Culture

An enzyme found in fat tissue in the centre of our bones helps control the production of new bone and fat cells, shows a study in mice published today in eLife.

The findings may help scientists better understand how the body maintains fat stores and bone production in response to changing conditions, such as during aging. They may also suggest new approaches to treating conditions that cause bone loss in older adults.

Fat cells, including those found in the bone marrow, are increasingly recognised as an important part of the body that helps regulate body weight, insulin sensitivity and bone mass. Fat tissue in the bone marrow expands as people age, or when they take certain diabetes medications, and during prolonged fasting.

"This expansion of bone marrow fat is strongly associated with bone loss in mice and humans," explains lead author Nicole Aaron, PhD, a graduate student at Columbia University Vagelos College of Physicians and Surgeons, New York, US. "But how these changes occur is still not well understood."

Aaron and her colleagues conducted a series of experiments to explore these processes further. They fed mice a calorie-restricted diet and found that this caused fat in their bone marrow to grow and increased the production of an enzyme called adipsin. The levels of adipsin were also high in mice treated with a diabetes drug called rosiglitazone, which increases bone marrow fat and decreases bone mass. Aging also caused similar changes in the animals.

The team then carried out similar experiments in mice that were genetically engineered to lack adipsin. They found that the animals were resistant to these changes, and had less bone marrow fat and stronger bones. Specifically, these experiments showed that adipsin appears to cause stem cells in the bone marrow to develop into fat cells rather than bone cells.

"Similarly, results from our human studies also revealed that the expansion of bone marrow fat with fasting was associated with a marked increase in adipsin and evidence of bone breakdown," says author Clifford Rosen, Director of Clinical and Translational Research at Maine Medical Center, Portland, Maine, US. "These findings may help explain the link between expansion of bone marrow fat tissue and bone strength, particularly during aging."

Drugs that block adipsin are currently being developed to treat people with a form of age-related vision loss. The current study also suggests these drugs might help increase bone mass in older people with diseases such as osteoporosis that cause progressive bone loss.

"There is the potential for these existing treatments to be repurposed to treat and prevent age-related skeletal disorders," concludes senior author Li Qiang, PhD, Assistant Professor of Pathology and Cell Biology at Columbia University Vagelos College of Physicians and Surgeons. "These treatments could also potentially be targeted to individuals who develop bone loss as a result of eating disorders, such as anorexia, or aging."

DETROIT - Jessica Damoiseaux, Ph.D., an associate professor with the Institute of Gerontology at Wayne State University, recently published the results of a three-year study of cognitive changes in older adults. The team followed 69 primarily African American females, ages 50 to 85, who complained that their cognitive ability was worsening though clinical assessments showed no impairments. Three magnetic resonance imaging scans (MRIs) at 18-month intervals showed significant changes in functional connectivity in two areas of the brain.

"An older adult's perceived cognitive decline could be an important precursor to dementia," Damoiseaux said. "Brain alterations that underlie the experience of decline could reflect the progression of incipient dementia and may emerge before cognitive assessment is sensitive enough to detect a deficit."

The resulting paper, "Longitudinal change in hippocampal and dorsal anterior insulae functional connectivity in subjective cognitive decline," appeared in the May 31 issue of Alzheimer's Research & Therapy. Damoiseaux conducted the study with graduate student Raymond Viviano, Ph.D., who is first author.

Subjective cognitive decline, defined as a perceived worsening of cognitive ability not noted on clinical assessment, may be an early indicator of dementia. Previous cross-sectional research has demonstrated aberrant brain functional connectivity in subjective cognitive decline, but longitudinal evaluation has been limited.

Viviano and Damoiseaux's three-year study found that persons reporting more subjective cognitive decline showed a larger decrease in connectivity between components of the default mode network and a larger increase in connectivity between salience and default mode network components. The functional connectivity changed in the absence of a change in cognitive performance.

Since these brain changes occurred without concomitant cognitive changes, they could indicate that brain changes underlie the perception of decline. These changes could be a sensitive marker for nascent dementia months or years before assessments detect any cognitive deficit.

(Boston)--Lung cancer remains the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for 80-85 percent cases of lung cancer and when diagnosed early, has a five-year survival rate of 50-80 percent. Black patients have lower overall incidence of NSCLC than white patients, but are more likely to be diagnosed at later stages. They also are less likely to receive surgery for early-stage cancer.

Now a new study from Boston University School of Medicine (BUSM) highlights the impact that structural racism and residential segregation has on NSCLC outcomes.

The researchers analyzed patient data from the Surveillance, Epidemiology and End Results Program--a database of Black and white patients diagnosed with NSCLC from 2004-2016 in the 100 most populous counties. They found that Black lung cancer patients living in the most segregated U.S. counties were 49 percent more likely to be diagnosed at an advanced stage, compared to those living in the least segregated counties. Among those with early-stage lung cancer, Black patients in highly segregated areas were 47 percent less likely to receive surgery. Segregation was used in this study as a proxy for historic housing discrimination and the enduring structural racism that has resulted from it.

"Our study suggests that Black patients have a greater likelihood of presenting at advanced stage than their white counterparts, a disparity that disappears at low levels of segregation. Similarly, higher residential segregation is associated with increased risk of advanced stage for Black patients but not white. This may be due to factors such as lack of access to routine medical care and lack of routine screenings for Black patients in segregated areas," explained corresponding author Kei Suzuki, MD, assistant professor of surgery at BUSM.

According to the researchers, fewer Black patients are considered eligible for lung cancer screening criteria and also are less likely to complete screening. For many diseases including lung cancer, Black patients of lower socioeconomic status tend to present to their physician only when symptomatic, aligning with a later stage of disease.

"Broadly, urban policy can serve to address the structural factors leading to these outcomes. Most immediately, clinicians and healthcare institutions can focus screening efforts in these minoritized communities and realize the racialized socioeconomic implications that may impact access to care, which may delay definitive care," adds Suzuki, who also is a thoracic surgeon at Boston Medical Center.

These findings appear online in the journal Annals of Thoracic Surgery and was presented virtually as an oral presentation at the Society of Thoracic Surgery 2021 Annual Meeting on Jan. 31, 2021.

