Culture

In the brain, as in business, connections are everything. To maintain cellular associates, the outer surface of a neuron, its membrane, must express particular proteins--proverbial hands that reach out and greet nearby cells. And, like a creepily long handshake, surface molecules can overstay their welcome: A protein that lingers too long on the membrane may compromise the connections, or synapses, between cells.

In a new study, Rockefeller scientist Mary E. Hatten and research associate Hourinaz Behesti demonstrate that the protein ASTN2 helps move proteins away from the membrane in a timely fashion. The researchers also propose a mechanism by which ASTN2 defects lead to neurodevelopmental disorders such as autism and intellectual disabilities.

Proteins that need proteins

Neurons send messages to one another in the form of chemicals, or neurotransmitters, which activate receptor proteins on the surface of neighboring cells. Chemical communication is highly dynamic, which means that receptors must be dynamic too: they perpetually rotate on and off the membrane, ensuring rapid response to incoming signals. This process requires assistance from additional proteins, so-called traffickers that nudge receptors to move along.

Hatten, the Frederick P. Rose Professor, has demonstrated that the protein ASTN2 acts as such a trafficker during cell migration in early development. When Behesti joined Hatten's lab, she proposed that the protein might also play a role later in life, an idea supported by the fact that ASTN2 had been shown to be present in the adult brain. Specifically, the protein appears to be disproportionally expressed in the cerebellum--a brain region that some researchers suspect may govern complex aspects of cognition, in addition to its more-established role in regulating movement.

Hatten and Behesti wanted to better understand the function of ASTN2 in the adult cerebellum. An initial clue came by way of collaborators at Johns Hopkins University, who identified a family that had multiple members with ASTN2 mutations and neurodevelopmental disorders, including autism and language delays.

Concurrently, an independent study of a large population showed that ASTN2 mutations are associated with a wide variety of brain disorders. Hatten and Behesti therefore set out to determine how defects in this protein might disrupt cerebellar circuitry, and brain activity at large.

On the surface

The researchers used a special microscopy technique to determine where ASTN2 is expressed in the mouse cerebellum. They found that it appears primarily in components of neurons responsible for moving proteins around, and they identified a collection of molecules that attach to ASTN2. These "binding partners" included proteins involved in synapse formation and protein trafficking.

When the researchers increased the expression of ASTN2 in mouse neurons, levels of its binding partners decreased, suggesting that ASTN2 attaches to these proteins and then ushers them away from the membrane for degradation within the cell. Working with researchers at Duke University, the scientists also observed that cells with heightened ASTN2 formed stronger synapses; and they suspect that decreased ASTN2 yields the opposite effect.

"Our data suggest that people who have mutations in ASTN2 make less of the protein, which leads to slower or weaker synapses," says Behesti.

The researchers propose that without sufficient ASTN2, proteins accumulate on the cell surface, which hinders neuronal connections and communication.

"Synapses aren't static. They need to respond in real time to dynamic stimuli; and one of the ways they do this is by changing their surface protein expression," says Behesti.

This research supports a broader view that the disruption of surface protein composition may underlie a number of neurodevelopmental disorders. It also points to the cerebellum as a potentially fruitful research subject for understanding these conditions.

"People are just beginning to realize that the cerebellum isn't just there to control movement and motor learning," says Hatten. "It has much more complex roles in cognition and language."

Scientists at The University of Manchester have discovered a genetic mutation in humans linked to a 17-fold increase in the amount of dangerous fungal spores in the lungs.

The study, published in Nature Communications could allow doctors to screen patients at risk from Aspergillus, and could easily be developed into a test.

When breathed in, Aspergillus can be life threatening and also make asthma much worse, especially in people with compromised immune systems. It is found in soil, pillows and compost but is capable of living anywhere in a moist environment, so breathing it in is unavoidable.

Aspergillus is normally cleared from the lungs but 4% of people have this newly discovered mutation and in them, Aspergillus thrives in the airways.

"People with asthma, who have had transplant surgery, TB and many other illnesses that lower immunity could feasibly be screened for this genetic mutation. And early detection could save lives," said Dr Paul Bowyer who led the study funded by the Fungal infection Trust and supported by the NIHR Manchester Biomedical Research Centre.

Dr Sara Gago discovered the increased risk by comparing normal human cells to cells which had been gene edited to contain the mutation. The gene - known as ZNF77 - is mainly responsible for the extracellular matrix of the lungs' epithelial tissue- the membrane that protects them. These mutated cells had a weak response to Aspergillus showing how key epithelial cells are to normal defences against this airborne fungus.

Dr Bowyer said: "Until now we never really understood why some people have a much higher Aspergillus load than others. Now that we do, it's quite a significant advance in understanding this disease. We don't yet know how or why the mutation occurs but nevertheless this discovery provides the basis for a simple and inexpensive DNA test in those who people who are more at risk from Aspergillus."

Dr Gago is a Research Fellow funded by the National Centre for the Replacement, Reduction and Refinement of animals in research. She added: "ZNF77 doesn't actually occur in mice, so the only viable animal models besides humans are primates. Having developed a way to adapt human cell lines so that they can carry mutations associated with disease, we have avoided using primates or any animals entirely."

