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Brain molecule identified as key in anxiety model

image: Boosting a single molecule in the brain can change 'dispositional anxiety,' the tendency to perceive many situations as threatening, in nonhuman primates, researchers from UC Davis and the University of Wisconsin-Madison have found. The molecule, neurotrophin-3, stimulates neurons to grow and make new connections.

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California National Primate Research Center

Boosting a single molecule in the brain can change "dispositional anxiety," the tendency to perceive many situations as threatening, in nonhuman primates, researchers from the University of California, Davis, and the University of Wisconsin-Madison have found. The molecule, neurotrophin-3, stimulates neurons to grow and make new connections.

The finding provides hope for new strategies focused on intervening early in life to treat people at risk for anxiety disorders, depression and related substance abuse. Current treatments work for only a subset of people and often only partially relieve symptoms.

"There are millions of people worldwide who suffer from debilitating anxiety and depressive disorders," said Andrew Fox, an assistant professor in the UC Davis Department of Psychology and a researcher at the California National Primate Research Center."These disorders are also some of the leading causes of disability and days lost to disability."

Fox co-led the study with Tade Souaiaia of the State University of New York Downstate Medical Center. Ned Kalin, chair of psychiatry at the University of Wisconsin-Madison School of Medicine and Public Health, is also a corresponding author on the study published August 15 in the journal Biological Psychiatry.

Anxiety disorders often emerge around adolescence and can continue to affect people for most of their lives. Currently, researchers can identify children who display an extreme anxious or inhibited temperament; these young people are at risk to develop stress-related psychopathologies as they transition to adulthood.

Changes in the amygdala

The roots of the study come from research done by the group about eight years ago in preadolescent rhesus macaques, when researchers got their first glimpse of molecular alterations in the dorsal amygdala, a brain region important in emotional responses.

The authors speculated that altered processes in this region might underlie early-life anxiety. Since then, the research team sequenced RNA from the dorsal amygdala to identify molecules related to dispositional anxiety and dorsal amygdala function. They eventually narrowed the potential molecules and selected neurotrophin-3, a growth factor, for further study.

The researchers used an altered virus to boost levels of neurotrophin-3 in the dorsal amygdala of juvenile rhesus macaques. They found that the increase of neurotrophin-3 in the dorsal amygdala lead to a decrease in anxiety-related behaviors, particularly behaviors associated with inhibition, a core feature of the early-life risk for developing anxiety disorders in humans. Subsequent brain imaging studies of these animals found that neurotrophin-3 changed activity throughout the distributed brain regions that contribute to anxiety.

Fox hopes other scientists can build on their research as an example of the kind of "deep science" that can transform how we understand psychopathology. The team has included a list of additional promising molecules that may warrant future investigation.

"We're only just beginning. Neurotrophin-3 is the first molecule that we've been able to show in a non-human primate to be causally related to anxiety. It's one of potentially many molecules that could have this affect. There could be hundreds or even thousands more," said Fox.

Credit: 
University of California - Davis

Compost key to sequestering carbon in the soil

image: Sampling soil at UC Davis' Russell Ranch Sustainable Agriculture Facility.

Image: 
Courtesy Nicole Tautges/UC Davis

By moving beyond the surface level and literally digging deep, scientists at the University of California, Davis, found that compost is a key to storing carbon in semi-arid cropland soils, a strategy for offsetting CO2 emissions.

For their 19-year study, published in the journal Global Change Biology, scientists dug roughly 6 feet down to compare soil carbon changes in conventional, cover-cropped and compost-added plots of corn-tomato and wheat-fallow cropping systems. They found that:

- Conventional soils neither release nor store much carbon.

- Cover cropping conventional soils, while increasing carbon in the surface 12 inches, can actually lose significant amounts of carbon below that depth.

- When both compost and cover crops were added in the organic-certified system, soil carbon content increased 12.6 percent over the length of the study, or about 0.07 percent annually. That's more than the international "4 per 1000" initiative, which calls for an increase of 0.04 percent of soil carbon per year. It is also far more carbon stored than would be calculated if only the surface layer was measured.

"If we take the time and energy to look a little deeper, there's always more to the story," said co-first author Jessica Chiartas, a Ph.D. student with the UC Davis land, air and water resources department. "The soil represents a huge mass of natural resource under our feet. If we're only thinking about farming the surface of it, we're missing an opportunity. Carbon is like a second crop."

COVER CROPS, COMPOST AND THE CARBON MARKET

Nationwide, many studies that investigated carbon change in the top foot of soil found that cover-cropped systems store carbon. The UC Davis study also found gains in the surface but, deeper down, enough carbon was released from cover-cropped systems that it resulted in an overall net loss.

"There are other benefits to cover crops that farmers may still enjoy, but in our systems, storing carbon is not necessarily one of them," said co-first author Nicole Tautges, a cropping systems scientist with the UC Davis Agricultural Sustainability Institute. "We'd make more progress by incentivizing compost."

The researchers did not compare composted systems without cover crops, but suspect the compost helped sequester carbon despite the cover crop, a notion they intend to investigate further.

MICROBES NEED A BALANCED DIET

Carbon has to filter through soil microbes to create stabilized forms of carbon in soil. Compost provides not only carbon but also additional vital nutrients for those microbes to function effectively.

"One reason we keep losing organic matter from soils is that our focus is on feeding the plant, and we forget the needs of others who provide important services in soil like building organic carbon," said senior author Kate Scow, director of the UC Davis Russell Ranch Sustainable Agriculture Facility. "We need to feed the soil, too".

Having a balanced diet can make the difference between how much carbon stays in the soil versus how much is released as carbon dioxide, Scow said.

