Culture

Researchers from Skoltech and their colleagues have shown that adaptation to similar environments hardly involves similar genomic positions when species are distantly related. The team investigated recurrent adaptations of wildlife birds' mitochondria to high altitude, migration, diving, wintering, and flight. Repeatable substitutions are rather a coincidence than adaptation, which confirms the scientific opinion that distant species "choose" different ways of similar trait evolution. The paper was published in the journal Genome Biology and Evolution.

If an organism wants to survive in unusual conditions, such as oxygen starvation typical for high altitudes or elevation of metabolism rate due to extreme temperatures, it has to adapt. If different species meet similar environment conditions, they will adapt independently and could even do it by same substitutions in identical genomic positions - this is called single-position molecular convergence.

"Convergent evolution is one of most fascinating topics of evolutionary biology: from a practical point of view, it helps to find particular genomic positions associated with adaptation; from a more theoretical one, it shows how repeatable evolution is. Yet detection of adaptive convergent single-position mutations is known to be hard, especially in phylogenetically distant species: scientists continue to argue about whether it is possible at all," Skoltech PhD graduate Valentina Burskaia says.

Burskaia, Professor Georgii Bazykin and their colleagues designed an unusually large dataset of 415 species in which similar traits appear independently dozens of times. The dataset allowed them to examine the problem deeply, as previous attempts to detect convergent single-nucleotide mutations in phylogenetically distant species were often limited by few numbers of convergent phenotype acquisitions.

"Mitochondrial genome was chosen for the study as it is small and thus sequenced for many species, yet full of extremely important genes. Mitochondrial genes are responsible for hypoxia and metabolism level tuning: this guided our selection of phenotypic traits of interest," Burskaia notes.

The team looked at birds who live at high altitudes and diving birds (likely to face hypoxia). To study adaptations which affect metabolism rate changes, scientists considered four groups of species: birds with outstanding flight abilities, long-distance migrants, flightless birds and wintering birds. By running powerful phylogenetic methods, where species are placed on a "tree" and coincident changes in phenotype and genotype are counted, the researchers were able to show that the majority of convergence events can be explained by random coincidences rather than adaptation.

The study, being conceptually close to recent attempts to search for single-position convergences in echolocating bats and marine mammals, confirms that evolutionary landscape at between-order distances is too different for single-position adaptive convergence.

Other organizations involved in this research include Lomonosov Moscow State University, Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, and Hong Kong University of Science and Technology.

Osaka, Japan - Scientists from the Department of Physics and the Research Center for Nuclear Physics (RCNP) at Osaka University, in collaboration with Kyoto University, used alpha particle inelastic scattering to show that the theorized "5α condensed state" does exist in neon-20. This work may help us obtain a better understanding the low-density nucleon many-body systems.

All elements besides hydrogen and helium must have been fused inside the nuclear furnace of a star. The yield during these reactions of carbon-12, which has six protons and six neutrons, is increased by an unusual quirk in that 12 is divisible by 4. This means that given a little extra energy, the nucleons in carbon can form three alpha particles, consisting of two protons and two neutrons each, and these alpha particles can be condensed into the lowest-energy orbit in carbon-12. The existence of an alpha condensed state in heavier isotopes with atomic weights divisible by four, such as neon-20, has been theorized, but remained uncertain. These condensed states would provide a unique window into the world of nuclear physics. This is because the densities of most normal nuclei are very similar to each other, while the alpha condensed state would be an example of a low-density many-body system. Measuring the properties of protons and neutrons in such a dilute state would be very helpful for understanding the nature of low-density nuclear matter that exists on the surface of neutron stars.

Now, a team of researchers led by Osaka University have provided experimental evidence that these excited states do exist in neon-20. By firing alpha particles at a neon gas, they observed that the decay products indicated the existence of specific energy states in the original nucleus. These matched very well with predictions of the 5α condensed state, in which the 10 protons and 10 neutrons are grouped into five alpha particles in the lowest-energy orbit.

"We were able to obtain such precise results because we were able to measure the decay particles from the excited state," first author Satoshi Adachi explains. "We developed an isotopically enriched neon-20 gas target system with an ultra-thin gas-sealing window made of SiNx. We found it was crucial to measure inelastically scattered alpha particles at very forward angles including 0 degrees, where the alpha condensed state was selectively excited. This measurement was very difficult, but a high-quality beam provided by the well-tuned cyclotrons at RCNP enabled us to conduct it." These techniques allowed the scientists to carry out a detailed comparison between the statistical decay-model calculations and the experiment.

"We expect that this research will accelerate progress in our understanding of extreme environments, like the surface of a neutron star," senior author Takahiro Kawabata says. The work can also be extended to even heavier isotopes that follow the "divisible by four" pattern.

When cancers metastasize, cells from the primary tumor break away, travel through the blood or lymph system,
and form new tumors in other body parts. Although metastasis are responsible for more than 90% of all cancer
deaths, limited progress has been made in treating cancers that have spread.

Besides DNA, RNA is the other molecule of life. For several years now, RNA has become just as important as DNA in understanding the book of life. Especially, messenger RNA (mRNA), the basis of the Covid-19 vaccines, has been put in the spotlight. Just as with DNA, in addition to the 4 well known letters (A, U, G, C), there are further letters defining the RNA alphabet or 'RNA epigenetics'. One of these RNA letters, m6A plays a key role in gene regulation through an enzyme called FTO.

