Culture

Employers in Sweden more often reject job applications from transgender people - especially in male-dominated occupations. Moreover, transgender people face discrimination from two different grounds for discrimination. This is according to a study from Linköping University that was recently published in the journal Labour Economics.

Since 2017, gender identity and gender expression is one of the seven grounds for discrimination in Swedish discrimination legislation. However, transgender people, that is, people who identify with another gender than the one they were assigned at birth, report that they are often subject to discrimination in the workplace. Economics researchers at Linköping University in Sweden have now confirmed that this is the case. Their study is the first to prove this by way of an experimental method.

"From an economic point of view, it's interesting to ask why employers don't make use of these people's skills. We wanted to find out on which grounds employers discriminate against transgender people, because in this case there are two legislative grounds for discrimination that could apply: firstly, sex, and secondly, gender identity and gender expression", says Mark Granberg, doctoral student in economics at Linköping University.

Mark Granberg carried out the study together with Ali Ahmed, professor in economics, and Per A. Andersson, doctoral student in psychology.

Previous studies show that transgender people experience workplace discrimination in various forms. In an American study from 2011, half of the transgender people reported that they had been subject to, among other things, harassment at work. But there has been a lack of experimental studies - as opposed to self-report studies - into workplace discrimination of transgender people.

The study is the first to use a correspondence test to investigate employer discrimination against transgender people. The correspondence test is a common method when studying discrimination: the participants do not physically meet the employer, they submit a written application. The Linköping researchers sent in 2,224 fictitious applications for low-skilled jobs listed on the Swedish Public Employment Service's job database. The applications stated that the applicant had undergone a name change - in some cases from a male name to another male name, and in some cases the names crossed gender boundaries, e.g. Erik became Amanda. For every application, the researchers noted whether they received a reply, and if so, what the reply was.

The results show that it was 18 per cent more likely that a cis person - a person who identifies with the gender they were assigned at birth - got a positive response from the employer, compared to a transgender person.

The results also reveal differences between female and male-dominated occupations. With regard to positive replies to applications, the researchers found that the greatest differences between cis and transgender people were in male-dominated occupations. Here, cis men received a positive reply from the employer in 44 per cent of the cases, compared to 24 per cent for the transgender women - i.e. the cis men received nearly twice as many positive replies.

In the female-dominated occupations, the discrimination appeared to depend mainly on the gender with which the applicant identified at the time of application. In occupations where men and women are more or less equally represented, the researchers saw no statistically significant differences between the applicants.

"The study shows that the legislation is not sufficient to protect this group on the labour market. It also suggests that employers discriminate based on several grounds. For instance, it is likely that a transgender man is discriminated against for being transgender in male-dominated occupations, while in female-dominated occupations, the same person would probably face discrimination for being male."

In many studies, bariatric surgery has been highlighted as an almost magical method for weight loss and reversing type 2 diabetes. One question that has remained largely unanswered is how the effect of surgery differs from the effects of a strict low-calorie diet. This question has now been examined by researchers at Lund University in Sweden in a study published in the journal Diabetes.

By monitoring individuals who underwent a six-week low-calorie diet followed by a bariatric operation, they can for the first time show why several health markers improve.

"What we previously thought was an effect of the operation is actually due to the diet", says associate professor Nils Wierup, who led the study with associate professor Peter Spégel.

In a bariatric operation, a so-called gastric bypass, a large part of the stomach and the first part of the small intestine are disconnected. The patient needs to lose weight before the operation in order to reduce the size of the liver and the amount of fat around the internal organs. This is done to reduce the risk of complications.

Normally, the patient follows a strict six-week diet of fewer than 1 000 calories per day in order to achieve the weight loss. Previous research has studied the combined effect of the diet and surgery. What has been seen, in addition to weight loss, is improved blood sugar control, which has been considered a result of an increase in the hormones GLP-1 and GIP and enhanced insulin release. As a bonus, individuals with type 2 diabetes "recovered" just days after the procedure.

In a new study, researchers at the Lund University Diabetes Centre (LUDC) and the Centre for Analysis and Synthesis (CAS) have for the first time studied the effects of the strict low-calorie diet and the operation separately. The results show that the diet alone accounted for the greatest positive effect.

"More than 90 per cent of everything that occurred, happened as a result of the diet. Very little changed after the surgery", says Peter Spégel, who works at LUDC and CAS.

By measuring several hundred metabolites in the blood (substances formed by, among other things, sugar, protein and fat in our metabolism) before and after the low calorie diet and the operation, the researchers could see that the levels of the various metabolites after the diet went in the direction expected from a reduced food intake and improved health. The surgery itself caused very minor changes.

However, a few unique changes were observed that generally were the opposite of those that happened during the diet. The researchers could link some of these effects to the stress that surgery causes for the patient, and this was supported by the fact that virtually all the changes had disappeared six weeks after the operation.

The one most surprised by the results is Nils Wierup, who previously, unlike Peter Spégel, was convinced that it was the surgical procedure and the hormonal changes that accounted for the improved effect.

"What we previously thought was linked to the gastric bypass surgery is actually not. I have had to change my viewpoint", he says.

"It was very good for this project that at the start we had such differing expectations and hypotheses on the effects bariatric surgery and diet have on metabolism. We have therefore looked very carefully at all the results to elucidate the study from all conceivable angles", adds Peter Spégel.

The results are not to be interpreted as the low-calorie diet being beneficial in itself or that the operation is unnecessary. The procedure is necessary in order for the patient to maintain a limited food intake for a long period.

"A low-calorie diet is usually not harmful. The fact that we have now shown the effects previously associated with surgery actually arise during the preceding low-calorie diet, and not as a response to the surgery, may perhaps make gastric bypass surgery less magical.

