Culture

Winter weather patterns in North America are dictated by changes to the polar vortex winds high in the atmosphere, but the most significant cold snaps are more likely influenced by the tropics, scientists have found.

A team led by the University of Reading conducted the first ever study to identify how the four main winter weather patterns in North America behave depending on the strength of the stratospheric polar vortex. This is a ribbon of wind and low pressure that circles the Arctic at heights of 10-50km, trapping cold air inside.

It is already well established that the vortex wind strength influences weather in Europe and Asia, and the study revealed it also has a strong effect on three out of the four main winter weather patterns in North America, giving forecasters an additional tool to understand potentially high-impact weather during winter.

The study, published in Geophysical Research Letters, also revealed that, unlike in Europe, the most extreme cold snaps affecting the whole of North America are not most likely to occur after a weak vortex. Instead, the shape of the vortex and conditions in the tropics were identified as stronger influences of these conditions.

Simon Lee, atmospheric scientist at the University of Reading and lead author of the study, said: "Despite the most extreme cold snaps experienced in North America often being described as 'polar vortex outbreaks', our study suggests vortex strength should not be considered as a cause.

"We know that a weakened polar vortex allows cold air to flood out from the Arctic over Europe and Asia, but we found this is surprisingly not the case the other side of the Atlantic.

"In fact, our work suggests we should actually look south to conditions around the equator, rather than north to the Arctic, for the causes of these widespread freezing conditions in North America.

"Our results did reveal that the polar vortex strength provides useful information on the likelihood of most weather patterns over the US and Canada further in advance, including some potentially disruptive temperature changes or heavy rain. The more accurate information populations have about upcoming changes in weather, the better they can prepare."

One of the clearest suggested effects of a strong vortex was a 10-15% likelihood of extremely cold conditions in western parts of North America, including Alaska, but milder conditions in central and eastern parts of the US.

Another weather pattern found to most often follow neutral or strong vortex wind speeds brings temperatures 5°C above normal and wetter weather in the eastern US.

The exception in the results was that the weather pattern associated with the highest chance of the most widespread extreme cold in North America, in which average temperatures in the central US are more than 5°C below normal, was not found to have a strong dependence on a weaker vortex, as it does in Europe.

They found widespread extreme cold is more common when an area of high pressure extends up to Alaska, and the polar vortex stretches down towards North America - pushing cold Arctic air southward in the lower atmosphere.

The scientists say the influence of the stratosphere on weather patterns, as well as how this interacts with long-term weather patterns in the tropics like El Niño, should be studied further and incorporated into forecasts to improve their accuracy.

Recent evidence suggests a link between cholesterol metabolism and innate immunity. Upon viral infection, macrophages show reduced cholesterol synthesis accompanied by enhanced expression of antiviral genes, including type I interferon (IFN-I).

IFN-I can induce 25-hydroxycholesterol (25-HC) accumulation, which blocks viral entry. However, it has been unclear whether other cholesterol-associated metabolic products or enzymes regulate innate immunity.

A new study published in Immunity now provides important new information. WANG Hongyan's team from the Center for Excellence in Molecular and Cellular Science, Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences (CAS), in collaboration with Prof. WEI Bin at Shanghai University (the former PI of the Wuhan Institute of Virology of CAS), screened expression levels of multiple enzymes that regulate cholesterol metabolism to better understand how cholesterol metabolites combats infection.

In order to find the enzymes or corresponding natural cholesterol metabolites involved in antiviral infection, the researchers screened differentially expressed genes in liver tissue from patients infected with hepatitis B virus and from mice infected with vesicular stomatitis virus (VSV).

DHCR7 (7-dehydrocholesterol reductase) is an enzyme that converts 7-dehydrocholesterol (7-DHC) into cholesterol. Patients carrying Dhcr7 mutations have mental retardation. However, the role of DHCR7 in innate immunity has been unclear. This study shows that DHCR7 knock-out (KO) or DHCR7 inhibitor treatment can promote IRF3 activation and type I interferon (IFNβ) production to clear multiple viruses in vitro or in vivo.

Interestingly, Tamoxifen, a chemotherapy drug used to treat breast cancer, was approved by the U.S. Food and Drug Administration to inhibit DHCR7's enzyme activity.

This study also reveals that Tamoxifen treatment inhibits infection by VSV and the Zika virus at the cellular level, suggesting a possible application for Tamoxifen as an anti-infective. Mice treated with the DHCR7 inhibitor AY9944 showed a significant increase in serum 7-DHC concentration, which promotes IRF3 phosphorylation and enhances IFNβ production in macrophages, thus protecting mice against lethal doses of VSV or the H1N1 influenza virus.

In addition, the research shows that viral infection enhanced AKT3 expression and 7-DHC treatment further activated AKT3. AKT3 directly bound and phosphorylated IRF3 at Ser385, together with TBK1-induced phosphorylation of IRF3 Ser386, to achieve IRF3 dimerization and full activation.

In conclusion, this study reveals that both the intermediate cholesterol metabolite 7-DHC and DHCR7 inhibitors promote IFN-I production and an antiviral response by activating AKT3 and IRF3. These findings may aid in the development of new drugs to treat viral infections. The research also provides new insights on how cholesterol metabolism regulates innate immunity.

