Culture

The transport of amino acids and other molecules across the cell's membrane plays a crucial role in the metabolism of cells and, therefore, in human health. Current research hints that cancer, cystic fibrosis, aminoacidurias and neurodegenerative diseases may stem from missing or defective amino acid transport at the cell membrane. Now, researchers from ICIQ's Ballester group and IRBBarcelona's Palacín group have published a paper in Chem showing how a synthetic carrier calix[4]pyrrole cavitand can transport amino acids across liposome and cell membranes bringing future therapies a step closer.

Thanks to the BIST Ignite project Calix[4]trans, the scientists have assessed the properties of a calix[4]pyrrole cavitand (a container shaped molecule) in the transport of amino acid Proline through cell and liposomal membranes. "The BIST Ignite project has allowed us to combine the fundamental research done in our lab focused on making molecules and studying their interactions with the more applied research done in Palacin's group in the area of amino acid transporters and diseases. In my opinion, applied research must go hand in hand with basic research for a better understanding and advancement of science and the development of applications. In this case gaining knowledge about synthetic carriers for the long-term development of applications in the therapy of Proline-dependent diseases like some cancers and inherited hyperprolinemias" explains Gemma Aragay, scientific coordinator of ICIQ's Ballester group.

Figure_pressreleasechemThe scientists made liposomes with the cavitand embedded in their membranes. They observed a 30-fold increase in L-Proline transport activity when compared with the passive diffusion of the amino acid to the interior of "regular" liposomes as well as the cavitand's selectivity for L-Proline over other amino acids. "L-Proline is a suitable guest for the Calix[4]pyrrole cavitand because of the complementarity between the cavity's size, shape and functional groups with those of the amino acid," explains Aragay.

To study the impact of the cavitand on Proline transport in living cells, the scientists incubated synthetic vesicles infused with Calix[4]pyrrole in HeLa cultured cells to incorporate the cavitand in their membranes. The results obtained in cells reveal that the presence of the cavitand increases the diffusion of proline at high extracellular amino acid concentrations - although it represents a moderate increase when compared with the transport already carried out by the cells' proteins.

However promising the results are, "we need to further study the molecular structure of the cavitand-amino acid complex to increase the transport activity if we want to apply Calix[4]pyrroles as therapeutic tools," explains Pau Ballester, ICIQ group leader and ICREA professor.

"With this work, we hope to drive the development of artificial carriers to efficiently treat diseases of amino acid metabolism," concludes Manuel Palacín, Head of the Amino Acid Transporters and Disease lab at IRB Barcelona, group leader at CIBER of Rare Diseases, and Professor at the University of Barcelona.

A new plant species named Cardamine insueta appeared in the region of Urnerboden in the Swiss alps, after the land has changed from forest to grassland over the last 150 years. The inheritance of two key traits from its parent plants enabled the newly emerged species to grow in a distinct environmental niche, as researches from the University of Zurich now show.

The emergence of a new species is generally thought to occur over long periods of time. But - as the example of the plant Cardamine insueta shows - evolution can also happen quite quickly. C. insueta, a new bittercress species first described in 1972, has only recently emerged in Urnerboden, a small alpine village in central Switzerland. It evolved just within the past 150 years due to environmental changes in the surrounding valley: when the local people cleared the forest and turned it into pasture land.

New plant species allows to observe 'evolution in action'

"C. insueta proves to be an exceptional case to directly analyze the genetic traits and environmental responses of a new species. In other words: to observe 'evolution in action', a main topic of the university's corresponding University Research Priority Program," says Rie Shimizu-Inatsugi from the Department of Evolutionary Biology and Environmental Studies at the University of Zurich (UZH). The plant biologists were now able to unravel the genetic mechanisms underlying the plant's evolution.

C. insueta developed from two parent species with specific ecological habitats: while C. amara grows in and beside water streams, C. rivularis inhabits slightly moist sites. The land-use conversion from forest to grassland induced the hybridization of the two progenitors generating the new species that is found in-between the parents' habitats with temporal water level fluctuation. "It is the combination of genetic traits from its parents that enabled the new species to grow in a distinct environmental niche," says Shimizu-Inatsugi. In fact, C. insueta inherited one set of chromosomes from C. amara and two sets of chromosomes from C. rivularis. It therefore contains three sets of chromosomes making it a so-called triploid plant.

Inheritance of two key parental traits enabled the survival

To characterize the responses to a fluctuating environment, the research team used high-throughput sequencing to analyze the time-course gene expression pattern of the three species in response to submergence. They found that the gene activity responsible for two parent traits were key for the survival of the new species in the novel habitat. First, C. insueta can clonally propagate through leaf vivipary, meaning it produces plantlets on the surface of leaves that can grow into new plants. It inherited the ability for asexual vegetative reproduction from C. rivularis. Since C. insueta is sexually sterile, it would not have been able to survive without this trait.

