Earth

Changes to the environmental conditions that underpin the reproductive success of some corals may be causing their highly synchronized mass-spawning strategy to break down, a new study finds. This desynchronization - a previously unnoticed threat - could drive aging coral populations to extinction. When the water temperature and the moon align just so each year, entire colonies of coral reef release millions of tiny eggs and sperm into the ocean. Like cherry blossoms in a stiff breeze, the brightly colored gametes drift together in quantities so vast they can occasionally be seen from space. Because gametes only survive for a few hours, their highly synchronized release is crucial to ensuring successful fertilization. Previous studies have suggested that the synchronicity of coral reproduction relies on various environmental cues working in unison to determine the exact moment of spawning. Assuming these features are stable and consistent, researchers interested in threats to corals have focused on more observable damages, like bleaching events. However, given that changes associated with a changing climate are greatly contributing to mass mortality events worldwide, researchers have wondered if corals, too, are affected by these. Tom Shlesinger and Yossi Loya observed annual coral spawning events from the Red Sea's most abundant coral species and found that several have shifted the timing of spawning events. According to the authors, some species have experienced a complete breakdown in their reproductive synchrony, spawning in different months year to year, and even across several days within each month, severely reducing gamete fertilization potential. Findings from other reef communities indicate that reproductive asynchrony is likely occurring in different parts of the world as well, Shlesinger and Loya suggest. "[The authors] warn that coral populations around the globe might still appear healthy, while suffering silently from these reproductive struggles," write Nichole Fogarty and Kristin Marhaver in a related Perspective.

Results from a rapid-response oceanographic expedition in the North Pacific reveal a surprise about how lava from the K?lauea Volcano, which erupted on the island of Hawai'i during the summer of 2018, triggered a vast phytoplankton bloom. The study - a unique opportunity to study this rarely observed phenomenon in real time - informs how nutrient-poor marine ecosystems respond to both a massive influx of molten lava and nutrients. Beginning just three days after K?lauea's lava first began to pour into the ocean, a rapidly growing bloom of phytoplankton formed in the waters nearby, persisted throughout the two-month duration of the volcano's eruption and rapidly dissipated when the lava ceased to flow. At the height of K?lauea's discharge of lava into the ocean, Samuel Wilson and colleagues set sail to determine the cause and composition of the curious phytoplankton bloom. Using a suite of shipboard and subsea glider-based instruments, Wilson et al. sampled the seawater chemistry and phytoplankton diversity in different areas of the extensive bloom and revealed that unexpectedly high concentrations of nitrate played a key role in the particularly strong biological response to the influx of lava into the ocean. Lava, however, contains very little nitrogen indicating a non-volcanic source of micronutrients. The authors instead suggest that the rare phytoplankton bloom was fed by the lava heating water far below the surface and triggering the upwelling of nutrient-rich deep-water to the surface. Hugh Ducklow and Terry Plank highlight the implications of the novel biogeophysical process revealed by Wilson et al. in a related Perspective.

Intuitively, it is tempting to think that a child who has an elder brother or sister will grow up in a stimulating linguistic environment and will develop their language skills faster than the family's firstborn. However, several studies have shown the contrary: the acquisition of language in a child with an elder sibling is reported to be slower than a child who has none.

What is even more surprising is that apparently only elder brothers impact the language skills of their younger siblings, as a study conducted by a research team from the CNRS, the AP-HP, the EHESS, the ENS and the INSERM has just shown. The study finds that children who have grown up with an elder sister have identical development to children with no elder sibling.

More than 1000 children have been followed from birth to five and a half years old in the mother-child cohort EDEN*. Their language skills were evaluated at 2, 3 and 5.5 years old by tests measuring several aspects of language, such as vocabulary, syntax and verbal reasoning. Children who have an elder brother had on average a two-month delay in language development compared with children with an elder sister.

The scientists propose two hypotheses that may explain this result. The first is that elder sisters, in being more willing to talk to their younger siblings than brothers, may compensate for their parents being less available. Another hypothesis would be that elder sisters compete less than elder brothers for parental attention.

Though this study cannot separate these two hypotheses, it does show that early language development in a younger sibling tends to be slower when the elder is a boy. For their next project, the scientists want to examine the impact of culture (specifically geographical origin) on these results.

An international team of researchers has reported a new way to safeguard drones, surveillance cameras and other equipment against laser attacks, which can disable or destroy the equipment. The capability is known as optical limiting.

The work, published in the journal Nature Communications, also describes a superior manner of telecom switching without the use of electronics; instead, they use an all-optical method that could improve the speed and capacity of internet communications. That could remove a roadblock in moving from 4GLTE to 5G networks.

