Culture

WOODS HOLE, Mass. -- Octopuses have the most flexible appendages known in nature, according to a new study in Scientific Reports. In addition to being soft and strong, each of the animal's eight arms can bend, twist, elongate and shorten in many combinations to produce diverse movements. But to what extent can they do so, and is each arm equally capable? Researchers at the Marine Biological Laboratory (MBL) filmed 10 octopuses over many months while presenting them with a variety of challenges, and recorded 16,563 examples of these arm movements.

Amazingly, all eight arms could perform all four types of deformation (bend, twist, elongate, shorten) throughout their length. Moreover, each type of movement could be deployed in multiple orientations (e.g. left, right, up, down, 360º, etc.). Especially noteworthy was the clockwise and counterclockwise twisting that could occur throughout each arm during bending, shortening or elongating. This twisty strong arm is exceptionally flexible by any standard.

"Even our research team, which is very familiar with octopuses, was surprised by the extreme versatility of each of the eight arms as we analyzed the videos frame-by-frame," said co-author and MBL Senior Scientist Roger Hanlon. "These detailed analyses can help guide the next step of determining neural control and coordination of octopus arms, and may uncover design principles that can inspire the creation of next-generation soft robots."

Engineers have long wished to design "soft robotic arms" with greater agility, strength and sensing capability. Currently, most robotic arms require hard materials and joints of many configurations, all of which have limitations. The octopus presents a novel model for future robotic designs. Octopus arms are similar in function to the human tongue and the elephant trunk; they are muscular hydrostats that use incompressible muscle in different arrangements to produce movement. The current study provides a basis for investigating motor control of the entire octopus arm. Soft, ultra-flexible robotic arms could enable many new applications, e.g., inspecting unstructured and cluttered environments such as collapsed buildings, or gentler medical inspection of alimentary or respiratory pathways.

Early populations shifted from quasi-egalitarian hunter-gatherer societies to communities governed by a centralized authority in the middle to late Holocene, but how the transition occurred still puzzles anthropologists. A University of Maine-led group of researchers contend that population size and density served as crucial drivers.

Anthropology professor Paul "Jim" Roscoe led the development of Power Theory, a model emphasizing the role of demography in political centralization, and applied it to the shift in power dynamics in prehistoric northern coastal societies in Peru.

To test the theory, he, Daniel Sandweiss, professor of anthropology and Quaternary and climate studies, and Erick Robinson, a postdoctoral anthropology researcher at Utah State University, created a summed probability distribution (SPD) from 755 radiocarbon dates from 10,000-1,000 B.P., or before present.

The team found a correlation between the tenets of their Power Theory, or that population density and size influence political centralization, and the change in power dynamics in early Peruvian societies.

The team shared their findings in a report published in Philosophical Transactions of the Royal Society B.

"I've always been interested in how, in the space of just five to 10,000 years, humans went from biddy little hunter-gatherer groups in which nobody could really push anyone else around to vast industrial states governed by a few people with enormous power. From my fieldwork and other research in New Guinea, it became clear that leaders mainly emerged in large, high-density populations, and Power Theory explained why," Roscoe says. "Unfortunately, it was difficult until recently for archaeologists to get a handle on the size and densities of populations in the past. SPD techniques are a major help in bringing these important variables into understanding how human social life underwent this dramatic transformation."

Scientists have previously posited that population in northern coastal Peru rose during the Late Preceramic, Initial, Early Horizon and Early Intermediate periods, or between about 6,000-1,200 B.P. The SPD from Roscoe and his colleagues validates the notion.

The people who settled in the coastal plain first lived as mobile hunter-gatherers or incipient horticulturalists in low density groups, according to researchers. Millennia afterward in the Late Preceramic period, however, several developments brought increased interaction and shareable resources. People began farming, developed irrigation systems and became more settled as time passed. Eventually, some of the world's first 'pristine' states formed in the plain.

The onset and growth of agriculture, irrigation and sedentism, propelled by upticks in population size and density, fostered the capacity of political agents to interact with and manipulate others. Political centralization and hierarchy formed as a result, according to researchers.