However, as a result of this, we can also point to bariatric surgery not having any negative metabolic consequences", says Peter Spégel.

"If you are seriously overweight, calorie restriction is not necessarily harmful. Gastric bypass is a good treatment method for obesity. In addition to the weight loss being more considerable and long-lasting compared to a low-calorie diet, the surgery has the added effect that the patient's diabetes reverses", states Nils Wierup.

The results also raise new questions.

"If metabolism is primarily affected by the diet and not the surgery, what then is the function of the hormones GLP-1 and GIP?", says Nils Wierup.

The answers will possibly emerge from forthcoming studies in which the researchers will conduct a long-term follow up and compare their results in a European study.

The rainforests of Southeast Asia are among the fastest declining tropical ecosystems worldwide. Researchers from 13 institutions studied an area of tropical forest in Sabah, Malaysian Borneo that had suffered heavy logging in the 1980s but was subsequently protected from further deforestation or conversion to agricultural land.

This long-term study paid special attention to the forest's capacity to rebuild biomass. The researchers found that areas left to regenerate naturally recovered by as much as 2.9 tonnes of aboveground carbon per hectare per year. "This quantitatively confirms that if degraded forests get effective protection, they can recover well naturally", says Christopher Philipson, Senior Scientist at ETH Zurich's Chair of Ecosystem Management.

More importantly, the research team found that areas of forest that underwent active restoration recovered 50% faster, from 2.9 to 4.4 tonnes of aboveground carbon per hectare per year.

The research, published today in Science, has its origins in work that Professor Mark Cutler from University of Dundee carried out in Borneo almost 25 years ago. Cutler led the project with Professor David Burslem at the University of Aberdeen, and ETH Zurich's Christopher Philipson, first author of the paper, who carried out the research at ETH Zurich and Dundee.

Fostering damaged forest

Commercial, selective logging in Sabah has been going on for decades, and has severely degraded large areas of the forest estate. While Sabah retains over 50% natural forest cover (with almost half of this area being fully protected), relatively little of this forest is in pristine condition. Restoration - particularly in heavily logged lowland forests - is considered essential to maintain biodiversity, carbon sequestration, and other ecosystem services.

"This active restoration encourages naturally diverse forest, and is therefore much more beneficial for biodiversity than monocultures or plantation forests", stresses Philipson. The approach involves cutting lianas (climbing plants that thrive in degraded forests, competing with trees and reducing seedling survival and growth) as well as weeding, and 'enrichment planting' of seedlings. The latter seeks to increase the valuable, native tree species in degraded forests that have been reduced through commercial logging. "In this way, restoration helps previously over-?used forests not only to recover carbon, but also to become ecologically sound and diverse again", Philipson says.

Carbon price doesn't cover the cost

Now, for the first time, a long time-?series dataset has demonstrated that active restoration helps forests to regenerate after disturbances. However, the current price of carbon doesn't cover the cost of restoration, and this limits the impact that restoring forests could have as a means of mitigating climate change.

"The increase in forest regrowth from restoration coupled with average global restoration costs suggests carbon prices need to be much higher. If they were around US$40-80 per tonne CO2 in accordance with the 2016 Paris climate agreement, this would be an incentive to invest in restoration," argues Dundee's Professor Cutler. He sees protecting previously logged tropical forests from further degradation or even clearance as vitally important for reducing carbon emissions and conserving biodiversity. "We must find sustainable mechanisms for funding."

Collaborative partnership on the ground

According to David Burslem, last author and Professor at the University of Aberdeen, scientists have known for some while that tropical forests can regenerate from logging if left undisturbed for long enough. But the extent of the reduction in recovery time achieved by simple low-?tech restoration techniques certainly was a surprise. "We gained this insight through a sustained investment in research by a multi-?national team over more than 20 years", Burslem says.

For this study, Philipson ventured to remote areas of forest to measure the growth and biomass accumulation of trees. His work and indeed the entire study actively involved many local staff, scientists and organisations, while the Sabah government guaranteed effective protection of the forest. "The people and community of Sabah made this project successful; I'm looking forward to seeing more endeavours like this that promote the protection and restoration of tropical forests," he says.

Scientists sound the alarm: Lockdowns may escalate the obesity epidemic
Emotional stress, economic anxiety, physical inactivity and social distance - locking down society to combat COVID-19 creates psychosocial insecurity that leads to obesity, warn three Danish researchers. Counter measures are needed if we are to keep the public both metabolically healthy and safe from the coronavirus

Rates of obesity may explode because of strategies to limit the spread of COVID-19, warn a trio of researchers at the University of Copenhagen and Aarhus University. Investment in obesity research will help inform counter strategies that people eating healthily, feeling happy and staying active, while also combatting COVID-19.

"We are concerned that policy makers do not fully understand how strategies such as lockdowns and business closures could fuel the rise of obesity - a chronic disease with severe health implications, but with few reliable treatment options," says Associate Professor Christoffer Clemmensen, from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), at the University of Copenhagen.

Alone, inactive and hungry

In a letter published in the scientific journal Nature Reviews Endocrinology, Clemmensen and two co-authors outlined how COVID-19 containment strategies could increase rates of obesity.

Firstly, it is well documented that people with limited economic resources are more likely eat highly-processed and energy-rich food. These foods have been shown to stimulate people's appetites, so that they end up eating more calories than they need.

"It is likely that more people will turn to these forms of food, as more people lose their jobs and experience economic hardship," says co-author Professor Michael Bang Petersen, from the Department of Political Science at Aarhus University.

