Culture

New research reveals a cellular mechanism by which good bacteria can help the gut stay healthy. The study, which appears in the journal Immunity, shows that good bacteria, or the microbiota, interact with both the epithelial cells lining the gut and cells of the immune system to help balance the immune responses and protect the gut from unwanted inflammation. The study suggests that manipulating the microbiota to limit intestinal immune responses could have potential therapeutic benefits for conditions such as inflammatory bowel disease.

"A significant body of work currently indicates that the microbiota shapes the immune system and helps it to do its job," said corresponding author Dr. Gretchen Diehl, assistant professor of molecular virology and microbiology co-director of the Biology of Inflammation Center and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine. "Disease-causing microbes, such as Salmonella, evoke a strong inflammatory immune response that is directed at eliminating the microbe. But an inflammatory immune response, especially in the intestine, can be damaging to the healthy tissue. Here we defined a role for the microbiota in modulating the immune response in a way that reduces inflammation and limits the damage it can do to the gut."

For an effective immune response, immune cells called antigen-presenting cells direct other immune cells, called T cells, to mount an appropriate inflammatory response to fight microbial invaders. They also direct anti-inflammatory T cells, also known as regulatory T cells, to limit inflammatory immune responses against things like the food we eat and to turn off inflammatory immune responses.

The microbiota helps 'tune down' the inflammatory response by instructing the antigen-presenting cells to secrete the cytokine IL-10, an important anti-inflammatory molecule. IL-10 dampens inflammatory T cell responses and promotes regulatory T cell responses that keep the balance.

"The result is a balanced response that still can fight off an infection like Salmonella, but that is regulated to prevent damage to the healthy intestinal tissue," Diehl said. "We wanted to know how the microbiota could induce these kind of responses."

The microbiota-epithelium connection

"We found that when we gave the laboratory animals antibiotics, the antigen-presenting cells did not make IL-10. When we put back bacteria in the animals' guts, only bacteria that could attach to the intestinal epithelium triggered IL-10 production by antigen-presenting cells and reduced the inflammatory response," Diehl said. "It's somewhat counterintuitive because microbes that can attach to the intestinal epithelium are thought of as pathogens that can potentially cause disease. But in this case we found that the attachment of bacteria to the epithelium was not causing disease; on the contrary, it was necessary to promote a balanced regulation of the T cell responses and helped protect the gut."

The researchers indicate that their study is barely scratching the surface, and they are actively looking for other mechanisms by which microbes can promote a well-balanced intestinal environment.

Next, Diehl and her colleagues also plan on investigating the signaling pathways that are activated when the microbes attach to the epithelial cells to identify novel pathways for inducing a balanced immune response.

"A take home message for us is that a healthy microbiota is necessary to allow for a balanced response to not only protect us from infection, but also to limit potential tissue damage as the immune system attempts to eliminate pathogens," Diehl said.

MINNEAPOLIS - People who have been exposed to paint, varnish and other solvents and who also carry genes that make them more susceptible to developing multiple sclerosis (MS) may be at much greater risk of developing the disease than people who have only the exposure to solvents or the MS genes, according to a study published in the July 3, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

People with exposure to paint or other solvents are 50 percent more likely to develop MS than people with no exposure. People with exposure to solvents who also carry the genes that make them more susceptible to MS are nearly seven times as likely to develop the disease as people with no solvent exposure who do not carry the MS genes.

For people who have been smokers, the risk is even greater. Those who have been smokers with solvent exposure and the MS genes are 30 times more likely to develop MS than those who have never smoked or been exposed to solvents and who do not have the genetic risk factors.

"These are significant interactions where the factors have a much greater effect in combination than they do on their own," said study author Anna Hedström, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden. "More research is needed to understand how these factors interact to create this risk. It's possible that exposure to solvents and smoking may both involve lung inflammation and irritation that leads to an immune reaction in the lungs."

For the study, researchers identified 2,042 people who had recently been diagnosed with MS in Sweden and matched them with 2,947 people of the same age and sex. Blood tests were used to determine whether the participants had two human leukocyte antigen gene variants, one of which makes people more likely to develop MS and the other reduces the risk of MS. The participants were also asked whether they had been exposed to organic solvents, painting products or varnish and whether they had ever been a smoker.

In the group with neither of the MS genes and no smoking or exposure to solvents, there were 139 people with MS and 525 people without the disease. In the group with the MS genes and exposure to solvents but no smoking, there were 34 people with MS and 19 people without the disease. In the group with MS genes and exposure to solvents and smoking, there were 40 people with MS and five people without the disease.

