Culture

BUFFALO, N.Y. -- Exposure to heroin sharply reduces levels of the protein necessary for developing and maintaining the brain's synapses, a preclinical study by University at Buffalo researchers has found. The development of addiction relapse is directly related to the impact that reductions in this protein, called drebrin, have on specific cells involved in the brain's pleasure-seeking/reward pathways.

The UB research paper, one of the first to trace the pathophysiology of addiction relapse, was published online on Sept. 12 in Nature Communications.

The neurobiology of relapse

"Very few research studies have examined the molecular mechanisms of heroin relapse and there is almost nothing published about the specific cell types that these changes occur in," said David Dietz, PhD, senior author on the paper, chair of the Department of Pharmacology and Toxicology in the Jacobs School of Medicine and Biomedical Sciences at UB and a faculty member in UB's neuroscience program.

"These findings lead us to a better understanding of the neurobiology of relapse to opiates. In combination with other findings, the research will hopefully provide avenues toward treatments that can prevent relapse behaviors."

Most currently available treatments are replacement therapies, none of which address the fundamental changes that occur in addiction and lead to relapse, which remains an intractable issue.

Dietz and his colleagues have focused much of their research on relapse after opiate addiction and withdrawal and the structural plasticity in the brain that they cause. He was recently awarded more than $2 million from the National Institutes of Health (NIH) to continue research on drebrin and other potential targets for treating drug addiction.

Drebrin was of interest because loss of the protein has been previously implicated in brain diseases, such as Alzheimer's disease and Down syndrome.

"Since drebrin is responsible for developing and maintaining synapses, we wondered if it was also involved in addiction to drugs of abuse, ultimately leading to relapse," said Dietz.

In experiments with rodents, the UB team determined that exposure to heroin and morphine reduced drebrin levels in the nucleus accumbens, a key part of the brain's reward pathway.

Synaptic rewiring

The researchers found that opiate exposure causes synaptic rewiring in this part of the brain, as well as a decrease in drenditic spines, the protrusions on neurons that play key roles in neuronal transmission, learning and memory.

"Opiates fundamentally change how the brain communicates with itself," Dietz said.

The researchers found that the reduction in drebrin levels is regulated by changes in how an enzyme called HDAC2 facilitates access to the DNA. In addition, the study demonstrates that these changes occur exclusively in a specific type of cell within the nucleus accumbens, known as D1, which contains medium spiny neurons, the type of cells that make up this part of the reward center.

"Restoring drebrin back to normal levels in these specific brain cells was sufficient to reduce relapse behaviors," said Dietz.

The research provides a critical and understudied insight into the mechanisms behind addiction and relapse behaviors, which in combination with future studies may lead to a novel and effective treatment to prevent relapse.

"Our lab is focused on improving our understanding of the neurobiology of addiction and relapse so that we can figure out the best way to target these pathways for future therapeutic use," Dietz said.

PISCATAWAY, NJ - The total harm caused by excessive alcohol consumption is a staggering $2.05 per drink in the United States, and, of this, the government ends up paying about 80 cents per drink. However, the federal government and states only bring in about 21 cents per drink on average in alcohol taxes, according to new research in the Journal of Studies on Alcohol and Drugs. This leaves the majority of the cost of alcohol's harms borne by those who don't drink excessively or who don't drink at all.

"The disparity between alcohol-related cost to government and alcohol taxes amounts to a large taxpayer-funded subsidy of excessive drinking and alcohol companies," says senior author Timothy S. Naimi, M.D., M.P.H., of the Boston Medical Center and the Boston University School of Public Health.

Research shows that higher prices on alcohol, often through increased taxes, can lead to less excessive consumption, which in turn reduces a range of alcohol-related harms such as violence, motor vehicle injuries and liver cirrhosis.

"Increasing alcohol taxes could improve public health and reduce the disparity between alcohol-related costs and alcohol taxes in states," says Naimi.

"Policy debates around alcohol taxes have mostly centered on public health benefits, but I think our study might change the focus of the debate somewhat, since it seems fair that those who drink the most and who produce and sell alcohol should cover the costs to society," says study lead author Jason G. Blanchette, J.D., M.P.H., of the Boston University School of Public Health.

To calculate the total amount of federal and state tax per standard drink in each state, Naimi and colleagues analyzed state and federal tax data from 2010. Although the federal government charges a standard excise tax that applies in all states (the equivalent of 5, 4 and 16 cents per drink for beer, wine and distilled spirits, respectively), states can charge up to three additional taxes: specific excise taxes, ad valorem excise taxes, and state general sales taxes.

States may assess any combination of these taxes. In fact, Naimi and colleagues report that four states (Alaska, Delaware, Montana and Oregon) charged only specific excise tax, and no other kind of state tax, on alcohol. Other states and Washington, D.C., applied some combination of specific excise taxes on alcohol plus sales tax and/or ad valorem excise tax.

State and federal specific excise taxes are based on the volume of alcohol sold, not the price, and therefore can erode over time because of inflation. During the past 25 years, state excise taxes have declined by more than 30% on average in inflation-adjusted terms, and federal excise taxes have declined by almost 50% because they were last adjusted for inflation in 1991. Ad valorem excise taxes and state general sales taxes are based on a percentage of the retail price and, therefore, increase in tandem with the purchase price. However, although all states charge specific excise taxes, only a minority of states have ad valorem taxes and not all states apply sales taxes to alcohol.

Accordingly, the study found that specific excise taxes accounted for only one fifth of current tax revenue from alcohol. "All states have specific excise taxes because that was the standard when alcohol prohibition was lifted, but they haven't kept pace with inflation so now they're not worth much now," says Blanchette.

