Culture

The drugs currently used to treat Chagas disease, a neglected tropical disease, have serious side effects and limited use in those with chronic disease. Now, researchers have reported in PLOS Neglected Tropical Diseases that memantine, a drug currently used to treat Alzheimer's disease, can diminish the number of parasites in mice with Chagas disease, and increase the survival rate of the animals.

Chagas disease, caused by the protozoan Trypanosoma cruzi affects 5 to 6 million people in the Americas. The disease can be divided into acute and chronic phases, with the clinical phase causing heart, esophagus or intestinal symptoms. The two drugs that have been used to treat Chagas for the last 50 years--nifurtimox and benznidazole--are highly effective in the acute phase but used sparingly in the chronic phase due to serious side effects that occur with long-term treatment.

In the new work, Ariel M. Silber of Universidade de São Paulo, Brazil, and colleagues studied memantine, which works on the central nervous system of animals but has also been shown to kill protozoa. The researchers first studied the effect of different concentrations of memantine on cultured macrophages-- a type of white blood cell--that were infected with T. cruzi. Next, they tested the drug in T. cruzi-infected mice.

The team found that memantine reduced the number of T. cruzi-infected macrophages in a dose-dependent way; more drug led to a greater reduction in the infection. In mice with Chagas disease, memantine lowered levels of the parasite by 40% and increased survival rates from 7.5% to 12.5%. The mice treated with memantine also had 35.3% lower parasite levels in their hearts compared to control animals.

"All these findings point memantine as an interesting starting point for the development of an optimized alternative therapy for Chagas disease," the researchers say.

For the sheep of St. Kilda, growing old brings with it a late-life decline in immune resistance against pervasive parasitic worms, which greatly reduces the animal's chances of surviving overwinter, regardless of overall physiological condition. The study's findings, which compiled the life histories of hundreds of wild sheep into a 26-year record of life and death, offer new insight into the little-understood role of immunosenescence in the wild. How and why we age remains a perennial mystery in life sciences, and much of what we know about immunosenescence - the steady deterioration of immune function with age - is largely derived from human populations and laboratory rodent models. While it's thought that this process also plays a role in shaping the morbidity and mortality of natural populations, particularly as it relates to parasite infections, the large-scale longitudinal datasets required to evaluate such questions are lacking. However, according to Hannah Froy and colleagues, the lifetime monitoring of the sheep on St. Kilda provided the unique opportunity to study the interactions of immune function, parasite burden, health and mortality. Froy et al compiled the fates of 800 individual animals, each facing natural aging and infection pressures. The authors discovered that individual aged sheep showed a decline in the availability of an antibody associated with protection against helminth parasite infection, which predicted mortality risk in the wild and their probability of surviving the winter. "[Froy et al.'s] results unambiguously demonstrate that long-term studies are not only essential to answer major ecological and evolutionary questions but also provide an invaluable resource to address topical scientific questions from the entire life science spectrum," writes Jean-Michel Gaillard and Jean-Francois Lemaitre in a related Perspective.

WHAT:

Affecting at least 14,000 Americans, amyotrophic lateral sclerosis (ALS) is a paralyzing and highly fatal neurodegenerative disorder for which there are no effective treatments. Scientists peered inside neurons and watched the workings of annexin A11, a gene linked to a rare form of ALS. They found that neurons may normally use the gene to ship internal housekeeping instructions via a newly discovered "hitchhiking" system and that disease-causing mutations may tie up deliveries at the cell's loading docks. The study, published in Cell, was led by researchers in labs overseen by Michael Ward, M.D., Ph.D., investigator at the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health; Jennifer Lippincott-Schwartz, Ph.D., senior group leader at the Howard Hughes Medical Institute Janelia Research Campus; and Peter St. George-Hyslop, M.D., Wellcome Trust Principal Research Fellow, Cambridge Institute for Medical Research., United Kingdom.

Neurons, like other cells, constantly manufacture proteins, the cell's workhorses. Instructions for making proteins are encoded in chromosomal DNA and stored in the nucleus. Manufacturing starts when DNA instructions are transcribed into RNAs, which are packaged as granules and transported out of the nucleus to other parts of the cell for assembly. Unlike in other cells, RNA in neurons may have to travel over great distances - sometimes up to four feet - down stringy axons or through dendritic branches. Using advanced live cell microscopy, the researchers found that annexin A11 plays a role in this process by helping RNA granules hitch rides onto traveling lysosomes. Until recently, lysosomes were mainly viewed as garbage cans that roam around inside of cells cleaning up waste. These unexpected results suggest that lysosomes might moonlight as RNA transporters.

They also found that disease-causing mutations in annexin A11 prevented hitchhiking, which, in turn, prevented RNA from being delivered to the far reaches of neurons. Many genetic studies have found that ALS is often caused by mutations in genes known to play roles in either RNA processing or the control of lysosomes. These results suggest that there is a link between these seemingly different processes and that understanding this type of hitchhiking in neurons may lead to new treatments for ALS.

Using polymers and natural stone slurry waste, UBC Okanagan researchers are manufacturing environmentally friendly stone composites.

These new composites are made of previously discarded materials left behind during the cutting of natural structural or ornamental blocks for buildings, construction supplies or monuments. While reusing the waste material of natural stone production is common in cement, tile and concrete, adding the stone slurry to polymers is a new and innovative idea, explains School of Engineering Professor Abbas Milani.

