Culture

For an issue once expected to occur mostly in patients with severe COVID-19, heart conditions following SARS-CoV-2 infection are much more prevalent, writes Eric Topol in a Perspective. This became especially visible following cardiac involvement in young healthy athletes who had experienced mild COVID-19. "It is vital to determine what drives this pathogenesis," says Topol. He highlights unique attributes of the virus that have resulted in it damaging the hearts of COVID-19 patients both directly (for example, through heart muscle cells) and indirectly (for example, by infecting endothelial cells that line the blood vessels to the heart). He overviews the diverse spectrum of cardiovascular issues the virus has produced - ranging from limited necrosis of heart cells to cardiogenic shock (an often-fatal inability to pump enough blood). Topol notes that recent studies of COVID-19 patients undergoing MRI or echocardiography of the heart have provided some new insights about cardiac involvement, together raising concerns that heart involvement is far more prevalent than once thought, for this disease. But overall, he says, there have been minimal cardiac imaging studies in people who test positive for the virus. This and other factors - like the lack of cardiovascular assessments for people experiencing "long-COVID" - contribute to a fundamental and large hole in our knowledge base of how this virus impacts this major organ. "It would not be surprising in the future for patients to represent with cardiomyopathy of unknown etiology and test positive for SARS-CoV-2 antibodies," he writes. He says the most intriguing question in this space is why certain individuals experience heart issues after virus infection have when others don't. Whether it's a result of an individual's inflammation response, an autoimmune phenomenon, or some other explanation needs to be clarified, says Topol. He notes how the global spread of this disease and the "panoply of disease manifestations" will make this a truly daunting task.

While cannabis use during pregnancy is on the rise, researchers at Washington University in St. Louis have found evidence that the resulting children are more likely to have psychopathology in middle childhood.

The team's analysis are the first steps in studying the effects of cannabis on children as attitudes surrounding its use change rapidly -- recreational adult cannabis use is now legal in 11 states and the District of Columbia. Patterns of usage, too, are changing; one of the fastest-growing subsets of cannabis users may come as a surprise: the pregnant.

"There have been increasingly permissive and lenient attitudes toward cannabis use among pregnant people," said Sarah Paul, a clinical psychology graduate student. "It has skyrocketed in the past few years," she added, with data indicating a quick rise from 3% to 7% past-month use.

"Unfortunately, despite the increase in use, we know remarkably little about the potential consequences of prenatal cannabis exposure," Paul said. "Prior studies have linked prenatal cannabis exposure to birth-related outcomes such as lower birth weight and infant characteristics like disrupted sleep and movement. Relatively fewer studies have examined behavior and problems as children age," and, she said, "findings have been tenuous due to inconsistent replication and an inability to account for potential confounding variables."

Working with Ryan Bogdan, associate professor of psychological & brain sciences in Arts & Sciences, and director of the Brain Lab at Washington University, and faculty from the School of Medicine, a team of researchers led by Paul and Alexander Hatoum, a postdoc research scholar, poured through data to examine what, if any, effect maternal use of cannabis during pregnancy may have on children.

Their findings were published today in JAMA Psychiatry.

They looked at data from the Adolescent Brain and Cognitive Development Study (ABCD Study), an ongoing longitudinal study of nearly 12,000 children ages 9-11 and their parent or caregiver from 22 sites across the United States that began in 2016.

The researchers grouped participants into three mutually exclusive groups: Children who were not exposed to cannabis prenatally; children who were prenatally exposed to cannabis before the pregnancy was known, but not after; and children who had been exposed to cannabis after the pregnancy was known, regardless of exposure before.

The receptors that cannabis influences are not known to be expressed prior to five- to six-weeks' gestation. Researchers expected associations with the children's outcomes would only be present if cannabis exposure happened once those receptors had been expressed. Most people said they learned of their pregnancy after about seven weeks, which aligned with the time of endocannabinoid type 1 receptor expression.

The group hypothesized that prenatal exposure, regardless of when it occurred, would be characterized by adverse outcomes in childhood, but that only continued exposure after the pregnancy was known would have an independent association with these outcomes (after considering potential confounds -- things such as family history of psychopathology, whether alcohol or tobacco or prenatal vitamins were used during the pregnancy, as well as whether children had tried alcohol, among a host of others).

The data showed children who were exposed to cannabis in the womb (regardless of when that exposure occurred) were slightly more likely to have adverse outcomes. They had elevated psychopathology -- more psychotic-like experiences; more problems with depression and anxiety as well as impulsivity and attention; and social problems as well as sleep disturbance. They also had lower cognitive performance, lower indices of global brain structure during middle childhood as well as lower birth weight.

However, when the researchers included important familial, pregnancy and child-related covariates, Bogdan said, "This is when things got really interesting. All associations with prenatal exposure only prior to maternal knowledge of pregnancy were nowhere near significantly associated." This suggests that the association between prenatal cannabis exposure during early stages of pregnancy may not be independent of these confounding factors.

"Cutting to the chase ... clinicians and dispensaries should discourage cannabis use among those who are pregnant or are considering becoming pregnant.