Secondly, physical distancing increases anxiety by limiting our ability to socially interact. Feelings of loneliness and isolation, combined with confinement within a home setting, can impact our food behavior and lead us to overeat. This effect is compounded by lower levels of physical activity, as people are urged to work from home and venture out as little as possible.

Stopping the virus and protecting metabolic health

Co-author Professor Thorkild I.A. Sørensen from CBMR at the University of Copenhagen, stresses that we still do not exactly understand how a person's mental health and economic status end up increasing a person's risk of developing obesity.

"We know that there are links between obesity and a person's class and mental health, but we don't exactly understand how they make an impact," says Sørensen.

More research is needed to uncover the cause and effect, but the three co-authors say the scientific expectations are clear: physical distancing and rising rates of unemployment should lead us to expect increased rates of obesity.

Together they urge governments and decision makers to consider what impact COVID-19 containment strategies, such as lockdowns, will have on the public's metabolic health. With this in mind, counter strategies should be considered to ensure that the public remains healthy, happy and active - and also safe from the coronavirus.

Flavonoid compounds -- produced by the roots of some sorghum plants -- positively affect soil microorganisms, according to Penn State researchers, who suggest the discovery is an early step in developing a frost-resistant line of the valuable crop for North American farmers.

That is important because sorghum is a crop that can respond to climate change because of its high water- and nitrogen-use efficiency, according to Surinder Chopra, professor of maize genetics, and Mary Ann Bruns, professor of soil microbiology. A close relative to corn, it is the fifth most valuable cereal crop globally.

"Sorghum can be used for human food and animal feed and also can be grown as a bioenergy crop, producing more ethanol than corn when grown on marginal lands," they said. "Sorghum is better adapted than corn to stresses such as drought, salinity and heat. But increased sorghum production requires increasing its tolerance to chilling and frost stress, and this is especially true for the northeastern U.S."

Showing red flavonoids

To reach its full potential, sorghum needs to grow five months after being planted in the first week of June. If a frost occurs in early October -- which is not unusual in the U.S. Northeast -- farmers can be devastated. Because sorghum is so sensitive to being chilled, even a mild frost or an early cold snap can kill the crop.

Earlier studies by Chopra's research group in the College of Agricultural Sciences showed that sorghum produces potent flavonoids in its leaves when exposed to stresses such as fungi, insect feeding or frost. These flavonoids can allow the plant to adapt and survive. Bruns group has been working on understanding soil microbiomes in various stressed ecosystems.

Together, the researchers are testing whether interactions between those flavonoids and microorganisms in the root zone can lead to the development of sorghum varieties and compatible soil microbial additions to provide resistance to cold and frost. A collaborative effort between the two research groups enables them to connect the prevalence of plant-associated microbiomes, plant genetics and flavonoids.

In this study, researchers found evidence that plant genetic variation influences root flavonoids and the composition of the soil microbial community, and that low temperatures affect these relationships. In findings recently published in Phytobiomes Journal, they contend that plant-microbe interactions and secondary metabolite production may be important components to include for selective breeding of sorghum for frost stress tolerance.

"We think that the flavonoids can provide the needed tolerance against the stress of cold and frost," Bruns and Chopra said. "In addition, certain microorganisms present in the soil can interact with flavonoids to provide adaptability to the plant when it perceives cold or frost above ground."

The researchers grew selected lines of sorghum at Penn State's Russell E. Larson Agricultural Research Center at Rock Springs from seeds they acquired from the Grain, Forage and Bioenergy Research Laboratory maintained by the U.S. Department of Agriculture's Agricultural Research Service in Lincoln, Nebraska.

Of those "near-isogenic" lines of sorghum -- alike except for two genes involved in the production of flavonoids -- one set of lines inherently produced flavonoids, the second set lacked genes to produce flavonoids, and the third type only produced flavonoids when the plants were exposed to stress such as frost and fungal pathogens.

Researchers analyzed the community of microorganisms in the soils surrounding the roots to see if the presence or absence of flavonoids in the roots of some of the sorghum plants impacted communities of fungi and bacteria. Lead researcher Mara Cloutier, doctoral candidate in soil science and biogeochemistry, led the evaluation of microbiomes in the vicinity of the roots before and after a late-season frost.

Seed multiplication plot

The researchers analyzed roots for total flavonoids, total phenolics and antioxidant activity to determine whether sorghum genetic variation influenced root flavonoid concentrations and soil microbial communities. The researchers wanted to identify how frost affected these relationships.

"We found that a greater number of bacterial strains were correlated with total flavonoids compared with fungal species," she said. "Collectively, this study provides evidence that plant genetic variation influences root flavonoids and the soil microorganism community composition in the vicinity of the plant roots, and that these relationships are affected by frost."

The larynx is larger, more variable in size, and has undergone faster rates of evolution in primates than in carnivores, according to a study published August 11, 2020 in the open-access journal PLOS Biology by Daniel Bowling of Stanford University, W. Tecumseh Fitch of the University of Vienna, and colleagues.

The larynx is the main organ of vocal production, and a key target for evolutionary selection, particularly in those species that have a highly developed vocal communication systems. To shed light on the evolution of the larynx, Bowling and Fitch combined 3D computer models built from X-ray computed tomography scans with detailed digital measurements. They used these techniques to compare the larynx structure of 55 different mammalian species, representing a wide range of body sizes among primates and carnivores (from pygmy marmoset to gorilla and from dwarf mongoose to tiger). Carnivores were chosen as a comparable order of mammals with a similarly wide size range.