PROVIDENCE, R.I. [Brown University] -- What motivated Americans to wear masks and stay socially distanced (or not) at the beginning of the COVID-19 pandemic? More often than not, it was partisanship, rather than perceived or actual health risk, that drove their behavior, according to a new study co-authored by researchers at Brown University.

By analyzing the results of two online surveys of more than 1,100 adults in total, Mae Fullerton, a Class of 2021 Brown graduate, and Steven Sloman, a professor of cognitive, linguistic and psychological sciences, found that in spring and fall 2020, political partisanship was the strongest predictor of whether someone would wear a mask or practice social distancing to stem the spread of novel coronavirus.

Those who identified as liberal or moderate overwhelmingly said they wore masks and practiced social distancing, even when they believed their risk of contracting the novel coronavirus was minimal. Those who identified as conservative were much less likely to say they always wore a mask or socially distanced, even when they believed they were at high risk of contracting the virus and falling ill with COVID-19.

The findings were published on Friday, June 18, in the Journal of Health Psychology. Sloman said the results show that many Americans tend to remain fiercely loyal to their like-minded communities, even in situations where their health is on the line.

"It turns out that life is not the most important thing to people," Sloman said. "Many people are putting their partisan leanings ahead of their self-interest. We're willing to outsource our thinking to other people in our communities, even when our lives are at stake."

At the start of the study, Fullerton and Sloman predicted that respondents' risk of becoming sick with COVID-19, or at least their perception of risk, would be the primary factor guiding their mask uptake and social distancing. Instead, they found almost no correlation between behavior and risk -- whether perceived or real. Among survey respondents who considered themselves to be at high risk of contracting COVID-19, 59% reported they had limited their encounters to two or fewer people in the prior week. Meanwhile, among those who perceived they were at low risk of contracting COVID-19, 58% reported the same. In other words, people who felt they were in a high-risk group didn't seem any more likely to practice social distancing than their lower-risk peers.

The same was true of mask-wearing: 62% of those who reported that they were elderly or had no health insurance said they always wore masks when they anticipated coming within 6 feet of others, compared to 61% of those who were younger and had health insurance.

They found, in fact, that the biggest predictor of whether someone was likely to wear a mask and practice social distancing wasn't risk but political partisanship. Among those who identified as liberal or moderate, 66% reported that they always wore masks when they anticipated coming within 6 feet of others, compared to 45% of those who identified as conservative. And while 95% of self-identified liberals and moderates said they thought it was important to wear a mask to prevent the spread of the virus, only 74% of self-identified conservatives said they believed the same. Conservative-leaning respondents were also significantly less likely to practice social distancing (31%) than their moderate or liberal counterparts (49%).

Crucially, the researchers also found a high correlation between compliance with stay-at-home orders -- which were in effect for 95% of Americans at the time of the survey -- and peer agreement. Among those who said they believed it was "extremely important" to comply with orders to stay socially distanced, 86% said their peer group reportedly held similar views.

Fullerton said the findings confirm something behavioral scientists have known for a long time: that most people's health decisions have more to do with the behaviors of people around them than with scientific evidence. Studies have shown, for example, that people are more likely to quit smoking if someone close to them has quit smoking recently, and that the amount of food a person eats on Thanksgiving is often driven by how much others at the table are eating.

"This study supports other findings that preventive behavior is strongly influenced by social norms," Fullerton said. "People clearly are more motivated by their politics, their culture and their peers than by their likelihood of catching the virus and possibly suffering from terrible side effects. This suggests that communicating the risks of not wearing a mask and not staying socially distanced might not be the most effective way to stop the spread of a virus."

Both Fullerton and Sloman said the reason many conservative Americans didn't wear masks and socially distance may be in part because the people they trusted most -- people who include, according to past studies, family doctors, local television hosts and church leaders -- weren't wearing masks or staying distanced either. Getting buy-in from influential community figures, then, may be key in ensuring more unified compliance with public health recommendations in the future. And that might start with bringing more widely known trusted personalities on board, from television hosts to beloved celebrities to leading federal lawmakers.

"In some cases, communicating the risks via government-appointed experts might not be as effective as communicating the risks via political leaders people know and respect," Fullerton said. "That's a good lesson we can remember the next time we're facing a public health crisis."

Ultimately, both Fullerton and Sloman said, the key to keeping people safe and healthy is understanding their most sacred values. For example, Sloman said, many libertarians didn't refuse to wear masks just because some of their local politicians vocally opposed masking; some perhaps did it because individual freedom is their most sacred value, and they believed mask mandates infringed on that freedom. Many older people at high risk of severe COVID-19 due to other health challenges, Fullerton said, may have chosen not to practice social distancing because, to them, the costs -- not meeting a new grandchild, for example -- outweighed the benefits -- potentially living a few years longer.

"Americans can't be boiled down to figureheads and followers or believers and non-believers," Sloman said. "Getting into people's heads is complicated, but it matters."

Other study contributors were Nathaniel Rabb, a project manager at the Policy Lab at Brown; Sahit Mamidipaka, a student at Northview High School in Georgia; and Lyle Ungar, a professor of computer and information science at the University of Pennsylvania. The research was supported in part by a donation from Adobe.

New research published in the Journal of Medicinal Food suggests eating prunes each day can improve risk factors for cardiovascular disease (CVD) including raising antioxidant capacity and reducing inflammation among healthy, postmenopausal women.

Cardiovascular disease is the number one cause of death worldwide posing a significant public health challenge.

The research led by San Diego State University reveals that prunes can positively affect heart disease risk.

"When you look at our prior research and the research of others combined with this new data, you'll see consistent evidence that eating prunes can promote health," said lead researcher Shirin Hooshmand, Ph.D., RD, Professor at the School of Exercise and Nutritional Sciences at San Diego State University.

In this randomized, controlled study, researchers found that eating 50 grams of prunes (about 5-6 prunes) each day for just 6 months resulted in improved CVD risk biomarkers - including raising the body's "good" cholesterol, known as HDL, and lowering the ratio of total cholesterol to HDL.

Eating prunes daily also promoted higher antioxidant capacity and lowered levels of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha associated with CVD risk. Notably, body mass index and weight of the study participants were maintained during the trial despite adding prunes to the usual diet.

