Culture

Results from a study led by investigators at Massachusetts General Hospital may help to improve the diagnosis and treatment of allergies, pointing to a potential marker of these conditions and a new therapeutic strategy. The research is published in Nature.

Nearly one third of the world's population suffers from allergies. These conditions are caused by certain antibodies--called IgE antibodies--that bind to allergens such as peanuts and trigger a reaction that releases an array of molecules that cause allergic symptoms, and in extreme cases, potentially life-threatening anaphylaxis.

Scientists have been perplexed by the fact that many individuals have circulating allergen-specific IgE antibodies without ever developing allergy symptoms. For example, about half of the people who have peanut-specific IgE antibodies (or test positive to a peanut skin prick test) do not have peanut allergies. In addition, some allergic individuals outgrow their symptoms yet still retain detectable levels of circulating allergen-specific IgE.

To look into these mysteries, Robert Anthony, PhD, of the Center for Immunology and Inflammatory Diseases, and his colleagues compared IgE from individuals with peanut allergies with IgE from individuals without any allergies. The analyses revealed an increase in a particular sugar residue called sialic acid on IgE from peanut allergic individuals.

The researchers also found that adding sialic acid to IgE enhanced allergic reactions triggered by IgE in animal models, while removing sialic acid from IgE dampened these reactions and reduced anaphylaxis.

"Our results indicate that quantifying sialic acid on IgE may serve as a marker for more accurate diagnoses of allergic disease, and that removal of sialic acid from IgE is a novel strategy for treating affected patients," said Dr. Anthony.

Additional research on the mechanisms behind sialic acid's effects on IgE activity could provide additional insights into allergies and their causes. The team is currently planning studies to determine how removing sialic acid from IgE attenuates allergy, and develop strategies to exploit this therapeutically.

The automatic operation and maintenance of optical network is important for ensuring information communication and network operation. The growing variety of services has forced operation and maintenance personnel to face tremendous operational pressure. A recent study has constructed a control architecture called intent defined optical networks (IDON) to cope with the issue.

The research related paper "Intent Defined Optical Network with Artificial Intelligence-based Automated Operation and Maintenance" is recently published in a special focus on artificial intelligence for optical communications in SCIENCE CHINA Information Sciences. The paper is achieved by Hui Yang as the corresponding author and associate professor of Beijing University of Posts and Telecommunications. Researchers have adopted a self-adapted generation and optimization policy (SAGO) to perform control research on intent defined optical network architectures, revealing two key closed-loop operations, namely closed-loop strategies generation and closed-loop intent guarantee.

Traditionally, the operation and maintenance of optical networks rely on the experience of engineers to configure network parameters, including command line interfaces, middleware scripts, and troubleshooting. With the rapid development of Internet of Things and high bitrate applications beyond 5G and 6G, a large number of applications are presented on the network in the form of intentions, such as the Internet of Vehicles which closely interact with the environment. As an important support of the policy of "network power", the optical network faces the challenges of accurate match of the intent application and the complex control of highly dynamic applications, resulting in unsatisfactory levels of manual operation and maintenance. In such case, operators urgently need to consider the upgrade of their optical network architecture to achieve automatic intelligent operation and maintenance.

Research of intent defined optical network (IDON) introduces an adaptive generation and optimization (SAGO) strategy in a self-optimizing way. The IDON architecture can achieve intent-oriented configuration conversion, realize adaptive generation and optimization strategies, and perform closed-loop intent-guaranteed operations. IDON specifically addresses communication intent and uses natural language processing to construct semantic graphs to understand, interact, and operate the required network configuration. Then, deep reinforcement learning (DRL) is utilized to dynamically integrate fine-grained strategies to find a synthesis strategy which meets the requirements of the intent. Finally, a deep neural evolution network (DNEN) was introduced to respond to failures to achieve intent guarantee at the millisecond level. The researchers have validated feasibility and efficiency on an enhanced SDN test platform

The research result has enriched the research on intelligent operation and automation of optical networks based on artificial intelligence. IDON with SAGO is not only of great significance to the research of operation automation of optical networks, but also has very important scientific significance and reference value for the application of zero-touch operation and artificial intelligence in networks.

"To the best of our knowledge," the researchers wrote, "We have investigated and presented the functional entities of the architecture and interworking procedure in optical network automatic operation. The performances are demonstrated on the testbed for intent-based control. Our experiments verify that IDON with SAGO can effectively perform the intent translation and zero-touch configuration."

