Tech

Segmentation clock

Our vertebral column is a highly repetitive structure - 33 vertebrae from top to bottom. This arrangement is created in the embryo by the sequential formation of a long row of structures called somites (see image), which later give rise to the vertebrae and ribs. This periodic pattern of somites is created by a group of genes known as the segmentation clock. Molecular interactions within the cell cause the expression of these genes to oscillate, with gene activity rising and falling in a regular pattern over time (see movie below). For each oscillation, another somite is formed. Errors in this segmentation clock can cause hereditary disorders of the vertebrae, such as the rare condition spondylocostal dysostosis (SCD).

The dynamics of the human segmentation clock and related diseases cannot be studied directly in human embryos, so EMBL Research Scientist Mitsuhiro Matsuda and collaborators tried to create a system for studying this process in the lab. They created cell lines that each lacked a gene thought to be the causative mutation of SCD - which can be caused by any of several genes - in different patients. They cultured these cells to create simplified versions of an embryo that show many of the same characteristics. While cells lacking a gene called HES7 failed to show oscillations, cells lacking the genes DLL3 and LFNG surprisingly showed intact oscillations. However, despite oscillations occurring in these cell lines at the single-cell level, they did not properly coordinate across the tissue to form synchronised collective oscillations or travelling waves of gene activity.

Further tests

These experiments demonstrated that the culture system the scientists has created could reveal SCD mutations that had been engineered into otherwise healthy cells. But what about testing patients' cells directly? They established a new cell line from a patient with a mutation in DLL3, and tested it in vitro. As expected, this cell line failed to show travelling waves. To provide the strongest evidence that the DLL3 mutation was the cause, the researchers used the gene editing tool CRISPR-Cas9 to correct the patient's mutation. This restored the normal synchronisation of the segmentation clock in the in vitro tissue, proving that this specific mutation was responsible.

"The segmentation clock, the mechanism underlying the periodic structures of the vertebral column, has been recapitulated in vitro. We also succeeded in evaluating two important properties of the segmentation clock separately: oscillation and synchronisation," says EMBL group leader Miki Ebisuya. "HES7, DLL3, and LFNG were already known as causative genes of SCD. But, for many SCD patients, the causative genes are still unknown. Our next goal is to identify a novel causative gene of SCD by using our newly established in vitro model."

A protein called phytochrome B, which can sense light and temperature, triggers plant growth and controls flowering time. How it does so is not fully understood.

In a paper published in Nature Communications, a group of cell biologists led by Meng Chen, a professor of botany and plant sciences at the University of California, Riverside, reveal the phytochrome B molecule has unexpected dynamics activated by temperature, and behaves differently depending on the temperature and type of light.

As climate change warms the world, crop growth patterns and flowering times will change. A better understanding of how phytochromes regulate the seasonal rhythms of plant growth will help scientists develop crops for optimal growth under the Earth's new climate and might even shed light on cancer in animals.

Phytochromes switch between active and inactive forms like a binary switch controlled by light and temperature. In direct sunlight, such as in open fields, phytochromes switch "on," absorbing far-red light. This active form inhibits stem elongation, which limits how tall plants in direct sunlight can grow.

In shade phytochromes are less active, absorbing red. This "off" form releases the inhibition of stem growth, so plants grow taller in shade to compete with other plants for more sunlight.

Within the cell, light causes "on" phytochromes to coalesce into units called photobodies inside the cell nucleus. When phytochrome B is off, it resides outside the cell nucleus. It moves inside the nucleus when "on" and changes the expression of genes and growth patterns.

Changes in light alter the size and number of all foci. Chen's group has now shown temperature alters individual foci.

His group examined the behavior of cells exposed to different temperature and light conditions from the leaves and stems of Arabidopsis thaliana, a plant used as a standard model in botany science. The goal was to monitor how photobodies change in response to temperature.

The current understanding is that phytochromes form photobodies only in the "on" state.

Chen and co-authors Joseph Hahm, Keunhwa Kim, and Yongjian Qiu, members of Chen's research group at UC Riverside, expected increasing the temperature would have a similar effect to shade -- it would switch the phytochromes "off." They thought the photobodies would disappear, as in shade.

The results were completely unexpected.

The team found increasing the temperature did not cause all the photobodies to disappear at once. Instead, specific photobodies disappeared in specific ranges of temperature. Increasing the temperature incrementally reduced the number of photobodies as they disappeared selectively.

"We found that a subset of thermostable photobodies can persist even in warm temperatures," Chen said. "The rest of the foci would disappear at each stage of lower temperature. Before we thought all the foci were the same, but now we know they are all different."

