Culture

EVANSTON, Ill. --- A Northwestern University evaluation of a procedural justice training program involving more than 8,000 Chicago Police Department (CPD) officers shows it reduced complaints filed against police by approximately 10%. It also reduced use of force by 6% in the two years following officers' training.

"The CPD is undergoing significant reform on multiple fronts, through a consent decree, including new top leadership and now a response to an unprecedented health epidemic," said Andrew Papachristos, co-author of the study and a professor of sociology in the Weinberg College of Arts and Sciences at Northwestern. "Fundamental to such reforms is repairing trust with the larger community. Reducing force and misconduct in a way that is fair and transparent by adopting procedural justice strategies is one key way to repair trust."

Papachristos is also a faculty fellow in the University's Institute for Policy Research (IPR).

The study by IPR postdoctoral fellow George Wood, along with Tom Tyler of Yale University and Papachristos, shows that this approach to police training, which typically only takes one day, can reduce complaints and improve community relations.

"It's particularly notable that these reductions were achieved through a training program, which was scaled up to include a sizable majority of the officers within the CPD," Wood said.

The procedural justice model emphasizes transparency and responding to community concerns, as well as police treating citizens in encounters with dignity, courtesy and respect. Such training is one of the strategies recommended by President Obama's 2015 Task Force on 21st-Century Policing, which argues for transparency and efforts by officers to build popular legitimacy with civilians instead of harsher "command-and-control" police techniques.

The CPD officers who took part in the training also received fewer sustained complaints, or complaints that were found valid, and had fewer complaints that resulted in a settlement payout by the city. The researchers' estimates suggest 500 fewer incidents of use of force by trained officers between 2011 and 2016.

These results indicate that procedural justice training can reduce both police use of force and complaints related to police misconduct. The researchers tracked use of force over a five-year period by using official forms that must be filled out by an officer when engaging in certain actions, ranging from a wristlock to discharging a firearm. They tracked complaints using CPD administrative records.

The findings reveal that training police in how to adopt procedural justice principles is a promising strategy for reducing use of force and complaints against officers and can be successfully used in other communities.

"By reducing force and hostility, this type of training might help the process of rebuilding trust between police and civilians -- and because the training is relatively short and can be staggered over time, it will not be a major disruption of policing activities," Wood said.

The methodology used the phased roll-out of training in which officers were trained at different times over a four-year period between January 2012 and March 2016. This roll-out meant that, within a given time period, the researchers could compare trained officers to officers who had not yet undergone training. In the same model, they also compared officers after training to their own behavior before training.

The researchers also observe that procedural justice training significantly changes how officers behave in the field, and the impact of such training lasts for at least two years. They note that its effect could be even greater as officers trained in procedural justice share their knowledge throughout their departments. When officers are trained in such tactics, they behave in ways that are proven to promote public trust, compliance and cooperation between police and citizens.

According to the researchers, such training efforts could not only change police behavior on the streets, but reform how entire departments operate. That could be a major factor in reducing misconduct and the undue use of force.

"Procedural justice training reduces police use of force and complaints against officers," publishes April 20 in the journal Proceedings of the National Academy of Sciences (PNAS).

The Northwestern Neighborhood and Network Institute (N3), directed by Papachristos and where Wood is a postdoctoral fellow, has been researching the causes and consequences of police misconduct and use of force. N3 is also involved in the ongoing evaluation of a new Neighborhood Policing Initiative aimed at improving police-civilian relationships through new methods of community-focused policing practices.

NEW YORK -- Cannabis use makes young brains more sensitive to the first exposure to cocaine, according to a new study on rodents led by scientists at Columbia University and the University of Cagliari in Italy. By monitoring the brains of both adolescent and adult rats after giving them synthetic psychoactive cannabinoids followed by cocaine, the research team identified key molecular and epigenetic changes that occurred in the brains of adolescents -- but not adults. This discovery reveals a new interplay between the two drugs that had never previously been directly observed in biological detail.

These findings, reported this week in the Proceedings of the National Academy of Sciences, provide new understanding of how the abuse of cannabis during teenage years may enhance the first experience with cocaine and lead to continued use among vulnerable individuals.

"We know from human epidemiological studies that individuals who abuse cocaine have a history of early cannabis use, and that a person's initial response to a drug can have a large impact on whether they continue to use it. But many questions remain on how early cannabis exposure affects the brain," said epidemiologist Denise Kandel, PhD, who is a professor of Sociomedical Sciences in Psychiatry at Columbia's Vagelos College of Physicians and Surgeons and co-senior author of today's paper.

"Our study in rats is the first to map the detailed molecular and epigenetic mechanisms by which cocaine interacts with brains already exposed to cannabinoids, providing much-needed clarity to the biological mechanisms that may increase the risk for drug abuse and addiction," added co-author and Nobel laureate Eric Kandel, MD, codirector of Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and Senior Investigator of the Howard Hughes Medical Institute.

Previous research had revealed key differences in how cannabis and cocaine affect brain chemistry. "Studies on the addictive properties of cocaine have traditionally focused on the mesolimbic dopaminergic pathway, a brain system that underlies our motivation to pursue pleasurable experiences," said Philippe Melas, PhD, who was an associate research scientist in Eric Kandel's lab at Columbia's Zuckerman Institute and is the paper's co-senior author. "While cannabis enhances mesolimbic dopaminergic activity similarly to cocaine, it also affects an entirely different neurochemical system that is widespread in the brain called the endocannabinoid system. This system is essential for brain development -- a process that is still ongoing in adolescence."