A growing industrial demand for multifunctional bio-friendly raw materials is pushing researchers to develop value-added and energy-saving biocomposites and processes, he explains.

"Because the slurry is a waste material, it comes at a lower cost for recycled composite production," says Milani, director of UBC's Materials and Manufacturing Research Institute (MMRI).

Milani and his colleagues recently received UBC eminence funding to establish a cluster of research excellence in biocomposites. The cluster will develop novel agricultural and forestry-based bio-and recycled composites to minimize the impact of conventional plastics and waste on the environment.

The powdered stone waste used in the project provides flexibility to the new particulate polymer matrix composite. It can be mixed at different ratios into the finished product through appropriate heat or pressure to meet structural requirements or aesthetic choices, defined by industry and customers.

"This green stone composite can easily be integrated into a variety of applications," says UBC Research Associate Davoud Karimi. "These composites can be used in decorations and sanitation products ranging from aerospace to automotive applications."

The researchers varied the amount of stone added to the composites then tested several parameters to determine strength, durability and density along with thermal conductivity. The molding and mechanical tests were conducted in the Composites Research Network Okanagan Laboratory with collaboration from the MMRI.

By adding the stone waste to the composites, researchers determined that it not only increased the virgin polymer's strength and durability, but the composites' conductivity increased proportionally based on the amount of stone added.

"The increased strength is important, but the increased conductivity (up to 500 per cent) opens a huge door to several new potential applications, including 3D printing with recycled composites," explains Milani.

"Any time we can divert waste from landfills and generate a product with the potential of economic benefit is a win-win," Milani adds. "We hope that these sorts of products, that are carefully designed with the aid of multi-disciplinary researchers focused on 3R measures (repairable, reusable, and recyclable), can significantly contribute to the economy of our region and Canada as a whole."

Rapid eye movement, or REM, sleep is a fascinating period when most of our dreams are made. Now, in a study of mice, a team of Japanese and U.S. researchers show that it may also be a time when the brain actively forgets. Their results suggest that forgetting during sleep may be controlled by neurons found deep inside the brain that were previously known for making an appetite stimulating hormone. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

"Ever wonder why we forget many of our dreams?" said Thomas Kilduff, Ph.D., director of the Center for Neuroscience at SRI International, Menlo Park, California, and a senior author of the study published in Science. "Our results suggest that the firing of a particular group of neurons during REM sleep controls whether the brain remembers new information after a good night's sleep."

REM is one of several sleep stages the body cycles through every night. It first occurs about 90 minutes after falling asleep and is characterized by darting eyes, raised heart rates, paralyzed limbs, awakened brain waves and dreaming.

For more than a century, scientists have explored the role of sleep in storing memories. While many have shown that sleep helps the brain store new memories, others, including Francis Crick, the co-discoverer of the DNA double helix, have raised the possibility that sleep - in particular REM sleep - may be a time when the brain actively eliminates or forgets excess information. Moreover, recent studies in mice have shown that during sleep - including REM sleep - the brain selectively prunes synaptic connections made between neurons involved in certain types of learning. However, until this study, no one had shown how this might happen.

"Understanding the role of sleep in forgetting may help researchers better understand a wide range of memory-related diseases like post-traumatic stress disorder and Alzheimer's," said Janet He, Ph.D., program director, at NINDS. "This study provides the most direct evidence that REM sleep may play a role in how the brain decides which memories to store."

Dr. Kilduff's lab and that of his collaborator, Akihiro Yamanaka, Ph.D., at Nagoya University in Japan, have spent years examining the role of a hormone called hypocretin/orexin in controlling sleep and narcolepsy. Narcolepsy is a disorder that makes people feel excessively sleepy during the day and sometimes experience changes reminiscent of REM sleep, like loss of muscle tone in the limbs and hallucinations. Their labs and others have helped to show how narcolepsy may be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus, a peanut-sized area found deep inside the brain.

In this study, Dr. Kilduff worked with Dr. Yamanaka's lab and Akira Terao's, D.V.M., Ph.D., lab at Hokkaido University, Sapporo, Japan, to look at neighboring cells that produce melanin concentrating hormone (MCH), a molecule known to be involved in the control of both sleep and appetite. In agreement with previous studies, the researchers found that a majority (52.8%) of hypothalamic MCH cells fired when mice underwent REM sleep whereas about 35% fired only when the mice were awake and about 12% fired at both times.

They also uncovered clues suggesting that these cells may play a role in learning and memory. Electrical recordings and tracing experiments showed that many of the hypothalamic MCH cells sent inhibitory messages, via long stringy axons, to the hippocampus, the brain's memory center.

"From previous studies done in other labs, we already knew that MCH cells were active during REM sleep. After discovering this new circuit, we thought these cells might help the brain store memories," said Dr. Kilduff.

To test this idea, the researchers used a variety of genetic tools to turn on and off MCH neurons in mice during memory tests. Specifically, they examined the role that MCH cells played in retention, the period after learning something new but before the new knowledge is stored, or consolidated, into long term memory. The scientists used several memory tests including one that assessed the ability of mice to distinguish between new and familiar objects.

To their surprise, they found that "turning on" MCH cells during retention worsened memory whereas turning the cells off improved memories. For instance, activating the cells reduced the time mice spent sniffing around new objects compared to familiar ones, but turning the cells off had the opposite effect.

