Culture

Brown bears that are more inclined to grate and rub against trees have more offspring and more mates, according to a University of Alberta study. The results suggest there might be a fitness component to the poorly understood behaviour.

"As far as we know, all bears do this dance, rubbing their back up against the trees, stomping the feet and leaving behind odours of who they are, what they are, what position they're in, and possibly whether they are related," said Mark Boyce, an ecologist in the Department of Biological Sciences.

"What we were able to show is that both males and females have more offspring if they rub, more surviving offspring if they rub and they have more mates if they rub."

The research team led by Boyce and post-doctoral fellow Andrea Morehouse identified and collected bear hair samples from 899 bear rub spots, which included trees, fence posts and power poles, in the Alberta Rocky Mountains south of Highway 3 for a period of four years starting in 2011.

The team genotyped 213 individual brown bears (118 males, 95 females). Building on the work of Curtis Strobeck, who realized a decade earlier that emerging DNA methods could be used to identify individual bears, the team used previously collected data for more 2,043 individual brown bears in the area to create a family tree.

What the results showed was that bears that rub more frequently and at more sites do better.

For every rub object at which a male bear was detected, the predicted number of mates increased by 1.38 times. As well, for each additional occasion during which a male bear was detected, the predicted number of offspring is multiplied by 1.37.

The researchers also observed the same relationships for female brown bears. Females with more mates were detected at more rub objects and on more occasions than females with fewer mates. For each additional rub object and occasion during which a female was detected, the predicted number of offspring increased by 1.42 and 1.55 times respectively.

"It seems bears that are in good condition are more vigorous and they rub more, and that could be correlated with reproductive success," he said.

This study also showed that this rubbing behaviour helps females with cubs avoid territories of big males, by often choosing marginal habitat near ranch buildings or closer to roads.

"This is done by scent and the reason they do is that big males are notorious for killing cubs," said Boyce. "Big males won't go anywhere near a building, but for females with cubs, that's an acceptable risk."

He added further studies may also shed light on sexual selection in bears. While brown bears will fight tooth and nail to protect their territories, which will often include the territories of up to four females, females have a say.

In fact, previous research showed upwards of 17 per cent of all brown bear litters are sired by multiple males.

"Female choice is a big deal," said Boyce. "In this study, we proposed an alternative hypothesis that female brown bears use the information obtained from olfactory cues of rubbing males throughout the season to choose offspring paternity."

The study, "The smell of success: Reproductive success related to rub behaviour in brown bears," was published in PLOS ONE.

The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) has helped Gaia achieve millimagnitude (mmag) precision in photometry, according to a study led by researchers from National Astronomical Observatories of Chinese Academy of Sciences (NAOC) and Beijing Normal University (BNU).

Their study was published in The Astrophysical Journal.

If you look at the sky on a clear, starry night, you may notice that Aldebran is relatively red and Rigel is blue. Why? The answer stems from their intrinsic physical properties. Precisely measuring magnitudes and colors helps to explain such phenomena.

The ESA Gaia satellite is well known for its remarkable capacity for astrometric observation. It delivers the most precise photometric data ever, with much higher quality than ground-based telescopes.

However, in order for Gaia to cover a wide magnitude range from 6 to 22 magnitude (mag), different observation modes have been adopted for stars of different brightness. In addition, photometric data in the G, BP, and RP bands come from different instruments and CCDs. Therefore, magnitude and color-dependent systematic errors exist.

The researchers combined two datasets, Gaia Data Release 2 (DR2) and LAMOST Data Release 5 (DR5), then selected samples of high data quality and low extinction.

The samples comprised 779,691 main-sequence stars and 71,952 red giant branch stars. Stars from 13.3 to 13.7 mag in the G band were selected as the control sample in order to establish the empirical relationship between intrinsic colors and physical parameters deduced from LAMOST.

"Applying the relationship to the whole sample, the differences between the observed colors and model-determining colors at different G magnitudes represent the color correction terms," said Prof. LIU Jifeng from NAOC.

With the help of LAMOST's massive stellar spectrum, the researchers used a spectroscopy-based stellar color regression method to correct systematic errors that are magnitude- and color-dependent. The relationship between the intrinsic colors and physical parameters of stars represents the key focus of this method.

By using a sample of about 500,000 stars from LAMOST and Gaia, color correction curves for the F/G/K stars are derived. "With an unprecedented precision of about 1 mmag, systematic trends in the G magnitude are revealed for both G-RP and BP-RP colors in detail," said Prof. YUAN Haibo from BNU, the corresponding author of the study.

"Our work could be beneficial to studies where a high-precision color-color diagram is required, including the estimation of Gaia photometric metallicities, detection of peculiar objects, discrimination between binaries and single stars, and so on," said NIU Zexi, Ph.D. candidate from NAOC and lead author of the study.

In addition, another study by the same team on color corrections for Gaia Data Early Release 3 (EDR3) was published in The Astrophysical Journal Letters.

The polar vortex is a large area of upper-atmosphere cyclonic air circulation surrounding both poles. It is bounded by the polar jet stream and its associated cold air is usually confined to the polar regions. Within the Antarctic circle, and southern polar vortex, ozone quantities are the lowest, globally. A research published in Advances in Atmospheric Sciences, led by Dr. LUO Yuhan, corresponding author and Associate Professor at the Hefei Institutes of Physical Science (HFIPS), suggests that the polar vortex plays a key role in Antarctic stratospheric ozone depletion.