Roscoe and his colleagues demonstrated through their radio-carbon SPD that the rise in centralized authorities in early Peruvian communities that resulted from farming, irrigation and settlement coincided with an uptick in population size. The results of their work demonstrate "a broad, low-resolution congruence between the expectations of Power Theory and what is currently known about coastal Peruvian antiquity," they wrote in their study.

The project also highlights the capability of SPDs for examining the influence of demography in the growth of prehistoric political centralization. Determining the extent of that influence, however, requires additional study.

"We're hoping this work demonstrates the value of SPDs for understanding the role of demography in the emergence and development of power centers on Earth," Roscoe says. "What we need now is to increase the size of our SPD databases and filter out some of the weaknesses we know they contain."

The COVID-19 pandemic could result in net losses from $3.2 trillion and up to $4.8 trillion in U.S. Real Gross Domestic Product (GDP) over the course of two years, a new USC study finds.

The pandemic's economic impact depends on factors such as the duration and extent of the business closures, the gradual reopening process, infection rates and fatalities, avoiding public places, and pent-up consumer demand, according to the research by the USC Center for Risk and Economic Analysis of Terrorism Events (CREATE).

Real GDP is a measure, adjusted for inflation, that reflects the value and the quantity of final goods and services produced by a nation's economy in a given year.

"In a best-case scenario, we would see containment measures, such as masks and social distancing become more widespread, and possibly even a vaccine by next year, and then businesses and institutions would be able to reopen at an accelerated pace," said Adam Rose, study team leader who is the director of CREATE and a research professor at the USC Price School of Public Policy.

"But in a worst-case scenario, these countermeasures wouldn't materialize, and reopenings would happen slowly, particularly because we would continue to see waves of infection," he said. Then, more people would likely lose their jobs, and the impacts of this disaster would continue to mount."

The researchers found that the mandatory closures and partial reopenings alone could result in a 22% loss of U.S. GDP in just one year and an even greater loss of GDP over two years. Other key factors, though, will influence how disastrous the losses may be, they noted.

The research team noted that China has not sustained such losses due to aggressive containment measures resulting in a shorter lockdown period. They project that in a worst-case scenario, the U.S. GDP loss due to COVID will more than quadruple that of China.

The study was published on Nov. 30 in the journal Economics of Disasters and Climate Change.

In early March, several states responded to a rise in COVID-19 cases by ordering the closures of non-essential businesses such as restaurants, bars, salons and retail stores. Many also halted or reduced public services to limit the spread.

Researchers at CREATE who are experts on modeling economic consequences of disasters analyzed the potential economic impact in three scenarios ranging from moderate to disastrous.

Using a computerized economic model, the researchers accounted for these other factors in the three scenarios. They varied the decline in the workforce due to workers becoming sick with or dying of the virus, workers adopting new behaviors like staying home to avoid infection, increased demand for COVID healthcare, potential resilience through telework, increased demand for communication services, and increased pent-up consumer demand.

The researchers conducted a synthesis of the literature of projections on the severity and possible duration of the pandemic. For the scenarios, which span from March 2020 through February 2022, this compilation of findings indicated that the number of COVID-related deaths in the United States could range from more than 300,000 to, in a worst-case scenario, 1.75 million.

Anywhere from 365,000 to as many as 2.5 million COVID patients could end up in the ICU, while another 860,000 to nearly 6 million patients may be hospitalized but not treated in the ICU. The projected number of people who will be treated for COVID as outpatients may vary from about 2.6 million to 18 million.

Among other highlights of the study, the researchers projected:

54 million to 367 million work days would be lost due to people getting sick or die from COVID

2 million to nearly 15 million work days would be lost due to employees staying home to care for sick loved ones.

Job losses could range from 14.7% to 23.8%, and in the worst case affect an estimated 36.5 million workers.

Demand for health care has risen with COVID infections. Medical expenses due to COVID-19 from March 2020 to February 2022 could range from nearly $32 billion to $216 billion.

A loss in demand for some services -- such as the use of public transit and school attendance, restaurant dining and travel -- as people avoid public places and services to reduce their risk of exposure.

An uptick in demand for communication services, as many employees during this pandemic have had to work from home.

An increase in pent-up demand will arise since consumers are unable to spend money on big-ticket items such as cars, as well as on travel, restaurants, hotels, merchandise, fitness, sporting events and concerts during the closures, and, to a lesser extent, during the phased reopenings.