Using comparative methods known as phylogenetics, they showed that the larynx has evolved more rapidly in primates than in carnivores, resulting in a pattern of larger larynx size relative to body size, and greater variability in size. Acoustic vocalization data suggest that these differences are relevant to vocal communication. Moreover, larynx size is less tightly coupled to body size in primates than it is in carnivores, suggesting that the primate larynx has been freer to respond to fluctuations in evolutionary pressure. Taken together, the results imply fundamental differences between primates and carnivores in the balance of evolutionary forces that constrain larynx size, and highlight an evolutionary flexibility in primates that may help explain why we have developed complex and diverse uses of the vocal organ for communication.

USC researchers have found the likely order in which COVID-19 symptoms first appear: fever, cough, muscle pain, and then nausea, and/or vomiting, and diarrhea.

Knowing the order of COVID-19's symptoms may help patients seek care promptly or decide sooner than later to self-isolate, the scientists say. It also may help doctors rule out other illnesses, according to the study led by doctoral candidate Joseph Larsen and his colleagues with faculty advisors Peter Kuhn and James Hicks at the USC Michelson Center for Convergent Bioscience's Convergent Science Institute in Cancer.

Recognizing the order of symptoms also could help doctors plan how to treat patients, and perhaps intervene earlier in the disease.

"This order is especially important to know when we have overlapping cycles of illnesses like the flu that coincide with infections of COVID-19," said Kuhn, a USC professor of medicine, biomedical engineering, and aerospace and mechanical engineering. "Doctors can determine what steps to take to care for the patient, and they may prevent the patient's condition from worsening."

"Given that there are now better approaches to treatments for COVID-19, identifying patients earlier could reduce hospitalization time," said Larsen, the study's lead author.

Fever and cough are frequently associated with a variety of respiratory illnesses, including Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). But the timing and symptoms in the upper and lower gastrointestinal tract set COVID-19 apart.

"The upper GI tract (i.e., nausea/vomiting) seems to be affected before the lower GI tract (i.e., diarrhea) in COVID-19, which is the opposite from MERS and SARS," the scientists wrote.

The authors predicted the order of symptoms this spring from the rates of symptom incidence of more than 55,000 confirmed coronavirus cases in China, all of which were collected from Feb. 16-Feb. 24, 2020, by the World Health Organization. They also studied a dataset of nearly 1,100 cases collected from Dec. 11, 2019 through Jan. 29, 2020, by the China Medical Treatment Expert Group via the National Health Commission of China.

To compare the order of COVID-19 symptoms to influenza, the researchers examined data from 2,470 cases in North America, Europe and the Southern Hemisphere, which were reported to health authorities from 1994 to 1998.

The scientific findings were published Thursday in the journal Frontiers in Public Health.

"The order of the symptoms matter. Knowing that each illness progresses differently means that doctors can identify sooner whether someone likely has COVID-19, or another illness, which can help them make better treatment decisions," Larsen, the lead author, said.

Nylon manufacture could be revolutionised by the discovery that bacteria can make a key chemical involved in the process, without emitting harmful greenhouse gases.

Scientists have developed a sustainable method of making one of the most valuable industrial chemicals in the world - known as adipic acid - which is a key component of the material.

More than two million tonnes of the versatile fabric - used to make clothing, furniture and parachutes - is produced globally each year, with a market value of around £5 billion.

Industrial production of adipic acid relies on fossil fuels and produces large amounts of nitrous oxide - a greenhouse gas three hundred times more potent than carbon dioxide. A sustainable production method is urgently required to reduce the damage caused to the environment, the team says.

Scientists from the University of Edinburgh altered the genetic code of the common bacteria E.coli in the lab. The modified cells were grown in liquid solutions containing a naturally occurring chemical, called guaiacol, which is the main component of a compound that gives plants their shape.

Following a 24-hour incubation period, the modified bacteria transformed the guaiacol into adipic acid, without producing nitrous oxide.

The environmentally friendly approach could be scaled up to make adipic acid on an industrial scale, researchers say.

The study is published in ACS Synthetic Biology. It was funded by the Carnegie Trust and UK Research and Innovation.

Lead author Jack Suitor, a PhD student in the University of Edinburgh's School of Biological Sciences, said the team is continually exploring new ways of using bacteria to produce chemicals.

He said: "I am really excited by these results. It is the first time adipic acid has been made directly from guaiacol, which is one of the largest untapped renewable resources on the planet. This could entirely change how nylon is made."

Dr Stephen Wallace, Principle Investigator of the study, and a UKRI Future Leaders Fellow suggested microbes could help solve many other problems facing society.

He said: "If bacteria can be programmed to help make nylon from plant waste - something that cannot be achieved using traditional chemical methods - we must ask ourselves what else they could do, and where the limits lie. We are all familiar with the use of microbes to ferment food and beer - now we can ferment materials and medicines. The possibilities of this approach to create a sustainable future are staggering."

OAK BROOK, Ill. - There was a higher incidence and severity of physical intimate partner violence (IPV) among patients seen at a large, academic medical center in the U.S. during the COVID-19 pandemic compared with the prior three years, according to a new study published in Radiology.

"Our study showed a higher incidence of physical IPV, both in absolute numbers and proportion, with more severe injuries despite fewer patients reporting IPV," said Bharti Khurana, M.D., principal investigator and director of the Trauma Imaging Research and Innovation Center at Brigham and Women's Hospital in Boston, Massachusetts. "This indicates that victims are reporting to health care facilities in the late stages of the abuse cycle. Fear of contracting infection and closure of ambulatory sites might be preventing victims of mild physical or emotional abuse from seeking help compared to the pre-pandemic era."

Social distancing has proven to be effective for controlling the spread of coronavirus but with negative socioeconomic and psychological impacts. Service-oriented economies have seen increased unemployment and a higher incidence of substance and alcohol abuse and mental health disorders.

