Culture

ROCKVILLE, MD - Scientists are still a long way from being able to treat Alzheimer's Disease, in part because the protein aggregates that can become brain plaques, a hallmark of the disease, are hard to study. The plaques are caused by the amyloid beta protein, which gets misshapen and tangled in the brain. To study these protein aggregates in tissue samples, researchers often have to use techniques that can further disrupt them, making it difficult to figure out what's going on. But new research by Vrinda Sant, a graduate student, and Madhura Som, a recent PhD graduate, in the lab of Ratnesh Lal at the University of California, San Diego, provides a new technique for studying amyloid beta and could be useful in future Alzheimer's treatments. Sant and her colleagues will present their research on Friday, February 26 at the 65th Annual Meeting of the Biophysical Society.

Scientists have been studying the possibility of using nanoparticles, ultra-small structures that can be coated in therapeutics, to provide targeted treatments for a number of diseases. There are several potential applications for nanoparticles, such as coating them with chemotherapy agents and targeting them to a tumor for cancer treatment without toxic side effects for the rest of the body. Sant began researching bowl-shaped nanoparticles, which she calls "nanobowls," as a potential way to deliver treatments for Alzheimer's Disease.

Sant expected to have to coat the nanobowls in some kind of pharmaceutical in order to have them alleviate the amyloid beta protein plaques that contribute to Alzheimer's. But the amyloid beta proteins clung to the nanobowls even when they were just coated in a lipid-polymer without pharmaceuticals added, allowing the scientists to remove the toxic protein aggregates from the cells. "We were surprised to find that the nanobowls were therapeutic themselves," Sant says.

Sant says while using nanobowls as therapeutics for Alzheimer's Disease can be a potential application, it currently serves scientists who want to better understand the amyloid beta aggregates. In their recent research, Sant and team found that multiple forms of amyloid beta aggregates co-exist and not all forms directly convert into amyloid plaques, confirming what had been a hypothesis in the field. The research team is now working on using nanobowls to extract and further study amyloid beta protein aggregates. With amyloid beta being implicated in neurodegenerative diseases, cancer and cardiovascular conditions, nanobowls have potential for a range of diagnostics and treatments.

Our use of social media, specifically our efforts to maximize "likes," follows a pattern of "reward learning," concludes a new study by an international team of scientists. Its findings, which appear in the journal Nature Communications, reveal parallels with the behavior of animals, such as rats, in seeking food rewards.

"These results establish that social media engagement follows basic, cross-species principles of reward learning," explains David Amodio, a professor at New York University and the University of Amsterdam and one of the paper's authors. "These findings may help us understand why social media comes to dominate daily life for many people and provide clues, borrowed from research on reward learning and addiction, to how troubling online engagement may be addressed."

In 2020, more than four billion people spent several hours per day, on average, on platforms such as Instagram, Facebook, Twitter, and other more specialized forums. This widespread social media engagement has been likened by many to an addiction, in which people are driven to pursue positive online social feedback, such as "likes," over direct social interaction and even basic needs like eating and drinking.

While social media usage has been studied extensively, what actually drives people to engage, sometimes obsessively, with others on social media is less clear.

To examine these motivations, the Nature Communications study, which also included scientists from Boston University, the University of Zurich, and Sweden's Karolinska Institute, directly tested, for the first time, whether social media use can be explained by the way our minds process and learn from rewards.

To do so, the authors analyzed more than one million social media posts from over 4,000 users on Instagram and other sites. They found that people space their posts in a way that maximizes how many "likes" they receive on average: they post more frequently in response to a high rate of likes and less frequently when they receive fewer likes.

The researchers then used computational models to reveal that this pattern conforms closely to known mechanisms of reward learning, a long-established psychological concept that posits behavior may be driven and reinforced by rewards.

More specifically, their analysis suggested that social media engagement is driven by similar principles that lead non-human animals, such as rats, to maximize their food rewards in a Skinner Box--a commonly used experimental tool in which animal subjects, placed in a compartment, access food by taking certain actions (e.g., pressing a particular lever).

The researchers then corroborated these results with an online experiment, in which human participants could post funny images with phrases, or "memes," and receive likes as feedback on an Instagram-like platform. Consistent with the study's quantitative analysis, the results showed that people posted more often when they received more likes--on average.

"Our findings can help lead to a better understanding of why social media dominates so many people's daily lives and can also provide leads for ways of tackling excessive online behavior," says the University of Amsterdam's Bjo?rn Lindstro?m, the paper's lead author.

The koala retrovirus (KoRV) is a virus which, like other retroviruses such as HIV, inserts itself into the DNA of an infected cell. At some point in the past 50,000 years, KoRV has infected the egg or sperm cells of koalas, leading to offspring that carry the retrovirus in every cell in their body. The entire koala population of Queensland and New South Wales in Australia now carry copies of KoRV in their genome. All animals, including humans, have gone through similar "germ line" infections by retroviruses at some point in their evolutionary history and contain many ancient retroviruses in their genomes. These retroviruses have, over millions of years, mutated into degraded, inactive forms that are no longer harmful to the host. Since in most animal species this process occurred millions of years ago, the immediate health effects on the host at that time are unknown but it has been suspected for some time that the invasion of a genome by a retrovirus may have considerable detrimental health effects. The koala is at a very early stage of this process when the retrovirus is still active and these health effects can be studied.

