Culture

There are concerns that exposure to general anesthesia during surgery may contribute to an increased risk of Alzheimer's disease. To investigate, researchers compared exposure to general anesthesia versus regional anesthesia during elective surgery, looking for potential links to the development of dementia.

The Journal of the American Geriatrics Society study included 7,499 matched pairs of community-dwelling individuals aged 66 years or older who underwent surgery between 2007 and 2011 and were followed for up to 5 years.

The investigators found no difference in risk of being diagnosed with dementia for individuals who received general anesthesia when compared with those who received regional anesthesia.

"Many older adults experience changes in their cognition immediately following surgery and wonder what role the type of anesthetic might have played in these changes," said senior author Dallas P. Seitz, MD, PhD, FRCPC, of the University of Calgary, in Canada. "Our study provides evidence that anesthetic technique used during elective surgeries, general anesthesia or regional anesthesia is not associated with a long-term risk of developing dementia."

An analysis of relevant studies published to date has identified certain risk factors associated with suicidal behavior in adolescents. The analysis also revealed certain protective factors that may reduce the likelihood of suicidal behavior.

The analysis, which is published in the Journal of Child and Adolescent Psychiatric Nursing, included 66 studies. Internal risk factors included poor individual coping, smartphone abuse, nutritional imbalance, menstrual problems, poor lifestyle, and disturbed sleep patterns. External risk factors for adolescent suicide behavior included mental health history in parents, poor interactions in the family, and social problems.

Reframing to have a meaningful life, adequate nutrition, parent-child interactions, reading books and watching movies, and faith or religiosity are protective factors that may reduce the risk of suicidal behavior in adolescents.

"Loving others is imperative, loving yourself is courage. Don't be afraid to love yourself--you have to fight for yourself before fighting for others," said senior author Heni D. Windarwati, of the Universitas Brawijaya, in Indonesia.

Having a strong ethnic identity was linked with a lower risk of suicidal behaviors among Black college students in a recent study published in the Journal of Multicultural Counseling and Development.

The study examined the influence of cultural orientation (ethnic identity, Afrocentric worldview, and religiosity) and personal resources (resiliency and optimism) on suicidal behaviors among Black college students.

The investigators noted that for Black college students, especially as members of a racial/ethnic minority within the society, having a strong ethnic identity may be a stronger protective factor against suicidality as compared with religiosity and Afrocentric worldview.

Also, resilience and a sense of empowerment seemed to matter more than optimism in terms of decreasing suicidal behaviors. Black college students who endorsed a higher level of Afrocentric worldview, ethnic identity, or religiosity were more resilient, which in turn protected against suicidality.

"Most often, the uniqueness of Black persons' identity is viewed from a negative perspective. With increasing calls to respect and uphold Blacks' lives, our study sheds light to the positive role of Black ethnic identity in enhancing their psychological welfare," said co-author Pius N. Nyutu, PhD, of Fayetteville State University.

There's considerable risk that humans transmit SARS-CoV-2, the virus that causes COVID-19, to wildlife, according to a perspective article published in Mammal Review.

The authors noted that if SARS-CoV-2 were to infect and spread among wild mammals, it could potentially cause disease in some populations, in turn further endangering already threatened species.

Also, if SARS-CoV-2 could be sustainably transmitted among some mammalian populations or communities, this would create new animal reservoirs that could repeatedly source new outbreaks in humans and other animals.

The researchers urge people to take sanitary precautions when in direct or indirect contact with wild or feral mammal species to prevent human-to-wildlife SARS-CoV-2 transmission.

"We really should avoid turning our pandemic into a multi-species problem," said lead author Sophie Gryseels, PhD, of the University of Antwerp, KU Leuven, and the University of Arizona. "It's difficult enough to control the SARS-CoV-2 in human populations--imagine what it will be like if it spreads among wild mammals. They could also get sick and form a reservoir from which they can then again infect humans, but we can't ask animals to wear face masks and keep physical distance."

CLEVELAND, Ohio -- No one knows for sure how long they will live. A new study, however, suggests that leukocyte telomere length may offer some key insights into a woman's longevity and further demonstrates how maternal age at birth of last child affects telomere length and long-term health. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

This is not the first time that the length of a woman's leukocyte telomeres has been linked with her projected lifespan. Telomeres are repeating DNA-protein complexes that protect the ends of chromosomes and have proven to be critical for maintaining genomic stability. Previous studies have suggested a link between telomere length and various chronic conditions such as cardiovascular disease, type 2 diabetes, some neurologic conditions, and various cancers.

