Culture

Pioneering experiments using heated field plots to test the responses of crops to temperature have revealed an unexpected plus side of climate change for farmers.

The field trial experiment - the first of its kind - was set up to investigate the link between warmer Octobers in the United Kingdom and higher yields of oilseed rape.

The crop, planted in autumn and harvested early the following summer, is particularly sensitive to temperature at certain times of the year with annual yields varying by up to 30 percent as a result. It is known that warmer temperatures in October are correlated with higher oilseed rape yields, but the reason for this trend was unclear.

The results of this study by the John Innes Centre reveal that the temperature in October is surprisingly important for the timing of flowering, and that warmer Octobers result in a delay to flowering the following spring.

Professor Steve Penfield an author of the study says, "We found that oilseed rape plants stop growing when they go through the floral transition at the end of October, and that warmer temperatures at this time of year enable the plant to grow for longer, giving more potential for higher yields."

The good news for growers of oilseed rape is that Met Office data shows cold Octobers are now much less frequent than they were in the past.

"By establishing the link between autumn temperatures and yield, our study highlights an example of climate change being potentially useful to farmers. Cold Octobers have a negative effect on yield if you are growing oilseed rape, and these are now rarer," says Professor Penfield.

Temperature is critical for oilseed rape lifecycle because it determines at what point the plant goes through the transition from vegetative state to flowering, with delays in flowering being associated with higher yields.

This process called vernalisation is well understood in the lab as a requirement of a prolonged exposure to cold temperature. But an increasing body of research suggests vernalisation might work differently under more variable conditions experienced by a plant in the field.

In this study the team used soil surface warming cables to raise the temperature of field plots by between 4 and 8 degrees Celsius, simulating warmer October temperatures. Two varieties of oilseed rape with differing vernalisation requirements were trialled.

Lab tests on dissected plants showed that warming in October conditions delayed floral transition by between 3 and 4 weeks for both varieties. Genetic tests showed genes associated with vernalisation in cold conditions were also highly expressed in the warm conditions.

The study shows that vernalisation in oilseed rape takes place predominantly during October during which time the mean temperature is between 10-12 degrees Celsius.

The technology used in the study has been used before in natural grasslands to simulate winter warming but the trials conducted by the John Innes Centre research team are the first time it's been used on a crop in the field.

"This study was only possible because were able to create the lab into a field to simulate how climate change is affecting UK agriculture," says Professor Penfield. "It's important to be able to do this because yield is highly weather dependent in oilseed rape and it is very likely that climate change will have big consequences for the way we can use crops and the type of variety that we need to deploy."

LA JOLLA--(December 5, 2019) Bright light at night interrupts the body's normal day-night cycles, called circadian rhythms, and can trigger insomnia. In fact, circadian rhythms play a major role in health. Disrupted day-night cycles have even been linked to increased incidence of diseases like cancer, heart disease, obesity, depressive disorders and type 2 diabetes in people who work night shifts. Therefore, understanding how human eyes sense light could lead to "smart" lights that can prevent depression, foster sleep at night, and maintain healthy circadian rhythms.

In a Science study published December 5, 2019, researchers at the Salk Institute report the discovery of three cell types in the eye that detect light and align the brain's circadian rhythm to our ambient light. The study marks the first direct assessment in humans of light responses from these cells, called intrinsically photosensitive retinal ganglion cells (ipRGCs)--and the implications for health are substantial.

"We have become mostly an indoor species, and we are removed from the natural cycle of daylight during the day and near-complete darkness at night," says Salk Professor Satchidananda Panda, senior author of the paper. "Understanding how ipRGCs respond to the quality, quantity, duration, and sequence of light will help us design better lighting for neonatal ICUs, ICUs, childcare centers, schools, factories, offices, hospitals, retirement homes and even the space station."

This new understanding of ipRGCs may also fuel future research into developing therapeutic lighting that can treat depression, insomnia, Attention Deficit and Hyperactivity Disorder (ADHD), migraine pain, and even sleep problems among patients with Alzheimer's disease.

"It's also going to open a number of avenues to try new drugs or work on particular diseases that are specific to humans," says Ludovic Mure, a postdoctoral researcher in the Panda lab and first author of the new study.

While ipRGCs had been identified before in mouse retinas, these cells had never been reported in humans. For the new study, the Salk team used a new method developed by study co-authors Anne Hanneken of Scripps Research Institute and Frans Vinberg of John A. Moran Eye Center of the University of Utah to keep retina samples healthy and functional after donors passed away. The researchers then placed these samples on an electrode grid to study how they reacted to light.

They found that a small group of cells began firing after just a 30-second pulse of light. After the light was turned off, some of these cells took several seconds to stop firing. The researchers tested several colors of light, and found that these "intrinsically photosensitive" cells were most sensitive to blue light--the type used in popular cool-white LED lights and in many of our devices, such as smartphones and laptops.