"However, when we look at exposure after maternal knowledge of pregnancy, which corresponds to when endocannabinoid type 1 receptors are expressed in the fetal brain, the associations with child psychopathology largely remain -- these children tend to have more psychotic-like experiences, more impulsivity and attention problems, and social problems," he said. "This raises the intriguing possibility that prenatal cannabis exposure may plausibly impact child behavior. It in no way shows causation, but documenting that effects are independent of common confounding factors provides incremental support for potential causation."

"There are certainly other plausible reasons for this pattern of results," Hatoum said. It could be that the behaviors are a byproduct of genetic and environmental similarity and not causally related to cannabis use.

"However, that our measures of these potential confounds accounted for the associations with use prior to maternal knowledge, but not after, suggests that prenatal cannabis exposure may independently contribute, in a small way, to child outcomes," he said. "Potential causation underlying this association should be further evaluated using experimental non-human animal models, additional replication and other approaches (e.g., siblings discordant for exposure)."

"Cutting to the chase, my interpretation of these findings, is that clinicians and dispensaries should discourage cannabis use among those who are pregnant or are considering becoming pregnant," Bogdan said.

"Being attentive to substance use problems among family members and providing them with support and access to help is critical for anyone regardless of pregnancy status," Bogdan said. "Learning of one's pregnancy may produce additional reason to stop use. Someone who has just learned of a pregnancy and has previously used cannabis, might think, well I have already exposed the fetus to cannabis, so I may as well not stop. The current data might provide the clinician and parent-to-be with evidence that stopping after learning of the pregnancy may reduce the likelihood of negative outcomes among their children."

At the same time, Bogdan said, "It is also important not to stigmatize expecting parents who may be experiencing difficulties. Quitting substance use during pregnancy, which is already a challenging time, may not be straightforward. Physician support and empirical paradigms for quitting during pregnancy will be important. Lastly, couples who are planning to have a child may wish to consider combatting cannabis use before they begin attempting to conceive and the additional stressors of pregnancy begin to mount."

From a public health perspective, Bogdan suggested looking to the highly effective public health campaigns and clinician attention directed at reducing the use of tobacco and alcohol during pregnancy. In fact, he said, "This study found that prenatal cannabis exposures were more strongly and consistently associated with adverse child outcomes than prenatal tobacco or alcohol exposure."

Holocaust survivors have exhibited a wide range of emotional reactions to, and ways of dealing with, the COVID-19 pandemic. Some are dealing well with the current crisis while some experience considerable difficulties. The way they cope with the current crisis is largely derived from how they deal with their traumatic memories of the Holocaust.

For many Holocaust survivors COVID-19 pandemic health policy guidelines are reminiscent of various adverse conditions that existed during the Holocaust, among them prolonged isolation and separation from family members, but particularly the omnipresent risk of contracting infectious disease.

Previous studies have shown that survivors are more sensitive to various post-Holocaust stressful events, especially those that echo a past primary trauma. In a new study, Bar-Ilan University researchers examined whether exposure to specific Holocaust adversities would be related to amplified psychological reactions to COVID-19.

The study, recently published in the Journal of Psychiatric Research, focused on 127 Holocaust survivors and Jews of European descent who did not experience the Holocaust. All of them were born before 1945. Respondents were interviewed during the period of the gradual exit from Israel's first lockdown (April to June 2020).

PTSD and loneliness were more prevalent among survivors who contracted infectious diseases such as tuberculosis and dysentery during the Holocaust relative to older adults who did not experience the Holocaust (38.5% vs. 0% for PTSD; 53.8% vs. 22.6% for loneliness). Moreover, and surprisingly, worries related to COVID-19 were more frequent among survivors who contracted infectious diseases during the Holocaust (46.2%) relative to other survivors (22.1%) or those who were not exposed to the Holocaust (6.5%).

"We believed that most Holocaust survivors would manifest increased psychological distress during the pandemic because many of them still cope with PTSD symptoms and other impairments. However, heightened distress was evident mainly in a sub-group of survivors whose lives were endangered by infectious disease during the Holocaust," says Prof. Amit Shrira, of the MA Program in Gerontology and the Interdisciplinary Department of Social Sciences at Bar-Ilan University, who led the study in collaboration with Maya Frenkel-Yosef from the Nini Czopp Association, which provides social services to Dutch-Israeli Holocaust survivors and their families, and Bar-Ilan University PhD student Ruth Maytles. "Most other survivors manifested impressive resilience and were similar in some markers of psychological distress to older adults who were not directly exposed to the Holocaust."

Shrira, who also studies intergenerational transmission of trauma, and colleagues are currently analyzing data from a new study focusing on how descendants of Holocaust survivors are coping with the current pandemic.

Aerospace engineering graduate student Pranay Thangeda relies on the bus system in Champaign-Urbana to get to class and other meetings. He wanted to understand why, despite arriving at the bus stop well ahead of the schedule, he was sometimes late. He developed a tool that considers transportation variables weighed against how great a margin of error bus riders are willing to accept. The basic concept can also apply to getting a lunar rover where it needs to be, and with a high degree of reliability.