Plant seeds may strike the casual observer as unspectacular - but they have properties that are nothing short of superpowers. In a dry state they can store their energy for years and then suddenly release it for germination when environmental conditions are favourable. One striking example is the "super bloom" in the Death Valley National Park, when seeds that have endured the dry and hot desert for decades suddenly germinate at rainfall followed by a rare and spectacular desert bloom several months later. Seeds conserve a fully formed embryo, which only continues growing when conditions are right for it to do so. This may be the case only years - or in more extreme cases even centuries - later.

Seed germination is controlled by several plant hormones, which are researched intensely. However, not much was known about the processes that need to take place to allow the hormones to function. How is energy in the seed made available? How can energy metabolism be started early and efficiently? An international team of researchers has now been looking into these questions.

Using a new type of fluorescent biosensors, the researchers observed, in living seed cells, both energy metabolism and the so-called redox metabolism, which relies in sulphur. The researchers discovered that when the seeds came into contact with water, energy metabolism was established in a matter of minutes, and the plant cells' "power stations" - known as mitochondria - activated their respiration. The researchers also found out which molecular switches are activated to enable energy to be released efficiently - with the so-called thiol-redox switches playing a central role.

"By looking into the very early processes of germination control, we can gain a better understanding of the mechanisms driving seed germination," says Prof. Markus Schwarzländer from the University of Münster (Germany), who led the study. "In future we could think about how such switches could be used in crop biotechnology." The results of the study could be of relevance in farming, when seeds need to keep their germination vigour for as long as possible on the one hand, but should also germinate in synch and with minimal losses on the other hand. The study has been published in the journal PNAS (Proceedings of the National Academy of Sciences).

Background and method:

In order to be able to observe the activities taking place in the energy metabolism, the researchers visualized under the microscope adenosine triphosphate (ATP), the general currency for energy in the cell, and Nicotinamide adenine dinucleotide phosphate (NADPH), the electron energy, in the mitochondria. They compared seeds from thale cress: both dry seeds and seeds "imbibed" with water.

To find out whether the redox switches are important for kick-starting germination, the researchers deactivated specific proteins using genetic methods and then compared the reaction shown by the modified seeds with that of the unmodified ones. The researchers allowed the seeds to age artificially in the laboratory, and they saw that the seeds germinated much less actively if they lacked the relevant proteins.

The researchers' next step involved so-called redox proteome analysis, i.e. they examined the relevant redox proteins in their entirety with the use of biochemical methods. For this purpose, they isolated active mitochondria and flash-froze them in order to be able to study this state directly where the process was taking place. The researchers then used mass spectrometry methods to identify several so-called cysteine-peptides which are important for resource efficiency in energy metabolism.

"The process could be likened to the traffic control system of a large city. Before the rush hour - i.e. germination - starts, which puts large quantities of metabolites 'on the road', the traffic light and routing systems need to be switched on in the morning; and here this is done by the thiol redox switches," explains lead author Dr. Thomas Nietzel, who carried out most of the experiments as part of his PhD at the Institute of Crop Science and Resource Conservation at the University of Bonn and later as a postdoctoral researcher at the Institute of Biology and Biotechnology of Plants at the University of Münster.

Sperm are influenced by diet, and the effects arise rapidly. This is the conclusion of a study by researchers at Linköping University, in which healthy young men were fed a diet rich in sugar. The study, which has been published in PLOS Biology, gives new insight into the function of sperm, and may in the long term contribute to new diagnostic methods to measure sperm quality.

"We see that diet influences the motility of the sperm, and we can link the changes to specific molecules in them. Our study has revealed rapid effects that are noticeable after one to two weeks", says Anita Öst, senior lecturer in the Department of Clinical and Experimental Medicine at Linköping University, and head of the study.

Sperm quality can be harmed by several environmental and lifestyle factors, of which obesity and related diseases, such as type 2 diabetes, are well-known risk factors for poor sperm quality. The research group that carried out the new study is interested in epigenetic phenomena, which involve physical properties or levels of gene expression changing, even when the genetic material, the DNA sequence, is not changed. In certain cases such epigenetic changes can lead to properties being transferred from a parent to offspring via the sperm or the egg.

In a previous study, the scientists showed that male fruit flies which had consumed excess sugar shortly before mating more often produced offspring who became overweight. Similar studies on mice have suggested that small fragments of RNA known as tsRNA play a role in these epigenetic phenomena that appear in the next generation. These RNA fragments are present in unusually large amounts in the sperm of many species, including humans, fruit flies and mice. So far, their function has not been examined in detail. Scientists have speculated that the RNA fragments in sperm may be involved in epigenetic phenomena, but it is too early to say whether this is the case in humans. The new study was initiated by the researchers to investigate whether a high consumption of sugar affects the RNA fragments in human sperm.

The study examined 15 normal, non-smoking young men, who followed a diet in which they were given all food from the scientists for two weeks. The diet was based on the Nordic Nutrition Recommendations for healthy eating with one exception: during the second week the researchers added sugar, corresponding to around 3.5 litres of fizzy drinks, or 450 grammes of confectionery, every day. The sperm quality and other indicators of the participants' health were investigated at the start of the study, after the first week (during which they ate a healthy diet), and after the second week (when the participants had additionally consumed large amounts of sugar).

At the beginning of the study, one third of the participants had low sperm motility. Motility is one of several factors that influence sperm quality, and the fraction of people with low sperm motility in the study corresponded to that in the general population. The researchers were surprised to discover that the sperm motility of all participants became normal during the study.

