Brain

What The Study Did: This population-based study explored associations between parent and family stressors, such as parenting stress and lower household income, with child screen exposure and screen use paired with feeding in toddlers.

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

Authors: Katherine Tombeau Cost, Ph.D., of the Hospital for Sick Children in Toronto, is the corresponding author.

(10.1001/jamanetworkopen.2019.20557)

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, financial disclosures, funding and support, etc.

Researchers have designed an artificial intelligence (AI) model that is better able to predict how much students are learning in educational games. The improved model makes use of an AI training concept called multi-task learning, and could be used to improve both instruction and learning outcomes.

Multi-task learning is an approach in which one model is asked to perform multiple tasks.

"In our case, we wanted the model to be able to predict whether a student would answer each question on a test correctly, based on the student's behavior while playing an educational game called Crystal Island," says Jonathan Rowe, co-author of a paper on the work and a research scientist in North Carolina State University's Center for Educational Informatics (CEI).

"The standard approach for solving this problem looks only at overall test score, viewing the test as one task," Rowe says. "In the context of our multi-task learning framework, the model has 17 tasks - because the test has 17 questions."

The researchers had gameplay and testing data from 181 students. The AI could look at each student's gameplay and at how each student answered Question 1 on the test. By identifying common behaviors of students who answered Question 1 correctly, and common behaviors of students who got Question 1 wrong, the AI could determine how a new student would answer Question 1.

This function is performed for every question at the same time; the gameplay being reviewed for a given student is the same, but the AI looks at that behavior in the context of Question 2, Question 3, and so on.

And this multi-task approach made a difference. The researchers found that the multi-task model was about 10 percent more accurate than other models that relied on conventional AI training methods.

"We envision this type of model being used in a couple of ways that can benefit students," says Michael Geden, first author of the paper and a postdoctoral researcher at NC State. "It could be used to notify teachers when a student's gameplay suggests the student may need additional instruction. It could also be used to facilitate adaptive gameplay features in the game itself. For example, altering a storyline in order to revisit the concepts that a student is struggling with.

"Psychology has long recognized that different questions have different values," Geden says. "Our work here takes an interdisciplinary approach that marries this aspect of psychology with deep learning and machine learning approaches to AI."

"This also opens the door to incorporating more complex modeling techniques into educational software - particularly educational software that adapts to the needs of the student," says Andrew Emerson, co-author of the paper and a Ph.D. student at NC State.

The paper, "Predictive Student Modeling in Educational Games with Multi-Task Learning," will be presented at the 34th AAAI Conference on Artificial Intelligence, being held Feb. 7-12 in New York, N.Y. The paper was co-authored by James Lester, Distinguished University Professor of Computer Science and director of CEI at NC State; and by Roger Azevedo of the University of Central Florida.

By conveniently and painlessly collecting data, wearable sensors create many new possibilities for keeping tabs on the body. In order to work, these devices need to stay next to the skin. In a study described in ACS Omega, researchers tweaked a widely used polymer to create a potential new adhesive to keep these sensors in place.

Wearable devices are making an impact in medicine. For example, they are being used to monitor blood sugar without drawing blood, and some can automatically measure hospital patients' vital signs. Sensors like these are often put in place using acrylic-based medical bandages. However, the adhesives on these bandages can provoke allergic reactions or cause pain when removed. Another option, silicone-based adhesives, doesn't cause irritation, but also doesn't stay put. Other adhesives, including bio-inspired ones that mimic gecko feet and octopus suckers, are not yet practical for mass production. To develop a better alternative, Xi Chen and Tetsushi Taguchi turned to a polymer, poly (vinyl alcohol) (PVA), which is not irritating to the skin and is currently used in some wound dressings, contact lenses and other similar items.

Despite its many appealing properties, PVA can come off easily when wet. So, the researchers modified the compound by adding alkyl chains to try to improve its adhesion. They made versions with chains that contained three, six or nine methylene carbons, then tested them to see which performed best. It turned out that films made of longer chain versions were more hydrophobic, but had less tensile strength. Cells best tolerated the short chain known as 4C3-PVA, and in tests with pig skin, they found it bonded most strongly. The researchers conclude that 4C3-PVA is a promising adhesive for wearable devices.

Men who experienced a family member's incarceration are 64% more likely to have diabetes in later adulthood, compared to those who were not exposed to this childhood adversity, report researchers from the University of Toronto and University of Alabama in a recent study in SAGE-Open Medicine.

The study -- by Bradley White, an associate professor with the University of Alabama's Department of Psychology, and Esme Fuller-Thomson, a professor at the University of Toronto's Factor-Inwentash Faculty of Social Work (FIFSW) -- mirrors previous research by the authors, published in 2016, which found that the incarceration of a family member during childhood was also associated with a much higher risk of heart attacks in men, but not women.

Their recent study looked at a large representative sample of adults over the age of 40 across five US States. Of the men who were exposed to this childhood trauma, 7.9% had diabetes. Of the men who had not experienced the incarceration of a family member as a child, only 4.8% had the disease. The difference was much less for women (5.4% vs. 4.5%).