"The atmosphere over Antarctica is controlled by a strong polar vortex in winter, making it difficult to exchange with the mid-latitude atmosphere." said Dr. LUO. "The extremely low air temperatures (

Dr. LUO further explained that PSCs are primarily composed of nitrate trihydrate and water ice, along with smaller concentrations of other volatile compounds. These aerosols provide surfaces for heterogeneous reactions that convert halogen reservoirs to active halogens which cause severe ozone depletion.

The team used Zenith Scattered Light Differential Optical Absorption Spectroscopy (ZSL-DOAS) techniques to measure ozone depletion near the edge of the polar vortex at the Fildes Peninsula on King George Island (62.22S, 58.96W). ZSL-DOAS can accurately quantify the column density of ozone. The ozone columns were compared with the stratospheric ozone profiles from NASA's MERRA2 ozone database and PV profiles from the ECMWF dataset, which helped better understand the causes of ozone depletion.

"PV is used to characterize the polar vortex and determine the edge of polar vortex by Nash's criterion." said QIAN Yuanyan, a PhD candidate working with Dr. Luo, and the first author of this paper. Nash's criterion suggests that the vortex typically lies at or south of 65° equivalent latitude, based on PV values.

Results show that PV is positively correlated with total ozone columns, and both variables trend up and down at the same pace.

"The observations conducted in this study contribute to a base for further analysis to improve the prediction of the inter-annual variations of stratospheric ozone." said Dr. LUO. "This will provide a better understanding of ozone recovery and stratosphere-troposphere exchange over the polar vortex edge area."

Ishikawa, Japan - History tells us that games are an inseparable facet of humanity, and mainly for good reasons. Advocates of video games laud their pros: they help develop problem-solving skills, socialize, relieve stress, and exercise the mind and body--all at the same time! However, games also have a dark side: the potential for addiction. The explosive growth of the video game industry has spawned all sorts of games targeting different groups of people. This includes digital adaptations of popular board games like chess, but also extends to gambling-type games like online casinos and betting on horse races. While virtually all engaging forms of entertainment lend themselves to addictive behavior under specific circumstances, some video games are more commonly associated with addiction than others. But what exactly makes these games so potentially addictive?

This is a difficult question to answer because it deals directly with aspects of the human mind, and the inner workings of the mind are mostly a mystery. However, there may be a way to answer it by leveraging what we do know about the physical world and its laws. At the Japan Advanced Institute of Science and Technology (JAIST), Japan, Professor Hiroyuki Iida and colleagues have been pioneering a methodology called "motion in mind" that could help us understand what draws us towards games and makes us want to keep reaching for the console.

Their approach is centered around modelling the underlying mechanisms that operate in the mind when playing games through an analogy with actual physical models of motion. For example, the concepts of potential energy, forces, and momentum from classical mechanics are considered to be analogous to objective and/or subjective game-related aspects, including pacing of the game, randomness, and fairness. In their latest study published in IEEE Access, Professor Iida and Assistant Professor Mohd Nor Akmal Khalid, also from JAIST, linked their "motion in mind" model with the concepts of engagement and addiction in various types of games from the perceived experience of the player and their behaviors.

The researchers employed an analogy of the law of conservation of energy, mass, and momentum to mathematically determine aspects of the game-playing experience in terms of gambling psychology and the subjective/objective perception of the game. Their conjectures and results were supported by a "unified conceptual model of engagement and addiction," previously derived from ethnographic and social science studies, which suggests that engagement and addiction are two sides of the same coin. By comparing and analyzing a variety of games, such as chess, Go, basketball, soccer, online casinos, and pachinko, among others, the researchers showed that their law of conservation model expanded upon this preconception, revealing new measures for engagement while also unveiling some of the mechanisms that underlie addiction.

Their approach also provides a clearer view of how the perceived (subjective) difficulty of solving uncertainties during a given game can differ from and even outweigh the real (objective) one, and how this affects our behavior and reactions. "Our findings are valuable for understanding the dynamics of information in different game mechanics that have an impact on the player's state of mind. In other words, this helps us establish the relationship between the game-playing process and the associated psychological feeling," explains Professor Iida . Such insight will help developers make game content more engaging, healthy, and personalized both in the short and long term.

Further studies shall make the tailoring of game experiences much easier, as Professor Iida remarks: "Our work is a stepping-stone for linking behavioral psychology and game-playing experiences, and soon we will be able to mechanistically manipulate and adapt the notions of engagement and addiction towards specific needs and use-cases ." Let's hope these findings can take us one step towards deaddiction to games, while keeping the fun intact!

New research at Karolinska Institutet in Sweden suggests a link between psychosis and a genetic change that affects the brain's immune system. The study published in Molecular Psychiatry may impact the development of modern medicines for bipolar disorder or schizophrenia.

Psychosis affects approximately 2-3 per cent of the population and is characterized by a change in the perception of reality, often with elements of hallucinations and paranoid reactions.

Most of the people affected are patients with schizophrenia, but people with bipolar disorder may also experience psychotic symptoms.

The antipsychotics available today often have insufficient efficacy, and for patients, their life situation can be difficult.

The average life expectancy of people with schizophrenia is approximately 15 years shorter than that of the general population, according to Sweden's National Board of Health and Welfare.

"It is not entirely known what biological mechanisms cause psychosis, but recent research suggests that immune activation in the brain's glial cells may be the cause. People with psychosis have elevated levels of kynurenic acid in the brain, a messenger that transmits information from the brain's immune system to the neurons," says Goran Engberg, Professor at the Department of Physiology and Pharmacology, Karolinska Institutet, and the study's corresponding author.

Previous genome-wide association studies (GWAS) have shown that the protein GRK3 expresses itself via genetic changes in the immune system in patients with psychosis.

