IMAGE: AN ANIMATION DEPICTING SPECIFIC GENOMIC VARIANTS THAT CAUSE A DISEASE CALLED FAMILIAL MEDITERRANEAN FEVER (FMF) MAY ALSO CONFER INCREASED RESILIENCE TO THE PLAGUE. view more 

CREDIT: CREDIT: ERNESTO DEL AGUILA III, NHGRI.

Ancient disease may increase resilience to bubonic plague

Genomic variants that cause common periodic fever have spread in Mediterranean populations over centuries, potentially protecting people from the plague

NIH/NATIONAL HUMAN GENOME RESEARCH INSTITUTE

 

Researchers have discovered that Mediterranean populations may be more susceptible to an autoinflammatory disease because of evolutionary pressure to survive the bubonic plague. The study, carried out by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, determined that specific genomic variants that cause a disease called familial Mediterranean fever (FMF) may also confer increased resilience to the plague.

The researchers suggest that because of this potential advantage, FMF-causing genomic variants have been positively selected for in Mediterranean populations over centuries. The findings were published in the journal Nature Immunology.

Over centuries, a biological arms race has been fought between humans and microbial pathogens. This evolutionary battle is between the human immune system and microorganisms trying to invade our bodies. Microbes affect the human genome in many ways. For example, they can influence some of the genomic variation that accumulates in human populations over time.

"In this era of a new pandemic, understanding the interplay between microbes and humans is ever critical," said Dr. Dan Kastner, NHGRI scientific director and a co-author on the paper. "We can witness evolution playing out before our very eyes."

One such microbe is Yersinia pestis, the bacterial agent responsible for a series of well-documented bubonic plague epidemics that led to over 50 million deaths.

FMF, like the plague, is an ancient disease. It is the most common periodic fever syndrome, and symptoms of FMF include recurrent fevers, arthritis, rashes and inflammation of the tissues that line the heart, lungs, and abdominal organs. FMF may also lead to renal failure and death without treatment. The disease appears across the Mediterranean region and mostly affects Turkish, Jewish, Armenian and Arab populations.

Genomic variants in the MEFV gene cause FMF. MEFV encodes a protein called pyrin. In healthy people, pyrin plays a role in the inflammatory response of the body. Pyrin is activated when there is an immune response (for example, in the event of an infection). Pyrin increases inflammation and the production of inflammation-related molecules.

In contrast, FMF patients produce abnormal pyrin because of genomic variants (mutations) in the MEFV gene. Mutated pyrin does not need an infection or other immune trigger to be activated; rather, it is able to directly predispose people to seemingly unprovoked episodes of fever and inflammation.

The MEFV mutations also have other usual properties. Researchers have discovered that people with only one copy of a MEFV genomic variant that causes FMF do not get the disease. Also, prior to effective treatment, those with two copies have a high mortality rate by the age of 40 but usually live long enough to have children.

Despite the lower survival rate, almost 10% of Turks, Jews, Arabs and Armenians carry at least one copy of an FMF-causing genomic variant. If chance were the only factor, that percentage would be much lower.

The researchers proposed that this higher percentage was a consequence of positive natural selection, which is an evolutionary process that drives an increase in specific genomic variants and traits that are advantageous in some way.

"Just like sickle cell trait is positively selected for because it protects against malaria, we speculated that the mutant pyrin in FMF might be helping the Mediterranean population in some way," said Jae Jin Chae, Ph.D., senior author of the paper and a staff scientist in NHGRI's Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch. "The mutant pyrin may be protecting them from some fatal infection."

The team turned to Yersinia pestis, the infamous bubonic plague-causing bacterium, as a possible candidate for driving the evolutionary selection for FMF mutations in the Mediterranean population.

It turns out Yersinia pestis contains a particular molecule that represses the function of pyrin in healthy individuals. In doing so, the pathogen suppresses the body's inflammatory response to the infection. This way, the body cannot fight back.

"Inflammation is a process in which white blood cells protect the body from infection. From the host's point of view, inflammation helps us survive. From the bacteria's point of view, inflammation is something to be evaded by any means available," said Daniel Shriner, Ph.D., staff scientist in the Center for Research on Genomics and Global Health at NHGRI.

Researchers were struck by the fact that Yersinia pestis affects the very protein that is mutated in FMF. They considered the possibility that FMF-causing genomic variants may protect individuals from the bubonic plague caused by Yersinia pestis.

The idea that evolution would push for one disease in a group to fight another may seem counterintuitive. But it comes down to what is the least bad option.

The average mortality rate of people with bubonic plague over centuries has been as high as 66%, while, even with a carrier frequency of 10%, less than 1% of the population has FMF. Theoretically, the evolutionary odds are in the latter's favor.

But first, the team had to verify if two of the genomic variants that cause FMF had indeed undergone positive selection in Mediterranean populations.

For this, they performed genetic analysis on a large cohort of 2,313 Turkish individuals. They also examined genomes from 352 ancient archaeological samples, including 261 from before the Christian era. The researchers tested for the presence of two FMF-causing genomic variants in both groups of samples. They also used population genetics principles and mathematical modeling to predict how the frequency of FMF-causing genomic variants changed over generations.

"We found that both FMF-causing genomic variants arose more than 2,000 years ago, before the Justinian Plague and the Black Death. Both variants were associated with evidence of positive selection," said Elaine Remmers, Ph.D., associate investigator in NHGRI's Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch.

Researchers then studied how Yersinia pestis interacts with FMF-causing genomic variants. They took samples of particular white blood cells from FMF patients. In addition, they took samples from people who carry just one copy of the genomic variants (hence, do not get the disease).