Rockville, Md. (September 20, 2018)--A few minutes of high-intensity interval or sprinting exercise may be as effective as much longer exercise sessions in spurring beneficial improvements in mitochondrial function, according to new research. The small study is published ahead of print in the American Journal of Physiology--Regulatory, Integrative and Comparative Physiology.

Mitochondria, the energy centers of the cells, are essential for good health. Previous research has found that exercise creates new mitochondria and improves the function of existing mitochondria. Altered mitochondrial function in response to a single session of exercise generates signals that may lead to beneficial changes in the cells, lowering the risk for chronic disease. High-intensity interval exercise consists of short bursts of high-intensity aerobic exercise--physical activity that raises the heart rate--alternating with brief recovery periods. Whether the intensity of a workout affects mitochondrial response is unclear.

A team of researchers studied eight young adult volunteers as they participated in cycling workouts of varying intensity.

Moderate intensity consisted of 30 minutes of continuous exercise at 50 percent peak effort.

High-intensity interval exercise consisted of five four-minute cycling sessions at 75 percent peak effort, each separated by one minute of rest.

Sprint cycling consisted of four 30-second sessions at maximum effort, each separated by 4.5 minutes of recovery time.

The research team measured the amount of energy the volunteers spent on each workout and compared mitochondrial changes in the participants' thigh muscles before and after each exercise session. The researchers found that levels of hydrogen peroxide--a type of molecule involved in cell signaling called "reactive oxygen species" that contains oxygen and hydrogen--in different parts of the mitochondria change after exercise. While too much reactive oxygen species can be damaging to the cells, the researchers noted that the volunteers' levels were an appropriate amount to potentially promote cell responses that benefit metabolic function rather than cause damage.

In addition, the research team found that fewer minutes of higher-intensity exercise produced similar mitochondrial responses compared to a longer moderate-intensity activity. "A total of only two minutes of sprint interval exercise was sufficient to elicit similar responses as 30 minutes of continuous moderate-intensity aerobic exercise," the researchers wrote. "This suggests that exercise may be prescribed according to individual preferences while still generating similar signals known to confer beneficial metabolic adaptions. These findings have important implications for improving our understanding of how exercise can be used to enhance metabolic health in the general population."

Washington, DC (September 20, 2018) -- Children with kidney failure due to certain diseases may regain kidney function and therefore no longer need dialysis, and kidney transplantation might be postponed. The findings, which appear in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN), may help clinicians better allocate scarce donor kidneys to pediatric patients.

Although kidney failure is often irreversible, a small percentage of patients who need dialysis to stay alive regain kidney function. To study this issue in children, Marjolein Bonthuis, PhD (ESPN/ERA-EDTA Registry, Amsterdam UMC, University of Amsterdam, in the Netherlands) and her colleagues analyzed data for 6574 patients from 36 European countries who started dialysis before the age of 15 years between 1990 and 2014.

Within two years after dialysis initiation, 130 patients (2%) experienced enough recovery of their kidney function to stop dialysis, and the median time to such recovery was 5 months. Compared with patients with congenital anomalies of the kidney and urinary tract, recovery more often occurred in patients with vasculitis, ischemic kidney failure, and hemolytic uremic syndrome. Younger age and initiation on hemodialysis instead of peritoneal dialysis were also associated with recovery. For 42 patients (32%), recovery was transient, as they returned to dialysis or underwent kidney transplantation after a median recovery period of 19.7 months.

"Kidney transplantation is regarded the optimal treatment for children with end-stage kidney disease and pediatric nephrologists try to reduce the time on dialysis and schedule kidney transplantation as early as possible. However, we found that in children on dialysis with specific kidney diseases, as well as in very young children, recovery of the native kidney function was much more likely," said Dr. Bonthuis. "Therefore, the opportunity of recovery should be considered when planning early kidney transplantation in these children. Transplantation might be postponed in these children and scarce donor kidneys could be saved for later times or for other recipients."

DALLAS, Sept. 20, 2018 -- One of the largest and longest-running efforts to evaluate the potential benefits of the Mediterranean-style diet in lowering risk of stroke found that the diet may be especially protective in women over 40 regardless of menopausal status or hormone replacement therapy, according to new research in the American Heart Association's journal Stroke.

Researchers from the Universities of East Anglia, Aberdeen and Cambridge collaborated in this study using key components of a traditional Mediterranean-style diet including high intakes of fish, fruits and nuts, vegetables, cereal foods and potatoes and lower meat and dairy consumption.

Study participants (23,232 white adults, 40 to 77) were from the EPIC-Norfolk study, the United Kingdom Norfolk arm of the multicenter European Prospective Investigation into Cancer study. Over a 17-year period, researchers examined participants' diets and compared stroke risk among four groups ranked highest to lowest by how closely they adhered to a Mediterranean style diet.

In participants, who most closely followed a Mediterranean-style diet, the reduced onset of stroke was:

17 percent in all adults;

22 percent in women; and

6 percent in men (which researchers said could have been due to chance).

"It is unclear why we found differences between women and men, but it could be that components of the diet may influence men differently than women," said Ailsa A. Welch, Ph.D., study lead author and professor of nutritional epidemiology at the University of East Anglia, United Kingdom. "We are also aware that different sub-types of stroke may differ between genders. Our study was too small to test for this, but both possibilities deserve further study in the future."