Now researchers at Karolinska Institutet, the University of California, San Diego, USA, and the Mayo Clinic, Rochester, USA, have studied more specifically which parts of the immune system impact psychotic disorders.

The study is based on extensive data from mice that lack the GRK3 protein in the brain, as well as an analysis of the genome from 70 people with bipolar disorder and 48 healthy control subjects.

Results show that the loss of the GRK3 protein appears to increase the sensitivity of the immune system and triggers a cascade of effects in the brain, involving an increased release of the cytokine IL-1beta and kynurenic acid.

"Our experimental data are confirmed through genetic studies where we see a link between psychosis in patients with bipolar disorder and decreased expression of GRK3, which leads to an increased amount of kynurenic acid in the brain," says Carl Sellgren. He is a senior lecturer at the Department of Physiology and Pharmacology, Karolinska Institutet, and the study's first author together with Sophie Imbeault, senior researcher at the same department.

The data in the study provide a connection between immune activation and psychosis and thus presents a starting point for further study of novel antipsychotic drugs possessing immune modulatory functions.

The drugs currently used in psychosis treatment were developed in the 1960s.

"To develop effective, modern drugs, more knowledge is needed about the mechanisms in the brain that can trigger psychosis," says Sophie Erhardt, professor at the Department of Physiology and Pharmacology, Karolinska Institutet, and the study's last author.

Obsessive-compulsive disorder (OCD) in children and adolescents is associated with impaired education and worse general health later in life. Access to specialist treatment is often limited. According to a study from Centre for Psychiatry Research at Karolinska Institutet in Sweden and Region Stockholm, internet-delivered cognitive behavioural therapy (CBT) can be as effective as conventional CBT. The study, published in the prestigious journal JAMA, can help make treatment for OCD more widely accessible.

Obsessive-compulsive disorder (OCD) is a potentially serious mental disorder that normally debuts in childhood.

Symptoms include intrusive thoughts that trigger anxiety (obsessions), and associated repetitive behaviours (compulsions), which are distressing and time consuming.

Early diagnosis and treatment are essential to minimise the long-term medical and socioeconomic consequences of the disorder, including suicide risk.

The psychological treatment of OCD requires highly trained therapists and access to this kind of competence is currently limited to a handful of specialist centres across Sweden.

Earlier research has shown that while CBT helps a majority of young people who receive it, several years can pass between the onset of symptoms and receipt of treatment.

Researchers at Karolinska Institutet have spent three years evaluating whether low-intensity internet-delivered CBT for children and adolescents with OCD can be used in a stepped care model in order to improve access to treatment without compromising its efficacy.

The two-centre study was conducted in collaboration with Child and Adolescent Mental Health Services in the Stockholm and Vastra Gotaland regions and comprised 152 participants between the ages of eight and 17.

The participants were randomly assigned to one of two groups. One group first received therapist-guided digital CBT, and the other (control) received standard CBT through weekly in-person sessions with a therapist.

Each group received treatment for a period of 16 weeks, supported by their therapists and parents.

The researchers then followed up the participants three months after treatment in order to evaluate the therapeutic effect on OCD symptoms, daily function and depressive symptoms.

After the 3-month follow-up, the participants in both groups deemed in need of additional support received up to 12 extra sessions of conventional CBT up until the 6-month follow-up.

The results showed that stepped digital CBT reduced the participants' OCD symptoms as much as conventional CBT. Approximately 70 per cent of participants in both groups were treatment responders at the 6-month follow-up.

"The advantage of the stepped care approach is that it makes it easier for us to reach out to more children and adolescents with OCD in need of help," says the study's first author Kristina Aspvall, psychologist and researcher at the Centre for Psychiatry Research, part of Karolinska Institutet's Department of Clinical Neuroscience.

Crucially, the stepped care group required fewer resources: therapists spent an average of 9 hours per participant in the stepped treatment group and 14 hours per participant in the control group.

"The study demonstrates the potential of technology when it comes to increasing access to evidence-based therapy for young people with OCD," says principal investigator Eva Serlachius, adjunct professor at Karolinska Institutet's Centre for Psychiatry Research. "By offering low-intensity digital intervention as the first step of treatment, clinics can save precious resources and devote their limited time to treating more patients or focusing on more complex cases."

Internet CBT for OCD is currently being implemented in regular care through Region Stockholm's Child and Adolescent Mental Health Services (BUP Internetbehandling), which also collaborates with other health authorities across Sweden. The treatment was developed by researchers at Karolinska Institutet and Region Stockholm.

This rare fossil find comes from the Kimmeridge Clay Formation in England, a series of sedimentary rocks that was formed in a shallow, tropical-subtropical sea during the Upper Jurassic, about 150 million years ago. The fossil shark skeleton was found more than 20 years ago on the southern coast of England and is now held in the Etches Collection. Additional fossil shark specimens from it will be investigated in the years to come.

Due to their life-long tooth replacement shark teeth are among the most common vertebrate finds encountered in the fossil record. The low preservation potential of their poorly mineralized cartilaginous skeletons, on the other hand, prevents fossilization of completely preserved specimens in most cases.

The new study published in the journal PeerJ and led by Sebastian Stumpf from the University of Vienna now presents the fossil skeleton of a new ancient shark from the Kimmeridge Clay Formation of England, a fossiliferous rock sequence that was formed during the Late Jurassic in a shallow, tropical-subtropical sea.

The new shark fossil, which is about 150 million years old, is assigned to a previously unknown genus and species of hybodontiform sharks named Durnonovariaodus maiseyi. This extremely rare fossil find was made almost 20 years ago on the southern coast of England and is now held and curated in the Etches Collection, which houses one of the most scientifically significant fossil collections in England.