Since the outbreak of COVID-19, reports of IPV have increased worldwide during mandatory "lockdowns" to curb the spread of the virus.

Dr. Khurana and colleagues set out to assess the incidence, pattern and severity of injuries related to IPV at Brigham and Women's Hospital during COVID-19 pandemic. The demographics, clinical presentation, injuries and radiological findings of patients reporting physical abuse arising from IPV between March 11 and May 3, 2020, were compared with the same period over the past three years.

Data from 26 physical IPV victims from 2020 (37+/-13 years, 25 women) were evaluated and compared with 42 physical IPV victims (41+/-15 years, 40 women) from 2017 to 2019. While the overall number of patients reporting IPV was lower, the incidence of physical IPV was 1.8 times greater during the pandemic. Five victims of severe abuse were identified in 2020 (5/26=19%) compared to one each of the previous years.

The total number of deep injuries (injuries to deep internal organs) was 28 during 2020 versus 16 from 2017 to 2019. The number of deep injuries per victim was 1.1 during 2020 compared with 0.4 from 2017 to 2019. The incidence of high-risk abuse defined by mechanism (injuries due to strangulation, stab injuries, burns or use of weapons such as knives, guns and other objects that could inflict deep injuries) was 2 times greater. Patients with IPV during the COVID-19 pandemic were more likely to be ethnically white. Seventeen (65%) victims in 2020 were white, compared to 11 (26%) in the prior years.

"During the pandemic, victims experienced more injuries to the chest and abdomen compared to prior years," said coauthor Babina Gosangi, M.D., assistant professor of radiology at Yale New Haven Health in New Haven, Connecticut, and former emergency radiology fellow at Brigham and Women's Hospital. "For instance, one victim sustained multiple bilateral rib fractures with right pneumothorax and bilateral lung contusions--requiring hospital admission for more than 10 days--after she was repeatedly punched in the chest. Another victim was stabbed in the abdomen and had lacerations to the liver and kidney."

It is challenging to help IPV victims in the time of the pandemic when health care providers are overwhelmed by COVID-19 patients. In addition, alternative options for IPV victims to seek help have decreased. Many ambulatory clinics are no longer seeing as many patients in person due to the virus and are instead pivoting their services to virtual consultation. Telehealth visits limit the opportunity to visualize bruises or other signs of physical trauma and hamper the ability of the health care provider to gather nonverbal cues.

It may also be difficult for victims who are at home to report IPV, and health care providers may be omitting IPV screening questions altogether on these calls due to patient's limited privacy. Therefore, the role of radiologists in identifying victims of IPV through imaging exams has become crucial.

By recognizing high imaging utilization, location and imaging patterns specific to IPV, old injuries of different body parts, and injuries inconsistent to provided history, radiologists can identify victims of IPV even when the victims are not forthcoming.

Dr. Khurana, who is also assistant professor of radiology at Harvard Medical School in Boston, sees this as an opportunity for radiologists to use their expertise in providing patient-centered care and play a critical role in facilitating early intervention, preventing life-threatening injuries and saving lives by early identification of IPV victims.

"As health care providers, we are missing opportunities to identify victims early in the cycle during the pandemic," she said. "There is under-reporting by the victims, accentuated due to fear of seeking care due to COVID-19. At the same time, IPV-related injuries may be getting overlooked or misinterpreted, as our frontline physicians are overwhelmed by a vast number of COVID-19 patients in the Emergency Department."

The researchers emphasize that radiologists and other health care providers should proactively participate in identifying IPV victims and reaching out to vulnerable communities as an essential service during the pandemic and other crisis situations.

BOSTON - Investigators led by a team at Massachusetts General Hospital (MGH) have made discoveries at the single cell level to uncover new details concerning mitochondrial diseases-- inherited disorders that interfere with energy production in the body and currently have no cure. The findings, which are published in the New England Journal of Medicine, could eventually benefit affected patients.

Mitochondrial diseases result from failure of mitochondria, specialized compartments within cells that contain their own DNA and produce the energy needed to sustain life. Inherited mutations in mitochondrial DNA (mtDNA) often cause these diseases, and affected patients' cells contain a mixture of mutant and nonmutant mtDNA--a phenomenon called heteroplasmy. The proportion of mutant mtDNA varies across patients and among tissues within a patient. Also, symptoms range from mild to severe and depend on which cells of the body are affected.

"It is generally accepted that the fraction of mutant heteroplasmy is what determines whether or not a tissue will exhibit disease. To better understand heteroplasmic dynamics, we applied a brand new genomics technology--with single cell resolution--in which we could simultaneously determine the cell type and the fraction of mutant heteroplasmy in thousands of individual blood cells," said senior author Vamsi K. Mootha, MD, investigator in the Department of Molecular Biology at MGH.

The researchers examined mtDNA within different blood cell types from 9 individuals with MELAS, one of the most common forms of mtDNA disease associated with brain dysfunction and stroke-like episodes, with a wide range of severity across patients.

"What makes this study unique is that it is, to our knowledge, the first time anyone has been able to quantify the percentage of disease-causing mitochondrial DNA mutations in thousands of individual cells of different types from the same patient, as well as in multiple patients with inherited mitochondrial disease," said lead author Melissa A. Walker, MD, PhD, an investigator in the Department of Neurology at MGH.

The analysis revealed especially low levels of heteroplasmy in T cells, which play important roles in killing infected cells, activating other immune cells, and regulating immune responses.

"Our observations suggest that certain cell lineages within our body may have a process by which to guard against problematic mtDNA mutations, which is a potentially very exciting finding," said Walker.