"Previous studies have found that the incarceration of a parent plays havoc with the stability of housing, employment, and parental marital relationships. It has also been associated with psychosocial maladjustment and mental disorders in children, and often leads to considerable social and familial stigma," says White. "Less attention has been paid to the long-term physical health outcomes of the children as they grow up."

Family member incarceration during childhood is an under-investigated yet increasingly common childhood experience in the United States. One in every 17 respondents aged 40-64 had experienced a family member incarcerated, compared to one in every 63 respondents aged 80 and older. The vast majority of U.S. prison inmates are men, most of whom are fathers to children under 18.

While White and Fuller-Thomson's study was not designed to draw conclusions about the different results found between men and women, the researchers have developed several hypotheses that they would like to explore in the future.

"Prior evidence suggests men may be more vulnerable biologically to early adversities than women and experience stress-related testosterone suppression, which is linked to insulin resistance," says White. "In addition, incarceration also frequently interferes with fathers' contact with children, which may particularly impact their sons' abilities to cope with stress. Boys and men are also less likely than girls and women to seek psychosocial support in response to adverse events."

Since other adverse childhood traumas that have also been found to contribute to the development of health problems in later life are also more prevalent in households where a family member is incarcerated, six other forms of childhood traumas were adjusted for in the analysis in addition to known risk factors for diabetes, such as obesity and smoking. The six forms of trauma include sexual, physical, and verbal abuse, and parental addictions, parental mental illness and parental domestic violence.

"The results of our two studies suggests that the dramatic increase in incarceration rates may have detrimental long-term health effects for boys with a family member in prison, and these effects may persist into later life," says Fuller-Thomson, who is also director of the University of Toronto's Institute for Life Course and Aging and cross-appointed to the Department of Family & Community Medicine and the Faculty of Nursing.

"Our results support the consideration of alternatives to current incarceration policies and practice," said co-author Keri J. West, a doctoral candidate in the FIFSW at U of T.

"These alternatives include investment in diversion strategies to redirect individuals to community-based rehabilitative programs, facilitating family contact by placing incarcerated individuals in facilities close to their communities, and eliminating visitation policies that create excessive burden for family members, such as restrictive visitation hours and prohibitive fees for phone calls."

Tsukuba, Japan - Post-translational modification is the process whereby proteins are modified after their initial biosynthesis. Modification can take many forms, including enzymatic cleavage of the protein or the addition of sugars, lipids, or small chemical groups. Amongst other things, post-translational modification enhances protein stability, mediates interactions between proteins, and can be used to mark proteins for transport or degradation.

In a report published this month in Communications Biology, researchers from the University of Tsukuba have found that one such post-translational modification, called sumoylation, in Arabidopsis thaliana relies on a single zinc finger domain within SUMO E3 ligase SIZ1. Without this domain, the function of the SIZ1 protein is impaired, resulting in stunted plant growth and increased sensitivity to stressful conditions such as low temperature.

Sumoylation involves the attachment of small SUMO proteins to target proteins, affecting how they function, where they are situated within the cell, and when they are degraded. In plants, this post-translational modification is involved in the response to cold, salt, and drought stresses, as well as in innate immunity and the regulation of signalling pathways. In A. thaliana, the attachment of SUMO to target proteins is mediated by an E3 ligase called SIZ1, which, although very similar to homologous proteins in yeast and animals, contains a unique PHD zinc finger-like domain.

"The importance of SIZ1 for effective sumoylation in Arabidopsis is well known," explains lead author of the study Professor Kenji Miura. "However, the significance of the PHD finger in the function of SIZ1, and ultimately sumoylation, was less clear."

To investigate the biological importance of the PHD finger, the researchers expressed intact SIZ1 or SIZ1 missing the PHD finger in an Arabidopsis siz1 mutant. While intact protein restored normal growth, plants expressing SIZ1 without the PHD finger continued to show the growth retardation, cold sensitivity, and drought tolerance that are characteristic of the siz1 mutant, confirming that the PHD finger is required for SIZ1 function.

The researchers also showed that PHD containing a point mutation no longer recognized tri-methylated histone, a protein involved in gene regulation, and a SIZ1 protein containing this mutation also failed to rescue the siz1 phenotype.

"Based on our findings, we predict that PHD is essential for recognition of tri-methylated histone," says co-author Associate Professor Takuya Suzaki. "Because tri-methylated histone accumulates at high levels in the promotor region of a stress response-associated transcription factor in the siz1 mutant, it is likely that PHD is essential for transcriptional gene suppression by SIZ1/SUMO in response to abiotic stress in Arabidopsis."

People asked by experts to comment on the effectiveness of new psychiatric drug treatments appear to be unfairly biased even though they declare a conflict of interest, suggests research published online in the journal BMJ Evidence-Based Medicine today.

US researchers found potential positive bias among people who were meant to be giving objective opinion on drugs to experts before they decide to approve them for wider public use.