Since retroviruses can cause cancer, it was thought that there is a link between KoRV and the high frequency of lymphoma, leukemia and other cancers in koalas from northern Australia. To investigate this link, scientists at the Leibniz-IZW sequenced DNA from wild koalas suffering from cancer. This allowed them to accurately detect the number of copies of KoRV in the koala genomes and identify the precise locations where the retrovirus had inserted its DNA. By comparing this information between healthy and tumour tissues in single koalas, and by comparing insertion sites between koala individuals, they found multiple links between KoRV and genes known to be involved in the kind of cancers to which koalas are prone.

"Each koala carries around 80 - 100 inherited copies of KoRV in its genome. The genomic locations of most of these are not shared between koalas, indicating a rapid expansion and accumulation of KoRV copies in the population. Each time a retrovirus copies and re-inserts itself into the genome, it causes a mutation, potentially disrupting gene expression, which could be detrimental to the host," says Prof Alex Greenwood, Head of Department of Wildlife Diseases at the Leibniz-IZW. This means that by frequently copying itself to new locations in the genome, KoRV is currently conferring a high mutational load on the koala population. Tumour tissues contain many new copies of KoRV, indicating that KoRV is more active in tumour cells. These copies generally were located close to genes associated with cancer. New KoRV insertions in tumour tissues affected the expression of genes in their vicinity. Such changes in gene expression associated with cancer can cause increased cell growth and proliferation, which leads to tumours. Although other factors may also contribute to cancer in koalas, the mutational burden from KoRV likely increases the frequency of cells becoming cancerous and may shorten the time for cancer to develop.

In one koala, a copy of KoRV was found that had incorporated an entire cancer-related gene from the koala genome into its DNA sequence. This greatly increased expression of this gene and most likely caused cancer in this particular koala. If this mutated virus is transmissible, it would be of grave concern for koala conservation efforts. Comparing the genomic location of KoRVs between koalas also suggests that KoRV may predispose related koalas to particular tumours, with koalas sharing KoRV insertions in specific cancer-related genes suffering from similar types of cancer which they can pass on to their offspring. Across all koalas studied, there were "hot spots" in the genome where KoRV frequently inserts itself. These hot spots were also located in proximity to genes associated with cancer. "In summary then, we find multiple links at the genomic level between cancer-related genes and KoRV, revealing ways in which KoRV underlies the high frequency of cancer in koalas," explains Gayle McEwen, scientist at the Leibniz-IZW.

The results highlight the detrimental health consequences that wildlife species can suffer following germline infection by retroviruses. Germline invasions have been repeatedly experienced during vertebrate evolution and have shaped vertebrate genomes, including the lineage leading to modern humans. These were most likely associated with severe detrimental health effects, which must be endured and overcome to ensure species survival. The scientists at the Leibniz-IZW have previously shown that old retroviruses present in the koala genome aid the rapid degradation of KoRV. The koala finds itself in a race to survive the effects of KoRV long enough for the virus to be degraded. Considering the many threats to koalas, it is a race they need to win.

PHILADELPHIA-- Even though the use of rhythm control strategies for treating Paroxysmal Atrial Fibrillation (AF), a common abnormal heart rhythm, have increased overall in the United States, patients from racial and ethnic minority groups and those with lower income were less likely to receive rhythm control treatment - often the preferred treatment - according to new research from the Perelman School of Medicine at the University of Pennsylvania. The study is published in the JAMA Network Open.

"Research has demonstrated the pervasive impact of structural racism on health outcomes among minoritized patients. We know, for instance, that there is less use of novel cardiovascular therapies among Black, Latinx, and patients of lower socioeconomic status," said the study's lead author, Lauren Eberly, MD, MPH, a cardiology fellow at the University of Pennsylvania. "That's why we wanted to evaluate the rates of antiarrhythmic drugs and catheter ablation and investigate for the presence of inequities to see how we can do better from an equity standpoint."

Atrial Fibrillation is the most common sustained heart rhythm disorder, and is the cause of significant complications including heart failure and stroke, which can be deadly for some patients. The two forms of rhythm control are antiarrhythmic drugs and catheter ablation, which aims to eliminate the sources of atrial fibrillation. Evidence suggests that when doctors pursue these rhythm control strategies early in the course of the patient's disease, they are more likely to successfully control the condition, and long term cardiovascular outcomes are improved.

Researchers examined data from October 2015 to June 2019 from more than 100,000 diverse, commercially insured patients, and found that from 2016 to 2019 the cumulative percentage of patients treated with antiarrhythmic drugs and catheter ablation increased from 1.6 percent to 3.8 percent. Despite this overall increase, patients with Latinx ethnicity and those who lived in zip codes with lower median household incomes were less likely to receive catheter ablation treatment, and Black and lower-incomes patients were less likely to be prescribed antiarrhythmic drugs or treated with catheter ablation.

Overall, patients living in areas with median household incomes of less than $50,000 were 39 percent less likely to receive catheter ablation compared with those with a median household income of $100,000 or more.

According to researchers, the number of cardiology visits by each patient was one of the strongest factors associated with rhythm control and catheter ablation use, stressing the importance of access to care. The findings suggest that reduced access to specialty care, including cardiovascular care for Black patients, is a potential reason for differences in treatments.

"As evidence builds regarding the benefits of early rhythm control and particularly catheter ablation, we must ensure that all our patients benefit equally" said the study's senior author, David Frankel, MD, Associate Professor of Medicine and Director of the Cardiac Electrophysiology Fellowship.

Eberly also hopes that in addition this awareness will push primary care providers and non-cardiac providers to more readily consider rhythm-control strategies or referral to a specialist, particularly for those patients who have been historically marginalized by the healthcare system.