While the researchers have found that the mandatory closures and re-openings are the most influential factor in the economy's decline, consumer avoidance behavior also has a significant effect.

For the study, the researchers assumed that various people avoided work, did not attend in-person classes at schools, and stopped going to restaurants, activities and social gatherings to reduce their risk of infection.

"Because people have had to avoid activities, this has had a significant impact on economic losses," said Dan Wei, a CREATE research fellow and research associate professor at the USC Price School for Public Policy. "Based on our model, we estimate that avoidance behavior can result in nearly $900 billion losses in U.S. GDP in the worst-case scenario. Because consumers in places like California can't engage in many activities like eating inside a restaurant, they are saving their money."

The economic losses from closures and avoidance behavior could be partly offset by increased consumer spending after reopening, the researchers said.

"Pent-up demand is one of the most influential factors for the economy in this pandemic. While the mandatory closures and partial reopenings drive most of the economic decline, the extent to which pent-up demand leads to an increase in consumption after reopening, can be crucial to the economic recovery," said Terrie Walmsley, a USC CREATE research fellow and an adjunct assistant professor of practice in economics at the USC Dornsife College of Letters, Arts and Sciences.

"The key question is: When will we see a complete reopening across this country? We simply cannot predict that, especially in light of the fact that we have not gained control of the spread of the disease," Rose said.

UNIVERSITY PARK, Pa. -- Two genes that are important for the diverse colors and patterns of warbler plumage have evolved through two very different processes, according to a new study led by Penn State researchers. These evolutionary processes could help explain the rapid evolution of these songbirds into so many unique species.

"Wood warblers are an incredibly colorful and diverse group of birds, with more than a hundred species in total," said Marcella Baiz, postdoctoral researcher at Penn State and first author of the paper. "These species arose very quickly in evolutionary time in what biologists call a species radiation. To better understand this radiation, we studied genetic regions related to plumage coloration within a particularly colorful subset of warblers."

The research team sequenced the genomes of all 34 species within the Setophaga genus of wood warblers and created a phylogenetic tree that clarifies how each species is related to one another. Then, they focused on nine closely related pairs of "sister species." Each pair is the result of one species diverging into two. Seeing if similar evolutionary processes are at play in each of the pairs allowed the researchers to gain a better understanding of the overall radiation.

A paper describing their results appears today (Nov 30.) in the journal Current Biology.

"In most cases it is difficult to get at the genes underlying the diversification process because it can be hard to link specific genes to specific traits, like colors," said David Toews, assistant professor of biology at Penn State and leader of the research team. "But many species of warblers readily interbreed, producing hybrid offspring with a mix of the parent species' traits, so we were previously able to link certain color patterns with their underlying genetic regions. In this study, we focused on two coloration genes, but were able to study them across all the species in this large genus, to give us a window into the rest of the radiation."

The first gene, the Agouti-signaling protein (ASIP), is involved in producing the pigment melanin, which underlies brown and black plumage in these warblers. Within each pair of sister species where there were differences in the amount or location of the black or brown in their plumage, the team predictably found genetic differences near ASIP.

"We created an evolutionary tree based solely on the ASIP gene region, which more clearly shows how the gene has changed across the genus," said Baiz. "The patterns in this gene tree mirror patterns in the phylogenetic tree based on what we see across the whole genome. This implies that the differences we see in ASIP resulted from mutations that arose independently in different species. However, the gene tree from the second gene, BCO2, showed a very different pattern that did not match up with the whole genome tree, which suggests different processes are at play."

The second gene, beta-carotene oxygenate 2 (BCO2), is involved in producing carotenoid pigments, which result in bright yellow, red, and orange plumage. The researchers suggest that a process called introgression-- the exchange of genes between species that have evolved separately--may explain why the pattern of genetic changes in BCO2 didn't align with the overall radiation of the group.

"Introgression can occur when two separate species hybridize, and the hybrid offspring go on to mate with one of the original species," said Baiz. "After several generations, genetic material from one species can be incorporated into the other. The signal of this kind of ancient introgression can be maintained in the genomes of living individuals--like how ancestry tests can reveal how many Neanderthal genes you have. In this instance, we unexpectedly found evidence for ancient introgression at BCO2 in two otherwise distantly related warblers in this genus."