The researchers determined that the MS genes and exposure to solvents combined were responsible for an estimated 60 percent of the risk of developing MS.

"How this cocktail of MS genes, organic solvents and smoking contributes so significantly to MS risk warrants investigation," said Gabriele C. DeLuca, MD, DPhil, of the University of Oxford in the United Kingdom and a member of the American Academy of Neurology, in an accompanying editorial. "In the meantime, avoiding cigarette smoke and unnecessary exposure to organic solvents, particularly in combination with each other, would seem reasonable lifestyle changes people can take to reduce the risk of MS, especially in people with a family history of the disease."

One limitation of the study was that participants were asked to remember any exposure they had to solvents, so it is possible that they may not have remembered correctly.

If this surprisingly hot British summer has you fighting off unwelcome armpit aromas, you'll be pleased to learn that science has just brought us a step closer to blocking body odour (BO).

Researchers have unravelled a key part of the molecular process by which armpit bacteria produce the most pungent component of the noxious smell we recognise as BO.

The findings could result in more effective deodorants with targeted active ingredients, the researchers suggest.

The role of microbes, specifically bacteria, in the production of BO has been known for some time and scientists at the University of York recently made the discovery that a small number of species of Staphylococcus bacteria are responsible for the formation of the most pungent component of the whiff in our pits.

However, little has been understood about the process by which these bacteria are able to take up odourless compounds, which we secrete into our underarms when we sweat, and convert them into pungent volatile chemicals.

In a paper published in the journal eLife the researchers from the University of York, in partnership with colleagues at the University of Oxford, have deciphered the first step in this process by identifying and decoding the structure of the molecule - known as a "transport" protein - that enables bacteria to recognise and swallow up the odourless compounds secreted in sweat.

Solving the structure of the protein means that a new generation of deodorants could now be developed to disrupt its function.

Co-author of the research, Dr Gavin Thomas from the Department of Biology at the University of York, said: "The skin of our underarms provides a unique niche for bacteria. Through the secretions of various glands that open onto the skin or into hair follicles, this environment is nutrient-rich and hosts its own microbial community, the armpit microbiome, of many species of different microbes.

"Modern deodorants work by inhibiting or killing many of the bacteria present our underarms in order to prevent BO. This study, along with our previous research revealing that only a small number of the bacteria in our armpits are actually responsible for bad smells, could result in the development of more targeted products that aim to inhibit the transport protein and block the production of BO."

The researchers were able to see the transport protein's detailed molecular structure by crystallising it in laboratories at the University of Oxford and analysing the data at the nearby Diamond Synchrotron Facility; providing a blueprint for how it works and ways to target it.

The process provided insight that may also have important implications for medical science.

The Council of Europe's protocol on genetic testing for health purposes* came into force yesterday (Sunday 1 July). The protocol, an addition to the Convention on Human Rights and Biomedicine, lays down rules on the conduct of genetic tests, including direct-to-consumer testing. It specifies the conditions under which tests may be carried out on persons not able to consent, with particular attention to children, and addresses privacy issues and the right to information obtained through genetic testing. It also covers counselling and screening.

The protocol enters into force thanks to its ratification by five Council of Europe member states (Norway, Montenegro, the Republic of Moldova, Slovenia and Portugal). It has also been signed by five others - the Czech Republic, Finland, France, Iceland and Luxembourg.

"At a time when genetics and genomics are advancing so rapidly, issues surrounding genetic testing take on an even greater importance than before," says ESHG President Professor Gunnar Houge, University of Bergen, Norway. "New technologies and discoveries provide huge potential for the improvement of human health, but alongside that can go the potential for misuse. The ESHG therefore welcomes the Council of Europe protocol and believes that it will be an important factor in ensuring that genetic progress continues to be applied in the most ethical way possible to the benefit of all concerned."

BOSTON - Orthostatic hypotension (OH) - a rapid drop in blood pressure upon standing up from a sitting or lying down position - is a frequently encountered clinical sign among patients. Clinicians most often consider OH as indicative of dehydration. However, new research led by scientists at BIDMC bolsters the notion that adults with OH may have undiagnosed cardiovascular disease.

The team analyzed data from 9,139 participants ages 45 to 64 who enrolled in the long-running Atherosclerosis Risk in Communities (ARIC) Study between 1987 and 1989. These participants were followed for cardiovascular events and mortality through Dec. 31, 2015.

