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What The Study Did: For patients with HIV, CD4 counts reflect the health of their immune system and HIV RNA levels indicate their viral load. This observational study focused on how cancer treatments were associated with those two important clinical measures and risk of death in nearly 200 patients with HIV and cancer.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Keri L. Calkins, Ph.D., of the Johns Hopkins Bloomberg School of Public Health in Baltimore, is the corresponding author.

(doi:10.1001/jamaoncol.2019.4648)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

A fundamental change in our understanding of the childhood kidney cancer Wilms' tumour is on the horizon, after the discovery of its earliest genetic root by scientists at the Wellcome Sanger Institute and their collaborators. By comparing genome sequences from normal kidney tissue and tumours, the team identified patches of normal-looking kidney tissue that in fact carried DNA changes that cause Wilms' tumour.

The study, published in Science, uncovers a novel route by which cancers can form in the first few weeks of life, whereby an early cell gains the DNA modification associated with cancer and proliferates while the kidney is developing. Understanding the root of the cancer promises to improve treatment and help prevent recurrence of Wilms' tumour. This discovery also raises the possibility of one day being able to screen for cancers like this before tumours develop.

Wilms' tumour is a form of kidney cancer mainly affecting children under five years of age. Though kidney cancers in children are rare, Wilms' tumour is the most common type with around 80 cases per year diagnosed in the UK. Nine out of ten cases are curable by surgery to remove the affected kidney together with chemotherapy and sometimes radiotherapy. Usually the cancer only affects one kidney, but in around 10 per cent of cases both kidneys are affected*. It has been assumed that the cause of Wilms' tumour is one cell 'going wrong' as the kidney develops in the first few weeks of life.

This study is the first to compare healthy kidney tissue with Wilms' tumour tissue, using comparative genome analysis to investigate the cause of the disease. 66 tumour and 163 normal kidney tissue samples were collected by researchers at Addenbrooke's Hospital in Cambridge and Great Ormond Street Hospital in London. Scientists at the Wellcome Sanger Institute sequenced DNA from the samples to create 229 whole genome sequences, which were analysed to identify genetic changes between tumours and normal tissue.

In two thirds of children with Wilms' tumour, DNA changes associated with the disease were found to be shared by both normal kidney tissue and tumour tissue. This allowed the researchers to hone in on patches of genetically abnormal cells which, when looked at down a microscope, appeared to be normal.

These patches were found to have developed from a single rogue cell with a DNA change suppressing the H19 gene. Normally, the function of H19 is to ensure that cells grow in an orderly manner. This particular DNA change is what is known as an epigenetic change, where part of the DNA code becomes 'invisible' to the cells, rather than a physical alteration of the person's DNA***. This epigenetic change 'turns off' H19 and enables cells to grow rapidly into pre-cancerous patches of kidney tissue from which Wilms' tumour can arise.

Tim Coorens, first author of the study from the Wellcome Sanger Institute, said: "A good analogy for what we found is that Wilms' tumour is not just an isolated weed on an otherwise well maintained field. We discovered that the weed has an extensive root underneath the soil. Now we know we need to look for the patch of soil where the root has taken hold. If we remove that patch, the weed isn't going to return."

Due to the likelihood of recurrence, Wilms' tumour is usually treated by removing the whole kidney. Most people can live a relatively normal life with one kidney, but in the 10 per cent of Wilms' tumour cases that affect both kidneys, removing them entirely will have life-changing consequences for the patient**.

Dr Kathy Pritchard-Jones, Professor of Paediatric Oncology at the UCL Great Ormond Street Institute of Child Health, said: "Surgery for Wilms' tumour usually involves removing the whole kidney to ensure no tumour is left behind. However, some children need more precise surgery that preserves their kidney function, especially when they have tumours in both kidneys or are at increased genetic risk of further tumours. This study helps us understand how Wilms' tumours start off and provides a marker for kidney tissue that is at high risk of forming new tumours. My hope is that in future we'll be able to develop treatments that focus on these patches of abnormal tissue without having to sacrifice one or both kidneys."

