Culture

The Epstein Barr virus (EBV) is very widespread. More than 90 percent of the world's population is infected - with very different consequences. Although the infection does not usually affect people, in some it can cause glandular fever or various types of cancer. Researchers at the German Cancer Research Center (DKFZ) have now discovered why different virus strains cause very divergent courses of disease.

More than 90 percent of all people become infected with the Epstein Barr virus (EBV) during their lifetime. The infection usually remains undetected throughout their life. However, the virus can also cause diseases - with regional differences: Glandular fever (infectious mononucleosis) primarily occurs in Europe and North America and normally affects adolescents or young adults. In equatorial Africa, Burkitt lymphoma is associated with EBV infection. And in Taiwan, southern China and Southeast Asia, the virus often causes nasopharyngeal carcinomas, cancers of the nose and throat area. This is one of the most common types of cancer in young adults in these countries.

"Nasopharyngeal carcinomas are sometimes seen here too, but really very rarely," commented Henri-Jacques Delecluse from DKFZ. So how does EBV cause completely different diseases in different parts of the world? "One possible explanation is that different types of virus are responsible," Delecluse explained. "And we have now found evidence of precisely that." The DKFZ researchers are publishing their results in the journal Nature Microbiology.

In the laboratory, Delecluse and his team studied a virus strain that had previously been isolated from a nasopharyngeal carcinoma. M81, as this particular type of virus is called, has certain peculiarities. Thus the researchers had previously already discovered that M81 infects not only the immune system's B cells, but also epithelial cells of the nasal mucous membrane very efficiently. In contrast, virus strains that cause glandular fever in Europe almost only infect B cells. And although the virus strains that are common here cause the infected B cells to multiply in a Petri dish, they do not produce any new virus particles, unlike M81.

As the DKFZ researchers discovered, one of the reasons for this different behavior is a genetic element called EBER2, of which there are many different variations. EBER2 is what is called a "non-coding RNA" (ncRNA), in other words a piece of RNA that does not contain a blueprint for protein molecules. M81 has an EBER2 variant that is particularly often found in EBV strains from nasopharyngeal carcinomas.

To find out how this variant affects the behavior of the virus, the DKFZ researchers used molecular biology tools to extract EBER2 from the M81 genome. "The virus was indeed no longer able to multiply in the infected cells," Delecluse noted. Even when an EBER2 element from a virus strain that is widespread in Europe was inserted into the M81 virus, it was no longer able to produce virus particles.

The researchers also discovered how EBER2 helps M81 multiply. "EBER2 from M81 stimulates the production of CXCL8, a cytokine that plays an important role in inflammation and carcinogenesis," Delecluse explained, adding that this was not only true of the infected cells themselves. "The EBER2 RNA is wrapped in little envelopes in the infected cell and transported to neighboring cells, which then also begin to produce CXCL8," he continued, explaining that this ultimately stimulated the virus to produce offspring.

"We have therefore finally found evidence that different types of virus can be responsible for different diseases," said Delecluse, emphasizing the significance of his results. "This finding is a strong argument for pressing on with vaccine research in order to develop protection against the most dangerous strains of EBV in future," he concluded. The vaccination against human papillomavirus (HPV), which can cause cervical cancer, already uses a similar principle.

While using a wearable device alone may not always be enough to motivate more exercise, adding fun and competition can be the catalyst needed to drive real results, according to a new study from researchers at Penn Medicine and Deloitte Consulting LLP. The two teams combined behavioral insights, gaming elements such as points and levels, and social elements like support, collaboration, or competition to generate significantly positive results in a workplace physical activity program. But when the study, called STEP UP, turned off the gaming elements, participants in the competition arm were the only ones who sustained higher levels of physical activity. Results were published today in JAMA Internal Medicine.

"Gamification and wearable devices are used commonly in workplace wellness programs and by digital health applications, but there is an opportunity to improve their impact on health behaviors by better incorporating behavioral insights and social incentives," said Mitesh Patel, MD, MBA, the director of Penn Medicine's Nudge Unit and an assistant professor of Medicine and Health Care Management. "We found that a behaviorally designed gamification program led to significant increases in physical activity compared to a control group that used wearable devices alone. During the nine-month trial, the average person in the competition arm walked about 100 miles more than the average person in control."

For six months, roughly 600 Deloitte employees from 40 U.S. states took part in a physical activity program. Each participant who was classified as obese or overweight, had daily, personalized step goals, with steps recorded via wearable devices that provided feedback to the participants. Four groups were formed: One in which participants only had their goals and the device, and three others with games tied to their goals.

The "gamified" groups could achieve points and different tiers, or "levels." Importantly, the games were designed to use principles from behavioral economics. This included having all participants sign a commitment contract, before beginning, pledging to strive for their daily goal, agreeing to have points allocated upfront lost -- instead of gained -- if goals were not met, and having a "fresh start" each week with a new set of points. Additionally, there were five levels to the game. Each participant started at the middle, which allowed for progression or regression based on goal achievement. All of these elements were adapted from a previous clinical trial that tested a similar approach among families.

Each gamified group was built around a social element. The support group participants chose a "sponsor" who received a weekly notification of whether the step goals were reached and could provide encouragement or motivation.

The collaboration group was split into teams of three. Each day, a member was randomly selected to represent the team and, if they reached their goal on the prior day, the whole team kept its points.