The team reported that a material created using tellurium nanorods - produced by naturally occurring bacteria - is an effective nonlinear optical material, capable of protecting electronic devices against high-intensity bursts of light, including those emitted by inexpensive household lasers targeted at aircraft, drones or other critical systems. The researchers describe the material and its performance as a material of choice for next-generation optoelectronic and photonic devices.

Seamus Curran, a physics professor at the University of Houston and one of the paper's authors, said while most optical materials are chemically synthesized, using a biologically-based nanomaterial proved less expensive and less toxic. "We found a cheaper, easier, simpler way to manufacture the material," he said. "We let Mother Nature do it."

The new findings grew out of earlier work by Curran and his team, working in collaboration with Werner J. Blau of Trinity College Dublin and Ron Oremland with the U.S. Geological Survey. Curran initially synthesized the nanocomposites to examine their potential in the photonics world. He holds a U.S. and international series of patents for that work.

The researchers noted that using bacteria to create the nanocrystals suggests an environmentally friendly route of synthesis, while generating impressive results. "Nonlinear optical measurements of this material reveal the strong saturable absorption and nonlinear optical extinctions induced by Mie scattering overbroad temporal and wavelength ranges," they wrote. "In both cases, Te [tellurium] particles exhibit superior optical nonlinearity compared to graphene."

Light at very high intensity, such as that emitted by a laser, can have unpredictable polarizing effects on certain materials, Curran said, and physicists have been searching for suitable nonlinear materials that can withstand the effects. One goal, he said, is a material that can effectively reduce the light intensity, allowing for a device to be developed that could prevent damage by that light.

The researchers used the nanocomposite, made up of biologically generated elemental tellurium nanocrystals and a polymer to build an electro-optic switch - an electrical device used to modulate beams of light - that is immune to damage from a laser, he said.

Oremland noted that the current work grew out of 30 years of basic research, stemming from their initial discovery of selenite-respiring bacteria and the fact that the bacteria form discrete packets of elemental selenium. "From there, it was a step down the Periodic Table to learn that the same could be done with tellurium oxyanions," he said. "The fact that tellurium had potential application in the realm of nanophotonics came as a serendipitous surprise."

Blau said the biologically generated tellurium nanorods are especially suitable for photonic device applications in the mid-infrared range. "This wavelength region is becoming a hot technological topic as it is useful for biomedical, environmental and security-related sensing, as well as laser processing and for opening up new windows for fiber optical and free-space communications."

Work will continue to expand the material's potential for use in all-optical telecom switches, which Curran said is critical in expanding broadband capacity. "We need a massive investment in optical fiber," he said. "We need greater bandwidth and switching speeds. We need all-optical switches to do that."

How important is mom? What about dad?

According to the National Academies of Sciences, Engineering, and Medicine, the well-being of a child's primary caregiver is one of the most important factors associated with fixing and preventing health disparities among children.

Children from low-income or ethnic minority homes are more likely to have poorer physical health, suffer from behavioral and/or mental health problems and have substance abuse disorders. But decades of work by developmental psychologists, including researchers at Arizona State University, shows that being strongly connected to their primary caregiver can protect children from the effects of poverty, discrimination, trauma and chronic stress. Based on this work, the recently released National Academies report Vibrant and Healthy Kids: Aligning Science, Practice, and Policy to Advance Health Equity prioritizes supporting primary caregivers.

"We know that a child's primary caregiver - who is most often the mother - is a good buffer against the adversity a child might experience, and a strong relationship between caregiver and child can begin to level the playing field in terms of health disparities," said ASU's Suniya Luthar, who was part of the interdisciplinary 14-member committee responsible for writing the report.

The importance of the primary caregiver

The emphasis on the well-being of caregivers is a new target for improving children's lives. A 2000 report on children's health, From Neurons to Neighborhoods: The Science of Early Childhood Development, focused on promoting self-regulation in children. The ability to adjust behavior based on circumstances - for example whether one responds to a verbal insult with a witty reply versus aggression - can predict success in school and healthy social relationships.

What influences how, and how well, children self-regulate?

According to ASU's Nancy Eisenberg, an expert on self-regulation in children, the answer includes biological factors, like genetics, the child's environment and the primary caregiver. The quality of the relationship between caregiver and child affects how well children self-regulate.

Luthar, who is a Foundation Professor of Psychology at ASU, was one of just two psychologists on the National Academies committee. Along with other developmental psychologists, she keeps finding that if the primary caregiver is unwell or under stress, the bond between caregiver and child can become dysfunctional and children can suffer. This idea, recently highlighted in a special issue of Child Development, forms the core of Luthar's research on motherhood and her work on developing ways to help mothers under stress.

