Culture

Describing the genetic diversity of human populations is essential to improve our understanding of human diseases and their geographical distribution. However, the vast majority of genetic studies have been focused on populations of European ancestry, which represent only 16% of the global population. Scientists at the Institut Pasteur, Collège de France, and CNRS have looked at understudied human populations from the South Pacific, which are severely affected by a variety of diseases, including vector-borne infectious diseases such as Zika virus, dengue, and chikungunya, and metabolic diseases such as obesity and diabetes. Using genome sequencing of 320 individuals, the scientists have investigated how human populations have biologically adapted to the environments of the Pacific islands and how this has affected their current state of health. This study has also revealed hitherto unsuspected aspects of the history of human settlement in this region. This work is published in the April 14th, 2021 issue of Nature.

An international consortium of scientists organized by Etienne Patin (CNRS/Institut Pasteur) and Lluis Quintana-Murci (Collège de France/Institut Pasteur) was set up to characterize the genetic diversity of populations in the South Pacific, a region full of contrasts with its myriad islands that have been settled at very different time periods.

Indeed, shortly after humans left Africa, they settled Near Oceania (Papua-New-Guinea, the Bismarck Archipelago, and the Solomon Islands) approximately 45,000 years ago, while the rest of the Pacific, known as Remote Oceania (Vanuatu, the Wallis and Futuna Islands, Polynesia, etc.), remained uninhabited. It was only approximately 40,000 years later that Remote Oceania was peopled: it is currently accepted that a group of humans left Taiwan 5,000 years ago - a migration known as the 'Austronesian expansion' - passed through the Philippines, Indonesia, and the already-inhabited Near Oceanian islands to eventually settle Remote Oceania for the first time.

En route to these remote lands, the ancestors of South Pacific populations met with groups of archaic humans, with whom they interbred. While 2-3% of modern-day Oceanian populations' genetic material is inherited from Neanderthals (which all populations outside Africa also possess), up to 3% of their genomes is also inherited from Denisovans (relatives of Neanderthals thought to have originated in Asia). It was already known that modern humans inherited beneficial mutations from Neanderthals via admixture, which improved their ability to adapt to their environment, including resistance to viral infections (Cell, 2016 ). In this study published today, scientists from the Human Evolutionary Genetics Unit (Institut Pasteur/CNRS ) in collaboration with various laboratories in France , Germany, Sweden, Switzerland, China, and Taiwan have sought to shed light on how ancient admixture helped Pacific populations to adapt to their specific island environments, including any pathogens encountered.

Historical events traced using genetics

Based on whole-genome-sequencing of over 320 individuals from Taiwan, the Philippines, the Bismarck Archipelago, the Solomon Islands, Santa Cruz Islands, and Vanuatu, this work published in the Nature journal has helped tracing the history of the human settlement of Oceania. First, the scientists have dated the settlement of the various islands of Near Oceania back to approximately 40,000 years, thus confirming archaeological records. They have also demonstrated that this initial settlement was followed by a period of genetic isolation between islands. "Our results confirm that humans were able to cross the seas to reach new lands from an early stage. However, they also suggest that these voyages were relatively infrequent at this distant period in history," explains Etienne Patin, a CNRS scientist within the Human Evolutionary Genetics Unit at the Institut Pasteur. Moreover, the results of the study reveal a major reduction in the size of these populations just before the settlement.

Second, the study challenges the theory, known as the Out-of-Taiwan model, that a population left Taiwan approximately 5,000 years ago to rapidly settle Near and Remote Oceania. "Our analyses suggest that humans left Taiwan more than 5,000 years ago, and that admixture between the Austronesian incomers and the populations of Near Oceania started only 2,000 years later. The expansions from Taiwan therefore took some time, and may have involved a maturation phase in the Philippines or Indonesia," comments Etienne Patin.

The heritage of Neanderthals and Denisovans in South Pacific populations

Through this work, it has been possible to estimate the proportions of Neanderthal and Denisovan material in the genomes of South Pacific populations. "We were surprised to note that, contrary to the Neanderthal heritage, which is very similar among the twenty populations studied (approximately 2.5%), the Denisovan legacy varies considerably between populations, from virtually 0% in Taiwan and the Philippines to up to 3.2% in Papua-New-Guinea and Vanuatu" comments Lluis Quintana-Murci, Professor at the Collège de France, holder of the Chair in Human Genomics and Evolution, and Head of the Human Evolutionary Genetics Unit (Institut Pasteur/CNRS).

But this was not the only surprise. The study confirms that Neanderthals provided modern human populations with beneficial mutations associated with numerous phenotypes: skin pigmentation, metabolism, neuronal development, etc. However, the most surprising finding is that admixture with Denisovans has almost exclusively brought beneficial mutations related to immune response regulation. This suggests that the Denisovan heritage has been a reservoir of advantageous mutations, which have improved the Pacific populations' ability to survive local pathogens. Therefore, it appears that these populations have benefited from the advantages bestowed through admixture with both forms of archaic humans.