The team found that Yersinia pestis does not reduce inflammation in white blood cells acquired from FMF patients and people with one copy of FMF-causing genomic variants. This finding is in stark contrast to the fact that Yersinia pestis reduces inflammation in cells without FMF-associated mutations.

The researchers thought that if Yersinia pestis does not reduce inflammation in people with FMF, then perhaps this could potentially increase patients' survival rate when infected by the pathogen.

To test this hypothesis, the researchers genetically engineered mice with FMF-causing genomic variants. They infected both healthy and genetically engineered mice with Yersinia pestis. Their results showed that infected mice with the FMF-causing genomic variant had significantly increased survival as compared to infected healthy mice.

These findings, in combination, indicate that over centuries, FMF-causing genomic variants positively selected in Turkish populations play a role in providing resistance to Yersinia pestis infection. Whether the same is true for other Mediterranean populations remains to be seen. The study offers a glimpse into the unexpected and long-lasting influence of microbes on human biology.

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BU study: Nearly half of US youth have been stalked/harassed by partners

BOSTON UNIVERSITY SCHOOL OF MEDICINE

 

A new, first-of-its-kind Boston University School of Public Health (BUSPH) study finds that 48% of 12-18-year-olds who have been in a relationship have been stalked or harassed by a partner, and 42% have stalked or harassed a partner.

Published in the journal Youth & Society, the analysis is part of the first nationally-representative study of non-physical youth dating abuse.

"These victimization and perpetration numbers are unacceptably high," says study lead author Dr. Emily Rothman, professor of community health sciences at BUSPH. "Unfortunately, they are in line with estimates of similar problems like dating and sexual violence victimization, so they are both shocking and unsurprising at the same time."

Previous research shows that harassing and stalking behaviors, including destroying belongings or going through social media accounts, can lead to physical violence, Rothman says.

But perhaps especially in the time of COVID, non-physical dating abuse needs to be recognized as real and harmful in its own right, she says.

"Adolescents have already been fully aware of how harmful online forms of abuse can be--that it's valid to be interested in that and to try to address it," Rothman says. "COVID has in some ways made parents, teachers, and other adults more willing to see, right now, that what we do online matters and is fully part of our real lives."

Rothman and colleagues from NORC at the University of Chicago used data from the ongoing Survey on Teen Relationships and Intimate Violence (STRiV) study to look at responses from 148 boys and 172 girls who were currently in relationships or had been in relationships in the past year. The survey asked teens if a partner had ever followed or spied on them, damaged something that belonged to them, or gone through their online accounts. The survey also asked the teens if they had ever done any of these things to a partner.

They found that rates of perpetration and victimization were similar for boys and girls: 46.5% of boys and 50.6% of girls reported stalking or harassing a partner, and 44.6% of boys and 51.1% of girls reported a partner doing these things to them.

The researchers analyzed and controlled for a range of other factors to better understand why particular teens may be at higher risk of perpetration, victimization, or both.

Among boys, having worse relationships with parents and living in neighborhoods with higher rates of violent crime were both associated with higher risk of perpetration. Among girls, being in relationships at younger age, living in neighborhoods with higher rates of violent crime, using marijuana, and using alcohol were associated with higher risk of victimization and perpetration. By race/ethnicity, the researchers found that Latino boys and Black girls faced higher risk of both victimization and perpetration.

Further research will need to untangle these associations, but Rothman says the findings show that dating abuse is shaped by forces larger than the individual.

"We know from intervention research that the way to prevent stalking and harassment, or sexual and dating violence, is partly about addressing how young people think about relationships, gender norms, and improving their social-emotional skills, but these are also influenced by the context in which they are operating," she says.

"So, addressing racism, poverty, homophobia, misogyny, and disability-related discrimination is part of the solution, too."

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About the Boston University School of Public Health

Founded in 1976, the Boston University School of Public Health is one of the top five ranked private schools of public health in the world. It offers master's- and doctoral-level education in public health. The faculty in six departments conduct policy-changing public health research around the world, with the mission of improving the health of populations--especially the disadvantaged, underserved, and vulnerable--locally and globally.

Microbiome confers resistance to cholera

Not everyone exposed to infectious diarrhea-causing bacteria gets sick

UNIVERSITY OF CALIFORNIA - RIVERSIDE

 

IMAGE: VIBRIO CHOLERAE BACTERIUM, WHICH IS RESPONSIBLE FOR CAUSING CHOLERA. view more 

CREDIT: CENTERS FOR DISEASE CONTROL AND PREVENTION

Cholera can kill within hours if left untreated, and it sickens as many as 4 million people a year. In a new article in the journal Cell, researchers describe how gut bacteria helps people resist the disease.

Bacteria live everywhere on the planet -- even inside the human body. UCR microbiologist Ansel Hsiao studies whether the bacteria living in our bodies, collectively known as the human microbiome, can protect people from diseases caused by external bacteria such as Vibrio cholerae, which lives in waterways and causes cholera.

Hsiao's team examined the gut microbiomes from people in Bangladesh, where many suffer from cholera as a result of contaminated food, water and poor sanitation infrastructure. "When people get sick, the diarrhea gets flushed into water systems that people drink from, and it's a negative cycle," Hsiao explained.

His team wanted to see whether prior infections or other stresses, like malnutrition, make people more vulnerable, as compared to Americans who don't face these same pressures.

The findings surprised the group, which expected stressed Bangladeshi microbiomes would allow for higher rates of infection. Instead, they saw infection rates varied greatly among individuals in both populations, suggesting susceptibility is based on a person's unique microbiome composition -- not the place they're from.

Vibrio cholerae spends most of its time outside of humans in aquatic environments. It doesn't usually encounter bile, which mammals produce to help digest fats after a meal.