Second, C. insueta inherited the submergence tolerance from C. amara, since the genes responsible for this trait were active in both species. "The results show that C. insueta combined advantageous patterns of parental gene activity to contribute to its establishment in a new niche along a water-usage gradient. Depending on the environmental situation, the plant activates different set of genes it inherited from its two parent species." says Rie Shimizu-Inatsugi.

At a time when food production is one of the biggest climate culprits, it is essential that we seek out new food sources which can nourish us and, at the same time, not overburden the planet.

More and more people are opting to become vegetarians or, even more radically, vegans.

However, the large majority of people find it difficult to entirely shelve meat in the name of preventing climate change, according to Professor Ole G. Mouritsen of the University of Copenhagen's Department of Food Science.

"Many people simply crave the umami flavor that is, for example, found in meat. Therefore, it may be more realistic to consider a flexitarian diet, where one consumes small quantities of animal products, such as meat, eggs and milk, alongside vegetables. However, one can also begin thinking about alternatives to the juicy steak -- of which there are many," he says.

In a new meta-study, Professor Mouritsen and PhD student Charlotte Vinther, his colleague at the Department of Food Science, pick up on today's food trends.

They present alternative sources for protein and healthy fatty acids, while giving their take on what a sustainable diet of the future might look like.

Hello sand lance, gobi and sprat

Among other things, the researchers recommend that we look to the sea for foods of the future.

More specifically, we need to get to the bottom, where species typically associated with being bycatch and industrial fish live. These species emit far less CO2 than beef, pork and chicken.

"The climate-friendly bycatch fish currently used for pig feed or fish oil live near the bottom of the ocean. They include: sand lance, a fish which digs into the sandy bottom to lay eggs; sprat, a relative of herring which is widespread in Danish waters; and the black-mouthed gobi, another small, but tasty and overlooked fish," explains Mouritsen.

Sprat alone could satisfy 20 percent of Denmark's protein needs. And by fishing for sprat, we can avoid the over-exploitation of more well-known fish species such as cod, plaice and salmon, explains the professor.

À la carte algae, squid and seaweed

Seaweed and algae are also an overlooked and extremely climate-friendly food source.

However, only 500 of 10,000 species are currently exploited and recognized as food - despite the fact that marine algae are packed with incredibly healthy nutrients and vitamins.

Similarly, cephalopods are only fished to a small extent, with 30 out of approximately 800 species being used for food globally.

"Among other things, this has much to do with our culture and traditions. Food consumption habits take time to change. We have been eating and preparing meat for more than a million years. So even though seaweed, squid and mollusks contain important fatty acids and vitamins, and can taste great, we remain reluctant to count these species among our food sources," says Ole G. Mouritsen.

New technology can lend vegetables the umami taste of meat

One possible explanation for the fact that we find it difficult to green our diet is that we have an innate preference for sweetness and foods with an umami flavor. According to the professor:

"Sweetness signals calories and survival to the brain, and umami signals that we are consuming something good for our muscles. However, many seafoods, marine algae and vegetables have the potential to taste great, and that's something that we can use technology to help develop."

For example, by fermenting or adding enzymes to vegetables, sweet and umami tastes can be brought out, says Ole G. Mouritsen.

"Several Asian food producers have something called 'shio-koji', which can also be made at home. Koji is a salty solution of dead microscopic fungi with active enzymes. By adding it to sliced broccoli and putting them in the fridge for a few hours, you'll be able to taste more sweetness and umami in the pieces of vegetable," he says, concluding:

"It is essential that we continue to communicate these new opportunities to eat sustainably. By doing so, we will gradually effectuate change upon our eating habits and traditions. We hope that this study plays a part."

An international group led by researchers from the RIKEN Center for Integrative Medical Sciences have used a combination of genome-wide association analysis--or GWAS--and a trans-ancestry comparison of different GWAS studies, to come up with a more accurate predictor of coronary artery disease based on genetic factors.

It is known that coronary artery disease--the world's leading cause of death--is highly heritable, and in some cases, most notably the PCSK9 gene, the knowledge of genetic associations has contributed to the development of therapies. Genetic Risk Scores based on genetic information can accurately predict the onset of disease in individuals. However, studies so far have focused primarily on European populations, and it is not clear whether the results apply to other ancestry populations.

In the present study, published in Nature Genetics, the team performed two important tasks. First, they looked at the genetics of the disease in a Japanese population, by comparing the genome sequences of 25,892 coronary artery disease patients in the Biobank Japan and 142,336 controls, constituting the largest GWAS project on coronary artery disease in a non-European population. Using a reference panel they developed to estimate the genotypes of the individuals, they identified 48 genetic loci associated with a susceptibility to coronary artery disease, eight of which were previously unknown. In particular, they found one genetic variant in the RNF213 gene, which is known to be associated with a cerebrovascular disease known as moyamoya disease, which had never been identified in GWAS studies with European cohorts.