Furthermore, the study demonstrates that admixture with Denisovans did not occur at once, but over the course of at least four independent events. It shows that the Denisovans with whom the Pacific populations interbred were in fact highly diverse populations. This conclusion was impossible to deduce from the single genome of a Denisovan specimen found in Siberia: "One of the strengths of these analyses is that, by studying the 3% of archaic heritage present in the genomes of modern humans, one can 'resurrect' Denisovans' genomes, and thus show that they presented high levels of genetic diversity," comments Lluis Quintana-Murci.

Finally, besides the biological adaptation enabled by archaic admixture, the scientists have found that lipid metabolism, cholesterol in particular, was also a target of natural selection among Oceanian peoples. This insight will potentially improve our understanding of why recent changes in these populations' lifestyle may be associated with metabolic disorders.

By taking an evolutionary genetics approach, it is possible to shed light on the history of populations' biological adaptation to their environment, and provide the scientific community with valuable information on specific human traits. These large-scale genomic studies will eventually help us better understand the genetic causes of diseases affecting some regions of the globe, where medical research has hitherto been scarce.

What The Study Did: Data from the Ohio Department of Health were used to evaluate changes in drug overdose mortality in that state by type of drug and age of the user during the first seven months of the COVID-19 epidemic.

Authors: Janet M. Currie, Ph.D., of Princeton University in Princeton, New Jersey, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.7112)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

What The Study Did: The association between severity of eczema among children and risk of being diagnosed with a learning disability was investigated in this study.

Authors: Joy Wan, M.D., M.S.C.E., of the University of Pennsylvania Perelman School of Medicine in Philadelphia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamadermatol.2021.0008)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

A potential treatment for dementia and epilepsy could look to reduce the amounts of a toxic gas in the brain has been revealed in a new study using rat brain cells.

The research published in Scientific Reports today [Wednesday 14 April] shows that treatments to reduce levels of hydrogen sulfide (H2S) in the brain may help to ward off damage caused by the gas. By testing rat brain cells, the team of scientists from the University of Reading, University of Leeds and John Hopkins University in the USA found that H2S is involved in blocking a key brain cell gateway that helps the brain to communicate effectively.

Dr Mark Dallas, Associate Professor in Cellular Neuroscience at the University of Reading said:

"This is an exciting finding as it gives us new insights about the role of hydrogen sulfide in various brain diseases, such as dementia and epilepsy. There has been growing interest in the effect of hydrogen sulfide on the brain and this study shows how important the implications of its build-up on proper brain functioning may be.

"We saw that hydrogen suldife acts to disrupt the normal functioning of potassium channels. These channels regulate electrical activity across the connections between brain cells, and when these channels are blocked from working properly we see overexcitable brain cells which we believe is leading to nerve cell death.

"The implication for potential treatments is particularly exciting because finding drugs that target hydrogen sulfide production in our brains may have a host of benefits for diseases, and there are clear links between hydrogen sulfide build -up and other warning signs for diseases such as Alzheimer's."

In the study, cells taken from rat brains were charged with a H2S donor molecule, and then brain cell electrical signals were monitored. The resulting exposure to H2S increased the level of activity in brain cells, and the research was able to establish that the effect was specifically controlled by the potassium channel tested.

The team were also able to identify which part of the potassium channel was allowing this effect from H2S. They used a mutated form of the potassium channel, which has already been shown to protect nerve cells from a host of toxic stimuli, including amyloid beta and found that the mutation was resistant to the effect of H2S that was seen in natural cells.

The specific mutated channel now holds particular interest for research into Alzheimer's Disease, given the protective benefits against amyloid beta which is also implicated in dementia.

Dr Moza Al-Owais, Research Fellow at the University of Leeds said:

"This exciting study demonstrates the growing evidence that gasotransmitters play an important role as signalling molecules in the regulation of the physiological processes underlying Alzheimer's disease, which are relatively poorly understood, opening new avenues for investigation and drug discovery."

Chestnut Hill, Mass. (4/14/2021) -- Using abundant cobalt and a unique experimental approach to probe ways to speed a sluggish catalytic reaction to harvest hydrogen from water, researchers from Boston College and Yale University discovered a mechanistic switch in the oxygen evolution reaction, a significant step towards optimizing electrocatalysts for water splitting to produce clean energy.

The mechanism switches by varying the amount of voltage, or applied potential, the team reports in the journal Chem. At moderate potential, two oxygen atoms bound to the catalyst surface react to form the oxygen-oxygen bond. By contrast, at higher potentials, the oxygen-oxygen bond is formed by a water molecule attacking a surface-bound oxygen species.

The findings show that in this materials class, an electrocatalyst for this reaction should be chosen, or optimized, depending on the potential regime in which it is expected to operate in a reactor. In other words, a given catalyst may be particularly efficient in promoting one mechanism, but not the other.