Further experiments suggested that MCH neurons exclusively played this role during REM sleep. Mice performed better on memory tests when MCH neurons were turned off during REM sleep. In contrast, turning off the neurons while the mice were awake or in other sleep states had no effect on memory.

"These results suggest that MCH neurons help the brain actively forget new, possibly, unimportant information," said Dr. Kilduff. "Since dreams are thought to primarily occur during REM sleep, the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus - consequently, the dream is quickly forgotten."

In the future, the researchers plan to explore whether this new circuit plays a role in sleep and memory disorders.

Of the major food crops, only rice is currently able to survive flooding. Thanks to new research, that could soon change -- good news for a world in which rains are increasing in both frequency and intensity.

The research, newly published in Science, studied how other crops compare to rice when submerged in water. It found that the plants - a wild-growing tomato, a tomato used for farming and a plant similar to alfalfa - all share at least 68 families of genes in common that are activated in response to flooding.

Rice was domesticated from wild species that grew in tropical regions, where it adapted to endure monsoons and waterlogging. Some of the genes involved in that adaptation exist in the other plants but have not evolved to switch on when the roots are being flooded.

"We hope to take advantage of what we learned about rice in order to help activate the genes in other plants that could help them survive waterlogging," said study lead Julia Bailey-Serres, a UC Riverside professor of genetics.

In the study, the team examined cells that reside at the tips of roots of the plant, as roots are the first responders to a flood. Root tips and shoot buds are also where a plant's prime growing potential resides. These regions contain cells that can help a plant become more resilient to flooding.

Drilling down even further, the team looked at the genes in these root tip cells, to understand whether and how their genes were activated when covered with water and deprived of oxygen.

"We looked at the way that DNA instructs a cell to create particular stress response in a level of unprecedented detail," said one of the lead researchers, UC Riverside's Mauricio Reynoso.

"This is the first time that a flooding response has been looked at in a way that was this comprehensive, across evolutionarily different species," added study co-author Siobhan Brady, an associate professor of plant biology at UC Davis.

The genes involved in flooding adaptations are called submergence up-regulated families (SURFs). "Since evolution separated the ancestors of rice and these other species as many as 180 million years ago, we did not expect to find 68 SURFs in common," said co-author Neelima Sinha, professor of plant biology at UC Davis.

The study was an international collaboration funded by the National Science Foundation's Plant Genome Research Program. Researchers from UC Davis, as well as Emory, Argentina's National University of La Plata and Netherland's Utrecht University participated.

While UC Riverside researchers conducted flooding experiments and analysis of rice plant genomes, scientists at Davis did the same with the tomato species while the alfalfa-type plant work was done at Emory.

Though the SURFs were activated in all the plants during the flooding experiments, their genetic responses weren't as effective as in rice. The wild tomato species that grows in desert soil withered and died when flooded.

Climate change also produces periods of excessive drought, and separate efforts are under way to examine crop resilience to those conditions as well. However, Bailey-Serres said flooding responses are understudied compared to drought, making this work all the more important.

The group is now planning additional studies to improve the survival rates of the plants that currently die and rot from excess water.

This year is not the first in which excessive rains have kept farmers from being able to plant crops like corn, soybeans and alfalfa. Floods have also damaged the quality of the crops they were able to grow. As the climate continues to change, this trend is likely to continue. Without efforts to ensure our crops adapt, the security of the world's food supply is at risk.

"Imagine a world where kids do not have enough calories to develop," said Bailey-Serres. "We as scientists have an urgency to help plants withstand floods, to ensure food security for the future."

It is well established that weakened immune systems in old age affect people's health and fitness, but a study suggests that it is also an issue for wild animals.

Researchers studying wild Soay sheep on the remote St Kilda archipelago have revealed that the animals' immune responses to parasitic worms decline through adulthood.

Animals that show faster deterioration in resistance to the worms - which live in the sheep's gut - are more likely to die during the following winter.

The findings provide the first evidence linking declining immune function and survival in wild animals.

Deterioration of the immune system in old age - a process called immunosenescence - is a huge issue for human health, as it reduces people's ability to fight viruses and bacteria, researchers say.

The team believes their findings could offer insights into how people's ability to ward off larger parasites like worms might also decline in old age.

Researchers from the University of Edinburgh, Moredun Research Institute and Centre for Biodiversity Dynamics, Norway, made the discovery using blood samples taken from Soay sheep between 1990 and 2015.

Analysis of more than 2,000 samples taken across the lifetime of almost 800 animals revealed that levels of antibodies against a common worm infecting the sheep fell in old age.

The study, published in the journal Science, was supported by the Biotechnology and Biological Sciences Research Council, Natural Environment Research Council, and Scottish Government.

The research was carried as part of a long-term study of Soay sheep, which began in 1985. The animals have lived wild on the islands of St Kilda - a world heritage site owned and managed by the National Trust for Scotland - for thousands of years.

Professor Dan Nussey, from the University of Edinburgh's School of Biological Sciences, who co-led the study, said: "Our work provides the first evidence that deterioration in immune function in old age plays an important role in wild animal populations. It also provides rare clues from outside the laboratory that our ability to fight worm infection might fade as we age. Most studies of worm infections in humans focus on children and young adults in developing countries, with much less attention paid to older individuals."

Dr Tom McNeilly, of the Moredun Research Institute, said: "With the drive for more efficient farming practices, efforts are being made to extend the productive life-span of livestock species, with means the average age of farmed animals is likely to increase in future. Studies such as these are critical as they provide important information on the likely consequences of farming older animals in terms of their ability to fight infectious diseases."