On average, state alcohol taxes brought in an average of 13 cents per drink, the researchers found. Delaware brought in the least (3 cents) and Tennessee brought in the most (27 cents) per drink. Once Naimi and colleagues added in the average amount of federal taxes per drink, the total average tax amounted to 21 cents per drink.

However, this is only a fraction of alcohol-related costs from excessive drinking. "Total alcohol taxes accounted for a median of 26.7% of the economic cost to the government," the authors write, "and 10.3% of the total economic cost of excessive drinking." Total alcohol taxes per drink were compared with cost per drink based on a Centers for Disease Control and Prevention study that included medical costs, costs to the legal and criminal justice systems and lost productivity but did not include "intangible" costs such as pain and suffering.

Says Naimi, "the bottom line is that current alcohol taxes, even considering all types of tax including general sales taxes, don't come close to covering alcohol-related costs."

PISCATAWAY, NJ - Although the effectiveness of medications to treat adults with opioid use disorder has been well established, there has been little research about how -- or even if -- such treatment works in adolescents.

Now, a new review of the literature suggests that, in addition to adults, adolescents with severe opioid use disorder can be treated with one of three medications: methadone, buprenorphine (Subutex/Suboxone) or extended-release naltrexone (Vivitrol). The study was published in the latest issue of the Journal of Studies on Alcohol and Drugs.

"In 2017, 900 adolescents started misusing opioid pain relievers each day," the authors write. In addition to abusing prescription medication, some of these teens "initiate heroin use because of its ready availability, lower cost, and strong potency."

"Adolescents with severe opioid use disorder may benefit from a medication as part of a larger comprehensive treatment plan," says lead author Deepa R. Camenga, M.D., M.H.S., of the Yale School of Medicine. Further, "parents should try to consult with an addiction psychiatry or medicine specialist to see if there are additional treatments that may benefit their child."

In their research, Camenga and colleagues searched the scientific literature for investigations of the effects of medication in the treatment of opioid use disorder in adolescents. They identified 14 reports, published between 1973 and 2018. The number of adolescents in each study ranged from just a handful to several hundred.

Overall, the researchers report that the dangers of untreated opioid use disorder "far outweigh the risks" of treatment with methadone, buprenorphine, or naltrexone. However, few adolescents receive such therapy: Only about 2 to 5 percent of adolescents with an opioid use disorder receive treatment with one of these medications, compared with 12 to 26 percent of adults.

In general, methadone, buprenorphine and extended-release naltrexone improved the number of adolescents who remained in treatment, decreased opioid use, and led to more abstinence. But, the authors say, "research is still needed to understand the optimal treatment duration and how to retain adolescents in treatment."

The medications do have their challenges. For methadone, the authors say, the use of these medications needs to be closely monitored due to known side effects with high doses, including slow breathing and sedation, as well as heart rhythm problems. Further, methadone needs to be administered by a federally certified opioid treatment program, which can cause difficulty for adolescents who don't have transportation to such locations. Also, adolescents must receive special dispensation to receive it, and there is the risk that methadone itself can be abused.

Unlike methadone, buprenorphine can be administered on an outpatient basis. However, teens may need the oversight of an adult to help ensure the medication is taken properly and not misused.

For naltrexone, one challenge to treatment is that patients have to go through detoxification before starting treatment. Also, naltrexone may increase the risk of opioid overdose if a patient begins using opioids again once the medication wears off. Nonetheless, extended-release naltrexone is given by injection once a month and doesn't require the frequent visits of methadone or the oversight of buprenorphine.

However, there is a very limited number of health care professionals who treat teens with opioid use disorder. "There is a great need to improve adolescents' access to medications for the treatment of OUD and to increase workforce capacity to care for these adolescents," the authors conclude.

In a commentary that accompanies the review, a group of researchers led by Rachel Gonzales-Castaneda, Ph.D., M.P.H., of UCLA, writes that, because relapse occurs in more than half of the adolescents treated for opioid use disorder with standard approaches, alternatives such a treatment with medication may need to be considered. However, they add that researchers lack information on how medical treatment may interact with other mental or physical disorders, or their treatments, and that much more research is needed that addresses the needs of the adolescent population with opioid disorder.

In a second commentary, Noel Vest, Ph.D., of the Stanford University School of Medicine, and Keith N. Humphreys, Ph.D., of the Veterans Affairs Palo Alto Health Care System in California, sound a cautious tone about the use of medication to treat opioid use disorder in adolescents.

Specifically, they write that teens treated with methadone "may end up taking the medication for half a century or more" and that the risks of such lengthy treatment are unknown. Further, they suggest that the treatment retention noted in the review does not necessarily equate to patients refraining from drugs or alcohol.

Last, diagnosing an adolescent poses complications. "[I]t can be challenging to determine whether 16-year-olds are truly dependent on Vicodin if they have been frequenting parties in which they are among many teenagers who consume the drug," Vest and Humphreys write.

New Haven, Conn. -- Teens who misuse prescription or illicit opioids might benefit from opioid treatment medications, according to a new study led by a Yale researcher.

An estimated 900 adolescents started to misuse opioid painkillers every day in 2017, and some of them turned to cheaper and more potent illegal opioids like heroin. Yet little is known about the effectiveness of opioid medications -- the recommended treatment for adults with opioid use disorder -- in teens who are younger than 18.

The research team, led by assistant professor of emergency medicine at Yale School of Medicine Deepa Camenga, M.D., searched the scientific literature for studies examining the effect of opioid treatment medications on teens. Their review suggested that teens with severe opioid use disorder can be treated with the medications.

While there were only 14 reports identified between 1973 and 2018, they all favored treatment with one of the three medications for opioid use disorder: methadone, buprenorphine, or naltrexone.

The studies revealed that these medications increased the number of teens who remained in treatment, decreased their use of opioids, and increased abstinence, the researchers said.