"OH was associated with all measures of subclinical cardiovascular disease and was an important predictor of clinical CVD events in the future," said Stephen Juraschek, MD, PhD, Instructor of Medicine at BIDMC and Harvard Medical School. "When orthostatic hypotension is detected in middle-aged adults who do not have known cardiovascular disease, health care practitioners should be mindful of undetected heart disease."

Juraschek and colleagues' findings appeared online in the Journal of the American Heart Association on May 7.

"While there is controversy surrounding the association between OH and cardiovascular disease, our findings were unequivocal and consistent," said Juraschek. "These findings strongly support our hypothesis about OH being an important manifestation of undetected CVD. Many treatments for OH such as increasing sodium intake or stopping blood pressure medications have the potential to worsen blood pressure control and risk for CVD. Clinicians should be aware of the possibility that undiagnosed CVD may be present in adults with OH prior to starting treatments."

Tokyo - When a nuclear power plant accident occurs and radioactive material is released, it is vital to evacuate people in the vicinity as quickly as possible. However, it can be difficult to immediately predict where the emitted radioactivity will settle, making it impossible to prevent the exposure of large numbers of people.

A means of overcoming this difficulty has been presented in a new study reported in the journal Scientific Reports by a research team at The University of Tokyo Institute of Industrial Science. The team has created a computer program that can accurately predict where radioactive material that has been emitted will eventually land, over 30 hours in advance, using weather forecasts on the expected wind patterns. This tool enables evacuation plans and other health-protective measures to be implemented if another nuclear accident like in 2011 at the Fukushima Daiichi Nuclear Power Plant were to occur.

This latest study was prompted by the limitations of existing atmospheric modeling tools in the aftermath of the accident at Fukushima; tools considered so unreliable that they were not used for planning immediately after the disaster. In this context, the team created a system based on a form of artificial intelligence called machine learning, which can use data on previous weather patterns to predict the route that radioactive emissions are likely to take.

"Our new tool was first trained using years of weather-related data to predict where radioactivity would be distributed if it were released from a particular point," lead author Takao Yoshikane says. "In subsequent testing, it could predict the direction of dispersion with at least 85% accuracy, with this rising to 95% in winter when there are more predictable weather patterns."

"The fact that the accuracy of this approach did not decrease when predicting over 30 hours into the future is extremely important in disaster scenarios," Takao Yoshikane says. "This gives authorities time to arrange evacuation plans in the most badly affected areas, and to issue guidance to people in specific areas about avoiding eating fresh produce and taking potassium iodide, which can limit the absorption of ingested radioactive isotopes by the body."

A new Tel Aviv University study suggests there is hope of treating certain inborn congenital metabolic diseases -- a hope found in green tea and in red wine.

Most people with inherited metabolic disorders are born with a defective gene that results in a critical enzyme deficiency. In the absence of a cure, many patients with inborn congenital metabolic disorders must adhere to a strict and demanding diet their entire lives. This new research finds that certain compounds found naturally in green tea and red wine may block the formation of toxic metabolites.

The research was led by Prof. Ehud Gazit of TAU's Faculty of Life Sciences and his doctoral student Shira Shaham-Niv. It was published in the Nature group journal Communications Chemistry.

The researchers considered two compounds: (1) epigallocatechin gallate, known as EGCG, found naturally in green tea, which has attracted attention within the medical community for its potential health benefits; and (2) tannic acid, found in red wine, which is known to prevent the formation of toxic amyloid structures that cause neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

"In the case of inborn congenital metabolic diseases, the body does not produce a vital metabolic enzyme," Shaham-Niv said. "As a result, metabolites -- substances that are, among other things, the building blocks of DNA and proteins -- accumulate in the body. Such uncontrolled accumulation is toxic and can cause severe developmental and mental disorders.

"Our new study demonstrates once again the ability of nature to produce the best candidate of drugs to treat some of the worst human maladies."

Collectively, this group of disorders constitutes a significant portion of pediatric genetic diseases. The disease phenylketonuria (PKU), which produces the aggregation of the metabolite phenylalanine, is one common inborn metabolic disease. Infants with PKU must adhere to a strict diet free of phenylalanine for the rest of their lives. If they don't, they may face severe debilitating developmental problems.

"But this is an incredibly difficult task, since phenylalanine is found in most of the food products that we consume," Shaham-Niv said. "The avoidance of certain substances is the only way to prevent the debilitating long-term effects of inborn congenital metabolic disorders. We hope that our new approach will facilitate the development of new drugs to treat these disorders."

