Culture

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Lithium-ion batteries have made possible the lightweight electronic devices whose portability we now take for granted, as well as the rapid expansion of electric vehicle production. But researchers around the world are continuing to push limits to achieve ever-greater energy densities -- the amount of energy that can be stored in a given mass of material -- in order to improve the performance of existing devices and potentially enable new applications such as long-range drones and robots.

One promising approach is the use of metal electrodes in place of the conventional graphite, with a higher charging voltage in the cathode. Those efforts have been hampered, however, by a variety of unwanted chemical reactions that take place with the electrolyte that separates the electrodes. Now, a team of researchers at MIT and elsewhere has found a novel electrolyte that overcomes these problems and could enable a significant leap in the power-per-weight of next-generation batteries, without sacrificing the cycle life.

The research is reported in the journal Nature Energy in a paper by MIT professors Ju Li, Yang Shao-Horn, and Jeremiah Johnson, postdoc Weijiang Xue, and 19 others at MIT, two national laboratories, and elsewhere. The researchers say the finding could make it possible for lithium-ion batteries, which now typically can store about 260 watt-hours per kilogram, to store about 420 watt-hours per kilogram. That would translate into longer ranges for electric cars and longer-lasting changes on portable devices.

The basic raw materials for this electrolyte are inexpensive (though one of the intermediate compounds is still costly because it's in limited use), and the process to make it is simple. So, this advance could be implemented relatively quickly, the researchers say.

The electrolyte itself is not new, explains Johnson, a professor of chemistry. It was developed a few years ago by some members of this research team, but for a different application. It was part of an effort to develop lithium-air batteries, which are seen as the ultimate long-term solution for maximizing battery energy density. But there are many obstacles still facing the development of such batteries, and that technology may still be years away. In the meantime, applying that electrolyte to lithium-ion batteries with metal electrodes turns out to be something that can be achieved much more quickly.

The new application of this electrode material was found "somewhat serendipitously," after it had initially been developed a few years ago by Shao-Horn, Johnson, and others, in a collaborative venture aimed at lithium-air battery development.

"There's still really nothing that allows a good rechargeable lithium-air battery," Johnson says. However, "we designed these organic molecules that we hoped might confer stability, compared to the existing liquid electrolytes that are used." They developed three different sulfonamide-based formulations, which they found were quite resistant to oxidation and other degradation effects. Then, working with Li's group, postdoc Xue decided to try this material with more standard cathodes instead.

The type of battery electrode they have now used with this electrolyte, a nickel oxide containing some cobalt and manganese, "is the workhorse of today's electric vehicle industry," says Li, who is a professor of nuclear science and engineering and materials science and engineering.

Because the electrode material expands and contracts anisotropically as it gets charged and discharged, this can lead to cracking and a breakdown in performance when used with conventional electrolytes. But in experiments in collaboration with Brookhaven National Laboratory, the researchers found that using the new electrolyte drastically reduced these stress-corrosion cracking degradations.

The problem was that the metal atoms in the alloy tended to dissolve into the liquid electrolyte, losing mass and leading to cracking of the metal. By contrast, the new electrolyte is extremely resistant to such dissolution. Looking at the data from the Brookhaven tests, Li says, it was "sort of shocking to see that, if you just change the electrolyte, then all these cracks are gone." They found that the morphology of the electrolyte material is much more robust, and the transition metals "just don't have as much solubility" in these new electrolytes.

That was a surprising combination, he says, because the material still readily allows lithium ions to pass through -- the essential mechanism by which batteries get charged and discharged -- while blocking the other cations, known as transition metals, from entering. The accumulation of unwanted compounds on the electrode surface after many charging-discharging cycles was reduced more than tenfold compared to the standard electrolyte.

"The electrolyte is chemically resistant against oxidation of high-energy nickel-rich materials, preventing particle fracture and stabilizing the positive electrode during cycling," says Shao-Horn, a professor of mechanical engineering and materials science and engineering. "The electrolyte also enables stable and reversible stripping and plating of lithium metal, an important step toward enabling rechargeable lithium-metal batteries with energy two times that of the state-the-art lithium-ion batteries. This finding will catalyze further electrolyte search and designs of liquid electrolytes for lithium-metal batteries rivaling those with solid state electrolytes."