The competition group was also split into clusters of three who received a weekly leaderboard email showing their individual rankings compared to each other.

During the six-month intervention, the gamification with competition group increased their physical activity by 920 steps per day more than control, a significant difference. Support and collaboration also lead to significant increases of 689 and 637 steps more per day than control, respectively. The real difference between the arms of the study was seen in the three months after the gamification was turned off. The competition arm was the only one of the three gamification arms that had a lasting impact on its members, with a 569 daily step increase compared to control. Both former collaboration and support employees averaged more steps than the control group, but neither were significant.

"Many wellness solutions and patient engagement applications are implemented without proper testing of whether or not they actually work," said Greg Szwartz, managing director and leader for the advanced analytics and predictive modeling group in life science with Deloitte Consulting LLP. "We partnered with the Penn Medicine Nudge Unit to conduct a rigorous clinical trial that would provide evidence on the most effective approach overall and how to tailor future interventions for each individual."

Key to the next steps of this research will be the data that they collected from each participant on a wide range of characteristics including demographics, personality type, and social networks.

"Most interventions are designed as one-size-fits-all, in which a single intervention is deployed to a large population," said Patel. "Even if the program works on average, many participants may not benefit. Our next step will be to use data from this trial to develop behavioral profiles that could be used in the future to match the right intervention to the right person."

HIV infection significantly increases the risk of atrial fibrillation (AF) -- one of the most important causes of irregular heartbeats and a leading cause of stroke -- at the same rate or higher than known risk factors such as hypertension and diabetes, according to a study by researchers at UC San Francisco.

In a database review of nearly 17.3 million Californians, the researchers found that HIV infection was associated with an 80 percent higher risk of AF vs. 89 percent for hypertension and 22 percent for diabetes. Findings appear Sept. 9, 2019, in the Journal of the American College of Cardiology (JACC).

"This is the first paper demonstrating that HIV is a risk factor for AF, and the potency of that risk is similar to other well-established AF risk factors," said senior author Gregory Marcus, MD, MAS, a UCSF Health cardiologist and associate chief of cardiology for research in the UCSF Division of Cardiology. "Because AF can be asymptomatic and stroke may be the first manifestation, it's important for caregivers to be aware of patients at heightened risk."

With effective antiretroviral therapy, the life expectancy of HIV-positive patients has increased. However, previous studies have shown that these patients are at increased risk of cardiovascular diseases and sudden cardiac death, at least in part due to antiretroviral therapy. This is the first study to link HIV to irregular heartbeat, as well.

Atrial fibrillation affects an estimated 2.2 million Americans, according to the National Stroke Association, and about 15 percent of people who have strokes have AF. The stroke association estimates that up to 80 percent of strokes among people with AF can be prevented.

In the JACC study, Marcus and his colleagues utilized the Healthcare Cost and Utilization Project database to identify 17,293,971 California residents at least 21 years old (18,242 with HIV) who received care in an outpatient surgery unit, inpatient hospital unit or emergency department from January 2005 to December 2011.

Over an average follow up of 4.7 years, the data reflected 625,167 new AF diagnoses, with 1,076 in HIV-positive patients. After adjusting for demographics, number of clinical visits and cardiovascular comorbidities, the researchers found that HIV-positive patients had an incidence of 18.2 AF diagnoses per thousand person-years, compared to 8.9 in patients without HIV.

The association between HIV and AF risk was significantly higher in younger patients, African Americans and Hispanics, and those without hypertension, diabetes or alcohol abuse. The increased risk in African Americans was interesting, Marcus said, as previous studies have shown that whites are at significantly higher risk of AF.

"Physicians caring for HIV-infected patients should be aware of this strong relationship," said Marcus, who also holds the Endowed Professorship of AF research in the UCSF School of Medicine. "Increased awareness may help in recognizing the diagnosis and consequently result in more frequent prescription of appropriate therapies, such as anticoagulation, to reduce morbidity and mortality."

Microbial infection in HIV-positive patients also may influence AF risk. Future research should determine if antiretroviral therapies are an effective treatment, Marcus said.

One in four adults over age 40 is at risk for AF, with a projection of nearly 6 million people in the nation having the condition by 2050.

Nearly all premature babies receive antibiotics in their first weeks of life to ward off or treat potentially deadly bacterial infections. Such drugs are lifesavers, but they also cause long-lasting collateral damage to the developing microbial communities in the babies' intestinal tracts, according to research from Washington University School of Medicine in St. Louis.

A year and a half after babies leave the neonatal intensive care unit (NICU), the consequences of early antibiotic exposure remain, the study showed. Compared to healthy full-term babies in the study who had not received antibiotics, preemies' microbiomes contained more bacteria associated with disease, fewer species linked to good health, and more bacteria with the ability to withstand antibiotics.

The findings, published Sept. 9 in Nature Microbiology, suggest that antibiotic use in preemies should be carefully tailored to minimize disruptions to the gut microbiome - and that doing so might reduce the risk of health problems later in life.

"The type of microbes most likely to survive antibiotic treatment are not the ones we typically associate with a healthy gut," said senior author Gautam Dantas, PhD, a professor of pathology and immunology, of molecular microbiology, and of biomedical engineering. "The makeup of your gut microbiome is pretty much set by age 3, and then it stays pretty stable. So if unhealthy microbes get a foothold early in life, they could stick around for a very long time. One or two rounds of antibiotics in the first couple weeks of life might still matter when you're 40."