The new research is based on two previous studies conducted at Prof. Gazit's TAU laboratory. In the first study, phenylalanine was shown to be capable of self-assembly and of forming amyloid structures like those seen in Alzheimer's, Parkinson's and other neurodegenerative diseases. In the second study, by Shaham-Niv, other metabolites that accumulate in other inborn congenital metabolic diseases were also shown to undergo self-assembly processes and form toxic amyloid aggregates.

"Both studies led to an overhaul in the research community's understanding of metabolic diseases," Shaham-Niv said. "In our new study, we examined whether the molecules identified in past studies on Alzheimer's disease and other amyloid diseases, which are known to inhibit the formation of amyloid aggregates, could also help counteract the amyloid formation process of metabolites in metabolic diseases."

The new research focused on EGCG and tannic acid using test tubes and culture cell systems. The two substances were tested on three metabolites related to three innate metabolic diseases: adenine, cumulative tyrosine and phenylalanine. The results were promising. Both tannic acid and EGCG were effective in blocking the formation of toxic amyloid structures. The researchers also used computer simulations to verify the mechanism driving the compounds.

"We are entering a new era of understanding the role and the importance of metabolites in various diseases, including metabolic diseases, neurodegenerative diseases and even cancer," Shaham-Niv concluded. "The tools we have developed are ground-breaking and have tremendous potential to help a wide range of patients in the future."

New UK research has found that a new mindfulness based approach to tinnitus could transform the treatment of the condition.

Published in the journals Ear and Hearing and Psychotherapy and Psychosomatics, the research led by Dr Laurence McKenna from University College London Hospitals NHS Foundation Trust (UCLH) and Dr Liz Marks, from Department of Psychology at the University of Bath, found that Mindfulness based Cognitive Therapy (MBCT) helps to significantly reduce the severity of tinnitus compared to relaxation-based treatments, an approach recommended by many tinnitus clinics.

Tinnitus, described as a sensation or awareness of sound that is not caused by an external sound source, affects approximately six million people in the UK - 10 percent of the UK's population. Approximately 1 in 100 people are very distressed or disabled by it and as many as 1 in 20 people are at least moderately distressed by it. Tinnitus is associated with complaints of emotional stress, insomnia, auditory perceptual problems and concentration problems.

As yet there is no treatment to stop the tinnitus noise but this research, funded by the British Tinnitus Association (BTA), shows clearly that treatment can make it less severe, intrusive and bothersome.

Dr Liz Marks, from the Department of Psychology at the University of Bath, will explore the report's findings in more detail at the BTA's annual conference in Birmingham in September. She said: "We compared MBCT to relaxation therapy, a traditional treatment for people with chronic tinnitus, to determine if MBCT was a better option than the current recommended practice.

"In total 75 patients took part in the trial at UCLH's Royal National Throat, Nose and Ear Hospital receiving either MBCT or relaxation therapy. The study found that both treatments led to a reduction in tinnitus severity, psychological distress, anxiety and depression for patients.

"However, the MBCT treatment led to significantly greater reductions in tinnitus severity than the relaxation treatment, and this improvement lasted for longer. In addition, 182 patients who completed MBCT routinely in our clinic showed a similar level of improvement."

Relaxation therapy provides patients with specific skills to reduce stress arousal levels. In contrast, MBCT, taught by highly-trained clinical psychologists, teaches patients to pay purposeful, present-moment attention to experiences, rather than trying to supress those experiences. Practicing mindfulness meditation in this way can cultivate a more helpful way of responding to tinnitus. People learn how to 'allow' and 'accept' tinnitus, rather than having to 'fight it' or 'push it away'. Mindfulness does not aim to change the nature or sound of the tinnitus, but the therapy can lead to tinnitus becoming less intrusive, to a point where it is no longer a problem for people.

Dr Marks added: "MBCT turns traditional tinnitus treatment on its head - so rather than trying to avoid or mask the noise, it teaches people to stop the battle with tinnitus.

"The mindfulness approach is radically different from what most tinnitus sufferers have tried before, and it may not be right for everyone. We are confident, however, that the growing research base has demonstrated how it can offer an exciting new treatment to people who may have found that traditional treatment has not been able to help them yet. We hope the results of our research will be one of the first steps to MBCT becoming more widely adopted."

David Stockdale, chief executive of the British Tinnitus Association, said: "The results of this research are extremely encouraging particularly for people with chronic tinnitus who find that current treatments are not working for them. We really hope that more people will be able to benefit from this approach moving forward."