The next step is to scale the production to make it affordable. "We make it in one very easy reaction from readily available commercial starting materials," Johnson says. Right now, the precursor compound used to synthesize the electrolyte is expensive, but he says, "I think if we can show the world that this is a great electrolyte for consumer electronics, the motivation to further scale up will help to drive the price down."

Because this is essentially a "drop in" replacement for an existing electrolyte and doesn't require redesign of the entire battery system, Li says, it could be implemented quickly and could be commercialized within a couple of years. "There's no expensive elements, it's just carbon and fluorine. So it's not limited by resources, it's just the process," he says.

Researchers from Queen Mary University of London have developed a machine learning algorithm that ranks drugs based on their efficacy in reducing cancer cell growth. The approach may have the potential to advance personalised therapies in the future by allowing oncologists to select the best drugs to treat individual cancer patients.

The method, named Drug Ranking Using Machine Learning (DRUML), was published today in Nature Communications and is based on machine learning analysis of data derived from the study of proteins expressed in cancer cells. Having been trained on the responses of these cells to over 400 drugs, DRUML predicts the best drug to treat a given cancer model.

Speaking of the new method, Professor Pedro Cutillas from Queen Mary University of London, who led the study, said: "DRUML predicted drug efficacy in several cancer models and from data obtained from different laboratories and in a clinical dataset. These are exciting results because previous machine learning methods have failed to accurately predict drug responses in verification datasets, and they demonstrate the robustness and wide applicability of our method."

The research was funded by The Alan Turing Institute, Medical Research Council, Barts Charity and Cancer Research UK.

How does DRUML work?

The team used datasets derived from proteomics (the study of proteins within cells) and phosphoproteomics (the study of how these proteins are modified) analyses of 48 leukaemia, oesophagus and liver cancer cell lines as the input for DRUML to build models that may be applied to leukaemia and solid tumours.

By training the models using the responses of these cells to 412 cancer drugs listed in drug response repositories, DRUML was able to produce ordered lists based on the effectiveness of the drugs to reduce cancer cell growth. The team then verified the predictive accuracy of the models using data obtained from 12 other laboratories and a clinical dataset of 36 primary acute myeloid leukaemia samples.

Importantly, as new drugs are developed moving forwards, DRUML could be retrained to capture all clinically relevant cancer drugs.

Machine learning and personalised medicine

Cancers of the same type exhibit great variation in their genetic makeup and characteristics from patient to patient. In the clinic, this variation translates to patients having different responses to therapy. To address this issue, the field of personalised medicine aims to combine genetic insights with other clinical and diagnostic information to identify patterns that can allow clinicians to predict patient responses to therapies and select the most effective interventions.

The application of artificial intelligence and machine learning to biomedicine promises to aid personalised medicine and transform how cancers are diagnosed and treated in the future. This study represents a significant advancement in artificial intelligence in biomedical research, and demonstrates that machine learning using proteomics and phosphoproteomics data may be an effective way of selecting the best drug to treat different cancer models.

Many psychiatric disorders have genetic causes, but the exact mechanism of how genes influence higher brain function remains a mystery. A new study provides a map linking the genetic signature of functions across the human brain, a tool that may provide new targets for future treatments.

Led by Bratislav Misic, a researcher at The Neuro (Montreal Neurological Institute-Hospital) of McGill University, a group of scientists performed machine learning analysis of two Open Science datasets: the gene expression atlas from the Allen Human Brain Atlas and the functional association map from Neurosynth. This allowed them to find associations between gene expression patterns and functional brain tasks such as memory, attention, and mood.

Interestingly, the team found a clear genetic signal that separated cognitive processes, like attention, from more affective processes, like fear. This separation can be traced to gene expression in specific cell types and molecular pathways, offering key insights for future research into psychiatric disorders. Cognition, for example, was linked more to the gene signatures of inhibitory or excitatory neurons. Affective processes, however, were linked to support cells such as microglia and astrocytes, supporting a theory that inflammation of these cells is a risk factor in mental illness. The genetic signature related to affect was centred on a brain region called the anterior cingulate cortex, which has been shown to be vulnerable in mental illness.

