Culture

Advanced MRI scans may improve treatment of tremor, Parkinson's disease

image: Bhavya R. Shah, MD is first author of the study and an assistant professor of radiology and neurological surgery at UT Southwestern's Peter O'Donnell Jr. Brain Institute

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UT Southwestern Medical Center

DALLAS - June 14, 2020 - Recently developed MRI techniques used to more precisely target a small area in the brain linked to Parkinson's disease and essential tremor may lead to better outcomes without surgery and with less risk of negative effects, a new study led by UT Southwestern researchers suggests.

The study, published today in Brain, describes recently refined MRI methods designed to allow neuroradiologists to zero in on a pea-sized region in the brain's thalamus involved in movement. Using the images, doctors then can use high-intensity focused ultrasound (HIFU) to ablate, or burn away, problem tissue, says Bhavya R. Shah, M.D., first author of the study and an assistant professor of radiology and neurological surgery at UT Southwestern's Peter O'Donnell Jr. Brain Institute.

"The benefit for patients is that we will be better able to target the brain structures that we want," Shah says. "And because we're not hitting the wrong target, we'll have fewer adverse effects." The procedures are already Food and Drug Administration-approved for use in patients, and UTSW plans to begin employing them to treat patients when its Neuro High Intensity Focused Ultrasound Program opens this fall.

Adverse effects from imprecise targeting include problems walking or slurring words. While such effects are usually temporary, they can be permanent in 15 to 20 percent of cases, says Dr. Shah.

According to the National Institutes of Health, essential tremor affects up to 10 million Americans and Parkinson's disease impacts more than 1 million. Both are neurologic diseases thought to have genetic links. The first line of treatment for the involuntary trembling or shaking seen with these diseases is medication. However, approximately 30 percent of patients do not respond well to drugs, according to the study.

In the late 1990s, neurosurgeons began using a procedure called deep brain stimulation, opening the skull to permanently implant metal electrodes that could then be stimulated via a battery pack.

About a decade ago, a new MRI-guided procedure emerged that uses high-intensity ultrasound waves to heat and eliminate a small section of the thalamus linked to the disorders. MRI-guided HIFU is currently approved for treatment of essential tremor and tremors seen in Parkinson's disease patients. The outpatient procedure does not require opening the skull, and the patient is awake while it is performed, says Dr. Shah. "No cuts. No anesthesia. No implanted devices."

A challenge in both procedures has been locating the precise area inside the brain's thalamus to treat - the pea-sized ventral intermediate nucleus, says Dr. Shah.

Traditionally, doctors have relied on either landmarks or maps of the brain drawn from cadavers to help them pinpoint the correct location. However, every brain is different, Dr. Shah says, and tiny errors can lead to damage in surrounding tissue, or to missing portions of the correct target.

Three newly refined MRI techniques are better at delineating the target tissue, according to the study.

The most widely studied and perhaps most promising imaging method is called diffusion tractography, says Dr. Shah. It creates precise brain images by taking into account the natural water movement within tissues.

The other methods described are quantitative susceptibility mapping - which creates contrast in the image by detecting distortions in the magnetic field caused by substances such as iron or blood - and fast gray matter acquisition TI inversion recovery - which operates much like a photo negative, turning the brain's white matter dark and its gray matter white in order to provide greater detail in the gray matter.

Dr. Shah and his team plan to participate in a multicenter clinical trial with collaborators at the Mayo Clinic in Rochester, Minnesota, testing the diffusion tractography method in patients.

Credit: 
UT Southwestern Medical Center

COVID-19 in Geneva, less than 11% have been infected

A study carried out among 2'766 people by the University Hospitals of Geneva (HUG), the Geneva Centre for Emerging Viral Diseases, and the University of Geneva (UNIGE), Switzerland, reveals that, at the time of the decline of the Coronavirus pandemic, only 10.8% of the Geneva population had been infected with Covid-19. Moreover, compared to adults between 20 and 50 years of age, children between 5 and 9 years of age are three times less likely to be infected and those over 65 years of age half as likely. These results were published in The Lancet.

Over the five weeks of the study - from 6 April to 9 May - the overall seroprevalence increased from about 5% to about 11% of the population. Taking into account the time for antibodies to be produced after symptoms (with a median of 10.4 days), the researchers estimated that for every confirmed case, there were approximately 12 actual infections in the community.

These results suggest that only a minority of the Geneva population has been infected during this pandemic wave, despite the high rate of COVID-19 cases identified during the acute phase of infection (1% of the population in less than 2 months).

Children and elderly less affected

Young children (5-9 years) and the elderly appear to have a much lower seroprevalence than other age groups. Indeed, only 1 in 123 children in this age group tested positive. However, further studies will be needed to better understand the dynamics of infection and of antibodies in children under 5 years of age, and to determine whether children, in addition to being generally less susceptible to Cov2-SARS, are also less severely affected.

The study also reveals a high concentration of infections within households. For example, despite the low seroprevalence of children, 17.1% of children had at least one household member who tested positive, which may suggest that children are infected by adults. On the other hand, only 3.0% of participants over 65 years of age had a household member that tested positive.

Furthermore, lower seroprevalence estimates among the elderly tend to confirm the effectiveness of partial containment measures. However, their ability to produce antibodies may be reduced due to age-related weakening of the immune system..

Protective measures have certainly contributed to the decline of the pandemic.

The preliminary results of this study provide an important benchmark for assessing the outbreak status. At the time when Switzerland appears to be reaching the end of its first wave of the COVID-19 pandemic, only 1 in 10 people have developed antibodies to SARS CoV-2, despite the fact that Switzerland is one of the most affected countries in Europe. The results of this study - the largest population-based seroprevalence study to date - are consistent with preliminary reports from other teams around the world.

These results therefore underline that the decline of the epidemic may have taken place despite the fact that the vast majority of the population is not immune, which implies that other factors are at play.