The National Academies report includes a roadmap of recommendations for how to address health disparities in children. The first item on the roadmap is the usefulness of intervening early; the second is the importance of supporting a child's primary caregiver.

"But it is never too late to intervene," Luthar said.

Luthar added that a strong and healthy attachment between children and caregivers - one capable of buffering against challenges like growing up in poverty or experiencing chronic stress - is possible in all kinds of families and living situations. She has developed two of the scientifically validated supportive group interventions cited in the National Academies report. The Relational Psychotherapy Mothers Group is used with women who are living in poverty, and the Authentic Connections Group is used with mothers who are white collar professionals.

Fathers need support too

In 2018, fathers were the primary caregiver in 7% of American households, and the National Academies report emphasizes that understanding how best to ensure their well-being is also important.

"What mothers need and what fathers need can be very different, and what has been shown to work for supporting mothers might not work for fathers," Luthar said. "Instead of telling parents to do this or do that, we need to start asking how we can best equip mothers and fathers, individually, for success."

There are few evidence-based support programs designed specifically for male caregivers, but the report did mention one evidence-based program as a promising model for how to support fathers: The Family Check-Up.

Started by the late Thomas Dishion, the Family Check-Up teaches fathers and mothers parenting skills, like effective discipline methods, to help address problem behaviors in children. The Family Check-Up is one of the evidence-based interventions being implemented throughout the US and internationally by ASU's REACH Institute.

The program takes a holistic, wide angle perspective to problem behaviors in children, and involves all caregivers, whether they are mothers, fathers, grandparents, or guardians.

"What is happening with the child is not just about the child: it is about the family, the school, and even the neighborhood," said Anne Mauricio, who is an associate research professor of psychology at ASU who is currently working on scaling up the program.

Mauricio said support for the caregiver is a critical part of both the program's framework and its success.

Evidence-based interventions that provide support to primary caregivers -- like the Relational Psychotherapy Mothers Group, Authentic Connections and the Family Check-Up -- are a feasible and scalable way to leverage the caregiver-child relationship as a buffer against adversity like poverty, discrimination, trauma and chronic stress.

"The interventions just need to have the right ingredients, which are the same for low-income moms with addiction or mental health problems as they are for well-educated moms. Caregivers, just like their children, need ongoing, authentic love and support," Luthar said.

SILVER SPRING, Md. - Scientists from the Walter Reed Army Institute of Research joined a network of African scientists, the Plasmodium Diversity Network Africa, and Wellcome Trust Sanger Institute to publish a groundbreaking study about the genetic diversity of the world's most dangerous and prevalent species of malaria, Plasmodium falciparum across sub-Saharan Africa.

Malaria, infecting approximately 219 million individuals in 2017, remains a meaningful threat to public health and regional stability. One of the top five infectious disease threats to deployed Service Members, it is also a cause for concern for the U.S. military, whose investments in malaria research have supported the development of most FDA-approved malaria prevention and treatment drugs, as well as the world's most advanced malaria vaccine, RTS,S. Though infection rates have been decreasing, this decline has stagnated in recent years, necessitating novel interventions.

This study, published in Science, utilized whole genome data from 2263 P. falciparum isolates from 24 sites in 15 countries to provide novel insights into the depth of genetic diversity and distinct regional character of the parasite across the continent of Africa.

Human and natural history are the most likely explanations for the identified genetic variation. Human movement across the continent, driven at first by migration across the continent then subsequently colonization and slavery - or lack thereof in the case of Ethiopia which was not colonized - may explain the highly-differentiated parasite population from the rest of Africa. By contrast, parasites from distant former French colonies share genetic material.

The introduction of malaria drugs has also had a major impact on the divergence of the parasite. New signatures found in P. falciparum in Malawi and Ghana may be due to the selection pressure introduced by artemisinin-based combination therapies, first-line treatment for uncomplicated malaria in most of Africa. Geneflow between subpopulations could spread drug resistance from one subpopulation to the rest of the continent.

"Malaria is one of the most important parasitic diseases with one of the largest genomes dedicated to immune escape, a shape shifter that morphs into more than 12 different shapes and stages in two hostile environments in the human host and the vector," said Lt. Col. Edwin Kamau, an author on the paper and scientist at WRAIR, underscoring the difficulty of malaria control and elimination.