"I was following the real-time bus schedule but still ended up being late to my destination almost half of the time and being early the other half. I wanted to know what was happening," said Thangeda, who studies under faculty member Melkior Ornik in the Department of Aerospace Engineering at the University of Illinois in Urbana-Champaign.

Thangeda realized that most navigation apps only cared about the expected travel time: they only announce how long the trip is expected to take. If the expected travel time is 20 minutes but half of the time it takes them 10 minutes and half of the time takes 30 minutes, that is often unacceptable--the rider would be late half of the time.

"We started the research with Pranay's experience: sometimes bus riders care about reliability and not just the expected fastest route. They want to have a 90 percent or 95 percent certainty that they'll get there in time for their meeting," Ornik said.

When Thangeda and Ornik began building the model, they wanted real time data and a lot of it.

"We could have collected our own data, but I noticed that MTD's website had a good web application programming interface with open access, so we reached out to their operations manager," Thangeda said. "We met with Jay Rank at MTD's office, talked over the data and he got it for us in less than a week. He and Evan Alvarez were both very gracious and accommodating. We used the data to train the model to determine the underlying distribution of travel times on different road segments and their correlation."

Thangeda said there were a lot of variables to consider in the data.

"Each factor has its own unique implications on the distribution and uncertainties," Thangeda said. "Variations in pedestrian traffic, changes to road conditions due to the weather, bus breakdowns, and other conditions. What we focused on is how these factors are distributed by using the overall distribution of historical data and live data from all the bus apps available. That enhanced the model and reduces the uncertainty making it more feasible to predict what's going to happen next."

This first step in the research resulted in a proof-of-concept implementation.

"We showed the model can calculate the tradeoff between reliability and expectation between any starting bus stop and destination," Thangeda said. "The next step would be to develop an app so users can get the optimum route from any starting point to any ending point. Developing an app will depend upon resources and the time to create it."

Ornik said they'd like to develop an app that provides complimentary functionality to currently available apps.

"Google Maps has a public transit planner. You enter your starting and ending points and it tells you the route it wants you to take. But that route might be expected to be fast but have a low reliability. We want users to be able to set their starting and ending point, the exact time they need to be there, and a tolerance such as I'm okay with being late 5 percent of the time," Ornik said.

Given that many of the current apps are free, Ornik added that there's no incentive to develop a new app. "The hope is however that this work can steer us toward an academic or industry transport partnership," he said.

Thangeda and Ornik both described some surprises in the research.

"There were a few surprises in the data," Thangeda said. "We have a static model of the entire city that's updated every three months. There were a few errors that had to be fixed. There was also some noise possibly because of the way the sensors on the buses publish the data. Sometimes the stops were recorded in an uneven order, so we had to spend a lot of time on pre-processing the data."

Ornik said he was surprised at a specific point-to-point solution the tool recommended for a trip from downtown Urbana to the Illinois Terminal in Champaign where connections can be made to Amtrak and other bus services.

"Champaign-Urbana is a fairly tame environment in terms of traffic--there isn't a rush hour or even the high pedestrian numbers you have in cities like Chicago or New York City," Ornik said. "And yet, if you want to be more certain about your arrival time, it is better to take the Orange line that takes a longer route on University Avenue and avoids campus than to take the Green line that goes through campus. That route becomes questionable because of the large fluctuation of students on campus, which increases the variance of travel times. Consequently, it makes sense to take the Orange. I never thought of that. It was very satisfying to work with these data and demonstrate specific practical features like this one in Champaign-Urbana."

Ornik said the study only looked at peak times when school is in session. The Green line may be a good choice during the summer months when the student population in C-U is lower.

The same issues addressed in the study can be said of car travel.

"We are looking for ways to translate this work further away from public transit," Ornik said. "The big difference with cars is that there are no fixed routes. In a car, if you realize that the traffic is moving slowly you can switch to a different road. In a bus, there's not much you can do."

This work was partially funded by a 2018 NASA Early Stage Innovation Award, which is not directly related to public transit but has to do with optimal planning.

"The original case study was on a lunar rover which has the same principles," Ornik said. "The rover has an origin and a destination. We look at the reliability and expectation tradeoffs between the expected amount of energy or the expected amount of time that the rover will take to reach its destination based on the terrain and what we know of the agent's energy consumption. There's also the question of reliability. Can I ensure, not just expect, that the rover will reach its destination without running out of energy. I want hard guarantees here."

As the COVID-19 pandemic rages on, researchers are working overtime to develop vaccines and therapies to thwart SARS-CoV-2, the virus responsible for the disease Many efforts focus on the coronavirus spike protein, which binds the angiotensin-converting enzyme 2 (ACE2) on human cells to allow viral entry. Now, researchers reporting in ACS Central Science have uncovered an active role for glycans -- sugar molecules that can decorate proteins -- in this process, suggesting targets for vaccines and therapies.