"Because bile is specific to the intestines of humans and animals, many microorganisms, including cholerae, have evolved ways to deal with it," Hsiao said.

Once Vibrio cholerae enters a body, the presence of bile and lack of oxygen in the gut triggers previously dormant genes that enable it to survive in its human host. These genes are responsible for cholera's virulence, helping Vibrio cholerae attach to intestinal walls and cause diarrhea.

Hsiao's team identified one bacterium in the human microbiome, Blautia obeum, that can deactivate the cholera bacterium's disease-causing mechanisms, preventing it from colonizing the intestines. They also figured out how this feat is accomplished.

Cholera patients in Haiti, where an outbreak of cholera occurred after a 7.0 earthquake in 2010

Kendra Helmer/USAID

Blautia obeum produces an enzyme that degrades salts in bile, which Vibrio cholerae uses as signals to control gene activity. When these bile salts are corrupted, the cholera-causing bacteria does not receive the signal to activate the dormant genes that cause infection.

Since it's become clear that more Blautia obeum makes people less susceptible to cholera, a focus of future studies will be how to increase its presence in the gut. "We are extremely interested now in learning which environmental factors, such as diet, can boost levels of obeum," Hsiao said.

Similar studies are also underway with regard to the virus causing another global pandemic -- SARS-CoV-2. Hsiao is collaborating with several groups trying to understand how the microbiome changes with COVID-19 infection.

"One day, we may also understand whether and how the microbiome affects COVID-19 and makes people resistant to other illnesses we don't currently have treatments for," Hsiao said.

Ad blockers may benefit websites, users, and the market at large

SHARE THIS WITH ALL THOSE NEWS SITES NOW BLOCKING AD BLOCKERS

CARNEGIE MELLON UNIVERSITY

 

Millions of websites, including some of the largest Internet companies (e.g., Google, Yahoo), depend on advertising as their main source of revenue, allowing them to offer their content for free. The use of software that blocks ads has surged in recent years, presenting a challenge to platforms that depend on ad revenue. A new study sought to determine the effect of ad blockers on websites' ability to generate revenue and on users' experiences. The study found that contrary to common assumptions, ad blockers may offer some benefits to companies, users, and the market at large. The findings have implications for how online platforms make decisions about advertising.

The study, by researchers at Carnegie Mellon University and the City University of Hong Kong, appears in Management Science.

"While most speculations point to a grim outlook for advertisers and platforms as a result of ad blockers, the results of our study offer a glimmer of hope by arguing that ad blockers could actually benefit companies," suggests Kannan Srinivasan, Professor of Management, Marketing, and Business Technologies at Carnegie Mellon University's Tepper School of Business, who coauthored the study.

An ad blocker is a type of software, usually added by a user as an extension to an Internet browser, that prevents ads from appearing on the browsed webpages. When a user with an ad blocker visits a website with ads, the blocker identifies the ad content and prevents it from loading--as a result, the website does not receive ad revenue for that user.

Researchers devised an analytical model to assess the effects of ad blockers by modeling competition, the rate of advertising, and users' sensitivity to advertising. The authors identified two classes of users: one that is more sensitive to ads and uses ad blockers and one that does not use ad blockers. Based on the prevailing conditions, each platform had three options to manage the potential use of ad blockers by some users:

1. Ban ad blocking: Continue displaying ads and ban ad blocking. If a viewer used an ad blocker, he or she has to disable it to gain access to the site.
2. Allow ad blocking: Continue to display ads and allow ad-blocking software by any user who installs it.
3. Charge fees for ad blocking: Stop displaying ads and offer only an ad-free site with a subscription fee.

Based on their work, the researchers concluded that ad blockers may be helpful in one of four ways:

• They can make the market more efficient by filtering users who are sensitive to general ads, allowing websites to target more intense ads to the rest of the users.
• They benefit users by allowing the removal of ads that annoy them.
• They help regulate the ad industry by motivating the advertising platform to pay a fee to the ad-blocking company to include it in a list of ads that are allowed past the blocker.
• A more efficient market can boost the quality of websites' content, which also benefits users.

"Our study has implications for platforms dependent on ad revenue, providing general guidelines regarding how they should proceed with decisions about advertising," according to Stylianos Despotakis, Assistant Professor of Marketing at the City University of Hong Kong, who coauthored the study. "For example, if a website has users who are generally sensitive to ads, then its platform cannot expect to receive a lot of ad revenue, even when it prevents the use of ad blockers. By allowing ad blockers, both the platform and the users can benefit."

R. Ravi, Professor of Operations Research and Computer Science at Carnegie Mellon University's Tepper School of Business and a coauthor of the study, adds: "To estimate users' ad sensitivities, platforms can do tests under differing conditions to decide the ideal course of action to manage ad blocking."

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Study: Gay and bisexual youth more likely to abandon churchgoing as they reach adulthood

Prayer remains important to many, however

UNIVERSITY OF NEBRASKA-LINCOLN

 

Religious beliefs have shaped societal attitudes toward sexual minorities, with many religious denominations vocally opposing expanded sexual minority rights. Because of this stigmatization, lesbian, gay and bisexual individuals are less likely to affiliate with a religious group -- but research from the University of Nebraska-Lincoln and Old Dominion University suggests they are not abandoning their faith altogether.

In a new study, sociologists Brandi Woodell and Philip Schwadel found that emerging adults -- from adolescence to early adulthood -- with same-sex attraction are twice as likely to disaffiliate from organized religion than their heterosexual peers, but there was little change in prayer.

"I think that is something we expected, that there'd be a difference between affiliation on one hand and prayer on the other," said Schwadel, Happold Professor of Sociology at Nebraska. "In the previous research on adolescent religion, in particular, and in later adolescence or early emerging adulthood, we see a lot of declines in the organized aspects of religion, but we see less of a decline in prayer. Prayer is something people can often do on their own at home or wherever they want."