When a muscle grows, because its owner is still growing too or has started exercising regularly, some of the stem cells in this muscle develop into new muscle cells. The same thing happens when an injured muscle starts to heal. At the same time, however, the muscle stem cells must produce further stem cells - i.e., renew themselves - as their supply would otherwise be depleted very quickly. This requires that the cells involved in muscle growth communicate with each other.

Muscle growth is regulated by the Notch signaling pathway

Two years ago, a team of researchers led by Professor Carmen Birchmeier, head of the Developmental Biology/Signal Transduction Lab at the Berlin-based Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), showed that the development of stem cells into muscle cells is regulated with the help of two proteins, Hes1 and MyoD, which are produced in the progenitor cells in an oscillatory manner - i.e., there are periodic fluctuations in the number of cells produced.

Both proteins are involved in the Notch signaling pathway, a widespread mechanism by which cells respond to external stimuli and communicate with other cells. The signaling pathway is named after its receptor "Notch," onto which the ligand "Delta," a cell surface protein, latches.

A third protein, Delta-like1, plays a crucial role

"In our current study, we have provided unequivocal evidence that oscillation in muscle tissue is not just some strange phenomenon of the cells involved, but that these rhythmic fluctuations in gene expression are actually crucial for transforming stem cells into muscle cells in a balanced and controlled manner," says Birchmeier.

Together with researchers from Japan and France, Birchmeier and four other scientists at the MDC also uncovered the crucial role of a third protein that, along with Hes1 and MyoD, forms a dynamic network within the cells. As the team reports in the journal Nature Communications, this protein is the Notch ligand Delta-like1, or Dll1 for short. "It is produced in activated muscle stem cells in a periodically fluctuating manner, with the oscillation period lasting two to three hours," Birchmeier explains, adding: "Whenever a portion of the stem cells expresses more Dll1, the amount in the other cells is correspondingly lower. This rhythmic signaling determines whether a stem cell becomes a new stem cell or develops into a muscle cell."

The Hes1 protein sets the pace in the stem cells

In their experiments with isolated stem cells, individual muscle fibers and mice, Birchmeier and her team further investigated how the Hes1 and MyoD proteins are involved in muscle growth. "Put simply, Hes1 acts as the oscillatory pacemaker, while MyoD increases Dll1 expression," says Dr. Ines Lahmann, a scientist in Birchmeier's lab and a lead author of the study along with Yao Zhang from the same team. "These findings were demonstrated not only in our experimental analyses, but also in the mathematical models created by Professor Jana Wolf and Dr. Katharina Baum at the MDC," Birchmeier says.

Experiments with mutant mice provided the decisive proof

With the help of gene-modified mice, the researchers obtained the most important evidence that Dll1 oscillation plays a critical role in regulating the transformation of stem cells into muscle cells. "In these animals, a specific mutation in the Dll1 gene causes production of the protein to occur with a time delay of a few minutes," Birchmeier explains. "This disrupts the oscillatory production of Dll1 in cell communities, but does not alter the overall amount of the ligand."

"Nevertheless, the mutation has severe consequences on the stem cells, propelling them to prematurely differentiate into muscle cells and fibers," reports Zhang, who performed a large portion of the experiments. As a result, he says, the stem cells were depleted very quickly, which resulted, among other things, in an injured muscle in the mice's hind legs regenerating poorly and remaining smaller than it had been before the injury. "Quite obviously, this minimal genetic change manages to disrupt the successful communication - in the form of oscillation - between stem cells," Zhang says.

This knowledge could lead to better treatments for muscle diseases

"Only when Dll1 binds to the Notch receptor in an oscillatory manner and thus periodically initiates the signaling cascade in the stem cells is there a good equilibrium between self-renewal and differentiation in the cells," Birchmeier concludes. The MDC researcher hopes that a better understanding of muscle regeneration and growth may one day help create more effective treatments for muscle injuries and diseases.

New York, NY (February 26, 2020) - Molecules called microRNAs (miRNAs) that are measurable in urine have been identified by researchers at Mount Sinai as predictors of both heart and kidney health in children without disease. The epidemiological study of Mexican children was published in February in the journal Epigenomics.

"For the first time, we measured in healthy children the associations between urinary miRNAs and cardiorenal outcomes, including blood pressure, urinary sodium and potassium levels, and eGFR [estimated glomerular filtration rate, a measure of how well the kidneys are filtering or cleaning the blood]," says lead author Yuri Levin-Schwartz, PhD, a postdoctoral fellow in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. "These relationships represent an opportunity to develop novel biomarkers for early detection and treatment of kidney damage or dysfunction."

Working with research partners in Mexico, including the National Institute of Public Health in Cuernavaca and the National Institute of Perinatology in Mexico City, the Mount Sinai-led team extracted and measured microRNAs--single-stranded RNA molecules which regulate gene expression--in urine from 88 Mexican children ages 4 to 6. This led to the association of multiple miRNAs with a range of electrolyte biomarkers, including three that showed increased expression with sodium concentration, and 17 with the sodium-to-potassium ratio. Sodium and potassium levels are regulated by the kidneys and are known indicators of renal function and heart health.

The researchers further identified a number of miRNAs associated with blood pressure, including one (miR-27a-5p) that was linked to both lower systolic and diastolic blood pressure. Another biomarker (miR-520e), assessed later in childhood, was associated with lower eGFR, which indicates poorer kidney function.

"Our findings are encouraging for future studies of noninvasive indicators of kidney and heart health, especially for individuals at an increased risk of kidney dysfunction," says senior author Alison Sanders, PhD, Assistant Professor of Environmental Medicine and Public Health, and Pediatrics, at Icahn Mount Sinai. "Further research may discover different combinations of miRNAs that could inform early diagnosis of a wide range of kidney and cardiac diseases."