Researchers recruited 48 healthy, postmenopausal women who were divided into three groups - a control group who ate no prunes, and two treatment groups who consumed either 50 grams or 100 grams of prunes daily, throughout the six-month study. All other aspects of the women's diets and lifestyles remained similar to before the study. Various biomarkers of CVD risk were collected at the beginning and conclusion of the study to determine if there were any improvements in those biomarkers among those who consumed prunes. Interestingly, there were some similar positive results among those who ate 50 grams of prunes and those consuming 100 grams - suggesting that adding 5-6 prunes or more into the daily diet may have a positive effect on CVD risk.

"Reducing chronic inflammation and increasing antioxidant capacity in the body is associated with lower risk of CVD, along with many other diseases," said Mark Kern, Ph.D., RD, CSSD, Professor of Nutrition at the School of Exercise and Nutritional Sciences at San Diego State University. "Not only does this study show that prunes may be a good way to reduce inflammation and increase antioxidant capacity, it also suggests that eating prunes every day may improve cholesterol levels in postmenopausal women."

While the precise mechanisms and specific compounds that contribute to these beneficial effects have yet to be determined, naturally occurring antioxidant-powered phenolic compounds, fiber and other nutrients are thought to play a role. This study demonstrates that prunes may be a promising and convenient addition to the diet to reduce CVD risk and inflammation, while also improving antioxidant capacity.

The study adds to a growing body of evidence about the overall health and nutrition benefits of prunes, including bone health. Previous clinical research demonstrates a favorable bone response to prunes among postmenopausal women. Most recently, researchers reported that total bone mineral density increased in a postmenopausal woman with osteopenia after she consumed 50 grams of prunes daily for 16 months. This case study was published in the Bone Reports in May of this year.

Almost all cells in our body contain a nucleus: a somewhat spherical structure that is separated from the rest of the cell by a membrane. Each nucleus contains all the genetic information of the human being. So it serves as a kind of library - but one with strict requirements: If the cell needs the building instructions for a protein, it won't simply borrow the original information. Instead, a transcript of it is made in the nucleus.

The machinery required for this is very complex, not least because the transcripts are not simple copies. In addition to essential information, genes also contain numerous passages of meaningless "garbage". They are removed when the transcript is made. Biologists call this editorial revision "splicing".

"An important role in splicing is played by the SMN complex, a 'molecular machine' consisting of nine different proteins," explains Prof. Dr. Oliver Gruss from the Institute of Genetics at the University of Bonn, who is also a member of the university's transdisciplinary research area "Life and Health". "Interestingly, these machines are not evenly distributed in the nucleus. Instead, they accumulate at specific sites called Cajal bodies." However, there are no transport mechanisms in the cell nucleus that bring the SMN complexes to Cajal bodies. Instead, the SMN proteins themselves have certain properties that are responsible for their aggregation. Which ones these are, was unclear until now.

SMN complexes carry an unusually large number of phosphate groups

SMN complexes have a prominent feature: They carry an unusually large number of phosphate groups, which are small molecular residues with a phosphorus atom in the center. "We suspected that this phosphorylation promotes their mass clustering into Cajal bodies," explains Dr. Maximilian Schilling from the research group around Oliver Gruss.

Phosphate groups are not part of the actual blueprint of a protein - they are added later and can also be removed again. This is often how the cell regulates the activity of the respective protein. The phosphate group is attached in this process by certain enzymes, the kinases. "We have now inhibited each of the hundreds of human kinases individually and looked at how that affects the formation of Cajal bodies," Schilling says.

In this way, they encountered a network of kinases, which, when inhibited, caused the Cajal bodies to largely disappear. Further analyses showed that in the absence of these kinases, phosphorylation of SMN complexes at specific sites decreased sharply. This then causes the flash mobs in the nucleus to cease - the Cajal bodies disintegrate. The finding is particularly interesting because the kinases identified not only regulate splicing, but also the translation of the gene transcripts edited in this way into proteins. These are therefore enzymes that are crucial for various steps in this vital process.

Mutation causes severe disease

The SMN complex is known to human geneticists not only for its role in splicing: Individual mutations in its blueprint result in a serious disease, spinal muscular atrophy, in those affected. One in about 6,000 newborns is born with this genetic defect. Treatment is extremely expensive; the cost per patient runs into millions. "Some of the gene defects that cause spinal muscular atrophy are near the phosphorylation sites of the SMN complex," explains Gruss. "Affected individuals may therefore have impaired attachment of phosphate groups to these sites, and consequently also impaired formation of Cajal bodies. We suspect that this causes splicing to be impaired, which subsequently results in the disease symptoms."

The kinases identified may therefore also be suitable as a starting point for new therapies. Preliminary results from mouse model cells for human spinal muscular atrophy show that agents that increase kinase activity also improve Cajal body formation. "It is completely unclear whether these agents also ameliorate pathological changes in a complex organism," cautions Gruss against inflated expectations. "That new treatment options will eventually emerge from this is therefore still speculation at this stage."

The most comprehensive molecular study to date of the brains of people who died of COVID-19 turned up unmistakable signs of inflammation and impaired brain circuits.

Investigators at the Stanford School of Medicine and Saarland University in Germany report that what they saw looks a lot like what's observed in the brains of people who died of neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease.

The findings may help explain why many COVID-19 patients report neurological problems. These complaints increase with the severity of infection with SARS-CoV-2, the virus that causes COVID-19. And they can persist as an aspect of "long COVID," a long-lasting disorder that sometimes arises following infection. About one-third of individuals hospitalized for COVID-19 report symptoms of fuzzy thinking, forgetfulness, difficulty concentrating and depression, said Tony Wyss-Coray, PhD, professor of neurology and neurological sciences at Stanford.

Yet the researchers couldn't find any signs of SARS-CoV-2 in brain tissue they obtained from eight individuals who died of the disease. Brain samples from 14 people who died of other causes were used as controls for the study.

"The brains of patients who died from severe COVID-19 showed profound molecular markers of inflammation, even though those patients didn't have any reported clinical signs of neurological impairment," said Wyss-Coray, who is the D. H. Chen Professor II.