Healthy gut microbiomes have been linked to reduced risk of a variety of immune and metabolic disorders, including inflammatory bowel disease, allergies, obesity and diabetes. Researchers already knew that antibiotics disrupt the intestinal microbial community in children and adults in ways that can be harmful. What they didn't know was how long the disruptions last.

To find out whether preemies' microbiomes recover over time, Dantas and colleagues - including first author Andrew Gasparrini, PhD, who was a graduate student at the time the study was conducted, and co-authors Phillip I. Tarr, MD, the Melvin E. Carnahan Professor of Pediatrics, and Barbara Warner, MD, director of the Division of Newborn Medicine - analyzed 437 fecal samples collected from 58 infants, ages birth to 21 months. Forty-one of the infants were born around 2 ½ months premature, and the remainder were born at full term.

All of the preemies had been treated with antibiotics in the NICU. Nine had received just one course, and the other 32 each had been given an average of eight courses and spent about half their time in the NICU on antibiotics. None of the full-term babies had received antibiotics.

The researchers discovered that preemies who had been heavily treated with antibiotics carried significantly more drug-resistant bacteria in their gut microbiomes at 21 months of age than preemies who had received just one course of antibiotics, or full-term infants who had not received antibiotics. The presence of drug-resistant bacteria did not necessarily cause any immediate problems for the babies because most gut bacteria are harmless - as long as they stay in the gut. But gut microbes sometimes escape the intestine and travel to the bloodstream, urinary tract or other parts of the body. When they do, drug resistance can make the resulting infections very difficult to treat.

Moreover, by culturing bacteria from fecal samples taken eight to 10 months apart, the researchers discovered that the drug-resistant strains present in older babies were the same ones that had established themselves early on.

"They weren't just similar bugs, they were the same bugs, as best we could tell," Dantas said. "We had cleared an opening for these early invaders with antibiotics, and once they got in, they were not going to let anybody push them out. And while we didn't show that these specific bugs had caused disease in our kids, these are exactly the kind of bacteria that cause urinary tract and bloodstream infections and other problems. So you have a situation where potentially pathogenic microbes are getting established early in life and sticking around."

Further studies showed that all of the babies developed diverse microbiomes by 21 months of age - a good sign since lack of microbial diversity is associated with immune and metabolic disorders in children and adults. But heavily treated preemies developed diverse microbiomes more slowly than lightly treated preemies and full-term infants. Further, the makeup of the gut microbial communities differed, with heavily treated premature infants having fewer healthy groups of bacteria such as Bifidobacteriaceae and more unhealthy kinds such as Proteobacteria.

The findings already have led Warner, who takes care of premature infants in the NICU at St. Louis Children's Hospital, and her fellow neonatalogists to scale down their use of antibiotics.

"We're no longer saying, 'Let's just start them on antibiotics because it's better to be safe than sorry,'" Warner said. "Now we know there's a risk of selecting for organisms that can persist and create health risks later in childhood and in life. So we're being much more judicious about initiating antibiotic use, and when we do start babies on antibiotics, we take them off as soon as the bacteria are cleared. We still have to use antibiotics - there's no question that they save lives - but we've been able to reduce antibiotic use significantly with no increase in adverse outcomes for the children."

Tiny extracts of a precious metal used widely in industry could play a vital role in new cancer therapies.

Researchers have found a way to dispatch minute fragments of palladium - a key component in motor manufacture, electronics and the oil industry - inside cancerous cells.

Scientists have long known that the metal, used in catalytic converters to detoxify exhaust, could be used to aid cancer treatment but, until now, have been unable to deliver it to affected areas.

A molecular shuttle system that targets specific cancer cells has been created by a team at the University of Edinburgh and the Universidad de Zaragoza in Spain.

The new method, which exploits palladium's ability to accelerate - or catalyse - chemical reactions, mimics the process some viruses use to cross cell membranes and spread infection.

The team has used bubble-like pouches that resemble the biological carriers known as exosomes, which can transport essential proteins and genetic material between cells. These exosomes exit and enter cells, dump their content, and influence how the cells behave.

This targeted transport system, which is also exploited by some viruses to spread infection to other cells and tissues, inspired the team to investigate their use as shuttles of therapeutics.

The researchers have now shown that this complex communication network can be hijacked. The team created exosomes derived from lung cancer cells and cells associated with glioma - a tumour that occurs in the brain and spinal cord - and loaded them with palladium catalysts.

These artificial exosomes act as Trojan horses, taking the catalysts - which work in tandem with an existing cancer drug- straight to primary tumours and metastatic cells.

Having proved the concept in laboratory tests, the researchers have now been granted a patent that gives them exclusive rights to trial palladium-based therapies in medicine.

The study was funded by the Engineering and Physical Sciences Research Council and the European Research Council. It has been published in the journal, Nature Catalysis.

Professor Asier Unciti-Broceta, from the University of Edinburgh's CRUK Edinburgh Centre, said: "We have tricked exosomes naturally released by cancer cells into taking up a metal that will activate chemotherapy drugs just inside the cancer cells, which could leave healthy cells untouched."

Professor Jesús Santamaría, of the Universidad de Zaragoza, said: "This has the potential to be a very exciting technology. It could allow us to target the main tumour and metastatic cells, thus reducing the side effects of chemotherapy without compromising the treatment."