According to the researchers, these urinary biomarkers may be particularly useful as a diagnostic tool for newborns, especially premature infants, who are at greater risk for kidney dysfunction than those carried to full term. "Because these children are so fragile and kidney disease is so hard to detect this early, it's important to have a noninvasive biomarker to warn physicians of problems such as kidney failure," says Dr. Levin-Schwartz. He said these results suggest that miRNAs could potentially be used to screen entire populations--including children and adults--for heart and kidney disease, although more study would be needed to confirm that.

The study was conducted in Mexico because children there are at much higher risk than American children for many heart and kidney problems. Additional study is needed to confirm whether the specific miRNAs identified in this study can serve as biomarkers elsewhere. But the technique of using miRNAs generally as biomarkers should be applicable to other populations, the researchers said.

"So many children around the world are at risk of developing cardiorenal problems which can impact their health throughout their lives," points out Dr. Sanders, who is Director of the Environmental Nephrotoxicology Laboratory at Mount Sinai, which studies the effects of prenatal exposures on maternal and child renal health. "Assessment of microRNA expression on a targeted scale could present valuable opportunities to detect and intervene with kidney disease before it can progress. That's why we're so encouraged by our team's work in this vital field."

Who would have thought that a small basic compound like vitamin B6 in the banana or fish you had this morning may be key to your body's robust response against COVID-19?

Studies have so far explored the benefits of vitamins D and C and minerals like zinc and magnesium in fortifying immune response against COVID-19. But research on vitamin B6 has been mostly missing. Food scientist Thanutchaporn Kumrungsee hopes their paper published in Frontiers in Nutrition can be the first step in showing vitamin B6's potential in lowering the odds of patients becoming seriously ill with the coronavirus.

"In addition to washing your hands, food and nutrition are among the first lines of defense against Covid-19 virus infection. Food is our first medicine and kitchen is our first pharmacy," Kumrungsee, an associate professor at Hiroshima University's Graduate School of Integrated Sciences for Life, said.

"Recently, many scientists have published papers regarding the role of diets and nutrients in the protection against COVID-19. However, very few scientists are paying attention to the important role of vitamin B6," she added.

In their paper, she and her fellow researchers pointed out growing evidence showing that vitamin B6 exerts a protective effect against chronic illnesses such as cardiovascular diseases and diabetes by suppressing inflammation, inflammasomes, oxidative stress, and carbonyl stress.

"Coronaviruses and influenza are among the viruses that can cause lethal lung injuries and death from acute respiratory distress syndrome worldwide. Viral infections evoke a 'cytokine storm,' leading to lung capillary endothelial cell inflammation, neutrophil infiltration, and increased oxidative stress," they said.

Kumrungsee explained that thrombosis (blood clotting) and cytokine storm (hyper inflammation) might be closely linked to the graveness of COVID-19. Cytokine storms happen when the immune system dangerously goes into overdrive and starts attacking even the healthy cells. Meanwhile, blood clots linked to COVID-19 can block capillaries, damaging vital organs like the heart, lungs, liver, and kidneys.

Vitamin B6 is a known anti-thrombosis and anti-inflammation nutrient. Deficiency in this vitamin is also associated with lower immune function and higher susceptibility to viral infections.

"Vitamin B6 has a close relationship with the immune system. Its levels always drop in people under chronic inflammation such as obesity, diabetes, and heart diseases. We can see from the news that obese and diabetic people are at high risk for COVID-19," Kumrungsee said.

"Thus, our attempt in this paper is to shed light on the possible involvement of vitamin B6 in decreasing the severity of COVID-19."

The associate professor said she is looking forward to clinical trials that would test their hypothesis.

"It is of great interest to examine if vitamin B6 exerts protection against novel types of virus infection and pneumonia which will be encountered in the future. At present, there is few information regarding the protective role of nutrients against pneumonia and lung diseases," she said.

"After COVID-19, we should develop the area of nutrition for lung diseases such as pneumonia and lung cancer."

Living in a group has clear benefits. As a member of a societal group, one can share resources with the others, seek protection from predators, and forage in an efficient manner. In a 2020 paper published in Science Advances, the neuroscientist Jee Hyun Choi and her student Jisoo Kim of the Brain Science Institute in the Korea Institute of Science and Technology (KIST) argue that there are much more stories about the advantages of group living and social behaviors to the mammalian brain yet to be discovered. Their research was conducted using CBRAIN (Collective Brain Research Aided by Illuminating Neural activity), a unique neuro-telemetric device equipped with LED lights, which enables the measurement and real-time analysis of collective brain activities.

While many experiments were performed to determine the individual behaviors and stances under cost-benefit schemes, the question of how a group of animals form specific social behaviors has been receiving growing interests from the neuroscience community. Understanding how the individuals strategize to produce a concrete group behavior is central to understanding the social groups and their behavioral phenotypes. For instance, recent studies have found that the overall risk imposed on the predators during successful predation attempts is reduced when predation was coordinated as a group.

"In nature, animals are likely to encounter several threats during which behaving as a group may not be beneficial for all group members," explains the senior author Jee Hyun Choi. "Indeed, forming a tight cluster may make some members difficult to avoid predators effectively. We aim to find the collective brain activities which represent behavioral phenotypes emerging from the group in a complex environment and render the brain-behavior link characterized among the group members."