The mechanism that makes them disappear selectively must be different from the mechanism that makes them disappear in shade. This suggests individual photobodies could be sensors for specific temperature ranges.

The study also showed phytochrome B reacts to temperature from two different locations on the molecule. The first part senses temperature; the second part forms foci. Foci formed by this second location are insensitive to temperature. This shows light and temperature are sensed by the same part of the molecule but result in different behaviors.

"Photobodies are large, dynamic protein complexes. Our results suggest that each of them could have a different composition," Chen said. "What we think is that the unique composition of individual photobodies make them react to temperature differently. Future studies on understanding the unique features of each photobody will likely uncover the underlying mechanisms of temperature sensing and the regulation of temperature-responsive gene expression in plants."

In addition to helping develop plants that will thrive in a warming world, this work could help scientists learn more about cancer in animals. Proteins in animal cells also form foci related in some way to cancer, but their role in gene expression and regulation is unknown.

A new study in animals suggests that the social and interpersonal problems associated with opioid addiction might be reversible.

Researchers in the Arizona State University Department of Psychology previously used an animal model of opioid addiction and empathy to show that animals stopped prosocial behaviors - helping another animal - when heroin was available. The same research group has now shown that activating the anterior insula restored prosocial behaviors in opioid-addicted animals. The study will be published in Social Neuroscience and is now available online.

"As a master's student, I led support groups for opioid addicts, and the biggest problems people wanted help dealing with were social. Our finding in an animal model of opioid addiction that chemogenetic activation of the anterior insula restores prosocial behavior suggests a glimmer of hope that some of the social behavioral deficits in opioid addiction are not permanent," said Seven Tomek, who just defended her doctoral dissertation at ASU. Tomek is first author on the paper and received training in substance abuse treatment while earning her master's in clinical psychology from the University of North Carolina, Wilmington.

To measure prosocial behavior, the researchers trained animals to free another animal that was trapped in a clear plastic tube. The animals had access to heroin for two weeks and then were given the choice of consuming heroin or helping another animal. Like before, the animals again chose heroin over helping another.

To try and restore the prosocial behaviors in the animals, the research team targeted a brain region involved in both prosocial behaviors like helping and addictive behaviors like craving: the anterior insula.

"We designed our animal study based on work in people showing that damage in the anterior insula area - from a stroke for example - was correlated with easily quitting cigarette smoking," Tomek said. "This brain area is also important for motivation and emotions in people."

The insula is nicknamed the "hidden lobe" because it is tucked underneath the brain's frontal, parietal and temporal lobes. This location makes access difficult, so the research team used chemogenetic methods - called Designer Receptors Exclusively Activated by Designer Drugs, or DREADDs for short - to selectively activate the anterior insula in the animals. Using DREADDs is like installing a smart lock on specific neurons, and then only granting access the lock when scientists want to activate the neurons. The DREADD method inserts mutant receptors into neurons, and those receptors can only be activated by a chemical that is not naturally present in the body.

"Once we activated the excitatory DREADD in the anterior insula, the animals started rescuing the trapped animals again," Tomek said.

The research team tested the role of anterior insula activation twice. In the first experiment, the animals who underwent DREADD activation helped other animals 67% of the time when heroin was available. The control group only helped other animals 17% of the time. In the second experiment, activation of the anterior insula was again associated with helping other animals 67% of the time. The second control group helped other animals 44% of the time.

"This work demonstrates an important role for the anterior insula in opioid addiction and shows the possibilities of changing a social behavior that has been compromised by drug use," said Foster Olive, professor of psychology at ASU and senior author on the paper.

Nearly 2 million years ago, three hominin genera - Australopithecus, Paranthropus and the earliest Homo erectus lineage - lived as contemporaries in the karst landscape of what is now South Africa, according to a new geochronological evaluation of the hominin fossil-rich Drimolen Paleocave complex. Combined with other evidence, authors Andy Herries et al. argue that the site reflects a period of transition in southern Africa driven by climatic variability, one marked by endemic species, like Australopithecus, going extinct, while new migrants - Homo and Paranthropus - moved in. In their study, Herries and colleagues describe the geological context and age of two hominin crania fossils recently recovered from the Drimolen, representing Homo and Paranthropus. Using a combination of electron spin resonance, paleomagnetism and uranium-lead dating, Herries et al. pieced together the chronology of the Drimolen Main Quarry (DMQ). The results show that the Homo and Paranthropus fossils recovered from the region date to 2.04-1.95 million-years-old, which establishes both as the oldest definitive examples of their respective species (H. erectus and P. robustus). "If correct, Herries [et al.'s] results provide the most precisely dated remains in South Africa [and] add more than a hundred thousand years to the first appearance dates of at least H. erectus," writes Susan Antón in a related Perspective. The crania ages also indicate that early Homo and Paranthropus hominins lived at the same time as their older Australopithecus cousins roughly 2 million years ago, which suggests a period of transition at the site; as endemic species, like Australopithecus, went extinct, new migrants - Homo and Paranthropus - moved in, the authors suggest. What's more, the relative simplicity of the geological context of DMQ as revealed by the new geochronological techniques challenges the perceived complexity of other similarly aged South African paleocave sites, suggesting that much of what is known about the stratigraphy in these hominin-bearing sites may need to be reevaluated, according to the authors.