Before the SARS-CoV-2 spike protein can interact with ACE2 on a human cell, it changes shape to expose its receptor binding domain (RBD), the part of the protein that interacts with ACE2. Like many viral proteins, the SARS-CoV-2 spike protein has a thick coat of glycans on its surface. These glycans, which are attached at specific sites, help shield the viral proteins from the host immune system. Rommie Amaro and colleagues at University of California San Diego, Maynooth University (Ireland) and the University of Texas at Austin wondered whether certain glycans in the SARS-CoV-2 spike protein might also be active players in the process leading to infection.

To find out, the researchers used structural and glycomic data to build molecular dynamics simulations of the SARS-CoV-2 spike protein embedded in the viral membrane. The computer models, which presented a detailed snapshot of every atom in the spike glycoprotein, revealed that N-glycans linked to the spike protein at certain sites (N165 and N234) helped stabilize the shape change that exposes the RBD, which could help promote infection. The simulations also identified regions of the spike protein that weren't coated by glycans and thus could be vulnerable to antibodies, especially after the shape change. In laboratory experiments using biolayer interferometry, the team showed that mutating the spike protein so that it no longer had glycans at N165 and N234 reduced binding to ACE2. These results lay the foundation for new strategies to fight the pandemic threat, the researchers say.

PRICE, UTAH, USA - Some 92 to 66 million years ago, as the Age of Dinosaurs waned, giant marine lizards called mosasaurs roamed an ocean that covered North America from Utah to Missouri and Texas to the Yukon. The air-breathing predators were streamlined swimmers that devoured almost everything in their path, including fish, turtles, clams and even smaller mosasaurs.

Coloradoan Gary Thompson discovered mosasaur bones near the Delta County town of Cedaredge in 1975, which the teen reported to his high school science teacher. The specimens made their way to Utah's Brigham Young University, where, in 1999, the creature that left the fossils was named Prognathodon stadtmani.

"I first learned of this discovery while doing background research for my Ph.D.," says newly arrived Utah State University Eastern paleontologist Joshua Lively, who recently took the reins as curator of the Price campus' Prehistoric Museum. "Ultimately, parts of this fossil, which were prepared since the original description in 1999, were important enough to become a chapter in my 2019 doctoral dissertation."

Upon detailed research of the mosasaur's skeleton and a phylogenetic analysis, Lively determined the BYU specimen is not closely related to other species of the genus Prognathodon and needed to be renamed. He reclassified the mosasaur as Gnathomortis stadtmani and reports his findings in the most recent issue of the Journal of Vertebrate Paleontology.

His research was funded by the Geological Society of America, the Evolving Earth Foundation, the Texas Academy of Science and the Jackson School of Geosciences at The University of Texas at Austin.

"The new name is derived from Greek and Latin words for 'jaws of death,'" Lively says. "It was inspired by the incredibly large jaws of this specimen, which measure four feet (1.2 meters) in length."

An interesting feature of Gnathomortis' mandibles, he says, is a large depression on their outer surface, similar to that seen in modern lizards, such as the Collared Lizard. The feature is indicative of large jaw muscles that equipped the marine reptile with a formidable biteforce.

"What sets this animal apart from other mosasaurs are features of the quadrate - a bone in the jaw joint that also forms a portion of the ear canal," says Lively, who returned to the fossil's Colorado discovery site and determined the age interval of rock, in which the specimen was preserved.

"In Gnathomortis, this bone exhibits a suite of characteristics that are transitional from earlier mosasaurs, like Clidastes, and later mosasaurs, like Prognathodon. We now know Gnathomortis swam in the seas of Colorado between 79 and 81 million years ago, or at least 3.5 million years before any species of Prognathodon."

He says fossil enthusiasts can view Gnathomortis' big bite at the BYU Museum of Paleontology in Provo, Utah, and see a cast of the skull at the Pioneer Town Museum in Cedaredge, Colorado. Reconstructions of the full skeleton are on display at the John Wesley Powell River History Museum in Green River, Utah, and in BYU's Eyring Science Center.

"I'm excited to share this story, which represents years of effort by many citizen scientists and scholars, as I kick off my new position at USU Eastern's Prehistoric Museum," Lively says. "It's a reminder of the power of curiosity and exploration by people of all ages and backgrounds."

Predatory bacteria, capable of invading and consuming harmful bugs such as E .coli and Salmonella, use a unique tool to help them escape the cell they have invaded without harming themselves, according to a new study.

Researchers at the Universities of Birmingham and Nottingham have identified a particular enzyme used by the bacteria to rupture the cell wall of its prey bacteria and exit without damaging its own cell wall. Their findings are published in Nature Communications.

The bacterium, called Bdellovibrio bacteriovorus, is important because the types of cells they attack - Gram negative bacteria - are responsible for many infections that are resistant to currently available antibiotics. This means predatory bacteria could have the potential to be harnessed as a therapy against these infections.

Discovering precisely how Bdellovibrio bacteriovorus succeeds in invading, and then escaping its prey cells is an important step in this process.

The enzyme they discovered seems like a well-known enzyme called a lysozyme- one of the earliest- ever studied enzymes and found in human tears and saliva; but this one has a twist where it has changed to do something surprising.