Oxidation of primary alcohols to carboxylic acids is of importance in both organic chemistry and chemical industry because the oxidation products can be used to prepare various pharmaceuticals and useful chemicals. Photocatalytic oxidation process has been considered as a sustainable technology to achieve the selective oxidation under ambient conditions with irradiation from solar light. To develop superior photocatalysts with a broad-range of light absorption and efficient electron-hole separation, surface modification with metal nanoparticles such as Au and Pt allow for the fast transfer of photoexcited electrons to the surface active sites. Therefore, bimetallic Au and Pt catalysts would be desirable by combining the advantages of both surface plasmonic resonance effect on Au and activation effect on Pt to further enhance the efficiency for catalytic oxidation under visible light irradiation.

Hollow structured materials have shown great potential in a variety of applications, including catalysis, drug release and delivery, and energy storage and conversion. High specific surface area and discrete voids afford abundant accessible surface sites and immobilization of reactive centers for catalytic reactions. More reactant molecules can be adsorbed and enriched within the hollow structure to accelerate reactions. However, it remains challenge to develop a facile and mild synthetic method to simultaneously create efficient hollow photocatalytic nanoreactor with ordered porous channels on the shell, well-controlled metal location, broad-spectrum utilization and well-controlled mass transfer and diffusion.

In a new research article published in the Beijing-based National Science Review, scientists at Dalian Institute of Chemical Physics, Chinese Academy of Sciences, University of Surrey,University of Technology Sydney and The University of Sydney demonstrated a facile synthesis of hollow-structured photocatalysts with controllable spatial location of active metals, chemical compositions and tunable shell thickness. Hollow structures can be achieved through coating SiO2 on the surface of ZIF-8 and a subsequent hydrothermal treatment. The formation mechanism of hollow structure is systematically investigated and a "adhesive-contraction" model is proposed. AuPt@HMZS nanoreactors exhibited broader absorbance region under visible light and excellent catalytic activity in cinnamyl alcohol oxidation to cinnamic acid with 99% selectivity.

AuPt@HMZS nanoreactors has the following advantages: i) Broader absorbance region under visible light; ii) Multiple light scattering can be generated within a hollow void to enhance light-harvesting process and heat generated by the photo-thermal effect is collected; iii) The uniform channels are excellent to facilitate the reactant diffusion and mass transfer; iv) A synergetic effect among plasmonic hot electron injection and electron trapping improves solar energy utilization and electron-hole separation of photocatalysts; v) The strong metal-metal interactions at the alloy interface tune the reaction performance. "The proposed strategy to build hollow structures as multifunctional micro/nanoreactors is promising for the design of high-performance and sustainable catalysts for chemical synthesis." Prof. Jian Liu said. "It is an amazing technology for construction of micro/nanoreactors with precise spatial location of active sites" Prof. Jun Huang added.

Zombies or enemies flashing right before your eyes and the dizzying feeling of standing on the edge of a cliff using virtual reality and augmented reality (AR and VR) are no longer exclusive to the games or media industries. Those technologies allow us to conduct virtual conferences, share presentations and videos, and communicate in real time in the virtual space. But because of the high cost and bulkiness of VR and AR devices, the virtual world is not within easy reach.

Recently, a South Korean research team developed moldable nanomaterials and a printing technology using metamaterials, allowing the commercialization of inexpensive and thin VR and AR devices.

Professor Junsuk Rho of the departments of mechanical engineering and chemical engineering and doctoral student in mechanical engineering Gwanho Yoon at POSTECH with Professor Heon Lee and researcher Kwan Kim of department of material science at Korea University have jointly developed a new nanomaterial and large-scale nanoprinting technology for commercialization of metamaterials. The research findings, which solve the issue of device size and high production costs that were problematic in previous researches, were recently published in Nature Communications, a prestigious scientific journal.

Metamaterials are substances made from artificial atoms that do not exist in nature but they freely control the properties of light. An invisible cloak that makes an illusion of disappearance by adjusting the refraction or diffraction of light, or metaholograms that can produce different hologram images depending on the direction of light's entrance, uses this metamaterial.

Using this principle, the ultrathin metalens technology, which can replace the conventional optical system with extremely thinness, was recently selected as one of the top 10 emerging technologies to change the world in 2019 at the World Economic Forum.

In order to make metamaterials, artificial atoms smaller than the wavelengths of light must be meticulously constructed and arranged. Until now, metamaterials have been produced through a method called electron beam lithography (EBL)*.

However, EBL has hindered the commercialization or production of sizable metamaterials due to its slow process speed and high cost of production.