Addressing a major source of uncertainty in glacier-flow models, researchers present a new slip law to describe glaciers sliding on soft, deformable material. The findings may help create a universal slip law that could be used to constrain the models of the glaciers and ice sheets that could have the greatest potential impacts on global sea-level rise. Glaciers slip, slide and surge over a wide variety of terrain, ranging from solid bedrock (hard-bedded) to loose gravel-like sediments (soft-bedded). Friction, velocity and water pressure at the ice-bed interface beneath the glacier are all well-known factors that determine a glacier's movement and are used to inform glacier-flow models. However, accounting for these factors in relation to the material underlying the moving ice in models has been difficult. This is particularly true for many of the fast-flowing, marine terminating glaciers in Antarctica and Greenland that rest on deformable till. Because of this, many soft-bedded glaciers and ice sheets are imperfectly modeled, including the West Antarctic Ice Sheet. As a result, they often represent the largest source of uncertainty in estimations for future sea-level rise. Thus, it is critically important to better understand and parameterize glacier movement. Lucas Zoet and Neal Iverson designed an experimental physical model to determine the processes that govern glacier slip over water-saturated till to derive a new slip law for soft-bedded glaciers. Zoet and Iverson discovered that, despite differences in the physical mechanisms themselves, their soft-bedded slip law works both in the case of bed deformation and bed shear. When combined with parameterization for hard beds, the results create a generalized slip law for glacier-flow models.

In a Policy Forum, Charlie Wilson and colleagues explore the potential advantages of "granular" energy technologies - small-scale, lower-cost and modular technologies - for accelerating the low-carbon transformation of our global energy system. Opposed to the mainstream "bigger is better" upscaling of technology and infrastructure, Wilson et al. present new data and analyses demonstrating the benefits of granular energy technologies. In order to achieve international climate change and sustainable development goals, a rapid and transformative shift towards low-carbon energy technologies is required. According to the authors, policy support for granular technologies could help rapidly accelerate this shift while larger, more expensive technologies continue to develop. Of the 45 technologies deemed critical by the International Energy Agency for achieving global climate goals, which include many multi-million-dollar carbon neutral solutions like biorefineries and concentrating solar power plants, 38 require significant improvement in cost and performance before they can be deployed in the next several decades. While Wilson and colleagues note that granularity is not a universal solution to the challenges facing the global energy system, granular technologies can be empirically associated with faster diffusion, lower investment risk, faster learning, more equitable access, lower risk of lock-in and greater social legitimacy under certain conditions, their analyses show. Therefore, granularity should be an essential technological characteristic for policymakers to consider, the authors argue.

Researchers at the Max Planck Institute of Neurobiology are the first to describe different emotional facial expressions for mice. Similar to humans, the face of a mouse looks completely different when it tastes something sweet or bitter, or when it becomes anxious. With this new possibility to render the emotions of mice measurable, neurobiologists can now investigate the basic mechanisms of how emotions are generated and processed in the brain.

Pleasure, disgust, fear - the facial expressions that reflect these emotions are the same in every human. For example, if we are disgusted by something, our eyes become narrower, our nose wrinkles, and our upper lip distorts asymmetrically. Even newborn babies react with distinct facial expressions when they are sad, happy or disgusted. We also think to recognize feelings in the facial expressions of our pets. In contrast, the faces of other animals can appear expressionless to us. This is wrong, as the Max Planck scientists now show.

Using machine vision, the researchers were able to reliably link five emotional states to the facial expressions of mice: pleasure, disgust, nausea, pain and fear were clearly distinguishable for the computer algorithms. They could even measure the relative strength of these emotions.

