Publisher Health

Our gut microbiome — the ever-changing “rainforest” of bacteria living in our intestines — is primarily affected by our lifestyle, including what we eat or the medications we take, most studies show.
But a University of Notre Dame study has found a much greater genetic component at play than was once known.
In the study, published recently in Science, researchers discovered that most bacteria in the gut microbiome are heritable after looking at more than 16,000 gut microbiome profiles collected over 14 years from a long-studied population of baboons in Kenya’s Amboseli National Park. However, this heritability changes over time, across seasons and with age. The team also found that several of the microbiome traits heritable in baboons are also heritable in humans.
“The environment plays a bigger role in shaping the microbiome than your genes, but what this study does is move us away from the idea that genes play very little role in the microbiome to the idea that genes play a pervasive, if small, role,” said Elizabeth Archie, professor in the Department of Biological Sciences and a principal investigator on the study who is also affiliated with the Eck Institute for Global Health and the Environmental Change Initiative.
The gut microbiome performs several jobs. In addition to helping with food digestion, it creates essential vitamins and assists with training the immune system. This new research is the first to show a definitive connection with heritability.
Previous studies on the gut microbiome in humans showed only 5 to 13 percent of microbes were heritable, but Archie and the research team hypothesized the low number resulted from a “snapshot” approach to studying the gut microbiome: All prior studies only measured microbiomes at one point in time.

Proactive, frequent rapid testing of all students for COVID-19 is more effective at preventing large transmission clusters in schools than measures that are only initiated when someone develops symptoms and then tests positive, Simon Fraser University researchers have found. Professors Caroline Colijn and Paul Tupper used a mathematical model to simulate COVID-19’s spread in the classroom and published their research results today in the journal PLOS Computational Biology.
The simulations showed that, in a classroom with 25 students, anywhere from zero to 20 students might be infected after exposure, depending on even small adjustments to transmission rates for infected individuals or environments.
“When schools have reopened during the COVID-19 pandemic, in some places there have been large clusters of infections, and in others very little transmission,” says Colijn, SFU mathematics professor and Canada 150 Research Chair in Mathematics for Evolution, Infection and Public Health. “In our simulations, we explored what factors affect cluster size, and what interventions can be used to prevent large clusters.”
The researchers tested the effectiveness of two different transmission control strategies.
In the first, when a student (or teacher/staff member) develops symptoms, they are told to stay home, tested using a PCR test, and if the test result is positive, control measures are introduced in the classroom, such as telling the infected individual’s close contacts to stay home.
In the second strategy, all students in the class are tested using rapid tests on a regular basis, whether they have symptoms or not. When a student tests positive, there is an intervention to prevent further transmission.

Feeling anxious about health, family or money is normal for most people — especially during the COVID-19 pandemic. But for those with anxiety disorders, these everyday worries tend to heighten even when there is little or no reason to be concerned.
Researchers from Indiana University School of Medicine recently studied the behaviors associated with anxiety — published in Psychopharmacology — examining how biological factors impact anxiety disorders, specifically in females. They found that anxiety in females intensifies when there’s a specific, life-relevant condition.
The team, led by Thatiane De Oliveira Sergio, PhD, postdoctoral fellow in the laboratory of Woody Hopf, PhD, professor of psychiatry and primary investigator at Stark Neurosciences Research Institute, studied male and female rodent models to better understand sex differences in biological responses related to anxiety.
Anxiety disorders occur in twice as often in women than men, and social and cultural factors likely play an important role in the development of anxiety in females, De Oliveira said.
The COVID-19 pandemic heavily influenced anxiety in people. According to the Centers for Disease Control and Prevention, in June 2020 — a few months into the pandemic — 13 percent of Americans started using or increasing substance use to cope with their emotions and stress due to the unknowns at that time about the pandemic.
Knowing that women have more incidence of anxiety than men, De Oliveira said the roles for many women have amplified during the pandemic — working remotely, teaching children in virtual school, everyday tasks, errands. She said these life-relevant conditions could have increased their anxiety.