The newest work of the Laboratory of Cancer Epigenetics at the Faculty of Medicine at Université libre de Bruxelles and the ULB Cancer Research Center (U-CRC), led by Prof. François Fuks and Dr. Jana Jeschke, has revealed that FTO plays a key role in the deadly process of cancer metastasis. Analyzing data from thousands of cancer patients, the ULB researchers discovered that FTO is produced at lower levels in cancers than in healthy tissues. When they experimentally lowered the levels of FTO in cancer cells grown in plastic dishes or in animal models, they observed that these cells grew and spread faster than control cells. In cancer patients, they discovered a similar pattern in which low FTO levels correlated with more aggressive tumors, metastasis and earlier death. Using a new sequencing technology, which allows to measure m6A within all mRNAs, Prof. Fuks and Dr. Jeschke found that in FTO-low cancer cells m6A is enriched specifically in mRNAs that belong to a program, termed WNT signaling, that promotes metastasis.

As WNT signaling has been found upregulated in many cancers, therapies that aim to block this program have been developed and are currently tested in clinical trials. When the ULB researchers experimented with this new type of therapy, they observed that cancer cells or tumors with lowered FTO levels and enhanced WNT activity were more sensitive to WNT inhibitors. Thus, although FTO-low tumors are more aggressive and deadly, they are better treatable with Wnt inhibitor therapy. The findings were initially made in breast cancer but can be generalized to many other tumors, such as prostate, cervix or lung cancers.

Overall, the team of Prof. Fuks identified a new key regulator of cancer metastasis and a new therapeutic strategy to block the deadly spread of cancer. Details of this work, which offers encouraging prospects for cancer research and therapy, are published in the 23d June 2021 issue of the Nature Cancer journal.

Discovering and engineering nanobodies with properties suitable for treating human diseases ranging from cancer to COVID-19 is a time-consuming, laborious process.

To that end, University of Michigan researchers found a simple method for identifying nanobodies with drug-like properties suitable for preventing SARS-CoV-2 infections. They demonstrated the approach by generating nanobodies that neutralized the SARS-CoV-2 virus more potently than an antibody isolated from an infected patient and a nanobody isolated from an immunized animal.

Nanobodies are small antibody fragments which bind strongly to their target molecules and block their functions. Currently, antibody and nanobody discovery involves selecting initial lead antibody candidates, followed by time- and labor-intensive modifications to make them suitable for therapeutic applications, said Jennifer Zupancic, doctoral candidate in chemical engineering and co-first author, with Alec Desai, doctoral candidate in chemical engineering. The study is in Cell Chemical Biology.

"A key advantage to this method, both in terms of addressing pandemics and nanobody development more generally, is the ability to select nanobodies that bind strongly more rapidly than with current methods," said Zupancic.

"This unexpected discovery appears to be a key step toward addressing a long-standing challenge in the field, namely the rapid and simple generation of high-affinity agents (agents that bind strongly) such as nanobodies, without the need for extensive screening and optimization," said Peter Tessier, the Albert M. Mattocks Professor in Pharmaceutical Sciences and Chemical Engineering, and senior author. He's also a member of the U-M Biointerfaces Institute,

Nanobodies and antibodies bind to their targets via multiple flexible binding loops called the complementarity-determining regions. Researchers discovered that one or more of the individual binding loops from different lead nanobodies could be combined into single nanobody mutants with improved properties, Zupancic said. That process is called complementarity-determining region swapping.

"This process of CDR swapping resulted in substantial changes to the nanobodies we initially started out to modify," she said. "It was surprising to us that such large changes not only did not hinder the nanobodies' ability to bind and neutralize the SARS-CoV-2 virus, but actually greatly improved it."

Researchers discovered the method accidentally, but found and reported that the technique is simple to perform in a systematic manner.

Generally, approved antibody drugs must demonstrate drug-like properties, including high stability, specificity and solubility, and must also bind strongly to their target. Often, there are tradeoffs between these properties, which frustrate therapeutic antibody development.

"However, we observe that our nanobodies have drug-like properties and also bind to and neutralize the SARS-CoV-2 virus strongly," she said.

The new method likely can be used to develop nanobodies against other viruses and disease targets. That work is ongoing in the lab now, Zupancic said.

Many people don't realize that the trillions of bacteria, viruses, and fungi residing within the gastrointestinal tract--collectively called the gut microbiome-- are connected to overall health, and specifically to cancer.

Manipulating the gut microbiome to produce "beneficial" commensal microbes, which protect the host from pathogens and can boost immune responses, among other things, could potentially help patients respond better to cancer drugs called immune checkpoint inhibitors, a type of immunotherapy.

To that end, researchers at the University of Michigan have developed a new dietary fiber formulation that improves the potency of immunotherapies against cancer by modulating the gut microbiome. In the future, cancer patients treated with immune checkpoint blockers may benefit from consuming this inulin gel dietary fiber, said James Moon, the John G. Searle Associate Professor of Pharmaceutical Sciences in the College of Pharmacy. The findings appear in the June 24 issue Nature Biomedical Engineering.

Inulin, a dietary fiber found in chicory root, Jerusalem artichoke and other plants, is a prebiotic that helps produce colon-residing commensal bacteria. By formulating inulin into a more colon-targeted inulin gel formulation, the team was able to provide a rich source of nutrients to allow beneficial gut microbes to expand more in the gastrointestinal tract.