Additional studies are needed to determine whether differences in heteroplasmy across immune cell types affect the cells' function, and whether assessing such heteroplasmy may help clinicians diagnose and monitor mitochondrial diseases. "Our long-term vision is that single cell genomics may lead to improved blood tests for monitoring the progression of these diseases," said Mootha.

In addition, understanding the determinants of reduced T-cell heteroplasmy may motivate new therapeutic strategies for mitochondrial diseases, which currently lack any FDA-approved treatments.

Mootha added that mtDNA mutations also occur spontaneously during normal aging. "Although our work focused on rare, inherited diseases, it has potential implications for the heteroplasmic dynamics of aging as well," he said.

Progress against DIPG, a fatal childhood brain tumor, is usually a game of inches. Studies that hint at even small gains are cause for celebration.

That's why researchers at the University of Michigan and their collaborators are excited about discoveries that point toward a new potential treatment approach -- one that significantly lengthened survival times in two mouse models of DIPG.

The team's findings, which appear in the journal Cancer Cell, suggest that simultaneously targeting two energy-production pathways within the cancer cells could help overcome the effects of a cancer-causing mutation that is one of the hallmarks of DIPG, or diffuse intrinsic pontine glioma, and similar tumors.

"DIPGs have a characteristic, epigenetic histone mutation -- that is, a mutation in the spool that DNA wraps around, and which can affect gene expression," says the study's senior author Sriram Venneti, M.D., Ph.D., a neuropathologist and researcher at the U-M Rogel Cancer Center and Chad Carr Pediatric Brain Tumor Center. "It's not clear exactly how this mutation causes cancer, but it's associated with poor outcomes, which implies these mutations are aggressively driving the biology of these tumors."

An epigenetic change is one that affects how a gene gets used without changing the underlying DNA sequence -- similar to the way a playlist of songs can be altered without changing the songs themselves.

"What we discovered, unexpectedly, is that this mutation specifically increases activity in two metabolic pathways in the cell, and that these pathways also directly influence the epigenetic changes within the cell," Venneti says. "So the question was: Can we use metabolic drugs to interrupt these energy production pathways within the cancer cells and at the same time modify the cells' epigenome in a productive way?"

The result in two different mouse models of DIPG was a resounding yes.

Inhibiting each of the two metabolic pathways individually provided a small increase in how long the mice survived, while targeting both pathways at the same time caused the mice to live much longer.

In one model used in the study, DIPG is always fatal. When the two experimental compounds were given, however, 60% of the mice were still alive, when the experiments were ended.

"Treatments for DIPG are desperately needed. So, while these are still early stage, pre-clinical results, we are excited about continuing to develop this new strategy toward human clinical trials," Venneti says.

DIPG is usually diagnosed in children between the ages of 5 and 10, though it can develop at any age, including rare cases in adults. These tumors start in the brainstem, which makes them nearly impossible to remove surgically. In 2015, Chad Carr, the grandson of former U-M football coach Lloyd Carr, died at age 5 after being diagnosed with the disease 14 months earlier.

"The Chad Carr Pediatric Brain Tumor Center was started in 2018 and has placed the University of Michigan as one of the leading centers for DIPG research and patient care. We could not have performed this research without their strong support and critical funding from the Chad Tough Foundation," Venneti says.

Both of the compounds used in the study -- one of which was developed by the pharmaceutical company AbbVie and the other by Johns Hopkins University -- are able to penetrate the blood-brain barrier, which is critical for treating brain tumors, Venneti adds.

"The barrier is there for a reason," he says. "You don't want toxins to be able to reach your brain. The challenge in developing drugs against brain cancer is that you need the drugs to be able to cross through this barrier and attack the tumor cells. We were fortunate that both of the study compounds can do so."

The study also uncovered new information about the biology of DIPGs and related tumors through the analysis of cancer cells and imaging scans from DIPG patients. Along with shedding new light on the energy cycles of the cancer cells, researchers discovered why two different types of mutations -- one seen in children with DIPG and the other observed in adult brain tumors -- are mutually exclusive.

"We found that these two mutations use the same pathways, but in opposite ways, which explains why they can't occur at the same time," Venneti says.

Continuing to develop a better understanding of the underlying tumor biology will help researchers to develop and refine new treatment strategies, he notes.

Adopting a third-person, observer point of view when recalling your past activates different parts of your brain than recalling a memory seen through your own eyes, according to a new paper.

"Our perspective when we remember changes which brain regions support memory and how these brain regions interact together," explained Peggy St Jacques, assistant professor in the Faculty of Science'sDepartment of Psychology and co-author on the paper.

Specifically, the results show that recalling memories from an observer-like perspective, instead of through your own eyes, leads to greater interaction between the anterior hippocampus and the posterior medial network.

"These findings contribute to a growing body of research that show that retrieving memories is an active process that can bias and even distort our memories," added St Jacques.

"Adopting an observer-like perspective involves viewing the past in a novel way, which requires greater interaction among brain regions that support our ability to recall the details of a memory and to recreate mental images in our mind's eye."

Adopting an observer-like perspective may also serve a therapeutic purpose, explained St Jacques. "This may be an effective way of dealing with troubling memories by viewing the past from a distance and reducing the intensity of the emotions we feel."

This work builds on St Jacques' previous research on visual perspective in memory, which found that the perspective from which we recall a memory can influence how we remember them over time.

A recent paper published in The Economic Journal indicates that, in families with disabled children, the second born child is more adversely affected cognitively than the first-born child.