Thanks to these results, they were able to build a reference panel for the Japanese population, which could be used to gauge the risk of even variants found in a very small percentage of the population. "We found one variant in the LDLR gene," says Kaoru Ito, one of the authors of the study, "which is not very common, but it has an important effect on cholesterol metabolism, and Japanese people with this rare mutation raises the likelihood of developing coronary artery disease five-fold." The group also discovered mutations specific to the Japanese population that can reduce the livelihood of coronary artery disease.
The group's next step was to combine the results of the 170,000 Japanese subjects with two other datasets from European populations (approximately 180,000 from the CARDIoGRAMplusC4D study and 300,000 from the UK Biobank, to create one of the world's largest trans-ethnic GWAS in coronary artery disease with a total of more than 600,000 individuals. Doing this, they identified 35 new loci associated with disease, and one of them was in the HMGCR gene, which is the target of statin drugs.

A very positive result of the study was that the group was able to use the combined GWAs to create a genetic risk score that outperformed the results of GSCs crafted either According to Ito, "This is exciting, as it means that even when there are different frequency of variants in different populations, we can combine GWAS studies from different ancestries and use this to create a risk score that is more accurate than any of the individual ones, and this means that integrating existing data is a good way to develop GRSs in non-European populations."
He continues, "We hope that our study will help lead to the development of GRSs optimized for Japanese people, which could be used effectively in the future of precision medicine based on genetic information."

The COVID-19 pandemic is taking a heavy mental health toll even on people who are not directly impacted by the disease, shows a new study in Frontiers in Psychiatry.

In a first-of-its-kind Australian mental health survey, researchers found that people in countries with low rates of infection and fatalities--like Australia at the onset of the pandemic--still experience twice as much depression and anxiety. These outcomes are largely related to financial stress and disruptions to people's social lives.

"We already know from past pandemic research that the people who are most affected, such as those who become ill and/or are hospitalized and their carers, experience more severe impacts. However, the impacts of COVID-19 on the broader population in relatively less affected countries are also likely to be substantial," says lead author Dr Amy Dawel of the Australian National University in Canberra, Australia.

"Our data show that the by-products of COVID-19 are affecting populations broadly--notwithstanding how great the physical illness impact is--and the concern is that countries with strong restrictions, who appear to circumvent the worst of COVID-19, may overlook the indirect impacts of the pandemic."

To capture a snapshot of the population's mental health just after the first COVID-19 restrictions went into effect, Dr Dawel and her collaborators surveyed nearly 1300 Australian adults in March 2020. At this time, authorities had recently closed international borders, bars and restaurants, and limited social gatherings. The participants included a representative distribution of the population, with equal numbers of men and women and participants across all age groups over the age of 18 from every Australian state and territory.

In order to prevent any potential bias, the survey was designed so that participants would not know the aims of the study. Instead the researchers incorporated the survey into market research panels, without any mention of COVID-19 or mental health during study recruitment.

Since the survey occurred in the early stages of the pandemic, only 36 participants reported having received a COVID-19 diagnosis or having had a close contact who had been diagnosed. There were also relatively few people who had been tested, had self-isolated or who had known anyone who had any of these experiences.

Surprisingly, these cases of COVID-19 contact showed no link to mental health impacts. In contrast, financial distress and disruptions to work and social activities were significantly associated with symptoms of depression and anxiety, as well as lower psychological wellbeing. However, working from home wasn't associated with any negative effects.

Higher rates of mental health symptoms were also found among people who were younger, identified themselves as female or who reported having a pre-existing mental health condition.

"We hope that these data highlight that the way countries manage COVID-19 is likely to impact their population's mental health, beyond those most directly affected by the disease," says Dawel. "It's important that governments and policy makers recognize that minimizing social and financial disruption should also be a central goal of public health policy."

WEST LAFAYETTE, Ind. - A Purdue University team has developed a novel testing platform to evaluate how breast cancer cells respond to the recurrent stretching that occurs in the lungs during breathing. The technology is designed to better understand the effects that the local tissue has on metastatic breast cancer to study how metastases grow in a new tissue.

"One of the key features of breast cancer is that most patients survive if the disease stays local, but there is a greater than 70% drop in survival if the cells have metastasized," said Luis Solorio, a Purdue assistant professor of engineering, who co-led the research team. "However, once the cells leave the primary tumor, they are often no longer responsive to the drugs that initially worked for the patient. We wanted to develop a system that could help us better understand how the physiology of a new tissue space effected tumor cells upon invasion into the new organ."

The Purdue researchers created a magnetically moving cell culturing system where the cancer cells can be grown in 3D on a suspended extracellular matrix protein that is abundant in early metastatic lung tissue in order to evaluate the impact of mechanical forces.