Susan Bain, the National Trust for Scotland's Western Isles Manager, said: "For anyone who visits St Kilda, the Soay sheep are a highlight, being living artefacts of the archipelago's past - a relic from the earliest settlers. I therefore find it fascinating that these castaways from a lost culture still have things to teach us today. This new research shows that there is still a lot more to discover about this ancient breed and their environment."

People with psychopathic traits are predisposed toward antisocial behavior that can result in “unsuccessful” outcomes such as incarceration. However, many individuals with psychopathic traits are able to control their antisocial tendencies and avoid committing the antagonistic acts that can result.

A team of researchers at Virginia Commonwealth University and the University of Kentucky set out to explore what mechanisms might explain why certain people with psychopathic traits are able to successfully control their antisocial tendencies while others are not. Using neuroimaging technology, they investigated the possibility that “successful” psychopathic individuals — those who control their antisocial tendencies — have more developed neural structures that promote self-regulation.

Over two structural MRI studies of “successful” psychopathic individuals, the researchers found that participants had greater levels of gray matter density in the ventrolateral prefrontal cortex, one of the brain regions involved in self-regulatory processes, including the down-regulation of more primitive and reactive emotions, such as fear or anger.

“Our findings indicating that this region is denser in people higher on certain psychopathic traits suggests that these individuals may have a greater capacity for self-control,” said Emily Lasko, a doctoral student in the Department of Psychology in VCU’s College of Humanities and Sciences, who led the study. “This is important because it is some of the first evidence pointing us to a biological mechanism that can potentially explain how some psychopathic people are able to be ‘successful’ whereas others aren’t.”

The team’s findings will be described in an article, “An Investigation of the Relationship Between Psychopathy and Greater Gray Matter Density in Lateral Prefrontal Cortex,” that will be published in a forthcoming edition of the journal Personality Neuroscience. A preprint version of the article has been posted online.

The first study involved 80 adults in long-term relationships who were placed in an MRI scanner at VCU’s Collaborative Advanced Research Imaging center, where researchers took a high-resolution scan of their brain. Afterwards, participants completed a battery of questionnaires, including one that measured the “dark triad” of personality traits, individually assessing psychopathy (e.g., “it’s true that I can be mean to others”), narcissism (e.g., “I like to get acquainted with important people”), and Machiavellianism (e.g., “it’s not wise to tell your secrets”).

The second looked at another “successful” population: undergraduate students. The researchers recruited 64 undergraduate students who were assessed for psychopathic traits and tendencies using an assessment tool designed for use in community and student populations, measuring primary psychopathy (e.g., “I enjoy manipulating other people’s feelings”) and secondary psychopathy (e.g., “I quickly lose interest in the tasks I start”). The participants were then scanned at the University of Kentucky’s Magnetic Resonance Imaging and Spectroscopy Center.

In both studies, the researchers observed that gray matter density in the ventrolateral prefrontal cortex — which the researchers call “a hub for self-regulation” — was positively associated with psychopathic traits.

The researchers say their findings support a compensatory model of psychopathy, in which “successful” psychopathic individuals develop inhibitory mechanisms to compensate for their antisocial tendencies.

“Most neuroscientific models of psychopathy emphasize deficits in brain structure and function. These new findings lend preliminary support to the growing notion that psychopathic individuals have some advantages compared to others, not just deficiencies,” said study co-author David Chester, Ph.D., an assistant professor in the Department of Psychology who runs the Social Psychology and Neuroscience Lab, which conducts research on psychopathy, aggression and why people try to harm others.

Across the two samples of individuals who varied widely in their psychopathic tendencies, Chester said, the team found greater structural integrity in brain regions that facilitate impulse control.

“Such neural advantages may allow psychopathic individuals to counteract their selfish and hostile tendencies, allowing them to coexist with others in spite of their antisocial impulses,” he said. “To fully understand and effectively treat psychopathic traits in the human population, we need to understand both the shortfalls and the surpluses inherent in psychopathy. These new results are an important, though preliminary, step in that direction.”

The compensatory model of psychopathy offers a more optimistic alternative to the traditional view that focuses more on the deficits associated with psychopathy, Lasko said. The finding that the ventrolateral prefrontal cortex is denser in these individuals lends support for the compensatory model because that region is linked to self-regulatory and inhibitory behaviors, she said.

“Psychopathy is a highly nuanced construct and this framework helps to acknowledge those nuances,” she said. “People high in psychopathy have ‘dark’ impulses, but some of these individuals are able to either inhibit them or find a socially acceptable outlet for them. The compensatory model posits that these individuals have enhanced self-regulation abilities, which are able to compensate for their antisocial impulses and facilitate their ‘success.’”

Past research has indicated that approximately 1% of the general population, and 15% to 25% of incarcerated people, would meet the clinical criteria for psychopathy. By gaining a deeper understanding of the neurological advantages associated with “successful” psychopathic individuals, researchers may unlock new treatments and rehabilitation strategies for them, Lasko said. 

“We believe that it is critical to understand these potential ‘advantages’ because if we are able to identify biomarkers of psychopathy, and importantly, factors that could be informative in determining an individual’s potential for violent behavior and potential for rehabilitation, we will be better equipped to develop effective intervention and treatment strategies,” she said.