The researchers found evidence of introgression involving the yellow warbler and magnolia warbler and involving the prairie warbler and vitelline warbler, all species with colorful carotenoid coloration in their feathers. However, they note that with the current data it is difficult to tell the directionality of the gene transfer.

"One possibility is that the magnolia warbler version of BCO2 introgressed into the yellow warbler, and this 'new to them' version produced a broader deposition of carotenoids in the feathers of the yellow warbler," said Toews. "It is fun to think that ancient introgression is what made the yellow warbler so yellow!"

This is one of the first examples of carotenoid gene transfer among vertebrates. Collectively, the results of this study suggest that both introgression and a more standard mode of evolution, where mutations occur and are passed from parent to offspring, have played a role in generating the diversity of colors in this genus and could have helped enable the extreme diversification of warblers.

In the future, the researchers hope to link specific mutations in these genes to changes in plumage coloration and to map out the molecular pathways involved in pigment production. They would also like to expand their study to all 110 species of warblers.

"There's a possibility that there may be introgression from another genus entirely," said Toews. "Expanding to other warblers would allow us to explore this possibility, and to more broadly understand the radiation of these fascinating birds."

PHILADELPHIA-- The labyrinth of jumbled blood vessels in the tumor microenvironment remains one of the toughest blockades for cellular therapies to penetrate and treat solid tumors. Now, in a new study published online today in Nature Cancer, Penn Medicine researchers found that combining chimeric antigen receptor (CAR) T cell therapy with a PAK4 inhibitor drug allowed the engineered cells to punch their way through and attack the tumor, leading to significantly enhanced survival in mice.

The researchers discovered in laboratory experiments that vascularization in solid tumors is driven by the genetic reprogramming of tumor endothelial cells--which line the walls of blood vessels--caused by an enzyme known as PAK4. Knocking out that enzyme reduced abnormal tumor vascularity and improved T cell infiltration and CAR T cell immunotherapies in glioblastoma (GBM) mouse models, the Penn team found. GBM, the most common and aggressive type of brain cancer diagnosed in more than 22,000 Americans every year, is known for its prominent and abnormal vascularity and being immunologically "cold."

"The response in GBM patient from CAR T cell therapies is universally poor because the CAR T cells have a problem getting into the tumor," said senior author Yi Fan, PhD, an associate professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania. "Our study shows that turning off this endothelial cell genetic reprogramming with a PAK4 inhibitor may help open the door to let both T cells and engineered T cells reach the tumor to do their job."

First, the team performed a kinome-wide screening analysis of more than 500 kinases, or enzymes, that regulate blood vessel activation in human endothelial cells from GBM patients. They found that PAK4, which has previously been shown as a driver of growth in solid tumors, was the culprit. Knocking that enzyme out in GBM endothelial cells with a drug, they found, restored expression of adhesion proteins that are important for the recruitment of immune cells and stimulated T cell infiltration into the tumors. Notably, knocking down PAK4 shifted the endothelial cells' morphology, from a spindle-shaped appearance to a characteristic cobblestone in GBM, indicating a less chaotic formation of blood vessels. In other words, it "normalized" the microenvironment.

Next, in a GBM mouse model, they found that inhibiting PAK4 reduced vascular abnormalities, improved T cell infiltration, and inhibited tumor growth in the mice. Approximately 80 percent of PAK4 knockout mice survived for at least 60 days after the experiment was terminated, whereas all wild-type mice died within 40 days after tumor implantation.

Another experiment with a EGFRvIII-directed CAR T cell therapy and a PAK4 inhibitor showed a nearly 80 percent reduction in tumor growth compared to mice that only had CAR T therapy five days after infusion. Notably, nearly 40 percent of the mice in the combination therapy group still survived even when all of the mice in the other groups had died 33 days after tumor implantation.

Targeting PAK4 may provide a unique opportunity to recondition the tumor microenvironment, as well provide a much-needed opportunity to improve T cell-based cancer immunotherapy for solid tumors, the authors said. The findings also support the idea that vessel normalization by PAK4 inhibition can improve drug delivery and reduce oxygen deprivation known as hypoxia, leading to improved tumor responses to targeted therapy, radiation and chemotherapy.