Many people struggle to keep their weight in check as they get older. Now new research at Karolinska Institutet in Sweden has uncovered why that is: Lipid turnover in the fat tissue decreases during ageing and makes it easier to gain weight, even if we don't eat more or exercise less than before. The study is published in the journal Nature Medicine.

The scientists studied the fat cells in 54 men and women over an average period of 13 years. In that time, all subjects, regardless of whether they gained or lost weight, showed decreases in lipid turnover in the fat tissue, that is the rate at which lipid (or fat) in the fat cells is removed and stored. Those who didn't compensate for that by eating less calories gained weight by an average of 20 percent, according to the study which was done in collaboration with researchers at Uppsala University in Sweden and University of Lyon in France.

The researchers also examined lipid turnover in 41 women who underwent bariatric surgery and how the lipid turnover rate affected their ability to keep the weight off four to seven years after surgery. The result showed that only those who had a low rate before the surgery managed to increase their lipid turnover and maintain their weight loss. The researchers believe these people may have had more room to increase their lipid turnover than those who already had a high-level pre-surgery.

"The results indicate for the first time that processes in our fat tissue regulate changes in body weight during ageing in a way that is independent of other factors," says Peter Arner, professor at the Department of Medicine in Huddinge at Karolinska Institutet and one of the study's main authors. "This could open up new ways to treat obesity."

Prior studies have shown that one way to speed up the lipid turnover in the fat tissue is to exercise more. This new research supports that notion and further indicates that the long-term result of weight-loss surgery would improve if combined with increased physical activity.

"Obesity and obesity-related diseases have become a global problem," says Kirsty Spalding, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and another of the study's main authors. "Understanding lipid dynamics and what regulates the size of the fat mass in humans has never been more relevant."

AUSTRALIA, Sydney - September 10, 2019 - We've all heard that 'food is good for your mood'. Now a new study into mental health and nutrient supplementation has taken a leap forward by establishing the gold standard for which nutrients are proven to assist in the management of a range of mental health disorders.

As well as an established relationship between poor diet and mental illness, there is now a vast body of research examining the benefit of nutrient supplementation in people with mental disorders.

To unpack this research, an international team of scientists led by Sydney's NICM Health Research Institute, Western Sydney University examined the 'best of the best' available evidence. The aim was to provide a clear overview of the benefit of specific nutrient supplements - including dosage, target symptoms, safety and tolerability - across different mental disorders.

The world's largest review (a meta-synthesis) of top-tier evidence, published online today in World Psychiatry, examined 33 meta-analyses of randomised control trials (RCTs) and data from 10,951 people with mental health disorders including depression, stress and anxiety disorders, bipolar disorder, personality disorders, schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

Although the majority of nutritional supplements assessed did not significantly improve mental health, the researchers found strong evidence that certain supplements are an effective additional treatment for some mental disorders, supportive of conventional treatment.

All nutrient supplements were found to be safe when recommended dosages and prescriptive instructions were adhered to and there was no evidence of serious adverse effects or contraindications with psychiatric medications.

Summary of results:

The strongest evidence was found for omega-3 supplements (a polyunsaturated fatty acid) as an add-on treatment for major depression - reducing symptoms of depression beyond the effects of antidepressants alone.

There was some evidence to suggest that omega-3 supplements may also have small benefits for ADHD.

There was emerging evidence for the amino acid N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia.

Special types of folate supplements may be effective as add-on treatments for major depression and schizophrenia, however folic acid was ineffective.

There was no strong evidence for omega-3 for schizophrenia or other mental health conditions.

There is currently a lack of compelling evidence supporting the use of vitamins (such as E, C, or D) and minerals (zinc and magnesium) for any mental disorder.

Lead author of the study, Dr Joseph Firth, Senior Research Fellow at NICM Health Research Institute, Western Sydney University and Honorary Research Fellow at The University of Manchester said the findings should be used to produce more evidence-based guidance on the usage of nutrient-based treatments for various mental health conditions.

"While there has been a longstanding interest in the use of nutrient supplements in the treatment of mental illness, the topic is often quite polarising, and surrounded by either over-hyped claims or undue cynicism," Dr Firth said.

"In this most recent research, we have brought together the data from dozens and dozens of clinical trials conducted all over the world, in over 10,000 individuals treated for mental illness.

"This mass of data has allowed us to investigate the benefits and safety of various different nutrients for mental health conditions - on a larger scale than what has ever been possible before."

Senior author on the study, NICM Health Research Institute's Professor Jerome Sarris said as the role of nutrition in mental health is becoming increasingly acknowledged, it was vital that an evidence-based approach be adopted.

"Future research should aim to determine which individuals might benefit most from evidence-based supplements and to better understand the underlying mechanisms so we can adopt a targeted approach to supplement use in mental health treatment." Professor Sarris said.

"The role of the gut microbiome in mental health is a rapidly emerging field of research, however more research is needed into the role of 'psychobiotics' in mental health treatment."

For children fearful of undergoing MRI scans, an inexpensive everyday item used as a marker, such as a jelly baby lolly or a plastic, fish-shaped soy sauce container, might make the process a little less intimidating.

And thanks to a QUT study, these and other relatively cheap, common items have been shown to be visible, effective MRI markers, when placed on a patient's skin, to pinpoint specific anatomical areas or pathologies being scanned.