Joyful expression

The study shows that the facial expression of a mouse is actually not just a reaction to the environment. It reflects the emotional value of the trigger. "Mice that licked a sugar solution when they were thirsty showed a much more joyful facial expression than satiated mice," explains Nadine Gogolla, who led the study. Meanwhile, mice that tasted a slightly salty solution showed a "satisfied" expression, while a very salty solution led to a "disgusted" face. From these and other experiments, the researchers conclude that, uncoupled from the sensory stimulus, facial expressions actually reflect the inner, individual character of an emotion.

Emotions, however, are not simply a reaction to an external stimulus - they arise through mechanisms in the brain itself. The researchers thus investigated next, how neuronal activity in different brain regions affects the facial expressions. The neurobiologists were able to evoke different emotional facial expressions when they light-activated specific brain areas known to play a role in emotional processing.

Mechanisms behind emotions

The main benefit of the discovery of mouse facial expressions is that it is now possible to identify mechanisms giving rise to emotions. This, so far, was precisely the problem: without a reliable measurement of emotions, it has been difficult to study their origins in the brain. "We humans may notice a subtle facial change in the mice, but we can only recognize the emotion behind it with a great deal of experience and can hardly ever determine its intensity," says Nejc Dolensek, the study's lead author. "With our automated face recognition system, we can now measure the intensity and nature of an emotion on a timescale of milliseconds and compare it to the neuronal activity in relevant brain areas." One such brain area is the insular cortex, which is associated with emotional behavior and the perception of emotions in animals and humans.

When the scientists measured the activity of individual neurons using 2-photon microscopy and simultaneously recorded the emotional facial expressions of the mouse, something astonishing came to light: individual neurons of the insular cortex reacted with the same strength and at the exactly same time as the mouse's facial expression. In addition, each individual neuron was linked to only one single emotion.

These results suggest the existence of "emotion neurons", each reflecting a specific sensation - at least in the insular cortex. "By recording facial expressions, we can now investigate the fundamental neuronal mechanisms behind emotions in the mouse animal model," explains Nadine Gogolla. "This is an important prerequisite for the investigation of emotions and possible disorders in their processing, such as in anxiety disorders or depression."

COLUMBUS, Ohio - To truly understand an animal species is to observe its behavior and social networks in the wild. With new technology described today (April 2) in PLOS Biology, researchers are able to track tiny animals that divide their time between flying around in the sky and huddling together in caves and hollow trees - by attaching little backpacks to them with glue.

These high-tech backpacks, which can communicate with each other and ground-based receivers, provided data for the popular study published on Halloween in 2019 showing that vampire bats developed social bonds in captivity that they maintained in the wild.

The wireless network developed by a team of engineers, computer scientists and biologists contains functions similar to what we find in our smartphones - such as motion detection and Bluetooth-style connectivity - at a fraction of the weight and energy consumption.

Keeping the system automated and lightweight was critical to the success of the network to track adult vampire bats, which weigh between 1 and 1.5 ounces and grow to 3½ inches in length. Using devices that can track larger animals, such as those incorporated into harnesses or necklaces, wouldn't work for bats or other small species.

"Using backpacks on bats saves weight and it also makes sure the sensors fall off easily," said Simon Ripperger, lead author of the paper and a postdoctoral scholar in evolution, ecology and organismal biology at The Ohio State University. "We don't really want the bats to have that burden of additional weight for extended time periods."

The sensors often get scratched off in the bats' roost within about two weeks. The researchers retrieve them if they can to recycle the backpacks and recharge and reuse the batteries.

Though the study describes the complexity of constructing the network and testing its effectiveness on bats, the system would work for other animals, such as birds, rodents, reptiles and amphibians, Ripperger said. Hence the team's name for the network: Broadly Applicable Tracking System, or BATS.

When Ripperger was pursuing his PhD a decade ago, he used a much more primitive system to study bats. He relied on radio-telemetry, sometimes running after the animals, tracking their flight path with an antenna in hand. At best, he might be able to calculate where they were every two minutes over a 30-meter area.

"It was a time-consuming, exhausting and inaccurate method," he said.

With funding from the German equivalent of the National Science Foundation, the grant's principal investigators at the Museum of Natural History in Berlin and a number of German universities assembled an interdisciplinary team and set out to make a better system. Ripperger was a postdoc at the time at the natural history museum, and is still a visiting scientist there.

The work took about seven years, with computer scientists writing code from scratch to come up with the highest-performance network possible using ultra-low levels of energy. The capacity of each battery that powers the network amounts to about 5 percent of a AAA battery's capacity.