The value of seroprevalence studies

Seroprevalence surveys based on the detection of specific immunoglobulin type G (IgG) are used to measure the proportion of the population that has ever been exposed to coronavirus. However, they do not provide any indication of full or partial immunity to coronavirus or of the duration of such immunity.

Seroprevalence surveys are nevertheless crucial for estimating the dynamics of the epidemic and for preparing the appropriate public health response. They are also more accurate than studies based on nasopharyngeal smears and RT-PCR tests, which are largely dependent on screening policies and miss people with mild or no symptoms, or who do not come for testing.

This general population seroprevalence study is ongoing and will be refined to take into account symptomatology and socio-demographic factors.

2'766 participants

The study was conducted among a representative sample of the Geneva population drawn from the participants of the Bus Santé study, an annual survey that examines the health of the population of the Canton of Geneva. From 6 April to 9 May 2020, sampled people were invited, together with their family members, for a blood test and a questionnaire. This sample consisted of 52.6% women and 47.2% men, and included 4.4% children between 5 and 9 years of age and 13.3% people over 65 years of age. A total of 2,766 people from 1,339 households took part.

The study was carried out by a team from the HUG and UNIGE under the direction of Professor Idris Guessous, Head of the HUG Primary Care Division and professor at the Department of Community Health and Medicine of the Faculty of Medicine, of Dr. Silvia Stringhini, epidemiologist in charge of the Population Epidemiology Unit at the HUG and Privat-Docent at the Faculty of Medicine, and of Professor Antoine Flahault, Director of the Institute of Global Health of the Faculty of Medicine. The study received support from Professor Laurent Kaiser's Virology Laboratory and from the Geneva Centre for Emerging Viral Diseases, and was funded by the Swiss Federal Office of Public Health, the Swiss School of Public Health (Corona Immunitas programme), the Pictet Group's Charity Foundation, the Fondation Ancrage, the Fondation Privée des HUG and the Geneva Centre for Emerging Viral Diseases.

Credit: 
Université de Genève

The best parents: Genetically as divergent as possible with similar preferences

image: Evaluation of heterosis for grain yield in field trial.

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Photos: Norman Philipp/ IPK

It has shown that hybrids become more and more productive depending on the genetic distance between their parents. The question of whether there is an optmimal genetic distance could definitely be answered negatively. Assuming that the parents are adapted to similar environments. This research result can be read in the next issue of the scientific journal Science Advances.

For decades plant breeding has made use of the heterosis phenomenon: parents genetically as different as possible are crossed to produce offspring performing better than their parents on average. The so-called hybrid breeding is applied very successfully for maize, sugar beet, rye or sunflower. The maximum genetic distance between the parents to generate the best hybrid performance could not be clarified until now. Two studies in the 1960s came up with contradictory results. While one suggested that the genetic distance of the parents should be maximised, the other suggested that the increased performance of the offspring decreases again from a certain point of diversity.

"Thanks to progress in quantitative genetics, we were able to show that there is no optimum for the genetic distance of the parents," explains Prof. Dr. Jochen Reif. He heads the Department of Breeding Research at the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) and the affiliated Quantitative Genetics research group there. As the scientific coordinator of the research task, he knows: "Heterosis increases steadily with the genetic distance between the parents. Parent populations can be as far apart as possible without their offspring losing performance." This is a decisive finding for plant breeding, since it is no longer necessary to fear that the optimal genetic distance has been missed. However, it is important to be careful when it comes to the origin of the parent populations. The geneticist explains: "Parent populations must be adapted to the environment in which their offspring are to be cultivated, otherwise negative dominance effects can occur."

The team led by IPK Gatersleben was able to come to these results as part of a large-scale research cooperation project called ZUCHTWERT. It was funded by the Fereral Federal Ministry of Food and Agriculture and carried out by IPK Gatersleben, the State Plant Breeding Institute (Landessaatzuchtanstalt - LSA) at the University of Hohenheim and 15 well-known plant breeding companies. "Thanks to our latest developments in biometry and quantitative genetics, coupled with the extensive data material from the breeding industry, we were finally able to bring clarity to this long-standing issue," summarises Prof. Dr. Jochen Reif, adding: "In future, plant breeding will be able to select crossing partners on a rational basis for breeding new hybrid varieties, even for an organism as complex as wheat.

Credit: 
Leibniz Institute of Plant Genetics and Crop Plant Research

Cash me outside: Transfers to the poor linked to eco-benefits

image: A new study found that Indonesia's national anti-poverty program reduced deforestation in participating villages by about 30%.

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Mahastra Wibisono

In a new study, researchers recently discovered that Indonesia’s national anti-poverty program reduced deforestation by about 30%.

The study’s findings were published today in Science Advances.

“Two of the great global challenges of the 21st century are to reduce poverty and slow deforestation. Unfortunately, the solutions to those challenges are often perceived as conflicting with each other –progress on one front means retreat on the other,” says Paul Ferraro, Bloomberg Distinguished Professor of Human Behavior and Public Policy at the Johns Hopkins University and the study’s first author.

"Our study is the first of its kind to suggest that cash transfers to the impoverished can have a positive effect on forest conservation. In other words, reducing poverty does not have to create unavoidable environmental costs – we can make progress on both fronts,” says Rhita Simorangkir, co-author of the study and Research Fellow at the National University of Singapore.

Biodiversity and deforestation are disproportionately located in regions with high levels of poverty; for example, Indonesia is among the top ten biodiversity hotspots with the greatest area impacted by poverty. Indonesia also has the third-largest area of tropical forest and one of the highest deforestation rates, making it a strong study choice with findings that could be applied to other countries.

In the past, researchers only examined connections between poverty and the environment on the macroeconomic or local scales, says Ferraro. However, these studies are limited because they don’t allow researchers to clearly establish a link between specific poverty interventions and environmental impacts.

A clear link would be significant, the researchers say, because so much international and philanthropic aid is aimed at programs to alleviate poverty. If evidence shows that such aid can also benefit the environment, global leaders would have new considerations for budget allocations and environmental goals.