The study findings have been published in the British Medical Journal's BMJ Open.

Senior Research Fellow Dr Paige Little, from the QUT Biomechanics and Spine Research Group, said MRI uses strong magnetic fields to generate images of organs, bone and tissue inside the body and the loud noises made by the equipment adds to the challenges radiographers face to perform MRI scans successfully on children.

She said the impetus for looking at alternatives to commercial markers was the group's collaborative sleep postures research project.

"Single-use commercial markers cost between $6 and $10 each, and for our sleep posture study we had 50 participants, and we needed 50 markers for each participant, which made the cost prohibitive," Dr Little said.

"We needed to find a marker that was small, inexpensive and easily sourced, which showed up clearly on MRI and was easily distinguishable from bone and soft tissue.

"While makeshift markers of various types, including fish oil capsules, have been anecdotally trialled in clinical radiology departments over the years, we couldn't find a study in the scientific literature, so we did our own trial.

"We tested 17 items, including different lollies, a coffee bean, vitamin tablets and capsules, and the capped fish-shaped soy sauce containers that you can get when you buy sushi."

Dr Little said all the alternative markers, plus a commercial product for comparison, were tested on the thigh of a member of the research team, and scanned at Mater Medical Imaging using the five most commonly ordered MRI sequences.

"The visibility of some of the items, like the coffee bean, was poor, but overall we found the vitamin D capsule proved to be the best substitute for a commercial marker for all tests, and particularly good for smaller areas of the body like fingers and toes," Dr Little said.

"The jelly baby lolly, fish-shaped sauce container, and the fish oil capsule were also viable alternatives for some, although not all, of the MRI sequences.

"Our conclusion was that depending on the reason for imaging and the sequence selected, these four items were cheap and reliable alternatives to a commercial marker.

"Single-use markers are a significant component of an imaging department's costs, and also for researchers, so we thought this study was a practical examination of viable alternatives.

"And if using something familiar would help make the imaging process less frightening for children, particularly those children who have experienced many medical procedures, then that is a terrific bonus."

Dr Little said while the study didn't test at what point a vitamin capsule or sauce container might rupture and spill its contents, the research group has since used vitamin D capsules routinely in spinal studies, and in its Sealy of Australia-supported 'Science of Sleep' postures project, requiring multiple markers under body weight throughout extended MRI scanning sessions, and none had ruptured or degraded.

How is the retina formed? And how do neurons differentiate to become individual components of the visual system? By focusing on the early stages of this complex process, researchers at the University of Geneva (UNIGE), Switzerland, in collaboration with the École Polytechnique Fédérale de Lausanne (EPFL), have identified the genetic programmes governing the birth of different types of retinal cells and their capacity to wire to the correct part of the brain, where they transmit visual information. In addition, the discovery of several genes regulating nerve growth allows for the possibility of a boost to optic nerve regeneration in the event of neurodegenerative disease. These results can be discovered in the journal Development.

The visual system of mammals is composed of different types of neurons, each of which must find its place in the brain to enable it to transform stimuli received by the eye into images. There are photoreceptors, which detect light, optic nerve neurons, which send information to the brain, cortical neurons, which form images, or interneurons, which make connections between other cells. Though not yet differentiated in the early stages of embryonic development, these neurons are all produced by progenitor cells that, are capable of giving rise to different categories of specialized neurons. To better understand the exact course of this mechanism and identify the genes at work during retinal construction, researchers studied the dynamics of gene expression in individual cells. "To monitor gene activity in cells and understand the early specification of retinal neurons, we sequenced more than 6,000 cells during retinal development and conducted large-scale bioinformatic analyses," explains Quentin Lo Giudice, PhD student in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine and first author of this article.

Mapping a system under construction

In collaboration with Gioele La Manno and Marion Leleu of EPFL, the researchers studied progenitor's behaviour during the cell cycle as well as during their progressive differentiation. The scientists then mapped very accurately the different cell types of the developing retina and the genetic changes that occur during the early stages of this process. "Beyond their "age"--that is, when they were generated during their embryonic life--the diversity of neurons stems from their position in the retina, which predestines them for a specific target in the brain," explains Pierre Fabre, senior researcher in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine, who directed this work. "In addition, by predicting the sequential activation of neural genes, we were able to reconstruct several differentiation programs, similar to lineage trees, showing us how the progenitors progress to one cell type or another after their last division."

The researchers also conducted a second analysis. If the right eye mainly connects essentially to the left side of the brain, and vice versa, a small fraction of neurons in the right eye make connections in the right side of the brain. Indeed, all species with two eyes with overlapping visual fields, such as mammals, must be able to mix information from both eyes in the same part of the brain. This convergence makes it possible to see binocularly and perceive depths or distances. "Knowing this phenomenon, we have genetically and individually "tagged" the cells in order to follow each of them as they progress to their final place in the visual system," says Quentin Lo Giudice. By comparing the genetic diversity of these two neural populations, researchers discovered 24 genes that could play a key role in three-dimensional vision. "The identification of these gene expression patterns may represent a new molecular code orchestrating retinal wiring to the brain," adds Dr. Fabre.