"To our knowledge, we are the first to show how we can reprogram the whole vascular microenvironment with a PAK4 inhibitor and promote cellular therapy," Fan said. "Importantly, this may not only be limited to brain tumors; it could potentially be used for all types, including breast, pancreatic, and others, because vascular abnormality is a common feature for almost every solid tumor."

Researchers at ELTE Department of Ethology in Budapest compared how young companion dogs and companion pigs seek human proximity in a novel environment. It turned out that both dogs and pigs stay close to their owner if no other person is present; but if a stranger is also there, only dogs stay near humans, pigs prefer to stay away. The study reveals that living in a human family is not enough for early developing a general human preference in companion animals, species differences weigh in.

Dogs are known for being especially social with humans from a very early age. Even those with limited contact to humans readily approach and seek human proximity and dogs can also recognize familiar over unfamiliar humans. This special sociability of dogs has been assumed to be the result of both their domestication and socialization with humans during early development. "We were curious if being kept as a family member from a very early age, like dogs, would induce similar proximity-seeking behaviours towards their owner in another social domestic species, the pig"-explains PhD student Paula Pérez Fraga.

Nowadays, the domestic pig, especially the miniature variant, is a popular companion animal that occupies a similar social niche in the human family as the family dog. This new role of the pig creates the need to better understand the pig-human relationship in the household environment, and especially the relationship of the pigs with their owners. "The miniature pigs that are part of our Family Pig Project are raised in human families since their 6-8 weeks of age. This does not only provide a unique opportunity to investigate the pig-human relationship, but it also allows us to directly compare their human-oriented behaviour to those of dogs"- says Attila Andics, principal investigator of the MTA-ELTE 'Lendület' Neuroethology of Communication Research Group.

"In this study, the animals were led into a novel room, where their owner was paired with a familiar object or with an unfamiliar person, on two separate occasions. The subjects could freely choose to be anywhere in the room, e.g. staying near or further away from any of the humans or the object"-says Linda Gerencsér, research fellow at the Research Group. "We found that both pigs and dogs preferred to stay near their owner over the familiar object. However, neither species preferred their owner over the stranger, but for seemingly different reasons. Dogs preferred to stay near both humans over being elsewhere, whereas pigs rather stayed away from the social partners, which might reflect slight fear towards the unfamiliar human." Interestingly, the research also revealed a difference in how the two species behaved near their owner. "Pigs needed more physical contact" - adds Pérez Fraga. "They touched the owner with the snout, in a similar manner as they do with conspecifics, and they climbed to the owner's lap."

Watch our study's video abstract: https://www.youtube.com/watch?v=-srppJ6UupY.

This is the first study to investigate the proximity seeking behaviours of miniature pigs towards their owner. "The similar previous experience of both pigs and dogs might lead to a similar role of the owner for the two species" - adds Gerencsér. "However, being kept as a family member might not be enough for developing a general preference for human company in pigs. Species predispositions, including that dogs, have a longer socialization period and humans are more salient as a social stimulus for them, might play an important role."

BEER-SHEVA, Israel...November 30, 2020 - An end-to-end cyber-biological attack, in which unwitting biologists may be tricked into generating dangerous toxins in their labs, has been discovered by Ben-Gurion University of the Negev cyber-researchers.

According to a new paper just published in Nature Biotechnology, it is currently believed that a criminal needs to have physical contact with a dangerous substance to produce and deliver it. However, malware could easily replace a short sub-string of the DNA on a bioengineer's computer so that they unintentionally create a toxin producing sequence.

"To regulate both intentional and unintentional generation of dangerous substances, most synthetic gene providers screen DNA orders which is currently the most effective line of defense against such attacks," says Rami Puzis, head of the BGU Complex Networks Analysis Lab, a member of the Department of Software and Information Systems Engineering and Cyber@BGU. California was the first state in 2020 to introduce gene purchase regulation legislation.

"However, outside the state, bioterrorists can buy dangerous DNA, from companies that do not screen the orders," Puzis says. "Unfortunately, the screening guidelines have not been adapted to reflect recent developments in synthetic biology and cyberwarfare."