The network consists of the tiny computers - accelerometers producing data when the bats are moving and proximity sensors to show when they are close to each other - all encased in each 3D-printed plastic backpack that weighs less than a penny. A series of base stations on the ground pick up signals and record data on bats' social activities and flight trajectories. The components are asleep most of the time, waking up when they receive a signal from another bat and then broadcasting every two seconds.

"One key advantage of our system is these wake-up receivers. They are in energy-saving mode and only wake up when they receive a signal from another bat, and then they are shouting, 'I'm here, I'm here!' and there's another receiver that comes into full consciousness and exchanges data," Ripperger said. "That's one way we conserve power consumption."

Despite the low power, the network produced robust results in various studies of different species of bats. A two-week test in which 50 vampire bats were tagged produced data on almost 400,000 individual meetings. Researchers can download all the data from the system onto their phones in the field.

Ripperger described BATS and GPS, the most commonly used method for tracking animals on a grander scale, as highly complementary systems, with BATS able to collect signals in places where GPS cannot.

"If you want to study social behavior, once a bat enters a cave or tree trunk, a GPS logger doesn't give us information because the signal from the satellite gets interrupted. But inside the roost is where all the social behavior is happening," he said. "These are really two different approaches to studying animal behavior."

There is a definite novelty to learning about how vampire bats interact, but the research also has shown remarkable similarities between their social behavior and certain aspects of human relationships. Using this system to tag vampire bats and the cattle they feed on can also help scientists better understand the spread of rabies, Ripperger said. He and colleagues are currently designing a conservation study to tag protected sand lizards living near railway lines in Germany to determine how track maintenance affects their movement.

The same basic tools that allow computers to function are now being used to control life at the molecular level. The advances have implications for future medicines and synthetic biology.

Reporting April 2 in the journal Science, a team led by the University of Washington School of Medicine has created artificial proteins that function as molecular logic gates. These tools, like their electronic counterparts, can be used to program the behavior of more complex systems.

The team showed that the new designer proteins can regulate gene expression inside human T-cells. This development may improve the safety and durability of future cell-based therapies.

"Bioengineers have made logic gates out of DNA, RNA and modified natural proteins before, but these are far from ideal. Our logic gates built from de novo designed proteins are more modular and versatile, and can be used in a wide range of biomedical applications" said senior author David Baker, professor of biochemistry at the UW School of Medicine and director of the Institute for Protein Design.

Whether electronic or biological, logic gates sense and respond to signals in predetermined ways. One of the simplest is the AND gate; it produces output only when one input AND another are present.

For example, when typing on a keyboard, pressing the Shift key AND the A key produces an uppercase letter A. Logic gates made from biological parts aim to bring this level of control into bioengineered systems.

With the right gates operating inside living cells, inputs such as the presence of two different molecules -- or one and not the other -- can cause a cell to produce a specific output, such as activating or suppressing a gene.

"The whole Apollo 11 Guidance Computer was built from electronic NOR gates," said lead author Zibo Chen, a recent UW graduate student. "We succeeded in making protein-based NOR gates. They are not as complicated as NASA's guidance computers, but nevertheless are a key step toward programming complex biological circuits from scratch."

Recruiting a patient's own immune cells in the fight against cancer has worked for certain forms of the disease. Nonetheless, targeting solid tumors with this so-called CAR-T cell therapy approach has proven challenging.

Scientists think part of the reason has to do with T cell exhaustion. Genetically altered T cells can fight for only so long before they stop working. There may be a way around this. With protein logic gates that respond to exhaustion signals, the team from UW Medicine hopes to prolong the activity of CAR T cells.

"Longer-lived T cells that are better programmed for each patient would mean more effective personalized medicine," said Chen.

NASA analyzed the cloud top temperatures in the newly formed Tropical Cyclone Irondro using infrared light to determine where the strongest storms were located.

One of the ways NASA researches tropical cyclones is to use infrared data that provides temperature information. Cloud top temperatures identify where the strongest storms are located. The stronger the storms, the higher they extend into the troposphere, and the colder the cloud temperatures.

On April 2 at 5 a.m. EDT (0900 UTC), NASA's Aqua satellite analyzed the storm using the Moderate Resolution Imaging Spectroradiometer or MODIS instrument imagery showed the strongest storms were west of the center of circulation. In that area, MODIS showed the coldest cloud top temperatures were as cold as or colder than minus 80 degrees Fahrenheit (minus 62.2 degrees Celsius). That strongest area of storms was surrounded by slightly less strong storms with cloud top temperatures as cold as minus 70 degrees Fahrenheit (minus 56.6 degrees Celsius) that extended in a band of thunderstorms to the south and southeast of the center. There was also a fragmented area of strong storms east of center. NASA research has shown that cloud top temperatures that cold indicate strong storms that have the capability to create heavy rain.