There was also a 13 percent overall reduced risk of stroke in participants already at high risk of cardiovascular disease across all four groups of the Mediterranean-diet scores. However, this was driven mainly by the associations in women who showed a 20 percent reduced stroke risk. This benefit appeared to be extended to people in low risk group although the possibility of chance finding cannot be ruled out completely.

"Our findings provide clinicians and the public with information regarding the potential benefit of eating a Mediterranean-style diet for stroke prevention, regardless of cardiovascular risk," said Professor Phyo Myint, M.D., study co-author and former British Association of Stroke Physicians Executive Committee member, University of Aberdeen, Scotland.

"A healthy, balanced diet is important for everyone both young and old," said Professor Ailsa Welch.

Researchers used seven-day diet diaries, which they said had not been done before in such a large population. Seven-day diaries are more precise than food-frequency questionnaires and participants write down everything they eat and drink over the period of a week.

"The American Heart Association recommends a heart-healthy and brain-healthy dietary pattern that includes a variety of fruits and vegetables, whole grains, low-fat dairy products, fish, poultry, beans, non-tropical vegetable oils and nuts and limits saturated fat, trans fat, sodium, red meat, sweets and sugar-sweetened beverages; this dietary pattern reduces risk factors and risk for heart disease and stroke, "said Eduardo Sanchez, M.D., MPH, the American Heart Association's chief medical officer for prevention and chief of the Association's Centers for Health Metrics and Evaluation, who was not a part of this study. "This study provides more evidence that supports AHA's recommendation," said Sanchez.

The themes in television advertisements for health insurance plans have shifted over time, possibly reflecting the shrinking pool of health plans offered through the Affordable Care Act (ACA) as well as rising plan premiums, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

In the study, published online in the Journal of Health Politics, Policy and Law, the researchers analyzed the volume and content of media messages included in insurance advertisements that were aired over a million times in the U.S. from late 2013 through spring 2016. One key finding: explicit mentions of Obamacare or ACA declined sharply.

"These marketplace health plans that became available following the passage of the health care law under President Obama were heavily government-subsidized and contributed to substantial declines in uninsurance rates in the U.S.," says study lead author Colleen L. Barry, PhD, the Fred and Julie Soper Professor and Chair of the Department of Health Policy and Management at the Bloomberg School. "Yet, in the absence of an explicit mention of the law in ads, newly insured individuals may not have appreciated the connection between the law and the health benefits they were receiving."

The ACA, often called Obamacare, is a major health policy initiative enacted in 2010 that led to the introduction of new marketplace plans designed to make it easier for consumers to access health care through the individual and small group insurance market starting in 2014. Television ads for ACA plans, which are sponsored mostly by private insurers and through state and federal enrollment efforts, first began marketing to consumers in late fall 2013.

For the study, through the Wesleyan Media Project at Wesleyan University, the researchers obtained a database of video files for all of the health insurance-related television ads that aired in U.S. media markets during the first three ACA open-enrollment periods in 2013-14, 2014-15 and 2015-16. The study authors took a random sample of the ads, ending up with 875 unique advertisements that represented 1,074,653 airings in all 50 states.

The researchers viewed and coded each ad for characteristics including: the type of people featured in the ads, the activities they were engaged in, the references to ACA or Obamacare, and the messages about various benefits of the health plans available.

One finding, not unexpected, was that overtime the ads increasingly included content aimed at selling policies to younger, healthier people, whose enrollment in large numbers is essential to the long-term plan solvency. Relatively few airings focused on elderly or disabled people, smokers or people receiving medical care in a hospital or clinic--the kinds of people who tend to generate more costly health insurance claims.

"What we saw over the three enrollment periods is that as costs became a greater concern for insurers, advertising increasingly targeted so-called 'young invincibles'--younger and healthy individuals who may be tempted to forego insurance," Barry says.

The researchers also noted a shift, over the three open enrollment periods, toward messages emphasizing the availability of financial assistance with premiums, and away from messages emphasizing plan choice. The trend corresponded to sharp increases in average ACA plan premiums and reductions in plan choice as some major insurers pulled out of ACA marketplaces.

Even more dramatic, Barry and her colleagues found, was the trend towards ads that did not mention ACA. "By the third enrollment period in 2016 only about 10 percent of the airings by non-government sponsors specifically referred to ACA or Obamacare," Barry says. "So there was a real movement by those sponsors to avoid connecting their products with the law itself."

The researchers suggest that this trend may relate to a low level of public understanding of ACA, which advertisers may have increasingly recognized and accommodated--and which in turn may have worsened the public's understanding.

"Public opinion data have shown consistently that many Americans do not understand the key components of the law or believe they have benefited from it," Barry says.

The researchers worry that not making clear the connection between an individual's health care and a major government program is problematic--not just for ACA but for government-sponsored programs generally. They cite the political scientist Suzanne Mettler, who has argued that public support for governmental programs will remain low, and indeed trust in government will remain low, insofar as citizens fail to see the benefits they receive from the government.