Follow-up experiments revealed three distinct types of ipRGCs. Type 1 responded to light relatively quickly but took a long time to turn off. Type 2 took longer to turn on and also very long to turn off. Type 3 responded only when a light was very bright, but they turned on faster and then switched off as soon as the light was gone. Understanding how each ipRGC type functions may allow researchers to better design lighting or even therapeutics that can turn the cell activity on or off.

The new study actually helps explain a phenomenon reported in past studies of some blind people. These people, despite not being able to see, are still able to align their sleep-wake cycle and circadian rhythms to a day-night cycle. Thus, they must be sensing light somehow.

Now it appears that ipRGCs are the cells responsible for sending that light signal to the brain, even in people who lack the rod and cone cells needed to relay an image to the brain.

It also appears that, in people with functional rods and cones, ipRGCs actually work closely with these other visual cells. The new study suggests that ipRGCs can combine their own light sensitively with light detected by the rods and cones to add brightness and contrast information to what we see.

"This adds another dimension to designing better televisions, computer monitors and smartphone screens in which changing the proportion of blue light can trick the brain into seeing an image as bright or dim," says Panda.

Panda says the next step in this research will be to study the net output of these cells under different light colors, intensity and duration--for example, comparing how they react to short pulses of light versus a longer duration of a few minutes. The team is also interested in how the cells react to sequences of light, such as a blue light that turns orange or vice versa, which would mimic some of the variety of light we encounter in nature at dawn and dusk.

"Repeating these experiments in donor retina preparations from various ages will also help us understand whether or to what extent young and older individuals differ in their ipRGC function, which may help in designing indoor light for better day-night synchronization generally and perhaps even such applications as mood improvement among older individuals and patients with dementia," says Panda.

The human brain consists of several intricate networks or "circuits." One such complex circuit, called the "reward circuit," is involved in reward-associated learning, a process in which nerve cell activity changes in response to a "reward" stimulus (something that the brain perceives as a reward). This process is what usually causes feelings of desire and motivation, but excessive stimulus may also cause dependence and addiction. The main regulator involved in the reward circuit is dopamine, a chemical popularly called the "happy hormone." In a region of the brain called nucleus accumbens, this chemical targets a specific group of neurons, called the medium spiny neurons, and induces a series of molecular changes. Unfortunately, irregularities in this pathway are associated with several behavioral and cognitive disorders, including Parkinson's disease, compulsive behavior, autism, and schizophrenia. Drug addiction, especially to potent stimulants like cocaine and amphetamines, is also dependent on this pathway. Unequivocally, to develop effective therapies, it is important to understand exactly how the reward pathway works.

In a new study published in Cell Reports, a team of scientists in Japan, led by Prof Kozo Kaibuchi and Dr Yasuhiro Funahashi from Nagoya University, has identified a novel protein function involved in the reward circuit of the brain. They based their study on the fact that dopamine, when released in the brain, activates several proteins in response, and these proteins then cause certain changes in brain activity, such as reward-related gene expression and changes in nerve transmission or plasticity. But, how these changes happen at the molecular level was not well understood. The scientists at Nagoya University wanted to dig a little deeper. Prof Kaibuchi says, "Very little is currently known about how dopamine works in neurons to establish reward memory and cause addiction. This motivated us to pursue this study."

What was known so far was that dopamine activates multifunctional proteins, such as CREB-binding protein (CBP), which in turn promotes gene expression through interactions with other proteins. To find more detailed information, the scientists searched for proteins interacting with CBP in mice that experienced a conditioned reward. Using protein interaction-based experiments and database analyses, they successfully identified many such proteins. Of these, one protein, called Npas4, a "transcription factor" (a protein that binds to specific DNA sequences and regulates transcription from DNA to mRNA), was known to function in reward-related learning, and so the scientists moved on to find out its mechanism.

In a first for the scientific community, the group showed that a protein kinase called MAPK adds a phosphate group to Npas4 (a well-known intracellular process called phosphorylation, which "activates" proteins to carry out their functions), thereby facilitating its interaction with CBP. The scientists even identified the exact sites where MAPK phosphorylates Npas4. Moreover, they found that dopamine activates Npas4 in striatal medium spiny neurons, and so promotes the expression of genes related to "neural plasticity" (changes in neural connections). Thus, the three dopamine-stimulated proteins CBP, MAPK, and Npas4 interact with each other, leading to profound neural changes--Dr Funahashi and Prof Kaibuchi had unraveled a major mechanism of how dopamine affects the brain.

To investigate the function of Npas4 in reward-related behavior, the scientists then "knocked out" or inactivated Npas4 in the reward circuit neurons of mice. These mice and normal mice learned to expect a cocaine reward in only one of two chambers, after which chamber preference was measured. Compared to normal mice, the Npas4-deficient mice showed a >50% reduction in drug-seeking behavior, indicating a significant reduction in reward memory. Importantly, the drug-seeking behavior was restored after exogenous administration of Npas4 but not by phospho-deficient mutants of Npas4. This was exciting, as it confirmed that Npas4 and its phosphorylation play an important role in reward-related behavior.

