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Scientists have produced a comprehensive roadmap of muscle aging in mice that could be used to find treatments that prevent decline in muscle mobility and function, according to a report published today in eLife.

The study reveals which molecules in the muscle are most significantly altered at different life stages, and shows that a molecule called Klotho, when administered to mice in old, but not very old, age, was able to improve muscle strength.

Age-related loss of skeletal muscle mass and function - called sarcopenia - is associated with loss of mobility and increased risk of falls. Yet, although scientists know how sarcopenia affects the appearance and behaviour of muscle tissues, the underlying molecular mechanisms for sarcopenia remain poorly understood. Current treatments for sarcopenia largely involve prescribing physical activity or dietary modifications, and these have shown moderate success.

"Although there are no proven treatments for sarcopenia yet, there are some pharmaceutical treatments entering clinical trials. Interestingly, many of these act on mechanisms that also involve a protein called Klotho," says co-first author Zachary Clemens, Doctoral Student at the Department of Environmental and Occupational Health, University of Pittsburgh, Pennsylvania, US. "Evidence suggests that Klotho levels gradually decline with age, and so we wanted to test whether supplementation with Klotho may attenuate the development of sarcopenia."

The team first characterised and compared changes in the structure, function and gene activity in skeletal muscle across the lifespan in mice. They grouped mice into four age categories - young, middle-aged, old and oldest-old - and looked at muscle weight, type of muscle fibers, whether the muscles had accumulated fat, and skeletal muscle function. Although old mice displayed mild sarcopenia, the common clinical features of sarcopenia were only present in the oldest-old mice.

Next, they looked at changes in muscle gene activity and found a progressive disruption in genes known to be associated with the hallmarks of aging from the young to the oldest-old mice.

"To date, most studies in skeletal muscle have focused on the identification of specific pathways that are associated with sarcopenia to identify a molecular mechanism linked to the condition," explains co-first author Sruthi Sivakumar, Doctoral Student at the Department of Bioengineering, University of Pittsburgh. "We employed an integrative approach, where we created a network by converting gene expression levels to protein-protein interactions, and then we studied how this interaction network changed over time."

From this network, the team determined the 'network entropy' of the muscle cells as a means to estimate the loss of molecular order within the system over time. They found the greatest difference in order between the young and old age groups (at which point it reached maximal entropy), with little difference between the old and oldest-old mice. Additionally, when they looked at human muscle gene data from different age groups, they saw that entropy reached its lowest level in the fourth decade of life, after which time entropy escalated. This was of interest to the team as the fourth decade of life is the time point when sarcopenia often starts to develop.

Next, they looked at whether administering Klotho to mice would have beneficial effects on the muscle healing after injury. They found that applying Klotho after muscle injury reduced scarring and increased structures associated with force production in the animals. Injured mice that received Klotho also had better muscle function - such as muscle twitch and force production - and their whole-body endurance improved two-fold.

Finally, the team looked at whether giving the mice Klotho could reverse age-related declines in muscle quality and function. They found that Klotho administration led to some improvements in the old mice: force production was improved by 17% and endurance when supporting whole body weight was 60% greater compared to mice without treatment. But this was only seen in the old mice, and not in the oldest-old animals. Further investigation showed that Klotho affected genes associated with the hallmarks of aging in all age groups, but that the oldest-old mice showed a dysregulated gene response.

"Our data suggest that treatment with Klotho may be more effective in slowing the progression of sarcopenia at an earlier time point, rather than rescuing advanced age-related disease, by which time the gene responses seem to be more random," concludes senior author Fabrisia Ambrosio, Associate Professor at the Department of Physical Medicine and Rehabilitation, University of Pittsburgh. "It will be interesting in future studies to determine whether boosting Klotho levels at a younger age could prevent muscle declines into old, and even oldest-old, age."

The brain's auditory system tracks the speed and location of moving sounds in the same way the visual system tracks moving objects. The study recently published in eNeuro lays the groundwork for more detailed research on how humans hear in dynamic environments.

People who use hearing aids have trouble discriminating sounds in busy environments. Understanding if and how the auditory system tracks moving sounds is vital to improving hearing aid technology. Prior research utilizing eye movements to gauge whether the brain is following the trajectory of a moving sound indicates it cannot. A new study from García-Uceda Calvo et al. instead used head movements, a more accurate measure of sound tracking.

The team analyzed head movements of hearing participants as they tracked randomly moving sounds in a dark room. Their analysis revealed humans follow moving sounds, with great accuracy. The auditory system actively tracks the velocity of a sound, just like the visual system, rather than changes in position. The participants improved their sound tracking ability over the course of the experiment, a sign the auditory system was picking up on hidden patterns in the sound trajectories and making predictions. These results indicate the brain possess cells and circuits dedicated to tracking the velocity of sounds.

Optimal cell function requires a fine balance between the synthesis and degradation of biomolecules. Autophagy is the process by which cells degrade and recycle their own components, helping to clean up and maintain the cell's internal environment and ensure the smooth functioning of cellular processes. Autophagy is strongly induced when cells are subjected to stresses like nutrient deprivation, acting under such conditions to supply nutrients through its breakdown of unneeded cellular material.

Autophagy substrates are delivered to vacuoles in yeast or lysosomes in mammals for degradation by double-membrane vesicles called "autophagosomes". While autophagy was originally considered a non-selective process that isolates substrates in the cytoplasm of the cell in a random manner, studies have reported that certain cellular components, such as a subset of proteins and damaged or superfluous cell organelles, are isolated in a selective manner. In contrast to this well-established targeting of organelles and proteins by autophagy, the question of whether RNAs are subjected to autophagy and if they are selectively degraded has remained unanswered.