For this study, Ferraro and Simorangkir studied Indonesia’s national anti-poverty program, Program Keluarga Harapan, which provides poor households with conditional cash transfers. The team reviewed data from 7,468 rural forested villages exposed to the program between 2008 and 2012, totaling 266,533 households that received cash.

To estimate the program’s causal effect on deforestation, Ferraro and Simorangkir combined data on annual forest cover loss and data on how the program was phased in across villages, along with methods that help isolate the program’s effect on forests from all the other factors that also affect forests.

The authors estimated that the anti-poverty program reduced deforestation in participating villages by 30%, with roughly half of those avoided losses in biodiverse primary forests. Their findings also show that reductions were larger when more villagers received cash transfers and when a village participated for more years.

The authors say the anti-poverty program seems to reduce deforestation because cash provides recipients with a sort of insurance alternative to deforestation (i.e. poor farmers now have money to support themselves instead of deforesting more land when bad weather threatens to lower yields), as well as allows recipients to buy products on markets rather than obtain them by clearing forests.

“Other studies have shown that Indonesia’s program indeed lifted people out of poverty. But even if it had not done so, its environmental benefits are valuable. In fact, the economic value of the avoided carbon emissions alone compares favorably to program implementation costs. Similar programs in other countries should be evaluated in the same way, but if what we found in Indonesia generalizes to other biodiverse nations, it would provide some hope that global efforts to eradicate extreme poverty and reverse the loss of biodiverse ecosystems can be complementary,” says Ferraro.

Credit: 
Johns Hopkins University

Research links personality traits to toilet paper stockpiling

image: People who feel more threatened by COVID-19 and rank highly on scales of emotionality and conscientiousness were most likely to stockpile toilet paper in March 2020, according to a new study published June 12, 2020 in the open-access journal PLOS ONE by Lisa Garbe (University of Saint Gallen, Switzerland), Richard Rau (Westfalische Wilhelms-Universitat Munster, Germany), and Theo Toppe (the Max Planck Institute for Evolutionary Anthropology, Germany).

Image: 
Nori Blume

People who feel more threatened by COVID-19 and rank highly on scales of emotionality and conscientiousness were most likely to stockpile toilet paper in March 2020, according to a new study published June 12, 2020 in the open-access journal PLOS ONE by Lisa Garbe (University of Saint Gallen, Switzerland), Richard Rau (Westfalische Wilhelms-Universitat Munster, Germany), and Theo Toppe (the Max Planck Institute for Evolutionary Anthropology, Germany).

Following the fast spread of COVID-19 across Europe and North America in March 2020, many people began stockpiling commodities including toilet paper. Some companies reported an increase of up to 700% in toiled paper sales, despite calls from the government to refrain from "panic buying."

In the new study, researchers surveyed 1,029 adults from 35 countries who were recruited through social media. Between March 23 and March 29, 2020, participants completed the Brief HEXACO Inventory--which ranks six broad personality domains--and shared information on their demographics, perceived threat level of COVID-19, quarantine behaviors, and toilet paper consumption in recent weeks.

The most robust predictor of toilet paper stockpiling was the perceived threat posed by the pandemic; people who felt more threatened tended to stockpile more toilet paper. Partly, this effect was based on the personality factor of emotionality--people who generally tend to worry a lot and feel anxious are more likely to feel threatened and stockpile toilet paper. The personality domain of conscientiousness--which includes traits of organization, diligence, perfectionism and prudence--was also a predictor of stockpiling (p = .048). Other observations were that older people stockpiled more toilet paper than younger people and that Americans stockpiled more than Europeans. The researchers pointed out that the variables studied explained only 12% of the variability in toilet paper stockpiling, which suggests that some psychological explanations and situational factors likely remain unaccounted for.

The authors add: "Subjective threat of COVID-19 seems to be an important trigger for toilet paper stockpiling. However, we are still far away from understanding this phenomenon comprehensively."

Credit: 
PLOS

LJI scientists uncover immune cells that may lower airway allergy and asthma risk

image: These microscopic critters are hard to avoid, which means nearly everyone has been exposed.

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La Jolla Institute for Immunology

LA JOLLA--The world is full of house dust mites. Do some cleaning, and you'll probably stir some up. While everyone has immune cells capable of reacting to common allergens like house dust mites, most of us have no allergic symptoms.

Still, many people do react with the typical allergic symptoms: sneezing, a runny nose, and itchy, swollen nasal passages. Others have a much more severe reaction: a life-threatening asthma attack.

To treat the root cause of allergies and asthma, researchers need to know exactly what sets these patients apart from healthy individuals.

In a new Science Immunology study, published on June 12, 2020, scientists at La Jolla Institute for Immunology (LJI) offer a clue to why non-allergic people don't have a strong reaction to house dust mites. They've uncovered a previously unknown subset of T cells that may control allergic immune reactions and asthma from ever developing in response to house dust mites--and other possible allergens.

"We discovered new immune cell subsets and new therapeutic opportunities," says Grégory Seumois, Ph.D., instructor and director of LJI's Sequencing Core and co-leader of the new study. "This new population of cells could be one, out of many unknown mechanisms, that explains why healthy people don't develop inflammation when they breathe in allergens."

"The study highlights the power of unbiased single-cell genomics approaches to uncover novel biology," says LJI Professor Pandurangan Vijayanand, M.D. Ph.D., senior author of the new study.

The study builds on the Vijayanand lab's expertise in linking gene expression to disease development. The team also took advantage of the Immune Epitope Database, an LJI-led resource that houses information on how the immune system interacts with allergens like house dust mites.

Why house dust mites? These microscopic critters are hard to avoid, which means nearly everyone has been exposed. Even in people without a house dust mite (HDM) allergy, the immune system is likely to react in some way as it learns to recognize HDM molecules. This makes HDM a useful model for studying what causes allergies and asthma attacks.

The LJI team used a technique part of the "genomic revolution" arsenal of tools, called single-cell RNA-seq (or single cell transcriptomics) to see exactly which genes and molecules specific T cells produce in response to HDM allergens. They tested cells from four groups of people: people with asthma and HDM allergy, people with asthma but no HDM allergy, people with only HDM allergy, and healthy subjects.