And, not in an environment that may be stigmatizing toward sexual minorities, the authors wrote in the paper.

The scholars used two longitudinal surveys, the National Longitudinal Study of Adolescent to Adult Health, and the National Study of Youth and Religion to examine -- for the first time -- these declines in religiosity over time for sexual minorities in emerging adulthood.

"Almost all previous research was cross-sectional, only looking at, 'do people who identify as gay or lesbian -- are their religious activities and beliefs different?'" Schwadel said. "It didn't look at how they change over time, especially during this stage of the life course, when individuals are really figuring out who they are."

The study also showed a significant difference in religiosity declines between gay and bisexual individuals, further demonstrating that sexual minorities are not a monolithic group.

Woodell, a 2018 Nebraska alumna and assistant professor of sociology at Old Dominion University in Norfolk, Virginia, said this study joins a novel line of research examining the differences between bisexual, gay and lesbian individuals.

"Past research has most often combined sexual minorities into one group, and that was largely due to a lack of data that separated them, but some newer research has suggested there are differences, which led us to separate the groups out," Woodell said. "We found that those who identify as bisexual show a greater decline in their religious attendance than gay and lesbian individuals."

This difference could be explained by some research that has found bisexuals are less likely to be accepted than their gay counterparts, even in affirming denominations, Woodell said.

"There is newer research showing that bisexuals have experienced stigmatization in their congregation because their sexuality is viewed as a choice," Woodell said.

While the study found little change in prayer among the sexual minority groups, there was a small decline among bisexuals. Schwadel and Woodell said they are pursuing this research further, breaking down differences among gender.

"We're currently looking at how these things differ for men and women," Schwadel said. "We know that gender is strongly related to religiosity, and we expect that gender plays a role in terms of how sexuality is related to religious change."

Further research is also needed, they said, to examine how these declines in religiosity among lesbian, gay and bisexual individuals continue to change in later adulthood.

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Study: New leaders emerge as organizations go to virtual work spaces

In virtual environments, actions trump more traditional leadership traits

BRIGHAM YOUNG UNIVERSITY

 

When work meetings shifted online this spring, some may have noticed new standouts among their colleagues. According to new research, members of virtual teams identify leaders in significantly different ways compared to members of in-person teams.

The brand new study looked at "emergent leaders"--those who lack formal authority but are recognized as leaders by team members--in teams with varying levels of virtual interaction. Researchers found that in face-to-face gatherings, team members value those with "classic" leadership characteristics, such as extroversion and intelligence, but in virtual settings, those qualities take a backseat.

Online, perhaps because there are fewer cues available for human interaction and more opportunities for miscommunication, team members gravitate toward those who take concrete steps to ensure achievement, rather than toward those with charismatic personalities.

"On a virtual team, it's more important than in a face-to-face meeting to stand out as the one who helps others," said study coauthor Cody Reeves, an assistant professor at the Marriott School of Business at Brigham Young University. "Those who take the time to pause and assist others with tasks are more likely to be viewed as leaders."

Perceived differences between virtual and in-person leaders were "stark," according to Reeves. While it remained essential for leaders in virtual teams to connect socially, successful leadership online was driven primarily by small actions like monitoring timelines, providing feedback, and coordinating teamwork.

For the study, researchers observed 220 student teams at two Midwestern universities who met to work on assigned projects mostly virtually, mostly in person or in a mix of the two. The students completed surveys about their own and their team members' characteristics and behaviors, as well as whom they considered to be team leaders. Combining that data with transcripts of the students' virtual interactions, the researchers identified patterns in how leaders emerge across the spectrum of virtual to in-person teams.

As virtual work becomes more common for organizations, managers and team members alike would benefit from understanding that leadership traits and behaviors impact leadership perceptions differently in different virtual contexts, authors said. For example, organizations should not automatically promote individuals who have distinguished themselves as emergent leaders from a more in-person (and low virtual) context to leadership roles in a highly virtual context.

"In virtual environments, our actions speak loudly," said fellow study author Steven Charlier, a professor of management at Georgia Southern University. "The 'soft' skills that traditional managers rely on might not translate easily to a virtual environment."

Reeves agreed, noting that "a 'natural leader' who doesn't usually engage in these specific leader-like behaviors but always kind of 'has it' needs to be extra careful--because those are the types that are at the highest risk of no longer being viewed as a leader in virtual contexts."

With the "new normal" of work online, "now is the time for organizations and employees to gain virtual leadership competencies," said study lead author Radostina Purvanova of Drake University. "These are the skills of the future. Those companies that have already embraced virtuality are now reaping the benefits -- and the rest of us must catch up quickly, or else we will simply be left behind."

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The study was also co-authored by Lindsey M. Greco of Oklahoma State University and is published in the Journal of Business and Psychology.

Raw milk may do more harm than good

Not properly stored, it's a source of antibiotic-resistant microbes

UNIVERSITY OF CALIFORNIA - DAVIS

Raw or unpasteurized cows' milk from U.S. retail stores can hold a huge amount of antimicrobial-resistant genes if left at room temperature, according to a new study from researchers at the University of California, Davis. The study also found bacteria that harbored antimicrobial-resistant genes can transfer them to other bacteria, potentially spreading resistance if consumed. The study was published in the journal Microbiome.

"We don't want to scare people, we want to educate them. If you want to keep drinking raw milk, keep it in your refrigerator to minimize the risk of it developing bacteria with antibiotic-resistant genes," said lead author Jinxin Liu, a postdoctoral researcher in the Department of Food Science and Technology at UC Davis.