In their latest study, which was published in Nature Communications, researchers from the Tokyo Tech and RIKEN conducted a detailed analysis of the preferential degradation by autophagy of messenger RNAs (mRNAs), which contain the information required to make cellular protein and bind ribosomes for protein synthesis. Corresponding author Prof. Yoshinori Ohsumi of the Tokyo Tech, who was awarded the 2016 Nobel Prize in Physiology or Medicine for his pioneering work in the field of autophagy, explained the group's findings, stating "We have previously shown that RNA delivered to the vacuole via autophagy in yeast cells, where it is degraded by vacuolar nucleases. The question of whether RNA degradation by autophagy occurs preferentially, however, remains unaddressed. This difficult to address question was the starting point of this project."

As RNAs that accumulate in the vacuole are enzymatically degraded by the nuclease Rny1, they first constructed a yeast strain lacking this enzyme. Using this strain, they were able to isolate and identify RNAs that accumulated in the vacuole. Next, they used the drug rapamycin, which is known to induce autophagy, to assess unique features of mRNA species delivered to the vacuole in Rny1-deficient cells when autophagy is induced. Critically, they discovered that autophagy-mediated mRNA delivery to vacuoles is selective, not random, in nature.

The researchers then characterized the different mRNA species by conducting a broad analysis of the types of mRNAs in these cells, identifying 'vacuole-enriched' and 'vacuole-depleted' mRNAs. Interestingly, housekeeping mRNAs, such as those encoding proteins involved in amino acid biosynthesis, were most likely to be delivered to vacuoles. In contrast, mRNAs required for the synthesis of proteins with regulatory functions, such as protein kinases, were predominantly detected in the vacuole-depleted mRNA fraction.

Furthermore, they demonstrated that mRNAs undergoing translation are delivered to the vacuole, which is suggested to be a translation-dependent process. Moreover, persistent ribosome-mRNA association upon rapamycin treatment was found to be a key determinant of vacuolar mRNA delivery during autophagy-mediated degradation.

Dr. Makino and Prof. Ohsumi highlighted the importance of autophagy in gene regulation, remarking, "Our findings suggest that autophagy regulates mRNA degradation at the translation step, thereby enabling a rapid and sensitive switch from ribosome-associated mRNAs to expression of mRNAs that are essential for an effective response to stress. Preferential degradation of ribosome-mRNAs by autophagy is therefore very likely to determine the fate of individual mRNAs as cells adapt to new conditions."

It will take until at least 2080 before women make up just one-third of Australia's professional astronomers, an analysis published today in the journal Nature Astronomy reveals.

"Astronomers have been leaders in gender equity initiatives, but our programs are not working fast enough," says Professor Lisa Kewley, director of the ARC Centre of Excellence for All-Sky Astrophysics in 3 Dimensions (ASTRO 3D).

Kewley is also an ARC Laureate Fellow at the Australian National University's Research School for Astronomy and Astrophysics. She developed workforce forward modelling that can predict the fraction of women at all levels in astronomy from 2021 to 2060, given different initiatives in hiring or retention. The models show that Australia's university leadership need to adopt 50:50 or affirmative action hiring and introduce exit surveys and retention initiatives.

"With these initiatives we can reach one-third women in 11 years, growing to 50 per cent in 25," she said.

"The gender gap in astronomy is not unique to Australia. This is a worldwide issue, particularly at senior levels.

"The fraction of women in senior astronomy positions in the US, Germany, Canada, Australia, China and the UK has sat at 20 per cent or less for decades - even though women earn about 40 per cent of the PhDs in the field."

She said that female astronomers leave the industry two to three times more frequently than their male counterparts. Those who remain find advancement challenging due to a lack of senior role models at universities, and because they are often overlooked for invited seminars, grants, awards, and all-important telescope time.

In 2014, the Astronomical Society of Australia took steps to improve the ratio of women to men being hired and retained by introducing a gender equality rating system called the Pleiades Awards. The scheme triggered widespread change in many universities and other astronomy-centred research institutions.

These have made a difference, said Dr Anshu Gupta, an ASTRO 3D Fellow at Curtin University in Western Australia.

"I think the barriers to women in the field are lower than they used to be, but there are still serious reforms needed to retain and promote talented junior female academics into senior positions," she said.

Some institutions have also introduced hiring practices designed to attract and retain women. ASTRO 3D and the ARC Centre of Excellence for Gravitational Wave Discovery (OzGrav) have hiring ratios of 50:50. The University of Sydney School of Physics recently hit a target of 78 per cent women appointed to permanent positions.

But hiring is not enough, Professor Kewley's research shows. Retention initiatives are also needed to stem the flow of women out of the sector.

She said that successful retention policies include exit surveys, improving work-life balance for department members, clear action against sexism, insults, microaggression, exclusionary behaviour, and the removal of structural barriers by creating more permanent and fewer fixed-term positions.

"If this sort of program becomes widespread, the discipline can reach the 30 per cent target in a decade or so," said Professor Kewley.

ANU Vice Chancellor and Nobel Laureate Brian Schmidt commented:

"We as university leaders need to step up in areas like astronomy, but also across all the academic areas in our institutions where the male-female imbalance is large.

"Professor Kewley's research shows that workforce forward modelling is highly effective way to assess the potential impact and utility of new diversity policies and initiatives. I encourage my peers across the research sector to take a close look and use the tools to drive positive change."

Over the last 200 years, researchers have worked towards understanding the global distribution of species and ecosystems. But so far even the basic knowledge on the global geography of genetic diversity was limited.

That now changes with a recent paper from Globe Institute. Professor David Nogues Bravo and his team has spent the last eight years combining data from scientific gene banks with scenarios of future climate and land-use change. The result is the first ever global assessment of how it will impact the genetic diversity of mammals, e.g. when tropical forests are converted to agricultural land.

'Our study identifies both genetically poor and highly diverse areas severely exposed to global change, paving the way to better estimate the vulnerability to global change such as rise in temperature as well as land-use changes. It could help countries to find out how much of the genetic diversity in their own country may be exposed to different global change impacts, while also establishing priorities and conservation policies', says David Nogues Bravo.