In the US, the Psychopharmacologic Drug Advisory Committee is one of 33 advisory committees of the Food and Drug Administration (FDA) - the agency that ensures medicines and medical devices work and are safe - that is responsible for reviewing safety and efficacy data for human and investigational psychiatric drug products.

During committee meetings, an open public hearing takes place where speakers provide testimonies regarding the drug in question and are asked, but do not have to, mention a conflict of interest when speaking.

Previous studies have found a relationship between conflicts of interest of these public speakers and their likelihood for providing a positive testimony, but little is known about their effect in the field of psychiatry.

Medical student Will Roberts and colleagues from Oklahoma State University's Center for Health Sciences in the US therefore studied data on transcripts from 18 meetings of the Psychopharmacologic Drug Advisory Committee between April 2009 and March 2019.

During the 10-year period, there were 145 public speakers, the most common being from the general public (24.8%), non-profit organisations (20%), patients (17.2%), industry representatives (13.8%), medical organisation representatives (12.4%), friend or relative of the patient (10.3%) and patient advocate (less than 1%).

Of the 145 speakers, 52 disclosed a conflict of interest (COI).

Such conflicts can include reimbursement for travel and lodging by the pharmaceutical company to attend the meeting, previous or current payments for consulting from the pharmaceutical company, and compensation as a paid investigator in previously conducted clinical trials for the drug under review.

Among these 52 speakers, 82% provided a positive testimony about the psychiatric drug in question.

Those speakers who had the condition in question were not more likely to provide a positive statement than those who did not.

In addition, 24 out of the 145 public speakers did not mention their COI, and among these speakers, nearly half of them provided a positive testimony.

This is an observational study, so can't establish cause. Nevertheless, the authors concluded that the results showed that disclosing a COI was associated with increased odds of public speakers providing a favourable testimony for the recommendation of psychiatric drugs.

"The implications of these findings are concerning since COIs have the potential to skew public speaker's testimonies and persuade committee members to recommend a drug through emotionally charged tactics," they conclude.

The authors recommend that pharmaceutical companies should not be allowed to handpick the patients they want to speak during open public hearings, and instead that random video diaries from patients involved in the drug's clinical trial phases be played at these hearings to promote transparency and validity regarding the approval process.

They also recommend the FDA implement additional procedures regarding conflicts of interest, specifically stricter management of such conflicts or prohibition.

Russian researchers from the Moscow Institute of Physics and Technology, Valiev Institute of Physics and Technology, and ITMO University have created a neural network that learned to predict the behavior of a quantum system by "looking" at its network structure. The neural network autonomously finds solutions that are well-adapted toward quantum advantage demonstrations. This will aid researchers in developing new efficient quantum computers. The findings are reported in the New Journal of Physics.

A wide range of problems in modern science are solved through quantum mechanical calculations. Some of the examples are research into chemical reactions and the search for stable molecular structures for medicine, pharmaceutics, and other industries. The quantum nature of the problems involved makes quantum computations better-suited to them. Classical computations, by contrast, tend to return only bulky approximate solutions.

Creating quantum computers is costly and time-consuming, and the resulting devices are not guaranteed to exhibit any quantum advantage. That is, operate faster than a conventional computer. So researchers need tools for predicting whether a given quantum device will have a quantum advantage.

One of the ways to implement quantum computations is quantum walks. In simplified terms, the method can be visualized as a particle traveling in a certain network, which underlies a quantum circuit.

If a particle's quantum walk from one network node to another happens faster than its classical analogue, a device based on that circuit will have a quantum advantage. The search for such superior networks is an important task tackled by quantum walk experts.

What the Russian researchers did is they replaced the experts with artificial intelligence. They trained the machine to distinguish between networks and tell if a given network will deliver quantum advantage. This pinpoints the networks that are good candidates for building a quantum computer.

The team used a neural network geared toward image recognition. An adjacency matrix served as the input data, along with the numbers of the input and output nodes. The neural network returned a prediction of whether the classical or the quantum walk between the given nodes would be faster.

"It was not obvious this approach would work, but it did. We have been quite successful in training the computer to make autonomous predictions of whether a complex network has a quantum advantage," said Associate Professor Leonid Fedichkin of the theoretical physics department at MIPT.

"The line between quantum and classical behaviors is often blurred. The distinctive feature of our study is the resulting special-purpose computer vision, capable of discerning this fine line in the network space," added MIPT graduate and ITMO University researcher Alexey Melnikov.

With their co-author Alexander Alodjants, the researchers created a tool that simplifies the development of computational circuits based on quantum algorithms. The resulting devices will be of interest in biophotonics research and materials science.

One of the processes that quantum walks describe well is the excitation of photosensitive proteins, such as rhodopsin or chlorophyll. A protein is a complex molecule whose structure resembles a network. Solving a problem that formally involves finding the quantum walk time from one node to another may actually reveal what happens to an electron at a particular position in a molecule, where it will move, and what kind of excitation it will cause.

Compared with architectures based on qubits and gates, quantum walks are expected to offer an easier way to implement the quantum calculation of natural phenomena. The reason for this is that the walks themselves are a natural physical process.