Hybodontiform sharks are one of the most species-rich groups of extinct sharks and represent the closest relatives to modern sharks. They first appeared during the latest Devonian, about 361 million years ago, and went extinct together with dinosaurs at the end of the Cretaceous, about 66 million years ago. The new genus and species Durnonovariaodus maiseyi differs from all other previously described hybodontiform sharks, including those that are characterized by having similarly shaped teeth. "Durnonovariaodus maiseyi represents an important source of information for better understanding the diversity of sharks in the past as well as for new interpretations of the evolution of hybodontiform sharks, whose relationships are still poorly understood, even after more than 150 years of research," says Stumpf.

The scientific importance of the Kimmeridge Clay Formation is underlined by additional, but still undescribed hybodontiform shark skeletons, which are also held in the Etches Collection. The research of fossil sharks from the Kimmeridge Clay Formation of England, which will be continued in the years to come, will certainly contain further surprises to be yet discovered.

Wastewater testing is an effective way to identify new cases of COVID-19 in nursing homes and other congregate living settings, and it may be particularly useful for preventing outbreaks in college dormitories, a new University of Virginia study finds.

The research, a collaboration of UVA's School of Medicine and School of Engineering, was led by UVA Health's Amy Mathers, MD. It offers some of the first clear guidance on the most effective methods to perform testing to detect COVID-19 in wastewater.

The researchers evaluated and compared sampling and analysis techniques by testing them within buildings with known numbers of positive cases. They were then able to determine wastewater testing's strengths and limitations as a tool for monitoring COVID-19 in a building population. For example, the technique proved better at detecting initial infections than determining the number of occupants infected or how long they had been infected.

One important answer revealed by the research: Wastewater testing can detect even small numbers of asymptomatic cases, something not previously documented.

"This work could be applied to surveillance in buildings where people live in groups, where transmission may be hard to control but the risk of spread could be high," said Mathers, an infectious disease expert in the School of Medicine's Department of Pathology. "Since we can identify new infections with high sensitivity, it provides an early warning signal of when to test everyone in the building to find and isolate the newly infected persons before an outbreak becomes large."

Wastewater Testing for COVID-19

To evaluate the effectiveness of wastewater testing for detecting COVID-19, Mathers collaborated with Lisa Colosi-Peterson, PhD, an associate professor in UVA Engineering's Department of Engineering Systems and Environment, who connected with Mathers through UVA's Center for Engineering in Medicine. They and their colleagues monitored wastewater from two student dormitory complexes for eight weeks. The researchers found that the wastewater testing caught more than 96% of cases.

One limitation of wastewater testing: It could not distinguish between new infections and virus found in stool from those who had recovered and were no longer contagious. That means the wastewater testing detected both active and former cases. "The inability to distinguish recently infected but no longer contagious persons from new contagious infections within a building is an important finding, as it means that wastewater testing would be best for identifying new cases and isolating individuals in groups without recent infections," Mathers said.

UVA's new research also establishes useful protocols for wastewater testing. In a scientific paper outlining their findings, the researchers describe how they collected and tested the samples, noting that refrigerating the samples on ice adequately preserved them for testing that same day. Institutions that plan to send their samples elsewhere for testing, however, may need to take additional steps to preserve the samples for longer, the researchers note. Cleansers and disinfectants used in the facilities could also degrade the viral RNA over time, they caution.

While the researchers are urging further study, they conclude that wastewater testing holds great promise for detecting and controlling COVID-19 in places where people live in close quarters. "Passive pooled surveillance of wastewater is now serving as an early warning system in many dormitories, barracks and prisons to identify new cases in situations where transmission risk is high," Mathers said. "Applications for wastewater surveillance to inform and control infectious disease transmission will continue to evolve, but it is hard to believe how far and how fast we have come in the last year."

SASKATOON - Tepary beans--a high protein legume common to the southwest United States and Mexico--may hold the key to adapting bean crops for the increasingly harsh conditions brought on by a changing climate, according to research led by University of Saskatchewan (USask) and Michigan State University.

In a study just published in Nature Communications, the researchers found that as the mercury rises to 27oC at night--a temperature devastating for current bean crops--specific genes sensitive to heat stress in the tepary bean get activated, protecting the plant.

"We are interested in tepary beans because they are very stress tolerant, unlike their cousin the common bean," said Dr. Kirstin Bett (PhD), professor of plant breeding and genetics at USask and one of the senior authors of the study.

By 2050, the major regions growing common beans (Phaseolus vulgaris L.)--the most important legume protein source for human consumption--may be unsuitable and the overall nutritional quality of the crop will likely be reduced.

"Tepary beans are an under-appreciated protein crop that are ideal for production in marginal environments due to their inherent tolerance of temperature stresses," said Bett.

The team sequenced the genome of the tepary bean (Phaseolus acutifolis A. Gray) to study how the legume adapts more effectively to fluctuating temperatures than its common bean cousin, and to combine traits of the two species into a more sustainable crop variety.

Having been part of Indigenous diets in regions such as northern Mexico, the southwest United States and Africa for centuries, the tepary bean has been valued for its ability to survive in arid environments. While the tepary bean can handle heat and dry, the researchers found it is less capable of surviving the threat of disease.

"Tepary beans have fewer disease resistance genes, perhaps because they are typically grown in arid climates where disease pressure has been less than in the wetter regions where common beans have been grown," said Bett.