They were able to incorporate the strain amplitude and rate of breathing in this tissue mimic. The researchers found that the cells quit dividing under these conditions. The research is published in Advanced Functional Materials.

"Never before has the concept of motion been interrogated as a component of the tumor microenvironment," said Michael Wendt, a Purdue associate professor of medicinal chemistry and molecular pharmacology. "We now understand that healthy organs utilize motion to resist metastatic colonization. The development of this microactuator system will not only continue to yield increased biological understanding, of metastasis, but it will also serve as a platform for us to better evaluate pharmacological inhibitors of the most lethal aspect of cancer progression."

Hyowon "Hugh" Lee, an associate professor of engineering and a researcher at the Birck Nanotechnology Center, co-led the research team.

"This is the first attempt to engineer a cell culture system that can apply mechanical forces on a suspended tissue," Lee said. "Most bioreactors with mechanical stimulation capabilities rely on growing 2D cell culture on flat non-biological substrates, but we are using a custom magnetic actuator and suspending a layer of fibronectin to grow 3D cancer cells like a miniature tissue.

"Our system better mimics the physiological environment without using artificial substrates. Using this platform, we show that certain cancer cells slow down their proliferation due to the cyclic stretching of breathing."

This work was the collaboration of five different laboratories to characterize the mechanical and biological properties of the new device.

Sarah Calve, a Purdue adjunct professor of biomedical engineering, and Adrian Buganza Tepole, a Purdue assistant professor of mechanical engineering, interfaced with the mechanical characteristics of the stretching protein. They measured the response of the material to stretching and developing a mapping of the strains felt by the cancer cells at various locations on the device.

Angel Enriquez, a doctoral student in Lee's lab, said, "One key takeaway has been the benefits of collaboration with people outside of your field of expertise and how they can provide more complete research."

Sarah Libring, a doctoral student and a co-first author from Solorio's Lab, said, "It's been amazing to be part of the development of a new device like this because by bringing together the expertise of multiple professors and multiple labs, we are now able to study cancer cells on dynamically moving fibronectin fibrils that hasn't been previously possible."

A new study by Simon Fraser University (SFU) researchers has found clear evidence that wearing a mask can have a significant impact on the spread of COVID-19. The researchers, from SFU's Department of Economics, have determined that mask mandates are associated with a 25 per cent or larger weekly reduction in COVID-19 cases.

The finding of their study, still in preprint and not yet peer-reviewed, conclude that mandating indoor masks nationwide in early July could have reduced the weekly number of new cases in Canada by 25 to 40 per cent in mid-August, which translates into 700 to 1,100 fewer cases per week.

The study analysed the impact of mask mandates that were implemented across Ontario's 34 Public Health Units (PHUs) over the course of two months.

Researchers compared the results of PHUs that adopted mask mandates earlier to those that adopted mandates later. They determined that, in the first few weeks after their introduction, mask mandates were associated with an average weekly reduction of 25 to 31 per cent in newly diagnosed COVID-19 cases, relative to the trend in mask mandate absence, in July and August.

A further Canada-wide analysis with province-level data found a significantly negative association between mask mandates and subsequent COVID-19 case growth - up to a 46 percent average reduction in weekly cases in the first several weeks after adoption.

These results were supported by additional survey data that showed mask mandates increase self-reported mask usage in Canada by 30 percentage points, suggesting that the policy has a significant impact on behaviour.

Jointly, these results suggest that mandating indoor mask wear in public places is a powerful policy measure to slow the spread of COVID-19, with little associated economic disruption in the short term.

The study also found that relaxed restrictions on businesses and gatherings (including retail, restaurants and bars) were positively associated with subsequent COVID-19 case growth - a factor that could offset and obscure the health benefits of mask mandates.

The most stringent restrictions on businesses and gatherings observed in the data were associated with a weekly decrease of 48 to 57 per cent in new cases, relative to the trend in the absence of restrictions.

The study authors note that while the results are significant, their sample period does not allow them to definitively say whether the effect of mask mandates persists or weakens beyond the first few weeks after implementation. However, they conclude that, combined with other policy measures, mask mandates can be a potent policy tool for slowing the spread of COVID-19.

Key Finding:

Mask mandates are associated with a 25 to 46 per cent average reduction in weekly COVID-19 cases across Canada.

Requiring indoor masks nationwide in early July could have reduced new COVID-19 cases in Canada by 25 to 40 per cent in mid-August, which translates into 700 to 1,100 fewer cases per week.

Mask mandates were shown to increase self-reported mask usage in Canada by 30 percentage points.

The most stringent restrictions on businesses and gatherings (including retail, restaurants and bars) were associated with a weekly decrease of 48 to 57 per cent in new cases, relative to the trend in the absence of restrictions.