Children diagnosed with fetal alcohol spectrum disorders (FASD)--caused by prenatal alcohol exposure--often face lifelong developmental, cognitive and behavioral problems. Without the right support they are at high risk of mental health disorders and other life problems. Affecting around 2 to 5 percent of school-aged children in the United States, FASD is a major public health problem.

But children with FASD are not the only ones who struggle; often their parents and caretakers do, too. What can make the job of parenting a child with the disorder especially hard is the general lack of awareness surrounding FASD, and the dearth of available resources and specialists.

Unsurprisingly, these barriers contribute to the already high stress levels that go hand-in-hand with parenting a child with disabilities. Stress, of course, can have a direct bearing on family cohesion, as well as the caregivers' mental and physical health. That's why, according to experts, self-care for parents is a critical resource.

A new study by a team of University of Rochester researchers, published in the journal Research in Developmental Disabilities, examines how FASD caregivers' perceived confidence in and the frequency of self-care is related to stress, parenting attitudes, and family needs.

"We know that parents who are stressed tend to feel less effective and less satisfied as a parent," says lead author Carson Kautz, a graduate student in the Rochester Department of Psychology.

Kautz is working on interventions to reduce the adverse outcomes for children with developmental disabilities, particularly FASD, together with her faculty mentor and recognized FASD expert Christie Petrenko, an assistant professor and research associate at the University's Mt. Hope Family Center. Petrenko is a co-author of the study, as is Jennifer Parr, a graduate student at the University's Warner School of Education and a project coordinator and therapist at Mt. Hope Family Center.

"Of course, stress reduction is important for all parents," acknowledges Parr, "but it's especially critical in caregivers of children with special needs, given that we know of their already high stress levels."

This paper is the first to describe caregiver strategies for self-care and the obstacles and barriers parents face in raising their children while trying to care effectively for themselves. Based on interviews and questionnaires given to 46 caregivers of children with either an FASD diagnosis, or confirmed prenatal alcohol exposure, the researchers checked for child behavioral problems, parental stress levels, and grouped the various self-care strategies (such as practicing yoga, maintaining physical health, engaging in hobbies, and treating oneself to small luxuries) into seven categories.

"A strategy that really works well for one person may not work well for another, so it's good to see people figuring out what works for them," says Kautz.

Key findings

Caregivers who report greater confidence in their ability to use self-care also report reduced parental distress, higher family needs being met, and greater parenting satisfaction.

The frequency of self-care increases a caregiver's confidence that self-care really helps.

However, the frequency of self-care does not show a positive effect on any other measure of child or family functioning, such as child behavior, parent-child interactions, or perceived parenting effectiveness.

Caregivers report a range of useful self-care strategies, but say they can be hard to fit into busy lives.

Previous research has shown that stress-reduction interventions, such as behavioral parent training, coping skills education, and particularly mindfulness exercises have shown promise in reducing the stress levels of parents of children with developmental disabilities.

The Rochester team hopes that the findings in this study, which was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism, will inform future clinical work with parents of children with FASD.

Philadelphia, February 4, 2020 - Non-invasive prenatal tests (NIPTs) are used for fetal genetic disease screening in pregnant women. In contrast, invasive tests like amniocentesis carry the risk of causing fetal harm. A report in The Journal of Molecular Diagnostics, published by Elsevier, describes the development of a single-cell DNA assessment method with high sensitivity and specificity. This noninvasive test enables direct extraction of genetic information from live fetal cells for simultaneous evaluation, thereby improving the likelihood of detecting a fetal anomaly.

Established NIPTs have important limitations including noninformative results. Therefore, novel methods for noninvasive definitive diagnosis of fetal genetic abnormalities are needed. Using a modified single-cell-based droplet digital PCR (sc-ddPCR) NIPT, researchers conducted a proof of concept study that successfully assessed the genetic information of extremely rare fetal cells in maternal peripheral blood. This modified sc-ddPCR system makes it possible to directly assess single-cell DNA information from live cells without cell-fixation, cell-staining, and whole genome amplification steps.

"Because NIPTs currently analyze small DNA fragments, it can be challenging to ascertain whether the origin of each DNA fragment is the mother or her fetus," explained lead investigator Kenichiro Hata, MD, PhD, Chairman of Maternal-Fetal Biology at the National Research Institute for Child Health and Development, Tokyo, Japan. "We have observed that in some cases NIPT results are discordant with the fetal genetic information that has been reported. This study serves as a proof of concept for noninvasive prenatal diagnosis using circulating fetal cells without any strict cell purification."

With this modified technique, up to 3,000 cells per well can be encapsulated in each droplet and simultaneously analyzed. The original sc-ddPCR system simultaneously assesses single-cell genetic information with high sensitivity and specificity. However, the original system is only useful for cell suspensions with a clear background (i.e., washed cell lines or clearly sorted cells with fluorescence-activated cell sorting). Researchers modified this sc-ddPCR system to improve the PCR environment in each droplet with higher sensitivity and specificity, which makes it possible to now assess single-cell genetic information from crudely purified nucleated cell samples with impurities.