As malaria drug resistance develops and spreads between the distinct P. falciparum populations facilitated by human movement in all directions across Africa, understanding the regional characteristics of the parasites becomes increasingly critical to ensuring targeted, effective interventions. "The race is on to identify and validate drug resistance markers for ACTs and other interventions in Africa and other malaria endemic parts of the world," said Dr. Ben Andagalu another author on the paper who is at the U.S. Army Medical Research Directorate-Africa, a subordinate directorate of the WRAIR headquartered in Kenya.

WRAIR and its partners remain committed to developing novel interventions to prevent the transmission of malaria, including mosquito repellents, chemoprophylaxis, biologics and more in order to eliminate the threat towards Service Members.

The important nutrient phosphate may be less abundant in the global ocean than previously thought, according to a new paper in Science Advances. The researchers compiled data collected using highly sensitive techniques that measure phosphate to create a more accurate dataset to power global ocean models.

"This is a bit of a wake-up call that, as technology advances, we need to update the underlying data and processes that fuel ocean models to ensure they yield the best possible predictions," said Mike Lomas, senior research scientist at Bigelow Laboratory for Ocean Sciences and an author of the paper. "Models are our best chance to predict the many ways the oceans will respond as climate changes, but our predictions are only as good as the data underlying them."

Lomas and his coauthors found that data collected using high-sensitivity measurements reveal that phosphate in the surface ocean is less abundant than traditional measurements and models suggest. They also discovered previously-unknown patterns in phosphate levels in major ocean basins in both the Atlantic and Pacific. Ocean algae depend upon the mineral phosphate, which is essential to all life on Earth. Lower phosphate levels pose challenges for algae, which are already predicted to suffer as climate change makes ocean nutrients scarcer.

The research team compiled high-sensitivity phosphate datasets collected throughout the global ocean, including measurements Lomas collected over nearly two decades of intensive study in the Sargasso Sea. They mapped this new, more accurate dataset, and compared the result to that yielded by more common, lower-sensitivity methods. These methods are used widely because they require less time and less sophisticated equipment, but they don't allow researchers to detect phosphate levels as accurately.

"The reality is that we've been operating with a skewed view of ocean phosphate," Lomas said. "With this improvement, we will be able to make our models a little bit more realistic and better able to predict this aspect of climate change's impact on our oceans."

The element phosphorus is a key ingredient in the fundamental molecules of life, including the genetic code DNA and the molecule ATP, which provides the energy to fuel cells. It is rare in the ocean, and, unlike most other essential nutrients, the amount of phosphorus on Earth is finite. Knowing the true availability of phosphorus in the ocean is essential to accurately describing how the base of the food web functions - and how it will respond as climate change alters ocean chemistry.

Lomas hopes to continue this research by studying how ocean algae take in organic phosphorus dissolved in seawater, another potentially important - and poorly understood - source of the element. He believes this phosphorus may help support algae in low-phosphate regions, and that understanding its role has the potential to improve ocean models even further.

"There is a vast sea of existing data to explore, and it likely holds as many undiscovered truths as the bottom of the ocean," Lomas said. "As a global scientific community, we need to support more projects that help us capitalize on this trove for important insights into the ocean."

TALLAHASSEE, Fla. -- An overwhelming scientific consensus affirms that for thousands of species across the globe, climate change is an immediate and existential threat.

For the loggerhead turtle, whose vast range extends from the chilly shores of Newfoundland to the blistering beaches of Australia, the story isn't so cut and dried.

New research from conservation biologists at Florida State University and their collaborators suggests that while some loggerheads will suffer from the effects of a changing climate, populations in certain nesting areas could stand to reap important short-term benefits from the shifting environmental conditions.

In an investigation of 17 loggerhead turtle nesting beaches along the coast of Brazil, scientists found that hatchling production --the rate of successful hatching and emergence of hatchling turtles -- could receive a boost in temperate areas forecasted to warm under climate change. But those improvements could be relatively short lived.

"Even though hatchling success is projected to increase by the year 2100 in areas that currently have lower temperatures, it is likely that as climate change progresses and temperatures and precipitation levels approach negative thresholds, hatchling production at these locations will start to decrease," said study author Mariana Fuentes, an assistant professor in FSU's Department of Earth, Ocean and Atmospheric Science.

The study was published in the journal Scientific Reports.

During the incubation process, marine turtle eggs are heavily influenced by their environments. Air and sand temperatures can determine the sex of hatchlings, spikes in moisture content can drown developing embryos, and excessive solar radiation exposure can affect turtles' morphology and reduce their chances of survival.

In their study, the FSU researchers evaluated current and projected hatchling production under a variety of different environmental conditions throughout the expansive Brazilian coastline.