"My group was responsible for the wild genome assembly and the comparative mapping work that shows the genome-level relationships between wild and cultivated tepary bean and common bean," said Bett. "This will help us better understand how to transfer traits between the two species. We are trying to increase the stress tolerance of the common bean by crossing with tepary bean and selecting for lines that are more tolerant to cold and drought."

In the future, researchers hope to be able to leverage this genetic information to improve the vitality of bean crops that must thrive in extreme temperatures or changing environments.

"We are continuing to try to develop tepary bean varieties that will grow here in Saskatchewan and in other dry areas of the world," Bett said.

(Boston)--Chronic Obstructive Pulmonary Disease (COPD) is a disease caused by cigarette smoking that reduces lung function and causes difficulty breathing. It is the third leading cause of death worldwide. Current treatments for COPD only affect symptoms, not progression. Identifying who is going to get COPD before they get it is key to figuring out how to intercept the disease at an early stage.

Researchers from Boston University School of Medicine (BUSM) have identified a panel of genes that are active in smokers and ex-smokers who experience faster loss of lung function over time. They believe these genes could be useful to predict which people are most at risk for smoking-related decline in lung function.

"Our discovery that airway genes change before a rapid decline in lung function should give patients with COPD a lot of hope. A test like this could help doctors identify people at risk for COPD before they get it, and help scientists find new treatments to stop the disease before it gets worse," explained corresponding author Katrina Steiling, MD, MSc, assistant professor of medicine at BUSM.

Smoking, and diseases related to smoking, create changes throughout the airways and lungs. These changes can be detected using a procedure called a bronchoscopy, where a small flexible camera inserted through the nose or mouth is used to collect cells with brushes from the sides of the airways. The researchers tested airway brushings from 134 people who were current or former smokers. They found changes in the activity of specific genes in the people that went on to have more rapid worsening of their lung function several years after that initial airway brushing. Some of the genes were more active in the people who rapidly lost lung function while other genes were less active in these people.

According to the researchers, further study of these genes may provide clues as to what causes rapid lung function decline which could be used to develop to new treatments for preventing the development of COPD. "Being able to identify people most at risk for worsening lung function might also make clinical trials of COPD fighting medications easier, by enriching the trials testing new medications for people most likely to benefit from them," added co-author Beth Becker, PhD, a recent graduate from BU's bioinformatics program.

This study further shows another use for the 'airway field of injury' hypothesis. "Cigarette smoking causes changes to the cells in the lungs and airways. Because the changes in the airways are similar to those that occur deep inside the lung, testing the cells in the airways can be used to detect diseases deep within the lungs," added Marc Lenburg, PhD, professor of medicine and pathology and laboratory medicine at BUSM.

Researchers have mapped out the changes in metabolism that occur after a heart attack, publishing their findings today in the open-access eLife journal.

Their study in mice reveals certain genes and metabolic processes that could aid or hinder recovery, and might be good targets for treatments to prevent damage after a heart attack.

"Although some studies have looked at how changes in individual body tissues underlie mechanisms of disease, the crosstalk between different tissues and their dysregulation has not been examined in heart attacks or other cardiovascular-related complications," explains first author Muhammad Arif, a PhD student at KTH Royal Institute of Technology, Stockholm, Sweden. "In this study, we performed an integrated analysis of heart and other metabolically active tissues using a mouse model of heart attack and used systems biology approaches to get a systematic picture of the metabolic changes that occur."

Systems biology has aided the discovery of new treatment approaches in multiple diseases. Rather than take systems apart and analyse the components, it involves taking measurements from different cells and tissues and using them to reproduce the system being studied. In this research, the team used a systems biology approach called co-expression networks (CNs) to reveal how the functions of genes in different tissues were linked together.

First, they measured the activity of all the genes in four tissue types: heart, fat, skeletal muscle and the liver in mice that had a heart attack. They compared these with the gene activity in mice that did not have a heart attack to generate sets of differentially expressed genes (DEGs) unique to each tissue. Next, in the co-expression network analysis, they looked at the top 5% of genes that were most strongly connected within the four different tissues. They then used the DEG results to see how those top 5% of genes were altered 24 hours after a heart attack.

They found key clusters of genes that were altered in different tissues after a heart attack. In the heart and muscle, the gene changes tended to be linked to energy production and muscle contraction. In the liver, the gene changes were related to fat transport and metabolism, and the metabolism of cell-protecting substances such as glutathione.

The team then used this information to build a multi-tissue model of the metabolic response to a heart attack and compared their results with other studies of heart tissue. They found that four genes were consistently altered across all studies. These genes are known to play roles in energy production, muscle contraction and protein production, and at least one of them is being explored as a drug target for cardiovascular disease.

Taken together, the results reveal a downregulation of heart-specific functions and upregulation of fat metabolism and inflammation in the heart, muscle and fat tissue after a heart attack. By contrast, the team saw a different response in the liver where inflammation was reduced.

"Our integrative analysis highlights both common and tissue-specific biological responses to a heart attack across a range of metabolically active tissues," concludes senior author Adil Mardinoglu, Professor of Systems Biology at KTH Royal Institute of Technology, Sweden, and King's College London, UK. "The approach demonstrates a way of using multi-tissue gene activity data to identify changes in biological processes and pathways and systematically explore the effects of a disease. This opens up new opportunities for future research into the pathways identified, and the potential to use a similar approach to understand other complex human diseases."

A new study from the University of Chicago has found that the photosynthetic bacterium Synechococcus elongatus uses a circadian clock to precisely time DNA replication, and that interrupting this circadian rhythm prevents replication from completing and leaves chromosomes unfinished overnight. The results, published online on May 10 in Proceedings of the National Academy of the Sciences, have implications for understanding how interrupted circadian rhythms can impact human health.