To confirm the sensitivity of this modified sc-ddPCR system, investigators detected the genomic DNA of circulating male fetal cells in a crudely sorted cell suspension at the single-cell level derived from peripheral blood samples from mothers with male fetuses.

Investigators searched for the presence of the sex-determining region Y gene (SRY), which is responsible for the initiation of male sex determination. Analysis of 13 blood samples indicated that only circulating fetal cells from the three pregnant women carrying male fetuses tested positive for the SRY gene, unlike cells from the 10 pregnant women carrying female fetuses. This indicates that the modified sc-ddPCR system not only has high sensitivity, but also high specificity.

"In the future, by optimizing cell sorting and encapsulation, as well as generating a more effective PCR environment in each droplet, this modified sc-ddPCR system may be a breakthrough analysis method that can be applied to various research realms and possibly to clinical diagnostic testing," commented Dr. Hata.

Altruistic helping -- the act of giving away something desirable, even at a cost to oneself - is perhaps no more evident than when it comes to food.

Human adults often respond to hungry people, whether through food banks or fundraisers, or by simply handing over their lunch. But when, and how, does that spirit of giving start?

New research by the University of Washington's Institute for Learning & Brain Sciences, or I-LABS, finds that altruism may begin in infancy. In a study of nearly 100 19-month-olds, researchers found that children, even when hungry, gave a tasty snack to a stranger in need. The findings not only show that infants engage in altruistic behavior, but also suggest that early social experiences can shape altruism.

The study is published online Feb. 4 in Scientific Reports, an open-access journal from the Nature Publishing Group.

"We think altruism is important to study because it is one of the most distinctive aspects of being human. It is an important part of the moral fabric of society," said Rodolfo Cortes Barragan, a postdoctoral researcher at I-LABS and lead author on the study. "We adults help each other when we see another in need and we do this even if there is a cost to the self. So we tested the roots of this in infants."

Nonhuman primates have been found to cooperate, and to share resources under restricted conditions. But nonhuman primates, such as chimpanzees, don't actively hand over delicious food that they need themselves.

I-LABS researchers wanted to test whether human infants were able to act beyond self-interest, when faced with one of the most fundamental biological needs: food.

For this study, researchers chose kid-friendly fruits -- including bananas, blueberries and grapes -- and set up an interaction between child and researcher. The goal: to determine whether the child would, without encouragement, verbal instruction or reinforcement, spontaneously give an appealing food to an unfamiliar person.

In the experiment, the child and the adult researcher faced each other across a table at I-LABS, and the researcher showed the child a piece of fruit. What happened next was determined by whether the child was in the control group, or the test group. In the control group, the researcher gently tossed the piece of fruit onto a tray on the floor beyond reach but within the child's reach. The researcher showed no expression and made no attempt to retrieve the fruit.

In the test group, the researcher pretended to accidentally drop the fruit onto the tray, then reach for it unsuccessfully.

That reaching effort -- the adult's apparent desire for the food -- seemed to trigger a helping response in the children, researchers said: More than half the children in the test group picked up the fruit and gave it to the adult, compared to 4% of children in the control group.

In a second experiment with a different sample of children, parents were asked to bring their child just before their scheduled snack or mealtime -- when the child was likely to be hungry. Researchers reasoned that this would raise the "cost to self" that defines altruism. The control and test group scenarios were repeated, but with children who were now more motivated to take the fruit for themselves.

The results mirrored those from the previous study. Fully 37% of the test group offered the fruit to the researcher while none of the children in the control group did so.

"The infants in this second study looked longingly at the fruit, and then they gave it away!" said Andrew Meltzoff, who is co-director of I-LABS and holds the Job and Gertrud Tamaki Endowed Chair in psychology. "We think this captures a kind of baby-sized version of altruistic helping."

The research team also analyzed the data in different ways -- whether children offered fruit on the first trial of the experiment or got better during the process, for example, and whether children from particular types of family environments helped more.

The researchers found that infants helped just as well on the very first trial of the experiment as on later trials, which Barragan said is informative because it shows that the children did not have to learn to help during the study and needed no training. Indeed, children spontaneously and repeatedly helped a person from outside of their immediate family.

The researchers also found that children with siblings and from certain cultural backgrounds were especially likely to help the adult, indicating that the expression of infant altruism is malleable. These results fit well with previous studies with adults that show positive influences of having a cultural background that emphasizes "interdependence," that is, a background that places particular value on how much an individual feels connected to others.

Said Barragan, "We think certain family and social experiences make a difference, and continued research would be desirable to more fully understand what maximizes the expression of altruism in young children. If we can discover how to promote altruism our kids, this could move us toward a more caring society."

Researchers at Seoul National University and Inha University in South Korea developed photo-sensitive artificial nerves that emulated functions of a retina by using 2-dimensional carbon nitride (C3N4) nanodot materials. Further, through the photo-sensitive artificial nerves which selectively detected ultraviolet (UV) light and processed the information, smart window platform was demonstrated for in-situ modulation of exposure to UV rays depending on the degree of UV exposure and risk.