Large majorities of American news audiences care about climate change and want more information from the media on the topic, according to a new report from the University of Cincinnati, in partnership with Yale University and George Mason University.

"Our findings show that for several major American news sources, a majority of their audience thinks the media should be doing more to address the issue of climate change. A majority are interested in news stories about climate change topics. In fact, our study shows fewer than 20% of Americans in any of these news audiences feel they are 'very well informed' about climate change," says the report's lead author, Abel Gustafson, an assistant professor in the Department of Communication at UC.

"These findings put the ball in journalists' court," he says, because "much of their audience is saying they feel that climate change is an important issue to be covering in more depth."

The report uses three national surveys to measure public opinion on climate change among the regular audiences of Fox News, CNN, MSNBC, NPR, the Weather Channel and the national nightly network news on CBS, ABC or NBC. The survey measured many beliefs about climate change, including whether it is happening, is caused by humans, should be a high priority for elected officials and how this issue influences their choice of a candidate in the 2020 presidential election.

According to the report, majorities in each of these news audiences say global warming or protecting the environment will be important to their vote for president.
Gustafson says other takeaways from the report include:

*In each of the news audiences studied, large majorities underestimate the true strength of the scientific consensus on climate change. "Even among people who care deeply about climate change, most underestimate just how strong the scientific consensus is," he says, adding that, "Journalists can play an important role in fixing this misperception by emphasizing the strength of the scientific evidence when they cover climate change topics."

*Among the news audiences studied in this report, the Fox News audience is least accepting of climate science and thinks the issue is least important to them personally.
However, there are many differences among Fox viewers, he says. "The climate opinions of the Fox News audience are much more diverse than common stereotypes would suggest. In fact, nearly half of the regular Fox News audience say they are worried about climate change and think it should be at least a 'medium' priority for our elected government officials."

*In most news audiences, large majorities (over 80% for CNN, MSNBC and NPR) think global warming is happening, think it is human caused and are worried about it.

Overall, Gustafson says, "There's a clear gap between what people want from their news providers and what they are getting, because many Americans specifically say the media should be doing more to address this issue."

Though some believe prehistoric humans lived in harmony with nature, a new analysis of fossils shows human arrival in the Bahamas caused some birds to be lost from the islands and other species to be completely wiped out.

The researchers examined more than 7,600 fossils over a decade and concluded that human arrival in the Bahamas about 1,000 years ago was the main factor in the birds' extinction and displacement in recent millennia, although habitat fluctuations caused by increased storm severity and sea level rise could have played a role.

Many spectacular species, such as a colorful parrot, a striking scavenger called a caracara, and a number of hawks, doves, owls, and songbirds, were still found as recently as 900 years ago, and may have overlapped with people by a century before disappearing or retreating to only one or two islands in The Bahamas. "No other environmental change could explain their loss," said study co-lead Janet Franklin, a distinguished professor of botany and plant sciences at UC Riverside.

Full results of Franklin's study were published this week in the Proceedings of the National Academy of Sciences.

For example, the Abaco parrot is now only found on two islands in the Bahamas. There are many islands in between the two where the parrots now live that have the same habitat.

"We wondered why those parrots aren't found in the middle islands," Franklin said. "It turns out, they were, not that long ago." Franklin and her collaborator, ornithologist David Steadman of University of Florida, found Abaco parrot fossils were on all the islands until 1,000 years ago.

The study was also able to identify losses of bird species that lived in the Bahamas since the end of the last ice age, more than 10,000 years before people arrived. These species included a giant barn owl and giant eagle -- predators whose prey also disappeared from the islands after people arrived.

More than two thirds of the 90 bird species identified in the fossils that date from the end of the last ice age. Either they have gone altogether extinct or now only persist outside of the Bahamas.

The Bahamian islands are "treasure troves" of fossils because the limestone caves and flooded sinkholes there act as natural traps and are highly effective at preserving bones. Because they're relatively small land areas lacking mountains or steep, remote areas where plants and animals can retreat to avoid people, the islands are also places where humans can have a big impact.

Giant predator birds likely competed with people for food such as giant tortoises -- now extinct -- and hutia, the only native land mammal in the Bahamas, which resembles a large guinea pig. In addition, humans hunt birds that eat fruit, because they tend to be fatter and more delicious.

It isn't clear how much of the effect on birds is attributable to habitat change caused by people settling on the islands and how much was due to direct human predation. But Franklin said the wild habitat requires protections to preserve the animals that remain.

"The species here are the ones that survived," Franklin said. "They might be more adaptable than other birds, and less dependent on a niche or habitat that's strongly affected by human activity. But they are still vulnerable and worth conserving."

Furthermore, the researchers note in the study that "the related futures of biodiversity and humanity perhaps never have been at a crossroads more than now. The transfer of a zoonotic disease from wildlife to humans, which has resulted in a global pandemic, is directly linked to biodiversity loss."

