Culture

University of South Carolina scientists are exploring ways to make nerve regeneration happen faster and more successfully.

A new study published in Current Biology identifies the biological triggers that promote quicker nerve regeneration. From their previous studies, the researchers knew that damaged nerves regrow more quickly when "stress granules" in the site of the nerve injury are broken apart. Now they know what causes those stress granules to disassemble through a process called protein phosphorylation.

"The important thing is that we identified the protein that drives that process and showed how that's regulated," Jeff Twiss, a UofSC biology professor and co-author on the paper, said.

"It actually opens something new," Pabitra Sahoo, the paper's lead author, said. "In the future, it could help us design molecules that can promote phosphorylation."

Twiss said nerves typically regrow at 1 to 2 millimeters per day, meaning that an adult with nerve damage around their kneecap might require a year to recover as the nerve re-extends back to the foot. Given such a prolonged time to regenerate the nerve, atrophy makes a full recovery difficult.

"Finding ways to speed that up is critical to decreasing the amount of time that a person has loss of function, sensation and movement," said Twiss, the UofSC SmartState Chair in Childhood Neurotherapeutics. "But also, when you allow the nerve to find its way back to the target quicker, you can recover much more function."

Nerve cells contain the protein G3BP1 in clusters known as stress granules. When a nerve is severed, those granules begin to break apart through phosphorylation, a modification that makes G3BP1 become more negatively charged. This process releases mRNAs, important building blocks that the cell can use to build new proteins that extend the nerve. This phosphorylation makes the nerve grow faster, according to research that Sahoo and Twiss's team published in 2018.

The 2020 study took a step back to look for the processes that trigger the phosphorylation, in hopes that the entire process could be accelerated. The researchers determined that an enzyme known as Casein kinase 2-alpha (CK2α) is responsible for breaking up the G3BP1 granules through phosphorylation. When they increased CK2α levels, nerves grew faster, and the cell contained more phosphorylated G3BP1. When they decreased CK2α, the process slowed.

But where does the CK2α come from? The researchers placed a piece of nerve in a test tube, damaged it, and monitored the CK2α levels. Those levels increased, indicating that the damaged nerve synthesizes CK2α on its own at the injury site, rather than receiving it from its cell body. The process seems to be regulated by calcium ions.

These discoveries offer promising areas for further study. The UofSC researchers are already looking at methods for spurring the CK2α synthesis to speed up the nerve growth. Finding that key could lead to advances in medicine that result in faster healing after nerve injuries.

For a tiny embryo to develop into an adult organism, its cells must develop in precise patterns and interact with their neighbors in carefully orchestrated ways. To create complex tissues and organs -- from the pattern of rods and cones in the retina to the Byzantine filtration systems of the kidney -- all these developing cells must constantly answer a fundamental but surprisingly difficult question: Where am I?

"In the field of regenerative medicine, we can use stem cells to make organoids to study disease, but we can't yet put them into a person and have them repair a wound or heal sick tissue. A big part of that is that we don't have right signals to tell the cells where to go and what to do when they get there," said synthetic biologist Wendell Lim, PhD, Byers Distinguished Professor and chair of the UCSF Department of Molecular and Cellular Pharmacology.

One of the ways cells in developing organisms keep track of where they are and what they are supposed to be doing is through a type of chemical signal called a morphogen. These signals are produced by so-called organizer cells and diffuse outward through the local tissue. As the signal diffuses its concentration fades, telling local cells exactly how far they are from the source. With multiple organizer cells churning out different morphogens from key locations in a growing organism, cells can create a 3D spatial map that guides their development into complex tissues, much like a cellular GPS coordinate system.

Scientists are still working to understand how morphogens' signals are broadcast over just the right distances and how cells are calibrated to respond to the proper concentration at the appropriate time. But these questions are difficult to investigate because natural morphogens interact with their environment in many complex, hard to define ways.

Instead of deconstructing morphogens one interaction at a time, Lim's synthetic biology team at UCSF and a pair of research groups at the Francis Crick Institute in London -- led by Guillaume Salbreux, PhD, and Jean-Paul Vincent, PhD (himself once a post-doc with UCSF's Patrick O'Farrell, PhD) -- independently took the innovative approach of engineering a synthetic morphogen from the ground up. Their goals, as reported in two papers published October 16, 2020, in Science, were to study what makes morphogens work, and perhaps one day to create synthetic signals that could help control tissue regeneration or guide cellular therapies to heal wounds or fight cancers.

Lim's team, led by postdoctoral fellow Satoshi Toda, PhD, now an assistant professor at Kanazawa University's Nano Life Science Institute in Japan, started with an inert molecule called GFP, to which cells are normally completely deaf. To give cells the ability to respond to this new signal, the researchers used special types of antibodies to create GFP-responsive receptors. They genetically inserted these receptors into cells in laboratory dishes and linked them up to a cellular control system called SynNotch, which the lab had previously developed.

When the researchers instructed a subset of organizer cells at one end of the dish to produce GFP, the clouds of the fluorescent protein diffusing away from these anointed organizers activated the engineered receptors and imparted patterned gene activity in surrounding cells.

"I think it's pretty striking that a crude morphogen is not very hard to make," Lim said. "It gives us a sense of how simpler signaling molecules might have evolved to become morphogens in early days of multicellular evolution."