When their diet is out of balance, microbes seek out missing nutrients, mining them from existing soil organic matter. This results in the loss rather than gain of carbon. The authors think that deep in the soil, cover-crop roots provided carbon but not the other nutrients needed to stabilize it.

SEQUESTERING CARBON IN ARID CLIMATES

The study was conducted in California's northern Central Valley at the Russell Ranch Sustainable Agriculture Facility, part of the Agricultural Sustainability Institute at UC Davis. The results indicate that semi-arid Mediterranean climates like the study site may be capable of storing far more carbon in the soil than once thought possible.

"This work coming out of Russell Ranch at UC Davis is very timely as the state invests in programs to sequester carbon in soils," said Secretary Karen Ross of the California Department of Food and Agriculture. "Carbon sequestration in soils through the addition of compost is a key practice in our Healthy Soils Program and we are delighted that the science and policy efforts are aligning and supporting each other."

The results also indicate an opportunity for compost to provide multiple, interconnected benefits to farmers and the environment by improving soils, offsetting greenhouse gas emissions, and transforming animal and food wastes into a valuable product the soil needs.

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University of California - Davis

Study predicts modest impact from additional dose of rotavirus vaccine

New Haven, Conn. -- Giving children an additional dose of rotavirus vaccine when they are nine months old would provide only a modest improvement in the vaccine's effectiveness in low-income countries concerned about waning protection against the highly contagious disease, according to a new study led by the Yale School of Public Health and the Institute of Infection and Global Health at the University of Liverpool.

Rotavirus is the leading cause of morbidity and death from severe diarrhea in children worldwide. Rotavirus vaccines have had a substantial impact on reducing incidence of rotavirus-associated gastroenteritis or RVGE in high- and middle-income countries. The vaccines' impact in low-income countries has been less defined. The vast majority of rotavirus deaths occur in Asia and Africa.

Clinical trials have reported 85-99% vaccine efficacy in high-income countries compared to only 39-67% efficacy in low-income countries.

In response to concerns about the vaccines' effectiveness in low-income countries, a team of researchers led by Associate Professor Virginia Pitzer of the Yale School of Public Health and Professor Nigel Cunliffe of the University of Liverpool conducted a detailed mathematical analysis of rotavirus vaccinations and diarrhea cases reported at the main hospital in Blantyre, Malawi, a low-income country in southeastern Africa that introduced rotavirus vaccine in 2012.

Global health experts are concerned about reports of lower vaccine effectiveness in the second year of life and have proposed administering an additional vaccine dose to children at nine months of age. Children in Malawi are currently given rotavirus vaccine at 6 and 10 weeks.

With access to 12 years of pre-vaccination and 5 years of post-vaccination data acquired through the Malawi-Liverpool-Wellcome Trust Clinical Research Programme in Blantyre, Malawi, the researchers investigated the magnitude and duration of current vaccine protection and the potential waning of vaccine-induced immunity that was being reported. They also ran computer modeling simulations to evaluate strategies for improving vaccine effectiveness.

The analysis predicted that an additional dose of rotavirus vaccine at nine months of age would provide only a modest 5-16% reduction in overall RVGE incidence over the first three years. The findings also identified other possible reasons for why the vaccine reportedly wasn't working so well in low-income countries, besides the vaccine itself.

"Our analysis revealed that lower vaccine effectiveness during the second year of life is not necessarily indicative of waning rotavirus vaccine protection," said Pitzer, the study's lead author and an expert in the epidemiology of microbial diseases in the Yale School of Public Health's public health modeling unit.

The study documented a high rate of rotavirus transmission in Malawi; as a result, vaccination provides only partial protection and tends to delay cases among vaccinated infants to the second year of life, according to the study. A poor immune response to oral vaccination due to other causes of inflammation in the gut and interference from other vaccines, such as those for polio, may also impact vaccine effectiveness.

"Strategies to enhance the immune response to initial vaccination, including the use of next-generation vaccines that are currently in development, may lead to enhanced and more durable vaccine impact" said Cunliffe, an expert in gastrointestinal infections at the University of Liverpool's Centre for Global Vaccine Research.

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Yale University

The Lancet Child & Adolescent Health: Mental health harms related to very frequent social media use in girls might be due to exposure to cyberbullying, loss of sleep or reduced physical activity

First study to examine three mechanisms by which very frequent use of social media may harm mental health suggests efforts should be made to reduce young people's exposure to harmful content, and the impact it has on healthy activities (such as sleep and exercise). Authors suggest that direct effects, such as on brain development, are unlikely and so interventions to simply reduce social media use might be misplaced.

Very frequent use of social media may compromise teenage girls' mental health by increasing exposure to bullying and reducing sleep and physical exercise, according to an observational study of almost 10,000 adolescents aged 13-16 years studied over three years in England between 2013-2015, published in The Lancet Child & Adolescent Health journal. The impact on boys' mental health appears to mainly be due to other mechanisms, not revealed by this study.

In the UK, more than 90% of teenagers use the internet for social networking. There is growing concern about their use of social media and the impact on their mental health and wellbeing, although evidence for the impact remains contradictory. Half of all mental illnesses start by the age of 14, making adolescence a crucial period for promoting mental health. There is some evidence that social media use can positively influence health, for example by reducing social isolation. However, few long-term studies exist and few have examined the mechanisms that might impact on wellbeing.

"Our results suggest that social media itself doesn't cause harm, but that frequent use may disrupt activities that have a positive impact on mental health such as sleeping and exercising, while increasing exposure of young people to harmful content, particularly the negative experience of cyber-bullying," says Professor Russell Viner from the UCL Great Ormond Street Institute of Child Health, who led the research. [1]

For the current study, scientists analysed data from three sets of interviews with teenagers from nearly 1,000 schools across England, as they progressed from Year 9 in 2013 (13 to 14-year-olds) to Year 11 in 2015 (15 to 16-year-olds). It is the first observational study to track social media use and mental health over these important early adolescent years with enough participants to make it representative of the whole of England.