"Adolescents with severe opioid use disorder may benefit from a medication as part of a larger comprehensive treatment plan," said Camenga. Only 2%-5% of teens with an opioid use disorder receive medication treatment.

The dangers of leaving opioid addiction untreated far outweigh the risks of the medications, they noted. More research is needed to determine how long teen patients should receive medication treatment, and how to keep them in treatment, the researchers said.

"Parents should try to consult with a healthcare provider, and if they are able, an addiction psychiatry or addiction medicine specialist, to see if medications may benefit their child," Camenga said. The authors emphasized the need to improve teens' access to treatment and the capacity of providers to care for this population.

A new report from the Media, Inequality and Change (MIC) Center -- a joint project of the Annenberg School for Communication at the University of Pennsylvania and the School of Communication and Information at Rutgers University -- details the kinds of online privacy tradeoffs that disproportionately impact cell-mostly internet users, who are likely to be Black, Hispanic, and/or low-income.

Researchers Jan Fernback and Gwen Shaffer facilitated focus group discussions with 79 people in Philadelphia and Long Beach, California all of whom rely on their phones to go online. Through participant observation, the researchers also gained insight into the most popular apps for cell-mostly internet users and how much time they spend engaging with them.

Tanya, a 30-something African American woman who lives in Philadelphia, refuses to fill out online applications for jobs or credit cards. She doesn't own a computer and exclusively uses her phone to go online.

Shelly, a formerly homeless woman in her 50s who lives in Philadelphia and doesn't use a computer, is afraid to make purchases on her cell phone, in fear of having her information stolen.

Karla, another Philadelphia woman in her 50s who lives in transitional housing, worries about data collection by social media platforms. However, without a car or cash, posting to Facebook is a necessity to remain in touch with her family.

Jazmin, a Hispanic woman who lives in Long Beach, voiced similar concerns about social media platforms. In fact, she deleted Facebook from her phone after hearing about the company's repeated privacy violations, but ultimately installed it again.

The sentiments expressed by these cell-mostly internet users are not unique. Nearly all study participants shared stories of relinquishing their data privacy, which the researchers consider to be a basic human right, in exchange for the ability to access online services and platforms. Many people shared anecdotes about forgoing opportunities in an attempt to maintain data privacy.

However, participants lacked a clear understanding of how near-constant mobile internet use, including dependence on internet-connected apps, potentially compounds other inequalities that exist in their lives. Rather, study participants generally seemed resigned to their status as having little power and minimal social capital.

"Our findings shed light on the added dangers to information privacy that lower-income, cell-mostly internet users face, and how those dangers shape their online behaviors," Fernback said.

All individuals are vulnerable to security breaches, identity fraud, system errors, and hacking. But economically disadvantaged individuals who rely exclusively on their mobile phones to access the internet are disproportionately exploited through leakier phone models, lack of knowledge about phone security practices, and attitudes of resignation with regard to their agency over their own data. Such users are also more open to governmental surveillance if they participate in programs for low-income individuals and families or live in subsidized housing.

"The smartphone-dependent people we interviewed typically did not own a computer, and many lacked stable housing and relied on public services," said Shaffer. "Unfortunately, members of disadvantaged populations are frequent targets of data profiling by retailers hoping to sell them cheap merchandise or bait them into taking out subprime loans. They may be charged higher insurance premiums or find their job applications rejected. Ultimately, the inequities they experience off-line are compounded by online privacy challenges."

The researchers argue that privacy is a public good and a fundamental value in a democratic society. In fact, it is a requirement of basic human dignity. Because of the sheer ubiquity of digitized data compiled on individuals who rely on cell phones to access the internet, the need for privacy should be elevated from a personal liberty and legal right to a matter of social justice. Data privacy is not a luxury for those who cannot afford to invest the time, resources, and effort required to actively protect one's digital assets.

This study underscores the need for U.S. citizens, lawmakers, and activists to further consider the grassroots impact of data privacy and security and includes sets of recommendations at the policy, individual, and consumer advocacy levels. Understanding the symbiotic relationship between the material nature of mobile technology and the social construction of technology is a key means to safeguarding privacy in our increasingly digital lives.

The report is entitled "Cell Phones, Security and Social Capital: Examining How Perceptions of Data Privacy Violations among Cell-Mostly Internet Users Impact Attitudes and Behavior" and is available here.

A group of scientists from Skoltech's Computational and Data-Intensive Science and Engineering Center (CDISE) won the Best Paper Award at the prestigious 5th IEEE Internet of People conference (IoP 2019) for their research in artificial intelligence which helped them find a connection between an eSports player's movements and skill level. Their research findings show that machine learning methods help accurately predict a player's skill level in 77% of cases.

In just a few years, eSports that has its roots in video games for schoolkids has evolved into a full-fledged industry with professional teams, coaches, and huge investments. Like in any other sport, an eSports player can be a professional or an amateur, and telling one from another is essential for optimizing the training process.

Master's students from the Skolkovo Institute of Science and Technology (Skoltech), Moscow, Moscow Institute of Physics and Technology (MIPT) and the State University of Aerospace Instrumentation (SUAI), St. Petersburg, led by Skoltech professors, Andrey Somov and Evgeny Burnaev, looked for a connection between the proficiency and body movements of an eSports player seated on a chair.

"We assumed that there could be a link between a player's body movements and skill level. Also, it was interesting to look at the players' response to various game events, such as kills, deaths or shootings. We suspected that professional players and beginners would react differently to the same event," explains the first author of the study and Skoltech master student, Anton Smerdov.

The experiment involved a total of 19 players, including 9 professionals and 10 amateurs, who were asked to play Counter-Strike: Global Offensive (CS: GO) for 30 to 60 minutes. Their skills were evaluated in game hours, similarly to pilots, whose skills are assessed in flight hours. The data were collected using an accelerometer and a gyroscope embedded in the chair.