Scientists disagree about whether SARS-CoV-2 is present in COVID-19 patients' brains. "We used the same tools they've used -- as well as other, more definitive ones -- and really looked hard for the virus's presence," he said. "And we couldn't find it."

A paper describing the study will be published June 21 in Nature. Wyss-Coray shares senior authorship with Andreas Keller, PhD, chair of clinical bioinformatics at Saarland University. The lead authors are Andrew Yang, PhD, a postdoctoral scholar in Wyss-Coray's group, and Fabian Kern, a graduate student in Keller's group.

Blood-brain barrier

The blood-brain barrier, which consists in part of blood-vessel cells that are tightly stitched together and blob-like abutments created by brain cells' projections squishing up against the vessels, has until recently been thought to be exquisitely selective in granting access to cells and molecules produced outside the brain.

But previous work by Wyss-Coray's group and by others has shown that bloodborne factors outside the brain can signal through the blood-brain barrier to ignite inflammatory responses inside the brain. This could explain why, as Wyss-Coray and his colleagues have discovered, factors in young mice's blood can rejuvenate older mice's cognitive performance, whereas blood from old mice can detrimentally affect their younger peers' mental ability.

On hearing reports of enduring neurological symptoms among some COVID-19 patients, Wyss-Coray became interested in how SARS-CoV-2 infection might cause such problems, which resemble those that occur due to aging as well as to various neurodegenerative diseases. Having also seen conflicting reports of the virus's presence in brain tissue in other studies, he wanted to know whether the virus does indeed penetrate the brain.

Brain tissue from COVID-19 patients is hard to find, Wyss-Coray said. Neuropathologists are reluctant to take the steps required to excise it because of potential exposure to SARS-CoV-2 and because regulations often prohibit such procedures to prevent viral transmission. But Keller, who has worked in the Wyss-Coray lab as a visiting professor at Stanford, was able to access COVID-19 brain-tissue samples from autopsies conducted at the hospital that's associated with Saarland University.

Using an approach called single-cell RNA sequencing, the scientists logged the activation levels of thousands of genes in each of 65,309 individual cells taken from brain-tissue samples from the COVID-19 patients and the controls.

In neurons of the cerebral cortex, signs of distress

Activation levels of hundreds of genes in all major cell types in the brain differed in the COVID-19 patients' brains versus the control group's brains. Many of these genes are associated with inflammatory processes.

There also were signs of distress in neurons in the cerebral cortex, the brain region that plays a key role in decision-making, memory and mathematical reasoning. These neurons, which are mostly of two types -- excitatory and inhibitory -- form complex logic circuits that perform those higher brain functions.

The outermost layers of the cerebral cortex of patients who died of COVID-19 showed molecular changes suggesting suppressed signaling by excitatory neurons, along with heightened signaling by inhibitory neurons, which act like brakes on excitatory neurons. This kind of signaling imbalance has been associated with cognitive deficits and neurodegenerative conditions such as Alzheimer's disease.

An additional finding was that peripheral immune cells called T cells, immune cells that prowl for pathogens, were significantly more abundant in brain tissue from dead COVID-19 patients. In healthy brains, these immune cells are few and far between.

"Viral infection appears to trigger inflammatory responses throughout the body that may cause inflammatory signaling across the blood-brain barrier, which in turn could trip off neuroinflammation in the brain," Wyss-Coray said.

"It's likely that many COVID-19 patients, especially those reporting or exhibiting neurological problems or those who are hospitalized, have these neuroinflammatory markers we saw in the people we looked at who had died from the disease," he added. It may be possible to find out by analyzing these patients' cerebrospinal fluid, whose contents to some extent mirror those of the living brain.

"Our findings may help explain the brain fog, fatigue, and other neurological and psychiatric symptoms of long COVID," he said.

If only it were as simple as finding more grassland for an antelope.

The story of efforts to conserve the endangered oribi in South Africa represent a diaspora of issues as varied as the people who live there. On its surface, like many threatened species, you have conflict between a need for habitat and private landownership.

But dig a little deeper and you'll uncover a seedy underbelly of political corruption, gambling, struggles over land, and racial tensions. No matter how much success is made through more traditional conservation efforts, says a new study by a University of Georgia researcher, the species will continue to be threatened until the human conflicts can be mitigated or resolved.

"It's an interesting case study because the oribi is so dependent on habitat that's on private lands," said Elizabeth Pienaar, an associate professor at the University of Georgia Warnell School of Forestry and Natural Resources. "But it's also a species that has gotten trapped in much larger political and social conflicts. ... This is the dark side of conservation. We can say, look, the species needs X, Y and Z to survive and recover, but in cases like this, conservation efforts are mired in a complex political, social and historical framework. These much larger issues remain unresolved."

For the oribi (OR-uh-bee), said Pienaar, solutions start with access to native grassland that has rapidly disappeared on the South African landscape. This means education for farmers who own land where oribi graze, but quickly scales up to include enforcement to prevent illegal poaching and even de-escalation of racial tensions during a time when land reform (the return of white-owned farmland to Black residents) is causing considerable conflict.

Meeting with farmers can help

Threatened or endangered species in other parts of the world face different issues, but the success of their conservation is likely tied up in socio-political webs, said Pienaar. The study, published recently in the journal Endangered Species Research, is the first of two parts that aim to provide insights for conservation agencies and organizations navigating similar waters. It was co-authored by master's student Adrienne Louw and professor Adrian Shrader of the University of Pretoria.

Often, landowners want to conserve species because it's part of their cultural heritage or because they care about wildlife and land stewardship. But a misunderstanding of the animals' needs, a lack of outreach from government agencies due to budget constraints and a general mistrust of the government stemming from years of political conflict and corruption work against even the most basic education and outreach efforts.

"The farmers don't want to be told what to do, but you can give them advice and they will implement it as they see fit," added Pienaar. "That could be one of the most impactful things: somebody who is seen as a neutral third party going out there and just meeting with them. And the farmer will try a few things and if it doesn't affect their profit margin, they'll do it. That's what they're looking for--some advice."

Separately, said Pienaar, local communities require employment and food security to reduce the need for illegal hunting. Poverty is a serious problem in South Africa, where 65.4% of the population lives below the poverty line, and infrastructure and service delivery in rural areas is poor. Improved economic and social security, including options to purchase meat at affordable prices, may reduce conflicts and poaching pressures. But poverty extends beyond financial insecurity, she added. Poverty is a lack of voice, an inability to define one's future.