"What surprised us was how steeply the switch occurs from one mechanistic regime to another with applied potential," said Boston College Professor of Chemistry Dunwei Wang, a lead author of the report. "Only about 100 mV are necessary to toggle between the two mechanisms. It is a reminder of how sensitive reaction mechanisms are. More broadly, the facile switch may be another indication of how photosynthesis can adapt to changes in reaction environment for optimized performance."

Researchers have been working to split water into molecular hydrogen and oxygen in an effort to provide abundant renewable energy in the form of transportable and storable hydrogen gas. The splitting can be accomplished with electrocatalysis, a process in which the hydrogen and oxygen evolution reactions occur in spatially separated compartments on electrodes. That makes electrocatalysis a highly promising means for producing clean hydrogen gas.

However, the oxygen evolution reaction (OER) is slow, said Wang. As a result, the rate of the overall water splitting reaction is limited by the sluggish OER. The reaction needs to be facilitated by catalysts, that is, materials that promote the reaction without being themselves consumed in the process. To date, economically viable electrocatalysts for the promotion of the oxygen evolution reaction have not been developed yet. Wang and his colleagues focused on the OER in promising electrocatalysts in an effort to better understand the reaction processes and use those insights to design more efficient and stable electrocatalysts for this reaction.

They focused on the reaction in a class of electrocatalysts that are based on oxides of cobalt, a cheap and earth-abundant material, attributes that would translate efficiently to use on an industrial scale, Wang said.

In the last decade, various cobalt-oxide-based electrocatalysts have emerged as promising candidates for promoting the OER. In a collaboration with colleagues at Yale University, Wang and his team studied the OER on two types of cobalt-oxide electrocatalysts with electrochemical techniques, infrared spectroscopy, and density functional theory.

Wang said the team controlled the concentration of water by using water-in-salt electrolytes, which feature a concentration of salt that is approximately ten times higher than that of seawater. As a result, the researchers could control the activity of water by adjusting the amount of salt in the electrolyte. They monitored how the rate of the reaction responded to different concentrations of water. This revealed the mechanism of the OER on cobalt-based electrocatalysts, Wang said. Co-author and BC Associate Professor of Chemistry Matthias Waegele and his research team used infrared spectroscopy, which relies on the interaction of infrared light with molecules, to detect reaction intermediates of the OER under operating conditions.

They were able to detect a key reaction intermediate, which was predicted by the calculations by Yale chemist Victor Batista and his research group. Gary Brudvig, an inorganic chemist at Yale, also advised the team during the project.

Wang said the team wanted to look closely at the oxygen evolution reaction, particularly the characteristic that it is a step-by-step process, not a single event. Water contains only one oxygen atom. The product of the OER is molecular oxygen, which contains two oxygen atoms. Therefore, during the OER an oxygen-oxygen bond is formed, he noted.

Wang said researchers in this field have focused on two central questions: how does this oxygen bond form and in what step? Two principal mechanisms have been proposed in prior studies, however researchers had yet to resolve under what experimental conditions -- temperature, or applied electrode potential, for instance -- the oxygen-oxygen bond forms and which of the mechanisms is the dominant one.

Wang and his colleagues decided to look closely at how the applied electrode potential dictates the mechanism of the oxygen-oxygen bond formation step since reactions in electrocatalysis are driven by an electric potential that is applied to the catalyst.

The findings suggest that the mechanistic switch might be general for oxide-based electrocatalysts, Wang said.

"We are very interested in learning if this observation also applied to other promising electrocatalysts," he said. "In particular, we are currently working on catalysts with atomically defined active centers. In contrast to the cobalt-based electrocatalysts, whose atomic structure at the active center remains unresolved, our new study platform contains catalytic centers that are atomically well-defined. It will be very interesting to see if the potential-induced mechanistic switch also occurs on those catalysts."

In the cell nucleus histones play a crucial role packaging DNA into chromatin. Histones are however very sticky to both DNA and RNA, so to ensure they are transported to the cell nucleus after synthesis and bind to the right portion of DNA to organize the chromatin, they are guarded by complexes of histone chaperones.

Histone chaperones are proteins that bind to histones to help protect them from non-specific binding events until they reach their goal. This process fails sometimes and histones get stuck during their supply to chromatin without any purpose.

In a study published in Molecular Cell, researchers have shown that the protein DNAJC9 holds an important role in safeguarding histones and thereby chromatin.

Active fixer joins passive bystanders

"Until now researchers have assumed that histone chaperones only act to passively shield histones. We have found out that DNAJC9 actively engages the cellular protein folding machinery - which means it actively recruits enzymes and molecular chaperones to redeploy histones that have been trapped," says assistant professor Colin Hammond, who has lead the study. Hammond is part of the Protein Memory Program in the Novo Nordisk Foundation Center for Protein Research at University of Copenhagen.