Brothers and sisters share a unique bond. They typically grow up in the same household, with the same parents and similar genetics, and experience life events together. Siblings have important influences on each other's lives. Siblings might teach each other directly; they might also model behaviors. But they also share limited parental resources such as time, attention, and money directed towards one child might be time, attention, and money diverted from another.

The researchers, analyzing data from Florida and Denmark, studied how adverse health shocks to one child could propagate to their siblings. Specifically, they examined the effect of having a younger sibling with a disability on test scores of older children, measured when they were in elementary and middle school.

Sibling disability is significant, as millions of families have at least one disabled child. In 2012-13, for instance, in the United States alone over 6.4 million children aged 3 to 21 (12.9% of all students) were supported under Part B of the Individuals with Disabilities Education Act. The Florida analysis considers disabilities requiring special accommodations in school, while the Danish analysis is based on disabilities recorded in medical registries, so the two sites estimate the effects of fundamentally different types of disabilities. In Florida, the most common early childhood disabilities considered are speech impairment (48%), developmental delay (21%), and language impairment (17%). In Denmark, for the same age range, the most common disabilities considered are congenital malformations and deformations of the musculoskeletal system (20%), congenital malformations of the circulatory system (10%), and congenital malformations of genital organs (9%).

In order to causally identify sibling spillovers resulting from a younger child's disability, the researchers considered families with three or more children where a health shock (disability) occurred in the case of the third child. Within a family, the first- and second-born children face differential exposure to the affected third sibling. This differential exposure is related to the relative ordering of the two children; earlier-born children had more time in the family without the presence of the disabled third child, and are thus less exposed. The researchers did not find differential effect of exposure on birth and early postnatal outcomes for these children, outcomes that were measured prior to the arrival of third born child, disabled or not.

Despite the differences in settings and disabilities considered across Florida and Denmark, the researchers found evidence in both places consistent with there being a sibling spillover. They found that the second-born child in a family had worse outcomes (test scores in Florida, grade point average in Denmark) than did their older sibling when the third-born sibling was disabled, relative to the case in which the third-born sibling was not disabled. The magnitude of these differences is significant; for example, in Florida it is about half of the observed relationship between an extra year of maternal education and children's test scores. These results are concentrated in cases in which the third child's disability is observed early - and therefore, presumably, more likely to affect older siblings in early childhood. Furthermore, the results are driven by physical disabilities - which are likely to be more visible early and require more parental time and attention - rather than cognitive or behavioral disabilities.

"I think we all believe that individuals are affected by their siblings when they are growing up--either directly through their interactions with each other or indirectly through the allocation of parental resources such as money, time, and attention. However, it is very difficult to isolate empirically, because there are so many things simultaneously happening in the family that might also affect these children's outcomes," said the paper's lead author, Sandra Black. "It is exciting that we are able to make progress on this front and document the importance of siblings."

CLEVELAND--Luis Ortiz-Rodríguez grew up on the beaches of Puerto Rico--surfing, swimming and running in the hot sand--and swears he had never put on sunblock a day in his life.
 

Then the day came when he peered through an ultrafast laser spectrometer at the College of Arts & Sciences at Case Western Reserve University and observed and recorded pre-cancerous lesions forming on the DNA within three picoseconds after exposure to ultraviolet light.
 

That's picosecond, as in one trillionth of a second.
 

"It's amazing how quickly this happens," said Ortiz-Rodríguez, a PhD researcher in chemistry at Case Western Reserve University. "And it's true, when I was younger, I was always running shirtless on the beach or surfing and I thought sunblock was just for old people. Not anymore."
 

New research by Ortiz-Rodríguez and mentor Carlos Crespo, a professor and lead researcher in the The Crespo Group lab, reveals for perhaps the first time how quickly certain pre-cancerous lesions can form on the DNA of our skin when exposed to sunlight.
 

"That's important," Ortiz-Rodríguez said, "because we need and want to know how fast the mutations can form in the DNA, so that maybe researchers can find a better way to prevent skin cancer at a cellular level."

The 6-4 photo adducts mutation

Their research, recently published in the journal Nature Communications, shows how they've detected fast-forming mutations--called "DNA (6-4) photo adducts" by scientists." Photo adducts are lesions formed by a light-induced reaction in cellular DNA, which can lead to skin cancers. (The numbers 6-4 refers to the location of the relevant segment of DNA, see illustration at bottom).

Previous research published in Science by Crespo and collaborators has shown the other primary photo adduct linked to skin cancers, the thymine-thymine cyclobutane photo adduct, forms in less than 1 picosecond. But this work is the first to defined so precisely the formation mechanism of the 6-4 photo adduct.
 

They believe their findings will provide a stepping-stone toward a fuller understanding of how skin cancerous lesions actually form--a discovery that Crespo believes could have a big impact on the economics of treating and preventing skin cancer.
 

Skin cancer costs

With over 5 million cases diagnosed in the United States each year, skin cancer is America's most common cancer, according to the Skin Cancer Foundation, and the annual cost of treating skin cancers in the United States is about $8.1 billion.

The research also affirms that while most of us don't worry about the occasional sunburn because the discomfort fades in a few days, the longer-term damage stays hidden for decades, Crespo said.
 

"You're forming these mutations in your skin every second that you are exposed to sunlight, but enzymes in your cells repair more than 99% of them," Crespo said. "The problem is the less than 1% that remains un-repaired because they can accumulate in your body, often until you're much older and then they can lead to skin cancers."

The search for these precursors to skin cancer has actually been going on in earnest since the late 1960s, Crespo said. Until now, the timescale of its formation and the reactive-state precursor had eluded researchers around the world.
 