In other words, as humans increasingly take over wild habitat, particularly rainforests, there are more opportunities for diseases to jump from wildlife to people.

"Protecting rainforests and regulating wildlife trade helps the animals and is also a component of preventing pandemics," Franklin said.

Researchers from Tokyo Medical and Dental University (TMDU) identify a gene associated with symptoms of two severe genetic conditions

Tokyo, Japan - Temple and Kagami-Ogata syndromes are serious genetic conditions that can lead to a variety of health problems with neonatal lethality, and in the case of Temple syndrome, severe growth problems occur. However, the genetic mechanisms of these illnesses are not well understood. But now, researchers from Tokyo Medical and Dental University (TMDU) have identified a gene that appears to be responsible for symptoms of both conditions, with important implications for human evolutionary genetics.

In a study published last month in Development the research team has revealed that deficiency and overproduction of Retrotransposon Gag like 1 (Rtl1), which is a mouse ortholog of the human RTL1 gene, is significantly associated with muscle symptoms in models of Temple and Kagami-Ogata syndromes, respectively.

Temple and Kagami-Ogata syndromes are characterized by unique postnatal muscle-related symptoms and prenatal placental problems. Although Rtl1 has previously been found to be responsible for prenatal placental malformations in mouse models of these conditions, the causative gene for the muscle-related symptoms has not been identified. The researchers at Tokyo Medical and Dental University (TMDU) aimed to address this in their recent study.

"Although Rtl1 is essential for maintaining placental fetal capillaries," says lead author of the study, Moe Kitazawa, "Little is known about the role of Rtl1 in other forms of muscular abnormalities."

The researchers extensively examined the role of Rtl1 in fetal muscle development at both the cellular and tissue level. They used two previously generated mouse models, one with a loss of Rtl1 to model Temple syndrome, and one with an overproduction of Rtl1 to model Kagami-Ogata syndrome.

"Our data clearly demonstrate that RTL1 is of critical physiological significance," explains Fumitoshi Ishino, senior author. "In the mouse models of both Temple and Kagami-Ogata syndrome, we detected severe but distinct abnormalities in the neonatal muscles that are necessary for respiration, such as the intercostal, abdominal, and diaphragm muscles."

Particularly, the overproduction of Rtl1 in the mouse model of Kagami-Ogata syndrome led to respiratory problems and muscle damage, resulting in neonatal death and the loss of Rtl1 was a major cause of abnormal muscle tone, such as hypotonia, and likely to be associated with feeding difficulty/poor sucking function in Temple syndrome patients.

Thus, RTL1 appears to be the major gene responsible for muscle and placental defects in these two genetic conditions.

"This is the first demonstration that a form of RTL1 specific to eutherians (placental mammals) plays an important role in fetal and neonatal muscle development," says Kitazawa.

"This work demonstrates that LTR retrotransposons, which are a specific type of mobile DNA from which RTL1 originated, have influenced a variety of eutherian-specific traits, including the skeletal muscles, placenta, and the brain. Thus, these findings have important implications for understanding the acquisition of genes throughout the process of eutherian evolution", say senior authors Kaneko-Ishino and Ishino.

A new research report reveals that 94 individuals with rare inherited immune disorders, otherwise known as primary immunodeficiency (PID), who were infected with the SARS-CoV-2 coronavirus had similar disease outcomes to the general population. However, admission rates to intensive care tended to be higher in PID patients and the average age of affected patients was lower than in the general population.

The study, led by the Garvan Institute of Medical Research and KU Leuven, provides information for individuals affected by PIDs, their families and clinicians. The findings also contribute to an understanding of the components of the immune system that underpin an effective coronavirus immune response.

"We wanted to find out the impact of SARS-CoV-2 infection on those individuals with rare immune disorders, a group of patients assumed to be at-risk of severe COVID-19 disease if infected with SARS-CoV-2. As PID patients are so rare, this study was only possible through a large global research collaboration across 50 centres," says Prof Stuart Tangye, Leader of the Immunity and Inflammation Research Theme at Garvan and senior author of the study.

"The findings show that pre-existing immune deficiencies were generally not found to be a significant risk factor as the rate of fatality from COVID-19 was no higher in this group than the general population. Some immune defects even appeared to be protective against the dramatic immune pathology that is frequently seen in severe disease. However, our study suggests younger male patients with PIDs are more likely to endure severe COVID-19 and require ICU admission," says Isabelle Meyts, Professor at KU Leuven, and Clinical lead of the primary immunodeficiency care program at University Hospitals Leuven.

The researchers publish the findings in the Journal of Allergy and Clinical Immunology.

Inborn errors of immunity

The consequences of infection with the SARS-CoV-2 coronavirus are vastly different across individuals. Some infected people are more at risk than others, including older individuals and those with underlying health conditions. However, little is known about those with pre-existing rare inherited immune disorders.