In the northern equatorial nesting beaches where temperatures already soar, the team found persistent and accelerating climate change will increase air temperatures and escalate precipitation beyond the thresholds for healthy incubation -- a major hit to hatchling production.

For the temperate beaches farther down the coast, climate change will bring similar increases in air temperature and precipitation. But, hundreds of miles from the equator, the effects of those changes look considerably different.

"These cooler beaches are also predicted to experience warming air temperatures; however, productivity is predicted to increase under both the extreme and conservative climate change scenarios," said former Florida State master's student Natalie Montero, who led the study.

Over the coming decades, as the climate shifts and temperatures climb, these conventionally cooler beaches will become more suitable for healthy loggerhead incubation. But if climate change continues unabated, "these beaches could also become too warm for successful production, much like the warmer beaches in our study," Montero said.

The researchers also stress that changes associated with a warming climate -- beach erosion, unchecked coastal development and environmental degradation, for example -- pose urgent threats to marine turtle nesting beaches at all latitudes, regardless of air temperature or precipitation.

And while contemporary and future shifts in climate conditions could benefit select loggerhead populations, well-documented warming trends suggest the long-term prospects of these and other ancient sea turtle species remain precarious.

"Sea turtles have been around for a long time and have survived many changes to the global climate," Montero said. "However, climate changes of the past took a long time, allowing sea turtles to adapt to the changing conditions. Today's climate change is happening very quickly, and therefore sea turtles must adapt quickly or perish."

Washington, DC - September 3, 2019 - Researchers have developed an animal model to test HIV infection and therapies in infants, allowing them to develop biomarkers to predict viral rebound after antiretroviral therapy (ART) interruption. The simian-human immunodeficiency virus (SHIV)-infected infant rhesus macaque model, a collaborative effort among researchers at several institutions, is described in a recent issue of the journal mBio.

"To date, all of the animal models that have been developed for studying novel therapies in nonhuman primate models around HIV have been in adult animals. A lot of those are immune based strategies, and we know that infants have a developing immune system that has distinct qualities," said study principal investigator Sallie Permar, MD, PHD, professor of pediatrics in the Division of Infectious Diseases; professor of molecular genetics and microbiology, immunology, and pathology; and member of Duke Human Vaccine Institute. "It is important to develop a model by which we can study infected infants and study the interventions that can be implemented to reduce the viral reservoir and delay time to rebound after stopping antiretroviral therapy."

The new model allows for immune interventions against the HIV envelope protein through the use of a SHIV, as opposed to a SIV, a simian immunodeficiency virus that has a very different virus envelope than HIV. Differences exist in the infant modes of HIV acquisition and immune responses, compared with adults or adolescents who become infected mostly through the sexual route. Moreover, this model takes advantage of recent advances in SHIV development that fully replicated the clade C viruses that are involved in the majority of infant HIV transmission. Researchers at the University of Pennsylvania have developed a new way to make SHIV, in which mutations are made around the CD4 binding site that HIV uses for entry into cells."This opened up a new treasure trove of SHIVs that would be available for this type of model," said Dr. Permar.

In the study, the researchers infected the infant monkeys with the new SHIV in the first one to two months of life, simulating a breast milk transmission. They then started the animals on antiretroviral therapy 12 weeks later and stopped treatment after a few months.They evaluated plasma virus load and found that the virus reached high peak virus load and responded quickly to therapy, which simulates what is seen in human infants.

The researchers then compared the viral replication kinetics and reservoir in infant rhesus macaques to that seen in a separate study of adult rhesus monkeys infected with the same SHIV strain. Infant monkeys had their virus rebound a couple of weeks after stopping the drugs, which was similar to adults, but adults had better virus control after rebound. "There are going to be differences in the infant and adult based therapies that are aimed at extending the time to viral rebound after stopping antiretroviral therapies," said the lead author of the study Ria Goswami, PHD, a postdoctoral associate at the Duke Human Vaccine Institute. "Novel interventions that do not rely on daily adherence to antiretroviral therapy are needed to achieve sustained viral remission for perinatally infected children, who currently rely on lifelong ART."

The researchers are already at work using the new model to test novel immune-based therapies, including monoclonal antibody therapies directed against the HIV envelope, to extend the time to virus rebound after stopping therapies. "A few years ago, a Mississippi baby who went on treatment quickly after delivery and exposure to HIV, and was then taken off therapy unintentionally, had no detectable virus for over two years. Eventually, the virus did return," said Dr. Permar."We are interested in how we can make it more likely to have more children like that."

