Culture

Researchers at Baylor College of Medicine, Shandong University in China and other institutions may have found an explanation for dawn phenomenon, an abnormal increase of blood sugar only in the morning, observed in many patients with type 2 diabetes. They report in the journal Nature that mice lacking the circadian clock gene called Rev-erb in the brain show characteristics similar to those of dawn phenomenon.

The researchers then looked at Rev-erb gene expression in patients with type 2 diabetes comparing a group with dawn phenomenon to a group without it and found that the gene's expression followed a different temporal pattern between these two groups. The findings support the idea that an altered daily rhythm of expression of the Rev-erb gene may underlie dawn phenomenon. Future investigations may lead to therapies.

"We began this study to investigate what was the function of Rev-erb in the brain," said co-corresponding author Dr. Zheng Sun, associate professor of medicine-endocrinology, diabetes and metabolism at Baylor. "We are interested in this gene because it is a 'druggable' component of the circadian clock with potential applications in the clinic. Rev-erb is expressed only during the day but not at night. When we started, we did not know where this was going to lead us."

The researchers first developed a mouse model by knocking out the Rev-erb gene in GABA neurons. They chose this approach because the gene's expression is highly enriched in a particular brain area called the suprachiasmatic nucleus that is mainly composed of GABA neurons.

An unexpected finding

"We observed something very interesting in these mice," Sun said. "They were glucose intolerant - that is they had high glucose levels - only in the evening. Mice are nocturnal, meaning that they become active in the evening as people do in the morning."

When the body awakes and takes in food, insulin is secreted from the pancreas to signal the body to lower blood sugar. Insulin is more effective in doing this job upon waking than at other times of the day. This high insulin sensitivity is probably because the body is anticipating feeding behaviors upon waking up. In mice, high insulin sensitivity occurs in the evening, while in people it occurs in the morning.

Sun and his colleagues found that the abnormal higher glucose levels observed in the evening in Rev-erb knockout mice resulted from an insufficient suppression of liver glucose production by insulin. Their data demonstrate an essential role of neural Rev-erb in regulating the hepatic insulin sensitivity rhythm independent of eating behaviors or basal hepatic glucose production.

Next, the researchers looked to understand how defects in Rev-erb gene expression in the brain can result in changes in the ability of the liver to respond to insulin. They discovered that the suprachiasmatic nucleus GABA neurons in Rev-erb knockout mice had a higher firing activity than those neurons of normal mice when the animals woke up, and that this neuronal hyperactivity was sufficient and necessary to cause glucose intolerance in the evening. In normal mice, these GABA neurons drop their firing activity in the evening, lowering sugar blood levels. Interestingly, by re-expressing Rev-erb back in the knockout mice, the researchers found that Rev-erb expression is only needed during the day, but not needed at night, which is in line with the highly oscillatory expression pattern of endogenous Rev-erb in normal condition.

Connecting with dawn phenomenon

Mice having higher glucose levels in the evening reminded Sun and his colleagues of dawn phenomenon observed in people with type 2 diabetes. "Given the similarities of the phenomenon in mice and people, we thought that maybe this gene that we are studying could be linked to the biology of dawn phenomena in diabetic patients," said Sun, a member of Baylor's Dan L Duncan Comprehensive Cancer Center and the Huffington Center on Aging.

In collaboration with Qilu Hospital of Shandong University in China, the researchers followed 27 type2 diabetes patients with continuous glucose monitoring. They found that, although the patients had diabetes with similar severity in terms of their basal glucose levels, obesity and other parameters, about half of the patients had dawn phenomenon while the other half did not.

"We collected the patients' blood at different times of the day and determined the expression of the Rev-erb gene in white blood cells, which has been reported to correlate well with the central clock in the brain," Sun said. "Interestingly, we found that the gene's expression followed a temporal pattern that was different between those with dawn phenomenon and those without," Sun said. "We propose that the altered temporal pattern of expression of this gene may explain dawn phenomena in people. It is possible that, in the future, a drug might be used to regulate this gene to treat the condition."

WASHINGTON (March 25, 2021)--Although demand for COVID-19 vaccines currently seems high, vaccine hesitancy could pose a major threat to public health efforts to end the pandemic, according to an editorial published today in the journal Science.

The authors, including David A. Broniatowski, associate director of the George Washington University Institute for Data, Democracy & Politics, point out that public sentiment towards vaccines are volatile in the face of events such as the recent controversy surrounding the AstraZeneca vaccine clinical trial data. For example, some people could develop safety concerns due to the news reporting about the AstraZeneca vaccine and then turn down the chance to get an approved COVID-19 vaccine--thus putting them at risk.

Vaccine hesitant people may have anxiety over safety concerns, or they might belong to a community that historically has mistrusted the medical establishment, according to the editorial.

Unfortunately, public health officials might not address their concerns. The editorial notes that people who are hesitant about getting the COVID-19 vaccine are often dismissed as anti-science. At the same time, the vaccine hesitant can be influenced by false information posted on social media or the internet by anti-vaxx activists and organized anti-vaxx groups, the authors said.

"Vaccine hesitant people are targeted by anti-vaxxers and ridiculed by some health care providers." Broniatowski said, "They are therefore doubly at risk."

How can vaccine hesitancy be addressed?

Broniatowski co-authored the editorial with Professor Heidi J. Larson, Director of The Vaccine Confidence Project at the London School of Hygiene & Tropical Medicine.

"Messages about vaccines must be delivered in a way that is empathetic to avoid stigmatizing people who have questions about the vaccine. Particularly in the context of Covid-19, with all its uncertainties, people need to be reassured, and feel that their concerns are heard," Larson said. "And, if there is one thing we have learned in all our research, people's concerns can change. Listening needs to be ongoing."