Lasko emphasized that the researchers’ findings are preliminary.

“Although the findings are novel and definitely provide a promising avenue for future research, they still need to be replicated,” she said. “They are also correlational so we currently aren’t able to make any causal inferences about the [ventrolateral prefrontal cortex]-psychopathy relationship.”

In addition to Lasko and Chester, the study involved Lasko’s fellow doctoral students in the Social Psychology and Neuroscience Lab: Alexandra Martelli and Samuel West; and C. Nathan Dewall, Ph.D., professor of psychology at the University of Kentucky.

About VCU and VCU Health

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 217 degree and certificate programs in the arts, sciences and humanities. Thirty-eight of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 11 schools and three colleges. The VCU Health brand represents the VCU health sciences academic programs, the VCU Massey Cancer Center and the VCU Health System, which comprises VCU Medical Center (the only academic medical center in the region), Community Memorial Hospital, Children’s Hospital of Richmond at VCU, MCV Physicians and Virginia Premier Health Plan. For more, please visit www.vcu.edu and vcuhealth.org.

Journal

Personality Neuroscience

DOI

10.31234/osf.io/j2pwy

One of the top qualities that we look for in a long-term partner is kindness, according to new research by Swansea University.

In a paper published by the Journal of Personality, researchers had over 2,700 college students from across the globe build themselves an ideal lifelong partner by using a fixed budget to "buy" characteristics.

While traits like physical attractiveness and financial prospects were important, the one that was given the highest priority was kindness.

The study compared the dating preferences of students from Eastern countries, for example Singapore, Malaysia and Hong Kong, and Western countries such as the UK, Norway and Australia.

Students were given eight attributes they could spend "mate dollars" on: physical attractiveness, good financial prospects, kindness, humour, chastity, religiosity, the desire for children, and creativity.

While there were some differences in behaviour between Eastern and Western students - there were also some remarkable similarities.

People typically spent 22-26% of their total budget on kindness, and large parts of their budget on physical attractiveness and good financial prospects, while traits like creativity and chastity received less than 10%.

The research team also found some interesting sex differences - both Eastern and Western men allocated more of their budget to physical attractiveness than women (22% vs 16%) while women allocated more to good financial prospects than men (18% vs 12%).

The principle researcher, Dr Andrew G. Thomas, believes that studying mate preferences across cultures is important for understanding human behaviour.

"Looking at very different culture groups allows us to test the idea that some behaviours are human universals.

"If men and women act in a similar way across the globe, then this adds weight to the idea that some behaviours develop in spite of culture rather than because of it."

The results also showed a difference in a partner's desire for children, which was a priority only for Western women.

"We think this may have something to do with family planning," said Thomas. "In cultures where contraception is widespread, a partner's desire for children may predict the likelihood of starting a family.

"In contrast, in cultures where contraception use is less widespread, having children may be a natural consequence of sex within a relationship, making actual desire for children less relevant."

DURHAM, N.C. -- Broken bones are a bigger deal the older you are: even after they've healed, the bones of older people are weaker and more likely to re-fracture. And since more than 6 million Americans break a bone each year, figuring out how to help people heal better would make a big difference.

In a paper published in JCI Insight on Sept. 19, Duke scientists found that a certain protein, which is more prevalent in older people, interferes with bone healing. They hope this discovery will lead to new treatments to help people heal after injuries or surgeries.

"When we decreased the protein level, aging was reversed," said senior author Gurpreet Baht, Ph.D. an assistant professor in the Duke Department of Orthopaedic Surgery. "Not only was there more bone and healing happened faster, but it was also structurally more sound."

Baht's team confirmed that older people have more Apolipoprotein E, ApoE for short, than younger people. (If that protein name rings a bell, it's because ApoE is also implicated in Alzheimer's and heart disease).

The team found that 75-85 year olds had twice as much ApoE in their bloodstreams as 35-45 year olds, then found the same was true for 24-month-old mice versus 4-month-old mice, which approximate the same human age ranges.

Next, they wanted to figure out if and how ApoE affects the multi-step process of bone healing. When you break a bone, your body sends signals through the bloodstream to recruit cells to fix it. Some of those recruits, specifically skeletal stem cells, build up cartilage as a temporary scaffolding to hold the fracture together.

In the next step, more recruited cells mature into osteoblasts, bone-building cells, which lay strong, dense bone cells on top of the cartilage scaffolding. Finally, a different kind of cell eats up the cartilage scaffolds and osteoblasts fill those holes with bone.

"Over time, this cartilage will continue to be resorbed and osteoblasts will continue to deposit new bone," Baht explained. "After a few months of your arm or leg healing, there will be almost no cartilage anymore. And if you were to look at it five years out, there'd be no sign of an injury anymore."

That's if the bone healing process works perfectly. But the researchers found that if they added ApoE to a petri dish with skeletal stem cells, fewer cells developed into osteoblasts and the osteoblasts were worse at building bones.

"We wanted to see if the cell population was more or less capable of becoming osteoblasts," Baht said. "[Normally,] you put these cells down in a petri dish for about a month and the dish becomes so hard that you can't even scratch the surface because they've made two-dimensional bone there. ApoE-treated cells are still able to do this, they just don't do it as much or as well."

Next, the researchers created an intervention by injecting a virus which keeps mice from making ApoE protein. Circulating ApoE levels dropped by 75 percent and the healed bones contained one and a half-times more strong, hard bone tissue than bones of untreated mice.