To overcome these limitations, the joint research team developed a new nanomaterial based on nanoparticle composite that can be molded freely while having optical characteristics suitable for fabricating metamaterials. The team also succeeded in developing a one-step printing technique that can shape the materials in a single-step process.

The team succeeded in producing an ultrathin metalens that is 100 times thinner than the strand of a human hair by using this newly developed technology. Metamaterials can be made into one-thousandth of thickness of heavy glass or plastic lenses. This is the first time in the world such ultrathin metalens was produced in a single-step printing process.

If the cost of making a metalens at the performance of conventional glass lenses were one million won (USD 8,200) per unit, this technology enables the production at about 10,000 won (USD 8), which is 1/100 the cost and 1/10,000 the thickness in a simplified process.

Professor Rho, who led the research, stated, "This one-step printing technology of nanomaterials allows the fabrication of metamaterials over 100 times faster than the conventional electron beam lithography." He added, "These lenses can not only make the existing thick, large VR and AR lenses or glasses dramatically lighter and smaller, but can also be applied to curved or flexible panels, which facilitates the use of metamaterials in large omnidirectional invisible cloaks or in curved or bendable wearable devices at a fraction of the cost."

An alternating cycle of 50 days of strict lockdown followed by 30 days of easing could be an effective strategy for reducing the number of COVID-19-related deaths and admissions to intensive care units, say an international team of researchers.

The coronavirus pandemic has imposed an unprecedented challenge on global healthcare systems, societies and governments. The virus SARS-CoV-2, which causes COVID-19 disease, has been detected in every country, with more than 4.6 million confirmed cases and a death toll of 312,000 worldwide to date.

There are currently no effective treatments for the disease and a widely-available vaccine is likely to be at least a year away. The principal strategy to control the disease globally has focused on measures that minimise person-to-person transmission of SARS-CoV-2 through social distancing; including isolating suspected infected individuals, shielding vulnerable groups, school closures, and lockdowns.

While such measures are effective at slowing disease spread and preventing health systems becoming overwhelmed, these measures can also lead to significant job losses, financial insecurity and social disruption. As such, there is a growing concern that these interventions may be unsustainable over the long term. An alternative approach may be to alternate stricter measures with intervals of relaxed social distancing (with measures of effective "test-contact trace-isolate" and shielding of the vulnerable kept in place).

However, it is unclear what the frequency and duration of such dynamic interventions should be and which strategy could be adapted globally across countries with diverse health and economic infrastructures.

To address these uncertainties, an international team of researchers from the Global Dynamic Interventions Strategies for COVID-19 Collaborative Group modelled three scenarios across sixteen countries, from Belgium to India, that vary in setting and income. Their results are published today in the European Journal of Epidemiology.

In particular, the researchers were interested in the difference in impact between strategies aimed at mitigation and those aimed at suppression. Mitigation measures reduce the number of new infections, but at a relatively slow rate. These might include a combination of measures, such as general social distancing, hygiene rules, case-based isolation, shielding of vulnerable groups, school closures or restricting of large public events. On the other hand, suppression measures lead to a faster reduction in the number of new infections by applying additional interventions such as strict physical distancing, including lockdown.

The first scenario modelled the impact of imposing no measures. As might be expected, the number of patients requiring treatment in intensive care units (ICUs) would quickly exceed the available capacity significantly for every single country, resulting in a total of 7.8 million deaths across the 16 countries. Under this scenario, the duration of the epidemic would last nearly 200 days in the majority of the countries included.

The second scenario modelled a rolling cycle of 50-day mitigation measures followed by a 30-day relaxing. Such a strategy would be likely to reduce the R number (the number of people each infected individual goes on to infect) to 0.8 in all countries. However, it would still be insufficient to keep the number of patients requiring ICU care below the available critical care capacity. While proving effective for the first three months for all the countries, after the first relaxation, the number of patients requiring ICU care would exceed the hospital capacity and would result in 3.5 million deaths across the 16 countries. In this scenario, the pandemic would last approximately 12 months in high-income countries, and about 18 months or longer in the other settings.

The final scenario involved a rolling cycle of stricter, 50-day suppression measures followed by a 30-day relaxing. Such intermittent cycles would reduce the R number to 0.5 and keep ICU demand within national capacity in all countries. Since more individuals remain susceptible at the end of each cycle of suppression and relaxation, such an approach would result in a longer pandemic, lasting beyond 18 months in all countries. However, a significantly smaller number of people - just over 130,000 across the 16 countries modelled - would die during that period.