Researchers at the Francis Crick Institute have found a vital mechanism, previously thought to have disappeared as mammals evolved, that helps protect mammalian stem cells from RNA viruses such as SARS-CoV-2 and Zika virus. The scientists suggest this could one day be exploited in the development of new antiviral treatments.
On infecting a host, a virus enters cells in order to replicate. For most cells in mammals the first line of protection are proteins, called interferons. Stem cells, however, lack the ability to trigger an interferon response and there has been uncertainty about how they protect themselves.
In their study, published in Science today (8 July) the scientists analysed genetic material from mouse stem cells and found it contains instructions to build a protein, named antiviral Dicer (aviD), which cuts up viral RNA and so prevents RNA viruses from replicating. This form of protection is called RNA interference, which is the method also used by cells in plants and invertebrates.
Caetano Reis e Sousa, author and group leader of the Immunobiology Laboratory at the Crick says, “It’s fascinating to learn how stem cells protect themselves against RNA viruses. The fact this protection is also what plants and invertebrates use suggests it might be something that goes far back in mammalian history, right up to when the evolutionary tree spilt. For some reason, while all mammalian cells possess the innate ability to trigger this process, it seems to only be relied upon by stem cells.
“By learning more about this process, and uncovering the secrets of our immune system we are hoping to open up new possibilities for drug development as we strive to harness our body’s natural ability to fight infection.”
In laboratory experiments which exposed engineered human cells to SARS-CoV-2, the virus infected three times fewer stem cells when aviD was present in the cells compared to when the researchers removed this protein.
The scientists also grew mini brain organoids from mouse embryonic stem cells and found that, when infected with Zika virus, the organoids with aviD grew more quickly and less viral material was produced than in organoids without this protein. Similarly, when organoids were infected with SARS-CoV-2, there were fewer infected stem cells in the organoids with aviD.
Enzo Poirier, author and postdoc in the Immunobiology Laboratory at the Crick says, “Why stem cells use this different mechanism of defence remains a mystery. It might be that the interferon process would cause too much harm to stem cells, so mammals, including humans, have evolved to shield these precious cells from this damage. There is still a lot of uncertainty about how these cells are protected from viruses, which we’re excited to explore further.”
The researchers will continue this work, creating a mouse model which allows them to further study the effects and importance of aviD in mammalian stem cells.
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Materials provided by The Francis Crick Institute. Note: Content may be edited for style and length.

Light therapy can help improve the mood of people with seasonal affective disorder (SAD) during short winter days, but exactly how this therapy works is not well understood. A new study by Urs Albrecht at the University of Fribourg, published July 8th in the journal PLOS Genetics, finds that light therapy’s beneficial effects come from activating the circadian clock gene Period1 in a part of the brain involved in mood and sleep-wake cycles.
Nighttime light has strong effects on the physiology and behavior of mammals. It can reset an animal’s circadian rhythms, and in the form of light therapy, affect mood in humans. Albrecht and his colleagues investigated how nighttime light impacts mood using mice as a model. They exposed mice to a pulse of light at different points during the night and then tested them for depressive behavior. The researchers discovered that light exposure at the end of the dark period — two hours before daytime — had an antidepressant effect on the animals. The pulse of light activated the Period1 gene in a brain region called the lateral habenula, which plays a role in mood. Light at other times, however, had no effect. When they deleted the Period1 gene, the mice no longer experienced the light’s beneficial effects.
The new results provide evidence that turning on Period1 in the lateral habenula is the key to light’s mood-boosting powers. The discovery that mice appeared to be less depressed when exposed to light at the end of the dark period than the beginning is similar to findings in humans. Light therapy is more efficient in the early morning than in the evening for patients with SAD. However, the researchers caution against making too many direct comparisons to humans since mice are nocturnal animals.
The researchers add, “Light perceived in the late part of the night induces expression of the clock gene Per1, which is related to improvement of depression like behavior in mice.”