Towards regenerative medicine

Even before the neurons reach the brain, they must leave the retina through the optic nerve. The last part of this study identified the molecules that guide neurons on the right path. Moreover, these same molecules also allow the initial growth of axons, the part of neurons that transmits electrical signals to the synapses and thus ensures the passage of information from one neuron to another, as well as about twenty genes that control this process. This discovery is a fundamental step forward for regenerative medicine.

The more we know about the molecules needed to appropriately guide axons, the more likely we are to develop a therapy to treat nerves trauma. "If the optic nerve is cut or damaged, for example by glaucoma, we could imagine reactivating those genes that are usually only active during the embryonic development phase. By stimulating axon growth, we could allow neurons to stay connected and survive," explains Dr. Fabre, who plans to launch a research project on this theme. Although the regeneration capacities of neurons are very low, they do exist and techniques to encourage their development must be found. Genetic stimulation of the damaged spinal cord after an accident is based on the same idea and is beginning to show its first successes.

In the field of computer engineering, magnetically switchable materials play a significant role in data storage. A team from the Cluster of Excellence Ruhr Explores Solvation at Ruhr-Universität Bochum (RUB) has developed and manufactured a novel molecule called 3-methoxy-9-fluorenylidene. What's special about it: its magnetic properties can be controlled through light of different colours. This might be of use for computer industry.

The researchers working with Professor Wolfram Sander at the Chair of Organic Chemistry II outline their findings in the journal "Angewandte Chemie" on 14 August 2019.

Broad application range of magnetic materials

Magnetism is indispensable in computer engineering. Magnetism controls, for example, the information flow from the computer to magnetic storage media such as hard disks. Moreover, magnetic storage devices use read/write heads in the form of magnets that identify (i.e. read), or alter (i.e. write) the magnetisation patterns on the hard disk.

Methoxy group controls magnetic properties

Developed by Wolfram Sander and his team, the organic molecule 3-methoxy-9-fluorenylidene is based on a fluorine scaffold with a methoxy group attached in the shape of a rotational tail.

The researchers have figured out that the molecule's magnetic properties are determined by the orientation of the methoxy group, which changes its conformation depending on the kind of light that hits it.

Blue light switches the methoxy group into the "up" conformation forming the diamagnetic and less reactive singlet state. Whereas green light rotates the methoxy group down at the molecule, which results in the paramagnetic triplet state that has a higher reactivity against molecular hydrogen.

Interesting for research and industry

Because of its properties, 3-methoxy-9-fluorenylidene is of great interest to research. "Using this group of atoms, we can study the spin dependence of reactions. It could also play a role in the development of novel switchable magnetic materials and chemical sensors," predicts Sander.

Compared with traditional ferromagnetic materials, 3-methoxy-9-fluorenylidene offers considerable advantages: magnetism can be switched on and off through visible light. Moreover, organic magnets are not brittle like conventional magnets, but flexible and can be processed like plastics.

The snag

However, the molecule does have one drawback: it is stable only at extremely low temperatures. "This is why we are researching into magnetically switchable materials that can be used under ambient conditions," says Wolfram Sander.

Several fungal species from the order Trichosporonales are of interest for industrial applications because they might be used for the production of biofuels. However, to explore their biotechnological potential it is necessary to learn more about their biology. An team of researchers led by Associate Professor Minou Nowrousian from the Department of Molecular and Cellular Botany of the Ruhr-University Bochum (RUB) has now analyzed 24 genomes of Trichosporonales fungi with a focus on genes that are important for sexual development. The study was performed in collaboration with the laboratory of Prof. Dr. Joseph Heitman from Duke University, USA, who has an ongoing collaboration with the RUB and has been a visiting professor with the RUB Research School

The researchers published their results in the journal "Plos Genetics" on 6 September 2019.

The genes that regulate sexual development in fungi are called mating type genes. They must differ between mating partners to allow successful cell fusion. In fungi of the basidiomycetes, which comprise the Trichosporonales, but also well-known mushrooms like the button mushroom, the mating type genes are often located at two different positions within the genome, which are called mating type loci. However, there are species with fused mating type loci, where both loci are physically linked on the same chromosome. The chromosomes that contain the mating type loci often have functions similar to sex chromosomes in animals and plants.

Discovery of novel features

The team from Germany and the USA has analyzed the mating type genes in 24 species of the order Trichosporonales, and discovered physically linked mating type loci with previously unknown features.

The results showed that all analyzed Trichosporonales species have fused mating type loci with properties that are different than the properties of previously analyzed fused mating type loci in other basidiomycetes. Both the order of the genes within the fused loci as well as the sequences of the genes are highly conserved, in contrast to fused mating type loci in other basidiomycetes. This is unusual, because mating type as well as sex chromosomes tend to degenerate during evolution. The mechanisms that stabilize the Trichosporonales mating type loci will be analyzed in future studies.

Is there a lottery ticket that always wins? So goes the popular version of a theoretical conundrum posed in 1969 by English mathematician Adrian R.D. Mathias within the field of set theory, an area dealing with infinity in mathematics.

The problem remained a mystery throughout the 70's, 80's and 90's, as set theorists the world over tried their best to solve it. Associate Professor Asger Dag Törnquist of the University of Copenhagen's Department of Mathematics was introduced to the problem in 2002 while completing his doctoral dissertation at the University of California, Los Angeles (UCLA).