At 5 a.m. EDT (0900 UTC) on April 2, the Joint Typhoon Warning Center or JTWC noted that the center of Irondro was located near latitude 13.5 degrees south and longitude 69.9 degrees east with the center about 401 nautical miles south-southwest of Diego Garcia. Maximum sustained winds were near 35 knots (40 mph/65 kph).

The JTWC expects the storm will intensify to 75 knots (86 mph/139 kph) in a couple of days before turning east-southeast and becoming extra-tropical.

Typhoons/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

Before they were banned about a half century ago, psychedelic drugs like LSD and psilocybin showed promise for treating conditions including alcoholism and some psychiatric disorders. In a commentary publishing April 2 in the journal Cell, part of a special issue on medicine, researchers say it's time for regulators, scientists, and the public to "revisit drugs that were once used but fell out of use because of political machinations, especially the war on drugs."

Brain imaging over the past 20 years has taught scientists a lot about how these drugs act on different areas of the brain, says first author David Nutt (@ProfDavidNutt), a professor and neuropharmacologist at Imperial College London. "There's mechanistic evidence in humans of how these drugs affect the brain," he says. "By back-translating from humans to rodent models, we can see how these drugs produce the powerful neuroplastic changes that explain the long-term alterations we see in humans."

Nutt is a prominent proponent of conducting controlled trials to examine the potential benefits of psychedelics. He is also chair of the scientific advisory board for COMPASS Pathways, a for-profit company that is leading clinical research to test the safety and efficacy of psilocybin-assisted therapy for treatment-resistant depression. The treatment has been granted breakthrough therapy designation from the US Food and Drug Administration. The group also plans to launch a similar study for obsessive-compulsive disorder.

In the Cell commentary, Nutt and his colleagues write about the "psychedelic revolution in psychiatry." They explore specific questions in research, including what is known about the receptors in the brain affected by these drugs and how stimulating them might alter mental health. They also address what's been learned so far about so-called microdosing, the value of the psychedelic "trip," and what researchers know about why the effects of these trips are so long-lasting.

Brain imaging has shown that the activity of psychedelic drugs is mediated through a receptor in brain cells called 5-HT2A. There is a high density of these receptors in the "thinking parts of the brain," Nutt explains.

The key part of the brain that appears to be disrupted by the use of psychedelics is the default mode network. This area is active during thought processes like daydreaming, recalling memories, and thinking about the future--when the mind is wandering, essentially. It's also an area that is overactive in people with disorders like depression and anxiety. Psychedelics appear to have long-term effects on the brain by activating 5-HT2A receptors in this part of the brain. More research is needed to understand why these effects last so long, both from a psychological perspective and in terms of altered brain functioning and anatomy.

The authors note the challenges in obtaining materials and funding for this type of research. "Before LSD was banned, the US NIH funded over 130 studies exploring its clinical utility," they write. "Since the ban, it has funded none."

Nutt highlights the early potential of psychedelic drugs for treating alcoholism, which the World Health Organization estimates to be the cause of about one in 20 deaths worldwide every year. "If we changed the regulations, we would have an explosion in this kind of research," Nutt says. "An enormous opportunity has been lost, and we want to resurrect it. It's an outrageous insult to humanity that these drugs were abandoned for research just to stop people from having fun with them. The sooner we get these drugs into proper clinical evaluation, the sooner we will know how best to use them and be able to save lives."

CHAMPAIGN, Ill. -- Researchers used accelerometers to measure daily physical activity in 30 stroke survivors for a week, assessing how much the participants moved and how well they performed routine physical tasks. The study revealed that stroke survivors who engaged in a lot of light physical activity - taking leisurely walks or attending to nonstrenuous household chores, for example - also reported fewer physical limitations than their more sedentary peers.

The researchers describe their findings in the American Journal of Physical Medicine and Rehabilitation.

"Stroke is a major cause of disability in older adults," said Neha Gothe, a professor of kinesiology and community health at the University of Illinois at Urbana-Champaign who led the research. "We know that physical activity can improve how well people survive a stroke and recover after the fact. But almost no research has looked at how physical activity of different intensities affects physical function among stroke survivors."

Gothe and her research team used two measures of physical ability - the Short Physical Performance Battery, which measures balance, walking speed and lower-limb endurance, and the Late-Life Function and Disability Instrument, which asks participants to report how difficult it is for them to perform daily tasks such as getting in and out of a car or pouring water from a heavy pitcher.