At all three time points, young people reported the frequency with which they accessed or checked social media. Very frequent social media use was defined in the study as using social networks, instant messaging or photo-sharing services such as Facebook, Instagram, Twitter, Snapchat and WhatsApp multiple (three or more) times daily. The authors note that a limitation of the survey data is that it did not capture how much time the teenagers spent using social media, only how often they checked or accessed it.

In the second year of the study, participants completed the General Health Questionnaire (GHQ), for which a high score indicates psychological distress. They were also asked about their experiences of cyberbullying, sleep and physical activity. In the final year, participants were surveyed about three aspects of their personal wellbeing - life satisfaction, happiness and anxiety, using standard questions supplied by the Office for National Statistics. When the authors found any significant associations between the teenagers' social media use and psychological distress or wellbeing, they assessed the degree to which this could be attributed to cyberbullying, sleep and physical activity.

In 2013, of 13,000 children interviewed, 43% of boys and 51% of girls used social media multiple times a day. By 2014, this had increased to 51% and 68% respectively. In 2015, 69% of boys and 75% of girls used social media multiple times a day.

In both sexes, very frequent social media use was associated with greater psychological distress. In girls, the more often they accessed or checked social media, the greater their psychological distress - in 2014, 28% of girls who very frequently used social media reported psychological distress on the general health questionnaire, compared with 20% of those using it weekly or less. However, this effect was not as clear in boys.

The 2015 wellbeing survey revealed that persistent very frequent social media use across 2013 and 2014 predicted later lower wellbeing in girls, with girls who regularly used social media very frequently reporting lower life satisfaction and happiness and greater anxiety in 2015. In contrast, no significant associations were identified by the survey in boys.

Some previous studies have suggested that prior mental health problems are associated with greater social media use and the authors note that it's possible this was the case in the first year of the current study. However, in the second and third years, their findings strongly suggest causal links between social media use and mental health and wellbeing.

The authors found that almost all of the effect on girls' wellbeing in 2015 was down to cyber-bullying, reduced sleep and reduced physical activity. They also found that nearly 60% of the impact on psychological distress in girls in 2014 could be accounted for by their sleep being disrupted and by greater exposure to cyber-bullying. Reduced physical activity also played a lesser role.

In contrast, cyberbullying, sleep and physical activity appeared to explain only 12% of the impact of very frequent social media use on psychological distress in boys. These findings suggest that there are other mechanisms behind the effects of social media on boys' mental health. The authors suggest these influences are likely to be indirect, as they are for girls, rather than due to social media exposure per se, but further research is needed to reveal what these indirect influences might be.

Co-author, Dr Dasha Nicholls from Imperial College London, UK, says: "The clear sex differences we discovered could simply be attributed to girls accessing social media more frequently than boys, or to the fact that girls had higher levels of anxiety to begin with. Cyberbullying may be more prevalent among girls, or it may be more closely associated with stress in girls than in boys. However, as other reports have also found clear sex differences, the results of our study make it all the more important to undertake further detailed studies of the mechanisms of social media effects by gender." [1]

Writing in a linked Comment, Dr Ann DeSmet from Ghent University, Belgium, says: "These findings are important for at least two reasons. First, social media use among youngsters need not be as negative as often assumed. If the displacement of healthy lifestyles and cyberbullying can be attenuated, the positive effects of social media use, such as encouraging social interactions, can be more endorsed. These findings showing nearly full mediation paths may also inspire researchers to investigate mediators of other media use that is generally considered harmful (e.g. gaming). Second, the joint associations of several lifestyles with mental health indicate the importance of multi-behavioural, whole-school programs to promote mental health in youth. This paper demonstrates sleep, cyberbullying and physical activity may be important lifestyles to target in protecting and improving youth mental health."

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The Lancet

Deadly protein duo reveals new drug targets for viral diseases

ITHACA, N.Y. - New research from Cornell University details how two highly lethal viruses have greater pathogenic potential when their proteins are combined.

A research team led by Hector Aguilar-Carreno, associate professor in the Department of Microbiology and Immunology, has found a potentially similar scenario with a pair of viruses, in a study published in the Journal of Virology.

"Co-infections with these two viruses can occur in the same host, but we didn't know what would happen if their proteins combined," Aguilar-Carreno said. "We discovered that not only could they work together, they can work even better than they do separately."

Members of the Aguilar-Carreno research team are experts on how Nipah and Hendra viruses attach to, and fuse with, their hosts' cells. The viruses' natural host is the fruit bat; this relationship was captured in an illustration, chosen for the journal cover, by Aguilar-Carreno's husband, Armando Pacheco, a Cornell Institute of Biotechnology staff member.

The researchers' focus is on the viral fusion proteins (or F proteins) and attachment proteins (G proteins). In previous studies, the team unveiled how the two proteins physically interact to enable viral infections: A G protein attaches to the cell; G then triggers F to flip up and down, triggering fusion between the cellular and viral membranes - the first moment of infection.

Aguilar-Carreno knew this "dance" between G and F was a crucial step in viral infection, but was curious to know how the dance might change if the proteins got new partners. Since both Nipah and Hendra viruses can potentially co-infect fruit bats, a protein partner switch is likely to occur in the wild.

He and his team tested out different Nipah-Hendra protein combinations in the lab, using genetic approaches in human cells. In some pairings, the two gripped each other in a tight, tango-like embrace. But one hybrid - a Hendra F and Nipah G - behaved like Lindy Hoppers, allowing the F protein to perform "aerials" that heightened fusion between the virus and the cell.