The research was supported by the Duke Center for the Study of Aging and Human Development and Claude D. Pepper Older Americans Independence Center (AG028716 and K01AG056664), the Pathway to Stop Diabetes Initiator Award from the American Diabetes Association (1-16-INI-17) and a Borden Scholar Award.

Past researchers linked ApoE to Alzheimer's disease and atherosclerosis, a disease in which fatty plaques narrow the arteries. Too little ApoE, and fat builds up and can cause cardiovascular issues. The liver virus which turned off ApoE production in mice acts permanently, so Baht's next step is to investigate other interventions.

"You have to be careful," Baht said. "If a patient were to permanently decrease circulating ApoE levels, and then have a fatty meal, that fat might not get processed properly and could deposit in blood vessels. In our future studies, we're going to try to temporarily lower ApoE."

"As a treatment to improve bone healing, the patient could take a pill or an injection to lower ApoE for a short time rather than permanently, and there would be dietary restrictions during treatment. That would be probably a much safer model," Baht said.

(Boston)--A method to create a faster and lower cost alternative for a gene therapy tool has been developed by Boston University School of Medicine (BUSM) researchers.

Gene therapy is a clinical technique that introduce genes to treat disease. One approach is to use adeno-associated virus (AAV) as a tool to deliver the gene, but production of large quantities of AAV tends to be complicated and costly.

BUSM researchers have developed an advanced protocol to produce large quantities of AAVs, viral vectors that can deliver a specific gene into humans and animals.

According to the researchers, AAVs are also powerful research tools when combined with modern gene-editing technologies and can serve as a practical alternative to genetically modified animal models. However, a major drawback has been the time and cost to produce quantities of AAV to be used for animals in the lab. This advanced technique bypasses developmental effects that can arise from conventional gene manipulation in animals, while saving time, reducing the numbers of animals used in research and eventually research cost.

"Our protocol helps to produce AAVs efficiently and economically in regular laboratories so that researchers can easily conduct a pre-clinical trials for gene therapy," explained co-corresponding author Markus Bachschmid, PhD, assistant professor of medicine at BUSM.

"Several labs in the Boston area and Japan have already tested this new protocol and found it useful," said co-corresponding author Reiko Matsui, MD, assistant professor of medicine at BUSM. "Our hope is that many laboratories can adapt these procedures to accelerate research and promote gene therapy."

Gene therapy using AAV is a rapidly emerging field in clinical therapy. The recent release of the FDA approved AAV-based drug Zolgensma for treating spinal muscular atrophy is a landmark in human gene therapy and demonstrates the high potential of AAV.

Proteins are essential for every living cell and responsible for many fundamental processes. In particular, they are required as bio-catalysts in metabolism and for signalling inside the cell and between cells. Many diseases come about as a result of failures in this communication, and the origins of signalling in proteins have been a source of great scientific debate. Now, for the first time, a team of researchers at the University of Göttingen has actually observed the mobile protons that do this job in each and every living cell, thus providing new insights into the mechanisms. The results were published in Nature.

Researchers from the University of Göttingen led by Professors Kai Tittmann and Ricardo Mata found a way to grow high-quality protein crystals of a human protein. The DESY particle accelerator in Hamburg made it possible to observe protons (subatomic particles with a positive charge) moving around within the protein. This surprising "dance of the protons" showed how distant sections of the protein were able to communicate instantaneously with each other - like electricity moving down a wire.

In addition, Tittmann's group obtained high-resolution data for several other proteins, showing in unprecedented detail the structure of a kind of hydrogen bond where two heavier atoms effectively share a proton (known as "low-barrier hydrogen bonding"). This was the second surprise: the data proved that low-barrier hydrogen bonding indeed exists in proteins resolving a decades-long controversy, and in fact plays an essential role in the process.

"The proton movements we observed closely resemble the toy known as a Newton's cradle, in which the energy is instantly transported along a chain of suspended metal balls. In proteins, these mobile protons can immediately connect other parts of the protein," explained Tittmann, who is also a Max Planck Fellow at the Max Planck Institute for Biophysical Chemistry in Göttingen. The process was simulated with the help of quantum chemical calculations in Professor Mata's laboratory. These calculations provided a new model for the communication mechanism of the protons. "We have known for quite some time that protons can move in a concerted fashion, like in water for example. Now it seems that proteins have evolved in such a way that they can actually use these protons for signalling."

The researchers believe this breakthrough can lead to a better understanding of the chemistry of life, improve the understanding of disease mechanisms and lead to new medications. This advance should enable the development of switchable proteins that can be adapted to a multitude of potential applications in medicine, biotechnology and environmentally friendly chemistry.

An internationally respected group of scientists, including Professor Francois Engelbrecht from the University of the Witwatersrand, Johannesburg, have urgently called on world leaders to accelerate efforts to tackle climate change. Almost every aspect of the planet's environment and ecology is undergoing changes in response to climate change, some of which will be profound, if not catastrophic, in the future.

According to their study published in Science today, reducing the magnitude of climate change is also a good investment. Over the next few decades, acting to reduce climate change is expected to cost much less than the damage otherwise inflicted by climate change on people, infrastructure and ecosystems. Their research is being published only a few days ahead of the UN Climate Change Week in New York, in which international governments, business, academic institutions and non-profit organisations, among others, will be discussing the impacts of climate change on a global basis.