At UCSF, the researchers showed that these engineered morphogens could direct the formation of novel, user-defined striped patterns. At the Crick Institute, scientists used a similar approach in living flies -- showing that engineered morphogens could take the place of natural signals in successfully organizing the intricate patterns of the fly wing.

Because all the interactions in these systems are engineered, their characteristics are known and therefore amenable to mathematical modeling, the researchers say. These studies open the way to a testable theory of pattern formation by morphogens, and one day could help scientists program cells like robots to follow molecular trails to find and regenerate injured or diseased tissues.

Greenwood, SC (October 15, 2020) - A research team at the Greenwood Genetic Center (GGC) has successfully used small molecules to restore normal heart and valve development in an animal model for Mucolipidosis II (ML II), a rare genetic disorder. Progressive heart disease is commonly associated with ML II. The study is reported in this month's JCI Insight.

The small molecules included the cathepsin protease K inhibitor, odanacatib, and an inhibitor of TGFß growth factor signaling. Cathepsin proteases have been associated with later-onset heart disease including atherosclerosis, cardiac hypertrophy, and valvular stenosis, but their role in congenital heart defects has been unclear. The current study offers new insight into how mislocalizing proteases like cathepsin K alter embryonic heart development in a zebrafish model of ML II.

"Mutations in GNPTAB, the gene responsible for ML II, alter the localization and increase the activity of cathepsin proteases. This disturbs growth factor signaling and disrupts heart and valve development in our GNPTAB deficient zebrafish embryos," said Heather Flanagan-Steet, PhD, Director of the Hazel and Bill Allin Aquaculture Facility and Director of Functional Studies at GGC. "By inhibiting this process, normal cardiac development was restored. This finding highlights the potential of small molecules and validates the need for further studies into their efficacy."

Flanagan-Steet noted that she hopes the current work with ML II zebrafish will provide the basis to move one step closer to a treatment.

It's not a coincidence that dogs are cuter than wolves, or that goats at a petting zoo have shorter horns and friendlier demeanors than their wild ancestors. Scientists call this "domestication syndrome" -- the idea that breeding out aggression inadvertently leads to physical changes, including floppier ears, shorter muzzles and snouts, curlier tails, paler fur, smaller brains, and more.

The link appears to come from certain neural crest cells, present before birth and in newborns, that have a versatility akin to stem cells. These neural crest cells can turn into a handful of different things, specifically adrenal cells -- which boost the strength of the "fight or flight" response -- as well as physical traits like larger teeth and stiffer ears.

Ever since Darwin's time, some scientists have speculated that humans "self-domesticated" -- that we chose less aggressive and more helpful partners, with the result that we have shifted the trajectory of our own evolution.

"The evidence for this has been largely circumstantial," said Asif Ghazanfar, a professor of psychology and neuroscience. "It's really a popular and exciting idea but one that lacks direct evidence, a link between friendly behavior and other features of domestication."

To see if the story could be put on a robust foundation, Ghazanfar turned to marmoset monkeys. Like humans, marmosets are extremely social and cooperative, plus they have several of the physical markers consistent with domestication, including a patch of white fur on their foreheads that is common in domesticated mammals.

What does cooperation look like in a monkey? Friendly vocal exchanges, caring for each other's young, and sharing food, among other signs, said Ghazanfar.

The research team showed that the size of a marmoset's white fur patch was strongly related to how frequently it produced friendly vocal responses to another. This is the first set of data to show an association between a friendly behavior and a physical domestication trait in individual animals.

To show a causal link between the white patch and vocal behavior, the researchers tested infant twins in different ways. In very brief sessions, one twin got reliable vocal feedback from a simulated parent -- a computer programmed with adult calls that responded to 100% of their vocalizations -- while the other twin only heard parental responses to 10% of their sounds.

These experimental sessions lasted 40 minutes, every other day, for most of the first 60 days of the monkeys' lives. For the other 23+ hours of each day, the monkeys were with their families.

In previous work, Ghazanfar and his colleagues showed that the infants who received more feedback learned to speak -- or more precisely, developed their adult-sounding calls -- faster than their siblings. By also measuring the white fur patches on the developing monkeys' foreheads at the same time and for three more months, the researchers discovered that the rate of the white facial coloration development was also accelerated by increased parental vocal responses. This shows a developmental connection between facial fur coloration and vocal development -- they are both influenced by parents.

That connection may be via those neural crest cells that can turn into "fight or flight" cells and that also contribute to parts of the larynx, which is necessary for producing vocalizations.

Domestication in other species has also been linked to changes in vocal behavior. Foxes selected for tameness have altered their vocalizations in response to the presence of humans. Similarly, a tame Bengalese finch learns and produces a more complex song, and retains greater song plasticity in adulthood, than its wild cousins.

But this is the first study linking the degree of a social trait with the size of a physical sign of domestication, in any species, said the researchers. Their findings are detailed in an article published online in the journal Current Biology. Ghazanfar's co-authors include Daniel Takahashi, a former postdoctoral researcher who is now a professor of neuroscience at Federal University of Rio Grande do Norte, Brazil; Rebecca Terrett of the Class of 2016; Lauren Kelly, Ghazanfar's former lab manager, who now works at Rutgers-Robert Wood Johnson Medical School; and two collaborators from New York University, James Higham and Sandra Winters.