Circadian rhythms are the internal 24-hour clock possessed by most organisms on earth, regulating a diversity of biological functions including sleep/wake cycles, hormone production, digestion and body temperature. In humans, disruptions to the circadian rhythm -- such as working a shift-work job or experiencing frequent jet lag -- have been associated with an array of health problems, including obesity, cardiovascular and immune dysfunction, mood disorders and even cancer.

"In most species we've studied, if the circadian rhythm is disrupted or permanently changed, it's bad for the animal's health, but no one has really been able to explain what goes wrong if your clock is in the wrong state all the time," said senior author Michael Rust, PhD, Associate Professor of Molecular Genetics and Cell Biology at UChicago. "This cyanobacterial system is exciting because it gives us a chance to answer these mechanistic questions about how circadian rhythms are contributing to the health of an organism."

Despite the large evolutionary gap between humans and cyanobacteria, these tiny organisms can provide insights into critical cellular functions such as DNA replication. "The evidence suggests that circadian rhythms have evolved multiple times among different species, so there must be something very fundamental and important that's shared among these different species," said first author Yi Liao, a postdoctoral scholar in Rust's lab. "DNA replication is also a fundamental process, shared across species, which gave us a clue that it might be regulated by this clock."

The investigators were particularly interested in studying this process due to its lengthiness. "Some things are better to do during the day, like photosynthesis, while others are better at night, like fixing nitrogen," said Rust. "But DNA replication takes three to four hours to replicate the entire genome, so there's a fundamental need to predict the future. You commit to doing this thing and you don't know what the conditions will be like a few hours later. It seemed like maybe this process would use circadian rhythms to 'predict' the right time to start replication to ensure that it finishes during an optimal window of time."

Combining time-lapse fluorescent microscopy, mathematical modeling, molecular genetics and biochemical approaches, Liao and Rust were able to track DNA replication initiation, completion, and failures in bacteria exposed to different illumination patterns, including constant light, normal light/dark cycles and cycles with unexpected periods of darkness.

They found that the circadian clock creates rhythms in DNA replication even in the absence of environmental cues, such as the rising and setting sun. DNA replication typically begins when the clock state corresponds to the morning, and is suppressed when the clock predicts the arrival of night. However, when the internal clock of the bacteria predicts morning but the external environment unexpectedly becomes dark, ongoing replication can't be completed; the replication machinery disassembles, leaving cells with incomplete chromosomes.

"Many things are regulated by the circadian clock, but it is striking that it matters so much for DNA replication," said Rust. "If the clock is in the wrong state, it's the difference between completing the replication event, or the replication machinery falling apart completely."

These results, Liao says, open up even more questions. "What is the fate of these unfinished chromosomes? Does this lead to mutations?" he said. "Maybe this is a major driving force in the evolution of the circadian clock -- you want to avoid damaged DNA and unfinished chromosomes, so the clock has evolved multiple times in history to prevent those things from happening."

In a post-Industrial Revolution society, surrounded by artificial lights that can be turned on and off at will, these results could have implications for how circadian rhythms impact human health and why extensive disruptions can be so damaging.

"One question that we still need to answer is whether or not this failure to complete DNA replication leads to mutation and genomic instability," said Rust. "Organisms may experience unexpected darkness on occasion, but their clocks get very strong signals from the cycle of the sun rising and setting. In humans, where we can control the illumination of our environment and ignore the sun, we know there are changes in the circadian rhythm and we know it causes problems, but it's not clear where those problems come from. We're trying to put our finger on a molecular mechanism for what might be the biggest problem if your circadian clock is in the wrong state."

Argonne scientists across several disciplines have combined forces to create a new process for testing and predicting the effects of high temperatures on refractory oxides.

Cast iron melts at around 1,200 degrees Celsius. Stainless steel melts at around 1,520 degrees Celsius. If you want to shape these materials into everyday objects, like the skillet in your kitchen or the surgical tools used by doctors, it stands to reason that you would need to create furnaces and molds out of something that can withstand even these extreme temperatures.

That’s where refractory oxides come in. These ceramic materials can stand up to blistering heat and retain their shape, which makes them useful for all kinds of things, from kilns and nuclear reactors to the heat-shielding tiles on spacecraft. But considering the often-dangerous environments in which these materials are used, scientists want to understand as much as they can about what happens to them at high temperatures, before components built from those materials encounter those temperatures in the real world.

“I’m not saying humans aren’t great, but if we get help from computers and software, we can be greater. It opens the door for more experiments like this that advance science.” — Marius Stan, program lead, Intelligent Materials Design, Argonne

A team of researchers from the U.S. Department of Energy’s (DOE) Argonne National Laboratory has come up with a way to do just that. Using innovative experimental techniques and a new approach to computer simulations, the group has devised a method of not only obtaining precise data about the structural changes these materials undergo near their melting points, but more accurately predicting other changes that can’t currently be measured.

The team’s work has been published in Physical Review Letters.

The seed of this collaboration was planted by Marius Stan, leader of the Intelligent Materials Design program in Argonne’s Applied Materials division. Stan’s group had developed plenty of models and simulations about the melting points of refractory oxides, but he wanted to test them out.

“It’s rooted in the desire to see if our mathematical models and simulations represent reality or not,” Stan said. “But it has evolved into a study of machine learning. What I find most exciting is that there is now a way for us to predict interactions between atoms automatically.”

That innovation began by flipping a familiar script, according to Ganesh Sivaraman, lead author on the paper and an assistant computational scientist with the Data Science and Learning division at Argonne. He performed this work while he was a postdoctoral appointee at the Argonne Leadership Computing Facility (ALCF), a DOE Office of Science User Facility.