"Acting on climate change has a good return on investment when one considers the damages avoided by acting," says lead author, Professor Ove Hoegh-Guldberg from the ARC Centre for Excellence in Coral Reef Studies at the University of Queensland in Australia. The investment is even more compelling given the wealth of evidence that the impacts of climate change are happening faster and more extensively than projected, even just a few years ago. This makes the case for rapidly reducing greenhouse gas emissions even more compelling and urgent.

"We have underestimated the sensitivity of natural and human systems to climate change, and the speed at which these changes are happening," says Hoegh-Guldberg.

"We have underappreciated the synergistic nature of climate threats - with the outcomes tending to be worse than the sum of the parts. This is resulting in rapid and comprehensive climate impacts, with growing damage to people, ecosystems, and livelihoods."

For example, sea-level rise can lead to higher water levels during storm events. This can create more damage. For deprived areas, this may exacerbate poverty, creating further disadvantage. Each risk may be small on its own, but a small change in a number of risks can lead to large impacts.

Developing countries are especially vulnerable to climate change impacts, says co-author and Professor in Climatology at the Global Change Institute of the University of the Witwatersrand in South Africa, Francois Engelbrecht.

"The developing African countries are amongst those to be affected most in terms of impacts on economic growth in the absence of strong climate change mitigation," says Engelbrecht.

The southern African region may be regarded as a climate change hot-spot.

"The region has been warming drastically over the last five decades, at about twice the global rate of warming. Southern Africa is likely to become generally drier under low mitigation climate change futures."

Engelbrecht emphasises that by restricting global warming to 1.5°C future risks posed by droughts and heat-waves to the region can be reduced. At higher levels of global warming these risks are substantially higher, and more frequently occurring multi-year droughts may bring tipping points to the region in terms of water security, agriculture and livestock production.

Engelbrecht is a lead author of the IPCC Special Report on Global Warming of 1.5°C that was published in 2018. The new paper in Science reviews the findings of this report and assesses the latest scientific evidence of climate change impacts in a warming world, and the extent to which these impacts can be avoided/reduced through climate change mitigation.

In this research, Engelbrecht led the analysis of the identification of climate change hot spots and regional tipping points that may be reached under low mitigation climate change futures. Engelbrecht's research contributions to the Science paper also extended to the analysis of the projected changes in extreme weather events under different global degrees of global warming, with a focus on landfalling tropical cyclones and the drought in southern Africa.

Professor Daniela Jacob, co-author and Director of Climate Services Centre (GERICS) in Germany is concerned about these rapid changes associated with climate change - especially about unprecedented weather extremes.

"We are already in new territory," says Jacob, "The 'novelty' of the weather is making our ability to forecast and respond to weather-related phenomena very difficult."

These changes are having major consequences. The paper updates a database of climate-related changes and finds that there are significant benefits from avoiding 2oC of global warming and aiming to restrict the increase in global temperature to 1.5oC above pre-industrial global temperatures.

Professor Rachel Warren from the Tyndall Centre at the University of East Anglia in the UK assessed projections of risk for forests, biodiversity, food, crops and other critical systems, and found very significant benefits for limiting global warming to 1.5oC rather than 2oC.

"The scientific community has quantified these risks in order to inform policy makers about the benefits of avoiding them," says Warren.

Since the Paris Agreement came into force, there has been a race to quantify the benefits of limiting warming to 1.5oC so that policy makers have the best possible information for developing the policy required for doing it.

"If such policy is not implemented, we will continue on the current upward trajectory of burning fossil fuels and continuing deforestation, which will expand the already large-scale degradation of ecosystems. To be honest, the overall picture is very grim unless we act," says Warren.

A recent report from the United Nations projected that as many as a million species may be at risk of extinction over the coming decades and centuries. Climate change is not the only factor but is one of the most important ones.

Professor Michael Taylor, co-author and Dean of Science at the University of the West Indies says the urgency of dealining with climate change is not an academic issue. "It is a matter of life and death for people everywhere," he says. "People from small island States and low-lying countries are in the immediate cross-hairs of climate change. I am very concerned about the future of these people."

Professor Hoegh-Guldberg reiterated the importance of the coming year (2020) in terms of climate action and the opportunity to strengthen emission reduction pledges in line with the Paris Agreement of 2015.

"Current emission reduction commitments are inadequate and risk throwing many nations into chaos and harm, with a particular vulnerability of poor peoples. To avoid this, we must accelerate action and tighten emission reduction targets so that they fall in line with the Paris Agreement. As we show, this is much less costly than suffering the impacts of 2oC or more of climate change."

"Tackling climate change is a tall order. However, there is no alternative from the perspective of human well-being - and too much at stake not to act urgently on this issue."

MEDFORD/SOMERVILLE, Mass. (Sept. 19, 2019)--College-student voting rates in the 2018 midterm elections doubled compared to the 2014 midterms, marking a watershed election year for student voter turnout, according to a report today from the Institute for Democracy & Higher Education (IDHE) at Tufts University's Tisch College of Civic Life. The report, Democracy Counts 2018, is based on an analysis of the voting patterns of more than 10 million college students on more than 1,000 campuses participating in the National Study of Learning, Voting, and Engagement (NSLVE).

In 2018, the Average Institutional Voting Rate (AIVR) among campuses in the study was 39.1 percent, nearly 20 percentage points higher than 2014's average turnout rate of 19.7 percent. Turnout increases were widespread, with virtually all campuses seeing an increase over 2014.