For example, Northern Scandinavia will be heavily impacted by climate change and not so much from land use change, whereas the tropical areas of the world will suffer from both climate change and land-use change. However, David Nogues Bravo underlines that it is difficult to compare areas.

'The genetic diversity in Scandinavia is always going to be lower than in the tropics, but that doesn't mean that the overall diversity there is not important. If we lose populations and species such as the polar bear, it's just one species but it will it will impact the total stability of ecosystems. However, the largest threat to genetic diversity will be in the tropical areas, which currently harbor the largest diversity of the bricks of life, genes. These regions include ecosystems like mangroves, jungles and grasslands', says David Nogues Bravo.

Putting it all together

The researchers have looked into gene banks with mitochondrial data from mammals. The mitochondria also regulate the metabolism, and by looking how it has changed over time, it can also unveil changes in diversity.

'The mitochondrial diversity is a broad estimate of adaptive capacity. We also used to think that mitochondria was a neutral marker, when it is in fact under selection. That means that some selection may relate to the physiological limits of a species in relation to climate, which makes it a very useful tool for researchers to track how global change impacts the genetic diversity in a specific area', explains David Nogues Bravo.

For many samples, there were not any geographical information available. The researchers used artificial intelligence to add geographical locations and then they built models predicting how much genetic exits in places without data.

Then the researchers analyzed maps of genetic diversity, future climate change and future land-use change, to reveal how and where global change will impact mammals.

Interest from the United Nations-agency

The research has attracted the attention of Secretariat of the United Nations Convention on Biological Diversity. David Nogues Bravo hope that the assessment map could become an important tool for the high-level summits among countries to help define policies for biodiversity protection.

'We are only now starting to have the tools, data and knowledge to understand how genetic diversity changes across the globe. In a decade from now, we will be able to know also how much of that genetic diversity has been lost since the Industrial Revolution for thousands of species and in a stronger position to bring effective measures to protect it', he says.

In the coming years, he hopes that scientists will map the global genetic diversity of many other forms of life, including plants, fungi and animals across the lands, rivers and oceans.

'Have been attempts to map the genetic diversity for amphibians, birds and reptiles, but we don't have maps for plants, insects or fungi. And whereas there are around 5000 mammal species, there are many more insect or fungi species, maybe millions. We don't even know how many, yet. So it will take longer, but it will come in the next decade', he says.

'We hope to see more of these assessments in the next decade, and to complement then with long-term monitoring programs, in which we can monitor the genetic diversity of thousands of species and ecosystems across the planet continually', says David Nogues Bravo.

Psoriasis is a common inflammatory skin condition. The underlying genetic factors have not yet been sufficiently researched. The skin inflammation is usually triggered by external factors such as infections or stress. A research team at the Institute of Cancer Research of the Medical University of Vienna has now managed to identify a new factor in signal transmission of the immune system that plays a major role in the development of a psoriatic episode. The scientists have shown that symptoms can be alleviated by inhibiting the "c-Jun" protein in signal transmission.

The common clinical manifestation of psoriasis is a pinkish-grey thickening of the epidermis in distinct foci of infection, so-called plaques. Biomedical research into the molecular processes involved has shown that a disruption in the normal interaction between the immune system and dermal epithelial cells is responsible for the inflammation. However, it was hitherto unclear which signalling pathways regulate the activation of immune cells, thus contributing to pathogenesis.

Function deciphered

In the recent study published in the leading journal EMBO Molecular Medicine, it was demonstrated using patient data and animal models that a protein known as "c-Jun" in a particular immune cell, the dendritic cell, plays a major role in promoting psoriatic skin inflammation. "Inhibiting signal transmission by c-Jun alleviates symptoms in the animal model," says lead author of the study Philipp Novoszel from MedUni Vienna's Institute of Cancer Research. The protein that was studied, c-Jun, belongs to a larger family of transcription factors, DNA-binding factors, known as Activator Protein-1 (AP-1). Previous studies have already identified a significant role of these AP-1 proteins in psoriasis in dermal epithelial cells but its function in immune cells was not yet clear.

"In order to answer this question, we examined whether AP-1 proteins in immune cells have a role in the pathogenesis of psoriasis. We identified elevated values of c-Jun in dendritic cells in skin sections of psoriasis patients," explains Novoszel. "To further investigate the role of c-Jun, we deactivated the gene specifically in dendritic cells." When psoriasis-like skin inflammation was now triggered, we found that the deactivation of c-Jun reduced epidermal thickening and decreased the infiltration of immune cells.

Treatment option

Pharmacological inhibition of the c-Jun activating protein, known as JNK (c-Jun N-terminal Kinase) was likewise effective. "That represents a potential treatment option, since highly effective, selective JNK inhibitors are available and could be investigated," stresses Novoszel. A further analysis using human dendritic cells showed that c-Jun controls the secretion of a key molecule in the development of psoriasis, cytokine interleukin-23 (IL-23). High values are characteristically found in psoriasis patients and lead to activation of disease-triggering T cells. "The inhibition of c-Jun-dependent signal transmission could improve the clinical picture of psoriasis by reducing pathogenic IL-23."

"Our study findings describe a previously unknown, pro-inflammatory role of c-Jun in dermal dendritic cells. This occurs, on a molecular level, through the control of the cytokine interleukin-23. A therapeutic blockade of c-Jun-JNK signal transduction might therefore be a promising therapeutic approach for the treatment of psoriasis," says the study author in summary.

Atlantic bluefin tuna have returned to UK waters and can once again be seen during the summer and autumn months.

Their numbers appear to be increasing, following a long period of absence linked to population decline, according to research led by Cefas and the University of Exeter.

Marine scientists in the UK and Ireland have analysed multiple datasets, spanning a 16-year period, to document the increase in bluefin, which arrive into the waters of the Celtic Seas and off South West England, the Scilly Isles, and North West Ireland to feed in late summer and autumn.