Narcissism is driven by insecurity, and not an inflated sense of self, finds a new study by a team of psychology researchers. Its research, which offers a more detailed understanding of this long-examined phenomenon, may also explain what motivates the self-focused nature of social media activity.

"For a long time, it was unclear why narcissists engage in unpleasant behaviors, such as self-congratulation, as it actually makes others think less of them," explains Pascal Wallisch, a clinical associate professor in New York University's Department of Psychology and the senior author of the paper, which appears in the journal Personality and Individual Differences. "This has become quite prevalent in the age of social media--a behavior that's been coined 'flexing'.

"Our work reveals that these narcissists are not grandiose, but rather insecure, and this is how they seem to cope with their insecurities."

"More specifically, the results suggest that narcissism is better understood as a compensatory adaptation to overcome and cover up low self-worth," adds Mary Kowalchyk, the paper's lead author and an NYU graduate student at the time of the study. "Narcissists are insecure, and they cope with these insecurities by flexing. This makes others like them less in the long run, thus further aggravating their insecurities, which then leads to a vicious cycle of flexing behaviors."

The survey's nearly 300 participants--approximately 60 percent female and 40 percent male--had a median age of 20 and answered 151 questions via computer.

The researchers examined Narcissistic Personality Disorder (NPD), conceptualized as excessive self-love and consisting of two subtypes, known as grandiose and vulnerable narcissism. A related affliction, psychopathy, is also characterized by a grandiose sense of self. They sought to refine the understanding of how these conditions relate.

To do so, they designed a novel measure, called PRISN (Performative Refinement to soothe Insecurities about SophisticatioN), which produced FLEX (perFormative seLf-Elevation indeX). FLEX captures insecurity-driven self-conceptualizations that are manifested as impression management, leading to self-elevating tendencies.

The PRISN scale includes commonly used measures to investigate social desirability ("No matter who I am talking to I am a good listener"), self-esteem ("On the whole, I am satisfied with myself"), and psychopathy ("I tend to lack remorse"). FLEX was shown to be made up of four components: impression management ("I am likely to show off if I get the chance"), the need for social validation ("It matters that I am seen at important events''), self-elevation ("I have exquisite taste"), and social dominance ("I like knowing more than other people").

Overall, the results showed high correlations between FLEX and narcissism--but not with psychopathy. For example, the need for social validation (a FLEX metric) correlated with the reported tendency to engage in performative self-elevation (a characteristic of vulnerable narcissism). By contrast, measures of psychopathy, such as elevated levels of self-esteem, showed low correlation levels with vulnerable narcissism, implying a lack of insecurity. These findings suggest that genuine narcissists are insecure and are best described by the vulnerable narcissism subtype, whereas grandiose narcissism might be better understood as a manifestation of psychopathy.

CHAMPAIGN, Ill. -- Materials that contain special polymer molecules may someday be able to warn us when they are about to fail, researchers said. Engineers at the University of Illinois Urbana-Champaign have improved their previously developed force-sensitive molecules, called mechanophores, to produce reversible, rapid and vibrant color change when a force is applied.

The new study led by postdoctoral researcher Hai Qian, materials science and engineering professor and head Nancy Sottos, and Beckman Institute of Advanced Science and Technology director Jeffrey Moore is published in the journal Chem.

Moore's team has been working with mechanophores for more than a decade, but past efforts have produced molecules that were slow to react and return to their original state, if at all. This inability to produce an on/off-like response has limited their use as molecular probes that continuously report a material's mechanical condition, the study reports.

"The color change is the result of stress applied to the bonds that connect the mechanophores to a polymer chain," Qian said. "We are now bonding the mechanophores to polymer chains using a different arrangement scheme, called an oxazine structure. The new structure allows for an instantaneous and reversible color change, so instead of the polymer slowly becoming darker over time, the color changes quickly when the force is applied and disappears when the force is removed."

See a video demonstrating the new oxazine structure and the older spiropyran structure.

Materials that contain the new mechanophores could be used as stress sensors to enable researchers to study the effects of stress on materials before they fail.

"The rapid response and reversibility will allow engineers to better monitor, quickly detect and respond rapidly to an overstressed structure in the lab and eventually in the field," Sottos said.

A long-standing challenge in materials science has been making observations regarding mechanical load and other stresses in materials at the single-molecule level. Although this advancement cannot do this, Moore says the goal is nearer with the development of this new type of mechanophores.

"There is more work to do, but this advancement opens the door to detailed insight of what's going on at the molecular level in all sorts of materials," Moore said. "In the area of biomechanics, for example, we see this research as a steppingstone toward better monitoring of how our bodies react to external forces from the cellular level and beyond."

Researchers at GMI - Gregor Mendel Institute of Molecular Plant Biology of the Austrian Academy of Sciences, the University of North Carolina at Chapel Hill and The Howard Hughes Medical Institute (HHMI) use two complementary approaches to unveil a co-evolutionary mechanism between bacteria and plants and also explain complex immune response patterns observed in the wild. Together the papers change the way scientists have been thinking about the relationship of a bacterial antigenic component with its plant immune receptor. The two papers are published back to back in the journal Cell Host & Microbe.