Major research findings include:

In the 2018 midterm elections, college students turned out to vote at double the rate of the last midterm. Across all students in the study, the National Student Voting Rate (NSVR) in 2018 was 40.3 percent. Remarkably, this 2018 student turnout was closer to the NSLVE-estimated voting rate for the 2016 presidential election-51.3 percent-than to the previous midterm in 2014-19.3 percent.

According to the U.S. Elections Project, the voting rate among all Americans increased 13 percentage points in 2018 as compared to the prior midterm. By comparison, the college and university National Student Voting Rate (NSVR) rose 21 percentage points.

In 2018, the voting rates of 99 percent of campuses in the study increased from the 2014 midterms, and nearly half of all institutions saw their rate increase between 15-24 percentage points.

Women in college continued to vote at higher rates than men in 2018, with black women maintaining their position as the most active voters on campus, and Hispanic women making the largest gains.

The largest voting rate increase across racial/ethnic groups was among Hispanic students, up 22.5 percentage points and more than doubling-from 14 percent in 2014 to 36.5 percent in 2018.

While older Americans historically vote at higher rates than their younger counterparts, 2018 data showed a trend toward age parity. The turnout gap between students over 30 and those under 22 narrowed from 22.3 percentage points to 16.9 points.

There was relative consistency in voting rates between students attending two-year, four-year, public or private institutions. Women's colleges continued to vote at the highest rates among institutional types, but two-year, four-year, public, and private institutions showed consistent upward movement between 2014 and 2018.

Voting gaps between disciplines persisted in 2018. Turnout among students in STEM fields, as well as those majoring in business, lag behind students studying the humanities, social sciences, and education.

"At a time of increased activism and voter participation by all Americans, today's report highlights even greater interest among college students. It marks a watershed election year for student voter turnout, including promising progress in narrowing some persistent turnout gaps," said Nancy Thomas, director of the Institute for Democracy & Higher Education at Tufts University's Tisch College. "College students today are more diverse than ever, and while they are not a monolithic group, they represent a formidable voting bloc of nearly 20 million."

"While more work remains to fulfill higher education's mission to educate for democracy, it is clear that colleges and universities provide a valuable space for political learning, civic engagement and electoral participation," continued Thomas. "Being for democracy is not a partisan agenda."

Today's report is based on the National Study of Learning, Voting, and Engagement (NSLVE), conducted by IDHE, which is the only national study of college-student voting. NSLVE examines voter turnout by comparing college campuses of different regions and types, and by comparing across student demographics and fields of study. It is based on the voting records of more than 10 million students at more than 1,000 colleges and universities in all 50 states and the District of Columbia; IDHE does not receive any information that could individually identify students or how they voted. The study provides reports to participating colleges and universities, which will be distributed this week and used to support political learning and civic engagement, as well as to identify and address gaps in political and civic participation.

In the coming months, Tisch College researchers will use these data to examine important factors in campus political learning and voting in the run-up to the 2020 elections and beyond.

In order to meet the demands of growing human populations, agricultural production must double within the next 30 years. Yet the health of today's crops and the promise of their yield face a rising slate of threats--from pests to chaotic weather events--leading to an urgent need to identify effective, natural plant defense strategies.

Biologists have access to a wealth of genomic and biochemical data, but rapidly deciphering entire biochemical pathways that protect key crops of global significance remains a significant challenge. Scientists are peeling away at the layers of immunity in maize, a staple for diets around the world, to determine if there are key genes that enable surprisingly diverse antibiotic cocktails that can be produced as defensive blends against numerous disease agents.

Now, a systematic and combined approach to identifying such genes in crop defense has been developed by Yezhang Ding, Alisa Huffaker and Eric Schmelz of the University of California San Diego and their colleagues and is described in Nature Plants.

"We need to know which crop defense mechanisms are effective and what we can do sustain or further improve them," said Schmelz. "Coauthors and collaborators in China are already taking some of the maize genes we characterized and are using them to significantly improve disease resistance in rice."

Historically, defining a complete new biochemical pathway in crops has required stepwise progress and often the better part of an entire research career. In the new study, the UC San Diego biologists describe how they combined an array of scientific approaches to clearly define six genes that encode enzymes responsible for the production of key maize antibiotics known to control disease resistance.

Maize plants lacking small molecule antibiotic defenses, derived from a skeleton of 20 carbon atoms known as diterpenoids, commonly suffer dramatic increases in fungal disease susceptibility.

"Most people appreciate that pine trees are heavily protected by sticky acid resins that kill or deter a majority of microbes and insects," said Schmelz. "We describe a complete maize biosynthetic pathway that also makes acid resins on-demand at the site of fungal attack. Interestingly, almost the entire pathway is derived from evolutionarily recent gene duplications from diverse hormone pathways related to plant growth and human testosterone metabolism."

One of the evolutionary steps was a comparatively recent gene duplication three million years ago from the hormone pathway responsible for plant growth called gibberellins. In a step not clearly borrowed from hormone biosynthesis, two highly promiscuous oxidative enzymes (with broad substrate and product specificity) termed cytochrome P450s were characterized to produce unique reactions different from known conifer pathways. In total, the effort leveraged more than 2,000 plant samples, each with 36,861 transcripts, spanning 300 different maize lines to systematically narrow candidates and define a maize pathway for antibiotics effective against fungal pathogens.