LACKING IN PROBIOTICS

An estimated 3 percent of the U.S. population consumes unpasteurized, or raw, milk, which has not been heated to kill pathogens and extend shelf life. Raw milk is often touted to consumers as having an abundant supply of probiotics, or healthy bacteria, compared with pasteurized milk. UC Davis researchers did not find that to be the case.

"Two things surprised us," said Liu. "We didn't find large quantities of beneficial bacteria in the raw milk samples, and if you leave raw milk at room temperature, it creates dramatically more antimicrobial-resistant genes than pasteurized milk."

Bacteria with antimicrobial-resistant genes, if passed to a pathogen, have the potential to become "superbugs," so that pharmaceuticals to treat infection or disease no longer work. Each year, almost 3 million people get an antibiotic-resistant infection, and more than 35,000 people die, according to the Centers for Disease Control.

THE LONGER IT SITS, THE WORSE IT GETS

UC Davis researchers analyzed more than 2,000 retail milk samples from five states, including raw milk and milk pasteurized in different ways. The study found raw milk had the highest prevalence of antibiotic-resistant microbes when left at room temperature.

"Our study shows that with any temperature abuse in raw milk, whether intentional or not, it can grow these bacteria with antimicrobial resistance genes," said co-author Michele Jay-Russell, research microbiologist and manager with the UC Davis Western Center for Food Safety. "It's not just going to spoil. It's really high risk if not handled correctly."

Some consumers are intentionally letting raw milk sit outside of the refrigerator at room temperature to ferment, in order to make what's known as clabber. Co-author and Peter J. Shields Chair of Dairy Food Science David Mills said if consumers eat raw milk clabber, they are likely adding a high number of antimicrobial-resistant genes to their gut.

"You could just be flooding your gastrointestinal tract with these genes," said Mills. "We don't live in an antibiotic-free world anymore. These genes are everywhere, and we need to do everything we can to stop that flow into our bodies."

While more work is needed to fully understand whether antibiotic-resistant genes in raw milk translate into health risks for humans, Mills suggests that consumers instead use a starter culture if they want to ferment raw milk, which carries specific strains of bacteria to inoculate the milk.

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Other authors include Yuanting Zhu of UC Davis and Danielle Lemay of USDA ARS Western Human Nutrition Research Center. This study was funded with support from the National Institutes of Health and the Peter J. Shields Endowed Chair in Dairy Food Science.

New eye drops may prevent a common cause of blindness

COLUMBIA UNIVERSITY IRVING MEDICAL CENTER

 

IMAGE: EYEDROPS WITH A CASPASE-9 INHIBITOR PREVENT RETINAL INJURY FROM RETINAL VEIN OCCLUSION. IN THE LEFT IMAGE, RVO CAUSES SWELLING IN THE RETINA AND THE RETINAL LAYERS ARE LESS DISTINCT.... view more 

CREDIT: TROY LAB (CUIMC)

NEW YORK, NY (June 29, 2020) -- Researchers at Columbia University Irving Medical Center have developed eye drops that could prevent vision loss after retinal vein occlusion, a major cause of blindness for millions of adults worldwide.

A study, in mice, suggests that the experimental therapy -- which targets a common cause of neurodegeneration and vascular leakage in the eye -- could have broader therapeutic effects than existing drugs.

The study was published in Nature Communications.

What is Retinal Vein Occlusion?

Retinal vein occlusion occurs when a major vein that drains blood from the retina is blocked, usually due to a blood clot. As a result, blood and other fluids leak into the retina, damaging specialized light-sensing neurons called photoreceptors.

Standard treatment for the condition currently relies on drugs that reduce fluid leakage from blood vessels and abnormal blood vessel growth. But there are significant drawbacks. These therapies require repeated injections directly into the eye, and for the patients who brave this daunting prospect, the treatment ultimately fails to prevent vision loss in the majority of cases.

The new treatment targets an enzyme called caspase-9, says Carol M. Troy, MD, PhD, professor of pathology & cell biology and of neurology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Vagelos College of Physicians and Surgeons, who led the studies. Under normal conditions, caspase-9 is believed to be primarily involved in programmed cell death, a tightly regulated mechanism for naturally eliminating damaged or excess cells.

However, in studies of mice, the Troy lab discovered that when blood vessels are injured by retinal vein occlusion, the caspase-9 becomes uncontrollably activated, triggering processes that can damage the retina.

Eye Drops Prevent Retinal Injury

The Troy lab found that a highly selective caspase-9 inhibitor, delivered in the form of eye drops, improved a variety of clinical measures of retinal function in a mouse model of the condition. Most importantly, the treatment reduced swelling, improved blood flow, and decreased neuronal damage in the retina.

"We believe these eye drops may offer several advantages over existing therapies," says Troy. "Patients could administer the drug themselves and wouldn't have to get a series of injections. Also, our eye drops target a different pathway of retinal injury and thus may help patients who do not respond to the current therapy."

Next Steps

The researchers are preparing to test the eye drops in people with retinal vein occlusion during a phase I clinical trial.

Moving forward, the Troy lab will also study whether caspase-9 inhibitors can be used to treat other vascular injuries caused by overactivation of the enzyme, including diabetic macular edema (another common cause of blindness) and stroke.

"Vascular dysfunction is at the heart of many chronic neurological and retinal disorders, because high energy demands in the brain and eye render these tissues exceptionally vulnerable to disruption in blood supply," says the study's first author, Maria Avrutsky, PhD, postdoctoral research scientist in pathology & cell biology at Columbia University Vagelos College of Physicians and Surgeons.

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More Information

The study is titled, "Endothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion."