Once released from their trapped condition histones can re-engage histone chaperones like MCM2 and be assembled into nucleosomes to organize chromatin. When the protein DNAJC9 is mutated to lose its ability to recruit the protein folding machinery, the histones stay trapped and are thereby lost for proper chromatin deposition.

"This means that traditional histone chaperones cannot fully protect histone proteins from spurious interactions. Rather, the cell is dependent on the combined action of molecular chaperones and histone chaperones to safeguard these fundamentally important proteins during their dynamic lives," Colin Hammond underlines.

Strong collaboration necessary

The study is based on a strong international collaboration. Co-first author Hongyu Bao in Hongda Huang's lab and other partners from Southern University of Science and Technology in China, and Dinshaw Patel from Memorial Sloan Kettering Cancer Center, provided the structural discoveries of DNAJC9. The functional analysis was spear-headed by Colin Hammond in close collaboration with colleagues from the Proteomics Program at CPR, Ivo Hendriks and Michael Lund Nielsen, to dissect the function of the protein through in depth proteomic assays.

Relevant insights for cancer research

DNAJC9 is an essential protein in many cancer cell types and the levels of the protein correlate with the rates at which cancer cells proliferate. Chromatin in cancer cells may be more reliant on DNAJC9 compared to regular cells, and if this is the case DNAJC9 could be a target for the development of future cancer treatments.

"Although it's still early days, we hope this fundamental advance in our understanding of DNAJC9 biology helps to pinpoint a function essential for cancer cell viability with therapeutic potential," Colin Hammond says.

If you were to visit the Great Basin and Colorado Plateau a thousand years ago, you'd find conditions remarkably familiar to the present. The climate was warm, but drier than today. There were large populations of Indigenous people known as the Fremont, a who hunted and grew crops in the area. With similar climate and moderate human activity, you might expect to see the types of wildfires that are now common to the American West: infrequent, gigantic and devastating. But you'd be wrong.

In a new study led by the University of Utah, researchers found that the Fremont used small, frequent fires, a practice known as cultural burning, which reduced the risk for large-scale wildfire activity in mountain environments on the Fish Lake Plateau--even during periods of drought more extreme and prolonged than today.

The researchers compared lake sediment, tree ring data and archaeological evidence to reconstruct a 1,200 history of fire, climate, and human activity of the Fish Lake Plateau, a high-elevation forest in central Utah in the United States. They found that frequent fires occurred between the years 900 and 1400, a period of intense farming activity in the region. Prehistoric cooking hearths and pollen preserved in lake sediment show that edible plant species dominated the landscape during this period, indicating that Fremont people practiced cultural burning to support edible wild plants, including sunflowers, and other crops. Large-scale farming ceased after the year 1400. Hunters and foragers, ancestors of the Ute and Paiute, continued to burn, although less frequently than during the farming period. After Europeans made cultural burning illegal, the ecosystem returned to be dominated by a thick forest of trees.

"When you have people burning frequently, they're reducing the amount of surface fuels present on the landscape. It makes it much more difficult for a lightning fire to reach up to the canopy and burn down the entire forest," said Vachel Carter, postdoctoral research assistant at the U and lead author of the study. "Now we have an environment dominated by trees in a very dry environment, which are conditions prime for megafires. Is this a result of climate change? Definitely. But in the case at Fish Lake, it could also be attributed to a lack of cultural burning."

For millennia through the present, Indigenous people across North America have used cultural burning to drive game, ease travel, clear vegetation for fields and enhance regrowth of edible plants. European settlers banned the practice in favor of fire suppression, the strategy that's dominated forest management since the turn of the 20th century.

"All over North America, humans have always modified fire regimes to benefit themselves and their families," said Brian Codding, associate professor of anthropology at the U and senior author of the paper. "Cultural burning is something that needs to be considered when people are talking about how to manage forests, just like in the Fish Lake National Forest."

The paper published April 14, 2021 in the Nature journal Communications Earth and Environment.

It takes a village

The study is the first in the region to combine charcoal, pollen, tree ring and archeological site data together to assess human influence on prehistoric wildfires. The multiple disciplines allowed the researchers to make connections that would otherwise have been impossible.

"This is really showing us something that's kind of invisible otherwise," said Codding. "People have been trying to look at human impacts on fire regimes all over the place, and it's really hard. Because the changes might be really subtle, or our records just aren't fine-grained enough to record the types of changes that can reveal it."

Colleagues from Utah State University and Brigham Young University contributed tree ring data that document how the climate has shifted over time. Thick rings mean that the tree grew rapidly, indicating there was more moisture available. Narrow rings represent a slow growth year due to less moisture, a signature that can record periods of drought. For this study, they established a climatological timeline for the Fish Lake area.

Carter analyzed the contents of ancient sediments to reconstruct past worlds. Detritus from the local environment blows over the lake and settles at the bottom, building up layers as time passes. Each layer provides a snapshot of what the surrounding area was like at a particular time. She used charcoal as a proxy for fire abundance--more charcoal means more frequent fire--and analyzed pollen grains to determine what plant species dominated and compared how those changed over the last 1,200 years.