Immune responses have developed in virtually all organisms over evolutionary time scales to protect them from foreign invaders. A central aspect of the immune response of higher organisms, i.e., plants and animals, is the use of sensory systems that detect and respond to "non-self" molecular signals. These molecular signals generally determine the survival chances of the pathogen, a factor that prevents them from being eliminated by natural selection as a means to evade host recognition. Their evolutionary conservation is thus due to the functionality of these molecular signals to the foreign invader. However, the negative evolutionary pressure to maintain this functionality is counterbalanced by the positive evolutionary pressure to mediate the pathogen's immune evasion. The dissection of these co-evolutionary forces through synthetic and reverse evolutionary methods is one of the two research approaches that researchers from the Belkhadir lab at GMI and the Dangl lab at UNC- Chapel Hill team up to investigate. In an orthogonal approach, they also inquire into the natural diversity of molecular antigenic determinants (epitopes) in plant-colonizing bacterial communities (commensal communities) and map the complex immune response patterns they trigger in the plants. Jeffery Dangl, John N. Couch Distinguished Professor at UNC-Chapel Hill and an HHMI investigator explains: "To date, most science in this field has used a handful of epitopes. We sampled thousands, derived from synthetic biology and commensal communities. This depth of analysis allowed us to uncover a rich diversity of host response mediated by a single receptor."

Reverse evolution and new insights on co-evolution

The researchers examine how the Arabidopsis immune sensor FLS2 (flagellin sensing 2) influenced the evolution of its interacting epitope on the Pseudomonas flagellin, and how this, in turn, influenced Pseudomonas motility. Using reverse evolutionary methods, Parys et al. uncover a new mechanism of co-evolutionary force between FLS2 and flagellin, and frame it as a molecular form of the scarcely studied theory of antagonistic pleiotropy (AP) in plant immunology. AP is the ability of a gene to induce opposing effects in different contexts, a prevailing theory for the evolutionary origin of aging in humans. The researchers demonstrate that AP fosters stable colonization of Arabidopsis by commensal communities by weighing out bacterial motility against sensor detection. This strategy results in flagellin epitopes that either mildly activate or outright block the receptor (gain in virulence), while losing in motility as a trade-off (loss in virulence). Even more excitingly, they find signatures of these synthetic experiments in naturally occurring commensal communities, suggesting that natural microbiomes might be less dependent on flagella-mediated motility and willing to trade it off against another form of immune evasion in order to stay in harmony with the plant.

Friend or foe?

In the second, natural sampling approach, Colaianni et al. demonstrate that immune evasion mechanisms in plant root commensal communities are rampant and are a determining factor of the community's structure. Moreover, this conceptual breakthrough is accompanied by the corroborating findings of complex immune response fine-tuning mechanisms in Arabidopsis. The diversity of the ligand epitopes is translated in a complexity of the immune responses engaged by the plant, which is capable of detecting threshold variations in its microbiome, and thus, discriminating between "friend and foe."

On immune evasion and plant growth promotion

Asked about possible applications of this joint work, GMI group leader Youssef Belkhadir elaborates: "Sometimes, it is good to know how to turn on an immune response, but we often forget that, sometimes, it might also be good to turn it off. For example, you could help a growth-promoting microbe better colonize the plant by providing it with an additional way to evade the plant's immune response. And here we discovered synthetic antagonistic peptides that could do just that."

Back to the (plant) roots

This collaboration draws on an exchange in expertise between the alternating first authors of the two publications, but also refreshes long-dating, outstanding, scientific contacts. In fact, Nicholas Colaianni, Ph.D. student in the Dangl lab at UNC-Chapel Hill, is a computational expert, whereas the main fields of expertise of Katarzyna Parys (former Ph.D. student in the Belkhadir lab) lie in biochemistry and wet lab genetics. Colaianni also visited the Belkhadir lab at GMI and both he and Parys benefited from hands-on training in each other's field of expertise. In addition, as a third co-first author on both publications, Ho-Seok Lee, postdoctoral fellow in the Belkhadir lab, contributed his skills in microscopy imaging.

After many years of separate research, the two main principal investigators who share seniority and alternate corresponding authorships on the two publications, decided to make a comeback together. The shared seniority also includes Corbin Jones, Biology Professor at UNC-Chapel Hill and Colaianni's co-mentor. Youssef Belkhadir is a UNC-Chapel Hill alumnus who worked with Jeffery Dangl as a Ph.D. student. Referring to the UNC Tar Heels basketball team that Dangl loves, Belkhadir says "17 years after I co-authored my first paper with Jeff, it was a lot of fun to get on the court and 'slam-dunk' it with him once more!". Dangl adds "Just like basketball, science is a team effort and the best teams play fluidly together."

An international consortium

GMI and UNC-Chapel Hill share a deep commitment to international collaboration and the present work rallied an international consortium of scientists spearheaded by Youssef Belkhadir, including the University of Geneva and the University of Lausanne in Switzerland, the Max Perutz Labs of the University of Vienna in Austria and the University of Würzburg in Germany. The researchers also acknowledge the contribution of the Vienna Biocenter member institutes and facilities.

A pediatric heart transplant procedure pioneered by Canadian doctors--once deemed impossible--has been shown to be at least as effective as the traditional approach, according to newly published research in The Lancet Child & Adolescent Health.

ABO-incompatible heart transplantation was developed in the mid-1990s, after a Canadian transplant team led by Lori West realized that infants under the age of two have immature immune systems that would allow them to accept life-saving replacements for their defective hearts from donors with incompatible blood types.

"It's really important to see it has not only helped these very sick babies to get transplants faster, but also to live as long, with no more rejections, and better outcomes with regards to infections, as children who received a matched blood group heart," said principal investigator Simon Urschel, associate professor of pediatrics in the University of Alberta's Faculty of Medicine & Dentistry, director of pediatric cardiac transplantation at the Stollery Children's Hospital and member of the Women and Children's Health Research Institute (WCHRI).

ABO-incompatible heart transplantation is now routinely carried out in Canada and some other countries, but not everywhere. That should change thanks to these new study results, Urschel said.

"For example, Eurotransplant (the agency responsible for transplants in eight European countries) still considers it an inferior option to be used with caution," he said. "That concern will probably be relieved in those last places that were reluctant to do it, now that we have shown it is safe."