The other contributors, all from Columbia University Irving Medical Center except where indicated, are: Crystal Colón Ortiz, Kendra V. Johnson, Anna M. Potenski, Claire W. Chen, Jacqueline M. Lawson, Alexandra J. White, Stephanie K. Yuen, Fatima N. Morales, Elisa Canepa, Scott Snipas (Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA), Guy S. Salvesen (Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA), and Ying Y. Jean.

The study was funded by grants from the National Institute of Neurological Disorders and Stroke (RO1 NS081333, R03 NS099920), the National Eye Institute (T32 EY013933), the National Science Foundation (DGE-1644869), the National Institute on Aging (T35 AG044303), the National Institute of General Medical Sciences (R01GM09040), and the Department of Defense Army/Air Force.

The following authors have patent applications related to this research: Dr. Troy (US20150165061), Drs. Troy, Salvesen, and Snipas (US 20140024597), and Drs. Troy and Jean (WO2018013519). The remaining authors declare no competing interests.

Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the Vagelos College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cuimc.columbia.edu or columbiadoctors.org.

3D magnetotelluric imaging reveals magma recharging beneath Weishan volcano

UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA

 

IMAGE: CARTOON INTERPRETATION OF MAGMA RESERVOIRS BENEATH WEISHAN VOLCANO. view more 

CREDIT: GAO JI ET AL.

A collaborative research team from University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS) and China Geological Survey (CGS) have succeeded in obtaining a high-resolution 3D resistivity model of approximately 20 km depth beneath the Weishan volcano in the Wudalianchi volcanic field (WVF) for the first time. The study, published in Geology, revealed the image of potential magma chambers and the estimated melt fractions.

WVF in the northeast of China, comprised of 14 volcanoes that have erupted about 300 years ago, is one of the largest active volcanic areas. Volcanic activities are hazard to human life and have severe environmental consequences, thus it is important to characterize the magmatic system beneath the volcanoes to understand the nature of the eruption.

In conjunction with the Center for Hydrogeology and Environmental Geology, CGS, Prof. ZHANG Jianghai's group from School of Earth and Space Sciences, USTC, utilized magnetotelluric (MT) methods to image magma reservoirs beneath Weishan volcano and obtained its high-resolution spatial resistivity distribution up to 20 km deep. Their findings showed the existence of vertically distributed low-resistivity anomalies that are narrowest in the middle. This was further interpreted as magma reservoirs existing both in the upper crust and the middle crust, which are linked by very thin vertical channels for magma upwelling.

Meanwhile, they cooperated with Institute of Geodesy and Geophysics of CAS, combining both the velocity model from ambient noise tomography (ANT) and the resistivity model from MT imaging to estimate that the melt fractions of the magma reservoirs in the upper crust and the middle crust are reliably to be >~15%. This phenomenon demonstrated that there should be an even deeper source for recharging the magma chambers to keep the melt fraction increasing, and indicated that the volcano is still active.

Considering the significant melt fractions and the active earthquakes and tremors occurred around the magma reservoirs several years ago, the Weishan volcano is likely in an active stage with magma recharging. Although the melt fraction does not reach the eruption threshold (~40%), it is necessary to increase monitoring capabilities to better forecasting its potential future eruptions.

Overall, this study has revealed that the volcanoes in northeast China may be in an active stage. This poses a grave threat to man and environment, thus proper monitoring is required to forecast its hazardous implications.

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COMPASSIONATE CAPITALISM 

The price of taking a stance: How corporate sociopolitical activism impacts bottom line

UNIVERSITY OF ARIZONA

As the political climate in the United States becomes increasingly charged, some businesses are looking to have their voices heard on controversial issues. The impact of corporate sociopolitical activism on a company's bottom line depends on how the activism aligns with the firm's stakeholders, according to new research published in the Journal of Marketing.

Study co-author Nooshin Warren, assistant professor of marketing in the University of Arizona Eller College of Management, says that over the last 10 years, purpose-driven corporate actions have evolved from companies contributing to widely supported causes, such as cancer research, to companies taking stances on more divisive issues, such as gun control and LGBTQ rights. The movement from philanthropic activities to sociopolitical activism has significant effects on firm value and stock market performance, which vary depending on how the activism aligns with the views of a firm's customers, employees and state regulators.

"In the past few years, we have reached the intersection of politics and doing societal good," Warren said. "Companies still have value systems and want to advance society, but the biggest difference in this case is that societal good is debatable, political and partisan."

The researchers examined a dataset of 293 instances of corporate activism between January 2011 and October 2016 by 149 firms throughout the United States. The hot-button sociopolitical issues were selected based on the Pew Research Center's 2014 Political Polarization in the American Public report and Political Polarization and Typology Survey. Some corporate activism examples included Amazon removing Confederate flag merchandise from its website, JCPenney featuring two lesbian moms in a Mother's Day advertisement and the Kroger grocery chain issuing a statement in support of its policy allowing customers to carry firearms in its stores.

Researchers surveyed 1,406 people and asked them to label each corporate activism event on a scale from "very liberal" to "very conservative." A second survey of 375 people helped researchers identify a given company's typical customers as having more liberal or conservative views. The team gauged the political leanings of company employees through political contribution data from the U.S. Federal Election Commission. The researchers then looked at the political composition of the legislature of the state where each firm is headquartered.

Put simply, Warren said, if a company's activism aligns with the values of its customers, employees and state regulators, the impact will be positive. If it misaligns, the impact will be negative.

"The strongest effects come from alignment with consumers' values, and consumers are obviously the most vital source of revenue for a firm," Warren said. "Punishment from a government can have a sudden and significant impact on a company as well. Employees, although very important, have less of an immediate impact."