In addition, communities resent the loss of their traditional hunting rights under neocolonial management of wildlife. Poaching becomes a means of political protest against landowners and the government, particularly if the government is perceived to have failed communities by not providing needed services.

Underground gambling rings exacerbate the issue

These solutions only address a portion of the problem, though. Improving access to habitat and community services won't stop a serious threat to oribi: illegal hunting at night, with trained greyhounds and hunting dogs, which sustains underground gambling rings.

Called "taxi hunting," greyhound owners--who have the income or wealth to purchase these expensive hunting dogs--arrive at the edge of a farm under cover of night. The dogs, trained to run and capture the small antelopes, are fast and silent. Whoever's dog catches the oribi wins the pot of money, as does the dog that kills the most antelope.

If a farm owner can't stop the taxi hunt before the dogs are released, they are almost powerless to prevent it. It's illegal for them to shoot a hunting dog that is with its handler, even if it's on the farmer's land. And if they do, there could be retribution in the form of arson, property damage or arrest of the farmer for shooting the dogs.

Then, add race into the mix: Farm owners are white, while the taxi hunters are black. "So, the farmers feel threatened because not only is there a push for land reform, but they are dealing with increased rural crime while also trying to prevent poaching by people who are not at risk of poverty," said Pienaar. "It's not just about protecting the oribi. It's about protecting their family's safety, their property and their heritage."

And then there's the oribi, stuck in the middle.

"But it's not just the oribi. The oribi is a case study that is consistent with other species at risk, like rhinos and pangolins," said Pienaar. "Biologists and ecologists are fantastic in terms of what these species need in terms of habitat or maintaining viable populations. But if you cannot resolve larger socio-political conflicts, the animal is still at risk. Most conservation issues, that I'm aware of, are about people and the pressures they face."

Legend has it that Marie Antoinette's hair turned gray overnight just before her beheading in 1791.

Though the legend is inaccurate--hair that has already grown out of the follicle does not change color--a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons is the first to offer quantitative evidence linking psychological stress to graying hair in people.

And while it may seem intuitive that stress can accelerate graying, the researchers were surprised to discover that hair color can be restored when stress is eliminated, a finding that contrasts with a recent study in mice that suggested that stressed-induced gray hairs are permanent.

The study, published June 22 in eLife, has broader significance than confirming age-old speculation about the effects of stress on hair color, says the study's senior author Martin Picard, PhD(link is external and opens in a new window), associate professor of behavioral medicine (in psychiatry and neurology) at Columbia University Vagelos College of Physicians and Surgeons.

"Understanding the mechanisms that allow 'old' gray hairs to return to their 'young' pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress," Picard says.

"Our data add to a growing body of evidence demonstrating that human aging is not a linear, fixed biological process but may, at least in part, be halted or even temporarily reversed."

Studying hair as an avenue to investigate aging

"Just as the rings in a tree trunk hold information about past decades in the life of a tree, our hair contains information about our biological history," Picard says. "When hairs are still under the skin as follicles, they are subject to the influence of stress hormones and other things happening in our mind and body. Once hairs grow out of the scalp, they harden and permanently crystallize these exposures into a stable form."

Though people have long believed that psychological stress can accelerate gray hair, scientists have debated the connection due to the lack of sensitive methods that can precisely correlate times of stress with hair pigmentation at a single-follicle level.

Splitting hairs to document hair pigmentation
Ayelet Rosenberg, first author on the study and a student in Picard's laboratory, developed a new method for capturing highly detailed images of tiny slices of human hairs to quantify the extent of pigment loss (graying) in each of those slices. Each slice, about 1/20th of a millimeter wide, represents about an hour of hair growth.

"If you use your eyes to look at a hair, it will seem like it's the same color throughout unless there is a major transition," Picard says. "Under a high-resolution scanner, you see small, subtle variations in color, and that's what we're measuring."

The researchers analyzed individual hairs from 14 volunteers. The results were compared with each volunteer's stress diary, in which individuals were asked to review their calendars and rate each week's level of stress.

The investigators immediately noticed that some gray hairs naturally regain their original color, which had never been quantitatively documented, Picard says.

When hairs were aligned with stress diaries by Shannon Rausser, second author on the paper and a student in Picard's laboratory, striking associations between stress and hair graying were revealed and, in some cases, a reversal of graying with the lifting of stress.

"There was one individual who went on vacation, and five hairs on that person's head reverted back to dark during the vacation, synchronized in time," Picard says.

Blame the mind-mitochondria connection

To better understand how stress causes gray hair, the researchers also measured levels of thousands of proteins in the hairs and how protein levels changed over the length of each hair.

Changes in 300 proteins occurred when hair color changed, and the researchers developed a mathematical model that suggests stress-induced changes in mitochondria may explain how stress turns hair gray.

"We often hear that the mitochondria are the powerhouses of the cell, but that's not the only role they play," Picard says. "Mitochondria are actually like little antennas inside the cell that respond to a number of different signals, including psychological stress."

The mitochondria connection between stress and hair color differs from that discovered in a recent study of mice, which found that stress-induced graying was caused by an irreversible loss of stem cells in the hair follicle.

"Our data show that graying is reversible in people, which implicates a different mechanism," says co-author Ralf Paus, PhD, professor of dermatology at the University of Miami Miller School of Medicine. "Mice have very different hair follicle biology, and this may be an instance where findings in mice don't translate well to people."

Hair re-pigmentation only possible for some

Reducing stress in your life is a good goal, but it won't necessarily turn your hair to a normal color.

"Based on our mathematical modeling, we think hair needs to reach a threshold before it turns gray," Picard says. "In middle age, when the hair is near that threshold because of biological age and other factors, stress will push it over the threshold and it transitions to gray.

"But we don't think that reducing stress in a 70-year-old who's been gray for years will darken their hair or increasing stress in a 10-year-old will be enough to tip their hair over the gray threshold."

Looking for better ways to treat patients with esophageal cancer, University of Colorado Cancer Center member Martin McCarter, MD, is investigating whether a new treatment sequence will result in better outcomes.