"If you change the rate of the marmosets' vocal development, then you change the rate of fur coloration," said Ghazanfar. "It's both a fascinating and strange set of results!"

HOUSTON - (Oct. 15, 2020) - Education has long been linked to health -- the more schooling people have, the healthier they are likely to be. But a new study from Rice University sociologists found that the health benefits of a good education are less evident among well-educated bisexual adults.

"Education and health: The joint role of gender and sexual identity" examines health among straight, bisexual, gay and lesbian adults with various educational backgrounds. Authors Zhe Zhang, a postdoctoral research fellow at Rice, Bridget Gorman, a professor of sociology at Rice, and Alexa Solazzo, a postdoctoral research fellow at the Harvard University T.H. Chan School of Public Health, were particularly interested in bisexual adults, since they may experience distinctive health vulnerabilities.

The researchers found that while having at least a bachelor's degree was linked to better health among bisexual adults, they received less benefit than heterosexual and gay or lesbian adults with similar education. This effect was especially true for bisexual women.

"The health benefits of education are well established -- so much so that anything we do to promote and improve public education should really be viewed as health policy," Gorman said. "It's that impactful on health and well-being. That our analysis showed less health benefit associated with education among bisexual adults compared to heterosexual, gay and lesbian adults is concerning."

While the researchers could not pinpoint the exact cause, they theorized the problem might be social stigma and additional anxiety among women due to gender discrimination, Zhang said.

"Discrimination of any kind can take a heavy toll on health," Zhang said. "While we cannot say with certainty that is what is happening in this study, it's a very real possibility."

The authors based their study on data from the Behavioral Risk Factor Surveillance System, which included a sample of more than 1.2 million adults living in 44 U.S. states and territories from 2011-2017. They hope the study will raise awareness of the issue and help health professionals provide better care.

E-cigarettes might not be a safer alternative to smoking during pregnancy, according to the first known study into the effects of prenatal nicotine exposure on babies.

Psychologists at Durham University, UK, found that babies of mothers who smoked e-cigarettes during pregnancy displayed similar abnormal reflexes to infants whose mothers smoked traditional cigarettes.

Abnormal reflexes can include a baby not grasping a finger with their hand or not being startled if the hand supporting their head is suddenly removed.

When there are a number of these abnormal reflexes, this could be a sign of impaired brain development, which should be further investigated. Normal reflexes support the development of early motor milestones, such as crawling and rolling over.

The researchers say their findings have important implications for policy guidelines regarding the use and safety of e-cigarettes during pregnancy as a method of reducing the harm caused by smoking.

They recommend that more investigation is needed into the potential effects of e-cigarettes on babies and say the only safe way of reducing harm is not to smoke during pregnancy, whether that be traditional cigarettes or e-cigarettes.

Their findings are published in the journal E Clinical Medicine.

E-cigarettes are often considered as a less harmful alternative to cigarettes for pregnant smokers because they don't produce toxins like carbon monoxide, but they do contain nicotine.

The Durham study looked at the neurobehavioural outcomes of 83 one-month-old babies including 44 born to mothers who did not smoke during pregnancy, 29 who smoked cigarettes and ten who smoked e-cigarettes. Babies were born at least 37 weeks into pregnancy.

Overall the researchers found that the birthweight, gestation period and head circumference of babies did not differ between those born to mothers who smoked e-cigarettes during pregnancy and those who did not smoke at all.

Babies of mothers who smoked traditional cigarettes during pregnancy had significantly lower birthweight and head circumference in comparison.

However, babies exposed to nicotine in the womb, either from cigarettes or e-cigarettes, did have a greater number of abnormal primitive reflexes, as well as marginally decreased self-regulation abilities compared to the babies of non-smokers.

Self-regulation in infants can include self-relaxation when held, how consolable they are after crying, self-quieting skills and hand-to-mouth movements. Babies who show fewer self-regulation abilities are often more irritable and have difficulty consoling themselves or being consoled by others.

The study also found that higher amounts of nicotine correlated with less motor maturity in babies, such as how floppy or rigid a baby is when held.

The researchers acknowledge that while the sample size in their study is small, their findings do give a strong indication that nicotine exposure from smoking e-cigarettes could be harmful to the development of fetuses and have called for more studies to be carried out.

Lead author Suzanne Froggatt, a PhD Researcher in the Department of Psychology, Durham University, said: "Nicotine can cause widespread negative effects on the central nervous system, subsequently affecting brain development, with animal studies indicating the devastating effects within the brain.

"Although e-cigarettes might expose the mother to fewer toxins than cigarettes, given the uncontrolled amount of nicotine in e-cigarette consumption and the effects on the fetus which can be seen post-natally, we don't believe that mothers should be encouraged to use e-cigarettes during pregnancy.

"More investigation is needed into the potential harm to fetuses from e-cigarettes so health professionals can provide women with a better informed choice about harm reduction during pregnancy."

The researchers added that their findings suggest the effects of other forms of nicotine replacement therapy, such as nicotine patches, on fetal development might also need further research.

Co-author Professor Nadja Reissland, in the Department of Psychology, Durham University, said: "Mothers should not be encouraged to use e-cigarettes during pregnancy, while other forms of nicotine replacement therapy need to be researched in relation to neurobehavioural outcomes.