"The study shows that sperm motility can be changed in a short period, and seems to be closely coupled to diet. This has important clinical implications. But we can't say whether it was the sugar that caused the effect, since it may be a component of the basic healthly diet that has a positive effect on the sperm", says Anita Öst.

The researchers also found that the small RNA fragments, which are linked to sperm motility, also changed. They are now planning to continue the work and investigate whether there is a link between male fertility and the RNA fragments in sperm. They will also determine whether the RNA code can be used for new diagnostic methods to measure sperm quality during in vitro fertilisation.

A new study of the ecology of an enigmatic group of novel unicellular organisms by scientists from Ludwig-Maximilians-Universitaet (LMU) in Munich supports the idea hydrogen played an important role in the evolution of Eukaryota, the first nucleated cells.

One of the most consequential developments in the history of biological evolution occurred approximately 2 billion years ago with the appearance of the first eukaryotes - unicellular organisms that contain a distinct nucleus. This first eukaryotic lineage would subsequently give rise to all higher organisms including plants and animals, but its origins remain obscure. Some years ago,
microbiologists analyzed DNA sequences from marine sediments, which shed new light on the problem. These sediments were recovered from a hydrothermal vent at a site known as Loki's Castle (named for the Norse god of fire) on the Mid-Atlantic Ridge in the Arctic Ocean. Sequencing of the DNA molecules they contained revealed that they were derived from a previously unknown group of microorganisms.

Although the cells from which the DNA originated could not be isolated and characterized directly, the sequence data showed them to be closely related to the Archaea. The researchers therefore named the new group Lokiarchaeota.

Archaea, together with the phylum Bacteria, are the oldest known lineages of single-celled organisms. Strikingly, the genomes of the Lokiarchaeota indicated that they might exhibit structural and biochemical features that are otherwise specific to eukaryotes. This suggests that the Lokiarchaeota might be related to the last common ancestor of eukaryotes. Indeed, phylogenomic
analysis of the Lokiarchaeota DNA from Loki's Castle strongly suggested that they were derived from descendants of one of the last common ancestors of Eukaryota and Archaea. Professor William Orsi of the Department of Earth and Environmental Sciences at LMU, in cooperation with scientists at Oldenburg University and the Max Planck Institute for Marine Microbiology, has now been able to examine the activity and metabolism of the Lokiarchaeota directly. The results support the suggested
relationship between Lokiarchaeota and eukaryotes, and provide hints as to the nature of the environment in which the first eukaryotes evolved. The new findings appear in the journal Nature Microbiology.

The most likely scenario for the emergence of eukaryotes is that they arose from a symbiosis in which the host was an archaeal cell and the symbiont was a bacterium. According to this theory, the bacterial symbiont subsequently gave rise to the mitochondria - the intracellular organelles that are responsible for energy production in eukaryotic cells. One hypothesis proposes that the archaeal host was dependent on hydrogen for its metabolism, and that the precursor of the mitochondria
produced it. This "hydrogen hypothesis" posits that the two partner cells presumably lived in an anoxic environment that was rich in hydrogen, and if they were separated from the hydrogen source they would have become more dependent on one another for survival potentially leading to an endosymbiotic event. "If the Lokiarchaeota, as the descendants of this putative ur-archaeon, are also dependent on hydrogen, this would support the hydrogen hypothesis," says Orsi. "However, up to now, the ecology of these Archaea in their natural habitat was a matter of speculation."

Orsi and his team have now, for the first time, characterized the cellular metabolism of Lokiarchaeota recovered from sediment cores obtained from the seabottom in an extensive oxygen-depleted region off the coast of Namibia. They did so by analyzing the RNA present in these samples. RNA molecules are copied from the genomic DNA, and serve as blueprints for the synthesis of proteins. Their sequences therefore reflect patterns and levels of gene activity. The sequence analyses revealed that Lokiarchaeota in these samples outnumbered bacteria by 100- to 1000-fold. "That strongly indicates that these sediments are a favorable habitat for them, promoting their activity," says Orsi.

He and his colleagues were able to establish enrichment cultures from the Lokiarchaeota in the sediment samples in the laboratory. This enabled them to study the metabolism of these cells using stable carbon isotopes as markers. The results demonstrated that the microorganisms make use of a complex network of metabolic pathways. Moreover, the data confirmed that Lokiarchaea indeed use hydrogen for the fixation of carbon dioxide. This process enhances the efficiency of metabolism, and allows these species to maintain high levels of biochemical activity, in spite of the energy limited conditions of their anoxic natural habitat. "Our experimental evidence the hydrogen hypothesis for the first eukaryotic cell," says Orsi. "Consequently, the earliest eukaryotes could have originated in oxygen-depleted and hydrogen-rich marine sediments, such as those in which modern Lokiarchaeota are particularly active today."

WHAT:

Identical twins with autism spectrum disorder (ASD) often experience large differences in symptom severity even though they share the same DNA, according to an analysis funded by the National Institutes of Health. The findings suggest that identifying the causes of this variability may inform the treatment of ASD-related symptoms. The study was conducted by John Constantino, M.D., of Washington University School of Medicine in St. Louis, and colleagues. Funding was provided by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Behavior Genetics.

ASD is a developmental disorder that affects how a person behaves, interacts with others and learns. Previous studies have found that when one identical twin has ASD, chances are extremely likely that the other twin has it, too.