Published in the journal Nature Human Behaviour on March 25, 2021, this study draws a direct link between gene expression and higher brain function, by mapping gene signatures to functional processes across the human brain.

"In this work we found molecular signatures of different psychological processes," says Misic. "This is exciting because it provides a first step to understand how human thoughts and emotions arise from specific genes, biological pathways and cell types."

Pregnant women who consumed the caffeine equivalent of as little as half a cup of coffee a day on average had slightly smaller babies than pregnant women who did not consume caffeinated beverages, according to a study by researchers at the National Institutes of Health. The researchers found corresponding reductions in size and lean body mass for infants whose mothers consumed below the 200 milligrams of caffeine per day--about two cups of coffee--believed to increase risks to the fetus. Smaller birth size can place infants at higher risk of obesity, heart disease and diabetes later in life.

The researchers were led by Katherine L. Grantz, M.D., M.S., of the Division of Intramural Population Health Research at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development. The study appears in JAMA Network Open.

"Until we learn more, our results suggest it might be prudent to limit or forego caffeine-containing beverages during pregnancy," Dr. Grantz said. "It's also a good idea for women to consult their physicians about caffeine consumption during pregnancy."

Previous studies have linked high caffeine consumption (more than 200 milligrams of caffeine per day) during pregnancy to infants being small for their gestational age (stage of pregnancy) or at risk for intrauterine growth restriction--being in the lowest 10th percentile for infants of the same gestational age. However, studies on moderate daily caffeine consumption (200 milligrams or less) during pregnancy have produced mixed results. Some have found similar elevated risks for low birth weight and other poor birth outcomes, while others have found no such links. The current study authors noted that many of the earlier studies did not account for other factors that could influence infant birth size, such as variation in caffeine content of different beverages and maternal smoking during pregnancy.

For their study, the authors analyzed data on more than 2,000 racially and ethnically diverse women at 12 clinical sites who were enrolled from 8 to 13 weeks of pregnancy. The women were non-smokers and did not have any health problems before pregnancy. From weeks 10 to 13 of pregnancy, the women provided a blood sample that was later analyzed for caffeine and paraxanthine, a compound produced when caffeine is broken down in the body. The women also reported their daily consumption of caffeinated beverages (coffee, tea, soda and energy drinks) for the past week--once when they enrolled and periodically throughout their pregnancies.

Compared to infants born to women with no or minimal blood levels of caffeine, infants born to women who had the highest blood levels of caffeine at enrollment were an average of 84 grams lighter at birth (about 3 ounces), were .44 centimeters shorter (about .17 inches), and had head circumferences .28 centimeters smaller (about .11 inches).

Based on the women's own estimates of the beverages they drank, women who consumed about 50 milligrams of caffeine a day (equivalent to a half cup of coffee) had infants 66 grams (about 2.3 ounces) lighter than infants born to non-caffeine consumers. Similarly, infants born to the caffeine consumers also had thigh circumferences .32 centimeters smaller (about .13 inches).

The researchers noted that caffeine is believed to cause blood vessels in the uterus and placenta to constrict, which could reduce the blood supply to the fetus and inhibit growth. Similarly, researchers believe caffeine could potentially disrupt fetal stress hormones, putting infants at risk for rapid weight gain after birth and for later life obesity, heart disease and diabetes.

The authors concluded that their findings suggest that even moderate caffeine consumption may be associated with decreased growth of the fetus.

An international team of scientists has found evidence that SARS-CoV-2, the virus that causes COVID-19, infects cells in the mouth. While it's well known that the upper airways and lungs are primary sites of SARS-CoV-2 infection, there are clues the virus can infect cells in other parts of the body, such as the digestive system, blood vessels, kidneys and, as this new study shows, the mouth. The potential of the virus to infect multiple areas of the body might help explain the wide-ranging symptoms experienced by COVID-19 patients, including oral symptoms such as taste loss, dry mouth and blistering. Moreover, the findings point to the possibility that the mouth plays a role in transmitting SARS-CoV-2 to the lungs or digestive system via saliva laden with virus from infected oral cells. A better understanding of the mouth's involvement could inform strategies to reduce viral transmission within and outside the body. The team was led by researchers at the National Institutes of Health and the University of North Carolina at Chapel Hill.