"If we want the public to understand the value of major government initiatives like ACA, then it is important to highlight these connections between health care benefits and government initiatives more explicitly," Barry says.

A couple of sugars, a dash of enzymes, a pinch of salt, a splash of polyethylene glycol, carefully arranged in watery baths. And researchers had made a synthetic organelle, which they used in a new study to explore some odd cellular biochemistry.

The researchers at the Georgia Institute of Technology made the chemical medley in the lab to closely mimic membraneless organelles, mini-organs in cells that are not contained in a membrane but exist as pools of watery solutions. And their model demonstrated how, with just a few ingredients, the organelles could carry out fine-tuned biological processes.

The researchers published the results of their study in the journal ACS Applied Materials & Interfaces for the September 26, 2018 issue. The research was funded by the National Institutes of Health's National Institute of General Medical Science and by the National Science Foundation.

A quick look at membraneless organelles should aid in understanding the research's significance.

What are membraneless organelles?

The discovery of organelles that are pools of watery solutions and not objects with membranes is fairly recent. A prime example is the nucleolus. It resides inside of the cell's nucleus, which is an organelle that does have a membrane.

In the past, researchers thought the nucleolus disappeared during cell division and reappeared later. In the meantime, researchers have realized that the nucleolus has no membrane and that during cell division it gets diffused the way water bubbles do in vinaigrette dressing that has been shaken up.

"After cell division, the nucleolus comes back together as a single compartment of fluid," said Shuichi Takayama, the study's principal investigator and a professor in the Wallace E. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Membraneless organelles can be made up of a few different aqueous solutions, each with different solutes like proteins or sugar or RNA or salt. Differences in the thermodynamics of the solutions, that is, how their molecules bounce around, keep them from merging into a single solution.

Instead, they phase separate the way oil and water do, even after intermingling. But there's no oil in this case.

"They're all waters," Takayama said. "They just don't mix with each other because they have different solutes."

What lifelike processes did the synthetic experiment demonstrate?

During intermingling, important things happen. The nucleolus, for example, is vital to DNA transcription. But the synthetic set-up, a collection of watery solutions made by the study's first author, Taisuke Kojima, carried out a simpler series of reactions that demonstrated how the membraneless organelles could drive sugar processing.

"We had three phases of solutions that each held different reactants," Kojima said. "It was like a ball with three layers: an outer solution, an intermediate solution, and a core solution. Glucose was in the outer layer; an enzyme, glucose oxidase, was in the second layer, and horseradish peroxidase was in the core along with a colorimetric substrate that gave us a visible signal when the last reaction we were looking for occurred."

The glucose in the outer layer interfaced with the glucose oxidase in the second layer, which catalyzed the glucose to hydrogen peroxide. It landed in the second layer and interfaced with the horseradish peroxidase in the core layer, which catalyzed it in the core layer along with that compound that turns colors.

"This type of cascading reaction is what one would expect to see membraneless organelles perform," Takayama said.

The cascade even transported each reaction product from one compartment to the next, something very typical in biological processes, like organs digesting food or an organelle processing molecules.

What can a surprise discovery teach us?

Part of the reaction took the researchers by surprise, and it resulted in a novel discovery.

"When researchers think about membraneless organelles, we often think that the reactions inside them are more efficient when their enzymes and substrates are in the same compartment," Takayama said. "But in our experiments, that actually slowed the reaction down. We said, 'Whoa, what's going on here?'"

"When the substrate is in the same place where the product of the reaction also builds up, the enzyme sometimes gets confused, and that can impede the reaction," said Kojima, who is a postdoctoral researcher in Takayama's lab. "I was pretty surprised to see it."

Kojima put the enzymes and substrate into separate solutions, which interfaced but did not merge to a single solution, and the reaction in his synthetic organelle worked efficiently. This showed how unexpected subtleties may be fine-tuning organelle chemistry.

"It was a Goldilocks regime, not too much contact between substrate and enzyme, not too little, just right," Takayama said.

"Sometimes, in a cell, a substrate is not abundant and may need to be concentrated in its own little compartment and then brought into contact with the enzyme," Takayama said. "By contrast, some substrates can be very abundant in the nucleus, and it might be important to partition them off from enzymes to get just enough contact for the right kind of reaction."

MINNEAPOLIS - People who participate in light to moderate physical activity, such as walking at least four hours a week or swimming two to three hours a week, may have less severe strokes than people who are physically inactive, according to a study published in the September 19, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Stroke is a major cause of serious disability, so finding ways to prevent stroke or reduce the disability caused by stroke are important," said study author Katharina S. Sunnerhagen, MD, PhD, of the University of Gothenburg in Sweden. "While exercise benefits health in many ways, our research suggests that even simply getting in a small amount of physical activity each week may have a big impact later by possibly reducing the severity of a stroke."

For the study, researchers looked at two Swedish stroke registries and identified 925 people with an average age of 73 who had a stroke. The registries included data on stroke severity based on symptoms such as eye, arm and facial movements, level of consciousness and language skills. Of study participants, 80 percent had a mild stroke.

To determine physical activity, participants were asked after the stroke how much they moved or exercised during leisure time before the stroke. Questions about duration and intensity of exercise were used to determine the average amount of physical activity. Relatives were asked to confirm exercise levels when needed.