"Public health policymakers need to be aware that e-cigarette use is not risk free and that nicotine alone is not relatively harmless, but in fact it can have effects on the infant, despite not affecting birth outcomes."

ORLANDO, Fla. (October 15, 2020) - A group of three gene variants, commonly inherited together, may provide clues to more successful treatment of pediatric eosinophilic esophagitis (EoE), a chronic inflammation of the food pipe often confused with gastroesophageal reflux disease (GERD). A new study, led by researchers from Nemours Children's Health System and published in Clinical Gastroenterology and Hepatology, identifies genetic variants that help predict which children with EoE may not respond to proton pump inhibitor (PPI) medication therapy as a long-term solution.

"Our goal is to personalize therapy for children with EoE based on their unique genetic profile - finding the right medication, at the right dose for the right child," said James P. Franciosi, MD, senior author and Chief of Gastroenterology, Hepatology and Nutrition at Nemours Children's Hospital. "This novel research study identifies genetic variants that can help us predict which children with EoE will respond to PPI therapy over the course of one year and potentially avoid relapse and additional invasive procedures."

EoE is a chronic immune condition, often caused by reactions to certain foods, that leads to inflammation of the esophagus. Symptoms may include difficulty swallowing, chest pain, heart burn, abdominal pain, nausea, and vomiting. EoE is becoming increasingly more common with both new diagnoses and total number of patients increasing yearly. More than 30 percent of children receiving long-term treatment for EoE experience relapse, but currently it is not possible to predict who is likely to suffer a relapse. Children with this condition are often treated with PPI medications, which are also prescribed for common acid reflux-related conditions.

The research team found that having any of three STAT6 variants that are commonly inherited together increases the odds that PPI therapy will fail children with EoE at some point, either in the initial high-dose therapy phase or the subsequent year of low-dose maintenance therapy.

This prospective, longitudinal cohort study involved 73 children ages 2-16 years old who met the diagnostic criteria for EoE, responded to an initial eight weeks of 2mg/kg daily PPI therapy and were subsequently stepped down to 1 mg/kg daily PPI maintenance therapy for one year. Genomic DNA was isolated, and genotyping conducted. The research team found that patients who initially respond to PPI therapy but carry any of three specific STAT6 variants are at increased risk of relapse after one year of PPI maintenance therapy.

Franciosi noted that a dosage that is too low or too high could lead to treatment failure or PPI-associated side effects including upper respiratory and GI tract infections.

"There is more work to be done before we can say with certainty which children will respond to PPI therapy for this painful condition," said Edward B. Mougey, PhD, lead author of the study, and a researcher with Nemours' Center for Pharmacogenomics and Translational Research. "Research is ongoing, and our goal continues to be to personalize, as much as possible, the treatment and care we provide to each child."

"My son is currently in remission and has been responsive to PPIs, but EoE is still a constant condition he is managing - from determining what he can eat, to maintaining his weight and energy levels," said Laura Moore, of Jacksonville, Fla. and mother of a child with EoE. "This research will help improve my son's treatment going forward, but also help other kids will have better experiences in the future."

Anyone who has experienced "butterflies in the stomach" before giving a big presentation will be unsurprised to learn there is a physical connection between their gut and their brain. Neuroscientists and medical professionals call this connection the "gut-brain axis" (GBA); a better understanding of the GBA could lead to the development of treatments and cures for neurological disorders such as depression and anxiety, as well as for a range of chronic auto-immune inflammatory diseases such as irritable bowel syndrome (IBS) and rheumatoid arthritis.

Right now, these conditions and diseases are primarily diagnosed by patients' reports of their symptoms. However, neuroscientists and doctors are investigating the GBA in order to find so-called "biomarkers" for these diseases. In the case of the GBA, that biomarker is likely serotonin.

By targeting this complex connection between the gut and the brain, researchers hope they can uncover the role of the gut microbiome in both gut and brain disorders. With an easily identifiable biomarker such as serotonin, there may be some way to measure how dysfunction in the gut microbiome affects the GBA signaling pathways. Having tools that could increase understanding, help with disease diagnosis, and offer insight into how diet and nutrition impacts mental health would be extremely valuable.

With $1 million in National Science Foundation funding, a team of University of Maryland experts from engineering, neuroscience, applied microbiology, and physics has been making headway on building a platform that can monitor and model the real-time processing of gut microbiome serotonin activity. Three new published papers detail the progress of the work, which includes innovations in detecting serotonin, assessing its neurological effects, and sensing minute changes to the gut epithelium.

In "Electrochemical Measurement of Serotonin by Au-CNT Electrodes Fabricated on Porous Cell Culture Membranes" (https://www.nature.com/articles/s41378-020-00184-4), the team developed a platform that provides access to the specific site of serotonin production. The platform included a porous membrane with an integrated serotonin sensor on which a model of the gut lining can be grown. This innovation allowed researchers to access both top and bottom sides of the cell culture--important because serotonin is secreted from the bottoms of cells. The work is the first to demonstrate a feasible method for detection of redox molecules, such as serotonin, directly on a porous and flexible cell culture substrate. It grants superior access to cell-released molecules and creates a controllable model gut environment to perform groundbreaking GBA research without the need to perform invasive procedures on humans or animals.