The authors analyzed data from three previous studies comprising a total of 366 identical twin pairs with and without ASD. The severity of autism traits and symptoms in the twins was measured by a clinician's assessment or by parents' ratings on a standardized questionnaire. Some cases were diagnosed by both methods. The researchers determined a 96% chance that if one twin has ASD, the other has it, too. However, symptom scores varied greatly between twins diagnosed with ASD. The researchers estimated that genetic factors contributed to only 9% of the cause of trait variation among these twins. In contrast, among pairs of identical twins without ASD, the scores for traits were very similar.

The study authors do not know the reasons for differences in symptom severity, but they rule out genetic and most environmental causes because the twins share the same DNA and were raised in the same environment. Additional studies are needed to determine the cause.

Cancer patients who receive high-tech proton therapy experience similar cure rates and fewer serious side effects compared with those who undergo traditional X-ray radiation therapy, according to a study led by Washington University School of Medicine in St. Louis and the Perelman School of Medicine at the University of Pennsylvania.

The reduction in side effects -- particularly lower hospitalization rates and fewer emergency room visits -- could offset the higher initial cost of proton therapy, which often is not covered by private insurance because of its higher upfront expense and limited data on its effectiveness compared to X-ray radiation, according to the researchers.

The study is published Dec. 26 in JAMA Oncology. Some of the findings also were presented in June at the American Society of Clinical Oncology's annual meeting, in Chicago.

"We observed significantly fewer unplanned hospitalizations in the proton therapy group, which suggests the treatment may be better for patients and, perhaps, less taxing on the health-care system," said first author Brian C. Baumann, MD, an assistant professor of radiation oncology at Washington University and an adjunct assistant professor of radiation oncology at Penn. "If proton therapy can reduce hospitalizations, that has a real impact on improving quality of life for both our patients and their caregivers."

While radiation therapy can be curative for certain cancers, it also causes severe side effects -- such as difficulty swallowing, nausea and diarrhea -- that reduce quality of life and can, in some cases, require hospitalization, said Baumann, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

The study, which included almost 1,500 patients from Penn Medicine, is the first large review of data across several cancer types -- including lung, brain, head and neck, gastrointestinal and gynecologic cancers -- to show a reduced side-effect profile for proton therapy compared with X-ray radiation therapy for patients receiving combined chemotherapy and radiation. None of the patients had metastatic cancer, in which a tumor has spread to other parts of the body.

The researchers found no differences between the two groups in survival and cancer control, suggesting that proton therapy is just as effective in treating the cancer even as it caused fewer side effects. Overall survival at one year for the proton therapy group was 83 percent versus 81 percent for the X-ray radiation therapy group. This difference tipped slightly in favor of proton therapy but was not statistically significant.

The difference in side effects was more pronounced. Forty-five of 391 patients receiving proton therapy experienced a severe side effect in the 90-day time frame (11.5 percent). In the X-ray radiation therapy group, 301 of 1,092 patients experienced a severe side effect in the same period (27.6 percent). The patients receiving proton therapy experienced fewer side effects despite the fact that they were, on average, older and had more medical problems than those receiving standard X-ray radiation therapy. After taking steps to control for these differences, the researchers found that patients receiving proton therapy experienced a two-thirds reduction in the relative risk of severe side effects within the first 90 days of treatment, compared with patients receiving X-ray radiation therapy.

Both types of radiation therapy are approved by the Food and Drug Administration for cancer treatment. X-ray beams are made up of photons, which are electromagnetic particles that have almost no mass, allowing them to travel all the way through the body, passing through healthy tissue on the way out. Protons are relatively heavy, positively charged particles that hit their target and stop, essentially eliminating the exit dose of radiation.

Since the study found proton therapy to have fewer adverse events, Baumann said it could prompt radiation oncologists to design clinical trials to investigate whether increasing the dose of proton radiation would help patients do better, while still maintaining acceptable levels of side effects.

Similarly, the reduced side effects of proton therapy could allow older patients with additional medical conditions -- who are typically excluded from clinical trials because of their frailty -- to participate in trials investigating more intensive treatments that could be beneficial.

"Clinical trials often are limited to patients who have serious cancers but are otherwise quite healthy, and that's not the real-world cancer population," said Baumann. "Doctors, rightly, are concerned about toxicity. But with the reduced toxicity that we found with proton therapy, this might open the doors to the possibility of older patients with multiple medical problems getting cancer therapy they can tolerate that is more likely to be curative.

"With our aging population, this could have a big impact on a lot of patients," he added. "To me, that's an exciting implication of this research."

Washington, DC - Gay men and lesbian women have often been the targets of prejudice and even violence in society. To better understand what shapes these attitudes and prejudices, Maria Laura Bettinsoli, Alexandra Suppes, and Jamie Napier (all New York University - Abu Dhabi) tested how beliefs about gender norms (expectations of society for how men and women act and look) and people's attitudes towards gay men and women relate across the globe.

They found that globally, gay men are disliked more than lesbian women across 23 countries. Their results also suggest negative attitudes are guided by the perception that gays and lesbians violate traditional gender norms. But in three countries, China, India, and South Korea, the correlation between beliefs in gender norms and attitudes towards gays and lesbians was absent or even reversed.

The research appears online before print in Social Psychological and Personality Science.

The team assessed attitudes towards gay men and lesbian women separately, noting that most research focuses on homosexuality as a broad category and doesn't separate attitudes by gender.

Bettinsoli and colleagues were surprised at how consistently gay men were rated more negatively than lesbian women in a vast majority of their samples.