A smaller study previously suggested that maternal age at the birth of a woman's last child affected telomere length. This new, larger-scale study included more than 1,200 perimenopausal and postmenopausal women of various ethnicities and backgrounds from the National Health and Nutrition Examination Survey. In addition, unlike previous studies, this study took into consideration sociodemographic factors related to childbearing patterns and health decisions.

The study confirmed that maternal age at last birth is positively associated with telomere length, meaning that women who delivered their last child later in life were likely to have longer telomeres, a biomarker of long-term health and longevity. This finding was restricted to women with one or two live births or who had used oral contraceptives.

Results are published in the article "Maternal age at last birth and leukocyte telomere length in a nationally representative population of perimenopausal and postmenopausal women."

"More research is needed to determine whether older maternal age at last birth causes telomeres to lengthen or whether telomere length serves as a proxy for general health and corresponds with a woman's ability to have a child at a later age," says Dr. Stephanie Faubion, NAMS medical director.

A team of scientists has discovered an ancient form of rubisco, the most abundant enzyme on Earth and critical to life as we know it.

Found in previously unknown environmental microbes, the newly identified rubisco provides insight into the evolution of the photosynthetic organisms that underlie the planet's food chains.

"Rubisco is the primary driver for producing food, so it can take CO2 from the atmosphere and fix that into sugar for plants and other photosynthetic organisms to use," said Doug Banda, a postdoctoral scholar in the lab of Patrick Shih, a UC Davis assistant professor and the director of Plant Biosystems Design at the Joint BioEnergy Institute (JBEI), which is managed by Lawrence Berkeley National Laboratory (Berkeley Lab). "It is also one of the oldest carbon-fixing enzymes on the planet."

Form I rubisco, which is found in plants, algae, and cyanobacteria, has a deep evolutionary history with the planet, going back nearly 2.4 billion years to the Great Oxygenation Event, when cyanobacteria literally transformed the Earth's atmosphere by introducing oxygen to it through photosynthesis. Rubisco's role in this foundational event makes it a key focus of scientists studying the evolution of life, as well as scientists seeking to develop bio-based fuels and renewable energy technologies.

In a study appearing in Nature Plants, Banda and researchers from UC Davis, UC Berkeley, and Berkeley Lab report the discovery and characterization of a previously undescribed lineage of form I rubisco - one that the researchers suspect diverged from form I rubisco prior to the evolution of cyanobacteria.

Found through metagenomic analysis of environmental samples and synthesized in a lab, the new lineage, called form I' rubisco, gives researchers new insights into the structural evolution of form I rubisco, potentially providing clues as to how this enzyme changed the planet.

"This could've been what a rubisco looked like before the rise of oxygen more than 2.4 billion years ago," said Shih, noting that the form I' rubisco provides scientists with a window into how ancient microbes might've fixed carbon before the rise of cyanobacteria and the form I rubisco.

An invisible world

Form I rubisco is a hexadecamer, meaning it's built from eight core, large molecular subunits with eight small subunits perched on top and bottom. Each piece of this protein's structure is integral to photosynthesis, and thus the carbon fixation process.

Other functional forms of rubisco exist in bacteria and microorganisms of the Archaea domain. These variants come in different shapes and sizes, and all perform the same step of photosynthesis. However, form I rubisco is responsible for the vast majority of carbon fixation on Earth.

Study co-author and collaborator Professor Jill Banfield, of UC Berkeley's Earth and Planetary Sciences Department, uncovered form I' rubisco after performing metagenomic analyses on groundwater samples. Metagenomic analyses allow researchers to examine genes and genetic sequences from uncultured microorganisms found in the environment.

Using the genes and genetic sequences provided by Banfield, Banda, and Shih successfully expressed form I' rubisco in the lab using E. coli. To learn how this newly identified form functions and how it compares to previously discovered rubisco enzymes, the scientists needed to build precise, 3D models of its structure. For this task, the lead authors turned to Berkeley Lab structural biologists Paul Adams, Henrique Pereira, and Michal Hammel.