"Bdellovibrio bacteriovorus is known for its ability to invade prey bacteria and stay inside the cell for a few hours, effectively eating the bacteria alive," explains Dr Andrew Lovering, of the University of Birmingham's School of Biosciences. "At the end of this process, the predator is able to break the prey open and escape. Because the walls of both the predator and prey cells are made of very similar molecules, we wanted to find out how the predator was able to cut the cell wall material of the prey cell and get out without damaging itself in the process."

The team already knew part of the answer lay in an early action by the predator bacteria to remove a particular molecule, from the cell wall of the prey. This created a 'marker' identifying the prey wall material as different to the predator. This suggested subsequent action by a particular type of enzyme known as a lysozyme might be at work. Lysozymes are a family of enzymes which are known to play a role in the breakdown of cell walls of certain bacteria. This particular lysozyme had evolved and been changed in the predatory bacterium to take on the task of rupturing the uniquely modified cell wall to enable the escape to take place.

Identifying precisely which lysozyme had been diversified for this role was the result of painstaking work by PhD students Hannah Somers and Chris Harding, working with Swiss National Science Foundation Fellow Dr Simona Huwiler.

Professor Liz Sockett, from the University of Notttingham's School of Life Sciences and co-lead author of the paper, said: "Checking the timing of when the Bdellovibrio used each of its lysozymes in predation, and hours at the microscope seeing what happened to prey-escape when each lysozyme was missing, gave us strong hunch which might be the important one for escape."

"When we looked closely at the lysozyme it was clear we were on the right path," says Dr Lovering. "It looked like a conventional lysozyme but with a warped active site, which meant it was unable to recognise the wall material unless it had been modified and marked by the Bdellovibrio bacteria."

The next step was to confirm that the lysozyme was only active against the modified cell wall and the team worked with Dr Patrick Moynihan, also in the School of Biosciences at the University of Birmingham, on tests to verify this. This showed it to be a novel lysozyme with a different target to all those lysozymes previously studied in science.

Dr Simona Huwiler, in Professor Sockett's lab then carried out a series of experiments with the predator bacteria showing clearly how adding this novel lysozyme during the predation process led to the predator falling out from the prey cell early before finishing its meal. So the novel lysozyme is the key to exit.

"Understanding the mechanism and actions of this novel lysozyme may help us use it directly against pathogens which modify their own cell walls to resist the lysozymes in saliva and tears. It is is also an important step towards being able to use predatory bacteria themselves in new therapies against problematic bacteria," adds Professor Sockett.

Researchers at Karolinska Institutet have developed a method for fast, cheap, yet accurate testing for COVID-19 infection. The method simplifies and frees the testing from expensive reaction steps, enabling upscaling of the diagnostics. This makes the method particularly attractive for places and situations with limited resources. It is equally interesting for repeated testing and for moving resources from expensive diagnostics to other parts of the care chain. The study is published in Nature Communications.

"We started working on the issue of developing a readily available testing method as soon as we saw the developments in Asia and southern Europe, and before the situation reached crisis point in Sweden," says principal investigator Bjorn Reinius, research leader at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. "Our method was effectively finished already by the end of April, and we then made all the data freely available online."

The spread of the new coronavirus at the end of 2019 in China's Wuhan region quickly escalated into a global pandemic. The relatively high transmission rate and the large number of asymptomatic infections led to a huge, world-wide need for fast, affordable and effective diagnostic tests that could be performed in clinical as well as non-clinical settings.

Established diagnostic tests for COVID-19 are based on the detection of viral RNA in patient samples, such as nasal and throat swabs, from which RNA molecules must then be extracted and purified. RNA purification constitutes a major bottleneck for the testing process, requiring a great deal of equipment and logistics as well as expensive chemical compounds.

Making the current methods simpler without markedly compromising their accuracy means that more and faster testing can be carried out, which would help to reduce the rate of transmission and facilitate earlier-stage care.

The cross-departmental research group at Karolinska Institutet has now developed methods that completely circumvent the RNA-extraction procedure, so that once the patient sample has been inactivated by means of heating, rendering the virus particles no longer infectious, it can pass straight to the diagnostic reaction that detects the presence of the virus.

According to the researchers, the most important keys to the method's success are both the above virus inactivation procedure and a new formulation of the solution used to collect and transport the sample material taken from the patients.

"By replacing the collection buffer with simple and inexpensive buffer formulations, we can enable viral detection with high sensitivity directly from the original clinical sample, without any intermediate steps," says Dr Reinius.

Institutions and research groups around the world have shown great interest in the method since a first version of the scientific article was published on the preprint server medRxiv. The article was read more than 15,000 times even before it was peer-reviewed by other researchers in the field and officially published in Nature Communications.

"Thanks to the low cost and the simplicity of the method, it becomes a particularly attractive option at sites and in situations with limited resources but a pressing need to test for COVID-19," he says and adds: "I would certainly like to see that this test used in Sweden too, for example for cheap periodic testing of asymptomatic people to eliminate the spread of infection."

Pale, male and stale - it's certainly stereotypical, but it's a saying that still holds water when it comes to Australian boards, according to new research from the University of South Australia.

Assessing the influence of gender diversity on Australian boards, researchers found that a persistent boys' club mentality is impairing decision-making at the top, particularly in relation to corporate social responsibility (CSR) initiatives.