"Research in the area had gone dormant from the 1990's on because no one was making any progress towards a solution. I was fascinated because it was an old problem that dealt with our understanding of infinity in mathematics. Even then, it became a dream of mine to solve the mystery, even though I had no idea of how to accomplish what had been elusive for others over decades," he says.

MAD families

Mathias researched order and structure, things that occur spontaneously in sufficiently large mathematical systems. Today, this is known as Ramsey Theory, named after British mathematician and philosopher Frank Ramsey. Mathias' research pointed out that there was a profound correlation between Ramsey Theory and what he called MAD families, but he was unable to prove the existence of such a relationship.

"A MAD family is can be thought of as a kind of lottery ticket that always wins in a peculiar, infinite lottery game. In this game, lottery tickets have an infinite number of rows of whole numbers, and each row itself has infinitely many numbers. And, a ticket may have so many rows that they simply cannot be numbered," says Törnquist.

What Mathias asked the math world was, if the order and structure that we know is there, as per Ramsey Theory results, prevent the existence of a MAD family, i.e., a ticket that always wins.

The 'baby-mystery' proved decisive

Asger Dag Törnquist's shouldered his dream of solving Mathias' question for several years abroad until he began working at the University of Copenhagen's Department of Mathematical Sciences in 2011. This marked the beginning of a period during which Törnquist and David Schrittesser, his Austrian postdoctoral researcher, would gradually approach the solution.

"In 2014, I decided to rethink the problem from scratch and found a whole new way of tackling it. Alongside the original mystery, Mathias had formulated a sort of baby-version of the mystery. Neither had been solved. I managed to solve the baby version of mystery, which I then wrote an article about," explains Törnquist.

As a result, a great many mathematicians from around the world reacted. The article suddenly reignited research in the area. Researchers in other parts of the world began to build upon the UCPH researchers' article and more and more pieces of the puzzle began falling into place.

"We were in the midst of writing an article meant to address yet another small piece of the puzzle, when we realized that we may have been closer to solving the entire riddle than we had believed. From then on, things moved quickly. A few weeks later, we had the solution," recounts the mathematician.

Solution: An ever-winning lottery ticket does not exist

After five years of work, Asger Dag Törnquist and David Schrittesser had their research article on Adrian Mathias' "lottery ticket" accepted to the prestigious American scientific journal, The Proceedings of the National Academy of Sciences (PNAS). The two researchers discovered that complete coincidence does not exist.

"We found out that lottery ticket numbers clump up in such a way that there is no certainty of a winner, which was what Mathias had guessed would happen, but had been unable to prove. This confirms that one cannot assemble such a type of a lottery ticket without the emergence of certain patterns and regularities in ticket numbers. As such, there is no lottery ticket that always wins Mathias' lottery game," concludes Asger Dag Törnquist.

Some of these changes are long-lasting and can be detected even days after neuronal activation, as a form of genomic memory of the past neuronal activation.

The research, conducted in rodents and published in Nature Neuroscience, shows new molecular mechanisms that contribute to the plasticity of the adult brain. The changes initiated by neuronal activation are more complex and act at more levels than previously thought.

These findings, carried out by an international team led by researchers from the Instituto de Neurosciencias, UMH-CSIC in Alicante, with the participation of researchers from Emory University in Atlanta, describe for the first time the changes in the organization of genetic material in hippocampal excitatory neurons from adult mice upon activation.

"We wanted to know how the activation of a neuron can changes its future response; those changes constitute a form of cellular memory essential for the formation of memories," explains Dr. Ángel Barco, a researcher at the UMH-CSIC Neurosciences Institute that has led the research. "To achieve this goal we have used several techniques in neurogenomic that are applied for the first time in an intact mouse brain," says Dr. Barco.

The researchers wanted to know specifically what happens in a neuron that activates when the animal is exposed to a new context. "This response is important for memory formation, but it is very difficult to address experimentally. The group of neurons that respond to an experience like this is very small group of diffusely distributed through the brain, therefore it is very difficult to isolate them and see what happens inside", adds Dr. Barco.

To simplify, researchers have taken a shortcut. They have caused massive activation of mouse neurons, as in an epileptic process, and have looked at the changes taking place in chromatin.

Chromatin is a highly compacted structure in which almost two meters of genetic material (DNA) is stored in the tiny nuclei of cells thanks to the action of special proteins called histones. To get an idea of the degree of chromatin compaction, about one hundred thousand cell nuclei fit on the head of a pin.

"The advantage of the epilepsy model is that we have a lot of starting material to perform the analysis. It is easy to have 10 million cells. If we want to go to the most complicated memory model, only scalable techniques that require little starting material will work, because in this case the network of neurons is formed by about 2,000 cells" says prof. Barco.

"With what we learned in the simulation of epilepsy, we have been able to confirm these changes in a more physiological situation, such as the activation of groups of neurons that take place in the brain of a mouse when exploring a new place," he adds.

The researchers saw that in both cases a transcriptional "burst" occurs. That is, a very strong activation of specific genes to produce proteins. Transcription is the first step of gene expression. It leads to the formation of proteins, which are the molecules that direct almost all vital processes.

In turn, the transcription of the genetic material depends on the changes that take place in the chromatin. The degree of compaction of that chromatin and the interactions between separate regions of the chromatin contribute decisively to regulate transcription and therefore gene expression.