"We then cut the data into 3-minute sessions, assuming that 3 minutes were enough to understand the player's behavior and obtain a sample big enough for algorithm learning," Smerdov added.

The patterns extracted from each session were used to evaluate the players' behavior and check how intensively and how often they moved or turned around along each of the three axes and leaned back in the chair. A total of 31 patterns were obtained for each player, and 8 most important features were defined using statistical techniques. Machine learning methods were then applied to the key features. The popular Random Forest method displayed the best performance, correctly determining the player's skill level from a 3-minute session in 77% of cases. Also, the results showed that professional players move around more often and more intensively than beginners, while sitting perfectly still during shootings and other game events.

Launched within the Skoltech Introduction to Internet of Things course and Skoltech Cyber Academy initiative, this research project is being further developed at the Head Kraken eSports start-up, benefiting from the grants provided by Skoltech's STRIP program and the Russian Foundation for Basic Research (RFBR).

The team led by professors Andrey Somov and Evgeny Burnaev has been studying eSports players' psycho-emotional state and physical reactions to the game using sensors and machine learning methods since 2018. The data collected and analyzed include pulse, skin resistance, gaze direction, hand movements, environmental data (temperature, humidity, CO2 level), game telemetry, and other parameters.

A new gene therapy turns glial cells--abundant support cells in the brain--into neurons, repairing damage that results from stroke and significantly improving motor function in mice. A paper describing the new therapy, which uses the NeuroD1 gene, appears online in the journal Molecular Therapy. Once further developed, this NeuroD1-based gene therapy could potentially be used to treat stroke, which is a leading cause of disability in the U.S., with 800,000 new stroke patients every year.

"The current treatment for stroke has a narrow time window, typically within a few hours after the occurrence of stroke," said lead author Yuchen Chen, a postdoctoral fellow at Penn State. "Many patients cannot receive the treatment in time and as a result, often suffer from permanent disability caused by irreversible neuronal loss. There is an urgent need to develop a new therapy to regenerate new neurons and restore lost brain functions among stroke patients."

The human brain has approximately 86 billion neurons. While mini-strokes can be tolerated, moderate stroke involving the loss of billions of neurons leaves detrimental effects that do not spontaneously recover.

"So, the critical question that is still unanswered in the neuroregeneration field is how can we regenerate billions of new neurons in a patient's brain after stroke?" said Gong Chen, professor of biology and Verne M. Willaman Chair in Life Sciences at Penn State and leader of the research team. "The biggest obstacle for brain repair is that neurons cannot regenerate themselves. Many clinical trials for stroke have failed over the past several decades, largely because none of them can regenerate enough new neurons to replenish the lost neurons."

Gong Chen and his team pioneered a new approach to regenerate functional neurons using glial cells, a group of cells surrounding every single neuron in the brain that provide essential support to neurons. Unlike neurons, glial cells can divide and regenerate themselves, especially after brain injury.

"I believe that turning glial cells that are already present in the brain into new neurons is the best way to replenish the lost neurons," said Gong Chen. "These glial cells are the neighbors of the dead neurons in the brain and are likely to share the same ancestral cellular lineage."

Gong Chen's team previously reported that a single genetic neural factor, NeuroD1, could directly convert glial cells into functional neurons inside mouse brains with Alzheimer's disease, but the total number of neurons generated was limited. The research team believed that this limited regeneration was due to the retroviral system used to deliver NeuroD1 to the brain. In the current study, the research team used the AAV viral system, which is now the first choice for gene therapy in the nervous system, to deliver NeuroD1 into mouse motor cortex that had suffered from stroke.

Many neurons die after stroke but surviving glial cells can proliferate and form a glial scar in the stroke areas. The AAV system was designed to express NeuroD1 preferentially in the glial cells that form these scars, turning them directly into neuronal cells. Such direct glia-to-neuron conversion technology not only increased neuronal density in the stroke areas, but also significantly reduced brain tissue loss caused by the stroke.

Interestingly, the newly converted neurons showed similar neuronal properties to the neurons that were lost after stroke. This suggests a potential impact of the local glial lineage on the converted neuronal identity.

"The most exciting finding of this study is to see the newly converted neurons being fully functional in firing repetitive action potentials and forming synaptic networks with other preexisting neurons," said Gong Chen. "They also send out long-range axonal projections to the right targets and facilitate motor functional recovery."

A separate collaborative work led by Gregory Quirk, professor at the University of Puerto Rico, further tested the NeuroD1-based gene therapy in a rat stroke model. Quirk and colleagues also found that this direct glia-to-neuron conversion technology can rescue cognitive functional deficits induced by stroke.

"Because glial cells are everywhere in the brain and can divide to regenerate themselves, our study provides the proof-of-concept that glial cells in the brain can be tapped as a fountain of youth to regenerate functional new neurons for brain repair not only for stroke but also for many other neurological disorders that result in neuronal loss," said Yuchen Chen. "Our next step is to further test this technology and ultimately to translate it into clinically effective therapies to benefit millions of patients worldwide."

For years, scientists have explored ways to alter the cells of microorganisms in efforts to improve how a wide range of products are made - including medicines, fuels, and even beer. By tapping into the world of metabolic engineering, researchers have also developed techniques to create "smart" bacteria capable of carrying out a multitude of functions that impact processes involved in drug delivery, digestion, and even water decontamination.

But, altering the genetic and regulatory processes that take place within cells presents challenges.

To start, cells are already programmed to carry out their normal, everyday processes with maximum efficiency; any alterations that engineers make to increase a cell's production of a certain substance can, in turn, upset these processes and overburden the cell.