Light physical activity was defined as walking at least four hours a week. Moderate physical activity was defined as more intense exercise such as swimming, brisk walking, or running two to three hours a week. Of study participants, 52 percent said they were physically inactive before having their stroke.

It is important to note that participants reporting on their own physical activity after having a stroke is a limitation of the study. It is possible that memory may be affected by a stroke, and more so in people with more severe stroke.

Researchers found that people who engaged in light to moderate physical activity before their stroke were twice as likely to have a mild stroke rather than a moderate or severe stroke when compared to people who were physically inactive. Of 481 people who were physically inactive, 354 had mild stroke, or 73 percent. Of 384 who engaged in light physical activity, 330 had mild stroke, or 85 percent. Of 59 people who engaged in moderate physical activity, 53 had mild stroke, or 89 percent. Researchers found that light and moderate physical activity were equally beneficial.

"There is a growing body of evidence that physical activity may have a protective effect on the brain and our research adds to that evidence," said Sunnerhagen. "Further research is needed to better understand just how physical activity influences the severity of a stroke. Finally, physical inactivity should be monitored as a possible risk factor for severe stroke."

Sunnerhagen noted that the difference in physical activity did not account for a large amount of the difference in stroke severity. When combined with younger age, greater physical activity accounted for only 6.8 percent of the difference between the two groups.

Sunnerhagen also stated that the study does not prove that physical activity reduces stroke severity; it only shows an association.

(Boston)--Stroke significantly impacts the ability of individuals to function independently. Research suggests that individuals who are physically active before suffering a stroke tend to have better outcomes.

In an editorial in this week's Neurology, Nicole Spartano, PhD, research assistant professor of medicine at Boston University School of Medicine (BUSM), agrees that a recent study (Reinholdsson et. al.), which proposes that individuals who reported being physically active (defined as either two hours of moderate intensity or four hours of light activity per week) before their stroke had milder symptoms. She attributes this protection to maintenance of a complex network of blood vessels within the brain. "Animal studies have shown that exercise promotes redundancies in the cerebrovascular system, in which multiple arteries feed the same brain regions. While the mechanism for an active lifestyle's effect on stroke severity is not fully understood, current literature seems to suggest that these individuals may be protected."

Spartano acknowledges that while these studies are promising, more work remains to be done. "Further research will need to investigate the specific doses of physical activity (frequency, duration, and intensity) and contexts that can provide the most benefit for cerebrovascular health." She also notes larger studies that gather data about baseline level of physical activity before their stroke may help to remove some bias from the data. "A study design that assesses lifestyle factors retrospectively through self-report is prone to recall bias, potentially influenced by disease status/severity."

Ultimately, Spartano is optimistic that further study in this area can make a major difference in lowering the impact of stroke on patients' function and independence. "Reducing the size and severity of stroke has great potential to benefit individual and public health."

ROCHESTER, Minn. -- Premenopausal women who have their ovaries surgically removed face an increased risk of developing chronic kidney disease, according to a Mayo Clinic study published on Wednesday, Sept. 19, in the Clinical Journal of the American Society of Nephrology.

"This is the first study that has shown an important link between estrogen deprivation in younger women and kidney damage. Women who have their ovaries surgically removed have an increased long-term risk of chronic kidney disease," says Walter Rocca, M.D., a Mayo Clinic neurologist and epidemiologist, and senior author.

Previous research conducted in animals has shown that the female hormone estrogen protectively affects the kidneys. That led Mayo Clinic researchers to wonder how removing both ovaries would affect kidney function in premenopausal women.

Chronic kidney disease, also called chronic kidney failure, means a person's kidneys are damaged and unable to filter blood the way that they should. If an individual's kidney becomes severely damaged and starts to fail, treatment options are limited to dialysis and a kidney transplant. An estimated 30 million adults in the U.S. have chronic kidney disease, and it is the ninth leading cause of death in the U.S., according to the Centers for Disease Control and Prevention.

These results highlight the need for physicians to discuss the potential increased risk for chronic kidney disease with women considering having their ovaries removed, according to Dr. Rocca.

"For women who do not have an increased genetic risk for breast and ovarian cancer, we recommend against the removal of the ovaries as a preventive option due to the increased risk of diseases, including chronic kidney disease and the increased risk of death," Dr. Rocca says.

Using the records linkage system of the Rochester Epidemiology Project, the study compared 1,653 premenopausal women living in Olmsted County, Minnesota, who had their ovaries surgically removed prior to 50 to an equal number of women of similar ages who did not have their ovaries removed. The women were followed for a median of 14 years. Mayo Clinic researchers found that women who had their ovaries removed had a 6.6 percent higher risk of developing chronic kidney disease, compared to those who did not. The risk of kidney failure was even higher for women younger than 46. Those who had their ovaries removed before 46 had a 7.5 percent increased risk of chronic kidney disease.

Weight gain trajectories in early childhood are related to the composition of oral bacteria of two-year-old children, suggesting that this understudied aspect of a child's microbiota -- the collection of microorganisms, including beneficial bacteria, residing in the mouth -- could serve as an early indicator for childhood obesity. A study describing the results appears September 19 in the journal Scientific Reports.