Besides the dopaminergic system, both cannabis and cocaine appear to share some additional features. Recent studies have suggested that the development of cocaine craving is dependent on the brain's glutamatergic system. This system uses glutamate, a brain molecule that acts as a synaptic transmitter in the brain, enhancing the transmission of signals between the brain's neurons. According to previous research, as well as findings presented in today's new study, using cannabis during adolescence may also affect this glutamatergic signaling process.

To delve deeper into a potential link between the two drugs, Dr. Melas and the husband-and-wife team of Drs. Eric and Denise Kandel partnered with Paola Fadda, PhD, Maria Scherma, PhD, and Walter Fratta, PhD, researchers in the Department of Biomedical Sciences, at the University of Cagliari in Italy. The group examined the behavioral, molecular and epigenetic changes that occur when both adolescent and adult rats are first exposed to WIN, a synthetic cannabinoid with psychoactive properties similar to those of THC found in cannabis, and then are subsequently exposed to cocaine.

"We found that adolescent rats that had been pre-exposed to WIN had an enhanced reaction to their initial exposure to cocaine. Notably, we observed this effect in adolescent but not in adult rats," said Dr. Melas, who is now a junior researcher in the Department of Clinical Neuroscience at the Karolinska Institutet in Sweden.

Upon further examination, the team found that, when preceded by a history of psychoactive cannabinoid use in adolescence, exposure to cocaine sets off a battery of unique molecular reactions in the rat brain. These reactions included not only changes in the aforementioned glutamate receptors but also key epigenetic modifications. Epigenetic modifications are distinct, in that they affect the way genes are switched on or off but do not affect the sequence of the genes themselves.

The Columbia team had previously found similar epigenetic mechanisms in adult animals in response to nicotine and alcohol in the brain's reward center, known as the nucleus accumbens. In the present study, however, the epigenetic effects of cannabinoids were found to be specific to adolescents and to target the brain's prefrontal cortex. The prefrontal cortex, which plays a role in various executive functions, including long-term planning and self-control, is one of the last regions of the brain to reach maturity, a fact that has long been linked to adolescents' propensity for risky behavior.

Moreover, aberrant prefrontal cortex activity is often observed in patients suffering from addiction. Efforts to enhance the function of the prefrontal cortex are currently being evaluated in the treatment of addiction through the use of brain stimulation and other methodologies.

"Our findings suggest that exposure to psychoactive cannabinoids during adolescence primes the animals' prefrontal cortex, so that it responds differently to cocaine compared to animals who had been given cocaine without having previously experienced cannabis," said Dr. Melas.

These results in rats offer important clues to the biological mechanisms that may underlie the way that different classes of drugs can reinforce each other in humans. The results also support the notion that cannabis abuse during adolescence can enhance a person's initial positive experience with a different drug, such as cocaine, which in turn can have an effect on whether that person chooses to continue, or expand, their initial use of cocaine.

"This study suggests that teenagers who use cannabis may have a favorable initial reaction to cocaine, which will increase their likelihood of engaging in its repeated use so that they eventually become addicted, especially if they carry additional environmental or genetic vulnerabilities," said Dr. Denise Kandel.

Most research involving rodents and addiction has traditionally focused on adult animals. It has also largely been limited to studying one substance of abuse at a time, without taking into consideration a history of drug exposure in adolescence.

"These and other experiments are key to understanding the molecular changes to the brain that occur during drug use," said Dr. Eric Kandel, who is also University Professor and Kavli Professor of Brain Science at Columbia. "This knowledge will be crucial for developing effective treatments that curb addiction by targeting the disease's underlying mechanisms."

HOUSTON - (April 20, 2020) - If you're on skis, you want to avoid avalanches. But when the right kind happen in your brain, you shouldn't worry. You won't feel them. They're probably to your benefit.

Scientists at Rice University's Center for Theoretical Biological Physics (CTBP) have simulated the mechanics of a complex network that helps give neurons their ever-changing structures. They found the complex, Arp2/3, may be largely responsible for the "avalanches" observed in the cells' cytoskeletal networks.

The finding, published in the Proceedings of the National Academy of Sciences, provides another clue to how the brain forms and retains memories. It follows a study last year that detailed the interactions that allow neurons to accept the electrical signals that remodel their structures. An earlier study suggested actin filaments that control the shape of neurons may be the key to the formation and storage of long-term memories.

The new study led by Rice biophysicist Peter Wolynes, University of Houston physicist Margaret Cheung and Northeastern University biophysicist Herbert Levine suggests cytoskeletal avalanches within the neurons' dendritic spines may be one way they retain new information.

Much about the cytoskeleton in every cell remains a mystery, but neurons are particularly interesting to the research team that studies how they acquire information and store it for later use. Lego-like actin proteins assemble to form these spidery filaments that allow motor proteins to carry nutrients and other cargoes across cells. They also give cells the ability to move and divide.

Sometimes, these filaments form branched actomyosin networks that have been observed to collapse. The simulations revealed the presence of Arp2/3 is key to nucleating branched actin networks that occasionally convulse and release strain in the network. (Arp stands for actin-related protein.)