They were also surprised "at the consistency of the relationship between gender norm endorsement and sexual prejudice," says Bettinsoli. "Even though there were some non-Western countries that did not conform to the pattern, the majority of countries did."

These findings were true for western countries including Argentina, Australia, Belgium, Brazil, Canada, France, Germany, Great Britain, Hungary, Italy, Mexico, Peru, Poland, Spain, Sweden, and the USA. The same was true for Russia, South Africa, and Turkey too.

"We also found that, in line with previous research, the endorsement of gender norms was associated with anti-gay attitudes--toward both gay men and lesbian women--in every Western country in our sample," says Bettinsoli.

In South Korea, the researchers saw that endorsement of gender norms was unrelated to attitudes toward gays and lesbians, and in Japan, there was a small association between gender norm endorsement and attitudes toward gay men, but not towards lesbian women.

"In China and India, the reverse pattern emerged. Those who were highest on endorsement of traditional gender roles were the most positive toward gay men and lesbian women," says Bettinsoli.

While some of the countries show friendlier attitudes towards gays and lesbians, Bettinsoli notes that even in the more tolerant places discriminatory attitudes still exist.

The study is one of several appearing in a future special issue of Social Psychological and Personality Science focused on underrepresented populations.

Our brains have a remarkable knack for adaptability. Each and every day the neuronal connections within are constantly changing, molded by what we experience in our daily lives. The memories we make, information learned and skills we pick up spark this dynamic process, causing lasting changes to neuronal circuits. As the saying goes, experience is the best teacher and it couldn't be truer for our brains.

Along with learning and memory, sensory experiences such as listening to music or appreciating a stunning view also have a similar effect on the brain. Incoming sensory information activates neurons in the cortex, causing long term modifications to the circuitry depending on what we experience. This process called experience dependent plasticity, is part of the reason why our brains develop differently due to unique individual life experiences.

But how do our brains convert relatively short-lasting neuronal activity into the long-term changes driven by our sensory experiences? The key lies in specialized proteins called activity-dependent transcription factors. Responding to neuronal activity, these factors activate genes within the cell helping to translate rapid incoming signaling into slower, lasting changes. Despite the importance of activity dependent transcription to development and long-term plasticity in the brain is evident, it was impossible to directly monitor transcription factors activity. This was mainly due to the lack of available tools to study the interaction between neuronal activity and transcription factor activation that occurs in an intact, living brain.

In a recently published study in Neuron, Scientists in the Yasuda Lab at the Max Planck Florida Institute for Neuroscience (MPFI) have designed and developed novel biosensors that allow the simultaneous study of both sensory evoked neuronal activity and transcription factor dynamics. Coupling the specialized techniques of 2-photon calcium imaging with 2-photon fluorescence lifetime imaging (2pFLIM), scientists for the first time ever will have the unique ability to investigate how transcription factors function in a living brain with single cell resolution.

"Transcription factor activity in the brain isn't a static, but rather a very dynamic process that can occur on the order of hours to days after a sensory experience," explains Dr. Tal Laviv, Research Fellow in the Yasuda Lab and leading author of the paper. "Traditional methods of studying these proteins involve freezing brain tissue at a single moment in time. So, while these approaches can tell you if a certain factor is activated or not, they aren't good at capturing how experience shapes transcription factor activity over time. We wanted to develop a new way to study how this process is actually occurring in a living brain and chose to study CREB due to its strong involvement in plasticity, learning and memory."

MPFI scientists started by creating sensitive and specific 2pFLIM biosensors designed to report the direct activity of cAMP response-element binding protein or "CREB" for short. Packaging their newly generated sensors using an adeno-associated viral strategy (AAVs), the team then expressed them in a population of neurons within the somatosensory cortex of mice. Changes in environment are known to activate this brain region and in response, the neurons within modulate numerous signaling molecules including CREB. But little is known about the temporal dynamics of CREB activation after a change to the environment. Using the 2pFLIM CREB sensor, the team chronically monitored CREB activity in the same population of neurons while mice experienced an enriched environment. The enriched environment caused a significant increase in overall CREB activity. Interestingly, when mice were removed from the enriched environment for an extended period of time, CREB activity returned to normal levels indicating sensory experience as a driver for the sustained activity.

Next, MPFI scientists sought to unravel how sensory experiences and neuronal activation shape CREB activity in the living brain. To do so, the team expressed the CREB sensor and a sensor of neuronal activity (calcium sensor) in the visual cortex of mice. Previous studies have shown that when mice are temporarily deprived of visual stimuli and placed in dark housing, neuronal plasticity was increased in the visual cortex. In the new study, visual cortical neurons were imaged in dark-reared mice during presentation of a visual stimuli. Both calcium and CREB dynamics in single cells were simultaneously imaged for prolonged periods of time. The results revealed a dynamic regulation of CREB activity in the visual cortex: Dark reared mice displayed dramatically increased levels of visually evoked CREB compared to mice raised in normal light/dark conditions. In addition, CREB activity levels were maintained for a period of at least one day in dark-reared mice. Intriguingly this elevated CREB activity was not due to elevated calcium levels within individual neurons, indicating that sensory experience can finely tune the sensitivity of activity dependent transcription in the living brain.

This unique approach can be broadly applied to many different types of transcription factors in the future and will allow an unprecedented opportunity to unravel the transcriptional dynamics underlying experience-dependent plasticity in the brain.