"This combination of proteins had a looser interaction," Aguilar-Carreno said. "This looseness actually corresponded to greater fusion capability - and therefore an implied greater" ability to cause disease.

This hybrid protein power-couple has interesting implications.

"I find it fascinating - the tightness of the interaction is so crucial for these two proteins," Aguilar-Carreno said. "If they're too tight, they can't coordinate correctly to get into the cell. And now that we know this, we can leverage that to stop viral-cell fusion."

Aguilar-Carreno said this kind of therapeutic approach might be used to improve vaccine efficacy, or as an alternative to vaccines. His lab is working on vaccine approaches on animal models, as well as therapeutic approaches informed by this new discovery.

Aguilar-Carreno's lab is also working on related research that may lead to vaccine-free therapies or improved vaccines to treat enveloped viruses, which include infectious diseases such as human immunodeficiency virus (HIV) and influenza. Enveloped viruses are wrapped in an outer coat made from a piece of the infected cell's plasma membrane, which may protect the virus and help it infect other cells.

"Our work could lead to drugs," Aguilar-Carreno said, "that enable inventions such as a flu vaccine with broader protection and greater efficacy."

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Cornell University

A simpler way to choose the sex of offspring by separating X and Y sperm

A simple, reversible chemical treatment can segregate X-bearing sperm from Y-bearing sperm, allowing dramatic alteration of the normal 50/50 male/female offspring ratio, according to a new study by Masayuki Shimada and colleagues at Hiroshima University, published on August 13 in the open-access journal PLOS Biology. The study was performed in mice, but the technique is likely to be widely applicable to other mammals as well.

Most cells from male mammals contain both an X and a Y chromosome, but during sperm development (spermatogenesis), the X and Y chromosomes are segregated into different cells so that an individual sperm will carry either one or the other, with an X chromosome giving rise to daughters and a Y chromosome to sons.

Unlike the Y chromosome, which carries very few genes, the X chromosome carries many, some of which remain active in the maturing sperm. This difference in gene expression between X- and Y-bearing sperm provides a theoretical basis for distinguishing the two.

The authors found that almost 500 genes are active only in X-bearing sperm, of which 18 genes encoded receptors; because of their functions to response to ligand stimuli this made them good candidates for manipulating the sperm. They focused on a pair of receptors called Toll-like receptor 7 and 8 (TLR7/8) and found that a chemical that bound to the receptors slowed sperm motility without impairing either sperm fertilization ability or viability. They showed the effect was due to impaired energy production within the sperm and could be reversed by removal of the chemical from the medium.

Treatment of mouse sperm with this X-retarding chemical, followed by in vitro fertilization with the fastest swimmers, led to litters that were 90% male. When the slower swimmers were used instead, the litters were 81% female.

There are other procedures that can be used to separate X and Y sperm, but they are cumbersome, expensive, and risk damaging the DNA of the sperm. The procedure developed by these authors has the potential to greatly simplify sex selection for either in vitro fertilization (in which sperm and egg join in a lab dish) or artificial insemination (in which sperm are implanted into the female reproductive tract). Such techniques are widely used in the agricultural animal breeding field, as well as in human assisted reproduction.

"The differential expression of receptor genes by the two sex chromosomes provides the basis for a novel and potentially highly useful method for separating X and Y sperm and we have already succeeded the selectively production of male or female in cattle and pig by this method," Shimada said. "Nonetheless, use of this method in human reproductive technology is speculative at the moment, and involves significant ethical issues unaffected by the utility of this new technique."

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PLOS

Not just genes: Environment also shaped population variation in first Americans

The first Americans - humans who crossed onto the North American continent and then dispersed throughout Central and South America - all share common ancestry. But as they settled different areas, the populations diverged and became distinct. A new study from North Carolina State University shows that facial differences resulting from this divergence were due to the complex interaction of environment and evolution on these populations and sheds light on how human diversification occurred after settlement of the New World.

"If we want to understand variation in modern populations in Central and South America specifically, then we need to examine variation in prehistoric American populations during the formative period after they settled the continent but prior to European contact," says Ann Ross, professor of biological sciences at NC State and lead author of a paper describing the work.

In the first craniofacial variation study to look at the continent as a whole - a study 20 years in the making - Ross and co-author Douglas Ubelaker of the Smithsonian Institution examined skulls from across Mesoamerica and Central and South America. The skulls dated from 730 - 1630 A.D., and came from environments ranging from arid to alpine to coastal. Using a 3D digitizer, the researchers recorded standard anatomical landmarks on the skulls in order to get a consensus configuration for each population group. They compared the group configurations to determine the types of variation associated with each group.

"There's a lot of debate as to what models modern cranial variation," Ross says. "Mutations would insert the most variation, but they're very rare. Adaptation to environment is another possibility, but many researchers believe variation is largely due to a neutral process such as genetic drift, which occurs when populations separate and stop exchanging genes."

Ross and Ubelaker found that highland populations from across the region were similar to each other, as were lowland populations. But comparing highland with lowland populations showed higher variation between the two groups.

"That makes sense," Ross says. "You probably wouldn't travel from the mountains to the beach in order to find a mate. And we know that these groups were exchanging more than just pots."

While those results could be attributed in part to genetic drift, the researchers also found that other factors - such as adaptations to climate and altitude - also played a role in craniofacial differentiation between populations. Ross hopes that the work can serve as a baseline for future studies.

"Population divergence is a multifactorial process, a complex interplay of factors," Ross says. "If you want to find out why these populations diverge you have to look at multiple factors, not just genetics or DNA."