As they await the results of a group of clinical trials -- including one at the CU Cancer Center -- McCarter and other University of Colorado researchers (led by surgery resident Bobby Torphy, MD, PhD) looked at data from the National Cancer Database to see if they could identify other patients who have undergone the new sequence, and what the outcomes for those patients were. The group published a paper in the Annals of Surgical Oncology in April detailing their findings.

We sat down with McCarter, professor of surgical oncology at the University of Colorado School of Medicine, to talk about the data and the next steps in his research.

Q: What is the motivation behind these esophageal cancer clinical trials and your review of the National Cancer Database data?

A: The big picture is that outcomes for esophageal cancer are still very poor, even in patients who can undergo an operation, and we're constantly looking for ways to improve that. The current standard of care is a combination of chemotherapy and radiation given together, followed by surgery. Treatment sequencing has evolved in other areas, particularly rectal cancer, in what is referred to as a "total neoadjuvant approach," in which patients get prolonged chemotherapy, followed by radiation therapy, then followed by surgery. They've been doing that in rectal cancer, and that has resulted in some improvements in cancer outcomes. The data for this approach in esophageal cancer is limited but in our minds it would make sense to try it. There are a couple of early-phase trials looking at that sequence, to see if it can help improve things for patients with esophageal cancer-- including an investigator-initiated study here at CU led by CU Cancer Center member Jeffrey Olsen, MD. It's going to take a few years for those trials to mature, but in the meantime, we wanted to look at a large national database to see if we could determine if other people have been using this sequence. We used the National Cancer Database to ask that question, and we found about 5% of patients were getting this prolonged sequence. Based on the data, it appears that those patients actually have a better survival rate than patients who just get chemo and radiation prior to surgery.

Q: How does the sequence you're proposing differ from the current standard of care?

A: The current standard is that patients get five weeks of radiation, and they get a little bit of chemotherapy at the beginning and in the middle of that radiation therapy. Then they wait six or eight weeks, then they have surgery. This new approach adds chemotherapy for two to three months first, then transitions to chemo and radiation therapy, and then on to the surgery. The thought behind it is that in general, people don't die from the local cancer; they die from cancer that has spread microscopically before we even see it. If we treat them aggressively with chemotherapy first, then we are attacking the microscopic disease first and then following that by trying to control the local disease with radiation and ultimately with surgery as well.

Q: Is it easy to determine from the data if someone underwent this treatment sequence?

A: It is not. We had to make some assumptions and do some pretty significant modeling to answer the question. These determinations were based on dates within the database and the fact that the patients got pure chemo, followed by pure radiation, and then they got surgery. They had to have all three of those things, and then the dates had to be separated enough such that they weren't getting the standard chemo and radiation followed by surgery. The problem is we really don't know, just from the data, why they got chemo first. Maybe doctors were making some of the same assumptions we did, which is that we ought to hit them hard first, but they were doing that without a whole lot of guidance or trials.

Q: Could using this approach eliminate the need for surgery in esophageal cancer patients?

A: That's certainly the direction things have headed in rectal cancer. People are a little less likely to avoid surgery in esophageal cancer just because the surveillance techniques are pretty inadequate. We know that a number of patients probably have a complete response to the chemo and radiation and may not need an operation; the problem is we can't really predict who those patients are, even with our best diagnostic scopes and scans.

Q: What's the next step in this research?

A: The next step is awaiting the formal results from the current trial. As a phase 2 trial, it's evaluating the potential toxicity of using this sequencing, but also evaluating the responses. Do we see better pathologic responses, and in the long term are there patients who don't need the esophageal surgery, or for those who do get the esophageal surgery, do we see improvements in overall long-term five-year survivorship? This data study was to set the table and see if we can learn any more about this sequencing strategy because we have very little to go on right now.

Managing type 2 diabetes typically involves losing weight, exercise and medication, but new research by Dr. Makoto Fukuda and colleagues at Baylor College of Medicine and other institutions suggests that there may be other ways to control the condition through the brain. The researchers have discovered a mechanism in a small area of the brain that regulates whole-body glucose balance without affecting body weight, which suggests the possibility that modulating the mechanism might help keep blood sugar levels in a healthy range.

"A growing body of evidence strongly suggests that the brain is a promising yet unrealized therapeutic target for type 2 diabetes, as it has been shown that it can regulate glucose metabolism," said Fukuda, assistant professor of pediatrics-nutrition at Baylor. "To further materialize this concept, it is of great interest to identify potentially druggable molecular targets mediating the brain's antidiabetic effects."

Regulating whole-body glucose balance from the brain

Research has shown that within the hypothalamic region of the brain, a small area known as the ventromedial nucleus of the hypothalamus (VMH) contains glucose-sensing neurons and regulates glucose metabolism in peripheral tissues.

"VMH neurons are thought to be crucial mediators of the neural glucoregulatory mechanism," Fukuda said. "However, the signaling mechanisms within VMH neurons that mediate whole-body sugar control remain elusive. In this study, we identified a molecular pathway in the VMH that mediates whole-body glucose balance and involves Rap1, an enzyme known to mediate overnutrition-associated disorders."

The researchers worked with a diabetes model of high-fat diet-induced obesity in mice, in which they either activated or eliminated Rap1 specifically in VMH neurons by using either genetic or pharmacological techniques.

They discovered that activation of Rap1 in the hypothalamus exaggerated the high blood sugar levels or hyperglycemia in the diet-induced obesity mouse model. In contrast, genetic loss of hypothalamic Rap1 decreased hyperglycemia in dietary obesity.

"Interestingly, the changes in glucose levels were observed without alterations in body weight, suggesting a primary role of Rap1 in glucoregulatory function," Fukuda said. "Our findings that Rap1 activity can be regulated via pharmacological intervention provide proof-of-concept for the potential of targeting Rap1 signaling within the brain to improve glucose imbalance and induce antidiabetic effects."

While having no effect on body weight regardless of sex, diet and age, Rap1 deficiency in VMH neurons markedly lowered blood glucose and insulin levels and improved glucose and insulin tolerance.

Taken together, the data suggest that hypothalamic Rap1 is a molecular pathway for the control of glucose metabolism and mediates high-fat diet-induced glucose imbalance, thereby making it a potential target for therapeutics.