In comparison, the team found that after a continuous, three-month strategy of strict suppression measures, most countries would reduce new cases to near zero. Looser, mitigation strategies would require approximately 6.5 months to reach the same point. However, such prolonged lockdowns would be unsustainable in most countries due to potential knock-on impacts on economy and livelihood.

Dr Rajiv Chowdhury, a global health epidemiologist the University of Cambridge, UK, and lead author on the paper, said: "Our models predict that dynamic cycles of 50-day suppression followed by a 30-day relaxation are effective at lowering the number of deaths significantly for all countries throughout the 18-month period.

"This intermittent combination of strict social distancing, and a relatively relaxed period, with efficient testing, case isolation, contact tracing and shielding the vulnerable, may allow populations and their national economies to 'breathe' at intervals - a potential that might make this solution more sustainable, especially in resource-poor regions."

The researchers say that the specific durations of these interventions would need to be defined by specific countries according to their needs and local facilities. The key is to identify a pattern that allows countries to protect the health of the population not only from COVID-19 but also from economic hardship and mental health issues.

Professor Oscar Franco from the University of Bern, Switzerland, said: "Our study provides a strategic option that countries can use to help control COVID-19 and delay the peak rate of infections. This should allow them to buy valuable time to shore up their health systems and increase efforts to develop new treatments or vaccines.

"There's no simple answer to the question of which strategy to choose. Countries - particularly low-income countries - will have to weigh up the dilemma of preventing COVID-19 related deaths and public health system failure with the long-term economic collapse and hardship."

The largest prospective study of adult COVID-19 patients in USA to date confirms that critical illness is common among hospitalized patients (22%, 257/1150). Critically ill COVID-19 patients frequently require mechanical ventilation (79%, 203/257) and death rates among such patients are high (39%, 101/257). Risk factors associated with in-hospital death, including older age and chronic heart and lung disease, are consistent with reports from Italy, China and the UK.

A detailed report from 257 COVID-19 patients admitted to two hospitals in New York City, USA from 2 March to 1 April 2020, and followed for at least 28 days, is published today in The Lancet, offering a snapshot of how the virus affects adults requiring hospital care.

The study reports a high incidence of critical illness (22%, 257/1150) and a high dependency on mechanical ventilation to support breathing in critically ill patients (79%, 203/257). The researchers say this has important implications for US hospital systems and specifically the need to prepare for large numbers of patients requiring intensive care.

The findings mirror reports from China, Italy and the UK, with older age and pre-existing conditions being the strongest risk factors associated with poor outcomes.

Dr Natalie Yip, one of the authors of the study, from Columbia University Irving Medical Centre, USA, says: "In the USA, there have been almost 1.5 million confirmed cases of COVID-19 and nearly 90,000 deaths [1]. Although the clinical spectrum of disease has been characterised in reports from China and Italy, until now, detailed understanding of how the virus is affecting critically ill patients in the US has been limited to reports from a small number of cases. Our study aimed to identify risk factors associated with death in critically ill COVID-19 patients in a US hospital setting." [2]

The study focused on two hospitals in New York City, USA, affiliated with Columbia University Irving Medical Center in northern Manhattan. Between 2 March and 1 April 2020, 1,150 adults (aged 18 or over) were admitted to both hospitals with laboratory confirmed COVID-19. Of those admitted to hospital, 257 (22%) were critically ill and required treatment in a high dependency or intensive care unit. The most common symptoms reported were shortness of breath, fever, cough, muscle pain and diarrhoea. As of 28 April 2020, almost 40% of the critically ill patients had died (39%, 101/257) and more than one third remained in hospital (37%, 94/257). Less than one quarter had been discharged alive (23%, 58/257).

More than three quarters of the critically ill patients required mechanical ventilation to help them breathe (79%, 203/257). Patients spent an average of 18 days on a ventilator (range 9-28 days). This rate is higher than reported in smaller studies of cases from Washington state, USA [3, 4], but is in line with a recent report from Italy [5], the researchers say. In addition, almost one third of patients developed severe kidney damage and required therapy to support kidney function, such as dialysis (31%, 79/257).

The majority of critically ill patients were men (67%, 171/257). Critical illness was more common in older patients (median age 62 years) but around one in five patients were aged under 50 (22%, 55/257). More than 80% of critically ill patients had at least one chronic illness, the most common of which were high blood pressure (63%, 162/257) and diabetes (36%, 92/257). Nearly half of the patients were obese (46%, 119/257), consistent with trends seen in the UK. Almost two-thirds of critically ill patients were Hispanic or Latino (62%, 159/257) and around one in five were black or African American (19%, 49/257).