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North Carolina State University

Lost in translation: Researchers discover translator gene may play a role in disease

video: In this animation, the research team indicates where they observed variants in the tRNA structure. The blue represents areas that were found to be less frequently mutated and red represents areas more frequently mutated.

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Schulich Medicine & Dentistry, Western University

A molecule called tRNA, or transfer ribonucleic acid, is an essential component of the human genome that acts as a translator. It reads the genetic code and translates it into proteins - one of the key building blocks of the human body.

When researchers and clinicians investigate the genome's relation to disease, they have traditionally focused on mutations in the code for proteins. But now researchers at Western University have shown that the genes encoding tRNAs can also have mutations that cause the code to be misread, and in greater numbers than previously thought.

Think of it like a translator app on your phone - if it has errors in its software, the output is going to be all wrong, even if the original text is correct.

"This actually changes the way we think about the genetic code," said lead author Mathew Berg, a PhD Candidate at Western's Schulich School of Medicine & Dentistry. "We have shown that variation in tRNA has the potential to lead to a protein being made improperly, which can lead to misfolding and malfunction of the protein."

The research team, led by Schulich Medicine & Dentistry Professors Christopher Brandl, Robert Hegele and Patrick O'Donoghue, say this is significant because many human diseases like Alzheimer's disease and diseases of the heart muscle are linked to misfolded proteins.

"Genetic variation is one of the major reasons why some people acquire a disease while others do not and we expect that an individual with 10 abnormal tRNAs might be more likely to acquire a disease than someone with one," said Brandl. "Another interesting aspect of what we saw is that the profile of tRNAs in even the limited group we looked at was very diverse. No two individuals were the same."

The researchers point out that all previous evidence suggested that there were minimal variations in the tRNA genes, likely attributed to the fact that it hadn't been looked at this closely before. Based on previous evidence, the team only expected to find one or two mutants in the tRNA.

The group, including PhD Candidate Dan Giguere, came up with a new way to sequence and read the tRNA to get a better picture of the variation that exists between individuals. This deep sequencing data gathered at Western showed that human tRNA variation was previously underestimated by more than 30-fold.

In a group of 84 people in London, Ontario they found that individuals contain on average 66 variants in their tRNA genes.

"Because tRNA variation has been hard to analyze, it has largely been overlooked in genetic association studies. Our work suggests that it is important to look at the tRNA genes and we also provide the tools to do so," said Brandl.

Next, the group wants to get a better understanding of exactly how these genes are contributing to disease and determine whether it can be reversed. They also expect that they'll find even greater variation by looking at more diverse populations from other areas around the world.

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University of Western Ontario

Scientists discover key factors in how some algae harness solar energy

image: These are Phaeodactylum tricornutum diatoms.

Image: 
Ananya Agarwal/Rutgers Biophysics Molecular Ecology Laboratory

Scientists have discovered how diatoms – a type of alga that produce 20 percent of the Earth’s oxygen – harness solar energy for photosynthesis.

The Rutgers University-led discovery, published in the journal Proceedings of the National Academy of Sciences, could help lead to more efficient and affordable algae-based biofuels and combat climate change from fossil fuel burning.

Oceans and other waterways are rich with algae – energy factories that convert sunlight and carbon dioxide into chemical energy and help remove carbon from the atmosphere. Diatoms are among the most successful species of algae. Their fossil oils are the source of the highest quality petroleum on Earth.

The Rutgers-led team used a 3D bioimaging tool to reveal for the first time the architecture of the proteins known as Photosystem II that diatoms use to absorb sunlight and power their photosynthesis. They found that each cell includes two sets of these proteins, though only one set is active. The active set has a structure associated with pigment proteins, such as green chlorophyll that absorbs light, in an antenna to harvest light for photosynthesis. The inactive set lacks the antenna and does not participate in photosynthesis.

The Rutgers-led team is seeking to understand the limits of the power of photosynthesis in algae and to harnessing that power to produce biofuels. Algae store energy in the form of natural oils and, under the right conditions, can make a lot of oil that can be converted into biofuels for cars, trucks, trains and planes, according to the U.S. Department of Energy.

“The next steps are to try to understand the mechanisms that control the dynamics between the proteins and support robust biochemical energy production,” said senior author Wei Dai, an assistant professor in the Department of Cell Biology and Neuroscience in the School of Arts and Sciences.

“That would lay the groundwork for further research into developing more cost-effective biofuels from algae and displace petroleum,” said co-author Paul G. Falkowski, a Distinguished Professor who leads the Environmental Biophysics and Molecular Ecology Laboratory in the School of Environmental and Biological Sciences.

Scientists at Rutgers, Baylor College of Medicine in Texas and Xiangya Hospital at Central South University in China contributed to the study.

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.1906726116

Credit: 
Rutgers University

The growing threat of tarnished plant bug

image: This is the life cycle of the tarnished plant bug.

Image: 
Dominic Reisig

St. Paul, MN (August, 2019)--The tarnished plant bug is a profligate pest, which means it can feed on many different species, including cotton. Over the last 10 years, the tarnished plant bug has become one of the most important pests of cotton in North Carolina and Virginia. In the webcast "Tarnished Plant Bug in North Carolina and Virginia," Dominic Reisig (College of Agriculture and Life Sciences at North Carolina State University) introduces the pest, discusses its threat to cotton, and makes general management recommendations.

After detailing the life cycle of the tarnished bug plant, Reisig explains that the pest primarily damages cotton by feeding on its reproductive tissues. The tarnished bug plant can be easily managed in cotton, but it is important to sample correctly and apply the threshold properly. These processes are described along with general management tips, which include planting early, planting away from other hosts, and blocking cotton together. Farmers should also avoid overfertilizing and overirrigating.