When infants are started on HIV therapies in the earliest months of life and have to continue them lifelong, they are exposed to additive toxicities. "We are interested in having safer alternative strategies to antiretroviral drugs that will maintain virologic control for infected infants that are developed specifically for infants," said Dr. Permar."This is the first infant SHIV model to model HIV treatment and rebound."

Weight loss in older adults is accompanied by loss in bone mineral density (BMD) and an increased risk of bone fracture. A new study published in Obesity found that loss of hip BMD persists in the year following a weight loss intervention among older adults with obesity, regardless of whether they regain weight.

The study also found that losses in fat mass and lean mass contribute to reduced hip BMD; yet, loss in fat mass may signal improved trabecular bone score, which is a measure of bone texture and is a marker for the risk of osteoporosis.

The findings emphasize the importance of identifying and implementing interventions that can target fat mass, but not lean mass, loss to optimize bone health during weight loss in older adults.

Prior research identified four distinct dating trajectories from 6th to 12th grade: Low, Increasing, High Middle School, and Frequent. In a new study published in the Journal of School Health, researchers found that adolescents who were not in a romantic relationship had good social skills and low depression, and fared better or equal to peers who dated.

The study included 594 10th graders. Investigators compared the four dating groups using teacher ratings and student questionnaires.

The results refute the notion that non-daters are maladjusted. Efforts in schools that promote health should include non-dating as one option of healthy development.

"In the end, school health educators, mental health professionals, and teachers should affirm social norms that support adolescents' individual freedom to decide whether to date or not, indicating that both are acceptable and healthy options," said lead author Brooke Douglas, of the University of Georgia.

Immune checkpoint inhibitors are a type of therapy that uses the immune system to fight cancer. They have been hailed as game changing, garnering a Nobel Prize last year and quickly becoming the standard of care for many tumor types such as melanoma and certain lung and head and neck cancers. But among patients with non-small cell lung cancer (NSCLC) who receive checkpoint inhibitor immunotherapy, recent reports suggest that up to 19% may develop a dangerous complication: an inflammation of their lungs, dubbed checkpoint inhibitor pneumonitis (CIP). Now, Johns Hopkins researchers have for the first time studied the immune cells of NSCLC patients who have CIP and discovered what sets them apart from patients who don't develop CIP. The differences they pinpointed could lead to new ways to identify pneumonitis complications and treat them.

"We were seeing a lot of patients with this particular type of lung inflammation, but we really didn't know what was going on in terms of the biology of this disease until now," says Karthik Suresh, M.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and co-first author of the study's paper (along with Jarushka Naidoo, M.B.B.Ch., assistant professor of oncology at Johns Hopkins). The paper will be published September 4th, 2019 in The Journal of Clinical Investigation.

An immune checkpoint inhibitor (ICI) works by releasing the molecular brakes on components of the human immune system, coaxing the patient's immune system to attack cancer cells. But turning up the immune system's activity can also lead to unwanted side effects when the immune system attacks healthy tissues. With NSCLC, one of the relatively common side effects is CIP. Patients typically develop shortness of breath and a cough, but the illness can progress to be life threatening. Anyone with CIP must stop cancer treatment with immune checkpoint inhibitors, and many are treated with steroids instead. However, some cases don't respond to steroids, and there is no second-line treatment for CIP that is backed by research.

"There are patients who are seeing great results with checkpoint inhibitors when it comes to their cancer, but if they develop this complication, we have to stop their life-changing treatment," says Franco D'Alessio, M.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and a senior author of the new study. "So figuring out how to treat CIP is of paramount importance to be able to keep patients on track with their cancer treatment."

In the new work, Suresh, D'Alessio, Naidoo and their colleagues studied tissue collected from the lungs of 12 NSCLC patients with CIP andsix patients being treated with ICIs who hadn't developed CIP. Patients ranged in age from 55 to 77; 27.8% were female and 77.8% were Caucasian. Lung cells and surrounding molecules were collected through bronchoalveolar lavage, a procedure in which a small scope is inserted into the airways and fluid is squirted into the lung and then collected.

The team found that patients with CIP had higher levels of memory T cells -- a type of pro-inflammatory immune cell -- in their lungs than patients without CIP. While on average, memory T cells made up about 1% of the immune cells in patients without CIP, the cells were present at about 11% in those with the disease. Moreover, when the researchers analyzed regulatory T cells (Tregs) -- a type of anti-inflammatory immune cell that typically keeps inflammatory responses from becoming too excessive -- they found that the Tregs had significantly decreased levels of two important proteins: CTLA-4 and PD-1. In general, lower levels of these proteins indicate less active Tregs, the researchers say.

"This explains the exuberant immune response in CIP," says D'Alessio. "You not only have memory T cells that are awakened and reactive, but you have Tregs not being able to control those angry memory T cells."