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Materials provided by PLOS. Note: Content may be edited for style and length.

A multi-institutional study has discovered spontaneous mutations in RNF2 (RING2) gene as the underlying cause of a novel neurological disorder. This Undiagnosed Diseases Network (UDN) study was led by Dr. Shinya Yamamoto, investigator at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital and assistant professor at Baylor College of Medicine, and Dr. Vandana Shashi at Duke University Medical Center. Using a combination of comprehensive clinical tests, trio genome sequencing and functional studies in the fruit flies, and global gene matchmaking efforts, the teams found loss-of-function variants in RNF2 gene disrupt normal neuronal development and function that likely resulted in a wide gamut of symptoms from severe intellectual disabilities, hypotonia, impaired motor skills, epilepsy, growth retardation, seizures and feeding difficulties in two affected individuals. The study appeared in the journal Human Molecular Genetics.
The UDN is a National Institutes of Health-funded research study that brings together clinical and research experts from across the United States to solve the most challenging medical mysteries using advanced technologies. This often involves severely affected patients who, despite years of testing, are unable to get a definitive diagnosis for their medical problems — the crucial first step towards receiving appropriate treatment, support and clinical care.
This study was initiated with the enrollment of an adolescent female patient with the above-mentioned symptoms at one of the UDN’s Clinical sites at Duke University. Initially, researchers at Dr. Shashi’s lab at Duke performed a whole slew of genetic tests, all of which came back negative. Next, they performed trio whole-exome sequencing, a relatively newer sequencing technology that compares the DNA sequences of the parents and the affected individuals to identify a potential genetic alteration that might explain these symptoms. Using this method, they found this patient carried a rare mis-sense variant in the RNF2 gene, which was not present in genomes of either parent, indicating that the mutation arose spontaneously in the patient’s genome.
RNF2 belongs to a large family of evolutionarily conserved Polycomb group genes that encode about 20 proteins critical for brain and skeletal development and function. Mutations in 12 genes that encode proteins of this complex are known to be associated with neurological disorders. However, RNF2 variants had never been linked to a disease before. To identify more patients with this new mutation, the team utilized GeneMatcher, a web tool developed as part of the Baylor-Hopkins Center for Mendelian Genomics for rare disease researchers. This helped them find a younger female patient in France who had a different mis-sense variant in the same gene and suffered from similar symptoms. This was an exciting finding because it suggested that variations in RNF2 were the likely culprit behind these patients’ symptoms and linked RNF2 to a novel neurological disorder. However, to firmly establish a causal relationship between RNF2 variants and the new disease pathology, they needed to better understand the biological consequence of the variants found in the two patients, ideally in an in vivo animal model.
The UDN’s Model Organisms Screening Core (MOSC) led by Drs. Hugo Bellen, Shinya Yamamoto and Michael Wangler at the NRI and Baylor carried out this task by using the fruit fly, Drosophila melanogaster. Fruit flies are excellent model systems to test the function of variants identified in disease patients, and MOSC researchers have used this strategy to identify more than 20 new disease gene discoveries in the past few years. When the MOSC team expressed mutated versions of this gene in fruit flies, they were unable to functionally rescue i.e., compensate for the loss of function of this gene, which is in contrast to what they observed when they expressed the normal version of this gene in flies.
“Using fruit flies as a ‘living test tube,’ we demonstrated that loss-of-function mutations in RNF2 were likely the molecular cause of the symptoms in the two patients,” Yamamoto said. “This makes RNF2 the thirteenth Polycomb group gene to be linked to human disease. Although the incidence of each of these dozen diseases that arise from mutations in Polycomb genes is very rare, it is likely they share similar underlying pathogenic mechanisms. Therefore, we propose the term ‘polycombopathies’ to group and study them together.”
While further studies will be needed to better define the clinical spectrum and pathologies of this disorder caused by RNF2, the team is particularly excited by the future therapeutic possibilities that this investigation has opened up.