Codding and colleagues counted the number of sites that were occupied, using radiocarbon dates on items found at dwelling sites to establish when people were there. They also used food remnants in cooking hearths to establish the types of food people were eating. They analyzed sites within modern day Sevier County, the area around and including Fish Lake, the ancestral lands of the Ute and Paiute Tribes.

"From the cooking hearths found at Fish Lake, we got an indication of what people were eating, and when they were eating it. We knew that they were eating food in the sunflower family, the grass family, and the sedge family, all these plants that don't naturally dominate a high elevation forest," said Carter. "I counted the pollen from those species in the sediment cores and, sure enough, when the Fremont were present, those same plant species were present in much higher abundances than when the Fremont were absent."

"This piece really pulls the study together for linking how people living at this area, at higher densities, were actually modifying the environment to increase the resources that were available to them," Codding said.

Cultural burning for Pando

In Utah, many forests could benefit from frequent, smaller fires to mitigate wildfire risk. Perhaps one of the most urgent is in the Fish Lake National Forest that guards Pando, a stand of 47,000 aspen tree clones and the most massive organism on Earth. Pando has sat at the south end of Fish Lake for thousands of years, at least--some say the organism is a million years old. In recent years, the beloved grove has been shrinking. Low severity fires may help Pando, and other Utah forests, stay healthy.

"Fuels on the Fish Lake landscape are at the highest that they've been in the last 1,200 years. The climate is much warmer than it was in the past. Our droughts have not been as intense as we've seen in the past, but they're on their way," Carter said. "The Fremont likely created long-lasting legacies on the Fish Lake Plateau through their cultural burning. Moving forward, 'good fire,' like prescribed fire, will be needed to mitigate against wildfire risk."

Compared to newborns conceived traditionally, newborns conceived through in vitro fertilization (IVF) are more likely to have certain chemical modifications to their DNA, according to a study by researchers at the National Institutes of Health. The changes involve DNA methylation--the binding of compounds known as methyl groups to DNA--which can alter gene activity. Only one of the modifications was seen by the time the children were 9 years old.

The study was conducted by Edwina Yeung, Ph.D., and colleagues in NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Previous studies by the research team found no differences in growth and development for this group.

"Our study found only small differences in DNA methylation at birth and these were not seen in early childhood," Dr. Yeung said. "When considered along with our previous studies finding no differences in children's growth and development, our current study should be reassuring to couples who have conceived with fertility treatments and to those considering these methods."

IVF consists of collecting eggs and sperm, fertilizing the eggs in a lab, and then transferring the resulting embryo or embryos into the uterus. Another technique, intracytoplasmic sperm injection (ICSI), consists of injecting a sperm cell directly into the egg before placing the resulting embryo into the uterus.

Methylation changes were not associated with two other fertility treatments, ovulation induction (drug treatment to release the egg from the ovary) and intrauterine insemination (insertion of semen directly into the uterus).

According to a national report in 2018, almost 75,000 IVF-conceived infants (2.0% of all infants) were born in the United States. Of these, approximately 76% were conceived with ICSI. Another study found that 3 to 7% of births resulted from ovulation induction and intrauterine insemination.

When methyl groups are added to a gene, the gene is switched off and does not produce a protein. Methyl groups are added and removed from DNA throughout life, as genes are alternately switched on and off. Changes in methylation may occur in any step of IVF. These include exposure to hormones needed to bring the eggs to maturity so they can be collected or exposure to the culture medium in which the eggs are fertilized and embryos develop.

Previous studies have found associations between IVF and certain rare disorders. However, many of these studies were small and their results inconsistent. Also, many of the studies were conducted before ICSI was in widespread use.

For the current study, researchers evaluated data on DNA methylation differences in children beginning at birth and when they were 8 to 10 years old. The children were born in New York State from 2008 to 2010 and more than 70% of IVF birth were with ICSI.

Of the newborns, 157 were conceived with fertility treatments and 520 were conceived without treatments. Newborns conceived with IVF were more likely to have lower methylation levels in some parts of their DNA. The researchers did not find any methylation changes for newborns conceived by ovulation induction or intrauterine insemination.

Among the 152 children who provided DNA samples at 8 to 10 years old, 23 were conceived with IVF and 34 with ovulation induction or intrauterine insemination. For children conceived with IVF, lower methylation levels were seen for only one region, in the GNAS gene, which has been found in some previous studies but not others.

The study authors called for more research on how variations in fertility treatments could contribute to methylation differences in children, such as variations in the medium used to culture embryos.

HANOVER, N.H. - April 14, 2021 - Scientists have searched for years to understand how cells measure their size. Cell size is critical. It's what regulates cell division in a growing organism. When the microscopic structures double in size, they divide. One cell turns into two. Two cells turn into four. The process repeats until an organism has enough cells. And then it stops. Or at least it is supposed to.