A weakness in the U.S. Department of Health and Human Services (HHS) guidance for DNA providers allows screening protocols to be circumvented using a generic obfuscation procedure which makes it difficult for the screening software to detect the toxin producing DNA. "Using this technique, our experiments revealed that that 16 out of 50 obfuscated DNA samples were not detected when screened according to the 'best-match' HHS guidelines," Puzis says.

The researchers also found that accessibility and automation of the synthetic gene engineering workflow, combined with insufficient cybersecurity controls, allow malware to interfere with biological processes within the victim's lab, closing the loop with the possibility of an exploit written into a DNA molecule.

The DNA injection attack demonstrates a significant new threat of malicious code altering biological processes. Although simpler attacks that may harm biological experiments exist, we've chosen to demonstrate a scenario that makes use of multiple weaknesses at three levels of the bioengineering workflow: software, biosecurity screening, and biological protocols. This scenario highlights the opportunities for applying cybersecurity know-how in new contexts such as biosecurity and gene coding.

"This attack scenario underscores the need to harden the synthetic DNA supply chain with protections against cyber-biological threats," Puzis says. "To address these threats, we propose an improved screening algorithm that takes into account in vivo gene editing. We hope this paper sets the stage for robust, adversary resilient DNA sequence screening and cybersecurity-hardened synthetic gene production services when biosecurity screening will be enforced by local regulations worldwide.

More than one-third of kids who have COVID-19 are asymptomatic, according to a University of Alberta study that suggests youngsters diagnosed with the disease may represent just a fraction of those infected.

"The concern from a public health perspective is that there is probably a lot of COVID-19 circulating in the community that people don't even realize," said Finlay McAlister, a professor of medicine in the Faculty of Medicine & Dentistry.

"When we see reports of 1,200 new cases per day in the province of Alberta, that's likely just the tip of the iceberg--there are likely many people who don't know they have the disease and are potentially spreading it," he said.

For the study, McAlister's team analyzed results for 2,463 children who were tested during the first wave of the pandemic--March to September--for COVID-19 infection.

All told, 1,987 children had a positive test result for COVID-19 and 476 had a negative result. Of children who tested positive, 714--35.9 per cent--reported being asymptomatic.

"It speaks to the school safety programs," he said. "We can do all the COVID-19 questionnaires we want, but if one-third of the kids are asymptomatic, the answer is going to be no to all the questions--yet they're still infected."

Because of the asymptomatic nature of the disease in up to one-third of children, McAlister said the province was right to close schools for a longer period over Christmas.

"As far as we know, kids are less likely to spread disease than adults, but the risk is not zero," he said. "Presumably asymptomatic spreaders are less contagious than the person sitting nearby who is sneezing all over you, but we don't know that for sure."

The researchers also found that although cough, runny nose and sore throat were three of the most common symptoms among children with COVID-19 infection--showing up in 25, 19 and 16 per cent of cases respectively--they were actually slightly more common among those with negative COVID-19 test results, and therefore not predictive of a positive test.

"Of course, kids are at risk of contracting many different viruses, so the COVID-specific symptoms are actually more things like loss of taste and smell, headache, fever, and nausea and vomiting, not runny nose, a cough and sore throat," he said.

McAlister noted that his group has a similar paper coming out that shows sore throats and runny noses aren't reliable signs of COVID-19 in adults either, although the vast majority of adults (84 per cent) do show symptoms.

"Sore throat and runny nose means you've got some kind of upper respiratory tract infection, but fever, headache, and loss of taste or smell are the big ones for indicating that one may have COVID-19 rather than another viral upper respiratory tract infection," he said, adding nausea and vomiting wasn't as prominent in adults.

McAlister added that if people have any symptoms at all, they should stay home and get tested, while even those who feel well should still be doing everything they can to stay safe--wearing a protective mask, frequent handwashing, keeping distance, and avoiding meeting indoors.

"Some people with COVID feel well and don't realize they have it so they socialize with friends and unintentionally spread the virus, and I think that's the big issue," he said.