"Funding this kind of innovative research is a major part of what we do here at the BTA but as a charity, we rely heavily on the donations made to us. We hope more people will support us as we work tirelessly to grow the understanding and knowledge around tinnitus in order to help people with the condition to manage."

Dr McKenna and Dr Marks are now continuing their research in tinnitus looking at how Cognitive Behavioural Therapy can be used to treat tinnitus related insomnia.

It is currently recommended in Europe that screening for hepatitis C virus (HCV) should target people at high risk of infection. In France, public health data suggest that in 2014 approximately 75 000 people aged 18 to 80 were infected by HCV, but were unaware of their status. In at least one in ten cases, these people are at an advanced stage of the disease when diagnosed. Today's treatments of HCV infection are both highly effective and well tolerated, and cure the infection in a few weeks in over 95% of cases. In Professor Yazdan Yazdanpanah's Inserm research team, Sylvie Deuffic-Burban has developed a mathematical model that assesses the efficacy and cost-effectiveness of different screening strategies, including universal screening.

This study applied data from a 2004 InVS seroprevalence survey to 18- to 80-year-olds in France, excluding people with diagnosed chronic HCV infection. The researchers developed their analytical model using a combination of these seroprevalence data and findings from studies of the characteristics of people infected (age, sex, stage of the disease at diagnosis, alcohol intake, etc.), the natural progression of the disease, the efficacy of treatments, the quality of life of the patients treated, and the cost of treatment of infection. The screening strategies assessed targeted the following groups: the at-risk population only, all men aged between 18 and 59, all people aged between 40 and 59, all people aged between 40 and 80, and everyone aged between 18 and 80, ie, universal screening.

The modeling results show that universal screening is associated with better life expectancy adjusted for quality of life than other strategies. Universal screening is cost-effective if the patients tested for HCV infection are treated rapidly after diagnosis. Sylvie Deuffic-Burban points out that "Screening, on an individual basis, enables rapid treatment, which avoids the development of serious complications. In time, collective screening helps eliminate hepatitis C from a population that has been screened without restrictions." The results of this ANRS-funded study therefore argue in favor of universal screening for HCV in France, followed by immediate treatment of those diagnosed with HCV infection. Sylvie Deuffic-Burban concludes that "Although our model is unable to test the idea, the epidemiological similarities of HCV, HIV, and HBV suggest that universal and combined screening for these three viruses could be of particular interest."

Experts from the Higher School of Economics have determined that cultural diversity is beneficial for team performance in eSports, while language and experience diversity negatively affect performance. These results might be of interest to companies of similar industries aiming to maximize profits. The study, entitled 'Is Diversity Good or Bad? Evidence from eSports Teams Analysis,' was published in the journal Applied Economics.

Researchers at the HSE International Laboratory of Intangible-driven Economy analysed the results of a Counter-Strike: Global Offensive (CS:GO) game for 2013-2015 for the top 100 teams, made up of representatives from 23 countries.

Several types of diversity were identified: diversity of experience, diversity of culture, and diversity of language. The researchers used characteristics described in the work of Geert Hofstede to measure the cultural aspects of different countries: individualism, uncertainty avoidance, long-term orientation, masculinity, and power distance.

Using regression analysis, the authors of the study determined that the absence of diversity among team members reduces the amount of prize money by an average of 30%. When teams are diversified, profit increases. A representative from an additional country increases the prize money by almost 32%, all else being equal. This applies to typical teams comprised of representatives from two or three countries. Not all aspects of cultural diversity on teams positively impacts performance, however. For example, if a team has representatives of countries with different attitudes towards power distance inequality, productivity drops. While country heterogeneity for individualism and masculinity has a positive effect on team performance, the effect of the second character quality is less than the first. Other aspects do not have a substantial impact on team performance.

The researchers also analysed language diversity and determined that the more homogenous a team is, the better its performance will be. In other words, the best-performing teams are those with representatives of different countries that speak the same language, e.g., English-speaking players from the U.S. and Australia or Russian-speaking players from post-Soviet countries. Language and experience heterogeneity among players does not impact performance or can have a negative effect depending on the approach taken during analysis.

'We believe that the results obtained from the eSport industry can be used as an example for firms from similar industries. Companies in eSports, like in real business, are focused on results, use the same stimuli, and demonstrate a trend towards digitalisation. Additionally, the intellectual abilities of participants are more important than physical abilities,' says Petr Parshakov, the Deputy Head of HSE Perm's International Laboratory of Intangible-driven Economy.