Their analysis suggests that a subset of helper T cells, called interleukin (IL)-9 Th2 expressing HDM-reactive cells, is more prevalent in the blood of people with HDM-allergic asthma compared with those who are only allergic to HDM. Further analysis suggested that those IL9-TH2 cells are enriched in a group of molecules/genes that increased the cytotoxic potential of those cells. In other words, those specific T cells could kill other cells and drive inflammation.

In contrast, another subset of T cells stood out in the non-allergic subjects. These T cells express an "interferon response signature" and were enriched for a gene that encodes a protein called TRAIL. The work done by Seumois and his colleagues suggest that TRAIL could be important because it could dampen the activation of helper T cells.

This finding may mean that people with this specific cell population could have less T-cell driven inflammation in response to HDM allergens. At last, this could provide a clue to why some people develop allergies and asthma while others do not.

"Now if functional studies confirm this dampening effect, we're curious if there is a way to boost the activation of these T cells or induce their proliferation in asthmatic or allergic populations," says Seumois. "Can we act on those cells very early on, before asthma has developed?"

For example, genomics studies like this one may someday help identify children at risk of developing asthma and allergies. Early detection could open the door to preemptively acting on immune cells before development of allergy and asthma.

While Seumois emphasizes that there is much more work to be done, he says the transcriptomic method used for this study could accelerate future asthma and allergy research. "This is the first large-scale, single-cell, RNA-seq transcriptomic analysis for LJI," says Seumois. "Now that we have developed the bench know-how and analysis pipeline, it could be applied to many diseases."

Credit: 
La Jolla Institute for Immunology

Research links personality traits to toilet paper stockpiling

image: How much toilet paper a person tends to stockpile may depend on how threatened they feel by COVID-19 and, among other reasons, on their personality traits.

Image: 
Nori Blume

Following the fast spread of COVID-19 across Europe and North America in March 2020, many people began stockpiling commodities including toilet paper. Some companies reported an increase of up to 700 percent in toilet paper sales, despite calls from the government to refrain from "panic buying".

In the new study, researchers surveyed 1,029 adults from 35 countries who were recruited through social media. Between 23 and 29 March 2020, participants completed the Brief HEXACO Inventory - which ranks six broad personality domains - and shared information on their demographics, perceived threat level of COVID-19, quarantine behaviors, and toilet paper consumption in recent weeks.

The most robust predictor of toilet paper stockpiling was the perceived threat posed by the pandemic; people who felt more threatened tended to stockpile more toilet paper. Around 20 percent of this effect was also based on the personality factor of emotionality - people who generally tend to worry a lot and feel anxious are most likely to feel threatened and stockpile toilet paper. The personality domain of conscientiousness - which includes traits of organization, diligence, perfectionism and prudence - was also a predictor of stockpiling.

Other observations were that older people stockpiled more toilet paper than younger people and that Americans stockpiled more than Europeans. The researchers pointed out that the variables studied explained only twelve percent of the variability in toilet paper stockpiling, which suggests that some psychological explanations and situational factors likely remain unaccounted for. "Subjective threat of COVID-19 seems to be an important trigger for toilet paper stockpiling. However, we are still far away from understanding this phenomenon comprehensively", concludes Theo Toppe, co-author of the study.

Credit: 
Max Planck Institute for Evolutionary Anthropology

Pandemics and the environment: China's COVID-19 interventions reduced nitrogen dioxide levels

Pandemics and the Environment: China's COVID-19 Interventions Reduced Nitrogen Dioxide Levels
A new Special Collection of Science Advances papers will delve into how pandemics such as COVID-19 affect - and are affected by - global environmental conditions, underscoring the interconnectedness of global processes. "Economic lockdowns this year, designed to slow the spread of COVID-19, have been like pressing the pause button on environmental degradation and the resulting reductions in air and water pollution are dramatic," writes Kip Hodges and Jeremy Jackson in an Editorial that introduces the Special Collection. "Such trends remind us of how much our actions drive environmental quality and just how badly we have behaved as stewards of our planet." They emphasize that heavy investment in green energy, broader research perspectives, and widespread commitment to policy decisions that support the findings of scientific research will be crucial to achieving a more sustainable Earth.

In the first research paper of this Special Collection, an analysis of the environmental impact of China's COVID-19 policy interventions relied on satellite measurements to identify an average 48% drop in nitrogen dioxide densities over China from 20 days before to 20 days after the Lunar New Year on January 25, 2020. While this greenhouse gas - an indicator of fossil fuel consumption - typically decreases during the holiday, when traffic slows and most Chinese factories close, Fei Liu and colleagues observed that the reduction was about 21% greater than in 2015 through 2019. Fei Liu and colleagues conclude that this enhanced nitrogen dioxide reduction correlated to government announcements of the first reported COVID-19 case in each province and to the initiation of lockdowns, which further subdued both travel and business activity. The researchers monitored shifts in atmospheric nitrogen oxide (which can reflect changes in fossil fuel combustion in a matter of hours) over China using the Dutch-Finnish Ozone Monitoring Instrument (OMI) on board a NASA satellite launched in 2004, and the instrument's successor, the Tropospheric Monitoring Instrument (TROPOMI), which offers measurements with higher spatial resolution from its perch aboard an ESA satellite launched in 2017. Their findings suggest that the tropospheric vertical column density of nitrogen oxide dropped once after the government publicly reported the first COVID-19 case in each province, then dropped again after lockdowns were implemented. "While temporary, these substantial reductions in air pollution may have positive health impact for lives in otherwise heavily polluted areas," the authors write. "This unusual period offers a rare counterfactual of a potential society which uses substantially less fossil fuels and has lower mobility."

Credit: 
American Association for the Advancement of Science (AAAS)

Parasites and the microbiome

image: André Essiane and Eric Ngwang, members of the field research team, record patient health, informed consent, and ethnography information for study participants in southern Cameroon.