These unprecedented findings by Prof Kaibuchi and his team shed some light on the pathways involved in the reward circuit of the brain. Faulty functioning of the reward circuit is seen in various neuropsychological and cognitive disorders. By explaining in detail, the function and reward-associated mechanism of Npas4, these scientists have paved the way for new, effective therapies. Talking about the applications of the study, Prof Kaibuchi says, "Our study can help develop treatments for neuropsychiatric disorders such as schizophrenia. It can also be useful in tackling addiction to or dependence on cocaine and other stimulants."

Could a reward for this exciting study come in the form of a potential new treatment for behavioral disorders? Only time will tell. But, Prof Kaibuchi's team and their study certainly offer hope for the future.

Warm-sector heavy rainfall (WSHR) is a type of rainstorm proposed by Chinese meteorologists that had been found to only occur in South China. However, WSHR has also been found in other regions of China, according to Prof. Jianhua Sun from the Institute of Atmospheric Physics (IAP) of the Chinese Academy of Sciences.

"WSHR events often cause severe flooding, huge economic losses, and many casualties, but the operational prediction of these events is difficult and often inaccurate," says Prof. Sun. "To encourage more scientists to study this problem, we summarize existing researches and propose challenges presented by WSHR."

Prof. Sun and her team - a group of researchers from IAP, Beijing Municipal Weather Forecast Center, and China Meteorological Administration - reviewed research results on WSHR, including the categories and general features, the triggering mechanism, and structural features of the mesoscale convective system. Their study was published in Advances in Atmospheric Sciences (AAS) .

"After decades of research, we have a relatively deep understanding of the triggering mechanism and synoptic weather systems of WSHR in South China, but we only have a preliminary understanding of WSHR in other regions," said Prof. Sun.

WSHR events in South China are associated with four types of synoptic patterns (wind shear, a low vortex, southerly wind, and backflow), while those occurring in regions south of the Yangtze River and over the middle and lower reaches of the Yangtze River are associated with the synoptic patterns of a warm wind shear line, pre-cold front, and the edge of the western Pacific subtropical high.

The topography and land-sea contrast are important factors impacting the intensity and distribution of WHSR events in South China. However, the severe precipitation maxima in WSHR events of other regions in China are dispersed and occur over mountains, the borders of mountains and plains, and the shorelines of lakes.

WSHR events can also occur in North China, such as the extreme heavy rainfall case on July 21, 2012. Due to the lack of understanding of WSHR, forecasts of their occurrence are inaccurate and the forecast intensity is typically less than the actual precipitation record.

"Till now, forecasting WSHR has been very difficult because we do not fully understand the formation and developing mechanism," said Prof. Sun. "To improve the forecasting accuracy of heavy rainfall, the background conditions, triggering mechanism and predictability of WSHR in China are worthy of further study."

The amount of food needed to feed the world's population in the future is of vital importance. To date, scientists have only considered this question from the perspective of how much food people can afford to buy, how much food is healthy or what can be sustainably produced. However, researchers at the University of Göttingen have now analysed how the actual quantity of food that people would like to eat is likely to change. A rising Body Mass Index (BMI), which evaluates weight in relation to height, and an increasing body height lead to a marked increase in global calorie requirements. The results have been published in the journal PLOS ONE.

In most countries, average body height and body size is increasing. More needs to be eaten to maintain the higher weight. The development economist Professor Stephan Klasen, from the Faculty of Business and Economics at the University of Göttingen and his then doctoral student, Lutz Depenbusch, have designed a scenario to investigate how calorie intake could develop between 2010 and 2100. Earlier changes in the Netherlands and Mexico were used as a benchmark. "The developments in these countries are very pronounced," says Depenbusch, "but they do represent a realistic scenario." Even if both BMI and height were to remain constant, global calorie requirements would still increase by more than 60 percent by 2100 because of population growth. With rising BMI, as observed in Mexico, and increasing height, as seen in the Netherlands, there would be a further increase of more than 18 percent. This means, the increase in global calorie requirements between 2010 and 2100 would be one third larger, reaching a total increase of nearly 80%.

If global food production does not meet this increased need, the researchers fear that this problem will not be controlled by a corresponding decrease in BMI. While richer people will be able to maintain their eating habits, the poor would suffer greatly from higher prices due to increased demand. "This would lead to increased consumption of cheap food, often rich in calories but poor in nutrients," says Depenbusch. "As a result, body weight among the poor would continue to rise alongside malnutrition and poorer health outcomes."