When Arp2/3 was present, the simulations showed branched networks tended to relax significantly more slowly than unbranched networks do.

"There's an analogy I use," Wolynes said. "With memory, you have to have something that changes, then it has to remain relatively permanent, but then perhaps be able to change again.

"Suppose you have a pillow made up of a random array of feathers," he said. "They're basically rods, similar to the branched structure of actin. If you put your head on the pillow, you crush it down, and when you get up later it still has that same crushed shape. Another time, it could have a different shape. So it has memory."

Actin networks retain memory in somewhat the same way, Wolynes said. "Like your pillow, the rods in the network reconfigure when you put stress on them, in this case, an electrochemical signal input. When signaled, they undergo a series of avalanches that change the shape of the dendritic spine."

"These are also similar to earthquakes in a sense," Levine added. "In an earthquake, the ground is static for a long time and then you have a dramatic event that reconfigures things. This new configuration lasts for a long time.

"The novelty of what's being done here is that we're not just focusing on individual molecules, as we've often done in the past," he said. "We're figuring out how individual molecules and their properties can modulate structures at larger length scales."

The models showed branched actomyosin networks do not destabilize at specific concentrations, but that the avalanches depend on the initial configuration of the network as well as the history of past avalanches.

"Like your pillow, how flexible the network is depends on how often it has been compressed in the past," Wolynes said.

Cheung, whose lab continues to run three-dimensional MEDYAN models that combine mechanics and chemistry to study actomyosin dynamics, said many additional proteins are involved and are being studied by the team in order to understand memory.

The team hopes to tie its new findings to the earlier study led by Wolynes on how actin filaments exert force to stabilize long-term memories in prionlike fibers.

"One of the ways in which memory becomes more lasting is to change the global shape of the dendritic spine," Levine said. "That's not currently in our modeling framework, and it will be an extensive effort to get it to work, but I'm interested in how to extend these models to calculate how the shapes change."

Rice graduate student James Liman is lead author of the paper. Co-authors are Rice graduate student Carlos Bueno, University of Houston graduate student Yossi Eliaz, Rice academic visitor Nicholas Schafer and Neal Waxham, the William M. Wheless III Professor in Biomedical Sciences and a professor of neurobiology and anatomy at the University of Texas Health Science Center at Houston's McGovern Medical School.

April 20, 2020 -- Gender-based violence has been shown to increase during global emergencies. In a paper just published by Columbia University Mailman School of Public Health, researchers report that according to early evidence it is the same for the COVID-19 pandemic. The findings are online in the journal Bioethics.

Early results from China suggest that domestic violence has dramatically increased. For example, a police station in China's Hubei Province recorded a tripling of domestic violence reports in February 2020 during the COVID?19 quarantine. Other reports suggest that police have been reluctant to intervene and detain perpetrators due to COVID?19 outbreaks in prisons.

"Gender norms and roles relegating women to the realm of care work puts them on the frontlines in times of crisis, resulting in greater risk of exposure while excluding them from developing the response," said Terry McGovern, chair of the Heilbrunn Department of Population and Family Health at Columbia Mailman School, director of the Program on Global Health Justice and Governance, and senior author of the study.

For example:

Globally women perform three?quarters of unpaid care work, including household disease prevention and care for sick relatives, and there is not a country in the world where men provide an equal share of unpaid care work.

in China's Hubei province 90% of frontline healthcare workers are women as in many other parts of the world.

However, the researchers make the point that it is not too late to include the voices of women in tackling COVID-19:

Governments can incorporate gender considerations into their response.

Technology can be leveraged to ensure women continue to receive essential services when they need them most. For example, emergency services and victim support can be maintained via text, phone, and online services.

Telemedicine should be considered an alternative and secure way to provide women and girls access to contraceptives and abortion medication.

"Recognizing, valuing, supporting women's roles and giving them a voice in global health governance can go a long way in avoiding unintended consequences, building resilient healthcare systems, and reducing intersectional inequalities and vulnerabilities across gender, race, class and geography," noted Neetu John, first author and assistant professor in Columbia Mailman School's Heilbrunn Department of Population and Family Health, and the co-authors.

An exploratory randomized, controlled study on the safety and efficacy of either lopinavir/ritonavir (LPV/r) or Arbidol--antivirals that are used in some countries against HIV-1 and to treat influenza , respectively--as treatments for COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, suggests that neither drug improves the clinical outcome of patients hospitalized with mild-to-moderate cases of the disease over supportive care. The findings appeared April 17 in Med, a new medical journal published by Cell Press.

"We found that neither lopinavir/ritonavir nor Arbidol could benefit clinical outcomes for patients and that they might bring some side effects," says co-senior author Linghua Li, Vice Director of the Centre for Infectious Diseases of Guangzhou Eighth People's Hospital in Guangzhou, China. "And although the sample size is small, we believe it could still provide meaningful suggestions for proper application of LPV/r or Arbidol for COVID-19."