The researchers discovered that, on average, the stroke survivors logged only about seven minutes of moderate-to-vigorous activity per day.

"In contrast, they averaged more than three hours of light physical activity each day," Gothe said. "This includes things like walking at a leisurely pace, housekeeping, light gardening or other activities that do not cause a person to break a sweat."

The amount of moderate-to-vigorous physical activity was the best predictor of participants' performance on objective measures of physical function, the researchers found. But a person's self-reported ability to perform daily tasks was much more closely associated with the amount of time they engaged in light physical activity.

"Our findings are preliminary but suggest that - in addition to moderate-to-vigorous physical activity - those daily routines that keep us on our feet and physically engaged in lighter tasks also contribute to better physical functioning in stroke survivors. This aligns with the latest Physical Activity Guidelines for Americans that emphasize the need to move more and sit less," Gothe said. "Engaging in light physical activity can be healthy and beneficial, especially for those with chronic health conditions such as stroke."

2 April 2020 - Geneva, Switzerland: Currently, there are limited data on the impact of pre-existing liver disease and the course of SARS-CoV-2 infection, with many open questions.

However, patients with advanced liver disease and recipients of liver transplants represent vulnerable groups and are likely to be at an increased risk of infection and/or a severe course of COVID-19. In addition, the COVID-19 pandemic is placing an increasing burden on healthcare systems across the world, which could negatively impact the care of patients with chronic liver diseases who require ongoing medical attention.

To promote the best possible care in these challenging circumstances, this Position Paper provides recommendations for clinicians treating patients with chronic liver diseases.

Recommendations include: promoting telemedicine in the outpatient setting, prioritising outpatient contacts, and avoiding nosocomial dissemination of the virus to patients and healthcare providers while maintaining standard care for patients who require immediate medical attention. Additionally, the paper includes a flowchart on prioritising patient care in patients with chronic liver disease.

"While the threat COVID-19 poses to our populations is clear, it remains vital to maintain appropriate care for patients with chronic liver disease. Clinicians will need to identify ways to prioritise their care even when healthcare resources are limited. EASL has therefore published this joint Position Paper to help support clinicians facing these difficult challenges," said Prof. Phil Newsome, Secretary General of the European Association for the Study of Liver Disease (EASL) and Director of the Centre for Liver and Gastrointestinal Research & Professor of Hepatology at the University of Birmingham, UK.

The paper provides recommendations on the use of outpatient care, ways to reduce direct exposure to COVID-19, and advice on managing patients with compensated/decompensated liver disease, with hepatocellular carcinoma, and following liver transplantation. It also includes advice on liver-related diagnostic procedures (including endoscopy, ultrasound, and liver biopsy), on the collaboration with local healthcare providers and primary care physicians, and on inpatient care and treatments currently being suggested.

"These recommendations address the specific concerns of patients with liver disease and are meant to provide additional guidance for their care. It is important to stress that all general recommendations and guidelines with regards to prevention, diagnosis and treatment of COVID-19 from local authorities must be adhered to," said Prof. Thomas Berg, Vice-Secretary General of EASL and Head of the Section of Hepatology Acting Director of the Clinic of Gastroenterology, University Hospital Leipzig, Germany.

"This joint Position Paper is a major EASL-ESCMID collaborative effort on management of liver disease during the COVID-19 pandemic strengthening links between our societies," said co-author and ESCMID Fellow Prof. Mario Mondelli, Professor of Infectious Diseases, University of Pavia, Clinical Lead, Division of Infectious Diseases and Immunology, Fondazione IRCCS Policlinico San Matteo, Italy.

"Technical solutions are available to enable remote physician-patient interactions, which can be helpful during the pandemic. Health authorities should be urged to equip hospitals with such systems. This is not only to support COVID-19 patients in quarantine at home, but also to care for and guide patients needing to be protected from a potentially harmful infection in the hospital setting," commented lead author Dr Tobias Boettler, Department of Medicine II, Faculty of Medicine, University of Freiburg, Germany.

This Position Paper will also be published shortly in the open access journal, JHEP Reports.

A new study in Neuron offers clues to why autism spectrum disorder (ASD) is more common in boys than in girls. National Institutes of Health scientists found that a single amino acid change in the NLGN4 gene, which has been linked to autism symptoms, may drive this difference in some cases. The study was conducted at NIH's National Institute of Neurological Disorders and Stroke (NINDS).

Researchers led by Katherine Roche, Ph.D., a neuroscientist at NINDS, compared two NLGN4 genes, (one on the X chromosome and one on the Y chromosome), which are important for establishing and maintaining synapses, the communication points between neurons.