The inulin gel improved immune checkpoint inhibitor therapy in rodents with colon carcinoma as well as melanoma. For instance, when inulin gel was combined with an immune checkpoint inhibitor in a colon carcinoma rodent model, the rate of tumor eradication doubled (100% improvement), compared with the immune checkpoint inhibitor therapy alone.

"Consumption of the inulin gel expanded and increased the number of beneficial microbes in tumor-bearing mice," said Kai Han, postdoctoral fellow and first author of the study. "These are beneficial commensal microbes that are found in cancer patients who respond well to immune checkpoint inhibitors.

"The current approaches to restoring a healthy gut microbiome include oral ingestion of defined probiotics or fecal microbiota transplantation," Han said. "However, it would be very challenging to develop these as pharmaceutical products due to scale-up manufacturing and quality control."

The human microbiome has recently emerged as the next frontier in drug development. Intense research interest in the microbiome is driven by evidence linking the potential health benefits of modulating gut microbiota to treating various diseases, including cancer, diabetes, obesity and neurodegenerative diseases. In particular, a series of recent studies showed that the gut microbiome plays a crucial role in cancer patients' response rate to immune checkpoint inhibitors, Moon said.

"We and others have shown that the gut microbiome has a crucial role in our immune responses," Han said. "Close to 70% of lymph nodes in our bodies are located in the gastrointestinal tract and therefore, microbes residing in the gastrointestinal tract closely interact with our immune cells. Maintaining a healthy gut microbiome nurtures our immune system so that our immune cells can effectively fight against cancer."

The group chose inulin because it wanted something that could be readily translated to the clinic. Inulin is a dietary fiber that is widely consumed by the public and is present in many plants. It's used as a sugar substitute and in candies and butter. By making inulin into inulin gel, researchers found that inulin gel coats the gastrointestinal tract much better, leaving more nutrients to the commensal microbes.

The inulin gel also works with anti-PD-1 plus anti-CTLA-4 combo-therapy, (widely used immune checkpoint inhibitors) that treat many types of cancer, Han said.

Roughly 10-30% of cancer patients respond to immune checkpoint inhibitors, depending on the types of cancer, and there is risk of serious immune-related complications and side-effects, Moon said. For instance, inflammation in the gastrointestinal tract and skin are common. Previous studies have shown that inulin consumption may alleviate gastrointestinal inflammation, such as colitis and IBD.

"So, inulin gel may alleviate gastrointestinal inflammation induced by immune checkpoint inhibitors and we are testing this idea now," Moon said.

"Generation of systemic anti-tumour immunity via the in situ modulation of the gut microbiome by an orally administered inulin gel"

A cluster of comet fragments believed to have hit Earth nearly 13,000 years ago may have shaped the origins of human civilisation, research suggests.

Possibly the most devastating cosmic impact since the extinction of the dinosaurs, it appears to coincide with major shifts in how human societies organised themselves, researchers say.

Their analysis backs up claims that an impact occurred prior to start of the Neolithic period in the so-called Fertile Crescent of southwest Asia.

During that time, humans in the region - which spans parts of modern-day countries such as Egypt, Iraq and Lebanon - switched from hunter-gatherer lifestyles to ones centred on agriculture and the creation of permanent settlements.

It is thought that the comet strike - known as the Younger Dryas impact - also wiped out many large animal species and ushered in a mini ice age that lasted more than 1,000 years.

Since it was proposed in 2007, the theory about the catastrophic comet strike has been the subject of heated debate and much academic research. Now, researchers from the University of Edinburgh have reviewed evidence assessing the likelihood that an impact took place, and how the event may have unfolded.

The team says a large body of evidence supports the theory that a comet struck around 13,000 years ago. Researchers analysed geological data from four continents, particularly North America and Greenland, where the largest fragments are thought to have struck.

Their analysis highlights excess levels of platinum, signs of materials melted at extremely high temperatures and the detection of nanodiamonds known to exist inside comets and form during high-energy explosions. All of this evidence strongly supports the impact theory, researchers say.

The team says further research is needed to shed more light on how it may have affected global climate and associated changes in human populations or animal extinctions.

The research is published in the journal Earth-Science Reviews. An Open Access version of the paper is available here: https://www.research.ed.ac.uk/en/publications/the-younger-dryas-impact-hypothesis-review-of-the-impact-evidence

Dr Martin Sweatman, of the University of Edinburgh's School of Engineering, who led the study, said: "This major cosmic catastrophe seems to have been memorialised on the giant stone pillars of Göbekli Tepe, possibly the 'World's first temple', which is linked with the origin of civilisation in the Fertile Crescent of southwest Asia. Did civilisation, therefore, begin with a bang?"

The Third Pole centered on the Tibetan Plateau is home to the headwaters of multiple rivers in Asia. Despite the importance of these rivers, scientists have not known exactly how much water flows out of the mountains of the Third Pole as river runoff.

Now, however, researchers from the Institute of Tibetan Plateau Research (ITP) of the Chinese Academy of Sciences have quantified the total river runoff of 13 major rivers in the region.

The study was published in the Bulletin of the American Meteorological Society and was based on data from an observational network of "water meters" at mountain outlets in the Third Pole.

The network generates comprehensive discharge data for 13 major Third Pole rivers and was established by Pan-TPE, a research program under the Chinese Academy of Sciences. The water meters integrate both ground-based observations and numerical simulations.