The researchers chose to study LPV/r and Arbidol because the antivirals had been selected as candidates for treating COVID-19 in a guidance issued on February 19, 2020, by the National Health Commission of China, based on in vitro cell tests and previous clinical data from SARS and MERS. Other researchers had already found that LPV/r did not improve outcomes for patients with severe COVID-19. "It is important to know if lopinavir/ritonavir is effective for mild/moderate cases with COVID-19," Li says. "If it is, the medicine could prevent mild/moderate cases from deteriorating to severe status and help reduce the mortality rate."

The study assessed 86 patients with mild-to-moderate COVID-19, with 34 randomly assigned to receive LPV/r, 35 to Arbidol, and 17 with no antiviral medication as a control. All three groups showed similar outcomes at 7 and 14 days, with no differences between groups in the rates of fever reduction, cough alleviation, or improvement of chest CT scan. Patients in both drug groups experienced adverse events such as diarrhea, nausea, and loss of appetite during the follow-up period, while no apparent adverse event occurred in the control group.

"Our findings suggest that we need to cautiously consider before using these drugs," Li says. "Researchers need to keep working to find a really effective antiviral regimen against COVID-19, but meanwhile, any conclusions about antiviral regimens need strict and scientific clinical trials and appropriate caution. The general public, however, shouldn't panic just because currently there's no specific antiviral medicine currently. Quarantine and good personal health protection could help us prevent people from getting infected with COVID-19, and even in case of infection, the present comprehensive treatment can still enable the vast majority of patients to return to health."

New Rochelle, NY, April 20, 2020--A new study analyzing tweets about COVID-19 found that users with larger social networks tend to use fewer uncivil remarks when they have more positive responses from others. The study, which used computer-assisted content analysis, is published in Cyberpsychology, Behavior, and Social Networking, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Cyberpsychology, Behavior, and Social Networking website.

Bumsoo Kim, PhD, The Hebrew University of Jerusalem (Israel), is the author of "Effects of Social Grooming on Incivility in COVID-19." Dr. Kim defines social grooming as building strong social ties through informational exchange and emotional support. He concluded that social network size is a negative predictor of incivility. Furthermore, the linguistic choices that a user makes also differs depending on the size of their social network.

"In a time of isolation and collective trauma, social media allows for an immediate sharing of intense emotions. Prosocial behavior and positive affect may help to promote societal resilience," says Editor-in-Chief Brenda K. Wiederhold, PhD, MBA, BCB, BCN, Interactive Media Institute, San Diego, California and Virtual Reality Medical Institute, Brussels, Belgium.

Now you see it, now you don't.

What astronomers thought was a planet beyond our solar system has now seemingly vanished from sight. Though this happens in science fiction, such as Superman's home planet Krypton exploding, astronomers are looking for a plausible explanation.

One interpretation is that, rather than being a full-sized planetary object, which was first photographed in 2004, it could instead be a vast, expanding cloud of dust produced in a collision between two large bodies orbiting the bright nearby star Fomalhaut. Potential follow-up observations might confirm this extraordinary conclusion.

"These collisions are exceedingly rare and so this is a big deal that we actually get to see one," said András Gáspár of the University of Arizona, Tucson. "We believe that we were at the right place at the right time to have witnessed such an unlikely event with NASA's Hubble Space Telescope."

"The Fomalhaut system is the ultimate test lab for all of our ideas about how exoplanets and star systems evolve," added George Rieke of the University of Arizona's Steward Observatory. "We do have evidence of such collisions in other systems, but none of this magnitude has been observed in our solar system. This is a blueprint of how planets destroy each other."

The object, called Fomalhaut b, was first announced in 2008, based on data taken in 2004 and 2006. It was clearly visible in several years of Hubble observations that revealed it was a moving dot. Until then, evidence for exoplanets had mostly been inferred through indirect detection methods, such as subtle back-and-forth stellar wobbles, and shadows from planets passing in front of their stars.

Unlike other directly imaged exoplanets, however, nagging puzzles arose with Fomalhaut b early on. The object was unusually bright in visible light, but did not have any detectable infrared heat signature. Astronomers conjectured that the added brightness came from a huge shell or ring of dust encircling the planet that may possibly have been collision-related. The orbit of Fomalhaut b also appeared unusual, possibly very eccentric.

"Our study, which analyzed all available archival Hubble data on Fomalhaut revealed several characteristics that together paint a picture that the planet-sized object may never have existed in the first place," said Gáspár.

The team emphasizes that the final nail in the coffin came when their data analysis of Hubble images taken in 2014 showed the object had vanished, to their disbelief. Adding to the mystery, earlier images showed the object to continuously fade over time, they say. "Clearly, Fomalhaut b was doing things a bona fide planet should not be doing," said Gáspár.

The interpretation is that Fomalhaut b is slowly expanding from the smashup that blasted a dissipating dust cloud into space. Taking into account all available data, Gáspár and Rieke think the collision occurred not too long prior to the first observations taken in 2004. By now the debris cloud, consisting of dust particles around 1 micron (1/50th the diameter of a human hair), is below Hubble's detection limit. The dust cloud is estimated to have expanded by now to a size larger than the orbit of Earth around our Sun.

Equally confounding is that the team reports that the object is more likely on an escape path, rather than on an elliptical orbit, as expected for planets. This is based on the researchers adding later observations to the trajectory plots from earlier data. "A recently created massive dust cloud, experiencing considerable radiative forces from the central star Fomalhaut, would be placed on such a trajectory," said Gáspár. "Our model is naturally able to explain all independent observable parameters of the system: its expansion rate, its fading, and its trajectory."