To address this problem, William E. Bentley, a University of Maryland bioengineering professor and director of the university's Robert E. Fischell Institute for Biomedical Devices, is working with a team of researchers to focus on engineering microbial consortia, wherein cell subpopulations are engineered to work together to carry out a desired function. This strategy - which others in the field have also explored - allows engineers to design specialized cells and divvy up the target workload among a group of cells. The tradeoff is that driving a consortium to carry out a specific set of tasks requires engineers to somehow regulate how many of each cell subpopulation are present.

Despite this challenge, few scientific studies have focused on the development of devices or systems that could regulate the compositions of cellular subpopulations within a consortium. Most often, such studies require engineers to rely on manual or user-controlled techniques to strike a balance among cell subpopulations.

As such, Bentley and his team realized that a more powerful approach would be to reengineer the cells themselves to coordinate their subpopulation densities autonomously. Their technique was highlighted in a Nature Communications paper published today.

Like others in the field, Bentley and members of his Biomolecular and Metabolic Engineering Lab previously investigated quorum sensing (QS) - a bacterial form of cell-to-cell communication - to engineer communication circuits amongst and between bacterial strains in order to coordinate their behaviors. QS involves the synthesis of small signaling molecules, called autoinducers (AI), which are secreted by individual bacteria but serve to coordinate their responses. Once the AI level reaches a threshold - signaling a "quorum" of cells - the AI signals are transported intracellularly, where they activate gene expression and enable coordinated responses.

But, Bentley and his team took the research a step further. The group developed the first known platform for autonomous and targeted regulation of consortia composition based on the presence of an environmental cue known as autoinducer-2 (AI-2). AI-2 is considered a universal QS signal, which means it is both recognized and produced by many species of bacteria. It broadly indicates cell population density, and is considered to be an important signal in naturally occurring consortia and microbiomes.

To create an autonomous system, Bentley and his team rewired the bacterial QS systems at play in two strains of E. coli so that the growth rate of communicating cell subpopulations within the consortia would be dictated by signaling between the cells. Their system works like a feedback loop. The first strain senses AI-2 and, in response, yields an output of autoinducer-1 (AI-1). The second E. coli strain, considered the"controller" strain, is engineered to carry out a signal-driven, tunable growth rate of the consortia cells, regulated by none other than the AI-1 produced by the first strain. In this way, the team's system employs its own process of checks and balances between AI-1 and AI-2 that, in turn, regulates the makeup of synthetic consortia.

"Increasingly, consortia of microbes will be tasked with converting raw materials into valuable products," Bentley said. "The raw materials may be wastes or byproducts of industrial processes. The synthetic capabilities of consortia may far surpass those of pure monocultures, so methodologies that help to align consortia will be needed. This could prove especially valuable in situations where processing equipment isn't available, such as in the gastrointestinal (GI) tract."

Two palaeontologists working on the world-renowned Burgess Shale have revealed a new species, called Mollisonia plenovenatrix, which is presented as the oldest chelicerate. This discovery places the origin of this vast group of animals--of over 115,000 species, including horseshoe crabs, scorpions and spiders--to a time more than 500 million years ago. The findings are published in the prestigious journal Nature on September 11, 2019.

Mollisonia plenovenatrix would have been a fierce predator--for its size. As big as a thumb, the creature boasted a pair of large egg-shaped eyes and a "multi-tool head" with long walking legs, as well as numerous pairs of limbs that could all-together sense, grasp, crush and chew. But, most importantly, the new species also had a pair of tiny "pincers" in front of its mouth, called chelicerae. These typical appendages give the name to the group of scorpions and spiders, the chelicerates, which use them to kill, hold, and sometimes cut, their prey.

"Before this discovery, we couldn't pinpoint the chelicerae in other Cambrian fossils, although some of them clearly have chelicerate-like characteristics," says lead author Cédric Aria, a member of the Royal Ontario Museum's Burgess Shale expeditions since 2012, and is presently a post-doctoral fellow at the Nanjing Institute of Geology and Palaeontology (China). "This key feature, this coat of arms of the chelicerates, was still missing."

Other features of this fossil, including back limbs likened to gills, further suggest that Mollisonia was not some "primitive" version of a chelicerate, but that it was in fact already close morphologically to modern species.

"Chelicerates have what we call either book gills or book lungs," explains Aria. "They are respiratory organs are made of many collated thin sheets, like a book. This greatly increases surface area and therefore gas exchange efficiency. Mollisonia had appendages made up with the equivalent of only three of these sheets, which probably evolved from simpler limbs."

The authors believe that Mollisonia preferentially hunted close to the sea floor, thanks to its well-developed walking legs, a type of ecology called benthic predation. Because Mollisonia is so modern-looking, chelicerates seem therefore to have prospered quickly, filling in an ecological niche that was otherwise left poorly attended to by other arthropods at that time. The authors conclude that the origin of the chelicerates must lie even deeper within the Cambrian, when the heart of the "explosion" really took place.

"Evidence is converging towards picturing the Cambrian explosion as even swifter than what we thought," says Aria. "Finding a fossil site like the Burgess Shale at the very beginning of the Cambrian would be like looking into the eye of the cyclone."

The importance of the Burgess Shale and similar deposits, such as the Chengjiang biota in China, lies in their exceptional preservation of the earliest marine animal communities at a time of uniquely rapid diversification of body forms called the "Cambrian explosion." Fossil animals from these sites are notable for preserving an extensive array of morphological features, such as limbs and eyes, but also guts and, much more rarely, nervous system tissues.