Every cell in our body contains two sex chromosomes. Females have two X chromosomes; males have one X and one Y chromosome. Until now, it was assumed that the NLGN4X and NLGN4Y genes, which encode proteins that are 97% identical, functioned equally well in neurons.

But using a variety of advanced technology including biochemistry, molecular biology, and imaging tools, Dr. Roche and her colleagues discovered that the proteins encoded by these genes display different functions. The NLGN4Y protein is less able to move to the cell surface in brain cells and is therefore unable to assemble and maintain synapses, making it difficult for neurons to send signals to one another. When the researchers fixed the error in cells in a dish, they restored much of its correct function.

"We really need to look at NLGN4X and NLGN4Y more carefully," said Thien A. Nguyen, Ph.D., first author of the study and former graduate student in Dr. Roche's lab. "Mutations in NLGN4X can lead to widespread and potentially very severe effects in brain function, and the role of NLGNY is still unclear."

Dr. Roche's team found that the problems with NLGN4Y were due to a single amino acid. The researchers also discovered that the region surrounding that amino acid in NLGN4X is sensitive to mutations in the human population. There are a cluster of variants found in this region in people with ASD and intellectual disability and these mutations result in a deficit in function for NLGN4X that is indistinguishable from NLGN4Y.

In females, when one of the NLGN4X genes has a mutation, the other one can often compensate. However, in males, diseases can occur when there is a mutation in NLGN4X because there is no compensation from NLGN4Y.

The current study suggests that if there is a mutation in NLGN4X, NLGN4Y is not able to take over, because it is a functionally different protein. If the mutations occur in regions of NLGN4X that affect the protein levels, that may result in autism-related symptoms including intellectual deficits. The inability of NLGN4Y to compensate for mutations in NLGN4X may help explain why males, who only have one X chromosome, tend to have a greater incidence of NLGN4X-associated ASD than females.

"The knowledge about these proteins will help doctors treating patients with mutations in NLGN4X better understand their symptoms," said Dr. Roche.

Bottom Line: An analysis of a large Swedish cohort revealed that breast density, microcalcifications, and masses are heritable features, and that breast density and microcalcifications were positively associated with a genetic predisposition to breast cancer.

Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research

Author: Natalie Holowko, PhD, postdoctoral researcher in the department of Medical Epidemiology and Biostatistics at the Karolinska Institutet in Stockholm

Background: "Breast features identified through mammography are important for identifying women at high risk of developing breast cancer in the short term," said Holowko. "It is important to understand the genetic determinants of these traits, as the underlying mechanisms for their association with breast cancer is not well understood."

Holowko explained that the heritability of breast cancer is roughly 30 percent, and previous studies have estimated that the heritability of breast density is roughly 60 percent. While breast cancer and breast density have overlapping single nucleotide polymorphisms (SNPs), the heritability of other mammographic features, such as microcalcifications, masses, or breast density change, have not been previously reported, she noted. "We wanted to study the heritability of these traits, as this could help us identify important loci for breast cancer susceptibility, which could be used to better identify women who are at increased risk for developing breast cancer," Holowko said.

How the Study was Conducted: Holowko and colleagues evaluated mammographic screening history and detailed questionnaire data from the KARMA prospective cohort study in Sweden. Women were enrolled between January 2011 and March 2013; mammograms were continually collected and participants were followed for diagnosis of breast cancer. Women younger than 40 or older than 75 years were excluded, as were women with a prior breast cancer diagnosis, breast enlargement, or breast reduction. The data cutoff was October 2017.

Results: The researchers calculated the heritability of four mammographic features - breast density, average density change per year (cm2/year), microcalcifications, and masses - using 1,940 sister pairs. The heritability of breast density was estimated to be 58 percent, similar to previously reported findings. The heritability of microcalcifications and masses were estimated to be 23 percent and 13 percent, respectively. Breast density change was not determined to be an inherited trait.

Holowko and colleagues investigated the associations between mammographic features and genetic predisposition to breast cancer, as determined by a polygenic risk score (PRS), among 9,365 women in the KARMA cohort. They found statistically significant positive associations between PRS quintiles and breast density and microcalcifications.

Author's Comments: "If we can better understand the mammographic features that are associated with breast cancer risk, then we can aim to improve how these features are measured and hopefully improve early breast cancer detection," Holowko said.

Study Limitations: "We identified some limitations with modeling assumptions for density change, however, sensitivity analyses indicated almost no heritability, so we believe the presented results are reliable," noted Holowko.