The research is part of the Defra-funded "Thunnus UK" research project.

Thunnus UK was established to improve knowledge of this species, as an essential first step in ensuring a positive future for Atlantic bluefin tuna around the UK.

Central to the project's success has been a concerted effort to share and combine important data on where people have observed Atlantic bluefin tuna.

This will help to identify where and when these fish are found in UK waters.

Nearly 1,000 unique observations were recorded between 2013 and 2018 by citizen scientists, scientists, fishers and eco-tour leaders.

Researchers found that Atlantic bluefin tuna begin to arrive in May and stay as late as January.

However, peak numbers were recorded between August and October each year.

The research draws on five key data sources:

The general public: A total of 80 sightings recorded by the public and submitted to http://www.thunnusuk.org

Eco-tourism: three eco-tourism vessels collecting data on more than 1600 boat tours off the SW coast of England between 2008 and 2018.

Opportunistic scientific surveys: 40 days of surveys with >2500 km of effort conducted by Cefas and University of Exeter experts off the Northwest Coast of Ireland and SW England in 2016 and 2018.

Fisheries independent surveys: (1) data collected by MarineLife during the Peltic survey by Cefas between 2013 and 2015, and (2) data collected by the Irish Whale and Dolphin Group during the Irish Marine Institute's Celtic Sea Herring Acoustic Survey between 2014 and 2018

Bycatch in commercial fisheries: Bluefin tuna were accidentally caught (bycatch) in the Irish commercial fishery for albacore tuna between 2003 and 2017.

Lead author Tom Horton, of the University of Exeter, said: "Atlantic bluefin tuna are once again a feature in nearshore waters off the UK and Ireland.

"We've been able to document this story by using data from a wide variety of sources.

"We need to work together to ensure a future for Atlantic bluefin tuna, both in the UK and Ireland and more broadly throughout their range in the Atlantic Ocean.

"This is a really exciting study and the return of these fish suggest an important role in the UK's ecosystem."

Jeroen van der Kooij, Principal scientist and Peltic Survey Lead, Cefas, said: "The unique data collected during our annual pelagic ecosystem survey of SW English waters is fundamental to this research.

"Marine animal observers from MARINELife on board our research vessel recorded not only the arrival, but also a subsequent year-on-year increase in sightings of bluefin tuna in the area.

"We will continue to collect this information, which, in combination with data on their prey fish and habitat collected during the same survey, will hopefully increase our knowledge of these exciting yet enigmatic animals."

The Andes Mountains of South America are the most species-rich biodiversity hotspot for plant and vertebrate species in the world. But the forest that climbs up this mountain range provides another important service to humanity.

Andean forests are helping to protect the planet by acting as a carbon sink, absorbing carbon dioxide and keeping some of this climate-altering gas out of circulation, according to new research published in Nature Communications.

The study -- which draws upon two decades of data from 119 forest-monitoring plots in Colombia, Ecuador, Peru, Bolivia and Argentina -- was produced by an international team of scientists including researchers supported by the Living Earth Collaborative at Washington University in St. Louis. The lead author was Alvaro Duque from the Universidad Nacional de Colombia Sede Medellín.

"Based on the information that we have, Andean forests are a carbon sink -- capturing more carbon than they emit," said J. Sebastián Tello, a co-author of the study and a principal investigator for the Living Earth Collaborative working group titled, "A synthesis of patterns and mechanisms of diversity and forest change in the Andes: A global biodiversity hotspot."

"The amount of carbon that is stored in the aboveground biomass in the stems and leaves of trees is actually increasing through time, potentially offsetting some of the carbon dioxide emissions that are released to the atmosphere," said Tello, an associate scientist at the Center for Conservation and Sustainable Development at the Missouri Botanical Garden.

Tello leads the Madidi Project, a long-term study that the Missouri Botanical Garden has supported for nearly 20 years, involving plant diversity and forest change in Bolivia. Twenty-six of the forest plots included in this study were from the Madidi Project.

"Two critical research questions are how and why the functioning of ecosystems is being impacted by climate change," added Jonathan Myers, associate professor of biology in Arts & Sciences at Washington University, another co-author of the new study. "Carbon storage is one of the most important ecosystem services that helps to mitigate the effects of rising carbon dioxide levels under climate change and temperature warming.

"This study provides insights into how species on the move, under climate change, might be impacting these broader ecosystem services important to humanity," Myers said.

Carbon is an important building block of life on Earth, but the element contributes to global warming when it is released into the atmosphere as carbon dioxide. Living plant tissues such as the stems, bark, branches and twigs of trees can act as a carbon sink because they absorb carbon dioxide from the atmosphere during photosynthesis.

By locking in carbon, trees in forests around the world play a role in maintaining global climate stability. Some forests play a bigger role than others -- the Andes prime among them, the study found.

Tropical and subtropical ecosystems are believed to account for nearly 70% of all the carbon sequestered by Earth's forests. But previous estimates of tropical carbon uptake were largely based on studies of lowland ecosystems, such as the Amazon.

This study incorporates data from forest plots spanning a range of more than 3,000 meters (10,000 feet) in elevation across the subtropical and tropical Andes. The results indicate that the Andes are similar to other tropical forests in that they are acting as aboveground carbon sinks. However, the overall relative strength of the Andean carbon sink exceeds estimates from previous studies conducted in lowland tropical forests in Amazonia, Africa or Southeast Asia, the researchers discovered.

Factors such as precipitation, temperature and size-dependent mortality of trees tend to drive carbon storage dynamics in Andean forests.

Because of its vast size, the Amazon forest currently accumulates more carbon than the Andean forest. But recent research has suggested that the Amazon might become saturated with carbon in the near future. Under this scenario, the continued net uptake of carbon in Andean forests will become even more important.