In collaboration with Sung Q Lee of the ETRI in South Korea, the research team developed CBRAIN, a wireless recording device with an edge-illuminated LED that fits on the head of a mouse. This tiny device was implanted in the subcortical brain to collect the voltage signals from specific sub-region of the amygdala called the basolateral amygdala (BLA), which is a brain area known to be highly sensitive to emotional stimuli such as stress and anxiety. When the frequency-specific rhythmic activity on the board occurs during a real-time scanning of the neural activities, the LED on the device is lightened up. These rhythmic events, along with the signals from a group of mice, are transmitted to a receiver. CBRAIN's ability to generate a live report of collective brain activities is striking in contrast to other neural recording devices that analyze the signals after all experiments are completed.

Choi and her team developed experimental protocols to confirm the electrode coordinates and calibrated transient fast rhythms in BLA comprised of the gamma frequency range, called the gamma bursts, across mice. The researchers studied this bursting phenomenon during active and passive displays of fear when a large group of mice was under attack by a spider-like robot. Using CBRAIN, they observed that the occurrence of the gamma bursts during fear-driven behaviors were dependent on the social situations. Mice displayed less gamma bursts when they encountered the robot as a group, and the mice avoided and defended themselves against the robot in a group, just as they do in the nature.

Post-hoc analysis of the movement trajectories computed by deep learning tools revealed that the forms of aggregation are correlated with the gamma activities. While the mice at the edge of the cluster showed higher gamma activity, those located inside the group showed the level of gamma activity similar to the level when no robot was present. "The reduction of gamma bursts in amygdala might reflect the social buffering effect resulting from being together," said Jisoo Kim, the first author of the paper. "However, testing the activity in various ecological situations and different population structures is required to reach a definitive conclusion."

With respect to a newly developed technology and the prospect of socio-behavioral neuroscience, many neuroscientists are optimistic. "We analyze the data acquired by CBRAIN in a way identical to that of conventional neural recordings, but direct observation without first having to record and inspect data gives us a greater degree of freedom in discovering functions of specific brain activities," concludes Choi. "I believe this work serves as an exemplary study highlighting the efficacy of real-time edge-lighting neural recordings of individuals in a group, and the instant linking of a brain and behaviors will expand our understanding of the motives behind complex social behaviors."

The centre is part of the German Federal Institute for Risk Assessment (BfR). With the help of microscopy and artificial intelligence, the "E-Morph" test reliably identifies substances that can have oestrogen-like or even opposing effects, according to the research team's report in the specialist journal "Environment International". "E-Morph is a milestone on the way to, one day, replacing animal experiments currently required to detect hormone-like effects," says BfR President Prof. Dr. Dr. Andreas Hensel.

Link to the specialist publication (ScienceDirect):
https://www.sciencedirect.com/science/article/pii/S0160412021000350

Link to the article in BfR2GO, the BfR science magazine:
https://www.bfr.bund.de/cm/429/16_protection_of_laboratory_animals.pdf

The test is based on the observation that substances with an oestrogen-like effect can loosen the connection between cells in the mammary gland. This makes it easier for breast cancer cells to detach themselves from the tissue - a crucial step in the spreading (metastasis) of tumours. In the E-Morph test, a test substance is given to cultured human breast cancer cells. The cells are then examined to detect whether the cell contacts loosen as if under the influence of oestrogen. This effect is easy to observe under the microscope and can be evaluated fully automated using artificial intelligence. The robot-assisted test including evaluation is quick and enables many substances to be tested in short time. Potential future uses of the test include testing chemicals that have already been marketed as well as those that are about to be launched. The test can also be used to develop new drugs, improve diagnostic tests to detect breast cancer, and optimise therapies.

A number of brain areas change their activity before we execute a planned voluntary movement. A new study by Umeå University identifies a novel function of this preparatory neural activity, highlighting another mechanism the nervous system can use to achieve its goals.

Voluntary movements are prepared before they are executed. For example, such 'preparation' occurs in the period between seeing a coffee cup and starting to reach for it. Neurons in many areas of the brain change their activity during movement preparation in ways that reflect different aspects of the goal, such as the intended movement direction.

It is well-known that preparation improves reaction time and the overall quality of movements, but it has been unclear how preparatory brain activity gives rise to improved motor performance. There have been no evidence of goal-related preparatory changes in muscles. However, a new study from Umeå University has identified a specific preparatory neural mechanism that can lead to improved motor performance.

"Our study demonstrates a preparatory change in the sensitivity of muscle spindle receptors and the motor reflexes they enable", says Dr. Michael Dimitriou who headed this study and is a Research Fellow at the Department of Integrative Medical Biology of Umeå University.

Muscle spindle receptors or "sensors" normally measure the amount of stretch in a muscle. Spindles also supply the signals that trigger and shape stretch reflex responses. In contrast to other receptor types in muscle and skin, muscle spindles have their own motor or 'fusimotor' supply. That is, the nervous system itself can adjust the sensitivity of muscle spindles independently.

"By modulating the sensitivity of spindles and stretch reflexes during preparation, the nervous system can adjust muscle stiffness independently of concurrent muscle force", says Dr. Dimitriou.

Muscle stiffness refers to the mechanical resistance of muscle to being stretched. Muscle and joint stiffness is a critical parameter for motor performance and successful interaction with our environment. Too much or too little stiffness can be detrimental to motor performance. For example, too much muscle stiffness is a hallmark of spasticity disorder.

"When preparing to reach in a particular direction, we found that reflex sensitivity and muscle stiffness is selectively decreased in muscles that are about to stretch. To facilitate reaching the goal, the nervous system seems to independently modulate the 'breaks' in an advantageous manner before initiating movement" says Dr. Dimitriou.