"There has been substantial anxiety within the PID community that their immune condition would result in a more severe clinical outcome should they contract SARS-CoV-2 and develop COVID-19," says Prof Meyts.

The researchers invited clinical immunologists from around the world who manage patients with inborn errors of immunity to complete a questionnaire, if their patients had contracted the SARS-CoV-2 virus. Data was collected from patients in the USA, UK, France, Spain, Italy, Germany, the Netherlands and Latin America.

Of the 94 reported patients, 25 had mild disease and were treated as outpatients, while 59 (63%) required hospitalisation. Of those hospitalised, 13 required non-invasive breathing assistance, and 15 were admitted to intensive care for invasive ventilation.

Sadly, nine of the 94 patients passed away from COVID-19 (9.6%), which is within the range of global data of COVID-19 mortality (1-20%). However, admission rates to ICU were higher and the average age was lower in PID-affected patients than in the general population.

"Our findings warrant a recommendation for further stringent personal protective measures for patients affected by PIDs," says Prof Meyts.

Similar to the general population, adult patients in the study cohort who succumbed to SARS-CoV-2 infection had existing comorbidities, such as heart failure, chronic kidney or lung disease, and diabetes.

Searching for genes essential for COVID-19 defence

The study further revealed insights for the components of the immune system that may be involved in SARS-CoV-2 immune defence.

"More than half the patients we surveyed (56%) had a deficiency in their ability to produce antibodies. Surprisingly, these patients had similar outcomes to the rest of the cohort. And patients who were completely unable to produce antibodies all recovered following infection," says Prof Meyts.

The findings also revealed that patients with gene defects that resulted in the body being unable to respond to the pro-inflammatory effects of interleukin 6 (IL-6) developed little or no disease when infected with the SARS-CoV-2 virus. IL-6 is a signalling molecule released by the body in response to infections, and helps regulate the human immune response.

"Our findings suggest that certain forms of immune suppression, which reduce the function of IL-6, are protective against the pathological effects of the cytokine storm frequently observed in patients," says Prof Tangye.

The researchers say further studies are needed to gain a comprehensive understanding of which components of the immune system are crucial to a successful coronavirus defence. "We hope such studies will contribute to a greater understanding of COVID-19 disease progression and new therapeutic approaches," says Prof Tangye.

Astronomers from The University of Western Australia's node of the International Centre for Radio Astronomy Research (ICRAR) have developed a new way to study star formation in galaxies from the dawn of time to today.

"Stars can be thought of as enormous nuclear-powered processing plants," said lead researcher Dr Sabine Bellstedt, from ICRAR.

"They take lighter elements like hydrogen and helium, and, over billions of years, produce the heavier elements of the periodic table that we find scattered throughout the Universe today.

"The carbon, calcium and iron in your body, the oxygen in the air you breathe, and the silicon in your computer all exist because a star created these heavier elements and left them behind," Bellstedt said.

"Stars are the ultimate element factories in the Universe."

Understanding how galaxies formed stars billions of years ago requires the very difficult task of using powerful telescopes to observe galaxies many billions of light-years away in the distant Universe.

However, nearby galaxies are much easier to observe. Using the light from these local galaxies, astronomers can forensically piece together the history of their lives (called their star-formation history). This allows researchers to determine how and when they formed stars in their infancy, billions of years ago, without struggling to observe galaxies in the distant Universe.

Traditionally, astronomers studying star formation histories assumed the overall metallicity--or amount of heavy elements--in a galaxy doesn't change over time.

But when they used these models to pinpoint when stars in the Universe should have formed, the results didn't match up with what they were seeing through their telescopes.

"The results not matching up with our observations is a big problem," Bellstedt said. "It tells us we're missing something."

"That missing ingredient, it turns out, is the gradual build-up of heavy metals within galaxies over time."

Using a new algorithm to model the energy and wavelengths of light coming from almost 7000 nearby galaxies, the researchers succeeded in reconstructing when most of the stars in the Universe formed--in agreement with telescope observations for the first time.

The designer of the new code--known as ProSpect--is Associate Professor Aaron Robotham from ICRAR's University of Western Australia node.

"This is the first time we've been able to constrain how the heavier elements in galaxies change over time based on our analysis of these 7000 nearby galaxies," Robotham said.

"Using this galactic laboratory on our own doorstep gives us lots of observations to test this new approach, and we're very excited that it works.

"With this tool, we can now dissect nearby galaxies to determine the state of the Universe and the rate at which stars form and mass grows at any stage over the past 13 billion years.

"It's absolutely mind-blowing stuff."

This work also confirms an important theory about when most of the stars in the Universe formed.

"Most of the stars in the Universe were born in extremely massive galaxies early on in cosmic history--around three to four billion years after the Big Bang," Bellstedt said.