The complete chain of events that causes cell division to stop at the right time is what has confounded scientists. Beyond being a textbook problem, the question relates to serious medical challenges: Cells that stop dividing too soon can cause defects in growing organisms. Uncontrolled cell growth can lead to cancers or other disorders.

A study from Dartmouth, published in Current Biology, provides a new answer to the question by tackling the problem in reverse: The research focused on large cells that reduce their size through division until enough cells are formed to move to other stages of development.

"The early embryo is an ideal place to study cell size control," said Amanda Amodeo, an assistant professor of biology at Dartmouth and the lead researcher. "The cells we work with are eggs that are visible to the eye. They don't need to grow before dividing, so it allows us to look at connections that are obscured in adult cells."

According to the study, a set amount of the protein histone H3 is loaded into an embryo before fertilization and is used up as the embryo divides into more cells. As histones are consumed to accommodate the growing number of nuclei, they release the enzyme Chk1 to bind with another protein, CDC25, to stop the multiplication of cells.

The research is technical, but the mechanism is relatively straightforward: With histone H3 out of the way in a growing cell, the stop enzyme Chk1 finds and disables the protein that triggers cell cycle progression, CDC25.

"The key to our research result was coming up with the possibility that unusually large amounts of histone H3 may feed into the stop enzyme," said Yuki Shindo a postdoctoral research fellow at Dartmouth and first author of the paper. "Once we noticed that, we were able to test this idea in our living test tube, fruit fly eggs."

The new research builds on earlier studies which found that a biological constant exists between the size of a genome and the size of a cell. Researchers knew that once a balance point was achieved, cells would stop duplicating, but didn't understand how cells could determine the ratio.

To find the answer to the long-running question, the research team studied fruit fly eggs. Because of their large size compared to other cells, the team was able to get a different perspective on the cell cycle.

"We've had all of the pieces for years but couldn't quite get them to fit together," said Amodeo. "Once we recognized that H3 interacts directly with both DNA and Chk1, the work went very fast. Everything worked the first time, which is a good sign that the hypothesis is right."

Since the same molecules that control cell division--histone H3, CDC25 and Chk1--are all identified in cancer and other ailments, the finding can help researchers that are seeking answers to questions related to development and disease.

"We were originally curious about a basic biological question on how cells in a growing egg make a decision to stop at the correct timing," said Shindo. "We are now excited that our findings may also have an important implication for a broader context such as disease."

A new study based on daily COVID-19 data from Brazil details the fast spread of both cases and deaths in the country, with distinct patterns by state, and where inequities regarding the implementation of policies and resources exacerbated the spread in lower-income regions. Despite an extensive network of primary care availability, Brazil - which did not pursue a coordinated national pandemic response strategy - has suffered greatly during the COVID-19 pandemic. "[T]he federal response has been a dangerous combination of inaction and wrongdoing," write Marcia Castro and colleagues. Using daily data from State Health Offices, Castro et al. comprehensively analyzed the spatial and temporal patterns of COVID-19 cases and deaths in Brazil from February to October 2020. Reflecting problems in surveillance, data reporting, and low testing capacity, deaths clustered about a month before cases were reported, the data show. Patterns suggest undetected (and thus unmitigated) introduction and propagation of the virus for some time. After the virus's introduction in São Paulo, both cases and deaths progressively moved north until week 20 (starting May 10), when the epidemic started to recede in Amazonas and Ceará but gained force in Rio de Janeiro and São Paulo. In Rio de Janeiro, political chaos, among other factors, compromised a prompt and effective response, and cases and deaths were high. Overall, a higher percentage of COVID-19 cases and deaths were observed outside capital cities. Further analyses by Castro and colleagues revealed how policies adopted at the national and local levels impacted movement of COVID-19 toward the interior states. The authors highlight several complex issues unique to Brazil that drove the virus's fast spread but also show that some states, such as Ceará, were resilient; others such as Rio de Janeiro that comparatively had more resources failed to contain the propagation of COVID-19. They conclude by noting Brazil's current perilous state, as a new virus variant of concern (P.1) is circulating. "Without immediate containment, coordinated epidemiological and genomic surveillance measures, and an effort to vaccinate the largest number of people in the shortest possible time, the propagation of [the new variant]" will likely resemble the patterns here demonstrated, leading to unimaginable loss of lives," they say.

A new report tracks the evolution of a variant lineage of SARS-CoV-2 associated with rapid transmission in Manaus, Brazil, that evolved in November 2020. The study's authors suggest this variant, "P.1," may be more transmissible and more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Manaus, Brazil, reached unprecedented levels of SARS-CoV-2 transmission in mid-2020. And after a momentary respite, cases surged with fatal consequences. Using molecular clock analysis, Nuno Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which possesses 17 mutations, including three (K417T, E484K and N501Y) in the spike protein. Following a period of accelerated evolution, this variant emerged in November 2020. It is more transmissible and more lethal than its predecessor and more likely to evade immunity, the authors say. Enhanced global genomic surveillance of such variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness, the authors say.