The main result of the study is that companies might benefit from diversity in their workforces, as the absence of diversity reduces performance by 30%. It is important to note, however, that different aspects of diversity affect performance in different ways.

MISSOULA, Montana - Forests, one of the most dominate ecosystems on Earth, harbor significant biodiversity. Scientists have become increasingly interested in how this diversity is enhanced by the sheltering microclimates produced by trees.

A recent University of Montana study suggests that a warming climate in the Pacific Northwest would lessen the capacity of many forest microclimates to moderate climate extremes in the future.

The study was published in Ecography: A Journal of Space and Time in Ecology. It is online at http://bit.ly/2KcO1iC.

"Forest canopies produce microclimates that are less variable and more stable than similar settings without forest cover," said Kimberley Davis, a UM postdoctoral research associate and the lead author of the study. "Our work shows that the ability of forests to buffer climate extremes is dependent on canopy cover and local moisture availability - both of which are expected to change as the Earth warms."

She said many plants and animals that live in the understory of forests rely on the stable climate conditions found there. The study suggests some forests will lose their capacity to buffer climate extremes as water becomes limited at many sites.

"Changes in water balance, combined with accelerating canopy losses due to increases in the frequency and severity of disturbance, will create many changes in the microclimate conditions of western U.S. forests," Davis said.

Invigorating the idea of computers based on fluids instead of silicon, researchers at the National Institute of Standards and Technology (NIST) have shown how computational logic operations could be performed in a liquid medium by simulating the trapping of ions (charged atoms) in graphene (a sheet of carbon atoms) floating in saline solution. The scheme might also be used in applications such as water filtration, energy storage or sensor technology.

The idea of using a liquid medium for computing has been around for decades, and various approaches have been proposed. Among its potential advantages, this approach would require very little material and its soft components could conform to custom shapes in, for example, the human body.

NIST's ion-based transistor and logic operations are simpler in concept than earlier proposals. The new simulations show that a special film immersed in liquid can act like a solid silicon-based semiconductor. For example, the material can act like a transistor, the switch that carries out digital logic operations in a computer. The film can be switched on and off by tuning voltage levels like those induced by salt concentrations in biological systems.

"Previous devices were much more elaborate and complex," NIST theorist Alex Smolyanitsky said. "What this ion-trapping approach achieves is conceptual simplicity. In addition, the same exact device can act as both a transistor and a memory device--all you have to do is switch the input and output. This is a feature that comes directly from ion trapping."

The NIST molecular dynamics simulations focused on a graphene sheet 5.5 by 6.4 nanometers (nm) in size and with one or more small holes lined with oxygen atoms. These pores resemble crown ethers--electrically neutral circular molecules known to trap metal ions. Graphene is a sheet of carbon atoms arranged in hexagons, similar in shape to chicken wire, that conducts electricity and might be used to build circuits. This hexagonal design would seem to lend itself to pores, and in fact, other researchers have recently created crown-like holes in graphene in the laboratory.

In the NIST simulations, the graphene was suspended in water containing potassium chloride, a salt that splits into potassium and sodium ions. The crown ether pores were designed to trap potassium ions, which have a positive charge. Simulations show that trapping a single potassium ion in each pore prevents any penetration of additional loose ions through the graphene, and that trapping and penetration activity can be tuned by applying different voltage levels across the membrane, creating logic operations with 0s and 1s (see text box below).

Ions trapped in the pores not only block additional ion penetration but also create an electrical barrier around the membrane. Just 1 nm away from the membrane, this electric field boosts the barrier, or energy needed for an ion to pass through, by 30 millivolts (mV) above that of the membrane itself.

Applying voltages of less than 150 mV across the membrane turns "off" any penetration. Essentially, at low voltages, the membrane is blocked by the trapped ions, while the process of loose ions knocking out the trapped ions is likely suppressed by the electrical barrier. Membrane penetration is switched on at voltages of 300 mV or more. As the voltage increases, the probability of losing trapped ions grows and knockout events become more common, encouraged by the weakening electrical barrier. In this way, the membrane acts like a semiconductor in transporting potassium ions.

To make actual devices, crown ether pores would need to be fabricated reliably in physical samples of graphene or other materials that are just a few atoms thick and conduct electricity. Other materials may offer attractive structures and functions. For example, transition metal dichalcogenides (a type of semiconductor) might be used because they are amenable to a range of pore structures and abilities to repel water.