"Today, the Universe is almost 14 billion years old, and most new stars are being formed in much smaller galaxies."

Based on this research, the next challenge for the team will be to expand the sample of galaxies being studied using this technique, in an effort to understand when, where and why galaxies die and stop forming new stars.

Bellstedt and Robotham, along with colleagues from Australia, the UK and the United States, are reporting their results in the scientific journal the Monthly Notices of the Royal Astronomical Society.

Magnetic fields are used in various areas of modern physics and engineering, with practical applications ranging from doorbells to maglev trains. Since Nikola Tesla's discoveries in the 19th century, researchers have strived to realize strong magnetic fields in laboratories for fundamental studies and diverse applications, but the magnetic strength of familiar examples are relatively weak. Geomagnetism is 0.3-0.5 gauss (G) and magnetic tomography (MRI) used in hospitals is about 1 tesla (T = 104 G). By contrast, future magnetic fusion and maglev trains will require magnetic fields on the kilotesla (kT = 107 G) order. To date, the highest magnetic fields experimentally observed are on the kT order.

Recently, scientists at Osaka University discovered a novel mechanism called a "microtube implosion," and demonstrated the generation of megatesla (MT = 1010G) order magnetic fields via particle simulations using a supercomputer. Astonishingly, this is three orders of magnitude higher than what has ever been achieved in a laboratory. Such high magnetic fields are expected only in celestial bodies like neutron stars and black holes.

Irradiating a tiny plastic microtube one-tenth the thickness of a human hair by ultraintense laser pulses produces hot electrons with temperatures of tens of billion of degrees. These hot electrons, along with cold ions, expand into the microtube cavity at velocities approaching the speed of light. Pre-seeding with a kT-order magnetic field causes the imploding charged particles infinitesimally twisted due to Lorenz force. Such a unique cylindrical flow collectively produces unprecedentedly high spin currents of about 1015 ampere/cm2 on the target axis and consequently, generates ultrahigh magnetic fields on the MT order.

The study conducted by Masakatsu Murakami and colleagues has confirmed that current laser technology can realize MT-order magnetic fields based on the concept. The present concept for generating MT-order magnetic fields will lead to pioneering fundamental research in numerous areas, including materials science, quantum electrodynamics (QED), and astrophysics, as well as other cutting-edge practical applications.

Smartphones and wearable devices are not simple accessories for athletes. A CNRS researcher* has developed a simple mathematical model for studying the performance of endurance athletes. A recent collaboration with a scientist from the Polar Electro Oy company (Finland) made it possible to apply the model to data gathered from approximately 14,000 runners training in real conditions. According to their study, the mathematical model can estimate key physiological parameters such as maximal aerobic speed and endurance, which are known to be linked to health conditions and performance. The non-invasive gathering of this data offers new possibilities for treatments and monitoring. What's more, this model could be used to predict the future performance of athletes, such as the race time for a marathon, which would help with their recruitment for teams and competitions. The study, which appeared on October 6 in Nature Communications, opens new avenues for quantifying the health and sports performance of athletes in real conditions.

An international study led by the Institute of Environmental Science and Technology (ICTA-UAB) and the Department of Prehistory at the UAB has reconstructed the diets of pre-Columbian groups on the Amazon coast of Brazil, showing that tropical agroforestry was regionally variable.

During the past few decades, there has been an increased interest in the origin and evolution of pre-Columbian economies in the Amazon. However, the paucity of human remains from this period has limited our understanding of the contribution of plants, terrestrial animals and fish to individual diets and, therefore, their role in supporting population growth and cultural changes in this region before European contact.

This new study, published in Scientific Reports, used stable isotopic analysis and Bayesian Mixing Models to reconstruct the diets of human individuals living along the Brazilian Amazon coast between 1,000 and 1,800 years ago.

They found that despite the proximity to marine resources and the evidence of fishing, diets were based mainly on terrestrial plants and animals. Land mammals and plants were the main sources of caloric intake. Land animals were also the main source of dietary protein, compared to fish.

Among the taxonomically identified animals, they found rodents such as paca, cavia or cutia, a brocket deer and catfish. In the late Holocene a large variety of wild and cultivated plants such as cassava, corn, squash, among others, were consumed.

"The results call into question the widespread assumption that fish was the main economic component and the largest source of protein among pre-Columbian populations living in proximity to aquatic environments in lowland Amazonia", says Colonese. He adds that the results indicate these populations dedicated considerable efforts to hunting, forest management and plant cultivation.

"Our study provides unprecedented quantitative information on the extent to which distinct food categories from agroforestry systems fulfilled the caloric and protein requirements of populations in the pre-Columbian Amazon, and corroborates the growing consensus that these diversified subsistence economies fuelled cultural, demographic and environmental transformations in the eastern Amazon basin during the Late Holocene."