"Monitoring changes in river runoff at mountain outlets in the Third Pole is particularly important because rivers in this region support millions of people in Asia and are very sensitive to climate change," said Prof. WANG Lei from ITP, lead author of the study.

Using data from the network, the scientists made the first-ever estimate of annual total river runoff for the 13 Third Pole rivers. The results, for 2018, peg total runoff at 656 ± 23 billion m3.

The scientists also found that the annual readings of the water meters varied widely among the different rivers, ranging from 2 to 176 billion m3. The higher values mainly corresponded to rivers in the Indian monsoon domain in the southern Third Pole, rather than in the westerly domain in the northern Third Pole.

Readings from these water meters offer valuable information about regional water resources. They also provide information relevant to hazard risk management. This is particularly important in the context of climate change since river runoff has significantly changed as a result of increasingly rapid snow and glacial melting in the region.

"We also plan to collect and process data for major rivers in the region prior to 2018 and improve the accuracy of discharge estimates, so that better cryosphere-hydrology models can be built for different river basins across the Third Pole," said Prof. YAO Tandong, co-author of the study and chief scientist at Pan-TPE.

In a new study published in Circulation Research, Chen-Yu Zhang and Xiaohong Jiang's group from Nanjing University and Dongjin Wang's group from Nanjing Drum Tower Hospital reported a critical role of PGC1α in maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs) and highlighted the therapeutic potential of PGC1α for atherosclerosis.

The traditional view holds that aberrant proliferation of VSMCs promotes plaque formation after vessel injury and inflammation, whereas the presence of VSMCs in the fibrous cap of the plaque is beneficial. Although it has long been assumed that these seemingly contradictory functions of VSMCs during atherosclerosis arise from their remarkable plasticity, direct evidence that VSMCs undergo phenotypic switching during atherogenesis in vivo has only been proven recently by rigorous lineage tracing studies. These studies showed that the contribution of VSMCs to atherosclerosis has been greatly underestimated. Despite the importance of VSMC phenotypic modulation in lesion pathogenesis and plaque composition, the underlying molecular mechanisms remain to be elucidated.

Among the different animal models that have been used to study atherosclerosis, rabbits not only have provided many insights into the pathogenesis of human AS but also have contributed greatly to translational research. Rodents, such as mice and rats, are quite resistant to atherosclerosis due to high levels of HDL in circulation. Like humans but unlike rodents, rabbits are considered LDL mammals, which are sensitive to dietary cholesterol and spontaneously develop AS. However, due largely to the relative ease of their genetic manipulation and breeding, compared with those of rabbits, mice--such as ApoE-/- and LDLR-/- mice--are still the most wildly used laboratory models. However, owing to their unique features of lipoprotein metabolism, which are pathophysiologically more similar to those of primates than those of rodents, transgenic rabbits have still been used during the past decades to study humans atherosclerosis in order to bridge the gaps between mice and humans; thus, rabbits are an indispensable model for studying human atherosclerosis.

Although aberrant expression of PGC1α, a master regulator of mitochondrial biogenesis, has been shown to be associated with cardiovascular diseases, the role of PGC1α overexpression in VSMCs in the formation of atherosclerotic lesions has not been elucidated. In the current study, Wei et al. generated Tg rabbits with SMC-specific PGC1α overexpression and showed that overexpression of PGC1α in VSMCs significantly ameliorated high cholesterol diet-induced atherosclerotic plaque formation. After feeding cholesterol rich diet, the VSMCs from Tg rabbits exhibited a more contractile phenotype than their non-Tg littermates, which resulted in decreased macrophage infiltration, vascular inflammation, ROS production, vascular senescence, and VSMC proliferation. In addition, similar vasoprotective effects were observed in cultured human aortic SMCs and clinical samples. Collectively, their findings demonstrate a beneficial role for PGC1α in modulating VSMC phenotype and the pathogenesis of atherosclerosis.

This work is essential for the following reasons:

1. As the first and one of the best animal models for investigating AS, the rabbit model is a better overall approximation to humans. However, to date, only 22 lines of Tg rabbits have been established to study CVD due to the relative difficulty of genetically manipulating and breeding rabbits compared with mice. Most of these exogenous genes were either systemically or specifically expressed in rabbit liver cells and directly participated in lipoprotein metabolism, for example, apolipoproteins and their associated enzymes. Although many lipid metabolism related factors have been expressed in rabbit livers and macrophages, models with artery-specific overexpression of genes are lacking. By generating transgenic rabbits that expressed PGC1α under the control of a minimal SM22 promoter, whose activity was constitutive in arterial SMCs. Zhang's group found that after HCD feeding, although Tg rabbits developed hypercholesterolemia similar to that in their non-Tg littermates, the mean aortic lesion size in Tg rabbits was markedly reduced. This finding is consistent with previous observations in vitro studies in cultured VSMCs, indicating a direct atheroprotective role of PGC1α in arterial VSMCs.