About 50 per cent of the population is born with type O blood, while 35 per cent has A type and 15 per cent has B or AB type blood. Organs from a donor with type O blood can be accepted by anyone, but adult type O patients can receive only type O organs. The development of ABO-incompatible pediatric heart transplantation meant that twice as many organs would be available to type O infants born with heart defects.

Urschel and his team analyzed data from more than 2,200 infant transplant recipients in Canada, the United Kingdom and the United States from 1999 to 2018. The records were from the Pediatric Heart Transplant Society registry, an international research collaboration that collects data from 58 transplant centres. This resulted in more than 11,000 cumulative patient-years of observation, by far the largest study of its kind.

Three hundred sixty-four of the babies received ABO-incompatible transplants, while 1,842 received ABO-compatible hearts. "We wanted to compare apples with apples, so the children were matched by characteristics such as their underlying disease and the age at which they underwent surgery," Urschel said.

The researchers found the survival rate was the same between the two groups, as were the rates of acute and chronic organ rejection and the risk of developing leukemia after transplant. They also examined the rates of post-transplant bacterial, viral and fungal infections, which they were concerned might be higher among the ABO-incompatible transplant recipients.

"Interestingly, we found that there were fewer of the infections that we were worried about in the ABO-incompatible patients," Urschel said.

Earlier work by Urschel's research team showed that wait times for these patients were significantly shortened, with the average time to transplant being about 50 per cent shorter thanks to the innovative transplant technique.

"It's easier and faster to find a heart for these patients, which is crucial because they are extremely sick, often on mechanical heart support devices or on ventilators in intensive care units," he said. "This gives them a chance not only to survive, but to stay healthier and be in better condition before and after transplantation."

The pioneering pediatric heart surgeons who started it all in 1996--West and Ivan Rebeyka--refined their method after being recruited to join the U of A faculty, with help from other faculty members such as Urschel. Urschel and West's work has received funding from the Stollery Children's Foundation through WCHRI.

The "rule" requiring ABO-compatible donors was instituted for older patients and had never been revisited from the perspective of the immunologic immaturity of infants, said West, now Canada Research Chair (Tier 1) in Cardiac Transplantation, and director of the Alberta Transplant Institute and the Canadian Donation and Transplantation Research Program.

"This, in combination with an extremely high mortality for infants on our transplant waiting list, is why we instituted the first ABO-incompatible transplant protocol," she said.

"Transplantation has always been about pushing the boundaries of risks in order to offer reasonable options to patients who would otherwise have no options."

Urschel will continue his work to understand the mechanism in infant immune systems that allows them to accept blood type-incompatible hearts, in hopes of being able to one day use what is learned to help older transplant recipients. He is also involved in projects to improve the quality of life of young transplant patients and their families.

"It's a real lesson in the need for scientific vigour to guide our operationalization of clinical protocols, not just the blind adoption of previously accepted regulations," said West.

The fact that heart transplant recipients can now survive with a normal lifespan is a credit to both West and Rebeyka, who has a clinical faculty position with the U of A's Cardiovascular Research Centre, said Urschel, who continues to provide clinical care for teenage and young adult patients who received ABO-incompatible transplants as babies.

"It's just amazing to see them, knowing that at one time they were so sick in the intensive care unit that they might not make it to the next day," Urschel said.

How can we better understand how people move during the pandemic and how they spread COVID-19? New George Mason University's College of Health and Human Services research is one of the first individual-level studies to explore this question.

Dr. Janusz Wojtusiak led the study published in the Journal of Healthcare Informatics Research. Wojtusiak and colleagues tracked symptoms and movements of 175 volunteer individuals on George Mason University's campus. They found that there is no evidence that participants altered their movements based on the symptoms they reported.

"We could not detect any significant change of movement when people should self-quarantine. On the other hand some people almost did not leave home since the beginning of the pandemic, while others move freely around," said Wojtusiak.

Participants used the Mason COVID HealthCheckTM to record symptoms of possible COVID-19 infection and GPS and WiFi data to provide information on how they move during the pandemic. This allows the researchers to model and predict movements during the pandemic and in conjunction with any reported possible COVID-19 symptoms.

"By tracking individual movements and symptoms in our study, our findings could help inform effective public health interventions to reduce COVID-19 infections," explains Wojtusiak.

In addition, Wojtusiak and colleagues analyzed de-identified Mason COVID HealthCheckTM responses and found that a headache was the most frequently reported symptom, and a headache was always listed as a symptom when any other symptoms were reported. Other commonly reported symptoms were coughs and sore throats.

Movement patterns varied among participants, with some only going out for essential trips while others moved about more. As a group, movement was consistent over the study period, which included a period when Virginia was under a stay-at-home order and when it was not. Participants traveled a total average of 139 miles per week, visiting an average of less than six locations per week. This low average mileage and number of sites visited does suggest that COVID-19-related restrictions affected their movement. However, they also found that even when participants reported symptoms of COVID-19 or contact with others with COVID-19, they did not change their movements as recommended by public health guidance.

George Mason University has a very low COVID-19 infection rate, and during the period none of the study participants reported COVID-19 infection, so researchers weren't able to link COVID-19 positive tests and movement. Future analysis will include data from the winter of 2020 so may provide more information on movement after COVID-19 infection. The researchers are also conducting surveys and interviews to provide richer data including reasons for complying or not complying with social distancing.

Opioids are the main driver of fatal drug overdoses in the United States, according to the Centers for Disease Control and Prevention, resulting in 46,802 deaths in 2018, usually because the person stops breathing.

Naloxone -- a Food and Drug Administration-approved medication used to reverse overdoses from opioids, such as heroin, morphine and oxycodone -- works by restoring normal respiration to a person whose breathing has slowed or stopped.