"Beyond its role in movement preparation, the independent control of sensory receptors may be another way in which the nervous system routinely exerts goal-dependent control, in addition to the top-down control of muscle force and the selective processing of sensory signals. A better understanding of human sensorimotor function can inform new technologies in other areas, such as prosthetics and robotics control."

Cells rely on membranes to protect themselves from the outside world. But these membranes can't be fully closed because nutrients and other molecules have to be able to pass through. To achieve this, cell membranes have many types of channels and pores. Also, there are receptors, antennas if you like, imbedded in the membrane that continuously monitor the outside world and signal to the cell interior. Extensive collaboration between five VIB groups resulted in a better understanding of the machinery that plants use to regulate the protein composition of their outer membrane. This discovery, published in Science Advances, enhances our basic knowledge of how the plasma membrane composition can be adapted based on external stimuli, an essential process for life on earth.

The molecular architecture of TPLATE

Complex life has complex cells, also known as eukaryotic cells. Unlike bacteria, for example, the cells of complex life have many distinct internal compartments known as organelles. These organelles exchange material among themselves. To do so, the organelles have a few tricks. One of those tricks is vesicle trafficking. This means that they use a part of their own membrane as a bag for the goods to be exchanged.

A recent discovery showed that plants heavily rely on a protein complex named the TPLATE complex to do so. This complex is not only present in plants, but also in a wide range of other eukaryotes, which suggests it is evolutionary very old and part of a protein complex family of which all other members are intensively studied. However, because this particular complex is not present in the most-studied model organisms (animals and yeasts), its existence and function remained under the radar for a very long time.

In this study, VIB teams (the groups of Bert De Rybel, Geert De Jaeger, and Daniël Van Damme from the VIB-UGent Center for Plant Systems Biology, Remy Loris from the VIB-VIB Center for Structural Biology, and Savvas Savvides from the VIB-UGent Center for Inflammation Research) reveal TPLATE's molecular architecture for the very first time. They achieved this by crosslinking mass spectrometry and computer simulations. These new insights revealed the orientation of this complex towards the membrane as well as the delicate relationship between the different domains of its subunits.

These findings are important to increase our knowledge of crucial eukaryotic processes. Indeed, the structure of this complex now allows us to compare it with known structures of its close relatives that are present in all eukaryotes including animals and yeasts and this allows us to visualize the evolution of these trafficking complexes.

Collaborating for success

To obtain both structural and functional insight into this enigmatic complex an integrative, collaborative approach was needed. Five VIB research groups and one group from the Czech Republic contributed within their specific expertise to perform experiments ranging from lipid-binding studies to structural biology approaches.

The novel structural insight was mostly generated based on crosslinking mass spectrometry, performed with the help of the VIB Proteomics core facility.

'A major benefit of working at VIB is that it greatly encourages and facilitates access to knowledge and expertise that allows research groups to successfully embark on joint projects that lie far beyond their comfort zone.' - Prof. Daniel Van Damme

This study will form the foundation of further scientific work and will open doors for the generation of novel and safer herbicides or modulation of stress responses in plants.

The Korea Institute of Machinery and Materials (KIMM) successfully developed all-round gripper* technology, enabling robots to hold objects of various shapes and stiffnesses. With the new technology, a single gripper can be used to handle different objects such as screwdrivers, bulbs, and coffee pots, and even food with delicate surfaces such as tofu, strawberries, and raw chicken. It is expected to expand applications in contact-free services such as household chores, cooking, serving, packaging, and manufacturing.

*Gripper: A device that enables robots to hold and handle objects, similar to a human hand.

The team led by Chanhun Park of the Department of Robotics and Mechatronics under the Advanced Manufacturing Systems Research Division developed all-round grippers that facilitate contact-free services. Contact-free services require gripper technology for robots to freely handle objects regardless of object shape and material.

The all-round gripper was developed to hold objects of various shapes, sizes, and stiffnesses. The stiffness of the gripper surface in contact with the object is soft and fluffy enough to be similar to that of a tofu. This extremely low stiffness can inherently prevent damage to the object. In addition, only the area pressed by the object is selectively deformed, so the contact surface of the gripper can be deformed to perfectly match the target object contour, and this can help to realize firm grip.

"The soft structure technology allows the gripper surface to perfectly match target objects in extremely soft state using the honeycomb structure and stretchable mesh structure," said Sung-hyuk Song, senior researcher in charge of developing the gripper surface structure.

After the grabbing action, the gripper surface hardens, keeping the object stable in its grip. This feature allows it to safely hold objects, including those with fragile surfaces. The sense of stability provided by the gripper is such that users will feel as if it has been customized for the specific object.

The all-round gripper can hold a target object firmly instead of leaving it hanging unstably, so the gripper has the advantage of being able not only to transfer objects but also to perform complex tasks such as preparing a cocktail with a squeezed lemon, making chicken soup, and cooking a squid dish, none of which were possible to implement with existing grippers.

"Conventional grippers are applicable to only a few objects, but our all-round grippers can be applied to various objects of different shape and size, because the gripper's surface shape and rigidity can be transformed according to the target object. We hope the developed all-round gripper plays a key role in the advancement of contact-free services, where there is much need for innovation in gripper technology," said Chanhun Park, the head of the Department of Robotics and Mechatronics.

IRS refers to the application of insecticide onto the interior walls of houses.

The study, by the Wits Research Institute for Malaria (WRIM) and the London School of Hygiene and Tropical Medicine (LSHTM), was published in The Lancet on 25 February 2021.