Because Fomalhaut b is presently inside a vast ring of icy debris encircling the star, colliding bodies would likely be a mixture of ice and dust, like the comets that exist in the Kuiper belt on the outer fringe of our solar system. Gáspár and Rieke estimate that each of these comet-like bodies measured about 125 miles (200 kilometers) across (roughly half the size of the asteroid Vesta).

According to the authors, their model explains all the observed characteristics of Fomalhaut b. Sophisticated dust dynamical modeling done on a cluster of computers at the University of Arizona shows that such a model is able to fit quantitatively all the observations. According to the author's calculations, the Fomalhaut system, located about 25 light-years from Earth, may experience one of these events only every 200,000 years.

Gáspár and Rieke -- along with other members of an extended team -- will also be observing the Fomalhaut system with NASA's upcoming James Webb Space Telescope in its first year of science operations. The team will be directly imaging the inner warm regions of the system, spatially resolving for the first time the elusive asteroid-belt component of an extrasolar planetary system. The team will also search for bona fide planets orbiting Fomalhaut that might be gravitationally sculpting the outer disk. They will also analyze the chemical composition of the disk.

What astronomers thought was a planet beyond our solar system, has now seemingly vanished from sight. Astronomers now suggest that a full-grown planet never existed in the first place. The NASA/ESA Hubble Space Telescope had instead observed an expanding cloud of very fine dust particles caused by a titanic collision between two icy asteroid-sized bodies orbiting the bright star Fomalhaut, about 25 light-years from Earth.

"The Fomalhaut system is the ultimate test lab for all of our ideas about how exoplanets and star systems evolve," said George Rieke of the University of Arizona's Steward Observatory. "We do have evidence of such collisions in other systems, but none of this magnitude has ever been observed. This is a blueprint for how planets destroy each other."

The object was previously believed to be a planet, called Fomalhaut b, and was first announced in 2008 based on data taken in 2004 and 2006. It was clearly visible in several years of Hubble observations that revealed it as a moving dot. Unlike other directly imaged exoplanets, nagging puzzles with Fomalhaut b arose early on. The object was unusually bright in visible light, but did not have any detectable infrared heat signature. Astronomers proposed that the added brightness came from a huge shell or ring of dust encircling the object that may have been collision-related. Also, early Hubble observations suggested the object might not be following an elliptical orbit, as planets usually do.

"These collisions are exceedingly rare and so this is a big deal that we actually get to see one," said András Gáspár of the University of Arizona. "We believe that we were at the right place at the right time to have witnessed such an unlikely event with the Hubble Space Telescope."

"Our study, which analysed all available archival Hubble data on Fomalhaut b, including the most recent images taken by Hubble, revealed several characteristics that together paint a picture that the planet-sized object may never have existed in the first place," [1] said Gáspár.

Hubble images from 2014 showed the object had vanished, to the disbelief of the astronomers. Adding to the mystery, earlier images showed the object to continuously fade over time. "Clearly, Fomalhaut b was doing things a bona fide planet should not be doing," said Gáspár.

The resulting interpretation is that Fomalhaut b is not a planet, but a slowly expanding cloud blasted into space as a result of a collision between two large bodies. Researchers believe the collision occurred not too long prior to the first observations taken in 2004. By now the debris cloud, consisting of dust particles around 1 micron (1/50th the diameter of a human hair), is below Hubble's detection limit. The dust cloud is estimated to have expanded by now to a size larger than the orbit of Earth around our Sun.

Equally confounding is that the object is not on an elliptical orbit, as expected for planets, but on an escape trajectory, or hyperbolic path. "A recently created massive dust cloud, experiencing considerable radiative forces from the central star Fomalhaut, would be placed on such a trajectory" Gáspár said, "Our model is naturally able to explain all independant observable paramters of the system: its expansion rate, its fading and its trajectory."

Because Fomalhaut b is presently inside a vast ring of icy debris encircling the star, the colliding bodies were likely a mixture of ice and dust, like the cometary bodies that exist in the Kuiper belt on the outer fringe of our solar system. Gáspár and Rieke estimate that each of these comet-like bodies measured about 200 kilometers across. The also suggest that the Fomalhaut system may experience one of these collision events only every 200 000 years.

Gáspár, Rieke, and other astronomers will also be observing the Fomalhaut system with the upcoming NASA/ESA/CSA James Webb Space Telescope, which is scheduled to launch in 2021.

A team of scientists led by the University of Michigan Rogel Cancer Center and Case Comprehensive Cancer Center has identified the binding site where drug compounds could activate a key braking mechanism against the runaway growth of many types of cancer.

The discovery marks a critical step toward developing a potential new class of anti-cancer drugs that enhance the activity of a prevalent family of tumor suppressor proteins, the authors say.

The findings, which appear in the leading life sciences journal Cell, are less a story of what than how.

Scientists have known for a while that certain molecules were capable of increasing the activity of the tumor suppressor protein PP2A, killing cancer cells and shrinking tumors in cell lines and animal models -- but without information about the physical site where the molecules interact with the protein, trying to optimize their properties to turn them into actual drugs would require endless trial and error.