Neuromorphic electronics which emulate the biological nervous systems are promising candidates to overcome the challenges of von-Neurmann computing architecture such as energy efficiency, high-density integration, and data processing rate in the field of Artificial Intelligence (AI) and Internet of Things (IoT). Particularly, photo-sensitive neuromorphic electronics are regarded as core technology for application of next-generation smart sensors, because they can efficiently replicate the functions of biological synapses (interconnection between two neurons, key roles in learning and memorizing) and detect various types of external light information. However, previous investigations were only focused on the integration of light sensing and synaptic functions in a single device, so actual applications have not been explored.

The work reported in January 27 in Advanced Materials describes retina-inspired photo-sensitive neuromorphic devices by using ultraviolet (UV)-responsive 2-dimensional carbon nitride (C3N4) nanodot layers to selectively detect and process UV exposure information. UV light (wavelength from 10 to 400 nm) is harmful to human health, but the human retina cannot detect UV. Thus, by emulating the retina, photo-sensitive neuromorphic electronics that can selectively detect and process UV stimuli would expand the human visual sense beyond visible light and be applicable to healthcare devices. The research group synthesized C3N4 nanodots dominantly absorbing UV light, and this was introduced as a UV-responsive floating-gate layer in transistor geometry. The presented devices consumed only 18.06 fJ/synaptic event, which is comparable to the energy consumption of biological synapses. Furthermore, the research team at Seoul National University demonstrated in-situ modulation of exposure to UV light by integrating the devices with UV transmittance modulators. These smart systems would be further developed to combine detection and dose-calculation to determine how and when to decrease UV transmittance for preventive health care.

Professor Tae-Woo Lee, a professor at Seoul National University said "This smart system platform will be widely applicable to advanced electronic skin that is able to automatically adapt to the changing light-dose environment, smart windows that can selectively control transmittance of strong UV lights, smart glasses that detect and block harmful UV rays, smart sensors, artificial retina for soft humanoid robots, and neural prostheses compatible with biological optic nerves." Lee said, "The development of human-like robots, neural prostheses that replicate and expand the human sense, and preventive health care devices can benefit from our work."

FEBRUARY 3, 2020, NEW YORK -- A Ludwig Cancer Research study has devised a new type of chimeric antigen-receptor (CAR) T cell--a family of promising immunotherapies for cancer--that can be switched on and off on demand. The study, led by Melita Irving of the Lausanne Branch of the Ludwig Institute for Cancer Research, George Coukos, director of the Branch, and their colleague Bruno Correia of the École Polytechnique Fédérale de Lausanne (EPFL), addresses a central conundrum of CAR-T therapies: their tendency to provoke potentially deadly runaway immune responses against healthy tissues in patients. Their report appears in the current issue of Nature Biotechnology.

"We wanted to develop a way to dampen CAR-T cell therapy as a safety mechanism in the event of an adverse reaction in a patient," says Coukos. "To do that we designed CAR-T cells that can be reversibly inactivated with small molecules that can be given systemically and act rapidly."

CAR-T cells are designed to detect specific molecular markers, or antigens, and destroy the cancer cells that bear them. To that end, researchers engineer a chimeric molecule, expressed on a T cell, that is stitched together from the functional units--or "domains"--of a few key proteins. The external part of the CAR protein does the antigen detecting. The inner part has two other key components. One is the signaling domain of a protein named CD3-zeta that is absolutely required to activate the T cell. The other is the signaling part of another protein, usually CD28, that supports the proliferation and survival of the activated T cell.

These cellular immunotherapies have been approved for the treatment of some blood cancers, and researchers are working on targeting them at solid tumors. But the treatment has significant risks. CAR-T cells can inadvertently elicit cascading, systemic immune reactions known as cytokine release syndrome, which can cause serious side effects.

Researchers have sought to blunt these risks by, for example, engineering CAR-T cells to commit suicide on demand or require a drug to become activated. "The former approach leads, however, to the waste of a very expensive immunotherapy, while the latter has been challenged by the short half-lives of the drugs," says Irving. "Our approach offers novel and unique solutions to this difficult molecular engineering problem."

To build their "STOP-CAR-T" system, the researchers stuck the CD3-zeta activation domain on one molecule and the antigen-detecting portion on the another. To link the two chains together, so that they'd function as a single unit, they added to each chain the interacting domains of two unrelated proteins that spontaneously pair up inside the cell. The researchers also ensured that the binding could be disrupted by existing small molecules administered systemically. Elegant computational modeling and protein engineering done in Correia's laboratory identified ideal molecular partners for these binding domains and ensured that these newly added binding domains would not interfere with the complex protein interactions within the cell required for the signaling that activates T cells.