“Many drugs that modulate the activity of Polycomb group proteins and their interacting partners are currently being studied in the context of various cancers and there is mounting evidence pointing towards convergence in the disease pathologies of cancer and rare neurological diseases at the molecular level, which will greatly facilitate our goal to find therapies for ‘Polycombopathies,” Yamamoto added.
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Materials provided by Texas Children’s Hospital. Original written by Rajalaxmi Natarajan, PhD. Note: Content may be edited for style and length.

Researchers from the University of Sussex have determined the structure of a tiny multi-protein biological machine, furthering our understanding of human cells and helping to enhance research into cancer, neurodegeneration and other illnesses.
A biological nanomachine is a macromolecular machine commonly found within the cell, often in the form of multi-protein complexes, which frequently perform tasks essential for life.
The nanomachine R2TP-TTT acts as a molecular chaperone to assemble others in the human cell. It is especially important for constructing mTORC1 — a complicated nanomachine that regulates the cell’s energy metabolism, and which often becomes misregulated in human diseases such as cancer and diabetes.
Scientists from the School of Life Sciences at Sussex, working in collaboration with colleagues at CNIO Madrid, MRC-LMB Cambridge and the University of Leeds, used state-of-the-art cryo-electron microscopy (cryoEM) to build a detailed image of the R2TP-TTT nanomachine that shows the arrangement of all the proteins. It also reveals how the TTT proteins control the R2TP machine to allow it to hold components of mTORC1 ready for assembly.
Lead researcher, Dr. Mohinder Pal, working in the laboratories of Dr. Chris Prodromou and Professor Laurence Pearl FRS at Sussex, worked out how to make and purify all the proteins using an insect cell system, and apply them in an ultra-thin layer that could be frozen in liquid ethane to preserve their atomic structure. Images of the frozen protein particles magnified more than 50,000 times were then collected on cryo-electron microscopes in Madrid, Harwell and Leeds. These were then combined using a technology related to medical tomography, to give the final detailed image of the R2TP-TTT, in which the molecular detail could be seen and analysed.
Professor Pearl, who co-supervised the work with Dr. Prodromou and Prof. Llorca (Madrid), commented :
“Previously we’ve been able to work out the structures of protein molecules, using a technique called X-ray crystallography, but usually only individually or in pieces. The revolution in cryoEM technology over the last couple of years has given us the ability to look at the large assemblies of proteins as they actually exist in the cell, and really understand how they work as biological nanomachines.”
With the help of the RM Phillips Charitable Trust, the University of Sussex has made a multi-million pound investment to establish cryo-electron microscopy in the School of Life Sciences. The new state-of-the-art cryoARM200 cryo-electron microscope, made by the Japanese company JEOL, has just been installed in the John Maynard Smith building at the University, and will be fully functioning in the summer.
Professor Pearl said:
“Having our own instrument on site, will greatly increase the speed with which we can reveal the structures of a huge range of biological nanomachines being studied by colleagues in Life Sciences. This will massively enhance the world-leading work going on here at Sussex to understand cancer, neurodegeneration and viral diseases, and to develop new treatments.”
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Materials provided by University of Sussex. Original written by Stephanie Allen. Note: Content may be edited for style and length.

In a new study assessing the potential of a single-dose, intranasal COVID-19 vaccine, a team from the University of Iowa and the University of Georgia found that the vaccine fully protects mice against lethal COVID-19 infection. The vaccine also blocks animal-to-animal transmission of the virus. The findings were published July 2 in the journal Science Advances.
“The currently available vaccines against COVID-19 are very successful, but the majority of the world’s population is still unvaccinated and there is a critical need for more vaccines that are easy to use and effective at stopping disease and transmission,” says Paul McCray, MD, professor of pediatrics-pulmonary medicine, and microbiology and immunology at the UI Carver College of Medicine, and co-leader of the study. “If this new COVID-19 vaccine proves effective in people, it may help block SARS-CoV-2 transmission and help control the COVID-19 pandemic.”