As a neighbor to the relatively well-studied Amazon forest, much about Andean forest ecosystems remains comparatively unknown. Challenging mountain terrain combined with remoteness makes it harder for scientists to reach parts of the Andes. It's also hard to secure funding to support large-scale research projects that span multiple countries.

"This paper collects and integrates information from lots of different research groups that have been working for decades independently," Tello said. "It's one of the first big efforts to bring together the scientists who have been monitoring these forests."

William Farfan-Rios, a native of Cusco, Peru, and a postdoctoral research fellow of the Living Earth Collaborative, knows first-hand how difficult it is to conduct field research in the Andes. Since 2003, he has coordinated and led field campaigns and research projects with the Andes Biodiversity and Ecosystem Research Group, working along an elevational transect between the Andean and Amazonian forests in Peru. Farfan-Rios is also a co-author on the new study.

Farfan-Rios recalled the challenges associated with one particular forest survey effort, saying: "At the beginning, we were a team of 14 people from Cusco. And, at the end, I was the only one who was still surveying those plots. I was the only survivor of this initial team! Right now, I'm still collaborating with that group and using this information for my postdoc with the Living Earth Collaborative."

In only 1% of the Earth's land surface, the tropical Andes contain 15% of the world's plant species, or about 45,000 species in total. Approximately half of these plants -- about 20,000 species -- are endemic, meaning they are only found in the Andes. In addition to harboring extreme levels of biodiversity, Andean forests provide and protect sources of food, water and power for more than 50 million people. However, global environmental change -- including deforestation, human population growth and climate change -- is endangering Andean biodiversity and ecosystem services.

"Building on William's research and the finding that Andean forests are important carbon sinks and targets for conservation, it's important to understand how upward species migrations that are occurring under climate change might sustain those ecosystem services or functions in the future," Myers said. "Conservation initiatives not only support current forest biodiversity, but also habitats for species that will migrate to new areas in the future."

Alzheimer's disease (AD) is a form of progressive dementia interfering with daily living. It is caused by the decline in the number of brain cells resulting in the deterioration of our mental abilities. One of the main reasons for the worsening brain cells condition and even the brain shrinkage are molecules having a specific structure called β-amyloids (Aβ). They are peptides that tend to agglomerate around the nerve cells, becoming toxic and damage them. Recent studies, presented by scientists from the Institute of Physical Chemistry, Polish Academy of Sciences, led by dr. Piotr Pieta, give hope for inhibition of the β-amyloids' toxicity by applying the K162 molecule. Researchers present a tremendous protective impact on the biological membranes and explain its inhibition mechanism.

M like memory

Memory is an essential part of our transformation from newborns to adults. It is one of the crucial processes taking place in our brain determining who we are. Our memories are stored thanks to nerve cells - neurons processing and transmitting information by electrical and chemical signals. Within the formation of new projections and interconnections between them, some memories can stay with us for the whole life. If these neurons are inflamed, they can be degenerated, leading to brain volume loss, causing an even progressive form of dementia. As result, it negatively affects our memory as well as our thinking and behavior.

Unfortunately, many people struggle with the cruel and silent memory killer affecting the brain irreversibly, which is AD. It disrupts the communication among neurons, leading to their inflammation, loss of cells' functions, and following cells' death. It leads to memory loss and causes severe problems like confusion and affecting the general intellectual ability. Therefore, affected people lose all they have. It can affect even young people, developing AD silently in the brain for several years until giving fatal symptoms.

A like amyloids, B like the beta version

What is the cause of Alzheimer's disease, which promotes neuron inflammation and exacerbates their damage? One of the causes is misfolding and abnormal production of Aβ, which builds up in the brain and affects neurons. When Aβ occurs as monomers of a structure rich in α-helices and random coils, they are readily soluble in water exhibiting neuroprotective abilities and stimulates brain development. However, misfolding and overproduction lead to the production of a water insoluble Aβ of a structure rich in β-sheet, which easily aggregate to form toxic oligomers and damages biological membranes. Therefore, many studies are focused on inhibiting Aβ aggregation and decreasing the lifetime of toxic Aβ oligomers.

Dr. Piotr Pieta's team solved the mechanism of inhibiting the toxicity of small Aβ oligomers by the molecule with an intriguing abbreviation: K162. Researchers focused on molecular-level direct imaging, electrochemical, and molecular dynamics studies to show in detail the Aβ-K162 interactions in the absence and presence of a brain-like model membrane.

"K162 modifies Aβ aggregation by inhibiting toxic Aβ oligomers production and promoting non-toxic Aβ monomers, dimers, and fibrils formation. Unlike other inhibitors, K162 protects neurologically beneficial Aβ monomers. This unique mechanism of action of K162 may provide an alternative therapeutic fight strategy against AD". - remarks Dr. Piotr Pieta.

One of the most important properties of the K162 molecule is that it can easily cross the biological membranes and penetrate the blood-brain barrier. Furthermore, once it binds to nerve cells, it protects them against inflammation and neuronal damage. Currently, there are many difficulties in successful therapies protecting neurons from toxic clusters of amyloids, while thanks to the understanding of its inhibition mechanism we are a step closer to develop novel therapeutics. Experimental results were described in the ACS Chemical Neuroscience on 22nd January 2021.

Coral reefs are one of the most biologically diverse ecosystems on earth. In the northern Red Sea and Gulf of Aqaba corals also have exceptionally high tolerance to increasing seawater temperatures, now occurring as a consequence of global warming. This characteristic led coral reef scientists to designate this region as a potential coral reef refuge in the face of climate change - a reef where corals may survive longer than others that are being lost at an alarming rate due to human pressures.

However, global climate change will also result in more variable weather patterns, including extreme cold periods. Some researchers predict that the Red Sea region is entering a cooling phase. Therefore, researchers from Bar-Ilan University and Interuniversity Institute for Marine Science in Eilat conducted an experiment to investigate the effect of an unusually cold winter on corals from the Gulf of Aqaba.