A joint press release by Charité and the Max Planck Institute for Human Development

Members of a polar research expedition have provided researchers from Charité - Universitätsmedizin Berlin and the Max Planck Institute for Human Development with an opportunity to study the effects of social isolation and extreme environmental conditions on the human brain. The researchers found changes to the dentate gyrus, an area of the hippocampus responsible for spatial thinking and memory. Results from their study have been published in the New England Journal of Medicine*.

Setting off on an Antarctic expedition to Neumayer-Station III, a German Antarctic research station run by the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI), means having to face temperatures as low as -50 degrees Celsius (-58 degrees Fahrenheit) and almost complete darkness during the winter months. Life at the research station offers little in the way of privacy or personal space. Contact with the outside world is minimal, and cutting one's stay short is not an option - at least not during the long winter months. Emergency evacuation and deliveries of food and equipment are only possible during the relatively short summer. "This scenario offers us the opportunity to study the ways in which exposure to extreme conditions affect the human brain," says study lead Dr. Alexander Stahn of Charité's Institute of Physiology and Assistant Professor in the Perelman School of Medicine at the University of Pennsylvania. Working alongside Prof. Dr. Simone Kühn (Group Leader of the Lise Meitner Group for Environmental Neuroscience at the Max Planck Institute for Human Development), and supported by the AWI, Dr. Stahn set out to determine whether or not an Antarctic expedition produces changes to the structure and function of the human brain.

Five men and four women volunteered to participate in the study. They spent a total of 14 months at the Antarctic research station, nine of which were spent in isolation from the outside world. Before, during and after their mission, the participants completed a set of computer-based cognitive tests. These included evaluations of concentration, memory, cognitive reaction time and spatial thinking. Regular blood tests were carried out to measure levels of a specific growth factor known as brain-derived neurotrophic factor (BDNF), a protein responsible for promoting the growth of nerve cells and synapses in the brain. The researchers used magnetic resonance imaging to determine brain structure in each of the participants before and after their mission. They did so in order to record changes in brain volume, paying particular attention to the hippocampus, a structure located deep inside the brain. "For this, we used a high-resolution methodology which makes it possible to take precise measurements of individual areas of the hippocampus," says Prof. Kühn. A group of nine control participants underwent identical tests.

Measurements taken after the end of the exhibition revealed that the dentate gyrus, an area of the hippocampus with an important role in spatial thinking and memory formation, was smaller in members of the expedition team than in controls. These changes were also associated with a decrease in BDNF levels. After only three months in the Antarctic, levels of the growth factor had decreased to levels below those recorded prior to the start of the expedition and had not returned to normal one-and-a-half months after the expedition. Cognition tests showed effects on both spatial abilities and the so-called selective attention, which is necessary to ignore irrelevant information. Repeated testing is normally associated with improvements in test results. This learning effect, however, was reduced in participants whose dentate gyrus had decreased in volume, the reduction proportional to the extent of the volume lost.

"Given the small number of participants, the results of our study should be viewed with caution," explains Dr. Stahn, adding: "They do, however, provide important information, namely - and this is supported by initial findings in mice - that extreme environmental conditions can have an adverse effect on the brain and, in particular, the production of new nerve cells in the hippocampal dentate gyrus." As a next step, the researchers plan to study whether or not physical exercise might be able to counteract the observed changes in the brain.

Goblet cells are epithelial cells that produce mucins and disperse tears which help the surface of eyes maintain the wet environment. Goblet cells are closely related to autoimmune disease including dry eyes and chemical burns. Therefore, it is very important to examine the status of goblet cells to better understand and diagnose ocular disease.

Professor Ki Hean Kim and Mr. Seonghan Kim of POSTECH Department of Mechanical Engineering and Division of Integrative Biosciences and Biotechnology collaborated with Dr. Myoung Joon Kim, who is a former ophthalmology professor at Seoul Asan Medical Center and a doctor at Renew Seoul Eye Center, in finding a better technique goblet cells assessment and they successfully developed an imaging technology of conjunctival goblet cells with high definition and high image contrast.

The current standard imaging method of goblet cells is impression cytology. This method uses polymer paper attached onto the conjunctiva to extract conjunctival goblet cells and these cells are examined under the microscope after labeling them with special dying agent. However, it is rarely used because the process is very complicated and it can damage the surface of conjunctiva.

In the meanwhile, there has been a report on using confocal reflection microscopy (CRM) to image conjunctival goblet cells. The assessment is non-invasive, yet, it provides relatively low image contrast and, is hard to obtain precise results.

In an effort of developing a better imaging method, the research team has studied a clinically compatible cell image technique using fluoroquinolone antibiotics, which are used in eye drops, as fluorescent cell labeling agents. As a result, moxifloxacin, one of the fluoroquinolone antibodies used in eye drops, displayed stronger fluorescence in the goblet cells that are dispersed on the surface of conjunctiva.