The team's second paper, "A Hybrid Biomonitoring System for Gut-Neuron Communication" (https://ieeexplore.ieee.org/document/9123494), builds on the findings of the first: the researchers developed the serotonin measuring platform further so it could assess serotonin's neurological effects. By adding and integrating a dissected crayfish nerve model with the gut lining model, the team created a gut-neuron interface that can electrophysiologically assess nerve response to the electrochemically detected serotonin. This advance enables the study of molecular signaling between gut and nerve cells, making possible real-time monitoring of both GBA tissues for the first time.

Finally, the concept, design, and use for the entire biomonitoring platform is described in a third paper, "3D Printed Electrochemical Sensor Integrated Transwell Systems" (https://www.nature.com/articles/s41378-020-00208-z). This paper delves into the development of the 3D-printed housing, the maintenance of a healthy lab-on-a-chip gut cell culture, and the evaluation of the two types of sensors integrated on the cell culture membrane. The dual sensors are particularly important because they provide feedback about multiple components of the system--namely, the portions that model the gut lining's permeability (a strong indicator of disease) and its serotonin release (a measure of communication with the nervous system). Alongside the electrochemical sensor--evaluated using a standard redox molecule ferrocene dimethanol--an impedance sensor was used to monitor cell growth and coverage over the membrane. Using both these sensors would allow monitoring of a gut cell culture under various environmental and dietary conditions. It also would enable researchers to evaluate changes to barrier permeability (a strong indicator of disease), and serotonin release (a measure of communication with the nervous system).

People who live through traumatic experiences in childhood often suffer long-lasting consequences that affect their mental and physical health. But moreover, their children and grand-children can also be impacted as well. In this particular form of inheritance, sperm and egg cells pass on information to offspring not through their DNA sequence like classical genetic heredity, but rather via biological factors involving the epigenome that regulates genome activity. However, the big question is how the signals triggered by traumatic events become embedded in germ cells.

"Our hypothesis was that circulating factors in blood play a role," says Isabelle Mansuy, professor of neuroepigenetics at the University of Zurich's Brain Research Institute and the ETH Zurich's Institute for Neuroscience. Mansuy and her team demonstrated that childhood trauma does have a lifelong influence on blood composition and that these changes are also passed to the next generation. "These findings are extremely important for medicine, as this is the first time that a connection between early trauma and metabolic disorders in descendants is characterized," explains Mansuy.

Traumatic stress leads to metabolic changes across generations

In her study, Mansuy used a mouse model for early trauma that had been developed in her lab. The model is used to study how the effects of trauma in early postnatal life on male mice are transmitted to their offspring. To determine whether these early experiences have an impact on blood composition, the researchers conducted multiple analyses and found large and significant differences between blood from adult traumatized animals and blood from normal, non-traumatized control group.

Changes in lipid metabolism were particularly striking, with certain polyunsaturated fatty acids metabolites appearing in higher concentrations in the blood of traumatized male mice. These same changes were also observed in their offspring. Even more strikingly, when the serum of traumatized males was chronically injected into non-traumatized males, their offspring also developed metabolic symptoms of trauma - providing a direct link between circulating factors and germ cells, thus confirming the hypothesis that blood delivers stress signals to the gametes.

Comparison with traumatized children

The researchers then investigated whether similar effects are present in humans. For this, they assembled a cohort of 25 children from an SOS Children's Village in Pakistan who have lost their father and were separated from their mother, and analyzed their blood and saliva. When compared with children from normal families, the orphans showed higher level of several lipid metabolites - just like the traumatized mice.

"These children's traumatic experiences are comparable to those in our mouse model, and their metabolism show similar changes in blood," explains Mansuy. "This demonstrates the importance of animal research for providing us with fundamental insights into human health." Up to one fourth of children across the world experience violence, abuse and neglect, that can lead to chronic diseases later in their life, highlighting the importance of Mansuy's research.

Receptor interferes with gametes

Further experiments led the team to discover a molecular mechanism by which lipid metabolites can transmit signals to animals' germ cells. PPAR, a receptor at the surface of cells, plays a key role in this process; it is activated by fatty acids and regulates gene expression and DNA structure in numerous tissues. The researchers discovered that this receptor is upregulated in the sperm of traumatized males.

Artificially activating this receptor in male mice led to lower body weight and disturbances in glucose metabolism - an effect that was also seen in their offspring and grand-offspring. These and other experiments led researchers to conclude that PPAR activation in sperm cells plays a significant role in the heritability of metabolic dysfunctions caused by traumatic experiences in ancestors.

Trauma damages the health of offspring

"Our findings demonstrate that early trauma influences both mental and physical health in adulthood and across generations, which can be seen in factors like lipid metabolism and glucose levels," says Mansuy. "This is rarely taken into consideration in clinical settings." Improving the understanding of the underlying biological processes could help medical practitioners prevent the late-onset consequences of adverse life experiences in their patients in the future.

Autonomous vehicles (AV) are the wave of the future in the automobile industry, and there's extensive discussion about the impacts on transportation, society, the economy and the environment.

However, less attention has been focused on the potential health impacts of self-driving vehicles.

Texas A&M University researchers have developed a conceptual model to identify these health impacts systematically. They identified 32 transportation-related risk factors that affected health and concluded that 17 could negatively impact public health, while eight could have a positive impact. There were seven areas of uncertain implications that require further investigation.