"We used cryo-electron microscopy to obtain three-dimensional images of our tool-molecule, DT-061, bound to PP2A," says study co-senior author Derek Taylor, Ph.D., an associate professor of pharmacology and biochemistry at Case Western Reserve University and member of the Case Comprehensive Cancer Center. "This allowed us to see for the first time precisely how different parts of the protein were brought together and stabilized by the compound. We can now use that information to start developing compounds that could achieve the desired profile, specificity and potency to potentially translate to the clinic."

The researchers propose calling this class of molecules SMAPs -- for small molecule activators of PP2A.

Along with cancer, PP2A is also dysregulated in a number of other diseases including cardiovascular and neurodegenerative diseases. And the researchers are optimistic the findings could also open opportunities to develop new medicines against diseases like heart failure and Alzheimer's as well.

Team science

The research required a marriage of scientific disciplines and areas of expertise, notes co-senior author Goutham Narla, M.D., Ph.D., chief of the division of genetic medicine in the department of internal medicine at the U-M Medical School.

"It's an illustration of how collaboration and team science can solve some of the questions like this that scientists have been asking for many years," Narla says. "Solving the structure without the biological knowledge of how best to apply it against cancer, would only be half of the story. And if we were just activating PP2A, killing cancer cells and slowing the growth of cancer without the structural data -- that would be a really nice half-story as well. But working together, we now have a story about being able to drug this previously undruggable tumor suppressor."

The study was led by first authors Daniel Leonard, an M.D. and Ph.D. student and member of Narla's lab when the research was at Case Western Reserve and the Case Comprehensive Cancer Center, and research scientist Wei Huang, Ph.D., of the Taylor lab.

There has been a lot of activity and excitement in recent years around the development of kinase inhibitors -- small molecule compounds that go after the protein kinases whose dysfunction is involved in the explosive growth and proliferation of cancer cells. That is, turning off cancer's "on switch," Leonard explains.

The new research attacks cancer from the opposite side of the equation, turning on cancer's "off switch" by stabilizing protein phosphatases whose malfunction removes a key brake on cancer growth.

In the paper, the researchers speculate how a combination of both approaches simultaneously might offer an even more powerful one-two punch -- potentially helping to overcome cancer's ability to evolve to thwart a singular approach.

"The binding pocket we identified provides a launch pad for optimizing the next generation of SMAPs toward use in the clinic -- in cancer, and potentially other diseases," Huang adds.

What The Study Did: Rates and methods of detection of thyroid cancer diagnosed in male rescue/recovery workers at the World Trade Center site after the 9/11 terrorist attacks were compared with demographically similar individuals from Olmsted County, Minnesota, to see if increased rates of thyroid cancer among those workers were associated with the identification of asymptomatic cancers detected during heightened nonthyroid-related medical surveillance.

Authors: Rachel Zeig-Owens, Dr.P.H., M.P.H., of the Bureau of Health Services in Brooklyn, 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/jamainternmed.2020.0950)

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, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: Data from a study of environmental influences on child health and development were used to investigate the extent to which frequency of screen viewing and social activities such as parent-child play and reading through 18-months of age were associated with the risk of autism spectrum disorder (ASD) and ASD-like symptoms among 2,100 children at age 2.

Authors: David S. Bennett, Ph.D., of the Drexel University College of Medicine in Philadelphia, is the corresponding author.

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

(doi:10.1001/jamapediatrics.2020.0230)

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

An immunological test known as a "tetramer assay" can detect and quantify the T cells in a blood sample that are able to recognize a specific antigen, such as a viral protein. Making the molecular probes needed for this type of assay, however, has always been a difficult and time-consuming process.

Now, a team led by researchers at UC Santa Cruz has developed a method to create libraries of probes for high-throughput, large-scale assessments of T cell repertoires in blood samples. The new approach, described in a paper published April 20 in Nature Communications, opens up new opportunities for immunological research, development of cancer immunotherapies, and assessing the immune responses of patients with viral infections, including COVID-19.

"Every person in the field knows how cumbersome it is to make the probes for these assays," said corresponding author Nikolaos Sgourakis, assistant professor of chemistry and biochemistry at UC Santa Cruz. "With conventional methods, you would need about a week to make a single peptide complex, but now we can make a plate of 100 in a day."

T cells play a central role in the immune system, complementary to antibodies (produced by B cells). Antibodies recognize and bind to antigens (foreign proteins) in the blood and other body fluids, whereas T cells only bind to antigens displayed on the surfaces of cells in the body, enabling the immune system to detect infected or cancerous cells.

This difference makes antibody tests relatively straightforward and T cell assays much more challenging. To construct a probe for detecting a specific T cell receptor, the corresponding antigen must be incorporated into a molecular complex that mimics the way antigens are displayed on cell surfaces, bound to major histocompatibility complex (MHC) proteins. Sgourakis has been studying how protein fragments are selected and bound to MHC proteins in cells, and the new method builds on his lab's discoveries about the role of "molecular chaperones" in this process.

"Molecular chaperones are designed by nature to load MHC proteins with peptides in the cell, so we took our favorite chaperone and repurposed it," Sgourakis said.