Mollisonia was first described more than a century ago by the discoverer of the Burgess Shale, Charles Doolittle Walcott. However, so far, only rare exoskeletons of this animal were known. "It is the first time that evidence of the limbs and other soft-tissues of this type of animal are described, which were key to revealing its affinity," says co-author Jean-Bernard Caron, Richard M. Ivey Curator of Invertebrate Palaeontology at the Royal Ontario Museum (Canada). The exceptionally well-preserved fossils come from a new Burgess Shale sites near Marble Canyon, in Kootenay National Park, British Columbia.

"Marble Canyon is the biggest spotlight of my career so far. This area keeps giving us wonderful treasures year after year," says Caron, who has been leading the Royal Ontario Museum's Burgess Shale expeditions for the past 10 years. "I would not have imagined that we could, in a way, rediscover the Burgess Shale like this, a hundred years later, with all the new species we are finding."

The specimens of Mollisonia plenovenatrix described in this new research are better preserved than the ones found at the original Walcott quarry that is located about 40 kilometers northwest of the Marble Canyon quarry. Many other fossils found at Marble Canyon and surrounding areas have already played a critical role in our understanding of the early evolution of many animal groups. These notably include the vertebrates, our own lineage, thanks to numerous and exceptionally well-preserved specimens of the primitive fish Metaspriggina walcotti. Many new species await to be described; the latest one, a "flying saucer-like" new predatory arthropod with huge rake-like claws called Cambroraster falcatus, was just recently published on July 31, 2019.

The Burgess Shale fossil sites are located within Yoho and Kootenay national parks and are managed by Parks Canada. Parks Canada is proud to work with leading scientific researchers to expand knowledge and understanding of this key period of earth history and to share these sites with the world through award-winning guided hikes. The Burgess Shale was designated a UNESCO World Heritage Site in 1980 due to its outstanding universal value and is now part of the larger Canadian Rocky Mountain Parks World Heritage Site.

Mollisonia will be among the many exceptional fossils from the Burgess Shale planned to be on display in the ROM's future new gallery, The Willner Madge Gallery, Dawn of Life, scheduled to open in 2021.

Published in Nature today, scientists have shown how this hourglass-like feature, which dwarfs all other radio structures in the Galactic Centre, is likely the result of a phenomenally energetic burst that erupted near the Milky Way's supermassive black hole a few million years ago.

Using the South African Radio Astronomy Observatory (SARAO) MeerKAT telescope, Ian Heywood of the University of Oxford's Department of Physics and his colleagues mapped out broad regions in the centre of the galaxy, conducting observations at wavelengths near 23 centimetres. Radio emission of this kind is generated in a process known as synchrotron radiation, in which free-floating electrons are accelerated as they interact with powerful magnetic fields. This produces a characteristic radio signal that can be used to trace energetic regions in space. The radio light seen by MeerKAT penetrates the dense clouds of dust that block visible light from the centre of the galaxy.

Lead author Dr. Heywood, who processed the large amount of observational data which led to this result, said: 'The centre of our galaxy is relatively calm when compared to other galaxies with very active central black holes. Even so, the Milky Way's central black hole can become uncharacteristically active, flaring up as it periodically devours massive clumps of dust and gas. It's possible that one such feeding frenzy triggered powerful outbursts that inflated this previously unseen feature.'

By examining the nearly identical extent and morphology of the twin bubbles, the scientists believe they have found convincing evidence that these features were formed from a violent eruption that over a short period of time punched through the interstellar medium in opposite directions.

MeerKAT has unprecedented sensitivity and imaging capabilities which, coupled with its geographic vantage point for observing the Galactic centre, has resulted in the clearest ever image of the radio waves emanating from the centre of the Milky Way, a part of the sky that is notoriously difficult to image at such wavelengths.

These new observational capabilities are unlocking a "fossil record" which allows scientists to piece together the history of the Galactic centre and the supermassive black hole that lurks there. Although the structure is likely to be a few million years old it is still possible to observe it, and from there scientists can infer from where it came.

Head of Astrophysics at the University of Oxford, Professor Steve Balbus, said: 'It is extremely exciting to be able to peer at the centre of the Galaxy with such high definition and precision. This is the nearest supermassive black hole to us in the Universe, and MeerKAT has provided us with front row centre seats. We are going to learn an enormous amount about how black holes feed themselves and how they influence their environments. In the relatively brief time that MeerKAT has been up and running, the science that the team at Oxford has already produced has been transformational. Oxford can be rightly proud of their leadership involvement with the MeerKAT Project, and I personally can't wait to see what more there is to come - this is only the beginning of a new era in radio astronomy.'

Co-author, William Cotton, from the National Radio Astronomy Observatory in Charlottesville, Virginia, said: 'The shape and symmetry of what we have observed strongly suggests that a staggeringly powerful event happened a few million years ago very near our galaxy's central black hole. This eruption was possibly triggered by vast amounts of interstellar gas falling in on the black hole, or a massive burst of star formation which sent shockwaves careening through the galactic centre. In effect, this inflated energetic bubbles in the hot, ionized gas near the galactic centre, energizing it and generating radio waves which we could eventually detect here on Earth.'

The event, reported today in Nature, could also be the origin of the population of electrons that are required to power the radio emission from mysterious magnetised filaments. These thread-like structures have been seen nowhere but in the Galactic centre, and there has been no definitive explanation for their origin since they were first discovered 35 years ago. "Almost all of the more than one hundred filaments are confined by the radio bubbles," said co-author Prof. Farhad Yusef-Zadeh of Northwestern University in Evanston, Illinois.

Co-author Fernando Camilo of SARAO in Cape Town, said: 'These enormous bubbles have until now been hidden by the glare of extremely bright radio emission from the centre of the galaxy. Teasing out the bubbles from the background 'noise' was a technical tour de force, only made possible by MeerKAT's unique characteristics and propitious location in the Southern hemisphere. With this unexpected discovery we're witnessing in the Milky Way a novel manifestation of galaxy-scale outflows of matter and energy, ultimately governed by the central black hole.'