We refer to the microbiome as the community of microorganisms that exist in or on all organisms, including bacteria and fungi. A team from the Institute of Environmental Biotechnology at Graz University of Technology (TU Graz) led by Institute head Gabriele Berg has now investigated the microbiomes of apples and oil pumpkins in two independent studies. The researchers have found that bacteria useful to plants are largely "inherited," i.e., passed on to the next generation, while the community of fungi in the microbiome is highly dependent on the particular soil microbiome and thus on the locality.

Microbiome-guided breeding of oil pumpkins

The breeding of the Styrian oil pumpkin is relatively recent - it started about 150 years ago and is well documented. Through selective breeding of resistant, increasingly tasty and high-yielding pumpkins, the seed microbiome of the oil pumpkin has changed over the generations. Using a well-documented breeding line, the environmental biotechnologists at TU Graz were able to demonstrate for the first time that the microorganisms on the seeds of the pumpkin are inherited and probably crucial for certain plant traits. Peter Kusstatscher, one of the study authors, explains: "We studied bacteria and fungi on oil pumpkin seeds and found that the plant passes on much of its bacteria on the seed - up to 60 percent, in fact - to the next generation, while fungal diversity on the seed depends largely on the local soil microbiome." Kusstatscher continues, "It's mainly microorganisms that are useful for the plants that are inherited. In this respect, the plant behaves in a similar way to humans: babies also get their microbiome from their mothers."

The results published in Frontiers in Plant Science pave the way towards a microbiome-controlled breeding of oil pumpkins. Selective breeding of a beneficial seed microbiome results in plant traits that have a positive impact on yield, health and storability of oil pumpkins.

On the tracks of the universal apple microbiome

Apples are among the most popular and widely consumed fruits in the world. Fruit quality, yield, and storability are important factors for fruit growers, fruit trade, and consumers. In a worldwide study, the apple of the variety "Royal Gala" was examined for the first time with regard to the composition and possible local differences of its microbiome. An international team was able to show that the nature and structure of the fungal and bacterial communities of the apple at the time of harvest vary from region to region, i.e. they are strongly dependent on the geographical location and thus on the prevailing climatic conditions and management practices. In particular, the fungal diversity of the fruit is significantly dependent on the locality and suggests a relationship to the type and frequency of post-harvest diseases. On the other hand, a continental pattern can be drawn especially for the bacterial community which indicates adaptation of the apple microbiome to local environments.

Ahmed Abdelfattah, Marie Curie post-doctoral fellow at the Institute of Environmental Biotechnology at TU Graz and lead author of the study explains: "Despite the variations we observed in the apple microbiome, we were still able to identify a so-called 'core' microbiome i.e. members of the microbiome that are shared globally among the apples. This global 'core' microbiome is represented by several beneficial microbial indicators and makes up a large portion of the fruit's microbial community."

Similar to the study results on oil pumpkin, this study lays another foundation for new approaches to improving fruit quality and health, in this case of apples. Furthermore, the results form the basis for investigations of complex microbial interactions on the surface of apple fruits. The study results were published in Environmental Microbiology.

Both studies highlight the importance of the microbiome for health issues from the crop in the agro-ecosystem to humans who consume the food. At the same time, new avenues for microbiome management are opening up for environmentally friendly pest control.

A recent study has unveiled the reason behind the exceptional catalytic performance of non-noble metal-base mixed catalysts. This is thanks to a new synthetic strategy for the production of cube-shaped catalysts that could further simplify the structure of complex catalysts.

This breakthrough has been led by Professor Kwangjin An and his research team in the School of Energy and Chemical Engineering at UNIST, in collaboration with Professor Taeghwan Hyeon and his research team from Seoul National University. In their study, the researchers found a new principle that active charge transfer, which appears at the interface created between the two types of non-noble metals, could enhance the catalytic performance of complex oxide catalysts. The research team expects that their findings could contribute to the development of catalysts that could convert methane efficiently to fuels and high value-added chemicals.

The interface created between an active metal and oxide support has been known to affect the catalytic performance due to the charge transfer process. However, owing to their complex interface structures and synthetic challenges, oxide-oxide interfaces produced by supported spinel oxide catalysts have been less studied.

In this work, the research team proposed a synthetic strategy for heterostructured spinel oxide (Co3O4, Mn3O4, and Fe3O4) nanocubes (NCs) with a controlled CeO2 layer that enabled investigation of the role of the interface in catalytic oxidation of CO and H2. They developed a selective deposition process to produce CeO2-deposited spinel NCs with 1, 3, and 6 facets of CeO2 (MCe-1F, MCe-3F, and MCe-6F NCs for spinel oxide).