Lead researcher, UniSA's Dr Kathy Rao, says that many Australian boards suffer from a lack of gender diversity and a male pack mentality causes biased and unbalanced decisions.

"Women bring a unique set of values, perspectives and capabilities to top-level decision-making which can help boards address CSR issues in a more effective manner," Dr Rao says.

"But old-school attitudes tend to hold them back, partly because they don't have a critical mass to push new ideas over the line, but also because there are a few powerful older male directors who are so focussed on profit that they disregard CSR is 'soft' when it is raised by female directors.

"The challenge is, however, that CSR is incredibly important for ethical and sustainable business, so companies are essentially shooting themselves in the foot if they purposely, or inadvertently, avoid CSR strategies."

Despite an increasing focus on CSR and gender diversity in Australia and around the world - including a push for gender diversity targets and disclosures from key bodies such as ASIC, ASX and AICD - gender imbalances are compounded by 'like-attracting-like' recruitment practices.

Co-researcher, and Director of the UniSA Yunus Social Business Centre, Professor Carol Tilt, says unconscious bias is a massive issue for Australian boards.

"Board members' lack of awareness of their own bias is perhaps the single most damaging factor for effective leadership," Prof Tilt says.

"Australian companies need to be more proactive in offering training and incentives for more women to become actively involved in firm governance - and, to achieve this without regulatory pressures or token appointments simply to meet gender targets.

"Unfortunately, when boards look for new members, they're often reluctant to appoint female members or candidates who have different experiences to their own, defeating the capacity to recruit a diversity of views.

"Such a blinkered approach to governance is highly risky, and while members may not know they're operating in such a way, a lack of gender diversity almost guarantees this outcome.

"As you can appreciate, influence is king on boards; if you don't have it, you can't make much of an impact."

Tsukuba, Japan - Thalidomide is a medication with several different effects, one of which is promoting sleep in the context of insomnia. In a new study, researchers from the University of Tsukuba have discovered that thalidomide exerts its hypnotic effects through mechanisms distinct from those for the drug's notorious teratogenicity.

Thalidomide was first marketed under the trade name Contergan in the late 1950's in Europe to tackle anxiety, sleeplessness, and morning sickness in pregnant women. It was eventually removed from the market because of its teratogenic effects, which infamously led to phocomelia, or severe limb deformities. Today, thalidomide is used as a medication to modulate the immune system to fight off several types of cancer. The mechanism behind the teratogenic and immunomodulatory effects of thalidomide has been well-studied, whereby it was shown that the drug binds to the protein cereblon and blocks the cereblon-mediated ubiquitination pathway. This pathway is important for the degradation and removal of specific subsets of proteins within cells, and thus its blockage is expected to disrupt various cellular signaling mechanisms.

"Thalidomide is a powerful, yet controversial drug owing to its history," says corresponding author of the study Professor Masashi Yanagisawa. "The goal of our research was to investigate the as-yet undetermined molecular mechanism responsible for the hypnotic effects of thalidomide."

To achieve their goal, the researchers asked if cereblon-mediated ubiquitination is involved in the hypnotic effects of thalidomide or if thalidomide acts independently of cereblon to exert sleep-inducing effects. The researchers first treated normal mice with thalidomide, and recorded electroencephalography (EEG) and electromyography (EMG) to test whether the drug had an effect on the sleep of the animals. The researchers found that thalidomide increased non-REM (rapid eye movement) sleep without reducing REM sleep. Reduction of REM sleep is one of unwanted side effects of common sedatives.

The researchers then engineered a mutant mouse in which thalidomide no longer interacted with cereblon. Thalidomide had the same effects on the sleep of cereblon mutant mice as on that of normal mice, suggesting that thalidomide acts independently of cereblon to induce sleep (Figure). To corroborate these findings, the researchers investigated molecular pathways of known general anesthetics and sedatives in normal and cereblon mutant mice, and found that thalidomide acted on the same neurons as those drugs.

"These are striking results showing how thalidomide induces sleep independently of its known effects on the teratogenic cereblon pathway. Our findings could be helpful in developing novel thalidomide-like hypnotic drugs without thalidomide's teratogenic effects," says Professor Yanagisawa.

Osaka, Japan — As the current COVID-19 crisis has shown, the disruptions that occur when transportation cannot proceed as usual are system-wide, affecting individual lives, companies, and the global economy. Now imagine a similar problem inside your brain and spinal cord. A new study led by researchers from Osaka University and National Center of Neurology and Psychiatry reports that two common neurodegenerative diseases—ALS, also known as Lou Gehrig's disease, and frontotemporal lobar degeneration, or FTLD—result from reduced transportation of RNA by the protein TDP-43, which ultimately disrupts neuron function.

Because one of the biggest physiological changes in both ALS and FTLD is the disappearance of TDP-43 from the nucleoli of neurons, the team focused their research on finding out what TDP-43 normally does. TDP-43 is known to bind to RNA, and the team's first experiment showed that in neurons, TDP-43 attaches to RNA that codes for pieces of ribosomes, which are necessary for making proteins from RNA code.