The researchers recently published their findings in the December issue of Sustainable Cities and Society.

"A survey on the receptiveness of autonomous vehicles' impacts showed that there is a lack of awareness of the potential health impacts of AVs and low perceptions of the importance of AV health benefits," said Soheil Sohrabi, a doctoral student in the Zachry Department of Civil and Environmental Engineering and a graduate researcher at the Texas A&M Transportation Institute (TTI). "On the other hand, there are some unintended consequences of AVs' implementation that need to be studied before AVs find their way onto the road."

Sohrabi, with Dr. Dominque Lord, professor in the department and A.P. Wiley Faculty Fellow, and Dr. Haneen Khreis with TTI created a conceptual model to systematically identify the pathways through which AVs can affect public health. The proposed model summarizes the potential changes in transportation after AV implementation into seven points of impact: transportation infrastructure; land use and the built environment; traffic flow; transportation mode choice; transportation equity; and jobs related to transportation and traffic safety. The changes in transportation are then attributed to potential health impacts.

In optimistic views, AVs are expected to prevent 94% of traffic crashes by eliminating driver error, but AVs' operation introduces new safety issues such as the potential of malfunctioning sensors in detecting objects (pedestrians, bikes and cyclists, vehicles, obstacles, etc.), misinterpretation of data and poorly executed responses, which can jeopardize the reliability of AVs and cause serious safety consequences in an automated environment.

Another possible safety consideration is the riskier behavior of users because of their overreliance on AVs -- for example, neglecting the use of seatbelts due to an increased false sense of safety.

AVs have the potential to shift the people from public transportation and active transportation such as walking and biking to private vehicles in urban areas, which can result in more air pollution and greenhouse gas emissions and create the potential loss of driving jobs for those in the public transit or freight transport industries.

The model serves researchers in the fields of transportation engineering and urban planning as well as automotive makers, health sectors and policymakers to identify the potential pathways through which AVs can affect public health, and to investigate the impacts, quantify them and develop policies to mitigate them.

"Given the very fast-paced research related to AVs, this work provides very good preliminary guidelines about how AVs can negatively and positively affect the general health of people before their full deployment," Lord said. "Hence, engineers, planners and policymakers can already examine measures and policies that could mitigate the negative health effects."

"This study can urge public health sectors to enter the discussion about AVs and contribute to supporting policies that address the potential negative impacts," Sohrabi said. "It also increases the public awareness of the health impacts of AVs that can facilitate the acceptance of AV regulations and motivate them to use this new technology and ultimately, benefit the greater good."

In the future, Sohrabi said more research is needed to clarify public health impacts of AVs more accurately. This study was primarily focused on urban areas and does not take into account the affects of AVs in rural areas.

"The discussion about the health implications of AVs is new and limited," he said. "Next, we will be working on quantifying the health implications of AVs."

Researchers at the University of Colorado Boulder and the University of Colorado Anschutz Medical Campus have developed a new way to diagnose diseases of the blood like sickle cell disease with sensitivity and precision and in only one minute. Their technology is smaller than a quarter and requires only a small droplet of blood to assess protein interactions, dysfunction or mutations.

The team published its results Oct. 15 in the journal Small.

"In Africa, sickle cell disease is the cause of death in 5% of children under 5-years-old for lack of early diagnosis," said Angelo D'Alessandro, a coauthor of the study and associate professor in the departments of Biochemistry and Molecular Genetics and Medicine, Division of Hematology at CU Anschutz. "This common, life-threatening genetic disorder is most prevalent in poor regions of the world where newborn screening and diagnosis are rare."

Sickle cell disease affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. In some areas of the world where malaria is endemic, variants of hemoglobin have evolved that can cause red blood cells to assume a crescent, or sickle, shape.

"Almost all life activities involve proteins," said study coauthor Xiaoyun Ding, an assistant professor in the Paul M. Rady Department of Mechanical Engineering at CU Boulder. "We thought if we could measure the protein thermal stability change, we could detect these diseases that affect protein stability."

Proteins have a specific solubility at a specific temperature. When one bonds to another, or when the protein is mutated, the solubility changes. By measuring solubility at different temperatures, researchers can tell whether the protein has been mutating.

Before recent developments, study coauthor Michael Stowell, an associate professor in the Department of Molecular, Cellular and Developmental Biology (MCDB) at CU Boulder, and his colleagues used Thermal Shift Assays (TSAs) to assess protein stability under varying conditions. Such tests took about a day to run. Now, with the new technology, an Acousto Thermal Shift Assay (ATSA), they can do the same but faster and with greater sensitivity.

The ATSA utilizes high-amplitude sound waves, or ultrasound, to heat a protein sample. The tool then measures data continuously, recording how much of the protein has dissolved at every fraction of change in degrees Celsius.

"Our method is seven to 34 times more sensitive," said Ding. "The ATSA can distinguish the sickle cell protein from normal protein, while the traditional TSA method cannot."

Another benefit of the ATSA is cost reduction in terms of human labor and equipment.

"The traditional methods for thermal profiling require specialized equipment such as calorimeters, polymerase chain reaction machines and plate readers that require at least some technical expertise to operate," said Kerri Ball, a coauthor of the new study and a researcher who works with Stowell at CU Boulder. "These instruments are also not very portable, requiring samples to be transported to the instruments for analysis."