Also, the moxifloxacin-based fluorescence imaging of conjunctival goblet cells was tested in a mouse model. Moxifloxacin was injected into a mouse and it was examined under the CRM after one to two minutes of injection. The team verified that a bright cluster of conjunctival goblet cells on the surface of conjunctiva was shown. In comparison with the existing CRM, this fluorescence imaging method demonstrated high image contrast and could do real-time imaging at 10 frames per second.

This newly developed high-contrast conjunctival goblet cells imaging is the world's first of its kind as it uses the antibiotics safely applied in ophthalmology nowadays. Thus, it can be used to develop diagnostic medical devices. Furthermore, it can be utilized in precision diagnosis of dry eye syndromes and evaluation of treatment effect.

Professor Ki Hean Kim explained about his future plans, "This study is meaningful that it overcame the limitation of the conventional imaging method of conjunctival goblet cells. It creatively introduced a non-invasive and high-definition imaging method. We will further advance this imaging method to an assessment of conjunctival goblet cells. We hope to invent a medical device using this method which then can be applied to precision diagnosis of dry eye syndrome and their treatment effect evaluation."

WEST LAFAYETTE, Ind. - You cannot make glue out of a ham sandwich - but you may be able to use the components of that food to create a strong adhesive.

That's the thinking behind technology developed by a group of scientists at Purdue University, who have taken inspiration from the kitchen and the ocean to create strong glues. The team's work is published in the Oct. 8 edition of Advanced Sustainable Systems.

"Adhesives are used in almost every consumer product that we touch each day," said Gudrun Schmidt, an associate professor of practice in Purdue's College of Science, who helped lead the research team. "We would love to leave this planet a better place for the future generations. It turns out creating new adhesives is one way that we will get there."

Schmidt said almost all of the glues used in electronics and other consumer products are petroleum-derived, permanent and often toxic. The Purdue team chose compounds in foods, like nuts, fruits and plants, all of which might have similar chemistry to the adhesives seen in shellfish that stick to rocks.

The team included Jonathan Wilker, a Purdue professor of chemistry and materials engineering, who studies mussels and oysters to create adhesives based on how those shellfish stick to rocks.

"We have created high-performance, tunable adhesives that are nontoxic and degradable," Schmidt said. "We found that some combinations of zein protein and tannic acid could be reacted together in order to generate high-performance adhesives that could be alternatives to carcinogenic formaldehyde used in the glues that hold lots of furniture and other household items together. It would be a big health benefit if we could switch over to bio-based or even food-based adhesives."

Schmidt said other potential applications for the adhesives include cardboard packaging, cosmetics and construction materials like plywood.

Genes have been identified that confer resistance to multiple leaf rust species in barley. The findings by an international team, led by KAUST researchers, could transform the breeding of durable disease-resistant cereal crops and help support efforts to improve global food security.

"Disease is the exception and resistance is the rule--most microbes do not make us or cereal plants sick," says Simon Krattinger from KAUST's Center for Desert Agriculture. "This is called nonhost resistance--resistance of an entire species against all strains of a pathogen. However, nonhost resistance in cereals is poorly understood."

The cereal-rust relationship is ideal for studying nonhost resistance because all cereals belong to the grass family, but each cereal crop species is infected by only one specific rust (for example, wheat leaf rust only infects wheat). There are molecular factors in barley that prevent wheat leaf rust from establishing colonies; thus, pinpointing the genes responsible for generating this molecular barrier to infection would be invaluable for breeders.

"Importantly, nonhost resistance is more durable than host resistance--a plant's innate immune system provides some protection, but only until pathogens evolve to evade it," says Krattinger's postdoc Yajun Wang. "Our biggest challenge was to identify the nonhost resistance genes in barley plants, especially given that barley's genome is almost twice the size of the human genome."

All barley cultivars are resistant to leaf rusts of other cereals; therefore, there is no clear genetic variation within barley species that might indicate which genes are involved. KAUST's collaborators in the Netherlands devised a novel method of narrowing the search.

They infected 1733 barley cultivars with wheat leaf rust. Most plants were resistant, but a few lines developed hints of leaf rust at the seedling stage. This was not enough to create a full infection, but the team was able to crossbreed these lines to generate one line that was highly susceptible to wheat leaf rust. This was then crossed with a normal barley cultivar and analyzed to pinpoint the genetic variations conferring nonhost resistance.

"Through extensive genome analysis, we found the genes that encode a protein receptor kinase to create a barrier to wheat rust in barley," says Wang. "Transferring these genes into wheat could result in cultivars that are resistant to all races of wheat rust."

"This is a very promising strategy that could finally solve one of the biggest problems in global wheat production," notes Krattinger.

Sticks and stones may break one's bones, but healing them requires the production of a protein signal that stimulates the generation, growth and spread of vital nerve cells, or neurons, throughout the injured area. That's the finding of a recent Johns Hopkins Medicine study that used mice to demonstrate what likely takes place during human fracture repair as well.