"Due to NIH's all-hands-on-deck response to the pandemic, researchers at the National Institute of Dental and Craniofacial Research were able to quickly pivot and apply their expertise in oral biology and medicine to answering key questions about COVID-19," said NIDCR Director Rena D'Souza, D.D.S., M.S., Ph.D. "The power of this approach is exemplified by the efforts of this scientific team, who identified a likely role for the mouth in SARS-CoV-2 infection and transmission, a finding that adds to knowledge critical for combatting this disease."

The study, published online March, 25, 2021 in Nature Medicine, was led by Blake M. Warner, D.D.S., Ph.D., M.P.H., assistant clinical investigator and chief of NIDCR's Salivary Disorders Unit, and Kevin M. Byrd, D.D.S., Ph.D., at the time an assistant professor in the Adams School of Dentistry at the University of North Carolina at Chapel Hill. Byrd is now an Anthony R. Volpe Research Scholar at the American Dental Association Science and Research Institute. Ni Huang, Ph.D., of the Wellcome Sanger Institute in Cambridge, U.K., and Paola Perez, Ph.D., of NIDCR, were co-first authors.

Researchers already know that the saliva of people with COVID-19 can contain high levels of SARS-CoV-2, and studies suggest that saliva testing is nearly as reliable as deep nasal swabbing for diagnosing COVID-19. What scientists don't entirely know, however, is where SARS-CoV-2 in the saliva comes from. In people with COVID-19 who have respiratory symptoms, virus in saliva possibly comes in part from nasal drainage or sputum coughed up from the lungs. But according to Warner, that may not explain how the virus gets into the saliva of people who lack those respiratory symptoms.

"Based on data from our laboratories, we suspected at least some of the virus in saliva could be coming from infected tissues in the mouth itself," Warner said.

To explore this possibility, the researchers surveyed oral tissues from healthy people to identify mouth regions susceptible to SARS-CoV-2 infection. Vulnerable cells contain RNA instructions for making "entry proteins" that the virus needs to get into cells. RNA for two key entry proteins--known as the ACE2 receptor and the TMPRSS2 enzyme--was found in certain cells of the salivary glands and tissues lining the oral cavity. In a small portion of salivary gland and gingival (gum) cells, RNA for both ACE2 and TMPRSS2 was expressed in the same cells. This indicated increased vulnerability because the virus is thought to need both entry proteins to gain access to cells.

"The expression levels of the entry factors are similar to those in regions known to be susceptible to SARS-CoV-2 infection, such as the tissue lining the nasal passages of the upper airway," Warner said.

Once the researchers had confirmed that parts of the mouth are susceptible to SARS-CoV-2, they looked for evidence of infection in oral tissue samples from people with COVID-19. In samples collected at NIH from COVID-19 patients who had died, SARS-CoV-2 RNA was present in just over half of the salivary glands examined. In salivary gland tissue from one of the people who had died, as well as from a living person with acute COVID-19, the scientists detected specific sequences of viral RNA that indicated cells were actively making new copies of the virus--further bolstering the evidence for infection.

Once the team had found evidence of oral tissue infection, they wondered whether those tissues could be a source of the virus in saliva. This appeared to be the case. In people with mild or asymptomatic COVID-19, cells shed from the mouth into saliva were found to contain SARS-CoV-2 RNA, as well as RNA for the entry proteins.

To determine if virus in saliva is infectious, the researchers exposed saliva from eight people with asymptomatic COVID-19 to healthy cells grown in a dish. Saliva from two of the volunteers led to infection of the healthy cells, raising the possibility that even people without symptoms might transmit infectious SARS-CoV-2 to others through saliva.

Finally, to explore the relationship between oral symptoms and virus in saliva, the team collected saliva from a separate group of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 people who experienced symptoms, those with virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might underlie oral symptoms of COVID-19.