In a paper recently published in the journal PeerJ, they demonstrate that a winter even 1°C cooler than average results in a physiological stress response similar to that seen in other corals under heat stress. This result shows for the first time how perilously close Gulf of Aqaba corals live to their lower temperature threshold.

Previous studies conducted within the research group of Prof. Maoz Fine, of Bar-Ilan University's Mina and Everard Goodman Faculty of Life Sciences, have used controlled experiments in the Red Sea Simulator System to expose locally abundant corals to increased seawater temperatures expected to occur within and beyond this century. Multiple experiments found that corals from this region have an extraordinary tolerance to high temperatures, which kill corals elsewhere in the world. Prof. Fine's lab and researchers from other groups have tested multiple coral species and at different phases of their life cycle including the reproductive and larval phases, which are typically more sensitive to environmental change; all show similar tolerance.

"Whilst we have repeatedly demonstrated the high temperature tolerance of corals on the shallow reefs in Eilat, we wanted to test the possibility that this exceptional heat tolerance comes with the trade-off of being cold-sensitive," said Dr. Jessica Bellworthy, who conducted her doctoral research in Prof. Fine's lab. "Indeed we found that exposure to cold water periods causes a physiological response akin to bleaching." Better known as a response to high water temperatures, coral bleaching, is the loss of algal symbionts that must be present within the coral tissue in order to provide the coral with energy. Without the symbionts, the chances of coral mortality are high. Coral bleaching is the leading cause of coral decline in the world today. Therefore, while the corals of the Gulf of Aqaba can tolerate very high temperatures, even an acute cold spell may cause bleaching in this population.

However, Bellworthy and Fine's cold stressed corals did not die and recovered once water temperatures returned to normal. Experimental corals were maintained at normal temperatures and then underwent a second test - an anomalously hot summer. "It was an important discovery for us to understand that even those individuals that suffered the cold winter stress, still did not bleach at the high temperatures," says Bellworthy. This is good news for the corals in the Gulf of Aqaba; the high thermal tolerance is not lost and thereby corals should not undergo two bleaching events in the same year, a threat that faces others such as the Great Barrier Reef in Australia.

Coral reefs are highly sensitive to temperature change. Therefore, identifying those that respond differently to thermal stress aids in understanding the mechanisms of environmental adaptation in corals. In addition, researchers can focus attention on conserving and studying such unique reefs.

April 19, 2021 - An estimated 50 million people undergo surgery each year in the United States, and a significant proportion of them have undiagnosed or untreated sleep disorders (SD) or sleep-disordered breathing (SDB). Issues at the intersection of anesthesiology and sleep medicine are the focus of the Society of Anesthesia and Sleep Medicine (SASM) whose 10th anniversary is commemorated in the special theme May issue of Anesthesia & Analgesia.

The special issue looks back at a remarkable first decade of achievements in research and clinical practice by this young subspecialty society, while looking forward to further progress. A key focus is the potential for treating surgery and the perioperative period as an opportunity for recognition, diagnosis and effective treatment of patients with undiagnosed SD or SDB, according to an editorial by Satya Krishna Ramachandran, MD, Associate Professor of Anaesthesia at Harvard Medical School and President of SASM.

New insights on sleep apnea surgery, postoperative respiratory depression and more
The SASM theme issue presents 15 papers on key issues related to anesthesia and surgical management of patients with SD or SDB. Eric Brian Rosero, MD, MSc, and Girish P. Joshi, MBBS, MD, of University of Texas Southwestern Medical Center, Dallas, analyzed the outcomes of 3,208 patients undergoing sleep apnea surgery.

The study focused on complications and other outcomes for patients undergoing inpatient versus outpatient surgery. About two-thirds of patients had inpatient surgery, spending at least one night in the hospital. On initial analysis, the inpatient surgery group had a higher rate of hospital readmissions, repeat surgery, and complications: 6.8 versus 5.5 percent.

However, on further analysis of patients with similar risk factors (age, health conditions, etc.), the rate of adverse outcomes was almost identical for the inpatient and outpatient groups: 6.2 versus 5.9 percent. Certain factors were associated with a higher rate of adverse events, including diabetes and more complex surgery. "These risk factors could be used to determine the need for an overnight stay," Drs. Rosero and Joshi conclude.

A study led by Toby N. Weingarten, MD, of the Mayo Clinic, Rochester, Minn., used data from a previous study of patients undergoing continuous bedside monitoring after surgery to assess the occurrence of episodes of postoperative respiratory depression (RD). While postoperative RD events were once considered uncommon, recent studies suggest that they may occur in more than 40 percent of patients and often go unrecognized.

From the total of 250 patients, the researchers identified 155 patients with a total of more than 2,500 RD episodes within the first 24 hours after surgery. Initial RD episodes tended to occur within the first several hours after surgery. These initial episodes peaked in the late afternoon and early evening, often followed by repeated episodes during the early morning hours.

The rate and frequency of postoperative RD episodes were greater for patients who scored higher on a risk scale used in the original study. Dr. Weingarten and colleagues believe their unique data may have important implications for research and clinical practice, including the development of new postoperative monitoring strategies.

In his editorial, Dr. Ramachandran focuses on strategies to promote diagnosis and treatment of unrecognized sleep disorders in patients undergoing anesthesia and surgery. He writes, "If we in anesthesiology are indeed committed towards the fundamental tenets of perioperative medicine, the import of using the perioperative period to diagnose and initiate long-term medical care of SD or SDB cannot be overstated."

Assembled by invitation from the editors of Anesthesia & Analgesia, the SASM theme issue celebrates "a decade of research achievements in the common ground between sleep and anesthesia," according to an introductory editorial by Dr. Weingarten and his fellow guest editors. They add: "Among other things, these studies build the case for greater awareness of sleep issues among anesthesiologists and enhanced sleep training in anesthesia."