Image: 
Courtesy of the Tishkoff laboratory

Parasite infections are a constant presence for many people who live in tropical regions, particularly in less industrialized areas. These often chronic conditions are at best unpleasant; more seriously, children with parasite diseases that cause diarrhea can die of malnutrition or dehydration.

In Genome Biology, a study led by University of Pennsylvania scientists investigated the links between parasite infection and the gut microbiome. Using genetic methods to characterize the gastrointestinal microbiome of 575 ethnically diverse Cameroonian people representing populations from nine villages with meaningful differences in lifestyle, the researchers discovered that the presence of parasites was strongly associated with the overall composition of the microbiome.

"We found that we could look at someone's microbiome and use it to predict whether someone had a gastrointestinal parasite infection," says Meagan Rubel, who completed her doctorate degree at Penn and is now a postdoc at the University of California, San Diego. "Whether or not it was parasites changing the microbiome or something in the resident microbiota of a person that made them more susceptible to infection, we can't say, but the association was strong."

Rubel led the study in collaboration with Penn's Sarah Tishkoff, a Penn Integrates Knowledge Professor in the Perelman School of Medicine and School of Arts and Sciences, and Frederic Bushman, a microbiologist in the medical school. In addition to the microbiome and parasites, the research also examined markers of immune function, dairy digestion, and pathogen infection, a rich dataset.

The investigation entailed six months of field work, collecting fecal and blood samples from Mbororo Fulani pastoralists, cattle herders with a diet high in meat and dairy; Baka and Bagyeli rainforest hunter-gatherers, who practice a limited amount of farming but also forage for meat and plant-based foods; and Bantu-speaking agropastoralists, who both grow crops and raise livestock. As a comparison group, the study included data from two groups of people living in urban areas of the United States, with a diet heavier in animal fats, proteins, and processed foods.

In the field, the researchers tested for malaria and a number of other pathogens that infect both the blood and gastrointestinal system.

Of the 575 people tested in Cameroon, the researchers found nearly 40% were infected with more than one parasite before receiving an antiparasitic treatment, with hunter-gatherers, on average, most likely to be co-infected with multiple parasites. In particular, the team found that four soil-transmitted gut parasites tended to co-occur at a rate much higher than chance: Ascaris lumbricoides, Necator americanus, Trichuris trichiura, and Strongyloides stercoralis, or ANTS.

"Gut parasites are a global public health concern," says Rubel. "And you tend to see several of these parasites together in resource-poor settings where people may not have access to clinical care, piped water, and soap, so there's more opportunity for them to be transmitted."

Back in the lab at Penn, the researchers used genomic sequencing tools to take a snapshot of the participants' gut microbiomes. The composition of the microbiome, they found, could accurately predict a person's country (U.S. or Cameroon) and lifestyle (urban, pastoralist, agropastoralist, or hunter-gatherer). But after these two variables, the presence of ANTS parasites could be predicted with greater accuracy by the microbiome structure than any other variable the research team studied. Taken together, the microbiome could predict the presence of these four gut parasites with roughly 80% accuracy.

Infection with these parasites also led to upticks in immune system activation, specifically turning on pathways that promote inflammatory responses. Parasite infection was also associated with a greater likelihood of having bacteria from the order Bacteroidales, which are known to play a role in influencing digestion and immune system function.

In a second part of the study, the Penn-led team assessed the relationship between the gut microbiome and milk consumption in the Fulani pastoralist population. Earlier work by Tishkoff and colleagues illuminated how genetic mutations enabling lactose digestion arose in pastoralist communities in Africa, selected through evolution because of the important nutritional benefits of consuming dairy. In looking at the Fulani's microbiomes, they also tended to have an abundance of bacterial genes capable of breaking down galactose, a component of lactose, and fats, compared to other groups. "This enrichment of genes could help you extract more nutrition from the food you eat," Rubel says.

The researchers believe their findings, the largest-ever study on the link between gut microbiome composition and parasite infection from sub-Saharan Africa, can open new possibilities for future work. "The kinds of microbiome markers we found could be useful to predict the type of pathogens you have, or to shed light on the interplay between the microbiome and the immune system," says Rubel.

Eventually, she adds, more research could even illuminate strategies for purposefully modulating the microbiome to reduce the risk of a parasite infection or minimize the harm it causes to the body.

Credit: 
University of Pennsylvania

Face masks critical in preventing spread of COVID-19

A study by a team of researchers led by a Texas A&M University professor has found that not wearing a face mask dramatically increases a person's chances of being infected by the COVID-19 virus.

Renyi Zhang, Texas A&M Distinguished Professor of Atmospheric Sciences and the Harold J. Haynes Chair in the College of Geosciences, and colleagues from the University of Texas, the University of California-San Diego and the California Institute of Technology have had their work published in the current issue of PNAS (Proceedings of the National Academy of Sciences).

The team examined the chances of COVID-19 infection and how the virus is easily passed from person to person. From trends and mitigation procedures in China, Italy and New York City, the researchers found that using a face mask reduced the number of infections by more than 78,000 in Italy from April 6-May 9 and by over 66,000 in New York City from April 17-May 9.

"Our results clearly show that airborne transmission via respiratory aerosols represents the dominant route for the spread of COVID-19," Zhang said. "By analyzing the pandemic trends without face-covering using the statistical method and by projecting the trend, we calculated that over 66,000 infections were prevented by using a face mask in little over a month in New York City. We conclude that wearing a face mask in public corresponds to the most effective means to prevent inter-human transmission.

"This inexpensive practice, in conjunction with social distancing and other procedures, is the most likely opportunity to stop the COVID-19 pandemic. Our work also highlights that sound science is essential in decision-making for the current and future public health pandemics."

One of the paper's co-authors, Mario Molina, is a professor at the University of California-San Diego and a co-recipient of the 1995 Nobel Prize in Chemistry for his role in understanding the threat to the Earth's ozone layer of man-made halocarbon gases.