Unlike traditional vaccines that require an injection, this vaccine is administered through a nasal spray similar to those commonly used to vaccinate against influenza. The vaccine used in the study only requires a single dose and it may be stored at normal refrigerator temperatures for up to at least three months. Because it is given intranasally, the vaccine may also be easier to administer, especially for those who have a fear of needles.
“We have been developing this vaccine platform for more than 20 years, and we began working on new vaccine formulations to combat COVID-19 during the early days of the pandemic,” says Biao He, PhD, a professor in the University of Georgia’s Department of Infectious Diseases in the College of Veterinary Medicine and co-leader of the study. “Our preclinical data show that this vaccine not only protects against infection, but also significantly reduces the chances of transmission.”
The experimental vaccine uses a harmless parainfluenza virus 5 (PIV5) to deliver the SARS-CoV-2 spike protein into cells where it prompts an immune response that protects against COVID-19 infection. PIV5 is related to common cold viruses and easily infects different mammals, including humans, without causing significant disease. The research team has previously shown that this vaccine platform can completely protect experimental animals from another dangerous coronavirus disease called Middle Eastern Respiratory Syndrome (MERS).
The inhaled PIV5 vaccine developed by the team targets mucosal cells that line the nasal passages and airways. These cells are the main entry point for most SARS-CoV-2 infections and the site of early virus replication. Virus produced in these cells can invade deeper into the lungs and other organs in the body, which can lead to more severe disease. In addition, virus made in these cells can be easily shed through exhalation allowing transmission from one infected person to others.
The study showed that the vaccine produced a localized immune response, involving antibodies and cellular immunity, that completely protected mice from fatal doses of SARS-CoV-2. The vaccine also prevented infection and disease in ferrets and, importantly, appeared to block transmission of COVID-19 from infected ferrets to their unprotected and uninfected cage-mates.
In addition to McCray, UI researchers involved in the study included Kun Li, PhD, and associate research scientist, who helped lead the small animal studies at Iowa, documenting the vaccine’s efficacy, and David Meyerholz, PhD, UI professor of pathology.
The research was supported by CyanVac LLC, a startup company based at University of Georgia that is developing vaccines based on the PIV5. McCray, who does not have a financial relationship with CyanVac, also received support from the Roy J. Carver Charitable Trust.
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Materials provided by University of Iowa Health Care. Original written by Jennifer Brown. Note: Content may be edited for style and length.

Spreading fast in South America, the variant is still a mystery. No one knows whether it is more contagious than other variants or if it affects vaccines.Viruses evolve. SARS-CoV-2, the virus that causes Covid-19, is no exception. So the emergence of variants is no surprise, and not every new genetic mutation poses a serious threat.But in recent weeks, a growing drumbeat of news coverage has started to raise alarm about Lambda, a variant first detected in Peru late last year. The variant, initially known as C.37, has spread rapidly through parts of South America. On June 14, the World Health Organization designated it as a “variant of interest,” meaning, essentially, that experts suspect it could be more dangerous than the original strain.Lambda’s prevalence and its mutations, which resemble those found in several other highly contagious or worrisome variants, mean that it is worth watching, scientists said. But much remains unknown, and it is not yet clear how much of a risk it poses.“I think some of the interest is just based on the fact that there’s a new variant, and it has a new name,” said Nathaniel Landau, a microbiologist at the New York University Grossman School of Medicine who is studying the new coronavirus variants.