"Opioid overdoses cause the largest number of accidental and avoidable deaths," said Peter Davidson, PhD, associate professor in the Department of Medicine at University of California San Diego School of Medicine. "The human toll of drug addiction is devastating. Using naloxone to prevent opiate overdoses can and has saved many lives."

In a study published in the March 23, 2021 online edition of the International Journal of Drug Policy, Davidson and an international group of researchers, found that opioid users who participate in a 12-step abstinence program and recently stopped using drugs refused to take home naloxone, even if having it on hand might save lives.

For the study, trained interviewers visited areas known for high drug use in three Southern California counties: San Diego, Orange and Ventura. Forty-four participants were asked questions about drug use initiation, overdose experiences, both their own and observed and past treatments.

"In our research, individuals who were newly abstinent from opioid use believed that carrying naloxone symbolically tied them to a drug-use identity that they were trying to leave behind," said first author Jeanette Bowles, DrPH, who is now a postdoctoral fellow with the Centre on Drug Policy Evaluation in Toronto, Canada, but was a UC San Diego School of Medicine postdoctoral fellow at the time of the study.

"Twelve-step programs promote abstinence through social behaviors that include staying away from people, places and things considered to be tied to drug use. Naloxone was seen as an item linked to their drug use and clashing with these sober behaviors and their goal of abstinence."

To reduce the stigma associated with naloxone, researchers suggest reframing the meaning of carrying naloxone to represent a commitment to group safety and the wellbeing of those "who still suffer" and relabeling naloxone training programs in substance use disorder treatment settings as "overdose first aid."

In addition, researchers propose focusing on the lifesaving impact those trained to administer naloxone can have on their peers, and re-targeting naloxone distribution efforts to include persons at any phase of their drug use, including abstinence.

"It is very important that people understand that after periods of abstinence, the body is less tolerant if an individual resumes drug use, making them physiologically more vulnerable to overdose and death," said Davidson, co-corresponding author and principal investigator. "If someone is experiencing an opioid overdose, it is important to recognize the signs and respond quickly to prevent death."

In the United States, laws now allow people to access and use naloxone to respond to overdose with protection from liability.

The Addiction Recovery and Treatment Program at UC San Diego Health provides patients with outpatient behavioral treatment for substance use, such as cannabis, alcohol and opioids.

Skoltech scientists and their colleagues have proposed a new human height inheritance model that accounts for the interaction between various factors that influence adult human height. The research was published in the European Journal of Human Genetics.

Human height is a classical quantitative trait that depends on sex, genetics, and the environment.

Scientists from Skoltech, Novosibirsk State University, the Institute of Cytology and Genetics of the Siberian Branch of RAS, and the Institute of Science and Technology in Vienna analyzed the human height distribution across a population and its dependence on sex, genes, and the environment. The team used a huge set of data on over 369,000 U.K. individuals and average male and female heights from various ethnic groups across the world.

The classical human height model assumes the additivity of various factors. The team has shown that the interactions between these diverse factors should be taken into account when studying remote populations or large datasets. For instance, certain genetic variants are assumed to have a greater effect on the height in males than in females. The researchers proposed an alternative model in which the effects of sex, genes, and the environment are multiplied (and not added up) and can be regarded as independent.

"The conventional model would reveal different average heights in centimeters for males and females in each country, while our model straightforwardly shows a difference of 8%. The same goes for the environment and the genes which turned out to have the same relative effect in all the studied populations," explains Ivan Kuznetsov, a PhD student at the Skoltech Center for Life Sciences (CLS).

BIRMINGHAM, Ala. - Researchers have found an unexpected synergy between a T-cell stimulatory protein -- the ICOS ligand -- and interleukin-10, an immunoregulatory cytokine, to prevent inflammatory bowel disease in mice. The study will aid the understanding of, and future research into, this immune disorder, which includes Crohn's disease and ulcerative colitis. About 1.6 million Americans have inflammatory bowel disease.

Interleukin-10, or IL-10, was already known as a major player to prevent gut inflammation by establishing and maintaining immune homeostasis in the gut, where it is vital for the host to have a peaceful coexistence with normal intestinal microbes, while the immune system still stands guard against pathogens. IL-10 is produced by CD4+ T-regulatory cells in the gut.

ICOS ligand, or ICOSL, is expressed on B cells and dendritic cells of the immune system, and it helps to control T-cell activation and differentiation, two steps of the host immune response to microbes and microbial pathogens. Both IL-10 and ICOSL were known risk alleles for inflammatory bowel disease, but their synergistic interaction was not known.

The research, published in the Proceedings of the National Academy of Sciences, was led by Craig Maynard, Ph.D., assistant professor in the University of Alabama at Birmingham Department of Pathology.

"Collectively, our data identify a synergy between two inflammatory bowel disease-related pathways -- T-cell-derived IL-10 and ICOSL-dependent anti-commensal antibodies -- that promotes mutualism with the gut microbiota," Maynard said. "Furthermore, we identify ICOSL deficiency as an effective platform for exploring the functions of anti-commensal antibodies in host-microbiota mutualism."

In humans, complete deficiency of ICOSL or the ICOS receptor that ICOSL bind to causes a combined immunodeficiency with repeated bacterial and viral infections. In contrast, mice with ICOSL or ICOS receptor deficiencies maintain a healthy gut homeostasis under specific pathogen-free conditions.

In the current study, the UAB researchers found that ICOSL-deficient mice -- like the ICOS receptor-deficient mice Maynard's group has previously studied -- harbored increased frequencies and numbers of IL-10-producing CD4+ T cells, particularly in the proximal colon.

When researchers transiently depleted the IL-10-producing cells in the ICOSL-deficient mice, they saw a striking change -- rapid onset of severe inflammation in the proximal colon.