"Our study establishes very clearly that using a face mask is not only useful to prevent infected coughing droplets from reaching uninfected persons, but is also crucial for these uninfected persons to avoid breathing the minute atmospheric particles (aerosols) that infected people emit when talking and that can remain in the atmosphere tens of minutes and can travel tens of feet," Molina said.

Zhang said that many people in China have worn face masks for years, mainly because of the bad air quality of the country.

"So people there are sort of used to this," he said. "Mandated face-covering helped China in containing the COVID-19 outbreak."

Zhang said the results should send a clear message to people worldwide - wearing a face mask is essential in fighting the virus.

"Our work suggests that the failure in containing the propagation of COVID-19 pandemic worldwide is largely attributed to the unrecognized importance of airborne virus transmission," he said. "Social-distancing and washing our hands must continue, but that's not sufficient enough protection. Wearing a face mask as well as practicing good hand hygiene and social distancing will greatly reduce the chances of anyone contracting the COVID-19 virus."

Credit: 
Texas A&M University

All that base

image: BE-Hive's machine learning model predicts which base editor performs best to repair thousands of disease-causing mutations. The library is free and available for public use.

Image: 
Courtesy of the Liu lab

Gene editing technology is getting better and growing faster than ever before. New and improved base editors--an especially efficient and precise kind of genetic corrector--inch the tech closer to treating genetic diseases in humans. But, the base editor boom comes with a new challenge: Like a massive key ring with no guide, scientists can sink huge amounts of time into searching for the best tool to solve genetic malfunctions like those that cause sickle cell anemia or progeria (a rapid aging disease). For patients, time is too important to waste.

"New base editors come out seemingly every week," said David Liu, Thomas Dudley Cabot Professor of the Natural Sciences and a core institute member of the Broad Institute and the Howard Hughes Medical Institute (HHMI). "The progress is terrific, but it leaves researchers with a bewildering array of choices for what base editor to use."

Liu invented base editors. Fittingly, he and his research team have now invented a way to identify which are most likely to achieve desired edits, as reported today in Cell. Using experimental data from editing more than 38,000 target sites in human and mouse cells with 11 of the most popular base editors (BEs), they created a machine learning model that accurately predicts base editing outcomes, Liu said. The library, called BE-Hive, is available for public use. But the effort produced more than a neat catalog of BEs; the machine learning model discovered new editor properties and capabilities that humans failed to notice.

"If you set out to use base editing to correct a single disease-causing mutation," said Mandana Arbab, a postdoctoral fellow in the Liu lab and co-first author on the study, "you're left with a mountain of possible ways to do it and it is difficult to know which ones are most likely to work."

Base editors may be more precise than other forms of gene editing, but they can still cause unwanted, often unpredictable, edits outside the intended genetic target. Each editor has its own eccentricities. Different types operate within smaller or larger editing "windows," stretches of DNA about two to five letters wide. Some editors might overshoot or undershoot their targets; others might change just one of two As in a given window.

"If the sequence within the window is GACA," Liu said, "and you're using an adenine base editor to change one of those As, will one be preferentially edited over the other?"

The answer depends on the base editor, its paired guide RNA--the chaperone that ferries the editor to the appropriate DNA work site--and the surrounding DNA sequence. To corral all these complicating factors, the team first collected a massive amount of data. Over about a year, Arbab said, they equipped cells with over 38,000 DNA target sites and then treated them with the 11 most popular base editors, paired with guide RNAs. After the treatment, they sequenced the DNA of the cells to collect billions of data points on how each base editor impacted each cell.

To analyze this bounty, Max Shen, a Ph.D. student at the Massachusetts Institute of Technology's Computational and Systems Biology program, member of the Broad Institute, and co-first author designed and trained a machine learning model to predict each base editor's particular eccentricities. In a previous groundbreaking study, Shen and his lab mates trained a different machine learning model to analyze data from another common gene editing tool, CRISPR, and dispelled a popular misconception that the tool yields unpredictable and generally useless insertions and deletions, Shen said. Instead, they showed that even if humans can't predict where those insertions and deletions occur, machine learning could.

Now, researchers can put a target DNA sequence into BE-Hive, Shen's beefed up machine learning model, and see predicted outcomes of using each of the 11 base editors on that target. "BE-Hive predicts, down to the individual DNA sequence level, what will be the distribution of products that results from each of those base editors acting on that target site," said Liu.

Some of BE-Hive's predictions were surprising, even to the inventor of base editors. "Sometimes," Liu said, "for reasons that our primate brains aren't sufficiently sophisticated to predict, the model could accurately tell us that even though there are two Cs right in the editing window, this particular editor will only edit the second one, for example."

BE-Hive also learned when base editors can make so-called transversion edits: Instead of changing a C to a T, some base editors changed a C to a G or an A, rare and abnormal but potentially valuable quirks. The researchers then used BE-Hive to correct 174 disease-causing transversion mutations with minimal byproducts. And, they used BE-Hive to discover unknown base editor properties, which they used to design novel tools with new capabilities, adding a few more genetic keys to the ever-growing ring.

Credit: 
Harvard University

School may be the key to improvement for children in social care

image: Children in social care have poorer mental health and perform worse in school than other children. But they have trust in the school staff and perform better after individual assessment at school. These are findings in a doctoral thesis from Linköping University.

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Linköping University

Children in social care have poorer mental health and perform worse in school than other children. But they have trust in the school staff and perform better after individual assessment at school. These are findings in a doctoral thesis from Linköping University.

Every year, the social services assume the care of more than 10,000 children and adolescents, who for various reasons are not able to live at home. In 2018, for instance, 39,000 children and adolescents lived in foster families or at various types of homes. Previous research shows that these children constitute a risk group in terms of poorer health, abuse and developing drug addiction. Additionally, they have worse prospects at school and on the labour market.

Rikard Tordön's experiences as a psychologist spurred him to make his own contribution to the research into children in state and municipal care.