Inside your body, cell movement plays a crucial role in many significant biological processes, including wound healing, immune responses and the potential spread of cancer.

"Most people don't die from having a primary tumor," said Kolade Adebowale, a graduate student in chemical engineering, and a member of the Chemical Biology Interface (CBI) graduate program in Chemistry, Engineering & Medicine for Human Health (ChEM-H) at Stanford University. "The problem is when cancer cells from the tumor acquire the ability to metastasize or move to different parts of the body."

As an attempt to advance studies of cell migration, Adebowale and colleagues in the lab of Ovijit Chaudhuri, associate professor of mechanical engineering at Stanford, have worked to develop and test new types of material that closely imitate the real tissue that surrounds cells. New findings built on this work, published April 19 in Nature Materials, upend the "textbook" view of cell migration and bring better insight into the impact of a material's elastic and viscous properties on cells.

"We found that it makes a big difference if the cancer cells are on a very rigid plastic or if they're on a soft and viscoelastic material, like a Jell-O," said Adebowale, who is lead author of the paper. "This adds to a lot of recent evidence that the behavior of cancer is not just about the cancer cells - it is also about the environment that the cancer cells interact with."

Like silly putty

Cell migration is traditionally studied on a hard, transparent piece of polymer called "tissue culture plastic" or elastic hydrogels, like soft contact lenses. Based on these studies, the current belief is that cells cannot migrate on hydrogels that are too soft. However, the researchers aim to mimic the real-life biological tissues on which cells migrate - which are soft and not purely elastic, like a rubber band, but viscoelastic.

"They are solid materials, but they also have viscous and liquid characteristics that allow them to flow over longer timescales," Adebowale said.

Examples of viscoelastic materials like the ones created for the research include bread dough, mozzarella and silly putty, according to Chaudhuri. These materials initially resist deformation, like an elastic material, but viscously relax that resistance over time.

When the researchers studied the movement of cancer cells on their more tissue-like substrate, the results contradicted existing expectations.

"We found that when the substrate is viscoelastic, the cells can migrate quite robustly, even though it is soft," said Chaudhuri, who is senior author of the paper.

Not only did the study find that cells can migrate on soft, viscoelastic substrates, the researchers also discovered the migration movement is unique. On a stiff, 2D surface like tissue culture plastic, cells adhere to the surface and form a fan-like protrusion. This protrusion, called a lamellipodium, drives forward motion by extending the leading edge forward and pushing off the surface. On the viscoelastic materials the team created, the cells didn't spread out so extensively. Instead, they used thin, spike-like protrusions called filopodia to drive their movement. Further, their experiments showed the cells use what's called a "molecular clutch" to migrate on the substrates.

"Imagine you're moving on ice. If you don't have enough adhesion to the ice, and try to run, you're not going to go anywhere," said Chaudhuri. "You really need a strong grip to push off and move forward. That's what the molecular clutch does for cells."

Robustly migrating cells on rigid tissue culture plastic form strong adhesions to the substrate. The authors observed that cells on soft, viscoelastic substrates are also able to migrate robustly but, importantly, these cells are able to do so with fewer, weak adhesions - like the cells are moving on their tippy-toes, not their entire foot.

"I think what was most surprising was that the material property - viscoelasticity - can have such a dramatic impact on the ability of cells to migrate," said Adebowale.

Viscoelasticity and cell culture

The fact that the mode of cell migration that the researchers observed is not seen on hard substrates or substrates that are only elastic shows how viscoelasticity is essential to the behavior of cells - and therefore important to replicate in future studies.

"This challenges the textbook view of how we understand cell migration," said Chaudhuri. "Cells migrate differently on viscoelastic tissue than they do on glass, plastic petri dishes or elastic gels. So, if we want to study cell migration, we need to use viscoelastic substrates."

While the study looked at single-cell migration, cancer cells migrate as a group in the body and various stages in development involve the collective movement of cells. Next, the researchers hope to answer the question of how viscoelasticity impacts collective cell migration.

Researchers at Baylor College of Medicine and collaborators at other institutions have discovered that POT1, a gene known to be associated with risk of glioma, the most common type of malignant brain tumor, mediates its effects in a sex-specific manner. Researchers found that female mice with glioma that lacked the gene survived less than males. This led them to investigate human glioma cells, where they found that low POT1 expression correlated with reduced survival in females.

Published in the journal Cancer Research, the study also shows that, compared to males', female tumors had reduced expression of immune signatures and increased expression of cell replication markers, suggesting that the immune response and tumor cell proliferation seemed to be involved in favoring tumor growth.

This study began as a collaboration between Dr. Benjamin Deneen's lab at Baylor and Dr. Melissa Bondy's lab, previously at Baylor and now at Stanford University. Bondy and her group study familial or inherited forms of glioma from the epidemiologic standpoint. Their studies have linked mutations in the gene POT1 to the risk of glioma development.

In the current study, the researchers looked to determine whether Pot1 mutations affected glioma development in a mouse model of the condition developed in the Deneen lab.

"We began our study by knocking out the Pot1 gene in our mouse model and examining whether this affected the development and growth of glioma tumors," said first author Dr. Ali Jalali, assistant professor of neurosurgery at Baylor.

Jalali and his colleagues worked with male and female mice, and in their first analyses they pooled the data from both groups.

"This analysis showed that the absence of Pot1 did not seem to affect tumor growth," Jalali said. "But then, a team member looked at male and female responses separately. Unexpectedly, we were able to see that in the absence of Pot1, gliomas grew faster in female mice. Females also had a shorter survival than males."

The team then investigated whether the level of POT1 expression in glioma tumors was associated with sex-dependent survival in patients. "We found that a reduction of POT1 expression in human gliomas also had sex-dependent effects on tumor growth," Jalali said.