While the number of IL-10-producing CD4+ T cells was increased in the ICOSL-deficient mice, the numbers of colon-associated T-follicular helper cells and the plasma cells that produce immunoglobulin A and immunoglobulin G, or IgA and IgG respectively, were decreased.

The mice also had dramatic reductions in antibodies against normal gut microbes, which included a limited recognition of antigens implicated in the progression of inflammatory bowel disease. These included flagellin antigens derived from several members of the family Lachnospiraceae. These bacteria are known to enrich in the mucus-associated communities of the gut, and Crohn's disease patients have antibodies against two of the Lachnospiraceae flagellin antigens. The mice also had reduced IgA and IgG antibodies that targeted antigens from multiple species of anaerobic bacteria known to be associated with active inflammatory bowel disease.

Simultaneous ablation of both pathways, ICOSL and IL-10, in newborn mice caused severe colitis with evidence of disease as early as four weeks, if the mice were fostered with ICOSL-deficient dams. However, this early onset intestinal inflammation was delayed when the newborn mice were fostered by ICOSL-sufficient dams, showing a protective role for maternal antibodies.

Maynard says the overall results suggest that induction of ICOSL-dependent antibodies and T-cell-derived IL-10 may be simultaneous host adaptations to microbial occupation of a niche near the epithelium in the gut. "Future exploration of the specific microbes that drive these responses," he said, "could potentially identify novel antigen-specific approaches to bolster mucosal immune defenses."

Researchers from the Center for Health, Work & Environment (CHWE) at the Colorado School of Public Health have published a paper in the International Journal of Environmental Research and Public Health studying the effectiveness of applying Total Worker Health (TWH) in an international context. The study, led by a team at CHWE, is the first to examine how a TWH framework operates outside of a western context in Latin America workforces.

"Although recent reviews show that TWH intervention studies have had some global reach, the vast majority have been conducted in Western countries," says lead researcher Diana Jaramillo. "While global organizations, as well as governmental entities in Latin America, acknowledge the importance of this integrated approach to occupational health and safety, there are no studies exploring the implementation of the TWH approach in Latin America, to our knowledge." This region, which encompasses many low- and middle-income countries and diverse cultures, is in great need of TWH interventions to protect and promote the health of their workforce.

In the published manuscript, the researchers explored three novel concepts: the applicability of TWH theories in 1) a Latin American cultural setting; 2) a vertically integrated agribusiness; 3) within a multinational organization. The team took a community-based participatory research approach to adapt existing TWH tools and training. They convened stakeholders, interviewed health and safety champions and senior leaders, and identified TWH strategies that needed tweaking to meet the conditions of workers from very different backgrounds and with very different needs.

The case study documents the collaboration with Pantaleon, one of the largest agribusinesses in Latin America. CHWE partnered with the company in 2016 to engage in a series of projects to evaluate and address health and safety for the company's thousands of employees. One aspect was the process and adaptation strategy for conducting a TWH assessment at multiple organizational levels and in multiple countries including Guatemala, Nicaragua, and Mexico. The summary provides support for designing TWH interventions that can be adopted and implemented in global enterprise-level settings that span a diverse range of agriculture work functions from the corporate offices to the sugarcane fields.

"This case study represents a way to reach thousands of vulnerable workers in a large Latin American agribusiness and the opportunity to explore TWH research, translation and dissemination across different countries and cultures," adds Jaramillo. In the long term, they expect this approach to improve employee health, safety and well-being, and ultimately, productivity in meaningful and measurable ways.

Millions of years ago, aphid-like insects called whiteflies incorporated a portion of DNA from plants into their genome. A Chinese research team, publishing March 25th in the journal Cell, reveals that whiteflies use this stolen gene to degrade common toxins plants use to defend themselves against insects, allowing the whitefly to feed on the plants safely.

"This is an exceptional example of the horizontal gene transfer of a functional gene from a plant into an insect," says co-author Ted Turlings (@FARCE_lab), a chemical ecologist and entomologist at the University of Neuchâtel, in Switzerland. "You cannot find this gene, BtPMaT1, which neutralizes toxic compounds produced by the plant, in any other insect species."

Scientists believe that plants probably use BtPMaT1 within their own cells to store their noxious compounds in a harmless form, so the plant doesn't poison itself. The team, led by Youjun Zhang from the Institute of Vegetables and Flowers at the Chinese Academy of Agricultural Sciences, used a combination of genetic and phylogenetic analyses, to reveal that roughly 35 million years ago, whiteflies stole this defense gene, granting the insect the ability to detoxify these compounds for themselves.

"We think a virus within the plant may have taken up this BtPMaT1 gene and, after ingestion by a whitefly, the virus then must have done something inside the insect whereby that gene was integrated into the whiteflies genome," says Turlings. "Of course, this is an extremely unlikely event, but if you think about millions of years and billions of individual insects, viruses, and plants across time, once in a while this could happen, and if the acquired gene is a benefit to the insects, then it will be evolutionarily favored and may spread."

Whiteflies have become a major agricultural pest worldwide, able to attack at least 600 different species of plants worldwide. "One of the questions we've been asking ourselves is how these insects acquired these incredible adaptations to circumvent plant defenses, and with this discovery we have revealed at least one reason as to why," Turlings says.

Using this knowledge, Turlings' Chinese colleagues created a strategy to undo the whiteflies' stolen superpower. They developed a small RNA molecule that interferes with the whiteflies' BtPMaT1 gene, making the whiteflies susceptible to the plant's toxic compounds.

"The most exciting step of this design was when our colleagues genetically manipulated tomato plants to start producing this RNA molecule" says Turlings. "Once the whiteflies fed on the tomatoes and ingested the plant-produced RNA, their BtPMaT1 gene was silenced, causing 100% mortality of the insect, but the genetic manipulation had no impact on the survival of other insects that were tested."