The EurekAlert! 2019 Trending Release List is the most geographically diverse to date, with more than half of the top 10 from outside the United States. For the first time, news releases from Japan, Russia, and Norway occupied spots on the annual trending list, joined by returners from Canada and the U.K.

EurekAlert! is a non-profit news release distribution service operated by the American Association for the Advancement of Science (AAAS) as a free resource to journalists and the public. News releases hosted on EurekAlert! are produced and submitted by research institutions and journal publishers and must meet eligibility guidelines for acceptance.

Health-related releases dominated the Trending List, including the year's most popular release about a pair of studies in the journal Current Biology on the beneficial effects of the rocking motion on sleep and memory conducted by Swiss scientists. The news release, issued by the publisher Cell Press, received 278,119 views.

The 3rd most popular release of the year described a National Institute of Mental Health study about the Netflix show "13 Reasons Why." It found the release of the show was associated with a 28.9% increase in suicide rates among U.S. youth ages 10-17 in the month following the show's release.

The "femme fatale effect" was put to the test in six experiments and described in the 4th trending release by Washington State University. The research found that attractive businesswomen were considered by study participants to be less trustworthy, less truthful, and more worthy of being fired.

In long-term heterosexual relationships, passion is the only factor that determines the frequency of sex, according to the 5th most-visited release from the Norwegian University of Science and Technology.

IMAGE: The second most popular release featured an illustration depicting "time reversal."

CREDIT: @tsarcyanide/MIPT Press Office

A group of researchers at Osaka University revealed that ESAM (Endothelial cell-selective adhesion molecule), a surface marker for hematopoietic stem cells (HSCs) and vascular endothelial cells (ECs), played an important role in the ontogeny of hematopoiesis in mice, particularly in the development of adult-type erythropoiesis. Their research results were published in Stem Cell Reports.

In hematopoiesis, a process essential for growth and life maintenance for mammals, HSCs give rise to other blood cells for the organism's entire life. Hemangioblasts, the multipotent precursor cells, differentiate into hematopoietic and vascular endothelial cells. The microenvironment in bone marrow provides signals that regulate and support the production of blood cells necessary to maintain homeostasis of HSCs.

Functions of various types of known HSC surface markers, especially the role of hematopoietic cells in ontogeny and proliferation, were not well understood. In 2016, this group identified ESAM as an HSC surface marker, revealing that ESAM marked hematopoietic stem cells in humans as well as in mice. In the same year, this group also clarified that ESAM-deficient mice treated with an anti-tumor drug died before hematopoietic recovery. (Normally, red and white blood cells temporarily decrease after the administration of the anti-tumor drug and recover later.) They were aware that ESAM had an important function, but could not identify the role of ESAM during fetal life.

In this study, the group found that the adult-type hemoglobin synthesis ability of ESAM-null fetal livers was lower than that of wild-type mice and that expression of adult-type hemoglobin-related genes markedly decreased in ESAM-null HSCs. From these findings, they elucidated that ESAM played an important role in the development of definitive hematopoiesis, particularly of adult-type erythropoiesis.

In HSCs co-cultured with a murine stromal cell line, ESAM-null HSCs exhibited functional disruption of differentiation into adult-type blood cells. In fetuses from conditional ESAM-knockout mice, in which ESAM was deficient specifically in HSCs or ECs, the hematopoiesis-supporting ability was also impaired in ECs derived from ESAM-null mice. These results show that ESAM expressed on ECs as well as HSCs contribute to adult-type hematopoiesis. That is, both ESAM expressed on HSCs and ESAM expressed on ECs play an important role in developing definitive hematopoiesis. (Figure)

Lead author UEDA Tomoaki says, "Properties of HSCs and hematopoiesis mechanisms are not well understood because it is difficult to study hematopoiesis, especially in human fetal life. We'd like to continue our research so that our achievements will elucidate the mechanisms of hematopoiesis and lead to the identification of the cause of congenital disorders of the hematopoietic system, especially the cause of genetic anemia, and the development of treatment methods."

In this age of "big data," artificial intelligence (AI) has become a valuable ally for scientists. Machine learning algorithms, for instance, are helping biologists make sense of the dizzying number of molecular signals that control how genes function. But as new algorithms are developed to analyze even more data, they also become more complex and more difficult to interpret. Quantitative biologists Justin B. Kinney and Ammar Tareen have a strategy to design advanced machine learning algorithms that are easier for biologists to understand.

The algorithms are a type of artificial neural network (ANN). Inspired by the way neurons connect and branch in the brain, ANNs are the computational foundations for advanced machine learning. And despite their name, ANNs are not exclusively used to study brains.

Biologists, like Tareen and Kinney, use ANNs to analyze data from an experimental method called a "massively parallel reporter assay" (MPRA) which investigates DNA. Using this data, quantitative biologists can make ANNs that predict which molecules control specific genes in a process called gene regulation.

Cells don't need all proteins all the time. Instead, they rely on complex molecular mechanisms to turn the genes that produce proteins on or off, as needed. When those regulations fail, disorder and disease usually follow.

"That mechanistic knowledge--understanding how something like gene regulation works--is very often the difference between being able to develop molecular therapies against diseases, and not being able to," Kinney said.

Unfortunately the way standard ANNs are shaped from MPRA data is very different from how scientists ask questions in the life sciences. This misalignment means that biologists find it difficult to interpret how gene regulation occurs.