The researchers first confirmed in cell cultures that this two-protein CAR-T system--targeted to a prostate cancer antigen--worked as well as a similarly targeted but traditionally designed CAR-T system and could be switched off by a drug-like molecule. They then grew tumors expressing that antigen in the flanks of mice and showed that while both types of CAR-T cells could slow tumor growth, only the STOP-CAR-T system's effects could be abrogated with the administration of the small molecule before or after the initiation of CAR-T therapy.

"This really shows that, in principle, we should be able to directly control the activity of the STOP-CAR T cells in patients," says Irving.

The researchers are now developing a STOP-CAR-T system that can be controlled by an approved drug and tweaking the system in various ways to see if they can lower the amount of drug required to control the cells.

"This work itself, and its potential, is really exciting," says Coukos, "but I think it is also illustrative of how well-orchestrated, multidisciplinary collaborations can yield significant scientific breakthroughs. Working with EPFL and our other partners in the region, we hope to bring STOP-CAR-T therapy as quickly as possible to cancer patients."

Baltimore, MD - February 3, 2020 - People with autism spectrum disorder (ASD) appear to suffer malfunctions in a cell that produces a special coating around nerve fibers that facilitates efficient electrical communication across the brain. And correcting it could offer a potential new avenue for treatment, according to a new study published today in the journal Nature Neuroscience from scientists at the Lieber Institute for Brain Development (LIBD).

"This could be a sea change in our understanding of what causes people to suffer this serious brain disorder," said Daniel R. Weinberger, M.D., LIBD CEO & Director. "We're actively testing in experimental models drugs that might correct this abnormality."

The study revealed that people who suffer from ASD have a cellular abnormality that impairs production of myelin, a fatty substance that creates an insulative sheath around nerve fibers in the brain that allows them to efficiently communicate with one another. The production of myelin is part of a biological process critical to early brain development known as myelination, which Weinberger compared to laying a network of fiber optic cable across the brain that facilitates a range of neurological processes.

Brady Maher, Ph.D., LIBD's lead investigator on the study, said that in trying to understand the root causes of ASD, most researchers have focused on potential problems with neurons, the principal cells of the brain. But he said our new study indicates that problems with a supporting cell that is critical for insulating the nerve fibers may be a previously underappreciated mechanism.

"Myelination is essential to healthy brain development, it's a process that begins just before birth and continues throughout the lifespan. If impaired, it leads to abnormal brain development that likely results in communication and behavior challenges associated with ASD," Maher said.

As the name suggests, ASD can produce a wide spectrum of symptoms, ranging from difficultly navigating social and emotional interactions to severe language and behavior impairments. And while it is sometimes linked to extraordinary talents in certain individuals, even milder forms of ASD can make daily life very challenging.

The new insights into ASD emerged from the Lieber Institute's research on Pitt-Hopkins syndrome, a rare neurodevelopmental disorder known to produce ASD symptoms, that is caused by mutations in a gene called TCF4.

Working with mice with the same TCF4 gene mutation as people with Pitt-Hopkins, the researchers identified a genetic abnormality that disrupts the function of cells that control myelin production. These cells are called oligodendrocytes or OL for short.

The researchers then explored other ASD mouse models caused by different mutations associated with autism and found consistent evidence for abnormalities in oligodendrocytes. Remarkably, in a collection of donated brain tissue from deceased people with ASD who did not suffer from Pitt-Hopkins syndrome but had more common forms of ASD, they observed the same abnormality: problems with OL cells that impair myelin production, something that is not found in brains of non-ASD patients.

"It appears that in many people who suffer from ASD, their OL cells are not maturing sufficiently or functioning properly," Maher said. "This suggests they are not producing enough myelin insulation for their neurons, which could profoundly disrupt brain development and electrical communication in the brain.

He noted that previous studies have shown that people with ASD can exhibit a decrease in myelin thickness in certain regions of the brain. He said recent evidence, in addition to his own suggests, that people with ASD have fewer OL cells. But Maher said that previous research had not connected the dots--that there appears to be an underlying biological process in people with ASD limiting the capacity of OL cells to produce the myelin brains need for proper development. And that deficiency could be a key source of the neurological problems seen in people with this disorder. Also, he said given the different factors that influence myelin production in OL cells, the defects in myelination could vary considerably across individual cases of ASD, corresponding to the variation in the severity of symptoms across the autism spectrum.

Maher said he and his colleagues at the Lieber Institute are now testing compounds that may have the capacity to boost myelination in the brain. "Because myelination is a lifelong process it provides a unique therapeutic opportunity that we can tap into throughout the lifespan. Along these lines, we are eager to see whether enhancing myelination in these mice can improve their ASD-associated behaviors," he said. "Promising candidates could then be considered for clinical studies."

An international research group with Dr. Longjian Xie from the Bavarian Research Institute of Experimental Geochemistry & Geophysics (BGI) of the University of Bayreuth has succeeded for the first time in measuring the viscosity that silicate melt exhibit under the pressure and temperature conditions found in the lower earth mantle. The data obtained support the assumption that a bridgmanite-enriched rock layer was formed during the early history of the earth at a depth of around 1,000 kilometres - at the border to the upper mantle. In addition, the data also provides indications that the lower mantle contains larger reservoirs of materials that originated in an early magma ocean and have remained unchanged to this day. The researchers have presented their findings in the scientific journal "Nature Communications".