This study, published in Nature Neuroscience, demonstrates that this activation is associated with an increase in accessibility and the appearance of new interactions between separate regions of chromatin, necessary to allow the activation of genes. "The dynamic and large-scale adjustments of the genome topology observed in our study probably contribute to the rapid and coordinated transcriptional response associated with neuronal activation in both normal and pathological conditions," explains Jordi Fernández-Albert, the first author of the study.

These changes - called epigenetic because they do not affect the information contained in the genetic material but their expression - can permanently modify the expression and future response capacity of the genes involved in cognition, thus representing a type of genomic memory.

These epigenetic fingerprints in the chromatin could represent an appropriate substrate for lasting changes in behavior. They could participate in the establishment of memories by influencing the future response of neurons to the same stimuli that caused the change or to different ones. In addition, some of these lasting changes could be related to brain disorders such as epilepsy and cognitive dysfunction.

New research from North Carolina State University finds that being convicted of a crime is associated with a decline in one's physical health, even if the conviction doesn't lead to jail time. The study also confirms previous work finding that being arrested is associated with adverse mental health outcomes, even if an individual isn't ultimately charged with a crime.

"Many people often think of low-level interactions with the justice system as being inconsequential," says April Fernandes, author of a paper on the work and an assistant professor of sociology at NC State. "For example, if someone is arrested and released, it's seen as 'no harm, no foul.'

"We're learning that there can be significant mental health effects from low-level contacts. And there can be significant physical health effects even when convictions are associated with probation or fines, rather than jail time."

For this study, Fernandes looked at data from a nationally representative sample of about 9,000 young people who participated in the National Longitudinal Survey of Youth 1997, focusing specifically on data submitted between 1999 and 2010. The study participants were between the ages of 18 and 32.

Specifically, Fernandes evaluated self-reported physical and mental health assessments to determine whether there was a change in reported health status associated with justice system contact. Fernandes looked at four types of contact for study participants: being arrested; being charged; being convicted; and being sentenced to jail time.

"People reported increases in depression and stress across the continuum of contact, from arrest to jail time," Fernandes says. "That's consistent with previous work.

"And we knew that jail time affects physical health, for a host of reasons. But the fact that convictions were associated with physical health effects is particularly interesting. It would be worth exploring what drives those outcomes in greater detail."

Scientists have found that brain networks develop differently in males and females at puberty, with boys showing an increase in connectivity in certain brain areas, and girls showing a decrease in connectivity as puberty progresses. These analyses were focused on brain regions previously identified as conferring risk for mood problems in adolescents, suggesting an association, although this needs to be tested. This work is presented at the ECNP Congress in Copenhagen, and is based on a recent peer-reviewed publication.

According to lead researcher, Dr Monique Ernst (National Institute of Mental Health / NIH, Bethesda, Maryland, USA), "In our study, we showed that certain brain regions develop differently in boys and girls at puberty. Functional connectivity increases in boys and decreases in girls over puberty. Our next set of studies will aim to clarify the significance of these communication changes in the maturing brain, and to identify if the changes are protective or if they increase vulnerability."

"We looked at these brain areas because they had previously been identified as conferring risk for mood problems in adolescents. We know that mood upsets, particularly anxiety and depression, occur disproportionately in girls, and that women are twice likely as men to suffer from depression following the trend emerging during puberty. We found that the puberty period is associated with significant brain changes in these mood-related brain areas; however, we need to be cautious in interpreting these changes; we need to verify that the association we see between these brain changes and the coincident mood changes are linked. This work is underway."

The researchers analysed brain scans of 147 girls and 157 boys, aged between 13 and 15, from centres in Dublin, London, Dresden, Mannheim, and Paris.They were at varying puberty stages, from having not started their puberty to being fully mature. The researchers took images of the brain activity while the adolescent volunteers were lying still in an MRI scanner. These images were corrected for age and then were analyzed in a way that measures how strongly brain regions communicate with one another (known as "functional connectivity"). The values of the functional connectivity of these regions were correlated with the level of maturity at puberty.

Monique Ernst continued, "This is a first, because in the past, brain scans of adolescents have mostly been measured against a relatively wide chronological age, whereas, here, we were able to measure brain changes directly against their puberty status. We found that for an equivalent change in puberty status, the functional connectivity in these specific brain areas increased in boys by an average of around 6.5%, but decreased in girls by an average of around 7.2% (both these results were statistically significant). Specifically, these brain areas are within the medial prefrontal cortex and the parietal cortex.

Collectively these findings indicate that there are opposite changes of brain activity in boys and in girls as they go through puberty, and this male/female developmental pattern can be a key factor in in the role of pubertal development in the emergence of mood disorders. The next critical next step is to examine the role of these brain connectivities in the development of depression as these adolescents get older, using a longitudinal design."

Commenting, Dr Jaanus Harro (Division of Neuropsychopharmacology, Department of Psychology, University of Tartu and Psychiatry Clinic, North Estonia Medical Centre, Tallinn), said:

"This is particularly interesting in terms of demonstrating connectivity differences between boys and girls. While depression is more prevalent in females it still does occur in males too frequently, while the formal diagnostic criteria are identical. However, the neural pathways to depression in males and females might be partly different, as increasing number of gene-environment interaction studies has shown different interactions in boys and girls, on occasion quite opposite to one other. This imaging study offers a potential brain correlate to these distinct interactions, and it is quite plausible that they might arise during adolescence."

Dr Harro was not involved in this work; this is an independent comment.