"One in three children in the United States is overweight or obese," said Kateryna Makova, Pentz Professor of Biology and senior author of the paper. "If we can find early indicators of obesity in young children, we can help parents and physicians take preventive measures."

The study is part of a larger project with researchers and clinicians at the Penn State Milton S. Hershey Medical Center called INSIGHT, led by Ian Paul, professor of pediatrics at the Medical Center, and Leann Birch, professor of foods and nutrition at the University of Georgia. The INSIGHT trial includes nearly 300 children and tests whether a responsive parenting intervention during a child's early life can prevent the development of obesity. It is also designed to identify biological and social risk factors for obesity.

"In this study, we show that a child's oral microbiota at two years of age is related to their weight gain over their first two years after birth," said Makova.

The human digestive tract is filled with a diverse array of microorganisms, including beneficial bacteria, that help ensure proper digestion and support the immune system. This "microbiota" shifts as a person's diet changes and can vary greatly among individuals. Variation in gut microbiota has been linked to obesity in some adults and adolescents, but the potential relationship between oral microbiota and weight gain in children had not been explored prior to this study.

"The oral microbiota is usually studied in relation to periodontal disease, and periodontal disease has in some cases been linked to obesity," said Sarah Craig, a postdoctoral scholar in biology at Penn State and first author of the paper. "Here, we explored any potential direct associations between the oral microbiota and child weight gain. Rather than simply noting whether a child was overweight at the age of two, we used growth curves from their first two years after birth, which provides a more complete picture of how the child is growing. This approach is highly innovative for a study of this kind, and gives greater statistical power to detect relationships."

Among 226 children from central Pennsylvania, the oral microbiota of those with rapid infant weight gain -- a strong risk factor for childhood obesity -- was less diverse, meaning it contained fewer groups of bacteria. These children also had a higher ratio of Firmicutes to Bacteroidetes, two of the most common bacteria groups found in the human microbiota.

"A healthy person usually has a lot of different bacteria within their gut microbiota," said Craig. "This high diversity helps protect against inflammation or harmful bacteria and is important for the stability of digestion in the face of changes to diet or environment. There's also a certain balance of these two common bacteria groups, Firmicutes and Bacteroidetes, that tends to work best under normal healthy conditions, and disruptions to that balance could lead to dysregulation in digestion."

Lower diversity and higher Firmicutes to Bacteroidetes (F:B) ratio in gut microbiota are sometimes observed as a characteristic of adults and adolescents with obesity. However, the researchers did not see a relationship of weight gain with either of these measures in gut microbiota of two-year-olds, suggesting that the gut microbiota may not be completely established at two years of age and may still be undergoing many changes.

"There are usually dramatic changes to an individual's microbiota as they develop during early childhood," said Makova. "Our results suggest that signatures of obesity may be established earlier in oral microbiota than in gut microbiota. If we can confirm this in other groups of children outside of Pennsylvania, we may be able to develop a test of oral microbiota that could be used in clinical care to identify children who are at risk for developing obesity. This is particularly exciting because oral samples are easier to obtain than those from the gut, which require fecal samples."

Interestingly, weight gain in children was also related to diversity of their mother's oral microbiota. This could reflect a genetic predisposition of the mother and child to having a similar microbiota, or the mother and child having a similar diet and environment.

"It could be a simple explanation like a shared diet or genetics, but it might also be related to obesity," said Makova. "We don't know for sure yet, but if there is an oral microbiome signature linked to the dynamics of weight gain in early childhood, there is a particular urgency to understand it. Now we are using additional techniques to look at specific species of bacteria--rather than larger taxonomic groups of bacteria--in both the mothers and children to see whether specific bacteria species influence weight gain and the risk of obesity."

Encouraging children "to help," rather than asking them to "be helpers," can instill persistence as they work to fulfill daily tasks that are difficult to complete, finds a new psychology study.

The research, conducted by a team of New York University scientists, suggests that using verbs to talk about actions with children, such as encouraging them to help, read, and paint, may help lead to more resilience following the setbacks that they inevitably experience rather than using nouns to talk about identities--for example, asking them to be helpers, readers, or artists.

The results run somewhat counter to those of a 2014 study that showed asking children to "be helpers" instead of "to help" subsequently led them to help more.

The difference between the 2014 work and the new scholarship, both of which appear in the journal Child Development, is that the latter tested what happened after children experienced setbacks while trying to help, underscoring how language choice is linked to children's perseverance.

"The new research shows how subtle features of language can shape child behavior in ways not previously understood," explains Marjorie Rhodes, an associate professor in NYU's Department of Psychology and the senior author of the study. "In particular, using verbs to talk to children about behavior--such as 'you can help'--can lead to more determination following setbacks than using nouns to talk about identities--for instance, 'you can be a helper'."

The paper's other authors included Emily Foster-Hanson, an NYU doctoral student who led the study, as well as Andrei Cimpian, an associate professor in NYU's Department of Psychology, and Rachel Leshin, an NYU doctoral student.

The 2014 work, which did not include any of the latest study's researchers, found that asking children aged 4 to 5 to "be helpers" instead of "to help" subsequently led them to help on more tasks, such as picking up crayons that had fallen on the floor or assisting someone in opening a box that was stuck.