Ball said the ATSA requires only a power source, a microscope and a camera as simple as the one on your smart phone. Because the protein is concentrated, there is also no need to apply a florescent dye as is sometimes required to highlight protein changes in a traditional TSA.

A unique study conducted by University of Georgia entomologists led to the discovery of a distinctive supergene in fire ant colonies that determines whether young queen ants will leave their birth colony to start their own new colony or if they will join one with multiple queens.

Researchers also found that ants were more aggressive toward queens who don't possess the supergene, causing main colony workers to kill them. This critical finding opens the door to new pest control methods that may be more efficient in eradicating problematic fire ant colonies.

"Learning about the way fire ants behave is very important baseline information," said Ken Ross, a professor of entomology at UGA. "This information is key to helping us manage pest populations and predict what dissimilarities can happen in their environment."

A supergene is a collection of neighboring genes located on a chromosome that are inherited together due to close genetic linkage. Studying these unique genes is important to understanding the potential causes for differences among the social structure of fire ants, specifically for controlling the species and building on the existing knowledge base.

Researchers focused on young queen fire ants embarking on nuptial flights. They compared the supergene's impact on the fire ants' two primary types of social structures: monogyne, which is reproduction from queens that form a new nest, and pologyne, reproduction from queens that join an existing nest.

Ross initially worked alongside colleagues in his lab to discover a remarkable example of genetically encoded differences in social organization within the fire ant species Solenopsis invicta. The next step was to understand how these genetic differences result in complex behavioral and physiological variations among ants from single queen colonies versus colonies with multiple queens. Compounding this knowledge helps scientists further understand patterns of development in the species, increasing alternatives to combat invasive populations.

Led by a pair of UGA entomology graduate alumni, Joanie King, who earned her master's degree in 2017, and Samuel Arsenault, who earned his doctoral degree in 2020, the team developed an experimental design that utilized a collection of samples from two fire ant organs -- brain and ovarian tissues -- and the complete range of social chromosome genotypes and social forms within this fire ant species.

The innovative study incorporated various scientific methods, leading to a collaboration of tools and resources throughout many areas of the institution.

"UGA was a very supportive environment to conduct this research," said Brendan Hunt, associate professor of entomology. "We received help preparing samples for RNA sequencing from Dr. Bob Schmitz's lab in the genetics department, performed the sequencing at the Georgia Genomics and Bioinformatics Core, and utilized computational resources from the Georgia Advanced Computing Resource Center to analyze the data."

These types of student-led projects give young researchers the chance to grow in a hands-on environment with mentorship and guidance from scientists with proven track records in the field.

"The graduate students gained experience that helped them transition to the next stages of their careers," said Hunt. "Both have gone on to continue their studies of ant genetics."

TALLAHASSEE, Fla. -- Researchers are learning more about the brightly colored bacterial mats threatening the ecological health of coral reefs worldwide. In new research released this month, a Florida State University team revealed that these mats are more complex than scientists previously knew, opening the door for many questions about how to best protect reef ecosystems in the future.

FSU Assistant Professor of Biological Science Sophie McCoy and doctoral student Ethan Cissell published their findings in the journal Science of the Total Environment.

"By targeting the full biological diversity of these mat communities on reefs, and by studying the transcriptome, which gives us information about which biochemical processes are being used by those organisms, we're opening the door to a more complete understanding of the entire ecological role of mats," McCoy said.

Though these cyanobacterial mats have been examined in the past, scientists focused on characterizing the cyanobacteria. Cissell and McCoy found that cyanobacteria only made up about 47.57% of the mats. Their analysis showed that mats also contained a type of algae called diatoms, fungi, a single cell organism called archaea, viruses and other forms of bacteria.

"We know from other well-characterized systems that cyanobacteria, even in bloom-forming scenarios, associate with a diversity of other microorganisms that make significant and unique contributions to the overall dynamics and ecophysiology of these cyanobacteria-dominated consortia," Cissell said. "We set out to determine if similar associations are found in proliferating cyanobacterial mats on coral reefs."

Cyanobacterial mats have posed a huge problem for coral reef health. Coral reef bacteria have always played an important role in these ecological communities, but the growth -- largely attributed to local and global climate stressors -- has threatened to totally snuff out the life of precious corals.

Previously, the bacteria covered about 1% of reefs, but that has grown to 20 to 30% in some places.

Researchers said this greater understanding of the communities comprising the mats leads to more questions about how the mats form and grow.

"What this means is that the mechanisms controlling mat bloom dynamics on coral reefs are likely more complex than previously thought," Cissell said. "These data we present provide important baselines for future mechanistic-based exploration of the processes driving the growth, persistence, and decline of benthic cyanobacterial mats."

McCoy and Cissell conducted 29 diving expeditions in Bonaire, an island municipality of the Netherlands off the coast of Venezuela, for the project. They are currently conducting genetic sequencing on mat samples to get a better understanding of daily patterns of the communities comprising the mat. They are also examining samples taken from a dying mat to better understand compositional and functional shifts associated with mat death.