"When I worked as a psychologist in the foster care sector, I discovered that it is guided by values and political decisions, not by knowledge. I saw a lack of research about what actually works. My thesis shows that initiatives in school can help the children perform better. And these initiatives must be implemented", says Rikard Tordon, psychologist and new PhD at Linköping University's Department of Biomedical and Clinical Sciences. His previous roles include national coordinator for Skolfam, a programme aimed at increasing the school results of children in foster care.

More vulnerable and less trust in adults

Rikard Tordön's doctoral thesis consists of four studies, published in different scientific journals.

The first study confirms that abuse and mental illness are more common among final-year upper secondary pupils in out-of-home care (OHC). It also found that these children, compared to their non-OHC peers, are less inclined to disclose abuse, in particular to police and social services.

The doctoral thesis' second study shows that on the whole, pupils in OHC have less trust in the adults in their (foster) homes, compared to non-OHC pupils. Of pupils in OHC, one in five reported that it is difficult to turn to their foster parents, although they trust teachers, school nurses and healthcare professionals.

"It's positive that children in OHC trust professionals. This means we've found a channel for reaching these children", says Rikard Tordön.

School results suffer, but this can be remedied

The results from study three show that the intelligence of children in foster care is affected by their insecure situation. An assessment of 856 children in elementary school shows that children in foster care have lower values on tests of, e.g., literacy and mathematical skills. They have difficulty with text decoding, literacy and mathematics. However what surprised Rikard Tordön was not that intelligence was affected, but how much it was affected. Children in OHC had a mean value of 91 points, compared to 100 points for children who live with their parents.

But the good news is that this can be remedied. 475 of the children in the previous study took part in a second mapping, following individual intervention according to the Skolfam model. After a two-year individual training plan, the children performed better, in e.g. mathematics and literacy, so-called higher-order executive functions. However, lower-order executive functions and affective functioning, such as text decoding and impulse control, did not change. Moreover, intelligence increased from 91 to 95 points, as mean values, after the first two years of the intervention.

"It is possible to help these children do better in school, and school has a protective effect in the long-term. Now we have to start to measure, systematically, how good we are at helping our vulnerable children, so that we discover what works, and what doesn't work."

Credit: 
Linköping University

Addressing the drug problem in health and social care will produce better outcomes

The prevalence of drug use has increased for decades all around the world despite the strict measures taken. As the traditional prohibitionist drug policy has created social injustice, public health problems, and high social costs, decriminalization of drug use has emerged as a response.

Researchers at the Finnish Institute for Health and Welfare (THL) have evaluated the impact of decriminalization policy in different settings. The new study reviews reports, peer-review articles, and critical response papers on the topic.

The review shows that one of the essential steps in policy design is to alter the government approach in managing the drug problem. Drug policy has been considered a criminal justice issue for many decades. Today, it has been acknowledged that the system is not able to produce the best results.

"The power politics of government institutions play a significant role in policy design. However, the loosening of the role of law enforcement might be a crucial prerequisite for transition. The findings point out that intervening drug issues within a health framework will produce better outcomes," says Research Professor Pekka Hakkarainen.

Decriminalization policy reduces public health risks and overdose deaths

The findings in countries where decriminalization policy has been implemented provide substantial evidence for reducing infectious diseases and drug-related deaths among people who use drugs.

"For instance, if the aim is to prevent overdose deaths, more resources should also be devoted to harm reduction services. A simple change in the status in law in terms of personal drug use or possession is not an adequate response to reduce the number of overdose deaths. The outcomes should be defined more carefully, and the impacts of policy should be interpreted more cautiously," stresses Research Programme Director Tuukka Tammi.

The decriminalization policy provides an encouraging environment for seeking help and drug treatment. It also facilitates the integration of people who use drugs in the society and increases educational attainment and employment.

Besides, drug-related overloads on criminal justice have reduced tremendously, which reduces the cost of policing and prisoning.

Fear over increased drug use is a barrier for the adaptation of decriminalization

One of the main barriers to decriminalization policy adaptation is the fear of a rapid increase in overall drug use after implementation. However, the findings show that there is no significant increase in the long run.

"Since the legal status of the drugs is not the only predictor of drug use in a society, the focus should be on the regional trends, drug culture, and other drug-related policies to comprehend the drug initiation broadly," Hakkarainen says.

Decrimalization models vary between countries

The researchers stress that decriminalization is a generally used umbrella term, and every country must find the model that best fits its aims, values, and local circumstances.

"Since the way the issue has emerged in each country has varied, each design focuses on particular needs, which has led to different results. The report mainly draws attention to the underlying reasons of policy development in states where it has been implemented for a while. On the other hand, since the policy expectations define the means, the study shows that the context shapes the desired ends. To highlight the impact of the contextual factors, the report includes examples of policy successes or failures around the world", says visiting researcher Ali Unlu.

Credit: 
Finnish Institute for Health and Welfare

Versatile symbionts: Reed beetles benefit from bacterial helpers through all life stages

image: Bacterial symbionts in the Malpighian tubules of the common reed beetle, Donacia vulgaris.

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photo/©: Martin Kaltenpoth

Insects that feed only on plants have a number of challenges to overcome. But they also have some active helpers to assist them with the supply of important nutrients. So-called symbiotic microorganisms make essential amino acids, vitamins, and enzymes available and in this way supplement and enrich the limited diet of their host insects. Reed beetles with their semi-aquatic lifestyle also have such helpers that extend their range of available nutrients. Scientists at Johannes Gutenberg University Mainz (JGU) in collaboration with researchers at the Max Planck Institute for Chemical Ecology in Jena and partners in Hamburg and Japan have investigated the contributions that the symbiotic bacteria make to the unusual life cycle and diet of reed beetles. "Thanks to their symbiotic bacteria, reed beetles have been able to access new ecological niches. Although this means that the symbionts promote the ecological potential of their hosts, what is even more interesting is the fact that they can also restrict their adaptability," explained Professor Martin Kaltenpoth, head of the Department of Evolutionary Ecology at JGU.