While most experiments begin with a theoretical model — basically, an informed and educated guess at what will happen under real-life conditions — the team wanted to start this one with experimental data and design their models around that.

Sivaraman tells a story about a famous German mathematician who wanted to learn how to swim, so he picked up a book and read about it. Creating theories without considering the experimental data, Sivaraman said, is like reading a book about swimming without ever getting into a pool. And the Argonne team wanted to jump in at the deep end.

“It’s more accurate to build a model around experimental data,” Sivaraman said. “It brings the model closer to reality.”

To obtain that data, the computational scientists partnered up with physicist Chris Benmore and assistant physicist Leighanne Gallington of Argonne’s X-ray Science Division. Benmore and Gallington work at the Advanced Photon Source (APS), a DOE Office of Science User Facility at Argonne, which generates very bright X-ray beams to illuminate the structures of materials, among other things. The beamline they used for this experiment allows them to examine the local and long-range structure of materials at extreme conditions, such as high temperatures.

Of course, heating up refractory oxides — in this case, hafnium dioxide, which melts at around 2,870 degrees Celsius — comes with its own complications. Ordinarily, the sample would be in a container, but there isn’t one available that would withstand those temperatures and still allow the X-rays to pass through them. And you can’t even rest the sample on a table, because the table will melt before the sample does.

The solution is called aerodynamic levitation and involves scientists using gas to suspend a small (2-3 mm in diameter) spherical sample of material about a millimeter in the air.

View related video here.

“We have a nozzle connected to a flow of inert gas, and as it suspends the sample, a 400-watt laser heats the material from above,” Gallington said. “You need to tinker with the gas flow to get it to levitate stably. You don’t want it too low, because the sample will touch the nozzle, and might melt to it.”

Once the data were taken and beamline scientists had a good understanding of some of what happens when hafnium oxide melts, the computer scientists took the ball and ran with it. Sivaraman fed the data into two sets of machine learning algorithms, one of them that understands the theory and can make predictions, and another — an active learning algorithm — that acts as a teaching assistant, only giving the first one the most interesting data to work with.

“Active learning helps other kinds of machine learning to learn with fewer data,” Sivaraman explained. “Say you want to walk from your house to the market. There may be many ways to get there, but you only need to know the shortest path. Active learning will point out the shortest way and filter out the others.”

Computations were run on supercomputers at the ALCF and the Laboratory Computing Resource Center at Argonne. What the team ended up with is a computer-generated model based on real-life data, one that allows them to predict things the experimentalists didn’t — or couldn’t — capture.

“We have what is called a multi-phase potential, and it can predict a lot of things,” Benmore said. “We can now go ahead and give you other parameters, such as how well it retains its shape at high temperatures, which we did not measure. We can extrapolate what would happen if we go beyond the temperature we can reach.”

“The model is only as good as the data you give it, and the more you give it the better it becomes,” Benmore added. “We give as much information as we can, and the model becomes better.”

Sivaraman describes this work as a proof of concept, one that can feed back into further experiments. It’s a nice example, he said, of collaboration between different parts of Argonne, and of research that could not be done without the resources of a national laboratory.

“We will repeat this experiment on other materials,” Sivaraman said. “Our APS colleagues have the infrastructure to study how these materials melt at extreme conditions, and we are working with computer scientists to build the software and streaming infrastructure to rapidly process these datasets at scale. We can incorporate active learning into the framework and teach models to more efficiently process the data stream using ALCF supercomputers.”

For Stan, the proof of concept is one that may replace the necessary tedium of people working out these precise calculations. He has watched this technology evolve during his career, and now what once took months only takes a few days.

“I’m not saying humans aren’t great,” he chuckled, “but if we get help from computers and software, we can be greater. It opens the door for more experiments like this that advance science.”

May 11, 2021 - Like other medical specialties at the start of the COVID-19 pandemic, orthopaedic surgery rapidly pivoted from in-person visits to remote appointments via telemedicine. Analysis of that initial experience finds that some groups of patients faced persistent or worsening disparities as the shift to telemedicine occurred, reports Clinical Orthopaedics and Related Research® (CORR®), a publication of The Association of Bone and Joint Surgeons®. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"We found concerning disparities in access to orthopaedic care via telemedicine for patients, and we observed that those disparities were associated with race or ethnicity, primary language, and insurance status," according to the new report, led by Andrew J. Schoenfeld, MD, MSc, of Harvard Medical School.

Can telemedicine 'mitigate rather than exacerbate healthcare disparities'?

Telemedicine has the potential to improve healthcare access for hard-to-reach populations. But there are concerns that growing reliance on telemedicine might perpetuate or even worsen existing healthcare disparities - for example, adding new barriers for non-English speakers or people without computers and high-speed internet.

Dr. Schoenfeld's team studied these disparities by evaluating nearly 2,000 patients' experiences getting orthopaedic care via telemedicine at two Boston medical centers early in the pandemic, from March to May 2020, and comparing them to the experience of nearly 10,000 orthopaedic patients who had in-person visits during those same months in the year prior to COVID-19.

The telemedicine patients were slightly younger than those making in-person visits the previous year (average 56 versus 59 years). In analyses adjusting for this and other differences, disparities remained significant in three areas:

Race/ethnicity. The odds that a Hispanic patient would be seen by telemedicine during the pandemic was 41 percent lower than that of a white patient, and the odds that an Asian patient would be seen via telemedicine was 27 percent lower than those of a white patient.