"A better understanding of how nerve cells work in bones could spur the development of neuron regenerating therapies for people with diseases where nerve damage is common, such as diabetic neuropathy," says Aaron W. James, M.D., Ph.D., associate professor of pathology at the Johns Hopkins University School of Medicine and co-senior author of the study described in the Journal of Clinical Investigation.

“Typically, people with these conditions also have problems with bone repair," he adds.

Essentially, the scientists say their results in mice demonstrate that, at the fracture point, two proteins -- one called tropomyosin receptor kinase-A, or TrkA, and the other known as nerve growth factor, or NGF -- bind together to signal the start of innervation, the supplying of nerves, and subsequently, new bone. They say that this process may be similar to the mechanism for human bone repair.

"We showed that when TrkA, and in turn, NGF, were removed from the process, there was a dramatic reduction not only in innervation but also in the three follow-up activities critical to successful recovery from a fracture: blood vessel formation, production of bone-synthesizing cells and mineralization of new bone," says James. "In fact, the drop overall in these indicators of bone repair was between 60% and 80%."

First identified in the 1950s, NGF is now known to direct the growth, maintenance, proliferation and preservation of neurons throughout the body. It also helps neurons alert the brain when tissues, including bones, are experiencing pain from injury or disease. Studying this connection, James says, is what led researchers to suspect that NGF also might play a key role in skeletal repair.

"When drug companies in recent years developed and conducted human trials of anti-NGF agents to reduce pain from arthritis and other disorders, they found that a number of patients suffered unusual bone fractures," says Johns Hopkins researcher and co-senior author Thomas Clemens, Ph.D. "Other studies around the same time showed that the bones of children with a rare genetic mutation preventing the production of TrkA may not heal well after injury, suggesting a connection between this signaling pathway and bone repair mechanisms."

A 2016 study conducted by Clemens and others provided some of the first evidence that NGF promotes the ingrowth of nerves during the development of long bones in a mouse, and that without it, proper bone formation is hampered. The current study was designed to better define how NGF-TrkA signaling might be involved.

To accomplish this, James, Clemens and their colleagues studied mice with stress fractures of the ulna, the forelimb bone equivalent to the thinner and longer of the two bones in the human arm.

For their experimental groups, the researchers used two different methods to block neural ingrowth during repair. One group of mice were genetically bred not to respond to TrkA and given a drug that inactivates chemical signaling by the protein. The second group of mice were given a drug that kills the nerve fibers.

"Among the mice lacking TrkA signaling, there was a significant reduction -- as much as 80% compared with a control group of normal functioning mice -- in the number of nerve fibers that appeared at the fracture site," James says. "We also saw fewer osteoblasts [bone-producing cells] and in turn, less mineralization of new bone."

"These results indicate that fracture repair is truly dependent on the neural signaling directed by TrkA-expressing nerve fibers," he explains.

The researchers next plan to study how the NGF-TrkA signaling pathway and the resulting skeletal repair process respond when dealing with the removal of a bone segment, rather than just a break.

"This will help us learn if the signaling we linked to bone repair in mice controls that process for larger or more extensive injuries in a way similar to what we observed in small stress fractures," Clemens says.

The team led by biochemist Dr. Christian Münch, who heads an Emmy Noether Group, employs a simple but extremely effective trick: when measuring all proteins in the mass spectrometer, a booster channel is added to specifically enhance the signal of newly synthesised proteins to enable their measurement. Thus, acute changes in protein synthesis can now be tracked by state-of-the-art quantitative mass spectrometry.

The idea emerged because the team wanted to understand how specific stress signals influence protein synthesis. "Since the amount of newly produced proteins within a brief time interval is rather small, the challenge was to record minute changes of very small percentages for each individual protein," comments group leader Münch. The newly developed analysis method now provides his team with detailed insight into the molecular events that ensure survival of stressed cells. The cellular response to stress plays an important role in the pathogenesis of many human diseases, including cancer and neurodegenerative disorders. An understanding of the underlying molecular processes opens the door for the development of new therapeutic strategies.

"The method we developed enables highly precise time-resolved measurements. We can now analyse acute cellular stress responses, i.e, those taking place within minutes. In addition, our method requires little material and is extremely cost-efficient," Münch explains. "This helps us to quantify thousands of proteins simultaneously in defined time spans after a specific stress treatment." Due to the small amount of material required, measurements can also be carried out in patient tissue samples, facilitating collaborations with clinicians. At a conference on Proteostatis (EMBO) in Portugal, PhD student Kevin Klann was recently awarded with a FEBS journal poster prize for his presentation of the first data produced using the new method. The young molecular biologist demonstrated for the first time that two of the most important cellular signaling pathways, which are triggered by completely different stress stimuli, ultimately results in the same effects on protein synthesis. This discovery is a breakthrough in the field.