According to the research team, CeO2-deposited Co3O4 NCs exhibited a 12-times higher CO oxidation rate than the pristine Co3O4 NCs. Furthermore, various in situ characterization techniques, revealed that the deposited CeO2 prevents the reduction of Co3O4 by supplying oxygen. They also found that the maximized interface resulting from Co3O4 NCs with three facets covered by CeO2 layers exhibit the highest CO oxidation rate even under O2-deficient conditions, which resulted from the versatile variation in the oxidation state.

"This study provides a comprehensive understanding of the Mars-van Krevelen (MvK) mechanism, occurring on the nanoscale at the Co3O4-CeO2 interfaces," noted the research team. "The same activity trend and hot electron flow are observed for H2 oxidation reactions using catalytic nanodiodes, thereby demonstrating that the origin of the activity enhancement is charge transfer at the interface."

Intestinal worm infections can leave women in sub-Saharan Africa more vulnerable to sexually-transmitted viral infections, a new study reveals.

The rate and severity of sexually-transmitted viral infections (STI) in the region are very high, as are those of worm infections, which when caught in the intestine can change immunity in other parts of the body.

Researchers at the Universities of Birmingham and Cape Town led an international team which discovered that intestinal worm infection can change vaginal immunity and increase the likelihood of Herpes simplex virus type 2 (HSV-2) infection - the main cause of genital herpes.

Publishing their findings today in Cell Host and Microbe, the research team also notes that worm infections significantly increase the death of tissue in the vagina (necrosis), which can result in gangrene.

However, the researchers found that they could prevent this worm-induced changes in HSV2 pathology by targeting a particular type of immune cell called eosinophils - suggesting that this pathology could be prevented or reduced by using existing drugs.

Co-author Dr. William Horsnell, from the Institute of Microbiology & Infection at the University of Birmingham and Institute of Infectious Disease and Molecular Medicine, University of Cape town commented: "Our work identifies for the first time how a worm infection can influence a very important viral STI. This is important for health workers and may help them to explain why STIs are more virulent in areas where worm infections are common.

"We show that worm infections that never colonise the vagina cause a strong change in vaginal immunity. Following a viral vaginal sexually transmitted infection the pathology caused by the virus is hugely increased. Research into STIs has, until now, largely neglected the role of worm infections in influencing the severity of these important diseases."

Rates and severity of sexually transmitted viral infections in sub-Saharan Africa are very high and are one of the world's leading causes of pathological disease. Worm infection rates are also very high in this region, but do not colonise the female reproductive tract.

"Our research shows that eosinophils can have a very important role to play in vaginal immunity - we hope that this discovery will boost efforts to understand how parasitic worm infection indirectly influence control of sexually transmitted infections," added Dr Horsnell.

The research was funded by DFG, Poliomyelitis Research Foundation, Marie Curie and National Research Foundation (South Africa). The research team is currently studying in West Africa (Togo) and South Africa how existing and past worm infections associate with risk of women having an STI.

Non-alcoholic fatty liver, NAFLD, is associated with several health risks. According to a new registry study led by researchers at Karolinska Institutet in Sweden, NAFLD is linked to a 17-fold increased risk of liver cancer. The findings, published in Hepatology, underscore the need for improved follow-up of NAFLD patients with the goal of reducing the risk of cancer.

"In this study with detailed liver histology data, we were able to quantify the increased risk of cancer associated with NAFLD, particularly hepatocellular carcinoma," says first author, Tracey G. Simon, researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and hepatologist at Massachusetts General Hospital and Harvard Medical School. "We also found that all stages of NAFLD were associated with excess cancer risk, even early stages of the disease."

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Europe and the United States, affecting more than 100 million adults. A large proportion of patients progress to nonalcoholic steatohepatitis (NASH) with fibrosis, which in turn can lead to cirrhosis.

There is relatively little research on cancer development with NAFLD, and prior research has some limitations that make it difficult to draw far-reaching conclusions. Hence, there is a need for more information on links between cancer risk and NAFLD, and for improved monitoring strategies for high-risk patients with NAFLD.

In this study, researchers at Karolinska Institutet, in collaboration with researchers at Harvard University and Columbia University, examined the risk of cancer in people with NAFLD. The registry study included 8,892 Swedish patients with biopsy-confirmed NAFLD and 39,907 healthy controls.

Data on cancer were retrieved through the nationwide Swedish Cancer Register. Patients with NAFLD were identified through the ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden) cohort.

Individuals with NAFLD were at a 27 percent increased risk of any cancer. This risk was to a large extent driven by the 17-fold increased risk of hepatocellular carcinoma (HCC). Furthermore, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma, but no other cancers.

"These findings should be used to develop more targeted interventions designed to reduce cancer risk in patients with NAFLD," says corresponding author Jonas F. Ludvigsson, pediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. "They also highlight the need for more personalized strategies to screen for HCC in certain high-risk patients, such as those with NAFLD fibrosis and type 2 diabetes."