2. As a powerful orchestrator of energy metabolism, PGC1α is highly expressed in energy demanding tissues, such as brown fat, liver, brain, and muscles. The function of PGC1α is less studied in VSMCs, the ultimate effectors of vasomotion and a major cell type present at all stages of AS than in skeletal muscle and cardiac muscle cells. Although previous in vitro studies showed that PGC1α can inhibit pathological factor-induced VSMC proliferation and senescence, increased local PGC1α expression in AS has not been conclusively demonstrated in vivo. In the present study, based on RNA-seq analysis and a set of experimental assays of the aortic media from HCD-fed control and Tg rabbits, they found that the PGC1α level was positively associated with the VSMC-restricted contractile gene expressions, but negatively correlated with the atherogenic synthetic phenotype-related features of VSMCs, such as increased expression of proinflammatory factors and MMPs, enhanced ROS production and senescence, and elevated VSMC proliferation. These in vivo observations were also confirmed in cultured VSMCs, hence revealing the novel role of PGC1α in preserving the beneficial contractile phenotype of VSMCs and bolstering its antiatherogenic function.

3. Their data indicated a potential atheroprotective role of PGC1α in clinical atherosclerotic samples, yet further studies with more accurate lineage identification techniques are needed to address this possibility, and regulating PGC1α itself or increasing the level of PGC1α in VSMCs might be feasible therapeutic strategies for atherosclerosis.

Somnambulism - otherwise known as sleepwalking - is a phenomenon which has fascinated the public and neurologists for decades, but a lot of what causes it remains a mystery.

Affecting up to 4% of adults, sleepwalking is a non-rapid-eye movement (NREM) sleep parasomnia that not only gives someone a poor night's sleep, but also puts them at serious risk of injury and, in some cases, lead to unintended violence against others.

The following day can also prove challenging as the sleepwalker will feel unrested and a strong desire to fall asleep (somnolence).

Unfortunately for those predisposed to sleepwalking episodes, prolonged sleep deprivation increases both their frequency and complexity, making it harder for them to achieve the deep sleep the body needs to function healthily.

Now, in a paper published to Frontiers in Neurology, researchers at the University of Montréal and Montréal Sacred Heart Hospital, Canada aimed to further investigate the hypothesis that sleepwalking is a disorder of arousal and poorly regulated deep sleep (slow-wave sleep).

More specifically, they examined how the autonomic nervous system - measured via the heart rate - influences deep sleep in sleepwalkers.

Challenges of a sleepwalking study

14 adult sleepwalkers were recruited for the study as well as 14 sex- and age-matched normal controls. They were evaluated using video-polysomnography for one night and during recovery sleep following 25 hours of sleep deprivation.

According to corresponding authors Prof Antonio Zadra and Dr Andrée-Ann Baril of the University of Montréal, it can be a challenge to put together a study investigating the mysterious inner workings of sleepwalking.

"One challenge in studying large cohorts of sleepwalkers is the relatively low prevalence of the disorder in the adult population," they said.

"Fortunately, the Center for Advanced Research in Sleep Medicine, where this research was conducted, is a one-of-a-kind clinical and research facility in Canada affiliated with one of the country's largest and highly specialized sleep disorders clinics that assesses over 1,000 patients a year. As a general rule, however, adult sleepwalkers are readily willing to take part in research studies aiming to better understand the underlying causes and possible treatments of the sleep disorder."

Wakefulness and deep sleep at the same time

The autonomic nervous system regulates the body's physiological functions and is composed of the sympathetic branch, which underlies the 'fight or flight' response, and the parasympathetic branch, which underlies the 'rest and digest' response. Zadra, Baril, and the rest of their team found that sleepwalkers show an elevated rest-and-digest response and a lower fight-or-flight response during deep sleep.

"While the causes of sleepwalking remain unclear, we know that while asleep, sleepwalkers can experience an abnormal interplay between processes linked to arousal and to deep sleep, even outside of their episodes," Zadra and Baril said.

"In other words, sleepwalkers can present evidence of both wakefulness and deep sleep at the same time; a state out of which episodes of sleepwalking can arise. Our findings indicate that when compared to healthy adults, sleepwalkers' autonomic nervous system favors their parasympathetic activity, or rest-and-digest response, during sleep. This paves a new and broader way to understand the biological processes implicated in sleepwalking."

Surprising discovery

The results were "surprising", they added, as it had been assumed that the deep sleep of sleepwalkers would show an elevated fight-or-flight response that would predispose them to higher risks of experiencing sleepwalking episodes.

One limitation of the study is that measuring the influence of the sympathetic and parasympathetic branches on a person's heartbeat is an indirect approach and can be confounded by other factors.

"While our results indicate the presence of an altered autonomic nervous system during sleepwalkers' deep sleep, whether and how this atypical activity is involved in the occurrence of actual sleepwalking episodes remains to be determined," Zadra and Baril said.

"Since several pharmaceutical agents can be used to modulate autonomic effects, such treatment venues could be explored if our results are replicated and expanded upon."

The cultivated planet is withstanding record-breaking pressure to ensure food security. To meet the rising demand of food, energy, and fiber, a 70%-100% increase in crop commodities will be needed globally by 2050. However, rapid urbanization and industrialization have caused dramatic loss of high-quality cropland and hence threatened food security. To stabilize cropland area, cropland expansion to marginal lands has become a widespread phenomenon worldwide. This study developed a systems framework to represent the trade-off among crop yield, production, and environmental cost, according to the competitive relationship of production, settlement, and ecological space and the link of "land - food - environment - policy". Using China as a case study, the authors validated the systems framework by assessing the associated food benefits and environmental costs from large-scale cropland redistribution driven by economic development and policy implementation.