Making A Logic Operation in Liquid

NIST simulations showed that ion trapping depends on the voltage across the porous graphene membrane, suggesting the possibility of performing simple ion-based logic operations. At sufficiently low salt concentration, the membrane’s highly conductive (on) regime coincides with low trapped ion occupancy, and vice versa. Direct electrical measurement of the membrane’s voltage, which might be used in an electrical circuit, is what’s known as a “read” operation.

If a low voltage, denoted 0, is applied across the membrane with appropriate salt concentration, the membrane is nearly nonconductive (off) and its pores are fully occupied by the trapped ions. Therefore, the charge in the graphene circuit, measured at the membrane, is relatively high, denoted as 1. Conversely, when high voltage (more than 300 mV), denoted 1, is applied, the membrane is highly conductive (on), fewer ions are trapped, and thus a low (0) state of energy in the membrane itself is measured.

The input-output relationship can be viewed as a NOT logic gate or operation, in which input and output values are reversed. If 0 goes in, then 1 comes out, and vice versa. With two graphene sheets an OR (XOR) logic operation would be possible. In this case, the output value, or the difference between the two membrane states, is 1 only when either of the two sheets is highly conductive. Stated another way, the output is 1 if the inputs are different but 0 if the two inputs are identical.

Even a small variation in applied voltage results in a relatively large change in potential membrane charge or current, suggesting that sensitive switching may be possible. Thus, voltage-tunable ion trapping in crown pores might be used to store information, and simple, yet sensitive ionic transistors might be used to perform sophisticated logic operations in nanofluidic computing devices.

A research team found a novel function of fibroblast growth factor 2 (FGF2), a self-renewal factor for spermatogonial stem cell (SSC) which is the origin of the sperm production. Although it has demonstrated that both FGF2 and glial cell line-derived neurotrophic factor (GDNF) is indispensable for SSC self-renewal and survival in vitro, the present study revealed that FGF2 showed the different properties from GDNF in mouse testis. This finding will contribute to the regulation of SSCs in vivo for the treatment of male infertility.

This study was published in the June issued Stem Cell Reports.

Dr. Seiji Takashima, an Assistant Professor of the Faculty of Textile Science and Technology in Shinshu University and the corresponding author on the paper, successfully identified a novel function of FGF2 in mouse testis using a "biodegradable gelatin microsphere system" which is capable of sustained diffusion of self-renewal factors for several days in vivo.

Consecutive production of sperm is ensured by the repeat of self-renewal and differentiation of SSCs. It was well known that the self-renewal of SSCs is promoted by GDNF, while retinoic acid (RA) induces the differentiation toward sperm production. In 2015, Dr. Takashima found that FGF2 (fibroblast growth factor 2) also act as a self-renewal factor for SSCs in vitro. In the present study, his group demonstrated that FGF2 conversely acts as a differentiation promoting factor in vivo.

They found that FGF2-stimulated SSCs frequently expressed a receptor for RA when compared to those stimulated by GDNF, suggesting that FGF2 expands differentiation-susceptible subset of SSCs. Simultaneously, they also demonstrated that this molecule acts on testicular microenvironment, which is required for SSC function, to facilitate RA action. These results demonstrate that FGF2, which was shown to be 'bona fide self-renewal factor for SSCs in vitro' in 2015, can conversely act to facilitate SSC differentiation in vivo. Considering that GDNF/FGF2 ratio shows dynamic change during testicular development and regeneration, the functional balance between GDNF and FGF2 might play a pivotal role in the regulation of sperm production from SSCs.

The finding will contribute not only to understanding the principle of sperm production but also to future applications for male infertility treatment, breeding live stock, and conservation of endangered species.

In recent years, researchers have focussed on the enzyme TLK2 suspecting it of playing a main role in several diseases. A new study conducted at the University of Copenhagen now reveals that the enzyme displays lower levels of activity in intellectual disability and that it is possible to inhibit it in breast cancer, where it is overactive. The study thus suggests that the enzyme may be a target for potential therapies.

In order to maintain genome stability in the cells the enzyme TLK2 constantly strives to attach phosphate to proteins. It activates specific functions in the cell and helps to stabilise the cell nucleus, which is of critical importance.

In recent years the enzyme has been linked to various diseases. For example, researchers have discovered that the gene coding for the enzyme is overexpressed in patients suffering from ER-positive breast cancer and mutated in intellectual disability, but up until now no one has been able to outline the behaviour of the enzyme.