This webcast complements "Tarnished Plant Bug Management Strategies for Mid-Atlantic Cotton," which describes in more detail how to identify and control this economically important pest.

Both webcasts are available through the "Focus on Cotton" resource on the Plant Management Network. This resource contains more than 75 webcasts, along with presentations from six conferences, on a broad range of aspects of cotton crop management: agronomic practices, diseases, harvest and ginning, insects, irrigation, nematodes, precision agriculture, soil health and crop fertility, and weeds. These webcasts are available to readers open access (without a subscription).

The "Focus on Cotton" homepage also provides access to "Cotton Cultivated," a new resource from Cotton Incorporated that helps users quickly find the most current cotton production information available. These and other resources are freely available courtesy of Cotton Incorporated at http://www.plantmanagementnetwork.org/foco.

Credit: 
American Phytopathological Society

Preclinical research suggests anti-cancer effect of keto diet

image: University of Texas at Dallas researchers studied the effects of a ketogenic diet on mice genetically engineered to develop lung cancer that closely mimics human cancer. The mice develop both squamous cell carcinoma (green) and adenocarcinoma (red). Researchers found that in mice fed the keto diet (left), growth of squamous cell lung cancer was suppressed, while adenocarcinoma was unaffected by the diet. Lung tissue from a mouse fed a normal diet is shown at right.

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University of Texas at Dallas

It's well known that keeping blood glucose levels in check can help individuals avoid or manage diabetes, but new research led by biologists at The University of Texas at Dallas suggests that restricting blood glucose levels might also keep certain cancers at bay.

In a study published online Aug. 13 in the journal Cell Reports, researchers restricted circulating glucose in mice with lung cancer. Circulating glucose restriction was achieved by feeding the mice a ketogenic diet, which is very low in sugar, and by giving them a diabetes drug that prevents glucose in the blood from being reabsorbed by the kidneys.

"Both the ketogenic diet and the pharmacological restriction of blood glucose by themselves inhibited the further growth of squamous cell carcinoma tumors in mice with lung cancer," said Dr. Jung-Whan "Jay" Kim, corresponding author of the multinational study and an assistant professor of biological sciences at UT Dallas. "While these interventions did not shrink the tumors, they did keep them from progressing, which suggests this type of cancer might be vulnerable to glucose restriction."

While many types of cancer cells are suspected to be heavily dependent on glucose -- or sugar -- as their energy supply, Kim and his colleagues have shown in previous laboratory studies that one specific type -- squamous cell carcinoma -- is remarkably more dependent than other cancer types, such as adenocarcinoma.

"The key finding of our new study in mice is that a ketogenic diet alone does have some tumor-growth inhibitory effect in squamous cell cancer," Kim said. "When we combined this with the diabetes drug and chemotherapy, it was even more effective."

Kim noted that glucose restriction did not have any effect on non-squamous-cell cancer types.

"Our results suggest that this approach is cancer-cell-type specific. We cannot generalize to all types of cancer," he said.

The researchers also examined glucose levels in blood samples from 192 patients who had either lung or esophageal squamous cell cancer, as well as 120 patients with lung adenocarcinoma. The blood samples were taken at random parts of the day and classified into those containing glucose concentrations higher or lower than 120 mg/dL, which is one clinical measure of diabetes. None of the patients had been diagnosed with diabetes.

"Surprisingly, we found a robust correlation between higher blood-glucose concentration and worse survival among patients with squamous cell carcinoma," Kim said. "We found no such correlation among the lung adenocarcinoma patients. This is an important observation that further implicates the potential efficacy of glucose restriction in attenuating squamous-cell cancer growth."

Kim emphasized that more comprehensive and detailed clinical studies are needed, but the results indicate a potentially novel approach to enhancing cancer treatment.

"Manipulating host glucose levels would be a new strategy that is different from just trying to kill cancer cells directly," Kim said. "I believe this is part of a paradigm shift from targeting cancer cells themselves. Immunotherapy is a good example of this, where the human immune system is activated to go after cancer cells.

"Maybe we can manipulate our own biological system a little bit or activate something we already have in place in order to more effectively combat cancer."

Credit: 
University of Texas at Dallas

Cell biology: Compartments and complexity

Ludwig-Maximilians-Universitaet (LMU) in Munich biologists have taken a closer look at the subcellular distribution of proteins and metabolic intermediates in a model plant. The results of the study provide new insights into the dynamics of metabolic processes in cells.

Eukaryotic cells - in this context, plant cells - contain a variety of subcellular compartments in which specific sets of enzymatic reactions take place. In addition to the classical organelles, which are delimited by intracellular membranes, the soluble phase of the cytoplasm (commonly known as the cytosol) is the site of defined metabolic transformations. How metabolic processes in these diverse compartments are regulated and coordinated is poorly understood. Using the thale cress (Arabidopsis thaliana) as a model, a team led by biologist Thomas Nägele (Professor of Evolutionary Plant Cell Biology at LMU) has now succeeded in quantifying the subcellular distribution of a broad range of proteins and metabolites in leaf cells, thus revealing new aspects of the metabolic dynamics in these cells. The study appears in The Plant Journal.

"It is often the case that the effects of environmental factors on plant metabolism can only be vaguely characterized, because plant cells cannot be interrogated with the necessary precision," Nägele says. "For example, if certain products of metabolism accumulate in response to environmental stress, it has not been possible to determine where exactly in the cell they actually build up - whether in the fluid-filled plant vacuole which serves as a storage compartment, in the mitochondrion which supplies the cell with energy, in the cytosol where many metabolic reactions take place, or somewhere else." He and his colleagues have now modified a conventional method - known as 'non-aqueous fractionation' - to make it compatible with high-throughput analyses. With this approach, cells can be dismantled into their component compartments, and the contents of each can be separately analyzed.