The environmental impacts of cropland redistribution in China were invesgated. Due to urbanization-induced loss of high-quality croplands in south China (~8.5 t ha-1), croplands were expanded to marginal lands in northeast (~4.5 t ha-1) and northwest China (~2.9 t ha-1) during 1990-2015 to pursue food security. However, the reclamation in these low-yield and ecologically vulnerable zones considerably undermined local environmental sustainability, e.g., increasing wind erosion (+3.47%), irrigation water consumption (+34.42%), fertilizer use (+20.02%), and decreasing natural habitats (-3.11%). Forecasts show that further reclamation in marginal lands per current policies would exacerbate environmental costs by 2050. The future cropland security risk will be remarkably intensified due to the conflict between food production and environmental sustainability. Kuang et al.'s results suggest that globally emerging reclamation of marginal lands should be restricted and crop yield boost should be encouraged for both food security and environmental benefits.

The findings in this paper reveal that, under the influence of national macro policies, the competition of urban, agriculture and ecology systems driven by "the supplement of marginal lands and loss of high-quality croplands in the future" lead to the trade-off relationship between food production and environmental sustainability. The paper also confirms that the global or specific regional marginal lands beyond a certain threshold will not increase grain production, but will cause environmental unsustainability.

The rarity of these syndromes, caused by damage to a gene named HUWE1, means very few children are affected. Of course, the low absolute numbers are little consolation for children who are born with a severe intellectual disability as a result of gene mutation.

Many affected children have distinctive facial features, some struggle to learn to walk, and many never learn to speak. Some have an abnormally small head and have stunted growth.

There is no cure. Parents mainly focus on learning enough about how to cope to make everyday life workable.

A lot of parents struggle with guilt. Why did their child turn out like this? Could it be their fault?

Marte Gjøl Haug is the senior consultant in medical genetics at St. Olavs Hospital in Trondheim, Norway, and has met with many despairing parents.

In recent years, the number of referrals has increased significantly as genetic testing has become cheaper and more readily available.

"Many parents are afraid that the cause of their child's condition stems from something they could have avoided. A lot of parents have thought this for years before the child is referred and given a genetic diagnosis, which often adds an extra burden to their situation. Once they know that damage to a gene is the cause, many of them are hugely relieved. It wasn't the one glass of wine during the pregnancy that was the cause after all," says Haug.

The problems that result from the damaged HUWE1 gene have names like Juberg-Marsidi, Say-Meyer or Brooks syndrome.

The gene in question is one of more than 900 found on the X chromosome, the female sex chromosome. Girls have two X chromosomes. Boys have an X chromosome and a Y chromosome. Syndromes that are associated with the X chromosome, such as HUWE1, can therefore have differing degrees of severity in both girls and boys.

The damage to the gene occurs when a mutation occurs.

All genes have to be copied, but in instances when DNA fails to copy accurately, a mutation results that can lead to a number of diseases.

Damage to HUWE1 is known to lead to various syndromes, but this is the first time that anyone has figured out that all of the different syndromes have a common cause.

Professor Barbara van Loon is the researcher behind the discovery. She is a graduate of MIT and the University of Zurich, and came to NTNU, the Norwegian University of Science and Technology in Trondheim, from Switzerland. Her expertise is in the field of DNA repair.

Studying these syndromes is challenging because the number of individuals affected by each syndrome is very low.

The low number makes it difficult for researchers to obtain a large enough number of samples to be able to draw conclusions.

"Individually, many of the syndromes are rare, but a lot of people are affected if you combine all the rare syndromes," says van Loon.

Van Loon obtained blood cells from five boys with rare syndromes. In this way, she gathered enough genetic material to find a link.

To recreate the development of the disease, she created stem cells from skin cells from a child with a rare syndrome, and cultured mini-brains of these cells.

Her research allowed her to see that the cause of the syndromes was a protein called p53. This protein plays a major role in very basic neurological mechanisms.

If p53 gets out of control, a cell can develop into a cancer cell. It is well known that this gene is important in the development of cancer. Now, for the first time, van Loon and her colleagues have documented that it can also lead to such great problems with the brain's development to cause intellectual disabilities.

"Our findings don't mean that we can come up with a quick cure, but being able to explain the very basic mechanisms behind an illness is an important prerequisite for developing diagnostics and serving as a basis for future treatment. It's also important in itself to give the affected families more information about the disease and how it's developed," says van Loon.

Barbara van Loon works on basic research, which focuses on the very basic and fundamental processes in human beings. Her research is driven by the goal to discover completely new cell connections.

Van Loon's research findings are important pieces in the large puzzles that could result in a future breakthrough in how disease should be treated.

Knowledge gained through basic research is the most important source of major breakthroughs in medical treatment, but it can be years between a basic research discovery and clinical applications.

A study from the Centre for Nutraceuticals at the University of Westminster found that plant-based protein shakes may be potential viable alternatives to milk-based whey protein shakes, particularly in people with need of careful monitoring of glucose levels.

The study, published in the journal Nutrients, is the first to show potato and rice proteins can be just as effective at managing your appetite and can help better manage blood glucose levels and reduce spikes in insulin compared to whey protein.

During the study the blood metabolic response of participants was measured after drinking potato, rice and whey protein shakes. Appetite was also monitored in the following three hours to understand how these drinks may affect the participants' hunger and their desire to eat.