The project is funded by the European Research Council (ERC) as part of Starting Grant "MitoUPR", which was awarded to Münch for studying quality control mechanisms for mitochondrial proteins. In addition, Christian Münch has received funding within the German Research Foundation's (DFG, Deutsche Forschungsmeinschaft) Emmy Noether Programme and is a member of the Johanna Quandt Young Academy at Goethe. Since December 2016, he has built up a group on "Protein Quality Control" at the Institute for Biochemistry II at Goethe University's Medical Faculty, following his stay in one of the leading proteomic laboratories at Harvard University.

The tropical disease Leishmaniasis is being tackled by catching female sand flies who carry the parasite that causes the disease.

Scientists led by Dr Orin Courtenay of Warwick University and Professor Gordon Hamilton of Lancaster University, developed the concept as part of a £2.5M project funded by The Wellcome Trust and published in PLOS Neglected Tropical Diseases.

There are now plans to commercialise the research which involves using a synthetic copy of a male pheromone to attract female sand flies towards insecticide-treated areas.

Globally over 350 million people are at risk of infection from Leishmaniasis, with up to 300,000 new cases annually, and approximately 4,500 deaths each year in Brazil alone. Children under the age of 15 are disproportionately affected.

In Latin America, Europe, North Africa and parts of central and East Asia, the Leishmania parasite is transmitted from infected dogs by sand flies when they bite people. Visceral Leishmaniasis, affects the internal organs and is fatal if untreated as there is no human vaccine for the disease.

In Brazil, dogs are euthanized if they are found to be infected, but this has little effect on the number of human cases. Insecticide-impregnated dog collars can be used to protect dogs but these are too expensive for many people and like dog culling, protective coverage is patchy.

Professor Hamilton said: "We wanted to develop a less costly method to trap large amounts of sand flies to reduce the number of infected dogs which in turn act as a source of infection for people."

The researchers introduced a sachet of the male sand fly pheromone to attract female flies to chicken sheds already sprayed with insecticide.

"This killed a large number of the sand flies".

The beneficial effects of this "lure-and-kill" method reduced female sand flies by 49% compared with 43% for the insecticide-only collar.

Dr Orin Courtenay from the School of Life Sciences and Zeeman Institute at the University of Warwick comments: "The beneficial effects of the lure-and-kill method were most noticeable by reducing confirmed infection incidence and clinical parasite loads in dogs by about 50%, in addition to reducing sand fly abundance.

"Our approach will be a lot less expensive and gives just as good a result as the insecticide collar."

The next stage is to work with industry to synthesize the pheromone in bulk ready for use in affected areas.

Screams are prompted by a variety of emotions -- from joyful surprise to abject terror. No matter what sparks them, however, human screams share distinctive acoustic parameters that listeners are attuned to, suggests a new study published by the Journal of Nonverbal Behavior.

"Screams require a lot of vocal force and cause the vocal folds to vibrate in a chaotic, inconsistent way," says senior author Harold Gouzoules, a professor of psychology at Emory University. "Despite the inherent variation in the way that screams are produced, our findings show that listeners can readily distinquish a scream from other human calls. And we are honing in on how they make that distinction."

Jay Schwartz is first author of the paper and Jonathan Engleberg is a co-author. They are both Emory PhD candidates in Gouzoules' Bioacoustics Lab.

Gouzoules began researching monkey screams in 1980, before becoming one of the few scientists studying human screams about 10 years ago. He is interested in the origins of screams and the role they played in human development.

"Animal screams occur almost always in the context of a fight or in response to a predator," Gouzoules says. "Human screams happen in a much broader array of contexts, which makes them much more interesting."

Gouzoules' Bioacoustics Lab has amassed an impressive library of high-intensity, visceral sounds -- from TV and movie performances to the screams of non-actors reacting to actual events posted to online sites such as YouTube.

For the current study, the researchers presented 182 participants with a range of human calls. Some of the calls were screams of aggression, exclamation, excitement, fear or pain. Others calls included cries, laughter and yells.

The participants showed strong agreement for what classified as a scream. An acoustical analysis for the calls the participants classified as screams, compared to those they did not, included a higher pitch and roughness, or harshness, to the sound; a wider variability in frequency; and a higher peak frequency.

The current paper is part of an extensive program of research into screams by Gouzoules. In another recently published article, his lab has found that listeners cannot distinguish acted screams from naturally occurring screams. Listeners can, however, correctly identify whether pairs of screams were produced by the same person or two different people.

Thursday, December 5, 2019, CLEVELAND: Cleveland Clinic researchers have found that using lungs from donors who are considered high risk for certain infectious diseases compared to standard risk donors results in similar one-year survival for recipients. In addition, researchers saw no difference in rejection or graft (donor lung) survival after one year in patients receiving lungs from increased-risk donors.

The study was published recently in the Journal of Thoracic and Cardiovascular Surgery.