Now researchers from the University of Copenhagen and Institute for Research in Biomedicine Barcelona have taken a big step forwards and managed to outline the enzyme all the way to the molecular level using X-ray crystallography. Their study, which has just been published in the scientific journal Nature Communications, suggests that the enzyme activity diminishes in patients suffering from intellectual disability. Conversely, it seems to be possible to inhibit the enzyme in patients with breast cancer, where it is overactive.

'We are outlining the structure of this important and interesting enzyme. Once we know how it is structured, it will be much easier to develop drugs targeted at the enzyme, either inhibiting or strengthening it. This study thus points directly to drug design, as it has identified some concrete mechanisms that must be taken into account', says Head of the Study Guillermo Montoya, Professor at the Novo Nordisk Foundation Center for Protein Research.

Specific Genetics Inhibit the Enzyme

The researchers have studied the enzyme in detail at molecular level. They have used biochemical methods and advanced techniques within molecular biophysics to produce a so-called molecular description of the enzyme's crystal structure. This is important because it gives the researchers insight into the behaviour of the enzyme at atomic level.

They have also taken as their starting point previous studies showing that patients suffering from intellectual disability have a mutation in genes affecting the TLK2 enzyme. In this study they show that there is indeed a link between the genes and the enzyme, as these same genetic mutations compromise the activity of the enzyme.

In addition, they have drawn on knowledge from other studies revealing that the enzyme is overactive in so-called ER-positive breast cancer. On this basis they have tested several so-called small molecule drugs and learned that it is possible to inhibit the activity of the enzyme in material isolated from human cells.

The researchers will now seek to learn more about how the enzyme can be targeted and either be inhibited or activated in patients with these conditions.

Availability of family and friends key factor in deciding organ transplant suitability

This may sanction existing prejudices and widen inequalities in selection process, warn researchers

The availability of a supportive network of family and friends is a key factor in deciding on a person's suitability for an organ transplant, reveals research published online in the Journal of Medical Ethics.

But as this criterion is subjective, not grounded in evidence, and often not explicit, it may sanction existing prejudices and widen inequalities in the selection process, warn the researchers.

They base their findings on feedback from nearly 600 US organ transplant providers on the criteria influencing the selection process.

National guidelines stipulate the inclusion of subjective assessments of the extent of social support when considering an individual's suitability for an organ transplant, despite the dearth of evidence linking this factor with outcomes, point out the researchers. Potential candidates can be 'marked down' if their social support is deemed inadequate.

To find out how influential this criterion might be in the selection process for kidney transplant, they asked 584 transplant providers to choose between two pretend candidates, based on 7 factors.

These were: life expectancy with and without a transplant; quality of life after a transplant; time spent on the waiting list; extent of compliance with medical advice/drug treatment; age; and availability of supportive friends/family.

Around half of the respondents were men (257, just over 52%) and nearly half (282, 48%) were involved in the psychological/social evaluation of suitability. Of these, two thirds were social workers and 29 per cent doctors.

The remaining half (302, 52%) comprised medical/surgical providers, most of whom (more than 71%) were involved in kidney transplants.

Most (just under 89%) respondents said they had used inadequate social support as one of several factors to help them decide on transplant suitability. And most (just over 86%) agreed that patients with inadequate support were viewed less favourably than those who had good social networks to draw on.

Most providers (71.5%) thought social support was important for ensuring the transplanted organ didn't go to waste, yet nearly one in four (24%) thought using this criterion was unfair. And more than four out of 10 (42.5%) didn't feel that confident applying it to the selection process.

Analysis of the choices for the pretend scenarios revealed that, overall, a candidate's life expectancy after a transplant, how well they complied with medical advice/treatment, and how well supported they were by family and friends were the most influential factors when deciding on suitability for the procedure.

Social support emerged as the second most important factor, with providers 68 per cent more likely to choose a candidate who had a good social network of friends/family over one who didn't.

"This finding is striking, given the limited evidence base confirming the impact of social support on transplant outcomes and its potential for increasing disparities," write the researchers.

"Because reliance on social support is unpredictable, not evidence-based, and not always transparent, use of social support may contribute to unequal access to transplantation," they add.

And the lack of formal criteria on how to assess social support and its importance in the selection process, "leaves this criterion increasingly susceptible to implicit bias and may also contribute to disparities," they say.

This is particularly important, given that racial and ethnic minorities, those on low incomes, and those living in rural areas are already less likely to be selected for an organ transplant, while those with a mental illness or a history of substance misuse may be more socially isolated to begin with, they point out.