Taken together, the researchers said, the study's findings suggest that the mouth, via infected oral cells, plays a bigger role in SARS-CoV-2 infection than previously thought.

"When infected saliva is swallowed or tiny particles of it are inhaled, we think it can potentially transmit SARS-CoV-2 further into our throats, our lungs, or even our guts," said Byrd.

More research will be needed to confirm the findings in a larger group of people and to determine the exact nature of the mouth's involvement in SARS-CoV-2 infection and transmission within and outside the body.

"By revealing a potentially underappreciated role for the oral cavity in SARS-CoV-2 infection, our study could open up new investigative avenues leading to a better understanding of the course of infection and disease. Such information could also inform interventions to combat the virus and alleviate oral symptoms of COVID-19," Warner said.

Smoking cigarettes causes 480,000 premature deaths each year in the United States, due mainly to a two-fold risk of cardiovascular disease and a 20-fold risk of lung cancer. Although smoking rates have declined dramatically, there are currently 35 million smokers in the U.S.

In a commentary published in the Ochsner Medical Journal, Charles H. Hennekens, M.D., Dr.PH, senior author, the First Sir Richard Doll Professor, and senior academic advisor in the Schmidt College of Medicine at Florida Atlantic University, and colleagues, highlight how failure to institute smoking cessation in hospitalized patients is a missed opportunity to avoid many premature deaths.

Each year in the U.S., approximately 30 million hospitalizations occur in individuals 18 and older. Of these, more than 7 million are current cigarette smokers whose average hospital stay is several days. The authors comment that starting smoking cessation therapy during hospitalization and maintaining high adherence post-discharge can markedly improve permanent quit rates in these patients with minimal to no side effects. Smoking cessation therapy also should include long-term counseling and at least 90 days of a prescription drug, in particular, varenicline, which works by blocking the pleasurable sensations of nicotine on the brain.

"Providing multifactorial intensive counseling interventions during and after hospitalization and initiating and maintaining adherence to drug therapy are all independent predictors of permanent smoking cessation rates," said Hennekens. "All of these efforts have the potential to reduce many premature deaths from cigarette smoking, which remain alarmingly and unnecessarily high in the U.S. and has already become so worldwide."

Quitting smoking reduces the risk of dying from cardiovascular disease beginning with a matter of months reaching that of lifelong non-smokers within a few years, even among older adults. In contrast, reductions in mortality risk from lung cancer only begin to appear several years after quitting, and even by 10 years, the risk is reduced to only approximately midway between continuing smokers and lifelong smokers. This is because the risks of cardiovascular disease relate to the numbers of cigarettes currently smoked and the risks of cancer to the duration of the habit.

The authors dedicated this manuscript to the memory of the late Edward D. Frohlich, M.D., Ph.D., who was the Alton Ochsner Distinguished Scientist at the Ochsner Clinic Foundation and a staff member of the Ochsner Clinic. The authors refer to Frohlich as a "great man and a good man" who was a valued mentor, colleague and friend. As a member of the Ochsner family for more than 40 years, Frohlich's outstanding contributions helped to propel the Ochsner Clinic to a premier national and international research institution.

In recognition of his seminal discovery research on the hazards of cigarette smoking, Hennekens was the 29th recipient of the prestigious Alton Ochsner Award. Ochsner, a thoracic surgeon, and Michael DeBakey M.D., a future world-renowned cardiovascular surgeon, were early recipients of the award for their case series on smoking and lung cancer in the 1930s. Doll, a British physician, became the foremost epidemiologist of 20th century for pioneering epidemiologic studies, first with Sir Austin Bradford Hill and later with Sir Richard Peto - all who received the Alton Ochsner Award for their contributions to the enormous hazards of cigarette smoking.

From 1995 to 2005, Science Watch ranked Hennekens as the third most widely cited medical researcher in the world and five of the top 20 were his former trainees and/or fellows. In 2012, Science Heroes ranked Hennekens No. 81 in the history of the world for having saved more than 1.1 million lives. In 2016, he was ranked the No. 14 "Top Living Medical Scientist in the World."

Based in part on Hennekens' seminal work on the large clinical and public health hazards of smoking cigarettes, FAU President John Kelly adopted a university-wide tobacco free policy.