Targeted vs blanket Indoor Residual Spraying

Malaria still represents one of the world's largest health crises, particularly on the African continent where 94% of cases and deaths occur (World Health Organization, 2020).

Most countries in southern Africa have set the elimination of malaria within their borders as a policy target.

In South Africa, IRS has been effectively used since 1945. As a result, malaria transmission is low, but persistent. Malaria transmission is confined to the north-eastern border districts of Mpumalanga, Limpopo, and KwaZulu-Natal provinces.

IRS has been a highly effective strategy for controlling malaria in many countries. However, IRS is logistically challenging when deployed at scale and its costs are rising, due in part to the challenges posed in addressing resistance of malaria vector mosquitoes to low-cost insecticides.

Furthermore, it may be unwarranted and unsustainable to spray all houses in areas where malaria is rare (but not eliminated), particularly when resources are limited.

At a global level, spending on malaria prevention and treatment has remained stagnant for almost a decade, despite rising unit costs and growing populations. More efficient strategies are therefore urgently required to sustain malaria elimination efforts in low transmission settings.

"The increase in rural populations makes it very difficult to carry out IRS at the recommended coverage of 85% of all households before the malaria transmission season is in full swing," says Maureen Coetzee, Distinguished Professor in the WRIM and a co-author of the study.

"Reactive spraying and the substantial cost-saving make [targeted IRS] an effective strategy for the national and provincial malaria control programmes to adopt - based on good scientific data."

About the study

The study, titled Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa, was the first to investigate whether reactive, targeted IRS is non-inferior and more cost-effective compared with the standard practice of an annual mass spray campaign ahead of malaria season.

The trial was conducted in residential areas (clusters) in Bushbuckridge, Mpumalanga and in Phalaborwa, Limpopo province.

Clusters were randomly assigned to either the targeted or the standard approach. In the intervention arm of the trial, the teams only sprayed houses in response to a reported malaria case, and restricted spraying to just that house [the index case house] and up to eight neighbouring houses within 200m.

The targeted intervention therefore involved a substantial reduction in spraying, directed only at neighbourhoods where there had been recent evidence of malaria transmission as indicated by the occurrence of a recent malaria case.

Safe and cost-effective strategies

The findings proved that, within the pre-specified margin of 1 case per 1000 people per year, the targeted approach was no worse than the standard approach. Furthermore, the targeted approach proved highly cost-effective.

The average annual economic cost was $88 258 (±R1.2m, 2017 exchange rate) per 100,000 population for the targeted intervention, which is 52% less costly than the standard practice, which costs $184 319 (±R2.5m, 2017 exchange rate).

"The targeted intervention cost less because it involved spraying far fewer structures, did not use contract sprayers, and used substantially less insecticide, transport, and equipment," says Mr David Bath, Research Fellow in Health Economics at LSHTM and joint first author of the study with Dr Jackie Cook, Associate Professor in Malaria Epidemiology at LSHTM.

Targeted transmission solutions

The authors acknowledge that replacing an existing intervention, which has been standard practice for many years, would be politically and socially sensitive, and would require vigilance to avoid resurgence in cases. It is therefore important that strategies which reduce costs due to better targeting of IRS are based on robust evidence, as demonstrated by this study.

Mr Aaron Mabuza, co-chair of the South African Malaria Elimination Committee (SAMEC), co-author of the study and former manager of the Mpumalanga Provincial Malaria Control Programme, says: "I used to wonder whether there was an alternative to blanket IRS and this study on targeted IRS has addressed my question. The recommendations are realistic and implementable, and also tackle the problem of population increase, which now makes it nearly impossible for blanket IRS to be completed before high transmission starts."

Targeted IRS ensures the reallocation of saved resources to other life-saving malaria control and elimination activities, such as enhanced awareness campaigns, case management, surveillance, and epidemic preparedness

"The findings of the study represent an exciting development to divest funds into other areas contributing to malaria elimination in very low-transmission settings across southern Africa," says Coetzee.

Prior to the emergence of new mutants of the coronavirus, such as the British variant B.1.1.7, the SARS-CoV-2 variant named D614G had already mutated from the original SARS-CoV-2 pathogen that triggered the pandemic. D614G has rapidly spread to become the most abundant variant worldwide and this D614G mutation remains in all the new emerging variants. An international team including researchers from Bern has now been able to demonstrate in both the laboratory and in animal models why the D614G variant was able to gain the upper hand over the original SARS-CoV-2 virus. "Our approach also allows us to characterize emerging mutations such as the British variant B.1.1.7 better and quicker," says Volker Thiel of the Institute of Virology and Immunology (IVI), one of the four lead authors of the study. The findings are extremely important for assessing the risk of new mutants running rampant, as they show how a fitness advantage of virus variants can lead to higher transmission. First results were released earlier allowing for scientific discussion on what is known as a preprint server. The results of the study have now been published in full in Nature.

The D614G variant carries a mutation in the spike protein that makes it easier for the virus to dock onto human cells. The researchers at IVI and in David E. Wentworth's laboratory at the Centers for Disease Control and Prevention in Atlanta (USA) first demonstrated in human cell cultures from the upper respiratory tract, as well as from the nose, that the D614G variant binds more strongly and also replicates faster than the original virus. The increased replication of the D614G variant was also confirmed in vivo, in a new mouse model first described in this study. These experiments were also carried out at the IVI in Charaf Benarafa's group.