The novel fractionation strategy enabled the LMU researchers to show that a disabling mutation in the cytosolic enzyme hexokinase has a significant impact on processes that occur in chloroplasts (the sites of photosynthesis) and mitochondria. Hexokinase catalyzes the phosphorylation of carbohydrates. In doing so, it enables the production of intermediates required for many other metabolic pathways including plant respiration. "Our results demonstrate that glucose accumulates in the cytosol when the hexokinase is defective - and this is accompanied by a rise in the level of glucose in the vacuole, while concentrations of the amino acids glycine and serine in the mitochondria are significantly reduced," Nägele explains. These two amino acids are central intermediates in an important metabolic pathway known as photorespiration, which essentially counteracts photosynthesis and is stimulated in particular by drought stress. Therefore, the mutation in hexokinase most probably reduces the photorespiratory capacity of the cell. This assumption is supported by further analyses of the impact of the mutation on proteins that are known to play an important role in mediating photorespiration. "Our study demonstrates that analyses at the subcellular level can uncover central principles of the regulatory mechanisms that control plant metabolism," says Nägele. "Our improved methods have made it possible for us to identify novel markers that can now be employed in future investigations."

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Ludwig-Maximilians-Universität München

Researchers study protein ancestors to understand their role in growth

"Resurrecting" the ancestors of key proteins yields evolutionary insights into their role in human cells and in most cancers, a new study finds.

The study, published online August 13 in the journal eLife, revolves around the function of extracellular signal-regulated kinase (ERK), a protein that determines whether human cells divide and multiply as part of growth.

Led by researchers from NYU School of Medicine, the new study suggests that ERK was easily switched on in ancient one-celled creatures, but was carefully restrained as the first animals evolved 800 million years ago.

Specifically, the research team used computer analyses to determine the DNA sequences, and related protein structures, for ancient ERK relatives. By studying them, the researchers identified two key changes that likely brought ERK under more careful control across evolution.

The team also found that it was "surprisingly easy" to reverse those evolutionary changes and return ERK to its primitive, very active, ancestral state. This becomes important, the researchers say, because a similar process occurs as genetic mistakes convert normal cells into cancer. Modern-day ERK is part of "the most important signaling pathway in human cancers," along with the other protein switches that get stuck in the "on" position to cause abnormal growth.

"That ERK could continue to function while evolving reveals a flexibility that may explain how human cells evolved 500 different kinases that control all aspects of their biology - and why faulty kinases are so central to cancer growth," says senior study author Liam Holt, PhD, assistant professor in the Institute for Systems Genetics at NYU Langone Health. "Genetic changes are required for evolution to proceed, but many enzymes stop working when changes occur. ERK continues to signal."

Like all proteins, versions of ERK are assembled from combinations of molecular building blocks called amino acids. The growing variety of amino acid structures across the animal kingdom now catalogued in databases has made possible a new kind of analysis, say the authors. Researchers can make educated guesses about the amino acids occupying each position in the structures of their common ancestors.

Moving forward, the research team plans to resurrect a complete set of inferred ancestors for all proteins in ERK's class (kinases), and to screen drug candidates against them, says Holt. Their plan is based on the hypothesis that some mutations cause cancer because they return kinases to more ancient states that are not properly regulated.

To avert side effects and drug resistance, he says, future drugs might be designed to inhibit ancestor-like, cancer-causing kinase versions without turning off related, normal enzymes.

Credit: 
NYU Langone Health / NYU Grossman School of Medicine

How two water molecules dance together

An international research team has gained new insights into how water molecules interact. For the first time, the researchers were able to completely observe all of the movements between the water molecules, known as intermolecular vibrations. A certain movement of individual water molecules against each other, called hindered rotations, is particularly important. Among other things, the findings help to better determine the intermolecular energy landscape between water molecules and thus to better understand the strange properties of water.

The team led by Professor Martina Havenith from Ruhr-Universität Bochum and Professor Joel Bowman from Emory University in Atlanta, together with colleagues from Radboud University in Nijmegen and Université de Montpellier, describe the work in the journal "Angewandte Chemie International Edition" on 27 July 2019.

Unknown interactions

Water is the most important solvent in chemistry and biology and possesses an array of strange properties - for instance, it reaches its highest density at four degrees Celsius. This is due to the special interactions between the water molecules. "Describing these interactions has posed a challenge for research for decades," says Martina Havenith, head of the Bochum-based Chair of Physical Chemistry II and spokesperson for the Ruhr Explores Solvation (Resolv) Cluster of Excellence.

Experiments at extremely low temperatures

The team investigated the simplest conceivable interaction, namely between precisely two individual water molecules, using terahertz spectroscopy. The researchers send short pulses of radiation in the terahertz range through the sample, which absorbs part of the radiation. The absorption pattern reveals information about the attractive interactions between the molecules. A laser with especially high brightness, as is available in Nijmegen, was needed for the experiments. The researchers analysed the water molecules at extremely low temperatures. To do this, they successively stored individual water molecules in a tiny droplet of superfluid helium, which is as cold as 0.4 Kelvin. The droplets work like a vacuum cleaner that captures individual water molecules. Due to the low temperature, a stable bond occurs between two water molecules, which would not be stable at room temperature.

This experimental setup allowed the group to record a spectrum of the hindered rotations of two water molecules for the first time. "Water molecules are moving constantly," explains Martina Havenith. "They rotate, open and close." However, a water molecule that has a second water molecule in its vicinity cannot rotate freely - this is why it is referred to as a hindered rotation.