His previous research had shown that the chaperone can eject antigens that have low affinity for the MHC protein, ensuring that it binds only high-affinity antigens that can be displayed at the cell surface in the proper conformation to activate a T cell response. So Sgourakis designed a "placeholder" peptide for use in preparing large quantities of pre-loaded MHC complexes. When incubated with a high-affinity antigen, the placeholder is displaced, and this reaction can be performed in parallel with large numbers of antigens in a high-throughput system.

"It's a force multiplier, enabling us to perform these reactions at high throughput," Sgourakis said. "A lot of groups are working on similar methodologies, all of which have their pros and cons. This technology has the advantage of using the same system that cells use naturally, and we can combine it very elegantly with existing single-cell analytical tools."

This work was done in close collaboration with researchers at the New York Genome Center and the University of Pennsylvania's Children's Hospital and Perelman School of Medicine. The researchers started to use the new method to develop libraries of probes for assessing T cell responses to neuroblastoma and designing cancer immunotherapies.

Then came COVID-19, and the team began exploring ways to apply the new technology to address the challenges of the novel coronavirus. With a viral infection, there are many different fragments of the viral proteins that an infected cell can display, and it is important to determine which of these peptides elicit a strong immune response.

"Based on the coronavirus genome, we can predict all the possible peptides, synthesize them, load them onto MHC tetramers, and do a fishing expedition to find which ones are recognized by the T cells in blood samples from patients," Sgourakis explained. "Certain peptides are immunodominant--they steer the immune response--and those are the ones we want to discover so we can potentially use them in a vaccine."

This approach can also be used to compare the T cell receptor repertoires in different cohorts of patients. As people age, their T cell repertoire declines, resulting in a diminished ability to mount an immune response to a novel threat. This may be why older people are more vulnerable to COVID-19.

"One of the big questions is why there is so much variability in the severity of this disease," Sgourakis said. "We can use this technology to screen patients and see what the gaps are in their T cell repertoires, and maybe use this as a diagnostic for which patients will need more intensive treatment."

Genetic research throughout Europe shows evidence of drastic population changes near the end of the Neolithic period, as shown by the arrival of ancestry related to pastoralists from the Pontic-Caspian steppe. But the timing of this change and the arrival and mixture process of these peoples, particularly in Central Europe, is little understood. In a new study published in Nature Communications, researchers analyze 96 ancient genomes, providing new insights into the ancestry of modern Europeans.

Scientists sequence almost one hundred ancient genomes from Switzerland

With Neolithic settlements found everywhere from lake shore and bog environments to inner alpine valleys and high mountain passes, Switzerland's rich archeological record makes it a prime location for studies of population history in Central Europe. Towards the end of the Neolithic period, the emergence of archaeological finds from Corded Ware Complex cultural groups (CWC) coincides with the arrival of new ancestry components from the Pontic-Caspian steppe, but exactly when these new peoples arrived and how they mixed with indigenous Europeans remains unclear.

To find out, an international team led by researchers from the University of Tübingen, the University of Bern and the Max Planck Institute for the Science of Human History (MPI-SHH) sequenced the genomes of 96 individuals from 13 Neolithic and early Bronze Age sites in Switzerland, southern Germany and the Alsace region of France. They detect the arrival of this new ancestry as early as 2800 BCE, and suggest that genetic dispersal was a complex process, involving the gradual mixture of parallel, highly genetically structured societies. The researchers also identified one of the oldest known Europeans that was lactose tolerant, dating to roughly 2100 BCE.

Slow genetic turnover indicates highly structured societies

"Remarkably, we identified several female individuals without any detectable steppe-related ancestry up to 1000 years after this ancestry arrives in the region," says lead author Anja Furtwängler of the University of Tübingen's Institute for Archeological Sciences. Evidence from genetic analysis and stable isotopes suggest a patrilocal society, in which males stayed local to where they were born and females came from distant families that did not carry steppe ancestry.

These results show that CWC was a relatively homogenous population that occupied large parts of Central Europe in the early Bronze Age, but they also show that populations without steppe-related ancestry existed parallel to the CWC cultural groups for hundreds of years.

"Since the parents of the mobile females in our study couldn't have had steppe-related ancestry either, it remains to be shown where in Central Europe such populations were present, possibly in the Alpine mountain valleys that were less connected to the lower lands" says Johannes Krause, director of the Department of Archaeogenetics at MPI-SHH and senior author of the study. The researchers hope that further studies of this kind will help to illuminate the cultural interactions that precipitated the transition from the Neolithic to the Early Bronze age in Central Europe.

Scientists have discovered an earlier origin to the human language pathway in the brain, pushing back its evolutionary origin by at least 20 million years.

Previously, a precursor of the language pathway was thought by many scientists to have emerged more recently, about 5 million years ago, with a common ancestor of both apes and humans.

For neuroscientists, this is comparable to finding a fossil that illuminates evolutionary history. However, unlike bones, brains did not fossilize. Instead neuroscientists need to infer what the brains of common ancestors may have been like by studying brain scans of living primates and comparing them to humans.

Professor Chris Petkov from the Faculty of Medical Sciences, Newcastle University, UK the study lead said: "It is like finding a new fossil of a long lost ancestor. It is also exciting that there may be an older origin yet to be discovered still."

The international teams of European and US scientists carried out the brain imaging study and analysis of auditory regions and brain pathways in humans, apes and monkeys which is published in Nature Neuroscience.