The researchers noted a handful of other variations in the immune profiles of NSCLC patients with and without CIP, all of which help point to new ways to treat the disease. For instance, molecules that recruit lymphocytes -- which include memory T cells -- to the lungs were present in higher levels in CIP patients, as were proteins that make the memory T cells stick to lung tissue.

"Based on the cell types we found, our study suggests several new pathways that could be investigated as therapeutic targets," says Suresh. The findings also helped eliminate the use of some treatments -- for instance, some doctors had been using drugs called tumor necrosis factor (TNF) alpha inhibitors to try to treat CIP, but the new study did not observe increased levels of TNF alpha in the bronchoalveolar lavage fluid of CIP patients, perhaps explaining why the drugs have been less successful in treating CIP.

The researchers still have questions about why the lung's immune cells are altered in the first place in CIP patients, and exactly how immune checkpoint inhibitors set off the inflammation. They're planning follow-up studies to answer basic biology questions about the immune cells involved as well as to test drugs that may work against CIP.

A single incidence of traumatic brain injury (TBI) can lead to long-lasting neurodegeneration, according to a study of 32 individuals. In addition to clarifying the little-understood chronic effects of TBI, the study's methods could improve the diagnosis and monitoring of brain damage in patients who have suffered an injury. Research has shown that TBI can trigger progressive accumulation of tau, a protein associated with neurodegeneration that plays a major role in Alzheimer's disease. Scientists have studied the effects of TBI by combining PET imaging with flortaucipir, an imaging agent that binds to tau. Most imaging studies have been performed in athletes who have experienced multiple injuries, but it is less clear how the brain changes in survivors who experienced a single TBI. Nikos Gorgoraptis and colleagues performed flortaucipir PET scans to study the distribution of tau in 21 participants who experienced a TBI at least 18 years prior, due to either traffic accidents or assault. The experiment revealed that collectively, the TBI cohort showed more deposition of tau (as indicated by higher flortaucipir binding) compared to 11 healthy controls and performed more poorly on tests of memory and cognitive performance. Furthermore, TBI subjects with higher tau deposition showed more severe neurodegeneration, and tau deposition was also linked to damage to the brain's white matter - the tissue that insulates and nurtures neurons. The ability to detect tau in patients after TBI could help in the design of future trials of tau-targeting therapies, the authors add.

(MEMPHIS, Tenn. -Sept. 4, 2019) Like pirates on a treasure hunt, St. Jude Children's Research Hospital scientists have created the first 3D map of a mouse genome and used it to discover scientific gold. The gold includes insight from machine learning into genomic organization and function during development. The research appears today in the journal Neuron.

"Understanding the way cells organize their genomes during development will help us to understand their ability to respond to stress, injury and disease," said Michael Dyer, Ph.D., chair of the St. Jude Department of Developmental Neurobiology and Howard Hughes Medical Institute investigator. He and Xiang Chen, Ph.D., assistant member of the St. Jude Department of Computational Biology, are the corresponding authors.

The research focused on light-sensing rod cells in the mouse retina. More than 8,000 genes are turned on or off during retinal development. Thousands of regulatory regions across the genome also play a role. Researchers used technology called ultra-deep chromosome conformation capture or Hi-C analysis to map those interactions in mouse rod cells.

Previously, 3D genomics has focused primarily on understanding regulation of specific genes and worked with cells growing in the laboratory.

Using integrated analysis of data from a variety of sources and machine learning, investigators showed genomic organization changed in surprising ways at different stages of development. "These changes are not random, but part of the developmental program of cells," Dyer said.

Dyer and his colleagues have used the same approach to create a 3D genomic map of the mouse cerebellum, a brain structure where medulloblastoma can develop. Medulloblastoma is the most common malignant pediatric brain tumor.

Packaging

The human genome is encoded in the 3 billion chemical bases of human DNA. Since the first human genome was completely sequenced in 2003, researchers have used the technology to identify and study inherited or acquired genomic alterations that lead to cancer and other diseases.

Stretched its entire length, DNA from a single human cell measures about 6 feet long. To function, the DNA is packaged into a microscopic bundle that fits into the nucleus of cells. The resulting DNA loops can bring together otherwise distant regions of the genome. Key details, including a 3D map of loops and the interactions they fostered, were largely a mystery.

3D genome

The current study captured long-distance interactions between promoters (DNA regions that promote gene expression) and enhancers (regions that increase gene expression) at different stages of retinal development. Researchers also tracked changes in genome organization during development. That included the first use of machine learning to gauge how easily accessible genes are for transcription. Chen led the machine-learning effort.