However, the NYU findings showed that this effect backfires after children experienced difficulty while trying to be helpful.

In a series of experiments, children, also aged 4 to 5, were asked either to "be helpers" or "to help," and then were given the opportunity to assist the experimenter in cleaning up some toys. However, the situation was designed so that children would experience difficulties while they tried to help: for example, when children tried to pick up a box to move it to a shelf, the contents, due to a faulty box, spilled all over the floor--a problematic outcome similar to those young children experience in daily life.

The experiment continued with children getting three more opportunities to help the experimenter. The results showed that children who had originally been asked "to help" were more resilient after the setback than those asked to "be helpers."

After the setbacks, children asked "to help" were just as likely to help in challenging situations that benefited only the experimenter as in easy situations that also benefited themselves. On the other hand, children asked "to be helpers" rarely helped in the challenging situations that benefitted the experimenter--they did so only when it was easy and also benefited themselves.

"This research shows how talking to children about actions they can take--in this case, that they can do helpful things--can encourage more persistence following setbacks than talking to children about identities that they can take on," says Foster-Hanson.

A new Biotropica study examines mountain gorillas in Rwanda and their foraging for sodium-rich food in both national park areas and lands managed by local communities.

Obtaining sodium likely creates an incentive for the gorillas to leave park areas and make forays into high-altitude habitat. Both locations are not without risks: exiting their natural habitat and feeding on crops may increase human-wildlife conflict and visiting high-altitude areas may increase the risk of hypothermia.

The results may advance the discussion of how to adapt local human land use to effectively curb human-wildlife conflict.

"When gorillas raid eucalyptus stands outside the national park, they come in contact with local inhabitants, which puts both ape and human at risk. To discourage the gorillas from crossing into farmlands near the forest, agricultural practices may need to be reconsidered," said lead author Dr. Cyril Grueter, of The University of Western Australia, in Perth. "Ideally one would want to favor plant species that are nutritionally unattractive to the gorillas."

Starting in the spring of 2010, farmers from Sicily - the major pistachio production area of Italy - have been reporting a previously unknown disease on the trees. Characterised by cankers and declines, it sometimes leads to the collapse of the entire plant.

When the research team led by Salvatore Vitale, Centro di Ricerca Difesa e Certificazione, Italy, studied plants from a total of 15 pistachio orchards in Catania, Agrigento and Caltanissetta provinces, they identified cankers associated with vascular necrosis and tree decline on twigs, branches and stems, alongside abundant gummosis. There were also localised, sunken lesions with several central cracks. These lesions would deepen into the woody tissue, where discolouration and necrotic tissue were also present.

Additionally, the scientists conducted a series of pathogenicity tests on 5-year-old potted pistachio plants (Pistacia vera), which successfully reproduced the field observations. As a result, a previously unknown pathogenic fungus, which colonises the woody plant tissue, has been isolated.

The aetiology of the disease and the description of the new species, named Liberomyces pistaciae, are published in the open access journal MycoKeys. Despite cankers and subsequent decline of pistachio trees having been observed in Sicily for several years, the paper is the first work to successfully determine the causal agent.

"On the basis of the high disease incidence and the frequency of this species observed in several orchards in the last years, we believe that L. pistaciae represents amenace to pistachio production in Sicily," say the researchers.

Out of the 15 surveyed orchards, the scientists detected the presence of the fungus in ten of them. Most of the observations occurred in the winter period and during late spring, but the authors found the pathogen in asymptomatic trees as well, which suggests that the fungus has a dormant growth phase.

When already symptomatic, the plants begin to exudate gum. Often, the bark on their trunks and/or branches would scale, appearing as if cracking and peeling. The initial pale circular areas present in the bark turn dark and sunken with time. Later, the infected patches were seen to expand in all directions, yet faster along the main axis of the stems, branches and twigs. When the scientists examined beneath the bark, they saw discoloured and necrotic tissues. Once the trunk of the tree is encircled by a canker, they report, the whole plant collapses.

Other symptoms include canopy decline as well as wilting and dying inflorescences and shoots growing from infected branches or twigs.

The newly described fungus is characterised with slowly growing colonies. With time, they turn from white to pale to dark brown with a whitish slightly lobed margin.

The researchers warn that essential hazard for the further spread and promotion of the infection is the use and distribution of infected propagation material taken from nurseries and mechanical injuries or pruning wounds.

SEATTLE - New high-resolution maps pinpoint areas across Africa with concentrations of child deaths from diarrhea and show uneven progress over 15 years to mitigate the problem.

"Diarrhea is highly preventable, and tens of thousands of child deaths from diarrhea could be averted each year if interventions targeted mortality hot spots across Africa," said Dr. Bobby Reiner, lead author and Assistant Professor of Health Metrics Sciences at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington. "However, stakeholders need to recognize the uneven distribution of diarrhea within countries means national strategies will be much less effective than focused, local interventions."

The study, covering 2000 to 2015, maps the entire African continent in 5x5 square kilometer units and was published today in The New England Journal of Medicine. National and provincial maps of diarrhea in Africa often mask inequalities at the local community level, according to IHME researchers.