An international team led by scientists at the National Institutes of Health and the University of North Carolina at Chapel Hill, has found evidence that SARS-CoV-2, the virus that causes COVID-19, infects cells in the mouth.

While it's well known that the upper airways and lungs are primary sites of SARS-CoV-2 infection, there are clues the virus can infect cells in other parts of the body, such as the digestive system, blood vessels, kidneys and, as this new study shows, the mouth. The potential of the virus to infect multiple areas of the body might help explain the wide-ranging symptoms experienced by COVID-19 patients, including oral symptoms such as taste loss, dry mouth and blistering.

Moreover, the findings point to the possibility that the mouth plays a role in transmitting SARS-CoV-2 to the lungs or digestive system via saliva laden with virus from infected oral cells. A better understanding of the mouth's involvement could inform strategies to reduce viral transmission within and outside the body.

"Due to NIH's all-hands-on-deck response to the pandemic, researchers at the National Institute of Dental and Craniofacial Research were able to quickly pivot and apply their expertise in oral biology and medicine to answering key questions about COVID-19," said NIDCR Director Rena D'Souza, D.D.S., M.S., Ph.D. "The power of this approach is exemplified by the efforts of this scientific team, who identified a likely role for the mouth in SARS-CoV-2 infection and transmission, a finding that adds to knowledge critical for combatting this disease."

The study, published online March 25 in Nature Medicine, was led by Blake M. Warner, D.D.S., Ph.D., M.P.H., assistant clinical investigator and chief of NIDCR's Salivary Disorders Unit, and Kevin M. Byrd, D.D.S., Ph.D., at the time an assistant professor in the Adams School of Dentistry at the University of North Carolina at Chapel Hill. Byrd is now an Anthony R. Volpe Research Scholar at the American Dental Association Science and Research Institute. Ni Huang, Ph.D., of the Wellcome Sanger Institute in Cambridge, U.K., and Paola Perez, Ph.D., of NIDCR, were co-first authors.

Researchers already know that the saliva of people with COVID-19 can contain high levels of SARS-CoV-2, and studies suggest that saliva testing is nearly as reliable as deep nasal swabbing for diagnosing COVID-19. What scientists don't entirely know, however, is where SARS-CoV-2 in the saliva comes from. In people with COVID-19 who have respiratory symptoms, virus in saliva possibly comes in part from nasal drainage or sputum coughed up from the lungs. But according to Warner, that may not explain how the virus gets into the saliva of people who lack those respiratory symptoms. "Based on data from our laboratories, we suspected at least some of the virus in saliva could be coming from infected tissues in the mouth itself," he said.

To explore this possibility, the researchers surveyed oral tissues from healthy people to identify mouth regions susceptible to SARS-CoV-2 infection. Vulnerable cells contain RNA instructions for making "entry proteins" that the virus needs to get into cells. RNA for two key entry proteins--known as the ACE2 receptor and the TMPRSS2 enzyme--was found in certain cells of the salivary glands and tissues lining the oral cavity. In a small portion of salivary gland and gingival (gum) cells, RNA for both ACE2 and TMPRSS2 was expressed in the same cells. This indicated increased vulnerability because the virus is thought to need both entry proteins to gain access to cells.

"The expression levels of the entry factors in are similar to those in regions known to be susceptible to SARS-CoV-2 infection, such as the tissue lining the nasal passages of the upper airway," Warner said.

Once the researchers had confirmed that parts of the mouth are susceptible to SARS-CoV-2, they looked for evidence of infection in oral tissue samples from people with COVID-19. In samples collected at NIH from COVID-19 patients who had died, SARS-CoV-2 RNA was present in just over half of the salivary glands examined. In salivary gland tissue from one of the people who had died, as well as from a living person with acute COVID-19, the scientists detected specific sequences of viral RNA that indicated cells were actively making new copies of the virus--further bolstering the evidence for infection.

Once the team had found evidence of oral tissue infection, they wondered whether those tissues could be a source of the virus in saliva. This appeared to be the case. In people with mild or asymptomatic COVID-19, cells shed from the mouth into saliva were found to contain SARS-CoV-2 RNA, as well as RNA for the entry proteins.