The researchers measured changes in stock market value in the five-day window surrounding a corporate activism event. The team found if a company's action was misaligned with its key stakeholders, the company's stock market value decreased 2.45% compared to market expectations, as established by the Center for Research in Security Prices. If aligned with their stakeholders values, stock prices increased by .71%

The researchers further investigated the response of consumers to activism and found that as long as the activism is in line with consumers' political values, the company's quarterly and annual sales grow after the activism. When activism is highly deviated from customers and the government, sales growth suffers. This is especially true when activism highly deviates from all three key stakeholders, which resulted in a sales decline of 4%.

Warren says companies have important decisions to make concerning the current unrest over racial justice issues.

"I wish racial equality was not a polarizing issue, but given that it is, firms should carefully identify their consumers, employees and other stakeholders, and resonate with their values," Warren said. "But it is important to stay authentic, as society is watching carefully and will hold firms accountable for their actions as well as for their silence."

What Companies Should Know

If a company wants to engage in corporate activism and alleviate negative results, Warren said, it should consider five factors that the researchers showed can amplify the effects of alignment or misalignment.

The messenger. Warren says a statement means more to customers when it comes from a CEO rather than a public relations representative. She says that's especially true for "celebrity CEOs" like Facebook's Mark Zuckerberg or Amazon's Jeff Bezos.

Action vs. statement. Action provides more impact than statements, both positive and negative, Warren says. For example, she says Target providing transgender-inclusive bathrooms has a stronger impact than a company simply stating support for the LGBTQ community.

Number of firms. Warren says multiple companies taking a stance together can mitigate negative impact from misalignment with lawmakers, since regulators are much more likely to punish one firm than an entire industry.

Internal vs. external benefits. If a company's message or action is specifically for its own benefit or that of its employees, consumers may view that as less of a societal good, and more of a company simply thinking about its bottom line.

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The research team also included Yashoda Bhagwat, assistant professor of marketing at Texas Christian University; Joshua Beck, assistant professor of marketing at the University of Oregon; and George Watson IV, assistant professor of marketing at Portland State University.

Researchers look for answers as to why western bumblebees are declining

UNIVERSITY OF WYOMING

 

IMAGE: CHRISTY BELL, A PH.D. STUDENT IN THE UNIVERSITY OF WYOMING DEPARTMENT OF ZOOLOGY AND PHYSIOLOGY, OBSERVES A WESTERN BUMBLEBEE. BELL AND LUSHA TRONSTAD, LEAD INVERTEBRATE ZOOLOGIST WITH THE WYOMING NATURAL... view more 

CREDIT: CHRISTY BELL

A University of Wyoming researcher and her Ph.D. student have spent the last three years studying the decline of the Western bumblebee. The two have been working with a group of bumblebee experts to fill in gaps of missing information from previous data collected in the western United States. Their goal is to provide information on the Western bumblebee to the U.S. Fish and Wildlife Service while it considers listing this species under the U.S. Endangered Species Act.

"The decline of the Western bumblebee is likely not limited to one culprit but, instead, due to several factors that interact such as pesticides, pathogens, climate change and habitat loss," says Lusha Tronstad, lead invertebrate zoologist with the Wyoming Natural Diversity Database (WYNDD). "Western bumblebees were once the most abundant bumblebees on the West Coast of the U.S., but they are much less frequently observed there now. Pathogens (or parasites) are thought to be a major reason for their decline."

Tronstad and Christy Bell, her Ph.D. student in the Department of Zoology and Physiology, from Laramie, are co-authors of a paper, titled "Western Bumble Bee: Declines in the United States and Range-Wide Information Gaps," that was published online June 26 in Ecosphere, a journal that publishes papers from all subdisciplines of ecological science, as well as interdisciplinary studies relating to ecology.

The two are co-authors because they are members of the Western Bumble Bee Working Group and serve as experts of the Western bumblebee in Wyoming, Tronstad says.

Other contributors to the paper are from the U.S. Geological Survey; U.S. Fish and Wildlife Service; Canadian Wildlife Service; Xerces Society for Invertebrate Conservation in Portland, Ore.; British Columbia Ministry of Environment and Climate Change Strategy; University of Hawaii-Hilo; U.S. Department of Agriculture; The Institute for Bird Populations; University of Vermont; Utah State University; Ohio State University; Denali National Park and Preserve; and the Royal Saskatchewan Museum.

This paper is the result of the Western Bumble Bee Working Group, which is a group of experts on this species who came together to assemble the state of knowledge on this species in the United States and Canada, Tronstad says. The paper shows both what is known and knowledge gaps, specifically in the lack of samples and lack of knowledge about the species. Some prime examples of where spatial gaps in limited sampling exist include most of Alaska, northwestern Canada and the southwestern United States.

"Some areas in the U.S. have less bumblebee sampling in the past and present," Tronstad explains. "This could be for a variety of reasons such as lack of funding for such inventories, lack of bee expertise in that state, etc."

Using occupancy modeling, the probability of detecting the Western bumblebee decreased by 93 percent from 1998-2018, Tronstad says. Occupancy modeling is a complex model that estimates how often the Western bumblebee was detected from sampling events between 1998-2018 in the western United States.

"The data we assembled will be used by the U.S. Fish and Wildlife Service to inform its decision on whether or not to protect the Western bumblebee under the U.S. Endangered Species Act," Tronstad says. "At WYNDD, we collect data, and that data is used by managers. Our mission is to provide the most up-to-date data on which management decisions can be based."

Tronstad says there are several things that homeowners or landowners can do to help this species of bumblebee survive and thrive. These include:

• Plant flowers that bloom throughout the summer. Make sure these flowers have pollen and produce nectar, and are not strictly ornamental.
• Provide a water source for bees. Tronstad says she adds a piece of wood to all of her stock tanks so bees can safely get a drink.
• Provide nesting and overwintering habitat. Most bumblebees nest in the ground, so leaving patches of bare ground covered with litter or small mammal holes will benefit these bees. Be sure not to work these areas until after you see large bumblebees (queen bees) buzzing around in the spring, usually in April for much of Wyoming, so you can find out where they are nesting.