CHICAGO, Oct. 15, 2020 -- Although assumed to be at high risk for COVID-19, fewer than one percent of dentists nationwide were found to be COVID-19 positive, according to a first-of-its-kind report in the U.S. based on data collected in June 2020. The result is far below that of other health professionals in the U.S. In addition, 99 percent of dentists are using enhanced infection control procedures such as screening protocols and enhanced disinfection practices when treating patients. The report, published online ahead of print by The Journal of the American Dental Association, is the first large-scale collection and publication of U.S. dentists' infection rates and infection control practices related to COVID-19.
"This is very good news for dentists and patients," said American Dental Association (ADA) Science and Research Institute Chief Executive Officer Marcelo Araujo, D.D.S., M.S., Ph.D., the senior author of the report. "This means that what dentists are doing - heightened infection control and increased attention to patient and dental team safety - is working."

Dr. Araujo added that the authors of the report, researchers from the ADA Science and Research Institute and Health Policy Institute based in Chicago, are continuing to collect and will report infection rate data on dentists and have added hygienists to their ongoing survey, in collaboration with the American Dental Hygienists Association.
This report focused on nearly 2,200 dentists in June, finding that 82 percent of dentists were asymptomatic for one month prior to the survey and 16.6 percent reported getting a COVID-19 test. Those who tested positive were not clustered in any particular geographic region. Among those not tested, less than one percent (0.32) were given a probable COVID-19 diagnosis by a physician. The authors weighted the results to align with U.S. dentists demographically and geographically and found an estimated prevalence of less than one percent (0.9) with a margin of error of 0.5 percent.

"Understanding the risks associated with COVID-19 transmission in the dental setting is critical to improving patient and dental team safety," said Dr. Araujo. "This study brings us another step forward in understanding what works. Dentists are following ADA and U.S. Centers for Disease Control and Prevention (CDC) guidance, and it's helping to keep the dental team and their patients as safe as possible."

In March, The New York Times listed dentistry as one of the professions at highest risk of COVID-19 based on data from O*NET, a database maintained by the U.S. Department of Labor. It was presumed that virus transmission could occur because of the close proximity between dental professionals and patients and because many dental procedures generate aerosols that may contain viral particles from infected individuals.

This newly-published report, with the extremely low rate of COVID-19 infection among dentists, supports the effectiveness of the recommendations from the CDC and ADA in preventing virus transmission.

The ADA's guidance calls for the highest level of personal protective equipment (PPE) available--masks, goggles and face shields. The ADA's interim guidance also calls for the use of rubber dams and high velocity suction whenever possible and hand scaling when cleaning teeth rather than using ultrasonic scaling to minimize aerosols.

"The fact that dentistry was named one of the most at-risk professions for infection, but has a far lower prevalence of infection compared to other health professions, is not a coincidence," said Chief Economist and Vice President of the ADA Health Policy Institute Marko Vujicic, Ph.D. "The profession has taken this issue extremely seriously, and it shows. We will continue to track the rate of COVID-19 among dentists and other facets of the pandemic affecting dentistry so it can help inform the dental profession and other industries as well."

Of the six or more different species of early humans, all belonging to the genus Homo, only we Homo sapiens have managed to survive. Now, a study reported in the journal One Earth on October 15 combining climate modeling and the fossil record in search of clues to what led to all those earlier extinctions of our ancient ancestors suggests that climate change--the inability to adapt to either warming or cooling temperatures--likely played a major role in sealing their fate.

"Our findings show that despite technological innovations including the use of fire and refined stone tools, the formation of complex social networks, and--in the case of Neanderthals--even the production of glued spear points, fitted clothes, and a good amount of cultural and genetic exchange with Homo sapiens, past Homo species could not survive intense climate change," says Pasquale Raia of Università di Napoli Federico II in Napoli, Italy. "They tried hard; they made for the warmest places in reach as the climate got cold, but at the end of the day, that wasn't enough."

To shed light on past extinctions of Homo species including H. habilis, H. ergaster, H. erectus, H. heidelbergensis, H. neanderthalensis, and H. sapiens, the researchers relied on a high-resolution past climate emulator, which provides temperature, rainfall, and other data over the last 5 million years. They also looked to an extensive fossil database spanning more than 2,750 archaeological records to model the evolution of Homo species' climatic niche over time. The goal was to understand the climate preferences of those early humans and how they reacted to changes in climate.

Their studies offer robust evidence that three Homo species--H. erectus, H. heidelbergensis, and H. neanderthalensis--lost a significant portion of their climatic niche just before going extinct. They report that this reduction coincided with sharp, unfavorable changes in the global climate. In the case of Neanderthals, things were likely made even worse by competition with H. sapiens.

"We were surprised by the regularity of the effect of climate change," Raia says. "It was crystal clear, for the extinct species and for them only, that climatic conditions were just too extreme just before extinction and only in that particular moment."

Raia notes that there is uncertainty in paleoclimatic reconstruction, the identification of fossil remains at the level of species, and the aging of fossil sites. But, he says, the main insights "hold true under all assumptions." The findings may serve as a kind of warning to humans today as we face unprecedented changes in the climate, Raia says.

"It is worrisome to discover that our ancestors, which were no less impressive in terms of mental power as compared to any other species on Earth, could not resist climate change," he said. "And we found that just when our own species is sawing the branch we're sitting on by causing climate change. I personally take this as a thunderous warning message. Climate change made Homo vulnerable and hapless in the past, and this may just be happening again."