Understanding the sequence of human DNA gives scientists information about diseases, including potentially how to diagnose or treat them. In a new paper published in Nature Biotechnology, scientists from the School of Life Sciences at the University have shown that it is now possible to selectively sequence fragments of DNA more quickly and cost effectively than previously, without searching through DNA strands that are not relevant to the biological question, reaching that answer quicker than before.

This could have major implications in how genetic diseases are understood are diagnosed.

Professor Matt Loose, of the DeepSeq Sequencing Facility in the School of Life Sciences at the University led this project. He said: "In simple terms, we can now sequence the bits of DNA that we want to and ignore bits we don't. The advances we present here mean we can search through and sequence regions from genomes even as large as the human genome."

The new study shows how the team can now rapidly scan human genomes and detect genetic abnormalities on the MinION, a portable DNA sequencer. They illustrate this by locating a change in the DNA responsible for a specific type of cancer in less than 15 hours. A human genome has 3 billion data points, and a typical whole genome analysis might take several days. Thus, the team have shown that this method can now be used to 'scan' genomes at high speeds to see if there are obvious problems without having to sequence entire genomes, or perform elaborate lab processes to select the genomic regions of interest.

The team have developed a new selective method, called ReadFish, which allows the DNA sequencer to select just those regions of the human genome (or any genome) of interest for a specific question and so only need to use a single sequencing run.

Prof Loose continues: "This breakthrough will enable us to look at a range of applications, such as rapidly searching fragments of the human genome to find evidence of genetic conditions or changes which may lead to illness such as cancer - which would have major implications for diagnosis.

"We are already seeing people using the method to identify the underlying causes for diseases in a host of different individuals for the first time*."

Alexander Payne, the study's lead author, says: "Having truly adaptive sequencing, that can respond as the experiment progresses, brings lots of exciting opportunities for customising and tuning your sequencing for the question at hand. I am really looking forward to seeing how ReadFish is used by the nanopore community."

Gordon Sanghera, CEO of Oxford Nanopore, makers of the real-time, portable sequencing technology on which this work was performed, said "Alexander Payne, Matt Loose and the team have taken advantage of real time sequencing technology to intelligently zoom in on specific areas of interest in the substantial human genome. The potential impact of this work could be profound in enabling more rapid answers, on devices that are small, low cost and easy to use. This research perfectly illustrates our goal of enabling the analysis of any living thing by anyone, anywhere"

The latest study follows on from the team's previously published research in 2016, where they initially demonstrated the novel technique for highly selective sequencing. This method used real-time nanopore sequencing and enabled, for the first time, people to analyse only DNA strands that contain pre-determined signatures of interest.

In 2018, this same team led an international consortium to sequence the entire human genome on the Oxford Nanopore Technologies hand held pocket sized MinION portable DNA sequencer. At the time this required more than 40 individual sequencing runs on the portable sequencer; the technology had advanced materially since then.

What The Study Did: Researchers linked administrative health care and demographic data from Medicare to the Federal Reserve Bank of New York/Equifax Consumer Credit Panel to characterize the financial presentation of Alzheimer disease and related dementias before and after diagnosis.

Authors: Lauren Hersch Nicholas, Ph.D., M.P.P., of the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins University School of Medicine in Baltimore, 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/jamainternmed.2020.6432)

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.

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What The Study Did: Nationally representative data were used to examine if racial disparities in the occurrence of dementia in the United States changed from 2000 to 2016.

Authors: Melinda C. Power, Sc.D., of George Washington University in Washington, D.C., 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/jamaneurol.2020.4471)

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.

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Media advisory: The full study and editorial are linked to this news release.

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What The Study Did: The distribution of race/ethnicity among cases of COVID-19]-associated multisystem inflammatory syndrome in children reported to the New York City Department of Health and Mental Hygiene is described in this observational study.

Authors: Ellen H. Lee, M.D., of the New York City Department of Health and Mental Hygiene in Long Island City, New York, 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.2020.30280)

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About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

What The Study Did: This observational study assessed whether receiving unemployment insurance is associated with lower health-related social needs, better health care access and better mental health during the COVID-19 pandemic.

Authors: Seth A. Berkowitz, M.D., M.P.H., of the University of North Carolina at Chapel Hill, 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/jamainternmed.2020.7048)

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.

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Media advisory: The full study is linked to this news release.