"Even though it is well established that formation of the 6-4 photo adduct is an initial pre-cancer lesion leading to skin cancer, we didn't fully understand the mechanistic aspects of it formation, so our paper provides important information in the characterization and understanding of these reactions," Crespo said. "Understanding the chemical processes could help us design better sunblock or maybe avoid the damage to the DNA before it occurs."
 

A Princeton team has developed a class of light-switchable, highly adaptable molecular tools with new capabilities to control cellular activities. The antibody-like proteins, called OptoBinders, allow researchers to rapidly control processes inside and outside of cells by directing their localization, with potential applications including protein purification, the improved production of biofuels, and new types of targeted cancer therapies.

In a pair of papers published Aug. 13 in Nature Communications, the researchers describe the creation of OptoBinders that can specifically latch onto a variety of proteins both inside and outside of cells. OptoBinders can bind or release their targets in response to blue light. The team reported that one type of OptoBinder changed its affinity for its target molecules up to 330-fold when shifted from dark to blue light conditions, while others showed a five-fold difference in binding affinity -- all of which could be useful to researchers seeking to understand and engineer the behaviors of cells.

Crucially, OptoBinders can target proteins that are naturally present in cells, and their binding is easily reversible by changing light conditions -- "a new capability that is not available to normal antibodies," said co-author José Avalos, an assistant professor of chemical and biological engineering and the Andlinger Center for Energy and the Environment. "The ability to let go [of a target protein] is actually very valuable for many applications," said Avalos, including engineering cells' metabolisms, purifying proteins or potentially making biotherapeutics.

The new technique is the latest in a collaboration between Avalos and Jared Toettcher, an assistant professor of molecular biology. Both joined the Princeton faculty in 2015, and soon began working together on new ways to apply optogenetics -- a set of techniques that introduce genes encoding light-responsive proteins to control cells' behaviors.

"We hope that this is going to be the beginning of the next era of optogenetics, opening the door to light-sensitive proteins that can interface with virtually any protein in biology, either inside or outside of cells," said Toettcher, the James A. Elkins, Jr. '41 Preceptor in Molecular Biology.

Avalos and his team hope to use OptoBinders to control the metabolisms of yeast and bacteria to improve the production of biofuels and other renewable chemicals, while Toettcher's lab is interested in the molecules' potential to control signaling pathways involved in cancer.

The two papers describe different types of light-switchable binders: opto-nanobodies and opto-monobodies. Nanobodies are derived from the antibodies of camelids, the family of animals that includes camels, llamas and alpacas, which produce some antibodies that are smaller (hence the name nanobody) and simpler in structure than those of humans or other animals.

Nanobodies' small size makes them more adaptable and easier to work with than traditional antibodies; they recently received attention for their potential as a COVID-19 therapy. Monobodies, on the other hand, are engineered pieces of human fibronectin, a large protein that forms part of the matrix between cells.

"These papers go hand in hand," said Avalos. "The opto-nanobodies take advantage of the immune systems of these animals, and the monobodies have the advantage of being synthetic, which gives us opportunities to further engineer them in different ways."

The two types of OptoBinders both incorporate a light-sensitive domain from a protein found in oat plants.

"When you turn the light on and off, these tools bind and release their target almost immediately, so that brings another level of control" that was not previously possible, said co-author César Carrasco-López, an associate research scholar in Avalos' lab. "Whenever you are analyzing things as complex as metabolism, you need tools that allow you to control these processes in a complex way in order to understand what is happening."

In principle, OptoBinders could be engineered to target any protein found in a cell. With most existing optogenetic systems, "you always had to genetically manipulate your target protein in a cell for each particular application," said co-author Agnieszka Gil, a postdoctoral research fellow in Toettcher's lab. "We wanted to develop an optogenetic binder that did not depend on additional genetic manipulation of the target protein."

In a proof of principle, the researchers created an opto-nanobody that binds to actin, a major component of the cytoskeleton that allows cells to move, divide and respond to their environment. The opto-nanobody strongly bound to actin in the dark, but released its hold within two minutes in the presence of blue light. Actin proteins normally join together to form filaments just inside the cell membrane and networks of stress fibers that traverse the cell. In the dark, the opto-nanobody against actin binds to these fibers; in the light, these binding interactions are disrupted, causing the opto-nanobody to scatter throughout the cell. The researchers could even manipulate binding interactions on just one side of a cell -- a level of localized control that opens new possibilities for cell biology research.

OptoBinders stand to unlock scores of innovative, previously inaccessible uses in cell biology and biotechnology, said Andreas Möglich, a professor of biochemistry at the University of Bayreuth in Germany who was not involved in the studies. But, Möglich said, "there is much more to the research" because the design strategy can be readily translated to other molecules, paving the way to an even wider repertoire of customized, light-sensitive binders.

"The impressive results mark a significant advance," he said.

"Future applications will depend on being able to generate more OptoBinders" against a variety of target proteins, said Carrasco-López. "We are going to try to generate a platform so we can select OptoBinders against different targets" using a standardized, high-throughput protocol, he said, adding that this is among the first priorities for the team as they resume their experiments after lab research was halted this spring due to COVID-19.

Beyond applications that involve manipulating cell metabolism for microbial chemical production, Avalos said, OptoBinders could someday be used to design biomaterials whose properties can be changed by light.

The technology also holds promise as way to reduce side effects of drugs by focusing their action to a specific site in the body or adjusting dosages in real time, said Toettcher, who noted that applying light inside the body would require a device such as an implant. "There aren't many ways to do spatial targeting with normal pharmacology or other techniques, so having that kind of capability for antibodies and therapeutic binders would be a really cool thing," he said. "We think of this as a sea change in what sorts of processes can be placed under optogenetic control."