At its core, transportation gets things where they need to be at the proper time, whether they're people, goods, or molecules. In the body, items being sent from one place to another are often a response to what's happening to you. For instance, in response to dehydration, your brain sends a hormone through your blood to the kidneys where it forces water to be reabsorbed. In cells like neurons, the situation is similar, but there are no roads or arteries. Instead, many molecules get to their destination by being carried by other molecules.

"We discovered TDP-43 in axons and that it binds to ribosomal protein messenger RNA," says first author Seiichi Nagano. "That was strong support for the idea that TDP-43 carries the RNA to the axon where it can be used to make ribosomal proteins. This would allow local synthesis of proteins at ribosomes built in axons." Indeed, further experiments confirmed that hypothesis and showed that when TDP-43 was missing, the RNA in question could not be transported to the axon.

But what happens if the RNA cannot be transported? The researchers examined axon growth in culture as well as in mouse embryos. They found that in both cases, axon extension and outgrowth were stunted when TDP-43 was missing. However, outgrowth could be restored by forcing the neurons to overproduce ribosomal proteins.

"Now that we understand TDP-43's role in transporting the ribosomal protein messenger RNA, it should help us develop new strategies and new targets for ALS and FTLD treatments," says co-author of the study Hideki Mochizuki. "Our results in reversing stunted axon extension in mouse embryos is promising, but is just a first step."

Insomnia causing sleepless nights, daytime fatigue and poor health outcomes is a cycle worth busting, experts say, with depression, anxiety and stress a common co-occurrence.

A study of more than 450 insomnia patients in Australia has confirmed some positive results for such patients with insomnia.

The Flinders University researchers found not only that a program of targeted cognitive behavioural therapy for insomnia help relieve insomnia - but also has a positive effect on symptoms of depression, anxiety and stress.

"With COVID-19 and many other stressors in life, treating the worst effects of insomnia may have a transformative effect on a person's wellbeing, mental health and lifestyle," says lead researcher Dr Alexander Sweetman, from Flinders University's sleep research clinic, the Adelaide Institute for Sleep Health.

"We studied the impact of depression, anxiety, and stress on response to CBTi, in 455 'real world' insomnia patients, from pre-treatment to three-month follow-up," Dr Sweetman says.

"Insomnia symptoms improved by a similar amount between patients with and without symptoms of depression, anxiety and stress."

Symptoms of depression, anxiety, and stress show moderate-to-large improvement following CBTi, the results published in Sleep Medicine show.

Flinders Professor Leon Lack, who runs the insomnia therapy service at the Adelaide Institute for Sleep Health at Bedford Park, says CBT for insomnia ('CBTi') is recommended as the most effective and first-line treatment of insomnia.

As well as face-to-face CBTi therapy available at the Adelaide Institute for Sleep Health, the expert treatment is also available via telehealth options around Australia.

"The revamped insomnia treatment program at Flinders includes a range of treatments provided by experienced psychologists and physicians specialising in the management of sleep disorders, and treatment approaches which are directly based on the highest quality available scientific evidence," says Professor Lack.

"In line with many health services during the COVID-19 pandemic, the Flinders University insomnia treatment program is also available through online and telehealth platforms to people living in rural or remote areas of Australia."

The sleep research team is also rolling out the evidence-backed insomnia CBT program for general practitioners to support people with their sleep problems and avoid the use of sedative hypnotic medication over time.

Accumulation of assembled tau protein in the central nervous system is characteristic of Alzheimer's disease and several other neurodegenerative diseases, called tauopathies. Recent studies have revealed that propagation of assembled tau is key to understanding the pathological mechanisms of these diseases. Mouse models of tau propagation are established by injecting human-derived tau seeds intracerebrally; nevertheless, these have a limitation in terms of regulation of availability of human samples. To date, no study has shown that synthetic assembled tau induce tau propagation in non-transgenic mice.

A study by researchers from TMIMS confirms that dextran sulphate, a sulphated glycosaminoglycan, induces the assembly of recombinant tau protein into filaments in vitro. As compared to tau filaments induced by heparin, those induced by dextran sulphate were shorter in length, and showed higher thioflavin T fluorescence and lower resistance to guanidine hydrochloride, which suggest that the two types of filaments have distinct conformational features. Unlike other synthetic filament seeds, intracerebral injection of dextran sulphate-induced assemblies of recombinant tau caused aggregation of endogenous murine tau in wild-type mice. Tau accumulation stained with a antibody against phosphorylated tau (AT8) was present at the injection site one month after injection, from where it spread to anatomically connected regions. Induced tau pathologies were also stained by anti-tau antibodies AT100, AT180, 12E8, PHF1, anti-pS396 and anti-pS422. They were thioflavin- and Gallyas-Braak silver-positive, indicative of amyloid. In biochemical analyses, accumulated sarkosyl-insoluble and hyperphosphorylated tau was observed in the injected mice.

In conclusion, this study revealed that intracerebral injection of synthetic full-length wild-type tau seeds prepared in the presence of dextran sulphate caused tau propagation in non-transgenic mice. These findings establish that propagation of tau assemblies does not require tau to be either mutant and/or overexpressed.