Next, the researchers investigated what could be mediating the sex-dependent effects of lacking POT1 by comparing the genes expressed by glioma tumors with or without POT1. They conducted these analyses in both human glioma samples and in gliomas from the animal model.

"We observed that, in the absence of POT1, there was a sex-specific effect on expression of genes involved in the immune response, both in mice and humans," Jalali said. "Some of these genes are known to contribute to the activation of immune cells, such as T cells and macrophages, which have been shown to play a role in cancer growth. We also took a closer look at the tumors and found that female mice lacking the Pot1 gene had less immune cell infiltration into the tumors compared to males. This suggested the possibility that a sex-dependent change in immune response contributed to the observed gender differences in tumor aggressiveness driven by loss of Pot1."

In addition, Jalali and his colleagues compared the ability of glioma cells with and without Pot1 to proliferate and discovered that female glioma cells without Pot1 proliferate more than male glioma cells. They also saw concordant sex-dependent effects on the length of telomeres, the tips of the chromosomes, and in markers of DNA damage.

"Taken together, our results not only show that mutations in the Pot1 gene promote glioma development in a sex-dependent manner, but also support that the mutations might favor glioma development by increasing the tumor's ability to proliferate, by reshaping immune infiltration in tumors and probably other effects yet unexplored," said Deneen, corresponding author of the work and professor and Dr. Russell J. and Marian K. Blattner Chair of neurosurgery at Baylor. "Importantly, POT1 effects are sex-dependent both in our animal model and in human glioma. We are interested in understanding how POT1 leads to this sex-dependent effects in glioma and perhaps in other cancers and whether other genes that also are linked to glioma work in this way."

"This was a great collaboration," said Bondy, a co-author of this study. "It is exciting that we were able to translate what we found in epidemiological studies of human families into an animal model. We showed in the animal model that Pot1 has a functional significance affecting glioma growth. Understanding how POT1 mutations promote glioma development in a sex-dependent manner would provide important new insight into how to manage and treat the disease."

As the back-to-school rush begins, podiatry experts at the University of South Australia are encouraging parents to get their children's school shoes professionally fitted, as new research confirms that ill-fitted footwear can significantly impede foot movement and comfort.

In a new study, researchers tested the effect of shoe size on foot motion and comfort among children aged 8 to 12 years, finding that shoes that were one size too small restricted the normal movement of the heel, arch and big toe joint during walking.

The study also confirmed that a comfortable shoe fit can be determined by a 'rule of thumb', where the wearer's thumb width from their longest toe to the end of their shoe is an effective and accurate measure for comfortable fit.

Lead researcher and musculoskeletal expert, UniSA's Dr John Arnold says that well-fitted school shoes are important for children to feel comfortable at school.

"Thousands of school shoes are purchased every year with children wearing them for more than seven hours a day during school," Dr Arnold says.

"If a child's shoes don't fit well, they're likely to experience discomfort and pain, which can impact their participation and enjoyment of everyday activities such as play and sport.

"Importantly, our research found that when children's shoes were too small, they restricted foot and joint movements, which could create problems for children's feet in the future."

Co-researcher and podiatry expert, UniSA's Dr Helen Banwell says when it comes to the back-to-school rush, parents cannot afford to overlook the benefits of a well-fitted school shoe.

"The start of a new school year can creep up quickly, and it's easy to overlook or rush through the purchase of new shoes," Dr Banwell says.

"Our research shows that school-aged children can easily help identify a good shoe fit, by rating their level of comfort in the heel and toes.

"A good shoe fit will absolutely start your school year on the right foot."

Sophia Antipolis - 17 April 2021: Elevated blood pressure, high cholesterol and diabetes increase the risk of heart disease. But a large study today reveals that in people with these conditions, increasing activity levels is associated with a reduced likelihood of heart events and mortality. The research is presented at ESC Preventive Cardiology 2021, an online scientific congress of the European Society of Cardiology (ESC).1

Study author Dr. Esmée Bakker of Radboud University Medical Center, Nijmegen, the Netherlands said: "Previous research showed that improvements in physical activity are beneficial to health. However, those studies were performed in the general population. In our study, we were interested to see if there were similar effects in individuals with cardiovascular risk factors such as high blood pressure, high cholesterol, and diabetes."

The study included 88,320 individuals from the LifeLines Cohort Study. Participants underwent a physical examination and completed questionnaires about their medical history and lifestyle including exercise. The questionnaires were repeated after approximately four years.

Study participants were divided into five groups according to activity levels at baseline and four years: large reduction, moderate reduction, no change, moderate improvement, and large improvement.2 Participants were followed-up for a median of seven years after the first assessment for the occurrence of cardiovascular disease or death.

A total of 18,502 (21%) individuals had high blood pressure, high cholesterol, and/or diabetes at the start of the study. The average age of this group was 55 years. After adjusting for age, sex, and baseline physical activity, the researchers found that those with a moderate to large improvement in physical activity were around 30% less likely to develop cardiovascular disease or die during follow-up compared to those who did not change their activity level.

The remaining 69,808 (79%) participants did not have high blood pressure, high cholesterol, or diabetes at the start of the study. The average age of this group was 43 years. After adjusting for age, sex, and baseline physical activity, the researchers found that those with large reductions in physical activity had a 40% higher risk of cardiovascular disease or death compared to those who did not change their activity level.

Dr. Bakker said: "Our study suggests that to prevent heart attacks and strokes and boost longevity, healthy individuals should maintain their physical activity levels, while those with risk factors need to become more active. The associations we found were even more pronounced in people who were relatively sedentary at the start of the study, indicating that inactive people have the most to gain."

To prevent heart disease, European guidelines recommend at least 150 minutes a week of moderate
intensity or 75 minutes a week of vigorous intensity aerobic physical activity or an equivalent combination.3

Dr. Bakker said: "If you are currently sedentary, walking is a good activity to start with. If you are already hitting the recommended amount, try doing 10 minutes more each day or increasing the intensity."