The new mutation clearly prevails

The spread of SARS-CoV-2 viruses can be studied better in other animals rather than mice. Hamsters and ferrets are well established in infection research and are especially suitable animal models. To compare the two variants, a mixture of equal parts of the original version of the SARS-CoV-2 virus and the D614G variant was applied into the nose of each animal under light anesthesia. After one day, experimentally infected animals were rehoused with another healthy sentinel animal of the same species, to evaluate the transmission of the two variants in direct competition with each other. The experiment was repeated with six pairs of animals in total. In virtually all sentinel animals, the proportion of transmitted SARS-CoV-2 viruses was massively dominated by the D614G variant early on. The differentiation of the variants was carried out using the latest sequencing technology and PCR techniques by Martin Beer's team at the Friedrich Loeffler Institute, Federal Research Institute for Animal Health, in Greifswald-Insel Riems (D). "Our study stands out because we were able to clearly discern the more efficient transmission of the mutated variant in direct comparison with the original variant," says Volker Thiel.

A fitness test for further mutations

This approach can even be used to test any single mutation or a specific combination of mutations that are present in a number of currently circulating viral variants. The IVI relies on a cloning technique developed in Bern a year ago, in which SARS-CoV-2 viruses can be exactly reproduced in the laboratory. The British virus, for example, is known to have not just one but often more than 14 mutations, eight of which occur in the spike protein. Thus, with the help of the cloning technique, any number of mutations of variants can be reproduced and used to compete against each other in the established cell cultures and animal models. The results show how single mutations affect the fitness and transmissibility of new variants. "Our testing strategy allows us to rapidly examine why other, newly emerging virus variants have become established," says Volker Thiel.

Similar research projects on infectious pathogens could also be carried out in the future at the newly established Multidisciplinary Center for Infectious Diseases and Immunity (MCIDI) at the University of Bern.

A study, led by researchers at the Instituto de Astrofísica de Canarias (IAC) and carried out with OSIRIS, an instrument on the Gran Telescopio Canarias (GTC), has found the most densely populated galaxy cluster in formation in the primitive universe. The researchers predict that this structure, which is at a distance of 12.5 billion light years from us, will have evolved becoming a cluster similar to that of Virgo, a neighbour of the Local Group of galaxies to which the Milky Way belongs. The study is published in the specialized journal Monthly Notices of the Royal Astronomical Society (MNRAS).

Clusters of galaxies are groups of galaxies which remain together because of the action of gravity. To understand the evolution of these "cities of galaxies" scientists look for structures in formation, the so-called galaxy protoclusters, in the early universe.

In 2012 an international team of astronomers made an accurate determination of the distance of the galaxy HDF850.1, known as one of the galaxies with the highest rate of star formation in the observable universe. To their surprise, the scientists also discovered that this galaxy, which is one of the most studied regions on the sky, known as the Hubble Deep Field/GOODS-North, is part of a group of around a dozen protogalaxies which had formed during the first thousand million years of cosmic history. Before its discovery only one other similar primordial group was known.

Now, thanks to a new piece of research with the OSIRIS instrument on the Gran Telescopio Canarias (GTC, or GRANTECAN), the team has shown that it is one of the most densely populated regions populated with galaxies in the primitive Universe, and have for the first time carried out a detailed study of the physical properties of this system. "Surprisingly we have discovered that all the members of the cluster studied up to now, around two dozen, are galaxies with normal star formation, and that the central galaxy appears to dominate the production of stars in this structure" explains Rosa Calvi, formerly a postdoctoral researcher at the IAC and first author of the article.

Witnesses to the infancy of the local Universe

This recent study shows that this cluster of galaxies in formation is made up of various components, or "zones" with differences in their evolution. The astronomers predict that this structure will change gradually until it becomes a galaxy cluster similar to Virgo, the central region of the supercluster of the same name in which is situated the Local Group of galaxies to which the Milky Way belongs. "We see this city in construction just as it was 12,500 million years ago, when the Universe had less than 10% of its present age, so we are seeing the childhood of a cluster of galaxies like those which are typical in the local Universe" notes Helmut Dannerbauer, an IAC researcher who is co-author of this article.

The distance measured to these studied sources agrees perfectly with the predictions based on photometric observations taken previously on GRANTECAN by Pablo Arrabal Haro, formerly a doctoral student at the IAC, supervised by José Miguel Rodríguez Espinosa, an IAC researcher and Assistant General Secretary of the International Astronomical Union (IAU), and Casiana Muñoz-Tuñón, a researcher and Deputy Director of the IAC, all of them co-authors of the present article. Arrabal developed a method for selecting galaxies with normal star formation rates, based on the photometric survey SHARDS (Survey for High-z Absorption Red and Dead Sources), a Large Programme of the European Southern Observatory (ESO) carried out on the GTC. "I am very happy to see that the method developed during my doctoral thesis works so well in finding and confirming a region highly populated with galaxies in the distant Universe" states Arrabal.

The SHARDS programme has been led by Pablo Pérez-González, researcher at the Centro de Astrobiología (CAB, CSIC-INTA) and also author of the paper. As Pérez-González explains, "measuring exactly how these structures are forming, especially at the beginning of the Universe, is not easy, and we need exceptional data such as those we are taking with the GTC telescope as part of the SHARDS and SHARDS Frontier Fields projects, which allow us to determine distances to galaxies and between galaxies at the edge of the Universe with a precision never achieved before."

In addition, Stefan Geier, GTC support astronomer and co-author of the paper points out that "this highly surprising result would not have been possible without the extraordinary capacity of OSIRIS together with the large colllecting area of the GRANTECAN, the largest optical and infrared telescope in the world."

The Gran Telescopio Canarias and the Observatories of the Instituto de Astrofísica de Canarias (IAC) are part of the network of Singular Scientific and Technical Infrastructures of Spain.