If sport is good for the body, it also seems to be good for the brain. By evaluating memory performance following a sport session, neuroscientists from the University of Geneva (UNIGE) demonstrate that an intensive physical exercise session as short as 15 minutes on a bicycle improves memory, including the acquisition of new motor skills. How? Through the action of endocanabinoids, molecules known to increase synaptic plasticity. This study, to be read in the journal Scientific Reports, highlights the virtues of sport for both health and education. School programmes and strategies aimed at reducing the effects of neurodegeneration on memory could indeed benefit from it.

Very often, right after a sporting exercise - especially endurance such as running or cycling - one feels physical and psychological well-being. This feeling is due to endocannabinoids, small molecules produced by the body during physical exertion. "They circulate in the blood and easily cross the blood-brain barrier. They then bind to specialise cellular receptors and trigger this feeling of euphoria. In addition, these same molecules bind to receptors in the hippocampus, the main brain structure for memory processing," says Kinga Igloi, lecturer in the laboratory of Professor Sophie Schwartz, at UNIGE Faculty of Medicine's Department of Basic Neurosciences, who led this work. "But what is the link between sport and memory? This is what we wanted to understand," she continues.

Intense effort is more effective

To test the effect of sport on motor learning, scientists asked a group of 15 young and healthy men, who were not athletes, to take a memory test under three conditions of physical exercise: after 30 minutes of moderate cycling, after 15 minutes of intensive cycling (defined as 80% of their maximum heart rate), or after a period of rest. "The exercise was as follows: a screen showed four points placed next to each other. Each time one of the dots briefly changed into a star, the participant had to press the corresponding button as quickly as possible", explains Blanca Marin Bosch, researcher in the same laboratory. "It followed a predefined and repeated sequence in order to precisely evaluate how movements were learnt. This is very similar to what we do when, for example, we learn to type on a keyboard as quickly as possible. After an intensive sports session, the performance was much better."

In addition to the results of the memory tests, the scientists observed changes in the activation of brain structures with functional MRI and performed blood tests to measure endocannabinoid levels. The different analyses concur: the faster individuals are, the more they activate their hippocampus (the brain area of memory) and the caudate nucleus (a brain structure involved in motor processes). Moreover, their endocannabinoid levels follow the same curve: the higher the level after intense physical effort, the more the brain is activated and the better the brain's performance. "These molecules are involved in synaptic plasticity, i.e. the way in which neurons are connected to each other, and thus may act on long-term potentiation, the mechanism for optimal consolidation of memory," says Blanca Marin Bosch.

Improving school learning or preventing Alzheimer's disease

In a previous study, the research team had already shown the positive effect of sport on another type of memory, associative memory. However, contrary to what is shown here, they had observed that a sport session of moderate intensity produced better results. It therefore shows that, as not all forms of memory use the same brain mechanisms, not all sports intensities have the same effects. It should be noted that in all cases, physical exercise improves memory more than inaction.

By providing precise neuroscientific data, these studies make it possible to envisage new strategies for improving or preserving memory. "Sports activity can be an easy to implement, minimally invasive and inexpensive intervention. For example, would it be useful to schedule a sports activity at the end of a school morning to consolidate memory and improve learning?"

Improving academic learning or preventing Alzheimer's disease

In a previous study, the research team had already shown the positive effect of sport on another type of memory, associative memory. But, contrary to what is shown here, they had observed that a sport session of moderate intensity, not high intensity, produced better results. Thus, just as not all forms of memory use the same brain mechanisms, not all sports intensities have the same effects. It should be noted that in all cases, physical exercise improves memory more than inaction.

By providing precise neuroscientific data, these studies make it possible to envisage new strategies for improving or preserving memory. "Sports activity can be an easy to implement, minimally invasive and inexpensive intervention. Would it be useful, for example, to plan a moment of sport at the end of a school morning to consolidate school learning," Kinga Igloi wonders, who, with her colleagues at Sophie Schwartz's laboratory, aims to achieve such practical objectives.

Neuroscientists are currently pursuing their work by studying memory disorders, and in particular by studying populations at high risk of developing Alzheimer's disease. "Some people as young as 25 years of age may experience subtle memory deficits characterised by overactivation of the hippocampus. We want to evaluate the extent to which sports practice could help compensate for these early deficits that are precursors to Alzheimer's disease.», conclude the authors.

A recent study found that a prior induced abortion did not negatively impact a woman's psychological well-being or her thoughts about her competence as a parent when she later became a mother.

In the Acta Obstetricia et Gynecologica Scandinavica study, questionnaires were administered to 492 first-time mothers, 37 of whom had previously had an abortion, and their partners when their child was 18 months old.

A prior abortion was not predictive of maternal or paternal well-being or feelings of parental competence.

"Since induced abortion is the only type of pregnancy loss that women have influence over themselves, information about the consequences is crucial when the issue is under consideration," the authors wrote. They noted that Nordic countries are characterized by permissive abortion legislation, and an induced abortion is no longer considered a taboo in Finland.