A multidimensional energy map

The interaction of the water molecules can also be represented in the form of what is known as water potential. "This is a kind of multidimensional map that notes how the energy of the water molecules changes when the distances or angles between the molecules change," explains Martina Havenith. All the properties, such as density, conductivity or evaporation temperature, can be derived from the water potential. "Our measurements now allow the best possible test of all potentials developed to date," summarises the researcher.

Credit: 
Ruhr-University Bochum

Poo's clues: Moose droppings indicate Isle Royale ecosystem health

image: An adult moose must eat approximately 40 pounds of vegetation per day just to keep itself going. Yet despite their need to consume large volumes of food every day, moose do not eat everything they come across. Instead, moose are considerably more selective than is obvious when deciding which plant species to eat.

Image: 
Sarah Hoy/Michigan Tech

Given the choice between ice cream and vegetables, for many people it'll be the ice cream. But sometimes it depends on the situation. If you'd eaten ice cream every day for a week, you might prefer the salad. Human preferences for different foods often depend on what's common fare and what's rare.

For non-human animals, like moose, the situation is equally complicated. An adult moose must eat approximately 40 pounds of vegetation per day just to keep itself going. Yet despite their need to consume large volumes of food every day, moose do not eat everything they come across. Instead, moose are considerably more selective than is obvious when deciding which plant species to eat.

Sarah Hoy, assistant research professor, and John Vucetich, distinguished professor, in the School of Forest Resources and Environmental Science at Michigan Technological University, in collaboration with scientists from the United States Geological Survey (USGS) and the University of Wyoming, have developed a method to analyze why moose choose to eat what they do, how their choices change in the presence of predation and how moose diets actually affect the stability of entire ecosystems.

The results appear in "Negative frequency-dependent foraging behaviour in a generalist herbivore (Alces alces) and its stabilizing influence on food web dynamics" published in the Journal of Animal Ecology.

"The research shows how what you would think is a simple decision -- what to eat -- is a complex process that depends on many environmental factors, such as how common food types are, how likely a moose is to be killed by a predator and how difficult deep snow makes it to move around and find food," Hoy said. "The moose eat upwards of 40 pounds each day. You'd think if you had such dietary requirements you'd stuff your face with anything you can find, but that doesn't appear to be the case."

"Something one might consider small, even trivial -- what a moose chooses to eat -- appears to have a stabilizing effect on the whole food web." -- Sarah Hoy, assistant research professor

The advantage to moose of taking the time to seek out and eat plant species that are relatively rare is a well-balanced diet, which requires nutrients that might be found only in those rarer plants. Many plants also contain chemicals that are toxic to moose in large quantities, which means that moose can ingest them only in limited amounts. However, a moose whose palate is too discerning pays a price; a cost of focusing too much on the rare plants is the time spent on the search. Additionally, a moose in search of a delicacy might be a more likely target for a wolf.

"Moose have a choice: eat the rare stuff at risk of not eating enough food overall, or eat what is most common in the forest at risk of missing out on a well-balanced diet," Hoy said. "We hadn't really known how moose manage that choice until now."

Polarized Poop and Mathematics

By analyzing a decade's worth of moose droppings under a polarized light microscope -- a technique known as microhistology, which is further explored on Michigan Tech's Unscripted science and research blog -- to determine what exactly moose are eating on Isle Royale, the researchers concluded that moose preferred to eat what was relatively rare in their home range. If balsam fir is rare, they prefer it; if balsam fir is common, they show less preference -- even passing it up in many cases to find a less common plant. However, moose appeared to become less fussy eaters in years when the risk of being killed by wolves was high and in years when deep snow likely made it more difficult for moose to move around and find food.

By combining the evidence of years of meticulous fieldwork with a mathematical model representing the Isle Royale system, Hoy and her fellow scientists were able to draw conclusions about why it's important that moose are choosy eaters in the context of the ecosystem.

Enter Rongsong Liu, associate professor of mathematics at the University of Wyoming. Liu built a mathematical food chain model that she said, "demonstrates that the selective foraging strategies of moose can have an important stabilizing effect on community dynamics and provide a useful framework for assessing the influence of the other aspects of foraging behavior on community stability."

The model further illuminates the strength of the connections across three trophic levels of the Isle Royale landscape: vegetation, herbivore, carnivore.

"The mathematical model is a way to test how important the patterns in moose behavior we observed are for the community as a whole," Hoy said. "Moose may change their diet in response to a harsh winter or a high risk of being killed by wolves, but how important is that to the ecosystem?"

Don DeAngelis, a research ecologist for the USGS, has worked with Liu to develop and analyze models of herbivores of the boreal forest, including moose. One factor influencing what a moose prefers to eat is the aforementioned toxins in certain plants and how those toxins can effectively skew moose diets toward better overall balance.

"The data implied the moose were deliberately limiting their intake of coniferous vegetation, and also that this effect was related to the level of other environmental conditions, probably the level of predation by wolves," DeAngelis said. "My role was to work with Liu to translate the way that we think wolves, moose and forest vegetation all interact with each other into mathematical equations, and then use these equations to build a model that reflects the way that the Isle Royale ecosystem works."

Ecological theory indicates that simple food chains, such as that of Isle Royale National Park, are prone to extinction. Where there is a single predator -- wolves -- and a single herbivore -- moose, which eats two basic kinds of plants: deciduous and conifer trees -- there can be erratic population fluxes. However, Hoy, Vucetich and colleagues discovered that the foraging behavior of the moose might be one factor that favors the persistence of wolves, moose and the different tree species in the food chain.

This distinctive combination of theoretical models and field observations from the predator-prey study on Isle Royale provides ecologists with more insight about how and why populations tend to persist where basic theories of ecology otherwise suggest that they should not.

Credit: 
Michigan Technological University