The research observed that vegan protein shakes led to a lower rise in blood insulin compared to whey, while potato protein prevented any rise in insulin. This may explain the better blood glucose control following consumption of the plant-based protein and poses the question of whether vegan protein shakes are more suitable for individuals who need to need control their blood glucose levels such as diabetic and obese individuals.

Interestingly, release of the key appetite regulating hormone GLP-1 was greater after drinking the whey protein shake. However, the greater GLP-1 response did not translate to an increased feeling of fullness as there were no differences observed in appetite perception between the three different protein shakes.

Consumer trends in protein intake are on the rise with milk protein derivatives such as whey extensively used in consumer products such as protein shakes, fortified food and beverage products.

There are alternative protein products available for vegetarians and vegans such as soy, rice, wheat and pea proteins but there is a relative lack of evidence on their health benefits in comparison to milk proteins. Potato protein is a novel plant-based protein product that is obtained from the waste material from potato starch production and is a sustainable economic protein source. This study provides the first evidence to suggest that it may be an alternative to whey protein sources.

Professor M Gulrez Zariwala, corresponding author and Director of the Centre for Nutraceuticals at the University of Westminster, said: "Global concerns on sustainability have led to consumer shifts towards ethical eating and a change in dietary habits with increased adoption of vegetarian and vegan diets.

"However, research in this area is still lacking and it would be interesting to clarify whether proteins from plant sources can provide identical metabolic health benefits as those with traditional sources such as milk.

"Our results shed new light in this area and improves our understanding of how plant source proteins can be a more sustainable yet nutritionally beneficial food source. We plan to conduct follow-up studies further research this exciting area."

New research has uncovered a novel trick employed by the bacterium Staphylococcus aureus to thwart the immune response, raising hopes that a vaccine that prevents deadly MRSA infections is a little closer on the horizon.

Immunologists from Trinity College Dublin, working with scientists at GSK - one of the world's largest vaccine manufacturers - discovered the new trick of the troublesome Staphylococcus aureus, which is the causative agent of the infamous "superbug" MRSA.

They found that the bacterium interferes with the host immune response by causing toxic effects on white blood cells, which prevents them from engaging in their infection-fighting jobs.

Importantly, the study also showed in a pre-clinical model system that the toxicity could be lessened following vaccination with a mutated version of a protein specifically engineered to throw a spanner in the MRSA works. Ultimately, this suggests a vaccine could one day do the same thing in people.

The research was recently published in journal, mBio.

MRSA - a global killer

An estimated 700,000 deaths occur annually due to infections against which antibiotics are no longer effective. If this is allowed to continue, modern medicine as we know it will cease to exist; a common childhood infection or routine surgical procedure could become fatal, with the threat of AMR infection likened to that of climate change in some circles.

Immediate and significant action is required to turn the tide of AMR and the development of novel vaccines to prevent these types of infection in the first place, are an attractive and potentially very effective option.

Rachel McLoughlin, Professor in Immunology in Trinity's School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI), said:

"As a society we are witnessing first-hand the powerful impact that vaccination can have on curbing the spread of infection. However, on the backdrop of the COVID-19 epidemic we must not lose sight of the fact that we are also waging war on a more subtle epidemic of antimicrobial resistant infection, which is potentially equally deadly."

"In this study we have identified a mechanism by which a protein made by the bacterium - known as Staphylococcal Protein A (SpA) - attacks and rapidly kills white blood cells. This protein has been widely studied for its immune evasion capacity and has a well-documented role in rendering antibodies raised against the bacterium non-functional.

"Here we uncover a previously undocumented strategy by which SpA forms immune complexes through its interaction with host antibodies, that in turn exert toxic effects on multiple white blood cell types. This discovery highlights how important it will be for effective vaccines to be capable of disarming the effects of protein A."

Dr Fabio Bagnoli, Director, Research & Development Project Leader, GSK, said:

"Our collaboration with Trinity College Dublin and in particular with Professor Rachel McLoughlin, a worldwide recognised expert on staphylococcal immunology, is critical for increasing our knowledge on protective mechanisms against S. aureus."

The study documents the latest discovery made by this group at Trinity under an ongoing research agreement with GSK Vaccines (Siena, Italy) in which PhD students from Trinity have the unique opportunity to obtain training in applied vaccine research at the world's largest vaccine research company, thus equipping them with the skills to pursue world class discovery research in both academia and industrial settings.

Overall, this collaboration aims to increase understanding of the immunology of Staphylococcus aureus infection to advance development of next-generation vaccines to prevent MRSA infections.

Scientists using computer modelling to study SARS-CoV-2, the virus that caused the COVID-19 pandemic, have discovered the virus is most ideally adapted to infect human cells - rather than bat or pangolin cells, again raising questions of its origin.

In a paper published in the Nature journal Scientific Reports, Australian scientists describe how they used high-performance computer modelling of the form of the SARS-CoV-2 virus at the beginning of the pandemic to predict its ability to infect humans and a range of 12 domestic and exotic animals.

Their work aimed to help identify any intermediate animal vector that may have played a role in transmitting a bat virus to humans, and to understand any risk posed by the susceptibilities of companion animals such as cats and dogs, and commercial animals like cows, sheep, pigs and horses.

The scientists, from Flinders University and La Trobe University, used genomic data from the 12 animal species to painstakingly build computer models of the key ACE2 protein receptors for each species. These models were then used to calculate the strength of binding of the SARS-CoV-2 spike protein to each species' ACE2 receptor.