Additional highlights

The research also included the first report of a powerful regulator of gene expression, a super enhancer, that worked in a specific cell at a specific stage of development. The finding is important because super enhancers can be hijacked in developmental cancers of the brain and other organs.

In this study, the scientists determined that when a core regulatory circuit super-enhancer for the Vsx2 gene was deleted, an entire class of neurons (bipolar neurons) was eliminated. No other defects were identified. Deletion of the Vsx2 gene causes many more defects in retinal development so the super-enhancer is highly specific to bipolar neurons.

Researchers developed a genetic mouse model of the defect that scientists are using to study neural circuits in the retina.

Study data and an instructional video are available to researchers worldwide through St. Jude Cloud, an online, cloud-based data-sharing resource.

Based on climatic data from 36 years, and the location of 646 breeding sites in 30 countries, the model reveals for the first time where the species might overwinter after their trip to tropical Africa.

The new approach could be used to study potential effects of climate change in the behaviour of migratory insects

Researchers from the Institute of Evolutionary Biology (IBE), a joint research institute of the Spanish National Research Council (CSIC) and Pompeu Fabra University (UPF), in Barcelona, Spain, and from the University of Grenoble-Alpes in France, have developed a method for predicting where the populations of the migratory Painted Lady butterfly (Vanessa cardui) distribute along the year and across their Europe-Africa migratory range. Their findings are published today in the journal Proceedings of the Royal Society B.

In a previously published study, the researchers demonstrated that Painted Lady butterflies migrate from Europe to tropical Africa by the end of summer, crossing the Mediterranean Sea and Sahara Desert. In a follow-up study, the researchers showed that the offspring of these migrants reverse their migration towards Europe in spring. Thus, the Painted Lady butterfly travels 15,000 km between Africa and Europe through multiple generations to seasonally exploit resources and favourable climates in both continents.

"The challenge now is to understand how migratory species are able to optimize time and space as to properly find the environmental requirements that each generation need for their survival" states Gerard Talavera, the leading author, researcher at IBE and a National Geographic Explorer.

- The key is to find the caterpillars -

Migratory insects are in a continuous move, and it is difficult to track from where to where they migrate. One of the main reasons for species to migrate is to find the optimal environmental conditions to raise a new generation. The immatures (eggs, caterpillars and cocoons) are key stages in the butterfly life cycle, which, unlike the adults, cannot escape from adverse situations. Thus, their breeding habitat is a very good indicator of the specific requirements that the species need to survive.

The present study has gathered information of up to 646 breeding occurrences of Painted Lady butterflies in 30 countries. By using time-series of 35 years of monthly climatic data, the researchers have built a model that defines the breeding requirements of the species and produced a map of the most probable areas for the species to breed every month.

"We thought that we could learn about the movements of the adults by looking at where the caterpillars grow at different times of the year" says Mattia Menchetti, member of the research team. "If we can map in space and time the sites where they breed along the year, then we can understand from where to where the adults can migrate".

The species rely on their reproductive success in both continents: Africa and Europe

The model shows that the species is forced to move across its overall range, since suitable breeding habitat is rarely permanent all the year. "Because the species breeds continuously for the entire year, its reproductive success relies on both continents. The results show the relevance of the sub-Saharan winter population stock in sustaining the migrations of the species into Europe", says Talavera.

However, the situation could eventually revert if the overall permanent suitable extent grows substantially in the future, as a consequence of global warming. "We cannot discard that the impact of rapid climate change may affect the butterfly migratory phenomena in unpredictable ways, as has already been shown to happen in migratory birds", adds Talavera.

- The overwintering missing generations might be near the equator -

Even if it has been proved that most populations of the Painted Lady butterfly spend the winters in the sub-Sahara, many of the precise localities are still unknown. Thanks to this new modelling approach, the researchers have identified the potential niche requirements of the species during the winter in Africa, and thus the sites where these could aggregate to breed.

According to the results of the study, the butterflies could locate near the equatorial latitudes between December and February. This scenario confirms that the overall migratory circuit undertaken by the annual successive generations might encompass up to 15,000 km, from the equator (e.g. Kenyan and Cameroonian highlands) to northern Scandinavia.

- A global project -

The findings published in Proceedings of the Royal Society B are part of a wider project aimed at studying the Painted Lady's migratory behaviour and routes worldwide. With that goal in mind, the team lead a long-term global citizen science project called The Worldwide Painted Lady Migration, which invites citizens from all over the word to communicate observations of the Painted Lady butterfly. More information on this project is available here: http://www.butterflymigration.org.