With focused efforts to produce genetically modified crops that are able to silence the whitefly gene, this could function as a targeted strategy for pest control to combat agricultural devastation caused by whitefly populations.

"There are definitely still some hurdles this method needs to get over, most notably the skepticism about using transgenic plants," he says "But in the future, I do see this as a very clear way of controlling whiteflies because now we know exactly the mechanism behind it, and we are equipped to deal with possible changes in the whitefly gene that may arise.

Octopuses are known to sleep and to change color while they do it. Now, a study publishing March 25 in the journal iScience finds that these color changes are characteristic of two major alternating sleep states: an "active sleep" stage and a "quiet sleep" stage. The researchers say that the findings have implications for the evolution of sleep and might indicate that it's possible for octopuses to experience something akin to dreams.

Scientists used to think that only mammals and birds had two sleep states. More recently, it was shown that some reptiles also show non-REM and REM sleep. A REM-like sleep state was reported also in cuttlefish, a cephalopod relative of the octopus.

"That led us to wonder whether we might see evidence of two sleep states in octopuses, too," says senior author Sidarta Ribeiro of the Brain Institute of the Federal University of Rio Grande do Norte, Brazil. "Octopuses have the most centralized nervous system of any invertebrate and are known to have a high learning capacity."

To find out, the researchers captured video recordings of octopuses in the lab. They found that during 'quiet sleep' the animals were still and quiet, with pale skin and eye pupils contracted to a slit. During 'active sleep,' it was a different story. The animals dynamically changed their skin color and texture. They also moved their eyes while contracting their suckers and body with muscular twitches.

"What makes it more interesting is that this 'active sleep' mostly occurs after a long 'quiet sleep'--generally longer than 6 minutes--and that it has a characteristic periodicity," Ribeiro says.

The cycle would repeat at about 30- to 40-minute intervals. To establish that these states indeed represented sleep, the researchers measured the octopuses' arousal threshold using visual and tactile stimulation tests. The results of those tests showed that in both 'active' and 'quiet sleep' states, the octopuses needed a strong stimulus to evoke a behavioral response in comparison with the alert state. In other words, they were sleeping.

The findings have interesting implications for octopuses and for the evolution of sleep. They also raise intriguing new questions.

"The alternation of sleep states observed in the Octopus insularis seems quite similar to ours, despite the enormous evolutionary distance between cephalopods and vertebrates, with an early divergence of lineages around 500 million years ago," says first author and graduate student Sylvia Medeiros of the Brain Institute of the Federal University of Rio Grande do Norte, Brazil.

"If in fact two different sleep states evolved twice independently in vertebrates and invertebrates, what are the essential evolutionary pressures shaping this physiological process?" she asks. "The independent evolution in cephalopods of an 'active sleep' analogous to vertebrate REM sleep may reflect an emerging property common to centralized nervous systems that reach a certain complexity."

Medeiros also says that the findings raise the possibility that octopuses experience something similar to dreaming. "It is not possible to affirm that they are dreaming because they cannot tell us that, but our results suggest that during 'active sleep' the octopus might experience a state analogous to REM sleep, which is the state during which humans dream the most," she says. "If octopuses indeed dream, it is unlikely that they experience complex symbolic plots like we do. 'Active sleep' in the octopus has a very short duration--typically from a few seconds to one minute. If during this state there is any dreaming going on, it should be more like small videoclips, or even gifs."

In future studies, the researchers would like to record neural data from cephalopods to better understand what happens when they sleep. They're also curious about the role of sleep in the animals' metabolisms, thinking, and learning.

"It is tempting to speculate that, just like in humans, dreaming in the octopus may help to adapt to environmental challenges and promote learning," Ribeiro says. "Do octopuses have nightmares? Could octopuses' dreams be inscribed on their dynamic skin patterns? Could we learn to read their dreams by quantifying these changes?"

The Amazon rainforest is teeming with creatures unknown to science--and that's just in broad daylight. After dark, the forest is a whole new place, alive with nocturnal animals that have remained even more elusive to scientists than their day-shift counterparts. In a new paper in Zootaxa, researchers described two new species of screech owls that live in the Amazon and Atlantic forests, both of which are already critically endangered.

"Screech owls are considered a well-understood group compared to some other types of organisms in these areas," says John Bates, curator of birds at the Field Museum in Chicago and one of the study's authors. "But when you start listening to them and comparing them across geography, it turns out that there are things that people hadn't appreciated. That's why these new species are being described."

"Not even professional ornithologists who have worked on owls for their entire lives would agree about the actual number of species found in this group, so a study like ours has been awaited for a really long time," says Alex Aleixo, head of the research team responsible for the study, and currently curator of birds at the Finnish Museum of Natural History in the University of Helsinki, Finland.

The newly-discovered screech owls are cousins of the Eastern Screech Owls that are common in the United States. "They're cute little owls, probably five or six inches long, with tufts of feathers on their heads," says Bates. "Some are brown, some are gray, and some are in between." Until this study, the new species were lumped together with the Tawny-bellied Screech Owl and the Black-capped Screech Owl, which are found throughout South America.

Teasing out the differences between the species started with years of fieldwork in the Amazon rainforest as well as the Atlantic forest running along the eastern part of Brazil and surrounding countries. Bates, who usually conducts fieldwork during the day, says that doing fieldwork in the rainforest at night comes with new challenges. "For me it's more a feeling of fascination than being scared, but at the same time, you're running into spider webs. If you're wearing a headlight you see the eyeshine of the nocturnal animals. One time I was stepping over a log and I looked down and there was a tarantula the size of my hand just sitting there," says Bates. "If I had been a kid I would have been scared to death."

The owls that the researchers were looking for live in the trees, often a hundred feet above the forest floor. That makes studying them difficult. But the researchers had a secret weapon: the screech owls' namesake screech.