Tronstad says Bell's research will continue this summer, as Bell will investigate pathogens in the Rocky Mountains of Wyoming that affect Western bumblebees there. Max Packebush, a UW sophomore majoring in microbiology and molecular biology, from Littleton, Colo.; and Matt Green, a 2018 UW graduate from Camdenton, Mo., will assist Bell in her research. NASA and the Wyoming Research Scholars Program will fund Packebush to conduct his work. The U.S. Geological Survey and the U.S. Fish and Wildlife Service funded the research for this paper.

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Even when women outnumber men, gender bias persists among science undergrads

Is representation enough to improve gender diversity in science? A new study says there's more to the story

COLORADO STATE UNIVERSITY

 

Increasing gender diversity has been a long-sought goal across many of the sciences, and interventions and programs to attract more women into fields like physics and math often happen at the undergraduate level.

But is representation enough to improve gender diversity in science? In a new study, Colorado State University researchers say there's more to the story: They've found that even when undergraduate women outnumber men in science courses, women may still be experiencing gender biases from their peers.

The CSU team, combining expertise in gender psychology, instructional intervention and physical sciences, conducted a survey-based study among both physical and life science undergraduate courses at CSU, asking students how they perceived each other's abilities within those courses. Their results were published online June 25 in the journal PLOS ONE.

"The assumption has been that if you have the numbers, if you just increase the number of women, you won't have bias," said study co-author Meena Balgopal, professor in science education in the CSU Department of Biology. "But we find that's not the case."

For their study, the researchers focused on courses with a peer-to-peer learning component, such as group lab work, partner work or breakout sessions during lectures. They recruited instructors to administer surveys asking students how they perceived each other, with questions including: Are there any students in your class you are more likely to go to if you need help with the class? Thinking about your course, do any students stand out as particularly knowledgeable? Thinking about your course, who would you consider to be the best student(s) in the class? In total, they surveyed about 1,000 students.

Outnumbered and undervalued

Here's what the researchers found: In physical science classes - where women are more traditionally underrepresented - women were indeed outnumbered, and they had higher average GPAs, statistically higher course grades, and were 1.5 times more likely to earn an A or A-plus than men. However, the researchers found that both men and women presumed that the men in the class outperformed the women. In these classes, both women and men were less likely to select a woman as someone they would seek help from, find knowledgeable, or perceive as best in the class.

They saw a similar, albeit lesser effect in life science classes, where, in contrast to physical sciences, women tend to outnumber men, particularly in biology classes. In their study results, women both outnumbered and outperformed men in terms of GPA and statistically higher course grades. In these courses, men were equally likely to identify a woman or a man in all categories such as someone they'd seek help from, or find knowledgeable, or consider best in the class, and women identified women and men equally only in the category of "best in the class."

The researchers acknowledged limitations in their study: Although the surveys allowed participants to self-identify their own genders, when they referred to classmates, the researchers only recorded how students perceived the genders of their classmates. They also found that the surveys were not representative of the overall demographics of the courses; students who chose to answer the surveys were more likely to be STEM majors, white students, physical science students, and students with overall higher class grades and GPAs.

Also, while they wanted to perform intersectional analyses for women of color or gender minorities and how their peers perceived them, they did not have a large enough sample to draw meaningful conclusions from the data.

The researchers were inspired to conduct the study after a 2016 study by University of Washington researchers found a pro-male bias for ratings of students' abilities among male students in undergraduate biology courses. The CSU team wanted to see if the same effect could be found here, and their choice of methodology was intentionally similar.

Learning from the results

Balgopal said from an instructional design point of view, their results could reveal opportunities for more thoughtful attention to things like group work, and how instructors guide active learning.

"It would be really interesting to understand where these biases originate," said Balgopal, who, along with co-author A.M. Aramati Casper, is interested in pedagogical interventions that improve classroom learning outcomes.

For first author and gender psychologist Brittany Bloodhart, the most striking aspect of the study was not that gender bias persists among undergraduate STEM students, but that it's happening at the same time when women are consistently outperforming men in these fields, rather than being negatively affected in performance.

Among the research that shows girls and women are better in STEM, it's often discounted in various ways - girls work harder, are more attentive in class, study more, etc., which leads to better grades, Bloodhart said. When women perform worse than men on standardized tests, some claim that this reflects a difference in natural ability because they consider such tests the "real" measures of STEM ability. However, many studies support the view that standardized tests are also biased, and a poor predictor of actual STEM ability.

There is also a "variability hypothesis," which says that on average, girls and women have better outcomes in STEM than boys and men, but there is less variation in women's natural STEM talent compared to men.

"Our study refutes that variability hypothesis," Bloodhart said. "We didn't find any evidence that men were more variable than women or that they were more likely to get the top scores."

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The study's authors were Bloodhart, a former CSU postdoctoral researcher and now an assistant professor at Cal State San Bernardino; Balgopal, who is a professor of discipline-based education research in the biology department; Casper, a research scientist in engineering education; Laura Sample McMeeking; associate professor and director of the CSU STEM Center, and Emily Fischer, associate professor in the Department of Atmosphere Science.

The research team first came together under the CSU Office of the Vice President for Research Pre-Catalyst for Innovative Partnerships, or PRECIP program, which provides seed funding for interdisciplinary research partnerships across campus.

The study is titled "Outperforming yet undervalued: Undergraduate women in STEM."

Link to paper: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234685