"If we gain weight, blood glucose seems to be disturbed. That's why obese people may have diabetes," Fukuda said. "But in this mouse model we discovered that by modulating the activity of Rap1 in a small brain area we could regulate whole-body glucose metabolism without body weight change. There is still much work to do, but our findings suggest that maybe in the future obese people with diabetes could lower blood sugar levels by manipulating this mechanism of Rap1 in the brain without having to lose weight."

Find all the details of this study in JCI Insight.

BINGHAMTON, N.Y. -- Political institutions such as the timing of elections and presidentialism had a larger influence on COVID-19 strategies than the institutions organizing national healthcare, according to a research team led by a professor at Binghamton University, State University of New York.

Olga Shvetsova, a political scientist at Binghamton University, and fellow researchers explored policy strategies on public health by the federal incumbents worldwide. Specifically, they looked at whether national incumbents led the charge as the pandemic unfolded or waited for the states (provinces) to enact the measures.

Multiple levels of government contributed to the COVID-19 policy response in federations and non-federations both. Decentralization in a country did not diminish the stringency of the overall government pandemic response. Early on, policies in federations were more stringent than those in non-federations.

"Our evidence shows that, by and large, the coordination among the federal and subnational governments in federations did not fail, and the incumbents in federations collectively managed to provide at least as much protection to their citizens as the incumbents in unitary states, though the balance of federal versus subnational policy contributions varied," said Shvetsova.

Still, different federations responded in different ways. The researchers discovered a large variation across federations, so significant that they believe it deserves an institutional explanation.

Specifically, scholars explored how "political incumbents' strategies in mitigating . . the COVID-19 pandemic were influenced in federations by the constitutional/electoral and health-related political institutions.

"We developed conjectures about the institutional variables conducive to more stringent public health policies and about institutional determinants of greater involvement of the federal government in pandemic public health policies," Shvetsova said.

They found that political institutional variables influenced COVID-19 federal strategies, even to a greater extent than countries' healthcare institutions.

"Diffusion of executive accountability, such as in a multiparty executive and with more fragmented parliaments, possibly increased the willingness to engage in more stringent policy response to the virus," Shvetsova said.

The research found that presidential executives avoided making stringent policies if the next election date was closer. Also public health policies of Left national executives were on average more stringent.

The paper, "Federal Institutions and Strategic Policy Responses to COVID-19 Pandemic," was peer reviewed and is in the process of being published in Frontiers in Political Science - Elections and Representation.

If you listen to songbirds, you will recognize repeated melodies or phrases. Each phrase is made up of distinct sounds, strung together. A study from researchers at McGill University has found that the song phrases of many songbird species follow patterns that are similar to those used in human speech. At least in some respects.

The songbirds the researchers studied, like humans---no matter what language they speak---tend to use shorter elements (whether these are words or sounds) when they are putting together longer phrases. Linguists speculate that this pattern, known as Menzerath's Law, may make communication more efficient by making things easier to understand or say.

But the McGill team suggest that, at least in songbirds, physical factors such as muscle fatigue and limited lung capacities may also play a role. They also speculate that similar factors could contribute to seeing Menzerath's Law in humans.

Do physical elements play a role in songbird (and human) vocal patterns?

"Although we see Menzerath's Law in all the songbird species we looked at, and others have seen it among primates and penguins, we aren't sure this necessarily reflects enhanced communication efficiency in non-human animals," said Jon Sakata, a professor in McGill's Biology Department and the senior author on the paper that was recently published in Current Biology. "It is possible that these patterns of communication that we saw in songbirds are caused by physical predispositions and constraints."

Interestingly, Sakata also notes that the brain mechanisms regulating breathing and vocal muscles seem to be organized in similar ways in birds and humans.

Even song from untutored birds follow similar patterns

The idea that physical elements may play a role in these song patterns is supported by the fact that when the researchers compared the song patterns of birds that had been typically reared and tutored by their parents with those that had not been taught to sing by their parents (untutored birds), they found the same patterns.

"The individual units of sound made by untutored birds were very different from those made by the typically raised birds," said Logan James, the first author on the paper and a former PhD student in Professor Sakata's lab, now a post-doctoral Fellow at the University of Texas at Austin. "However, the 'rules' by which they organize these aberrant elements is indistinguishable from typically raised birds. These results suggest that physical predispositions or limitations may play a role in producing these song patterns."

Further work will need to be done in this area to see whether this is indeed the case. For example, work linking species variation in the strength of Menzerath's Law to species variation in the biomechanics of vocal production would be a useful next step.

RIVERSIDE, Calif. -- Communities surrounding the Salton Sea, the inland body of water straddling California's Riverside and Imperial counties, show high rates of asthma due, possibly, to high aerosol dust levels resulting from the sea shrinking over time.

Scientists suspect, however, the Salton Sea plays an additional role in pulmonary health.

A University of California, Riverside study performed on mice has found Salton Sea aerosol turns on nonallergic inflammation genes and may also promote lung inflammation. For comparison, aerosolized fungal allergen (Alternaria) -- a common household fungal allergen -- produces an allergic inflammation in the lungs of mice.

"Our work strongly suggests that soluble components in Salton Sea water promote a unique inflammation-associated response," said Dr. David Lo, a distinguished professor of biomedical sciences at the UC Riverside School of Medicine, who led the study published in the journal Science of The Total Environment. "What relationship this response may have to asthma is not yet understood."

Lo's team exposed the mice to aerosolized suspensions generated from three separate sources: aqueous solutions of Alternaria filtrate, Salton Sea water, and Pacific Ocean water. Each exposure study lasted seven days and was performed in an exposure chamber and a control chamber, the latter receiving only pumped filtered air.

The researchers found exposure to aerosolized Alternaria triggered a dramatic allergic inflammation in the lungs of the mice. Aerosolized Salton Sea water increased B cell activity in the lung tissue of the mice; B cells are immune cells that make antibodies to fight bacteria and viruses. In contrast, mice exposed to Pacific Ocean aerosol showed no lung response.