This precision health mapping helps clinicians and policymakers identify communities where children are most vulnerable to dying from the disease and tailor appropriate interventions.

The Bill & Melinda Gates Foundation funded the study, part of a five-year grant that enables IHME researchers and collaborators globally to map a range of health metrics in 5x5 square kilometer units. The research is part of the Local Burden of Disease project at IHME and led by Dr. Simon I. Hay, Director of Geospatial Science at IHME and Professor of Health Metrics Sciences at the University of Washington.

Accounting for more than 330,000 child deaths in 2015, diarrhea was the third leading cause of death and disease in children in Africa. The vast majority of diarrheal diseases are attributable to preventable causes. Established interventions include rotavirus immunization; ensuring access safe drinking water; sanitation and hygiene programs; and minimizing exposure to contaminated food.

The study examines prevalence and incidence of diarrhea and diarrhea-related mortality for children under age 5. Diarrhea is defined as three or more abnormally loose or watery stools within the previous 24 hours in a child younger than 5 years of age. Study findings cover 52 of 54 countries in Africa, excluding the island nations of Mauritius and Seychelles.

Researchers found more than half of all diarrhea-related deaths among children occurred in 55 of 782 total first-level administrative subdivisions (i.e. states, provinces, or regions) across Africa; these jurisdictions are home to 35% of the total population of Africa.

While many countries reduced their diarrhea child mortality burden uniformly at the local level, others saw divergent trends emerge. In Nigeria, for example, mortality rates were improving in some local areas at the same time as they were worsening in others. As a result, in 2015, child mortality rates among Nigerian states differed six-fold, with estimates ranging from 1.6 deaths per 1,000 children in Bayelsa state in the southwest to 9.5 deaths per 1,000 in Yobe state in the northeast.

Despite mortality reductions across nearly all locations in Africa over the 15-year period, several countries saw increases at the local level in certain parts of the Central African Republic, Gabon, Ivory Coast, Nigeria, and Zimbabwe.

"We observed diarrhea mortality declines across nearly all locations, but several areas across Africa with persistently high mortality from 2000 through 2015 are at risk of falling even further behind," said Reiner. "Our precision public health maps are critical tools for calling attention to areas where diarrhea-related child mortality is stagnating or worsening, despite proven interventions."

Additional findings include:

Ninety percent of first-level administrative subdivisions (i.e. states, provinces, or regions) saw declines in diarrhea-related child mortality between 2000 and 2015, with several locations achieving substantial reductions:

Timbuktu, Mali: 19.25 child deaths per 1,000 in 2000 to 4.08 in 2015

Gao, Mali: 16.23 in 2000 to 3.48 in 2015

Luanda, Angola: 13.78 in 2000 to 1.76 in 2015

Benguela, Angola: 13.63 in 2000 to 2.11 in 2015

Cuanza Sul, Angola: 13.05 in 2000 to 1.99 in 2015

Uige, Angola: 12.75 in 2000 to 1.85 in 2015

Cabinda, Angola: 12.46 in 2000 to 1.62 in 2015

Huambo, Angola: 12.54 in 2000 to 1.78 in 2015

Kuanza Norte, Angola: 12.32 in 2000 to 1.73 in 2015

Maradi, Niger: 13.87 in 2000 to 3.11 in 2015

Some areas in northeastern Nigeria, southeastern Niger, and southern Chad saw their high diarrhea-related child mortality rates change very little over the 15-year span.
For example, eight regions in Chad with high mortality rates in 2000 also had rates higher than six deaths per 1,000 children in 2015:
1. Hadjer Lamis: 8.73 in 2000 and 6.69 in 2015
2. Kabia: 9.14 in 2000 and 6.43 in 2015
3. Logone Occidental: 9.45 in 2000 and 6.32 in 2015
4. Logone Oriental: 9.38 in 2000 and 6.03 in 2015
5. Mayo-Boneye: 8.90 in 2000 and 6.33 in 2015
6. Mont De Lam: 9.31 in 2000 and 6.09 in 2015
7. Tandjile Est: 9.51 in 2000 and 6.23 in 2015
8. Tandjile Ouest: 9.76 in 2000 and 6.46 in 2015

Many of the concentrated areas of diarrhea-related child mortality in 2015 were found in Nigeria, Ethiopia, and Niger.

For example, three states in Nigeria - Yobe, Bauchi, and Gombe - accounted for six percent of all diarrhea-related deaths in Africa, while encompassing only one percent of the population at risk.

The first-level administrative subdivisions (i.e. states, provinces, or regions) with the highest diarrhea-related child mortality rates in 2015 were the following:

1. Yobe [Nigeria]: 9.51 deaths per 1,000 children, increased from 8.05 in 2000
2. Bauchi [Nigeria]: 8.25
3. Gombe [Nigeria]: 7.86, increased from 7.68 in 2000
4. Hadjer Lamis [Chad]: 6.69
5. Tandjile Ouest [Chad] 6.46
6. Kabia [Chad] 6.43
7. Borno [Nigeria]: 6.35
8. Jigawa [Nigeria]: 6.34
9. Mayo-Boneye [Chad]: 6.33
10. Logone Occidental [Chad]: 6.32