"To draw the birds out, we used tape recordings," explains Bates. "We'd record their calls and then play them back. The owls are territorial, and when they heard the recordings, they came out to defend their territory."

The scientists compared the birds' calls and found that there were variations in the sounds they made, indicative of different species. They also examined the birds' physical appearances and took tissue samples so they could study the owls' DNA at the Field Museum's Pritzker DNA Lab.

Altogether, 252 specimens, 83 tape-recordings, and 49 genetic samples from across the range of the Tawny-bellied Screech Owl complex in South America were analyzed. A significant number of specimens were collected by the research team itself, especially the study's lead author Sidnei Dantas, who spent a good share of his time in graduate school searching for and tape-recording screech owls in South American rainforests. In addition, natural history collections and their materials collected over the centuries were essential to complete the study´s unprecedented sampling.

"The study would not have been possible if it were not for the great biological collections in Brazil and USA which I visited during my work, and that sent us essential material, either genetic and morphological. This highlights the importance of such research institutions for the progress of science and hence of the countries they represent," says Dantas, who conducted the study as part of his PhD dissertation at the Goeldi Museum in Belém and is currently working as a nature guide in Brazilian Amazonia.

The combination of genetic variation, physical differences, and unique vocalizations led the team to describe two new species in addition to the previously known Tawny-bellied Screech Owl: the Xingu Screech Owl and the Alagoas Screech Owl. The Xingu owl's scientific name is in honor of Sister Dorothy May Stang, an activist who worked with Brazilian farmers to develop sustainable practices and fight for their land rights; its common name is for the area where the owl is found near the Xingu River. The Alagoas owl's name is a reference to the northeastern Brazilian state of Alagoas where the owl is primarily found.

While the owls are new to science, they're already in danger of disappearing forever. "Both new species are threatened by deforestation," says Jason Weckstein, associate curator of Ornithology in the Academy of Natural Sciences of Drexel University and associate professor in the university's Department of Biodiversity, Earth, and Environmental Science. "The Xingu Screech Owl is endemic to the most severely burned area of the Amazon by the unprecedented 2019 fires, and the Alagoas Screech Owl should be regarded as critically endangered given the extensive forest fragmentation in the very small area where it occurs," says Weckstein, who is a co-author and began work on this project as a postdoctoral researcher at the Field Museum.

Bates says he hopes that the study will shed light on how varied the Amazon and Atlantic forests are and how simply protecting certain areas isn't enough to preserve the forests' biodiversity. "If you just say, 'Well, you know Amazonia is Amazonia, and it's big,' you don't end up prioritizing efforts to keep forests from being cut in these different parts of Amazonia. That could mean losing entire faunas in this region," says Bates.

In addition to the study's conservation implications, the authors highlight the international collaboration that made the work possible. "This study shows how important it is to train the next generation of scientists at a global level," says Bates. "That means to having students like Sidnei come from Brazil and work in the Field's Pritzker Lab and measure specimens in our collection for their research. It's a great thing to build those connections."

Scientists estimate that dark matter and dark energy together are some 95% of the gravitational material in the universe while the remaining 5% is baryonic matter, which is the "normal" matter composing stars, planets, and living beings. However for decades almost one half of this matter has not been found either. Now, using a new technique, a team in which the Instituto de Astrofísica de Canarias (IAC) has participated, has shown that this "missing" baryonic matter is found filling the space between the galaxies as hot, low density gas. The same technique also gives a new tool that shows that the gravitational attraction experienced by galaxies is compatible with the theory of General Relativity. This research is published today in three articles in the journal Monthly Notices of the Royal Astronomical Society (MNRAS).

In designing this new technique they have analyzed the changes in the electromagnetic spectrum, its shift to the red, caused by the reddening of the light from the galaxies as they speed away from us. In the Universe, the sources which move away show a redder spectrum, and those which approach us show a bluer spectrum. This effect has given essential data for the development of modern cosmology. Almost a century ago, Edwin Hubble discovered that the redshifts of galaxies are bigger the further away from us they are, and this was the initial evidence which eventually led to the Big Bang model of the universe. Since then these redshifts have been used to find the distances to the galaxies and to build three dimensional maps of their distribution in the Universe.

In the work we are reporting here a new method has been developed, which studies the statistics of the redshifts of galaxies, without converting them to distances. In their first article, the team shows that these maps are sensitive to the gravitational attraction between galaxies on cosmological scales. In a second article, the same team compare the maps with observations of the cosmic microwave background,, and they permit, for the first time, a complete census of the baryonic matter during 90% of the life of the Universe.

"Most of this 'ordinary' matter is invisible to us because it is not sufficiently hot to emit energy. However, by using maps of the redshifts of the galaxies we find that all of this matter fills the space between them", explains Jonás Chaves-Montero, a researcher at the Donostia International Physics Center (DIPC) and first author of this article.

Finally, as found in a third article, the researchers have also used the redshift maps of the galaxies to study the nature of gravity. "In contrast to previous approaches, our new method is not based on any conversion of redshift to distance, and it is shown to be robust agains noise and data impurities. Thanks to that it allow us to conclude with high accuracy, that the observations are compatible with Einstein's theory of gravity", notes Carlos Hernández-Monteagudo, an IAC researcher who is the first author on this third article.

These studies have been performed by researchers Carlos Hernández-Monteagudo, Jonás Chaves-Montero, Raúl Angulo and Giovanni Aricò, who designed the research during their time at the Centre for Studies of Cosmic Physics of Aragón (CEFCA), even though now they are working at other Spanish research centres, such as the Instituto de Astrofísica de Canarias, and the Donostia International Physics Center. In one of the articles there was participation also by J. D. Emberson, a Canadian researcher at the Argonne National Laboratory, Illinois, USA.