Now, Kinney and Tareen developed a new approach that bridges the gap between computational tools and how biologists think. They created custom ANNs that mathematically reflect common concepts in biology concerning genes and the molecules that control them. In this way, the pair are essentially forcing their machine learning algorithms to process data in a way that a biologist can understand.

These efforts, Kinney explained, highlight how modern, industrial AI technologies can be optimized for use in the life sciences. Having verified this new strategy to make custom ANNs, Kinney's lab is applying it in investigating a wide variety of biological systems, including key gene circuits involved in human disease.

The results were officially announced in Vancouver, Canada at the 1st Conference on Machine Learning in Computational Biology on December 13. They can be viewed as a preprint on CSHL's bioRxiv server.

A randomized controlled study recently published in Ethnicity & Disease in their Autumn 2019 Hypertension issue found that the Transcendental Meditation (TM) technique helps to prevent abnormal enlargement of the heart compared to health education (HE) controls. Also known as left ventricular hypertrophy (LVH), it can lead to chronic heart failure and death, and is especially prevalent among African Americans.

Risk factor for cardiovascular disease

Despite advances in medical care, cardiovascular disease (CVD) is the leading cause of death in the USA. Abnormal enlargement of heart, medically known as left ventricular hypertrophy (LVH), is an important risk factor for CVD. It doubles the risk of heart attacks, arrhythmias, stroke, heart failure, and death from CVD.

Heart disease death rates are significantly higher in African Americans than in whites, in part because the rate of LVH is double in African Americans compared to whites.

The disproportionately high rates are suggested to be associated with the burden of psychosocial stress.

A recent scientific statement from the American Heart Association emphasized the potential for stress-reduction methods to prevent heart disease and premature mortality in African Americans.

Prevented further heart enlargement

The trial included 85 African Americans with high blood pressure who were randomly assigned to Transcendental Meditation or to a health education (HE) control group, in addition to usual medical care.

This trial tested the effects of stress-reducing meditation to prevent LVH in this high-risk population. It found that stress reduction with TM practice prevented heart enlargement in hypertensive African American patients.

After six months, the control group showed nearly 10% progression of abnormal heart enlargement while the TM group maintained their baseline level of heart size.

The findings of this study suggest that TM practice is an effective nondrug method for preventing heart enlargement in African American hypertensives who are especially at high risk of developing associated CVD.

"This is a form of heart disease where nondrug treatments are relatively understudied," said Professor Robert Schneider, MD, FACC, first author. "Since the physiology of stress contributes to cardiac enlargement, we hypothesized that managing one's mind-body connection with Transcendental Meditation might prevent the disease process."

Use of echocardiography to detect hypertrophy

Echocardiography is a noninvasive diagnostic test that uses ultrasound waves to create an image of the heart muscle. Ultrasound waves that rebound or echo off the heart can show the size, shape, and movement of the heart's valves and chambers as well as the flow of blood through the heart. It can therefore be used to detect heart chamber or wall enlargement known as hypertrophy.

Echocardiography was issued at the start of the study to both TM and HE groups. After six months of practice, repeat testing with echocardiography found that the HE control group progressed on cardiac enlargement while the TM group showed prevention of enlargement. There was a significant change in left ventricle mass index (LVMI) between the groups after the six-month intervention.

11% reduced risk of cardiovascular mortality

Dr. Komal Marwaha, MD, PhD, an Associate Professor in the Department of Physiology and Health at Maharishi International University (formerly Maharishi University of Management), worked on this study as part of her PhD thesis. She said, "By preventing left ventricle mass index progression in the present study, TM may reduce the likelihood of cardiovascular morbidity and mortality associated with LVH. Devereux reported that every 23.5 gm/m2 increase in LVMI, increases the risk of cardiovascular mortality by 38% and all-cause mortality by 28%. Based on these findings, patients randomized to TM in the current study would have an 11% reduced risk of cardiovascular mortality and 8% reduced the risk of all-cause mortality compared with the control group."

Dr. Schneider, dean of MIU's College of Integrative Medicine, said these reductions are significant. "These results suggest that an effective technique for stress reduction may prevent the progression of left ventricular hypertrophy and thereby help to prevent premature heart disease and cardiac mortality."

Keith Norris, MD, PhD, Professor of Medicine at UCLA, and one of the study's co-authors, added: "We hope these findings will lead to more investigations into nondrug interventions for the prevention and early intervention of heart disease that are sorely needed given the high cost of health care in our nation and the impact of health care cost on low income and disproportionately minority communities."

The research was conducted in conjunction with Martin Luther King Hospital and Charles R. Drew University of Medicine and Science in Los Angeles, and was funded by a grant from the National Institutes of Health.

Possible study limitations

Of the 85 original subjects, roughly 50% in each group were available for the final echocardiograph tests after the 6-month study period. The high attrition might have reduced power for some of the findings.

However, the attrition was not significantly different between the TM and the HE groups, thus reducing potential subject bias in the final sample. Moreover, the attritors and completers were not significantly different in demographic or physiological characteristics at baseline that prevented the occurrence of systematically biased treatment outcomes. No record of compliance for home TM practice was collected. However, the record of meeting attendance was significantly higher in the TM (80.6%) as compared with HE (50.2%) group (P=.001).