“But I don’t think there’s any more reason to be concerned than before we knew about this variant,” Dr. Landau added. No evidence so far suggests that Lambda will outcompete Delta, the highly transmissible variant that’s now dominating most of the world. “There’s no reason to think that this is now something worse than Delta.”Pablo Tsukayama, a microbiologist at Cayetano Heredia University in Peru who documented Lambda’s emergence, concurred. Latin America has “limited capacity” to do genomic surveillance and follow-up laboratory investigations of new variants, he said. That has led to an information gap fueling concerns about Lambda. “I don’t think it’s going to be worse than any of the ones that we have already,” he said. “It’s just that we know so little that it lends itself to a lot of speculation.”As of mid-June, Lambda had been reported in 29 countries, territories or areas, according to a June 15 update from the W.H.O. The variant had been detected in 81 percent of coronavirus samples sequenced in Peru since April, and 31 percent of those in Chile to date, the agency said.The variant accounts for less than 1 percent of samples sequenced in the United States, according to GISAID, a repository for viral genome data. Isolated cases have been reported in a number of other countries.The variant contains eight notable mutations, including seven in the gene for the spike protein, found on the surface of the virus. Some of these mutations are present in other variants and might make the virus more infectious or help it evade the body’s immune response.But big questions remain unanswered. It is not yet clear whether Lambda is more transmissible than other variants, whether it causes more severe disease or whether it renders vaccines less effective.“We don’t have a lot of information, compared to the other variants,” said Ricardo Soto-Rifo, a virologist at the University of Chile who has studied Lambda.Preliminary laboratory studies, which have not yet been published in peer-reviewed journals, provide reason for both concern and reassurance. In these studies, research teams led by Dr. Soto-Rifo and Dr. Landau found that antibodies induced by the Pfizer, Moderna and CoronaVac vaccines are less powerful against Lambda than against the original strain, but that they are still able to neutralize the virus.The findings suggest that these vaccines should still work against Lambda, the scientists said. Moreover, antibodies are not the body’s only defense against the virus; even if they’re less potent against Lambda, other components of the immune system, like T cells, may also provide protection.“This decrease in the neutralizing antibodies does not mean that the vaccine has decreased effectiveness,” Dr. Soto-Rifo said. Real-world studies of how well the vaccines hold up against the variant are still needed, he said.The researchers also reported that like several other variants, Lambda binds more tightly to cells than the original strain of the virus does, which may make it more transmissible.Although many questions remain, Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle, said that he does not find Lambda as worrisome as Delta and does not expect it to become as dominant globally.“Lambda has been around for a little while, and it’s hardly invaded the U.S. at all, for example, compared to, say, even Gamma” — the variant first identified in Brazil — “which has done pretty well here.” He added, “I think all the focus should be on Delta.”

If you’ve ever been to an eye doctor, there’s a good chance you’ve felt the sudden puff of air to the eye that constitutes a traditional test for glaucoma. It’s no one’s favorite experience, but the puff is non-invasive and harmless.
Scientists use a similar method to test learning and memory in animals and humans. Like Pavlov’s classic experiments linking a neutral stimulus with a physiological response, the eyeblink test pairs a light or sound with a quick puff of air to the eye. With repetition, the animal learns to close its eye, or blink, in response to the light or sound only. It’s called associative learning, and the response is ruled by a brain region known as the cerebellum.
While the eyeblink test has been around since 1922, it had never been attempted in pigs until now. In a new study in Frontiers in Behavioral Neuroscience, researchers prove the eyeblink test works in 3-week-old pigs, a model species for nutritional neuroscience research in human infants.
“The idea is, if we can improve structural development in the brain through nutritional interventions, it should take pigs fewer trials to learn the rule. We’re in the process of assessing the nutrition piece now, but we had to get the test to work first,” says Ryan Dilger, professor in the Department of Animal Sciences at the University of Illinois and co-author on the study.
Dilger specializes in the effects of nutrition on the developing brain, with much of his work feeding directly into the infant formula industry. He uses neonatal pigs because, unlike rodents, their brain anatomy and structure, gut physiology, and nutritional requirements are strikingly similar to human infants.
Dilger’s team typically studies pig brain response to new ingredients through magnetic resonance imaging, MRI, which focuses on the structure and size of various brain regions. They also rely on well-validated behavioral tasks, such as novel object recognition, that reflect activity in the hippocampus and striatum, some of the brain regions related to learning and memory.