of the four different types of building blocks. Too much or too little of either of them causes mutations that may eventually lead to cancer.

The so-called master switch is the specific part of the enzyme that regulates the number of different building blocks. When a sufficient number of building blocks for DNA copying or repair has been produced, the enzyme is switched off with the help of the master switch. Without this function, the enzyme would constantly be working to produce more building blocks.

The protein module functions something like a molecular epoxy glue, since it has the inbuilt capacity to stick the proteins together but can only do so when the "hardener", one of the DNA building blocks, is present in high enough concentration. This acts as a signal that the enzyme needs to be switched off.

The researchers have now investigated this enzyme in a marine bacterium and, for the first time, discovered that the on/off switch of the enzyme was in a different location.

"The switch has genetically jumped from one subunit to another, yet it continues to perform the exact same task. This was a major surprise to us and demonstrates nature's ability to use existing components in completely new ways", says Derek Logan, senior lecturer in Chemistry at Lund University in Sweden.

The researchers conducted a detailed study of how the master switch works when switching on and off. By closing and opening, the subunits literally stick together or let go.

Derek Logan studied the switch function together with colleagues from universities in Stockholm, Uppsala, Umeå and Tel Aviv. The researchers show how the RNR enzyme continues to regulate the number of different building blocks, despite its unusual location.

Although the study concerns a marine bacterium, the researchers believe it is generally interesting that this type of basic regulation can take different evolutionary paths. The research findings may prove useful in the future for developing new antibiotics and in industrial contexts where it is important to be able to switch enzymes on and off in the production of chemicals.

"This function could potentially be used to stick other unrelated proteins together to prevent them from working if needed", concludes Derek Logan.

ATLANTA--Carbon monoxide can improve the effectiveness of antibiotics, making bacteria more sensitive to antibiotic medication, according to a study led by Georgia State University.

Researchers paired carbon monoxide with the antibiotic metronidazole and found carbon monoxide enhanced the efficacy of the antibiotic against H. pylori, a type of bacteria that infects the stomach and causes peptic ulcers. The findings are published in the journal Organic Letters.

"We found that if you administer carbon monoxide together with an antibiotic called metronidazole, it can sensitize bacteria toward the same antibiotic by 25-fold," said Dr. Binghe Wang, Regents' Professor of Chemistry and director of the Center for Diagnostics & Therapeutics at Georgia State and a Georgia Research Alliance Eminent Scholar in Drug Discovery. "It makes the bacteria much, much more sensitive to the antibiotic.

"We always hear about the discussions of drug resistance. When we have drug resistance, it's not because these bacteria will not respond to antibiotics anymore. Most of the time, it means there is decreased sensitivity. If you can resensitize bacteria or sensitize them, then that would allow you to either use a smaller amount of antibiotic or use the same amount that would kill many, many more bacteria."

Carbon monoxide is infamous for its toxicity at high concentrations, but it also has promising potential as a medical gas. Produced naturally in the human body, carbon monoxide is essential for survival and plays an important role in reducing inflammation, promoting cell proliferation and regulating cellular immune response to pathogens. Studies have found carbon monoxide has antimicrobial effects.

In this study, the researchers developed a prodrug system that releases three components: carbon monoxide, an antibiotic (metronidazole) and a fluorescent molecule used to monitor the release of carbon monoxide. A prodrug is the precursor of a drug and must undergo a chemical conversion before becoming an active pharmacological agent. This prodrug system has a three-reaction sequence and becomes active when placed in water, which sets the reaction in motion.

They studied H. pylori bacteria in a culture dish and compared the effect of only the antibiotic metronidazole against the bacteria versus the prodrug system with metronidazole and carbon monoxide combined.

Finding a solution to the causes and impacts of marine litter is now widely recognised as one of the major environmental challenges of our time. And one of the key elements required to address the issue is encouraging people of all ages to move away from the current throwaway culture.

Now research led by the University of Plymouth has revealed that designing systematic and innovative education tools to teachers and students can make a significant and positive contribution to their understanding of the problem - and their willingness to do something about it.

The study, published in Marine Policy, was a collaboration with the Mediterranean Information Office for Environment, Culture and Sustainable Development in Greece and the Coastal and Marine Union in The Netherlands.

It is the first quantitative assessment of European students' and educators' attitudes to marine litter before and after participating in an online educational project designed to raise awareness and inspire action in the younger generation.

Dr Sabine Pahl, Associate Professor (Reader) in Psychology at the University of Plymouth, said: "It is clear that the education sector represents an important agent of social change in society. This study shows that working with educators and school students has much potential to facilitate greater public understanding of complex environmental issues and to make them part of the solutions. It has important implications for marine policy, and demonstrates that, beyond providing mere knowledge and facts, employing creative tools and techniques can enable action."

For the study, academics enrolled 120 educators from 18 countries across Europe in an online training course about marine litter, asking them to complete a series of assessments to ascertain how it changed their attitudes.

The results showed the educators had high intentions of implementing the materials in their teaching, and planned to encourage others in their network, which may lead to the training and resources to be distributed more widely.

They also invited 341 students aged seven to 18 from 12 European countries to take part in a video competition through which they were encouraged to make a two-minute video on the problem's potential sources, impacts and solutions.

After taking part, they said they were more concerned about the problem and perceived greater negative impacts and causes. They also reported performing more waste reduction behaviours.

The study builds on the University's interdisciplinary research into marine litter, with previous such studies showing marine litter can undermine the benefits of coastal environments and that the public's love of the seas could be the key to solving plastic pollution.

Professor Richard Thompson OBE, Head of the International Marine Litter Research Unit at the University and one of the study's authors, added: "Over recent years, the world has really woken up to the global threat posed by marine litter. But while recognising the problem is one thing, increasing knowledge and changing behaviours are a far greater challenge. This research demonstrates educators can play a lead role in that, and it is essential to educate young people now so that they and future generations can live in a world without the threat of plastic pollution."