They discovered a segment of this language pathway in the human brain that interconnects the auditory cortex with frontal lobe regions, important for processing speech and language. Although speech and language are unique to humans, the link via the auditory pathway in other primates suggests an evolutionary basis in auditory cognition and vocal communication.

Professor Petkov added: "We predicted but could not know for sure whether the human language pathway may have had an evolutionary basis in the auditory system of nonhuman primates. I admit we were astounded to see a similar pathway hiding in plain sight within the auditory system of nonhuman primates."

Remarkable transformation

The study also illuminates the remarkable transformation of the human language pathway. A key human unique difference was found: the human left side of this brain pathway was stronger and the right side appears to have diverged from the auditory evolutionary prototype to involve non-auditory parts of the brain.

The study relied on brain scans from openly shared resources by the global scientific community. It also generated original new brain scans that are globally shared to inspire further discovery. Also since the authors predict that the auditory precursor to the human language pathway may be even older, the work inspires the neurobiological search for its earliest evolutionary origin - the next brain 'fossil' - to be found in animals more distantly related to humans.

Professor Timothy Griffiths, consultant neurologist at Newcastle University, UK and joint senior author on the study notes: "This discovery has tremendous potential for understanding which aspects of human auditory cognition and language can be studied with animal models in ways not possible with humans and apes. The study has already inspired new research underway including with neurology patients."

Engineers at the McKelvey School of Engineering at Washington University in St. Louis have received federal funding for a rapid COVID-19 test using a newly developed technology.

Srikanth Singamaneni, professor of mechanical engineering and materials science, and his team have developed a rapid, highly sensitive and accurate biosensor based on an ultrabright fluorescent nanoprobe, which has the potential to be broadly deployed.

Called plasmonic-fluor, the ultrabright fluorescent nanoprobe can also help in resource-limited conditions because it requires fewer complex instruments to read the results. The National Science Foundation has awarded Singamaneni and his team a $100,008 grant toward developing a COVID-19 test using plasmonic-fluor.

Singamaneni hypothesizes their plasmonic-fluor-based biosensor will be 100 times more sensitive compared with the conventional SARS-CoV-2 antibody detection method. Increased sensitivity would allow clinicians and researchers to more easily find positive cases and lessen the chance of false negatives.

Plasmonic-fluor works by increasing the fluorescence signal to background noise. Imagine trying to catch fireflies outside on a sunny day. You might net one or two, but against the glare of the sun, those little buggers are difficult to see. What if those fireflies had the similar brightness as a high-powered flashlight?

Plasmonic-fluor effectively turns up the brightness of fluorescent labels used in a variety of biosensing and bioimaging methods. In addition to COVID-19 testing, it could potentially be used to diagnose, for instance, that a person has had a heart attack by measuring the levels of relevant molecules in blood or urine samples.

Using plasmonic-fluor, which is composed of gold nanoparticles coated with conventional dyes, researchers have been able to achieve up to a 6,700-fold brighter fluorescent nanolabel compared with conventional dyes, which can potentially lead to early diagnosis. Using this nanolabel as an ultrabright flashlight, they have demonstrated the detection of extremely small amounts of target biomolecules in biofluids and even molecules present on the cells.

The study was published in the April 20 issue of Nature Biomedical Engineering.

Gold nanoparticles serve as beacons

In biomedical research and clinical labs, fluorescence is used as a beacon to see and follow target biomolecules with precision. It's an extremely useful tool, but it's not perfect.

"The problem in fluorescence is, in a lot of cases, it's not sufficiently intense," Singamaneni said. If the fluorescent signal isn't strong enough to stand out against background signals, just like fireflies against the glare of the sun, researchers may miss seeing something less abundant but important.

"Increasing the brightness of a nanolabel is extremely challenging," said Jingyi Luan, lead author of the paper. But here, it's the gold nanoparticle sitting at the center of the plasmonic-fluor that really does the work of efficiently turning the fireflies into flashlights, so to speak. The gold nanoparticle acts as an antenna, strongly absorbing and scattering light. That highly concentrated light is funneled into the fluorophore placed around the nanoparticle. In addition to concentering the light, the nanoparticles speed up the emission rate of the fluorophores. Taken together, these two effects increase the fluorescence emission.

Essentially, each fluorophore becomes a more efficient beacon, and the 200 fluorophores sitting around the nanoparticle emit a signal that is equal to 6,700 fluorophores.

In addition to detecting low quantities of molecules, sensing time can be shortened using plasmonic-fluor as brighter beacons mean fewer captured proteins are needed to determine their presence.

The researchers have also shown that plasmonic-fluor allows the detection of multiple proteins simultaneously. And in flow cytometry, plasmonic-fluor's brightening effect allows for a more precise and sensitive measurement of proteins on cell surface, whose signal may have been buried in the background noise using traditional fluorescent tagging.

There have been other efforts to enhance fluorescent tagging in imaging, but many require the use of an entirely new workflow and measurement platform. In addition to plasmonic-fluor's ability to greatly increase the sensitivity and decrease the sensing time, it doesn't require any changes to existing laboratory tools or techniques.

The technology has been licensed to Auragent Bioscience LLC by Washington University's Office of Technology Management. Auragent is in the process of further development and scaling up the production of plasmonic-fluors for commercialization.