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A research team co-led by a scientist at the Hong Kong University of Science and Technology (HKUST) has developed a method to study how HIV mutates to escape the immune system in multiple patients, which could inform HIV vaccine design.

HIV, which can lead to AIDS, evolves rapidly and attacks the body's immune system. Genetic mutations in the virus enable it to evade immune responses mounted by T cells and antibodies, which makes it all the more difficult to design an effective solution. While there is no effective cure for the virus currently available, it can be controlled with medication.

Now, the international research team has devised a new method from conventional statistical physics to reveal patterns of selection in HIV evolution using 14 patient data sets, providing a means to efficiently distinguishing the mutations that help the virus escape the immune system from those that are only random variations.

"Our novel method enables us to sort out which genetic changes provide an evolutionary advantage from those that offer no advantage or have a deleterious effect," said Prof. Matthew MCKAY, a Professor from the Departments of Electronic and Computer Engineering and Chemical and Biological Engineering, who co-led the study with Prof. John BARTON, an Assistant Professor of Physics and Astronomy at University of California, Riverside.

"The method is quite general and could be used to study diverse evolutionary processes, such as the evolution of drug resistance of pathogens and the evolution of cancers. The accuracy and high efficiency of our approach enable the analysis of selection in complex evolutionary systems that were beyond the reach of existing methods," he added.

"Understanding the genetic drivers of disease is important in the biomedical sciences," said Prof. Barton. "Being able to identify genomic rearrangements is key to understanding how illnesses occur and how to treat them." Notable examples of genetic drivers of disease include mutations that allow viruses to escape from immune control, while others confer drug resistance to bacteria.

"It can be difficult, however, to differentiate between real, adaptive mutations and random genetic variation," he added. "The new method we developed allows us to identify such mutations in complex evolving populations."

"However, it is computationally difficult to extract this information from data," he said. "We used methods from statistical physics to overcome this computational challenge. Our method can be applied generally to evolving populations and is not limited to HIV."

Some well-known diseases that have known genetic causes are cystic fibrosis, sickle cell anemia, Duchenne muscular dystrophy, colorblindness, and Huntington's disease.

"Our approach isn't limited to HIV, but there are a few reasons why we focused on HIV as a test system," Prof. McKay said. "HIV has an extraordinary capability to mutate within humans to escape from the immune system. However, the details of these immune escape dynamics are not well understood. If we can gain a clearer picture of how HIV evolves within a person, this may help to develop better treatments against the virus."

November 30, 2020 - Insilico Medicine, a leading company in AI-powered drug discovery, today announced that the paper titled "Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models" was published in Frontiers in Pharmacology. In addition to the authors from Insilico Medicine and Neuromation, the author list includes Simon Johansson and Hongming Chen from AstraZeneca, Benjamin Sanchez Lengeling from Harvard University, and Alan Aspuru-Guzik from Vector Institute, Department of Computer Science, University of Toronto, and Canadian Institute for Advanced Research (CIFAR).

In 2018, Insilico Medicine presented Molecular Sets (MOSES) benchmarking platform that was employed by multiple research groups since then. MOSES contains a carefully curated dataset, a set of metrics, and a wide variety of baselines for comparing generative models for chemistry. Over the last two years, we extended the repository with new baselines, enhanced evaluation protocols, and implemented simple routines for using MOSES out of the box. Today, Insilico Medicine announces that the manuscript describing the platform has been accepted for publication in Frontiers in Pharmacology, "Artificial intelligence for Drug Discovery and Development" special issue. The paper will soon be available here: https://www.frontiersin.org/articles/10.3389/fphar.2020.565644. For more information on MOSES, please visit the GitHub repository https://github.com/molecularsets/moses.

"With the rapid development of new generative chemistry, it is crucial to compare machine learning models in a unified way; with MOSES, we can easily compare new models with existing approaches without reimplementing all the baselines. MOSES is a result of tight collaboration between multiple generative chemistry labs; together we polished the platform over the last two years and made it as simple and intuitive as possible. We are glad to help researchers obtain interpretable, reproducible results with our platform.", said Daniil Polikovskiy, senior author of the paper.

To cite the paper: https://www.frontiersin.org/articles/10.3389/fphar.2020.565644