First, Adams and Pereira performed X-ray crystallography - an approach that can generate images of molecules with atomic-level resolution - at Berkeley Lab's Advanced Light Source (ALS) (https://als.lbl.gov/). Then, to capture how the enzyme's structure changes during different states of activity, Hammel applied a technique called small-angle X-ray scattering (SAXS) using the SIBYLS beamline (https://sibyls.als.lbl.gov/) at the ALS.

SAXS is a lower-resolution technique, but unlike crystallography - which requires that sample molecules are frozen in crystal form - SAXS is performed in solution. When the data from the two approaches are combined, scientists can construct unprecedented models of complex molecules as they appear in nature.

"Like many enzymes key to life, rubisco has several protein domains connected together, and as it binds with other molecules during the photosynthesis reaction, it will cycle through different arrangements of those domains," said Hammel, a biophysicist in Berkeley Lab's Molecular Biophysics and Integrated Bioimaging (MBIB) Division. "Our techniques really worked hand-in-hand to reveal how this new, novel rubisco behaves in real-world, physiological conditions."

The ALS investigations showed that like form I rubisco, form I' rubisco is built from eight large subunits. However, it doesn't possess the small subunits that were previously thought to be essential to its carbon-fixing function.

The researchers now believe that form I' rubisco represents a missing link in the evolutionary history of form I rubisco's structure.

"The discovery of an octameric rubisco that forms without small subunits allows us to ask [evolutionary] questions about what life would've looked like without the functionality imparted by small subunits," said Banda.

Following the success of the structural investigation into form I' rubisco, Shih has enlisted Hammel, Adams, and Pereira to apply their complementary approach for studies of other crucial plant enzymes, including additional forms of rubisco.

"We've been working together at Berkeley Lab for over 10 years now, and it was really satisfying to be able to see what crystallography and SAXS combined can do to understand biology problems," said Pereira, an MBIB biophysicist. "Once, the scientists who use these different structural biology techniques would have seen themselves as in competition, racing each other to solve structures. But now it's pure collaboration."

The ALS is a Department of Energy (DOE) user facility and JBEI is a DOE Bioenergy Research Center. The crystallography beamline used in this research is operated by the Berkeley Center for Structural Biology and funded by the Howard Hughes Medical Institute. The SIBYLS beamline is supported by the National Cancer Institute grant Structural Biology of DNA Repair and the DOE Office of Science. This work was supported in part by the DOE Office of Science.

Since 2004, Claude Knauf (INSERM) and Patrice Cani (UCLouvain) have been collaborating on molecular and cellular mechanisms in order to understand the causes of the development of type 2 diabetes and above all to identify new therapeutic targets. In 2013, they created an international laboratory, 'NeuroMicrobiota Lab' (INSERM-UCLouvain), to identify links between the brain and intestinal bacteria.

Very quickly, they understood that the gut-brain axis plays a preponderant role in the regulation of sugar in the blood. When we eat, the gut (also called the 'second brain' owing to the neurons that compose it) contracts and digests food. Sugar and fat enter the body and their levels increase in the blood. Using this sugar and fat, the body then does its work or stores them. In a person with diabetes, this process malfunctions and the sugar level increases in abnormal proportions.

Taking a step further, the two researchers observed that the gut, when it digests, sends a signal to the brain, to find out what to do with the incoming fats and sugars. The brain then sends the message to various organs (liver, muscles, adipose tissue) to get ready to lower blood sugar and fat levels. In a diabetic individual, however, this mechanism doesn't work. Researchers have observed that the gut malfunctions and sends no signal to the brain. The cause is hypercontractility of the intestine, which interferes with communication with the brain. Suddenly, commands to get the sugar out of the blood no longer pass. The sugar remains, causing hyperglycaemia. The mechanism also impacts the action of insulin: no message means no insulin action, resulting in insulin resistance.

The researchers sought to understand this hypercontractility, by observing the differences in the constitution of the intestine as well as the action of prebiotics within the microbiota in 'normal' and 'diabetic' mice. They observed that a particular lipid was severely deficient in diabetic mice, but also in people with diabetes (although it's naturally present in the intestines of healthy patients). The team therefore tested the impact of the lipid on the use of sugars, on the contraction of the intestine and, ultimately, on diabetes. NeuroMicrobiota research team members Anne Abot and Eve Wemelle discovered the lipid is the key to restoring the use of sugar. It works by acting directly on the second brain.