Language. Patients whose primary language was not English or Spanish had one-third the odds of making a telemedicine visit than did an English-language speaker. There was no difference in the rate of telemedicine visits for Spanish versus English speakers.

Insurance. The odds of a patient with Medicaid coverage receiving a telemedicine evaluation during the early months of the pandemic were 13 percent lower than that of a patient with commercial insurance.

Dr. Schoenfeld's team proposed measures to help ensure access to telemedicine systems: targeting minority and low-income communities, addressing the needs of patients who lack computer access, ensuring that telemedicine is eligible for reimbursement, and providing expanded hours and interpreter services for telemedicine visits.

In an accompanying 'Take 5' interview, Dr. Schoenfeld and CORR® Editor-in-Chief Seth S. Leopold, MD agree that telemedicine will remain part of the healthcare landscape long after the pandemic is over. "I would hope that we can find ways to use new tools to mitigate, rather than exacerbate, healthcare disparities," Dr. Leopold writes.

When it comes to developing and ensuring equitable access to telemedicine systems, "I think the onus is on the healthcare organizations, not civic government," says Dr. Schoenfeld. He adds: "The funding, advertising, and infrastructure to support this would ideally come from the healthcare organization itself, who could partner with leaders, grassroots organizations, and community stakeholders to ensure members of the community are aware of telemedicine and have the ability to access the technology."

A new approach to road safety that relies on design and engineering principles--the "Safe System" approach--could lead to dramatic reductions in vehicle-related deaths and injuries if implemented in the U.S., according to a report from a consortium of experts convened by researchers at Johns Hopkins Bloomberg School of Public Health and the Institute of Transportation Engineers.

The Safe System approach engineers road systems so that they are safe when used intuitively, the way people tend to use them. A Safe System minimizes the chances for mistakes by drivers, pedestrians, and bicyclists, and reduces the intensity of crashes when they do occur. This approach--which may include the use of roundabouts, separated bike lanes, rumble strips, and other measures--has already been applied successfully in several other countries. In Sweden, where the approach was first implemented, road deaths fell by about 67 percent from 1990 to 2017.

The report's authors advocate that the Safe System approach can improve road safety equity if it is implemented in ways that close the safety gap between well-served and historically underserved communities.

According to the National Safety Council, highway deaths increased 8% last year over the previous year even though people were driving considerably less, with an estimated 42,000 deaths in motor vehicle crashes and 4.8 million injuries. Since 2009, the traffic death rate has remained relatively steady at about 11 deaths per 100,000 population, and crashes have persisted as the leading cause of death among young people. The rate of traffic deaths in the U.S. declined sharply between the 1960s and 1990, largely as a result of the car safety revolution.

The report, "Recommendations of the Safe System Consortium," was released on May 11. The Safe System Consortium, a group of more than two dozen leading highway engineers, scientists, and public health professionals, convened earlier this year to reimagine road safety and equity in this country, as a new presidential administration got underway.

"With this report, we're encouraging policymakers to adopt what would be a paradigm shift in the approach to road safety in the U.S., with the potential to dramatically reduce the vehicle-related injuries and deaths that we've been seeing on a daily basis," says co-author Shannon Frattaroli, PhD, associate professor in the Department of Health Policy and Management at the Bloomberg School and director of the Johns Hopkins Center for Injury Research and Policy.

"We see the Safe System approach as a way of engineering safety into the road system--making safety natural and intuitive for those who use the roads, so that the way they'll feel most comfortable driving or walking is the safest way," says co-author Jeffrey Michael, EdD, a former senior official at the National Highway Traffic Safety Administration who is now a Distinguished Scholar in the Department of Health Policy and Management and the Leon S. Robertson Faculty Development Chair in Injury Prevention at the Bloomberg School.

The traditional strategy for road safety in the U.S., the authors note, puts much of the burden of responsibility on the people driving, walking, or cycling on the roads. By contrast, the Safe System approach is designed to place a greater burden on the design of roads and vehicles.

"[N]ormal human lapses in judgment or diligence are expected, and roads are configured so that such errors do not lead to death or serious injury," the co-authors write. "Even with a forgiving design, crashes will occur in a Safe System, so roads are designed to limit crash forces to survivable levels."

Specific design changes in a Safe System include:

Lane reductions, on some multi-lane roads where pedestrians and bicyclists are present, that help slow vehicles and give drivers more time to react

Flashing beacons that alert drivers to pedestrian crosswalks

Roundabouts that slow traffic through dangerous intersections and prevent deadly side-impact collisions

Median barriers that, when used on some rural divided highways, reduce head-on collisions

As the authors of the report note, studies of Safe System measures indicate that they lead to dramatic drops in traffic deaths--for example, a roughly 80 percent reduction in severe crashes after the installation of roundabouts, and a 97 percent reduction in high-energy, head-on collisions with median barriers.

Overall, the Safe System approach has been linked to substantial traffic fatality reductions. Countries that adopted the approach in the 1990s show large drops in deaths between 1990 and 2017--with a 47 percent reduction in Australia, 48 percent reduction in New Zealand, 80 percent reduction in Spain, and 67 percent reduction in Sweden.

One of the Biden Administration's clearest priorities is to redress a history of underinvestment in road safety in communities of color, and the authors recommend that the Safe System approach be used to do this.

"Some communities currently have much more than their share of exposure to traffic-related hazards, due to larger thoroughfares going through their neighborhoods, for example, and/or fewer safety measures," Michael says. "It's how our transportation system developed over the years--but we now have an opportunity to change our approach."

The report's recommendations include requiring that Safe System principles be followed when federal funds are used for road design and operation, and setting up special programs to implement Safe System measures in historically underserved communities.