Surprisingly, the results showed that SARS-CoV-2 bound to ACE2 on human cells more tightly than any of the tested animal species, including bats and pangolins. If one of the animal species tested was the origin, it would normally be expected to show the highest binding to the virus.

"Humans showed the strongest spike binding, consistent with the high susceptibility to the virus, but very surprising if an animal was the initial source of the infection in humans," says La Trobe University Professor David Winkler.

The findings, originally released on the ArXiv preprint server, have now been peer reviewed and published in Scientific Reports (Springer Nature).

"The computer modelling found the virus's ability to bind to the bat ACE2 protein was poor relative to its ability to bind human cells. This argues against the virus being transmitted directly from bats to humans. Hence, if the virus has a natural source, it could only have come to humans via an intermediary species which has yet to be found," says Flinders affiliated Professor Nikolai Petrovsky.

The team's computer modelling shows the SARS-CoV-2 virus also bound relatively strongly to ACE2 from pangolins, a rare exotic ant-eater found in some parts of South-East Asia with occasional instances of use as food or traditional medicines. Professor Winkler says pangolins showed the highest spike binding energy of all the animals the study looked at - significantly higher than bats, monkeys and snakes.

"While it was incorrectly suggested early in the pandemic by some scientists that they had found SARS-CoV-2 in pangolins, this was due to a misunderstanding and this claim was rapidly retracted as the pangolin coronavirus they described had less than 90% genetic similarity to SARS-CoV-2 and hence could not be its ancestor," Professor Petrovsky says.

This study and others have shown, however, that the specific part of the pangolin coronavirus spike protein that binds ACE2 was almost identical to that of the SARS-CoV-2 spike protein.

"This sharing of the almost identical spike protein almost certainly explains why SARS-CoV-2 binds so well to pangolin ACE2. Pangolin and SARS-CoV-2 spike proteins may have evolved similarities through a process of convergent evolution, genetic recombination between viruses, or through genetic engineering, with no current way to distinguish between these possibilities," Professor Petrovsky says.

"Overall, putting aside the intriguing pangolin ACE2 results, our study showed that the COVID-19 virus was very well adapted to infect humans."

"We also deduced that some domesticated animals like cats, dogs and cows are likely to be susceptible to SARS-CoV-2 infection too," Professor Winkler adds.

The extremely important and open question of how the virus came to infect humans has two main explanations currently. The virus may have passed to humans from bats through an intermediary animal yet to be found (zoonotic origin), but it cannot yet be excluded that it was released accidently from a virology lab. A thorough scientific, evidence-based investigation is needed to determine which of these explanations is correct.

How and where the SARS-CoV-2 virus adapted to become such an effective human pathogen remains a mystery, the researchers conclude, adding that finding the origins of the disease will help efforts to protect humanity against future coronavirus pandemics.

In the animal kingdom, specific growth factors control body axis development. These signalling molecules are produced by a small group of cells at one end of the embryo to be distributed in a graded fashion toward the opposite pole. Through this process, discrete spatial patterns arise that determine the correct formation of the head-foot axis. A research team at the Centre for Organismal Studies (COS) at Heidelberg University recently discovered an enzyme in the freshwater polyp Hydra that critically shapes this process by limiting the activity of certain growth factors.

In particular, the proteins of the so-called Wnt signalling pathway play an important role in the pattern formation of the primary body axis. Wnt proteins, which arose early during evolution, are considered to be universal developmental factors. "Misregulation of Wnt factors can cause serious malformations during embryonic development and give rise to diseases such as cancer," explains Prof. Dr Özbek, a member of the "Molecular Evolution and Genomics" department led by Prof. Dr Thomas Holstein at the COS.

Now, the researchers have discovered an enzyme in the freshwater polyp Hydra that can break down Wnt proteins, thereby deactivating them. Hydra is a basal multicellular organism of the phylum Cnidaria that has long been used as a model organism to study the Spemann-Mangold organizer, an embryonic signalling centre in charge of forming the body's longitudinal axis. The Wnt proteins responsible for this process are continually produced in the mouth region of the adult polyp to maintain the body axis.

The researchers determined that the newly discovered HAS-7 enzyme develops in a ring-shaped zone below Hydra's tentacle wreath. This region separates the head from the body. If HAS-7 production is experimentally interrupted by suppressing the gene expression, a fully formed second head and a second body axis spontaneously develop. According to Prof. Özbek, something similar occurs when Wnt proteins are artificially produced in the animal's entire body.

In cooperation with Prof. Dr Walter Stöcker's group at Mainz University, the Heidelberg researchers were able to show that the HAS-7 enzyme is capable of specifically cleaving the Wnt protein to suppress its activity beyond the head. Without this inhibitory mechanism, the Wnt emanating from the head floods the body, creating a two-headed animal. The HAS-7 enzyme is a member of the astacin family of proteases, which were first identified in crayfish. "Members of the astacin protease family are also found in higher vertebrates. It is therefore likely that we have found a mechanism here that may play a role in humans as well," states Prof. Holstein.

In a follow-up project within the Collaborative Research Centre 1324 "Mechanisms and Functions of Wnt Signaling", the researchers will collaborate with Prof. Dr Irmgard Sinning of the Heidelberg University Biochemistry Center to study the molecular mechanism of Wnt cleavage by astacin. "We hope to be able to find clues on the precise point of attack in the Wnt protein," states Prof. Özbek.