In 2013, the proportion of non-standard risk-lung donors increased as the U.S. Public Health Service expanded the definition of what it means to be a "high risk" donor. The definition broadened the designation to include more organs in this category and changed the name to "increased risk" donors. The designation is used to identify risky donor behavior with the goal of reducing the transmission of HIV, hepatitis B, and hepatitis C. All organs considered for transplant are tested for infectious disease, but there is a very small possibility of an infection not showing up upon early initial testing because the immune system has not produced enough antibodies yet to be detected.

Increased risk behaviors include activities like non-medical intravenous drug use and sexual contact with a person known or suspected to have HIV, hepatitis B or hepatitis C infections. The broadened definition also encompasses donors whose medical or behavioral history cannot be obtained. Prior to the changes, about 8% of organs were considered "high risk;" after the changes, about 22% were considered "increased risk."

During the study, researchers looked at a total of 18,490 patients, with 64% transplanted during the high-risk-designation period and 36% during the increased-risk period. Researchers found no statistically significant differences in survival, acute rejection that was treated or organ survival for those receiving either increased risk or high-risk donor organs compared to those with standard-risk organs. This study did not look at recipients who accepted organs known to have hepatitis C, which, with new treatment options for the infection, is becoming more common.

Researchers worry the broadened definition has the potential to narrow the donor pool, because transplant candidates often refuse organs from increased risk donors. Transplant candidates must consent to use a non-standard-risk organ, and studies have shown up to 78% of waitlist candidates refuse an offer from an increased-risk donor. Due to organ shortages, approximately 10% of U.S. lung transplant candidates die on the waiting list every year.

"Our findings raise the question of the utility of the designation of 'increased risk' for donor lungs, since there is no impact on outcomes," said Carli Lehr, M.D., M.S., a transplant pulmonologist at Cleveland Clinic and lead author of the study. "Forgoing the designation, treating all donors as potentially at risk, and using appropriate post-transplant screening for infectious diseases may increase overall organ utilization and lessen deaths on the waitlist."

Currently, there about 1,450 people waiting for a lung transplant in the United States.

(Vienna, December 5, 2019) Young patients with inflammatory bowel disease (IBD) are five times more likely than the general population to develop viral infections that can lead to hospitalisation or permanent organ damage, a new study published in the UEG Journal has found.1

In the first study of its kind, researchers analysed almost 2,700 IBD patients in a Paris referral centre to understand the respective roles of IBD activity and drugs in promoting systemic serious viral infection (SVI). The study identified clinically active IBD and thiopurines (a class of immunomodulators used to treat an estimated 60% of IBD patients2) as the main drivers of infection. Despite the highest risk of infection being seen in young patients between the ages of 18 and 35, a three-fold increased incidence of severe viral infections was observed in IBD patients of all ages.

The study also uncovered a concerning link between thiopurine use and a number of harmful infections. Whilst IBD patients receiving no treatment were at a similar risk level to the general population, patients treated with immunomodulators were found to be six times more likely to develop an SVI. The most common SVIs developed by IBD patients were identified as Epstein-Barr virus (EBV), which is associated with a range of diseases such as glandular fever and Hodgkin's Lymphoma, and cytomegalovirus (CMV), an infection which can pose a risk to unborn babies.

A correlation was also found between thiopurine use and EBV-induced hemophagocytic lymphohistiocytosis (HLH), an aggressive disease associated with high mortality rates.3 With a third of patients estimated to be stopping thiopurine use due to adverse side effects, these new findings underline the need to find novel therapeutic approaches to tackle IBD.2

Lead researcher Professor Laurent Beaugerie, from the Department of Gastroenterology at Saint-Antoine Hospital, commented, "Clinicians need to be aware of the substantially increased risk of SVI in patients with IBD, which had previously remained unclear. Young IBD patients are the most vulnerable to the development of SVIs, as they are less likely to have been exposed to viruses such as EBV or CMV before. They will therefore mount a less effective immune response. Their risk is further elevated by the inhibiting effect of the immunosuppressive drugs they are treated with."

The number of individual IBD cases, which encompasses both Crohn's disease and ulcerative colitis, has shown a marked increase since 1990, rising from 3.6 million cases globally to over 6.8 million in 2017.4 Commenting on the increasingly heavy burden of IBD, Professor Beaugerie added, "The relation between IBD drugs and SVIs is especially concerning, as presently, hospitalisation due to the serious complications that accompany the disease is the main cost associated with the management of IBD. The growing prevalence of IBD across the globe will only add further to the pressure placed on healthcare structures."

New treatment pathways such as nutritional therapies in Crohn's disease and faecal microbiota transplantations (FMT), which are not evidenced to be associated with an increased risk of SVI, could potentially alleviate the strain placed on healthcare systems. Therapies such as these could transform the course of treatment and confer significant benefits to patients.

The study, which has cast new light on the strong association between IBD drugs and SVI, emphasises the need for further research and funding into the area to improve patient outcomes. An investigation into promising new treatments should become the next course of action if the risk of SVI in IBD patients is to be brought closer that of the general population.