For the viscosity measurements, the scientists used a heating element they developed, based on a boron-doped and therefore electrically conductive diamond. For example, they were able to examine material samples in a multi-anvil press at pressures of up to 30 giga-pascals and at temperatures of almost 3,000 degrees Celsius - i.e. under conditions similar to those prevailing in the lower mantle of the early earth. The samples were selected for composition similar to the main minerals present in the lower mantle. Using a super-fast camera (1000 frames/second), the melting processes taking place in the multi-anvil press were observed, and the viscosity of the molten material was measured.

The data obtained proved to be particularly revealing with regard to the magma ocean, from which the earth's mantle formed over the course of the earth's history. Based on their viscosity measurements, the researchers were able to show that the crystallization of the magma ocean was largely dependent on the level of pressure. This resulted in a so-called fractional crystallisation at a depth of around 1,000 kilometres. "Our measurement data support the assumption that a rock layer containing a high proportion of the mineral bridgmanite was formed at this depth due to crystallization processes. This layer could be responsible for the high viscosity observed at this depth in previous geophysical investigations," explains Dr. Longjian Xie, a post-doctoral researcher at BGI and lead author of the study now published. The other members of the international team of authors are working in Japan, at Okayama University and the electron synchrotron Spring-8, and in France at Université Clermont Auvergne and the synchrotron SOLEIL in Saint Aubin.

Bulky globular proteins require specialized transport systems for insertion into membranes. Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have determined the structure of such a system for the first time, and propose that it exploits the principle of the airlock.

Many proteins that are essential for cell viability must be transported across the membranes of intracellular organelles - such as mitochondria - in order to reach their sites of action. As a rule, transmembrane transport takes place before the newly synthesized protein has folded into its final functional shape, as the unfolded form can be extruded through a relatively narrow pore. The passage of folded proteins is a more difficult operation. They take up more space, so the pore must be correspondingly larger. Bacteria and chloroplasts utilize dedicated tunnels for this purpose. Although they are evolutionarily related to bacteria, mitochondria lack this type of aperture. Nevertheless, they manage to transfer one important protein in its folded state across their inner membrane. Now, researchers led by Professor Roland Beckmann at the LMU Gene Center have reported evidence which suggests that mitochondria accomplish this challenging feat by making use of the airlock principle. Beckmann and colleagues describe their findings in a paper that appears in the journal Nature Structural and Molecular Biology.

The Rieske protein (named Rip1 in baker's yeast) belongs to the 'iron-sulfur' class, and is a vital component of the process that enables mitochondria to generate ATP, which serves as the universal energy donor for biochemical reactions in cells. Rip1 is synthesized in a precursor form by cytoplasmic ribosomes, and transported in its unfolded state across the outer and inner membranes of the organelle into the compartment known as the matrix. Here, it is processed to yield the Rip1 protein. Incorporation of an 'iron-sulfur center' then allows it to adopt its functional conformation. Now, however, this globular protein must be inserted back into the inner membrane.

"Earlier work by our partners Walter Neupert and Nikola Wagener had shown that, in yeast, an enzyme called Bcs1 is involved in this final step," says Lukas Kater, lead author of the paper. "We have now determined the 3D structure of this enzyme with the aid of cryo-electron microscopy. - In fact, this is the first high-resolution structure of a eukaryotic translocator for folded proteins yet published." With a detailed map of the enzyme's configuration to hand, the team set out to decipher how Bcs1 manages to selectively mediate the passage of the folded form of Rip1 through the inner membrane without allowing other molecules or ions to slip through the pore.

Bcs1 belongs to a class of enzymes called AAA-ATPases. These typically consist of six identical subunits, which together form a ring-like pore. However, the structural data for Bcs1 revealed that it is comprised of seven subunits, and therefore forms a larger pore. But that's not all. - The pore is divided into two clearly defined chambers. One of these is directly accessible from the matrix of the mitochondrion, while the other is located within the inner membrane. Crucially, they are linked by a central domain which forms a seal between them - which can however be transiently opened, as the team went on to show.

"We therefore propose that transport through Bcs1 exploits the airlock principle," says Beckmann. The Rieske protein first passes through the large pore and into the matrix chamber. This induces a conformational change in Bcs1, which causes the seal between the two chambers to open, allowing Rip1 to enter the airlock, the chamber within the inner membrane. In the next step, the seal that separates the two chambers forms again. "We assume that the airlock then opens to provide access to an exit that allows the domain that contains the iron-sulfur center to emerge into the intermembrane space," Kater adds.

The results of the study not only provide insights into function and mode of action of Bcs1, it should also shed light on a number of mitochondrial diseases that have been linked to it, such as Gracile syndrome, which can lead to early postnatal death, and Björnstad syndrome which is associated with hearing loss. The availability of a high-resolution structure for the protein should make it possible to understand why the mutations associated with these diseases have such devastating consequences.