"What's interesting is that the aerosolized Salton Sea triggered an inflammatory response in the lungs that is clearly distinct from the characteristic allergic inflammatory responses produced by Alternaria exposures," said Lo, who directs UCR's Bridging Regional Ecology, Aerosolized Toxins, & Health Effects Center, or BREATHE. "What we may surmise from this is that while Salton Sea spray may not be sufficient to generate asthma alone, it could play an important role in the progression to asthma or other inflammatory diseases. More research is clearly needed."

In recent years, the Salton Sea has increased in salinity and shrunk in size, generating toxic dust threatening the health of disadvantaged and vulnerable low-income communities living around the sea, many of whom are migrant workers. Primarily fed only by agricultural runoff and inflow of three rivers, the sea is rapidly retreating, which exposes the surrounding dry lakebed or "playa" and increases the levels of aerosol dust. Childhood asthma rates in the region around the Salton Sea are 20%-22.4%, higher than the state average of 14.5%.

Lo cautioned the current work did not test the biological effects of actual dust generated at the playa.

"In this paper, we report only our first steps in identifying the potential aerosols that may be contributing to lung disease in residents near the Salton Sea," he said. "We know the Salton Sea water aerosols are neither the only contributor to inhaled aerosols nor the only source of potential aerosol toxins in the region."

Lo's group is already exploring whether the inflammatory response the researchers observed in mice serves as an aggravating factor, leading eventually to asthma; if the inflammatory response in the mice is identical to that seen in humans; and whether it's a predisposing factor for people born and raised in the Salton Sea region. For those already predisposed to asthma, the researchers are planning to study whether the inflammation resulting from Salton Sea water aerosols worsens their health outcomes.

"We are only just getting started in answering these and other questions," Lo said. "It's so early in the process that we don't even really know what disease we are looking at."

The work was done in close collaboration with scientists at the Marlan and Rosemary Bourns College of Engineering's Center for Environmental Research and Technology, or CE-CERT, and in partnership with members of the communities around the Salton Sea.

Lo was joined in the research by first author Trevor A. Biddle, Qi Li, Mia R, Maltz, Purvi N. Tandel, Rajrupa Chakraborty, Keziyah Yisrael, Ryan Drover, and David R. Cocker III.

In a first-of-its-kind study in the world conducted at Tel Aviv University, researchers found that water generated from the air in the heart of an urban area, the city of Tel Aviv, complied with all of the strict drinking water standards set both by the State of Israel and by the World Health Organization. The researchers examined the quality of the water produced from the water vapor in the urban atmosphere, which is characterized by industry and massive construction, and found that it was suitable for drinking. The test was performed using a dedicated facility of the Israeli company Watergen, which partnered in the study.

The study was conducted by a team of experts from the hydrochemistry laboratory at the Porter School of Environment and Earth Sciences at Tel Aviv University, led by graduate student Offir Inbar and supervised by Prof. Dror Avisar, Head of TAU's Moshe Mirilashvili Institute for Applied Water Studies. Also participating in the study was Watergen's research and development team, Prof. Alexandra Chudnovsky, and leading researchers from Germany. The study's results were published in two leading journals: Science of the Total Environment and Water.

The researchers explain that the growing global shortage of clean drinking water requires thinking outside the box and developing new technologies for producing potable water. The Earth's atmosphere is a vast and renewable source of water, which may be an alternative drinking water resource. Our atmosphere contains billions of tons of water, 98% of which is in a gaseous state - that is, water vapor.

Offir Inbar explains that this is the first study in the world to examine air pollution from another angle - its effect on drinking water generated from the air. According to Inbar, no filtration or treatment system was installed in the device used in the study; the water that was produced was the water that was obtained from the air. The researchers performed a wide range of advanced chemical analyses of the water, and found that in the vast majority of cases, including during different seasons and at different times of the day, the water extracted from the air in the heart of Tel Aviv was safe to drink. In addition, with the help of a variety of innovative technologies for monitoring the composition of the atmosphere and by applying advanced statistical methods, for the first time the researchers were able to quantitatively link the process the air goes through in the days leading up to the point of water production and the chemical composition of the dew.

Offir Inbar explains: "The study showed that wind direction greatly affects water quality, so for example when the wind comes from the desert we find more calcium and sulfur, that is, residues of desert dust aerosols, in the water. However, when the wind comes from direction of the sea, we find higher concentrations of chlorine and sodium, which are found in the sea. Moreover, we found that the distant sources from which the air came before it reached the point of water production can be identified in the water. For example, water produced from air coming from the Sahara region differs in composition from water produced from air coming from Europe."

The researchers note that water quality is also affected by anthropogenic pollution from transportation and industry. "Using advanced methods, we found a direct link between the concentrations of ammonia, nitrogen oxides and sulfur dioxide in the air and the concentration of their decomposition products in water," says Inbar. "We found low concentrations of copper, potassium, and zinc in the water, which probably come from man-made pollution. From a research point of view, the chemical link we found between the meteorological parameters and the composition of the water makes it possible for the first time to study the atmosphere using water extracted from it. And environmentally speaking, this link allows us to know what minerals should be added to water extracted from air in order to provide people with quality drinking water. In general, we found that potable water from air does not contain enough calcium and magnesium - and it is advisable to add these minerals to the water, as they are added to desalinated drinking water in some countries."

A significant portion of the water we drink today in Israel is desalinated seawater. According to Inbar, this is only a partial solution, and not one that can provide drinking water to the vast majority of the world's population. "In order to desalinate seawater, you need a sea, and there isn't access to the sea from every place in the world," says Inbar. "After desalination, a complete infrastructure must be built that will carry the desalinated water from the waterfront to the various towns, and large parts of the world don't possess the engineering and economic means to build and maintain such infrastructure. Water from the air, however, can be produced anywhere, with no need for expensive transport infrastructure and regardless of the amount of precipitation. From an economic perspective, the higher the temperature and humidity, the more cost-effective the production of water from the air is."

Devices for generating water from the air that include water purification and treatment systems can already be found in a large number of countries in the world, where they provide quality drinking water to people living in distressed areas.

"The concern was that water produced from air in the heart of an urban area would not be suitable for drinking - and we proved that this is not the case," Inbar concludes. "We are currently expanding our research to other areas in Israel, including Haifa Bay and agricultural areas, in order to investigate in depth the impact of various pollutants on the quality of water extracted from the air."