Today's result cements the great "discovery machine" potential of the new generation of radio telescopes as we move towards the construction of the Square Kilometre Array.

What The Study Did: Hidradenitis suppurativa is a painful skin condition where lumps form under the skin. This observational study examined the risk of new long-term opioid use among patients with the condition who hadn't previously used opioids.

Authors: Amit Garg, M.D., of the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in New Hyde Park, New York, is the corresponding author.

(doi:10.1001/jamadermatol.2019.2610)

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

A bio-inspired bot uses water from the environment to create a gas and launch itself from the water's surface.

The robot, which can travel 26 metres through the air after take-off, could be used to collect water samples in hazardous and cluttered environments, such as during flooding or when monitoring ocean pollution.

Robots that can transition from water to air are desirable in these situations, but the launch requires a lot of power, which has been difficult to achieve in small robots.

Now, researchers at Imperial College London have invented a system that requires just 0.2 grams of calcium carbide powder in a combustion chamber. The only moving part is a small pump that brings in water from the environment the robot is sat in, such as a lake or ocean.

The water and the calcium-carbide powder then combine in a reaction chamber, producing a burnable acetylene gas. As the gas ignites and expands, it pushes the water out as a jet, which propels the robot clear of the water and into a glide of up to 26 metres.

The details of the robot are published today in Science Robotics.

Lead researcher Dr Mirko Kovac, Director of the Aerial Robotics Laboratory at Imperial, said: "Water-to-air transition is a power-intensive process, which is difficult to achieve on a small-scale flying vehicle that needs to be lightweight for flight.

"We have used water-reactive chemicals to reduce the materials that the robot needs to carry. Since the chamber fills passively and the environmental water acts as a piston, we can create a full combustion cycle with only one moving part, which is the pump that mixes the water with the fuel."

The team tested the robot in a lab, in a lake, and in a wave tank, showing that it can escape from the water's surface even under relatively rough conditions. While similar robots often require calm conditions to leap from the water, the team's invention generates a force 25 times the robot's weight, giving it a greater chance of overcoming the waves.

The robot, which weighs just 160 grams, can 'jump' multiple times after refilling its water tank. This could allow it to float on water and take samples at multiple points without additional power, saving energy over longer distances compared to an electrically powered robot.

The team are now working with the Swiss Federal Laboratories for Materials Science and Technology (Empa) to build new vehicles using advanced materials and begin field trials of the robot in a range of environments, including monitoring the oceans around coral reefs and offshore energy platforms.

Raphael Zufferey, first author on the paper said: "These kinds of low-power, tether-free robots could be really useful in environments that are normally time- and resource-intensive to monitor, including after disasters such as floods or nuclear accidents."

An international team of astronomers has discovered one of the largest features ever observed in the center of the Milky Way - a pair of enormous radio-emitting bubbles that tower hundreds of light-years above and below the central region of our galaxy.

This hourglass-like feature, which dwarfs all other radio structures in the galactic center, is likely the result of a phenomenally energetic burst that erupted near the Milky Way's supermassive black hole a few million years ago.

"The center of our galaxy is relatively calm when compared to other galaxies with very active central black holes," said Ian Heywood of the University of Oxford and lead author of an article appearing in the journal Nature. "Even so, the Milky Way's central black hole can - from time to time - become uncharacteristically active, flaring up as it periodically devours massive clumps of dust and gas. It's possible that one such feeding frenzy triggered powerful outbursts that inflated this previously unseen feature."

Using the South African Radio Astronomy Observatory (SARAO) MeerKAT telescope, Heywood and his colleagues mapped out broad regions in the center of the galaxy, conducting observations at wavelengths near 23 centimeters. Radio emission of this kind is generated in a process known as synchrotron radiation, in which electrons moving at close to the speed of light interact with powerful magnetic fields. This produces a characteristic radio signal that can be used to trace energetic regions in space. This radio light easily penetrates the dense clouds of dust that block visible light from the center of the galaxy.

By examining the nearly identical size and shape of the twin bubbles, the researchers think they have found convincing evidence that these features were formed from a violent eruption that over a short period of time punched through the interstellar medium in opposite directions.

"The shape and symmetry of what we have observed strongly suggests that a staggeringly powerful event happened a few million years ago very near our galaxy's central black hole," said William Cotton, an astronomer with the National Radio Astronomy Observatory in Charlottesville, Virginia, and co-author on the paper. "This eruption was possibly triggered by vast amounts of interstellar gas falling in on the black hole, or a massive burst of star formation which sent shockwaves careening through the galactic center. In effect, this inflated bubbles in the hot, ionized gas near the galactic center, energizing it and generating radio waves that we could eventually detect here on Earth."

The environment surrounding the black hole at the center of our galaxy is vastly different than the environment elsewhere in the Milky Way, and is a region of many mysteries. Among those are very long and narrow filaments found nowhere else, the origin of which has remained an unsolved puzzle since their discovery 35 years ago. The filaments appear as radio structures tens of light-years long and approximately a light-year wide.

"The radio bubbles discovered by MeerKAT now shed light on the origin of the filaments," said Farhad Yusef-Zadeh at Northwestern University in Evanston, Illinois, and a co-author on the paper. "Almost all of the more than one hundred filaments are confined by the radio bubbles."

The authors suggest that the close association of the filaments with the bubbles implies that the energetic event that created the radio bubbles is also responsible for accelerating the electrons required to produce the radio emission from the magnetized filaments.

"These enormous bubbles have until now been hidden by the glare of extremely bright radio emission from the center of the galaxy," said Fernando Camilo of SARAO in Cape Town, and co-author on the paper. "Teasing out the bubbles from the background noise was a technical tour de force, only made possible by MeerKAT's unique characteristics and ideal location," according to Camilo. "With this unexpected discovery we're witnessing in the Milky Way a novel manifestation of galaxy-scale outflows of matter and energy, ultimately governed by the central black hole."