Symbionts help nourish reed beetle larvae under water

Reed beetles are an ecologically unusual subgroup of the leaf beetle family and consist of around 165 species that live all or part of the time in water. The larvae of these reed beetles are aquatic and attach themselves to underwater plant roots from which they suck the sap as food. The adult beetles of most species live in vegetation above the water level and eat the leaves of plants such as grasses, sedges, and water lilies. In contrast with many other leaf beetles, the food sources of the larvae and the adult insects of the same species differ considerably. "The aquatic life stage of the larvae is highly unusual," stated Kaltenpoth, pointing out that the larvae even produce a cocoon under water, from which the mature beetles hatch. Since the early 1930s it has been known that reed beetles live in close symbiosis with bacteria that colonize blind sacs in the midgut of the larvae, but in the adult beetles they occupy the so-called Malpighian tubules, which are comparable to our kidneys. Scientists were also aware that without these symbionts the larvae would not be able to form a cocoon. However, how exactly the symbiotic bacteria contribute to the sustenance of their hosts has, as yet, remained a mystery.

Using high-throughput sequencing techniques, the team led by Kaltenpoth sequenced the genetic material of the symbionts of 26 species of reed beetles from North America, Asia, and Europe. They reconstructed the entire genomes of the symbionts and were able to make predictions as to what these microbes actually do for their beetle hosts. It turns out that the bacteria can produce almost all of the essential amino acids, that is the ten protein components vital to life that the beetles cannot synthesize themselves. This is likely important for the larvae in particular, because the plant sap from roots does not supply sufficient amounts of amino acids - and most importantly, not enough to build the protein-rich cocoon. "We know this form of cooperation in which most or all of the essential amino acids are supplied from many plant sap-feeding Hemiptera, for example aphids and cicadas, but this is uncommon in beetles," said the evolutionary biologist.

Some of the symbionts help adult beetles to break down pectins

A second aspect of the coexistence of adult reed beetles and bacteria is even more interesting. Some of the symbionts provide one or two enzymes that can break down pectins. Pectins are present in the cell walls of plants and are difficult to digest. They can be broken down by pectinases in order to contribute to the carbohydrate and energy supply of the herbivorous insects.

The research team drew up a phylogenetic tree of the symbiotic bacteria to trace their evolutionary history. Interestingly, over the course of their evolution, the pectinases have disappeared from the symbiont genomes in four independent beetle lineages. Beetles that do not obtain pectinases through their symbiont are specialized to live on grasses and sedges, plants with low amounts of pectin. "These beetles have changed their food plant preferences. And because grasses and sedges only have small amounts of pectin in the cell wall, the pectinases provided by the symbionts were no longer useful and got subsequently lost," said Kaltenpoth. Beetles that continue to feed on water lilies, grass rush, or pondweed still have at least one pectinase.

Microbial symbiosis can extend as well as restrict ecological niches

The results reveal that, on the one hand, symbionts can broaden the ecological potential of their host and enable it to adapt to a new niche. However, they also show that symbiotic microbes can restrict the selection of host plants if their enzymatic abilities are lost. "We think that the species of reed beetle that live on grasses and sedges can no longer return to consuming pectin-rich host plants," concluded Kaltenpoth.

Reed beetles are among the few groups of beetles that have changed from a terrestrial to an aquatic life cycle. Symbiotic microorganisms have made a significant contribution to this move from land to water by supporting the nutrient supply of the larvae and adult beetles. However, as certain types of reed beetles no longer have pectinases available, they are also responsible for limiting the ecological environment their host can occupy.

Research funded by an ERC Consolidator Grant

Professor Martin Kaltenpoth's research on the microbial ecology of reed beetles is being supported by an ERC Consolidator Grant, which he was awarded in 2018 to investigate aspects of symbiosis between beetles and bacteria. The biologist has been Professor of Evolutionary Ecology at Johannes Gutenberg University Mainz since 2015. He has recently been appointed new director of the Max Planck Institute for Chemical Ecology in Jena, where he will be setting up the new Department of Insect Ecology and Evolution from February 2021.

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Johannes Gutenberg Universitaet Mainz

Our sleep during lockdown: Longer and more regular, but worse

Research assumes that many sleep disorders are caused by our modern lifestyle, which is characterized by pressure to constantly perform and be active. Rhythms of work and leisure activities thus set a cycle that is often at a mismatch with the body's internal biological clock. If the differences in sleep timing and duration between work days and days off become too large, this can lead to "social jetlag". With this in mind, restrictions that involve working from home could offer some benefits: flexible working hours, no commuting and potentially more time to sleep.

Researchers from the University of Basel and the Psychiatric Hospital of the University of Basel investigated the effects of the restrictions implemented to contain the Covid-19 pandemic on sleep rhythms and sleep behavior in a six-week online survey conducted between 23 March and 26 April 2020. Under the leadership of psychologist Dr. Christine Blume, a total of 435 people were surveyed in Switzerland, Austria and Germany. More than 85% of the respondents were working from home at that time. Overall, the participants slept rather well, 75% of them were women.

Less "social jetlag"

The survey found that a relaxation of social rhythms - for example, through more flexible working hours - led to a reduction in "social jetlag". "This suggests that the sleep-wake patterns of those surveyed were guided by internal biological signals rather than social rhythms," says Blume. Furthermore, 75% of those surveyed reported sleeping up to 50 minutes longer than before the lockdown. One factor contributing to this could be that people no longer had to commute to work in the morning, the sleep researcher explains.

Tip: outdoor activities

However, this reduction of "social jetlag" was not paralleled by an improvement in perceived sleep quality. To the contrary, those surveyed reported that their sleep quality actually deteriorated a little during the lockdown. This is not very surprising, explains Blume, as this unprecedented situation also was highly burdening in many ways. Financial and health concerns or stress related to child care are just a few relevant aspects.

The sleep expert has a tip for those whose sleep has deteriorated: "Our findings suggest that physical activity outdoors could counteract a deterioration in sleep quality."

Credit: 
University of Basel