As well as changing how we treat Wilms' tumour, these findings open up the possibility of one day screening for this and similar cancers.

Dr Sam Behjati, lead author of the study from the Wellcome Sanger Institute and Addenbrooke's Hospital, said: "The discovery of the genetic root of Wilms' tumour signals a shift in our understanding of this particular cancer and childhood cancer more generally. Our findings represent a radical departure from how we think about Wilms' tumour because we never expected to find the root of cancer in normal-looking tissue. It may even pave the way for us to begin to think about preventing childhood cancer."

Phil Brace, Chief Executive of The Little Princess Trust who were one of the funders of the research, said: "The Little Princess Trust are very pleased to have supported this important work. We are very excited to hear the potential impact of what has been discovered and the improved understanding as a result of this project. As a funder of paediatric cancer research, this was one of our earliest supported projects and we are very keen to support more work in this area."

Tropical species are six times more sensitive to forests being broken up for logging or farming than temperate species, says new research.

A team led by Oregon State University and including Imperial College London scientists found that sensitivity to forest fragmentation - the breakup of forests by human activities like logging or farming - increased six-fold at low versus high latitudes, putting tropical species at greater risk of extinction.

The finding, published today in Science, could allow researchers to design more effective conservation schemes, such as leaving larger areas of pristine forest intact in tropical areas.

Co-author Professor Rob Ewers, from the Department of Life Sciences at Imperial, led the data collection. He said: "Our research suggests that actions as simple as building roads through forests have far greater ecological impact in the tropics than they do in the temperate world. We need to tread very lightly in these sensitive ecosystems.

"It also provides important nuance in conservation planning. It explains why plans used in one place don't necessarily work in another, and gives us great insight into how we should be tailoring our plans to account for ecological history."

The researchers tested the 'extinction filter hypothesis', which suggests animals that evolved in environments that suffer regular disturbances - such as fires and hurricanes - should be more likely to cope with new disturbances like deforestation.

These disturbed conditions occur more regularly in temperate latitudes, so the species in those forests were expected to fare better under forest fragmentation.

The team gathered 73 datasets of forest species abundance around the world collected over the past decade and used modeling software to separate the effects of fragmentation from other factors. The datasets contained 4,489 species from four major taxa - arthropods (2,682); birds (1,260); reptiles and amphibians (282); and mammals (265).

They looked for 'edge avoidance' - animals that do not like living near the edges of forests, where conditions like light and moisture are markedly different from the dense core. Edges are created when forests are broken up by deforestation and other human activities like farming or roads, such that 70 percent of Earth's remaining forest is within one kilometre of the forest edge.

They found that in low-disturbance regions, nearer the equator, 51.3 percent of forest species tend to avoid edges compared to 18.1 percent in high-disturbance zones further from the equator.

First author Professor Matt Betts, from Oregon State University, said: "Biodiversity of vertebrates increases massively toward the equator, but even accounting for that, a greater proportion of species are more sensitive to fragmentation. Sensitivity increases six-fold at low versus high latitudes.

"That means that not only should we care about the tropics because so many species are found there that are found nowhere else on Earth, but those species are also more sensitive to how we treat the forests."

Although species at temperate latitudes are less sensitive to forest fragmentation, there are still some species that will be negatively impacted, and this is predicted to rise as species gradually move toward the poles in response to climate change.

Co-author Dr Cristina Banks-Leite, from the Department of Life Science at Imperial, said: "Tropical forests are at increasing danger from human activities. The results we obtained show how the expansion of roads and agriculture in the tropics can drive species extinction even when overall forest cover levels are maintained.

"These results allow us to better focus conservation and restoration activities depending on the history of disturbance of a region. In Brazil, for instance, the Atlantic Forest has a longer history of disturbance than the Amazon. So, in the Atlantic Forest we could expect that an increase in forest cover would lead to high gains of species, even if this new forest is fragmented. In the Amazon, on the other hand, either deforestation or simply the creation of a new road could lead to species losses."

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.