To determine if virus in saliva is infectious, the researchers exposed saliva from eight people with asymptomatic COVID-19 to healthy cells grown in a dish. Saliva from two of the volunteers led to infection of the healthy cells, raising the possibility that even people without symptoms might transmit infectious SARS-CoV-2 to others through saliva.

Finally, to explore the relationship between oral symptoms and virus in saliva, the team collected saliva from a separate group of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 people who experienced symptoms, those with virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might underlie oral symptoms of COVID-19.

Taken together, the researchers said, the study's findings suggest that the mouth, via infected oral cells, plays a bigger role in SARS-CoV-2 infection than previously thought. "When infected saliva is swallowed or tiny particles of it are inhaled, we think it can potentially transmit SARS-CoV-2 further into our throats, our lungs, or even our guts," said Byrd.

More research will be needed to confirm the findings in a larger group of people and to determine the exact nature of the mouth's involvement in SARS-CoV-2 infection and transmission within and outside the body.

"By revealing a potentially underappreciated role for the oral cavity in SARS-CoV-2 infection, our study could open up new investigative avenues leading to a better understanding of the course of infection and disease. Such information could also inform interventions to combat the virus and alleviate oral symptoms of COVID-19," Warner said.

LA JOLLA--(March 25, 2021) The brush of an insect's wing is enough to trigger a Venus flytrap to snap shut, but the biology of how these plants sense and respond to touch is still poorly understood, especially at the molecular level. Now, a new study by Salk and Scripps Research scientists identifies what appears to be a key protein involved in touch sensitivity for flytraps and other carnivorous plants.

The findings, published March 16, 2021, in the journal eLife, help explain a critical process that has long puzzled botanists. This could help scientists better understand how plants of all kinds sense and respond to mechanical stimulation, and could also have a potential application in medical therapies that mechanically stimulate human cells such as neurons.

"We know that plants sense touch," says co-corresponding author Joanne Chory, director of Salk's Plant Molecular and Cellular Biology Laboratory and holder of the Howard H. and Maryam R. Newman Chair in Plant Biology. "The Venus flytrap, which has a very fast response to touch, provides an opportunity to study a sensory modality that historically has been poorly understood."

Scientists have long been fascinated by Venus flytraps and carnivorous plants; Charles Darwin devoted an entire book to them. But while previous studies have looked at the structural mechanism of their bizarre leaves, not much is known about how they work at the cellular level. That's partly because flytraps are challenging to study. They're extremely slow to grow, and the flytrap genome had not been sequenced until recently, opening the door for deeper genetic research.

"Because they're so unusual, people have been interested in these plants for hundreds of years, so there's quite a bit known about them at the gross, macroscopic level, but the molecular details have been hard to tease out," says Carl Procko, a staff scientist in Salk's Plant Molecular and Cellular Biology Laboratory.

In the new study, the authors grew cloned flytraps from cuttings to get plants that were genetically identical. Then they carefully cut thousands of microscopic, touch-sensitive trigger hairs from these plants and used sequencing technology to identify which proteins were most abundant in the hairs.

Based on previous research, they knew that the proteins involved in sensing touch were likely to have the capability of moving an electrical current across the cell. Sure enough, this type of protein was the second most common type found in the hairs. The scientists named the new protein FLYCATCHER1. To test the protein, colleagues at Scripps Research put it into mammalian cells. The cells responded by producing an electrical current when touched, proving that the protein is sensitive to mechanical stimuli.

The team found the same protein in the tentacles of the sundew, a carnivorous plant that's a close relative of the Venus flytrap. In the sundew, these sticky tentacles sense the movement of a struggling insect, stimulating the leaf to curl up and trap its prey.

"These findings are further evidence that the FLYCATCHER1 protein plays a critical role in the trigger hairs of the Venus flytrap and the mechanisms of the plant that sense and respond to touch," says Chory.

As a next step, the study authors want to do a "knockout" test and grow genetically modified flytraps with the protein missing. If these flytraps are unable to sense touch, it will prove conclusively that the FLYCATCHER1 protein is responsible.