According to the researchers, the discovery of these bubbles relatively nearby in the center of our home galaxy brings us one step closer to understanding spectacular activities that occur in more distant cousins of the Milky Way throughout the universe.

Using computational tools to investigate gene transcription networks in large collections of brain tissues, a scientific team has identified a gene that acts as a master regulator of schizophrenia during early human brain development. The findings may lay the groundwork for future treatments for the highly complex neuropsychiatric disorder.

"Because hundreds, or even thousands, of genes may contribute to the risk of schizophrenia, it is crucial to understand which are the most important ones, orchestrating core networks in the disease," said study leader Kai Wang, PhD, of the Department of Pathology and Laboratory Medicine and the Raymond G. Perelman Center for Cellular and Molecular Therapeutics (CCMT) at Children's Hospital of Philadelphia (CHOP). "Pinpointing master regulators may help guide us toward priority targets for novel treatments in the future."

The study appeared online today in Science Advances. Wang co-led the research with Jubao Duan, PhD, the Charles R. Walgreen Research Chair and an associate professor at the Center for Psychiatric Genetics of North Shore University HealthSystem (NorthShore) and the University of Chicago, Evanston, Ill. The first author was Abolfazi Doostparast Torshizi, PhD, of the CCMT at CHOP.

Although schizophrenia affects about 1 in 100 adults, and is highly heritable, the genetic architecture of the neuropsychiatric disorder is notoriously complex, with many unsolved questions. Wang and colleagues contrast the current state of knowledge to recent advances in cancer research. Oncology researchers have identified many gene pathways and networks that when perturbed, result in specific types of cancer. That knowledge has permitted fine distinctions in diagnosing subsets among types of cancer, and has led to individualized treatments based on a patient's genetic profile.

The underlying genomic biology in neuropsychiatric disorders is likely more challenging. In the most extreme case, researchers have recently proposed an "omnigenic" model, in which nearly all the genes in a disease-relevant cell type contribute to a specific neuropsychiatric disorder, but Wang points out, "Not all the genes carry equal weight--the problem is to determine which are more important than others."

Thus, the study team used computational systems biology approaches to discern a disease-relevant core pathway in schizophrenia and to discover a master regulator in that pathway that affects hundreds of downstream genes.

Wang and colleagues analyzed two independent datasets of biological samples from schizophrenia patients and control subjects. One dataset, the CommonMind Consortium (CMC), is a public-private partnership with well-curated brain collections. The other was a collection of primary cultured neuronal cells derived from olfactory epithelium (CNON), generated by study co-authors at the University of Southern California and SUNY Downstate. The CMC dataset contained adult postmortem brain tissue, while the CNON dataset, used to validate findings from the CMC study, represented cell cultures that contain neuronal cells from nasal biopsies. Applying an algorithm developed at Columbia University to reconstruct gene transcription networks, the study team identified the gene TCF4 as a master regulator for schizophrenia.

Previous genome-wide association studies (GWAS) had indicated that TCF4 was a locus for schizophrenia risk, said Wang, but little was known of the gene's functional effects. The study team investigated those effects by knocking down, or decreasing, the gene's expression in neural progenitor cells and glutamatergic neurons derived from induced pluripotent stem cells in Duan's lab at NorthShore.

Observations on three different cell lines showed that, when knocked down, the predicted TCF4 regulatory networks were enriched for genes showing transcriptomic changes, as well as for genes involved in neuronal activity, schizophrenia risk genes having genome-wide significance, and schizophrenia-associated de novo mutations. Although some of the cellular effects of TCF4 dysregulation were previously shown in mice, Duan noted that the results from perturbing TCF4 gene networks in human stem cell models may be more relevant to the neurodevelopmental aspects of neuropsychiatric disorders.

The current study, said the researchers, sets the stage for further investigations. One direction, said Wang, is to use expanded datasets to explore whether other master regulators in addition to TCF4 may act in schizophrenia. If so, it may eventually be possible to classify patients with schizophrenia into subgroups more responsive to specific treatments, as is occurring in many cancers, to assist in implementing precision medicine in psychiatric diseases.

Other approaches, added Doostparast, may involve pursuing functional genomics at the level of single cells, to assess the cell types that are most influenced by dysregulating gene expression.

The study represents one of the first successful examples of combining computational approaches and stem cell-based experimental models to disentangle complex gene networks in psychiatric diseases.

Wang noted limitations in the study. The empirical validation focused on neural progenitor cells and glutamatergic neurons, but other cell types may be investigated in the future, such as interneurons and microglia, which have also been implicated in the development of schizophrenia.

Space agencies must invest more resources on field geology training of astronauts to take full advantage of scientific opportunities on the Moon and other planetary bodies, Kip Hodges and Harrison Schmitt urge, in an Editorial. The Moon represents a pristine archive of the early history of the Solar System, making it an ideal research target for scientists seeking a window into planetary formation. Key to the success of these efforts will be careful field geology prior to sample collection. Here, Hodges and Schmitt discuss whether space agencies are fully prepared to study these surfaces on future voyages to the Moon and Mars. They argue that conducting effective geological research on other planets will require extensive training, meaning that astronaut programs should place a stronger emphasis on field geology training of all astronauts and should include geologists with advanced degrees in mission crews. Furthermore, space agencies should develop aggressive research programs to develop new science operations strategies that integrate new technologies (e.g., augmented reality) to enable better field research. The authors recommend that both educational and research activities in this vein should involve scientists and engineers from academia as well as from the space agencies. Taking such steps will optimize the scientific productivity of missions to the Moon, Mars and beyond.