An international joint research team led by NIMS succeeded in fabricating a neuromorphic network composed of numerous metallic nanowires. Using this network, the team was able to generate electrical characteristics similar to those associated with higher order brain functions unique to humans, such as memorization, learning, forgetting, becoming alert and returning to calm. The team then clarified the mechanisms that induced these electrical characteristics.

The development of artificial intelligence (AI) techniques has been rapidly advancing in recent years and has begun impacting our lives in various ways. Although AI processes information in a manner similar to the human brain, the mechanisms by which human brains operate are still largely unknown. Fundamental brain components, such as neurons and the junctions between them (synapses), have been studied in detail. However, many questions concerning the brain as a collective whole need to be answered. For example, we still do not fully understand how the brain performs such functions as memorization, learning and forgetting, and how the brain becomes alert and returns to calm. In addition, live brains are difficult to manipulate in experimental research. For these reasons, the brain remains a "mysterious organ." A different approach to brain research?in which materials and systems capable of performing brain-like functions are created and their mechanisms are investigated?may be effective in identifying new applications of brain-like information processing and advancing brain science.

The joint research team recently built a complex brain-like network by integrating numerous silver (Ag) nanowires coated with a polymer (PVP) insulating layer approximately 1 nanometer in thickness. A junction between two nanowires forms a variable resistive element (i.e., a synaptic element) that behaves like a neuronal synapse. This nanowire network, which contains a large number of intricately interacting synaptic elements, forms a "neuromorphic network". When a voltage was applied to the neuromorphic network, it appeared to "struggle" to find optimal current pathways (i.e., the most electrically efficient pathways). The research team measured the processes of current pathway formation, retention and deactivation while electric current was flowing through the network and found that these processes always fluctuate as they progress, similar to the human brain's memorization, learning, and forgetting processes. The observed temporal fluctuations also resemble the processes by which the brain becomes alert or returns to calm. Brain-like functions simulated by the neuromorphic network were found to occur as the huge number of synaptic elements in the network collectively work to optimize current transport, in the other words, as a result of self-organized and emerging dynamic processes..

The research team is currently developing a brain-like memory device using the neuromorphic network material. The team intends to design the memory device to operate using fundamentally different principles than those used in current computers. For example, while computers are currently designed to spend as much time and electricity as necessary in pursuit of absolutely optimum solutions, the new memory device is intended to make a quick decision within particular limits even though the solution generated may not be absolutely optimum. The team also hopes that this research will facilitate understanding of the brain's information processing mechanisms.

Gamma-Ray Burst (GRB), generated in distant galaxies, is the most energetic astronomical event in the Universe. The physical origins of GRBs are still not well understood. From two widely-used theoretical models, a GRB is thought to be originated from the collapse of a massive star or the collision of two stellar objects. The burst time of a GRB is short, from ten milliseconds to several thousand seconds, making GRB hard to be caught with current observing techniques. After the burst, the ejected material will hit and interact with the interstellar gas, producing shocks which create the gradually fading emission, called 'Afterglow', which can be luminous across the whole electromagnetic spectrum. Multi-band observations of GRB afterglows provide unique opportunities for studying their progenitor and pre-burst medium. A afterglow has a longer duration time than the prompt emission, the longest afterglow at X band can be up to 6 months, and the duration of an afterglow increases when observed at radio wavelengths.

Up to now, Very Long Baseline Interferometry (VLBI) is the highest-resolution imaging technique in astronomical observations. Since GRBs are distant objects and their emission features are very compact, VLBI becomes the only approach enabling to probe the structural changes of their afterglows. By utilizing observations from VLBI network, scientists can accurately measure the scale, proper motion and intensity of an afterglow, and obtain important constraints on theoretical models. For example, in the study of a famous double neutron star merger event GW170817, two scenarios were debated - whether it forms structured jet that can break out of the circumstellar medium or the jet is choked and trapped by the external medium - until VLBI observations provided strong evidence of a successful jet , supporting the former scenario.

The target source of this experiment, GRB190114C, is a special case among the discovered GRBs ever as it is the only GRB that was detected by ground-based Cherenkov telescopes and has high-energy emission (>100 GeV), which makes GRB190114C a unique candidate for investigating the energy mechanisms of high-energy GRBs [1]. It's afterglow was detected by multi-band observations from X-ray to radio, which makes the target more particular.

An international team led by Prof. Tao An from Shanghai Astronomical Observatory proposed to observe GRB190114C with East-Asia VLBI network (EAVN, [2]) just after it was discovered. Its afterglow was observed on three epochs corresponding to 6, 15 and 32 days after the burst. After careful analysis of the correlated data, the team eventually came to a conclusion that no significant signal above 5-sigma level is detected in all the three observations. The non-detection results place strong upper limits to constrain parameters extracted from different theoretical models of GRBs.

According to the current theories and widely accepted GRB models, two different models of interstellar medium density distribution were considered to parameterize the energy distributions [Fig. 1, Wind-like medium (left) and uniform ISM medium (right)]. By applying the results from the observations, allowed parameter values are constrained. Figure 2 shows the direct comparison between the published predictions and observation measurements (yellow spots) in a light curve view, from which we can find good consistency between observed upper limits and theoretical predictions.

It is worth mentioning that this is the first EAVN observation of transients. To better probe the weak signal of GRBs in radio bands, phase-referencing mode was used during the observations. The current experiment not only becomes one of the contributions of the multi-wavelengths studies of GRB190114C, but also represents a significant step forward of the EAVN capacities on observing weak radio sources and transients.