Today, the team has discovered and understood how our gut bacteria (or gut microbiota) play an important role in altering the production of bioactive lipids, and from there to restore perfect communication between the gut and the brain. Hence some of these lipids are essential messengers which act on very precise targets in the second brain (enkephalins or opioid receptors). Treatment possibilities include modifying the body's production of such lipids, could or taking them orally. These avenues are under study.

Using the same approach, the INSERM-UCLouvain research team, contributed to the discovery of a new bioactive lipid that reduces intestinal inflammation. It is directly produced by certain gut bacteria, also identified in this study and therefore the two approaches, either the lipid or one or more bacteria, could serve as a therapeutic target.

One in three of the 150,000 humans who die every day is a victim of cardiovascular disease, according to WHO. Half the Belgian population is overweight and presents cardiovascular and type 2 diabetes risks. This UCLouvain and INSERM research could potentially have an impact on a large portion of the population.

Researchers at the University of Massachusetts Amherst have identified a single-measure biomarker in sperm mitochondrial DNA that may predict male reproductive health and pregnancy success.

The discovery applies not just to couples seeking care for infertility but also for the general population. This biomarker could become a more accurate predictor of male infertility than semen parameters, on which health care organizations and clinicians have long relied.

"Clinically, the diagnosis of male infertility really hasn't changed in decades," says UMass Amherst environmental epigeneticist Richard Pilsner, corresponding author of the study published today, Oct. 6, in the journal Human Reproduction. "In the last 10 to 20 years, there have been major advances in the understanding of the molecular and cellular functions of sperm, but the clinical diagnosis hasn't changed or caught up."

In addition to Pilsner, the team of UMass researchers included lead author Allyson Rosati, who wrote the paper as part of her undergraduate honors thesis and recently completed a master's in molecular and cellular biology; Brian Whitcomb, associate professor of epidemiology in the School of Public Health and Health Sciences. They collaborated with reproductive and perinatal epidemiologist Germaine Buck Louis, dean of the College of Health and Human Services at George Mason University, and Sunni Mumford and Enrique Schisterman at the National Institute of Child Health & Human Development.

"This project is a really nice example of interdisciplinary work and team science," Whitcomb says. "This research required measurement of biomarkers in the laboratory combined with statistical modeling. Answering scientific questions like this one benefits from a broad range of expertise."

Mitochondrial DNA is maternally inherited, and sperm mitochondrial DNA copy number (mtDNAcn) typically decreases eight-to-10 fold during spermatogenesis to ensure that it is low upon fertilization. In previous research by Pilsner, Whitcomb and others, increased mtDNAcn and mitochondrial DNA deletions (mtDNAdel) were associated with decreased semen quality and lower odds of fertilization in men seeking fertility treatment.

"The logical next step was to determine if the associations between sperm mitochondrial biomarkers and fertilization among couples seeking infertility treatment could be extended to couples from the general population," Pilsner says.

The researchers accessed sperm samples from the Longitudinal Investigation of Fertility and the Environment (LIFE) study, which recruited 501 couples from Michigan and Texas from 2005 to 2009 to examine the relationships between lifestyle, including environmental chemicals, and human fertility.

They assessed sperm mtDNAcn and mtDNAdel from 384 semen samples and analyzed their association with the probability of pregnancy within one year. They found that men with higher sperm mtDNAcn had as much as 50% lower odds of cycle-specific pregnancy and 18% lower probability of pregnancy within 12 months.

"Remarkably, we saw a strong inverse association between sperm mitochondrial biomarkers and couples' time-to-pregnancy," Pilsner says.

Adds Whitcomb, "Mitochondrial DNA in sperm seems to reflect some underlying physiological phenomenon that affects sperm function."

More research is needed to further examine the impact of changes in mtDNAcn and mtDNAdel, which may result from defective mitochondria or damaged mtDNA. "We need to take advantage of our understanding of the molecular toolkit that we have to develop a better predictor of male fertility, as well as fecundability," Pilsner says.

A next step is to examine the factors mediating the changes in sperm mitochondrial DNA. They could include environmental toxins or other causes of inflammation and oxidative stress, the scientists hypothesize.

"Understanding what is causing the retention of mitochondrial copy number during spermatogenesis will help us come up with better platforms to intervene and to promote better reproductive success," Pilsner says.

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.