People with pre-existing lung or heart conditions had the highest risk of poorer outcomes. High blood pressure was also associated with poorer survival for critically ill patients, consistent with reports from China and Italy.

5% of critically ill patients were employed as healthcare workers (13/257). It is not possible to determine with certainty whether they became infected while working in a clinical setting because the virus was already circulating widely in the community at the time. However, the finding highlights the risks facing frontline healthcare workers and underlines the importance of consistent access to personal protective equipment for hospital staff.

Dr Max O'Donnell, senior author of the study, from Columbia University Irving Medical Centre, USA, says: "Our study provides in-depth understanding of how COVID-19 may be affecting critically ill patients in US hospitals. Of particular interest is the finding that over three quarters of critically ill patients required a ventilator and almost one third required renal dialysis support. This has important implications for resource allocation in hospitals, where access to equipment and specialised staff needed to deliver this level of care is limited." [2]

The researchers caution that their findings may not be generalizable to other hospital settings as they only looked at patients from two hospitals in New York City. This is particularly important when considering the demographic characteristics of the patient population. Studies involving patient groups that are more racially, ethnically and geographically diverse will be needed in order to confirm these findings.

Writing in a linked Comment article, Dr Giacomo Grasselli, who was not involved in the study, from the University of Milan, said: "The study by Cummings and colleagues shows that clinicians can produce high-quality research even when facing an overwhelming clinical workload. However, despite providing important insights, this work leaves us with some unanswered questions. While waiting for the availability of a COVID-19 vaccine, further studies are required to improve and personalise patient treatment, with particular attention to the role of initial non-invasive respiratory support strategies, timing of intubation, optimal setting of mechanical ventilation, and efficacy and safety of immunomodulating agents and anticoagulation strategies."

When early tetrapods transitioned from water to land the way they breathed air underwent an evolutionary revolution. Fish use muscles in their head to pump water over their gills. The first land animals utilized a similar technique--modern frogs still use their head and throat to force air into their lungs. Then another major transformation in vertebrate evolution took place that shifted breathing from the head to the torso. In reptiles and mammals, the ribs expand to create a space in the chest that draws in breath. But what caused the shift?

A new study published on May 12 in Scientific Reports posits a new hypothesis--the intermediate step was driven by locomotion.

When lizards walk, they bend side-to-side in a sprawling gait. The ribs and vertebrae are crucial to this movement, but it was unclear how until now. Researchers captured the 3-D motion of lizard ribs and vertebrae using XROMM, a combination of CT scans and X-ray videos. They recorded three savannah monitor lizards and three Argentine black and white tegus walking slowly on a treadmill. The resulting images revealed that while the spine is bending, every rib in both species rotated substantially around its vertebral joint, twisting forward on one side of the body and backward on the other side alternatively with each stride. The mechanics follow nearly the same pattern as when the reptiles inhale and exhale.

"It's really exciting because we didn't previously have plausible hypotheses for how rib-breathing evolved," said first author Robert Cieri, a postdoc at the University of the Sunshine Coast and who conducted the research while at the University of Utah, where he is still affiliated. "We're proposing that these rib movements first started to facilitate locomotion, then were co-opted for breathing."

The work also included John Capano and Elizabeth Brainerd at Brown University, and undergraduate Samuel Hatch at the U.

Why did the lizard cross the road? To catch its breath.

Reptiles, birds and mammals, all considered amniotes, use costal aspiration where the ribs and vertebrae control breathing by expanding and contracting. The motion is facilitated by the ribs rotating around the vertebrocostal joints--where the ribs and vertebrae meet. It's possible that an early amniote ancestor first used these rib movements to enhance its lateral undulation, the side-to-side trunk motion that helps propel lizards forward. During locomotion, each limb has two phases: First is propulsion, which is when the foot is pushing against the ground. Second is swing, which is when the foot is in the air. The new research found that during the arm's propulsion phase, the ribs on the same side of the body rotate towards the head, and while it's in the swing phase, they rotate towards the tail. This mimics what the scientists previously found the ribs doing inhalation and exhalation--but this time simultaneously on both sides.

Early tetrapods used sprawling, undulatory locomotion, but likely still had a head-driven breathing system. The authors propose that rib movements and increased costal joint mobility evolved during locomotion to increase stride length, hold the thorax steady, or as the passive result of the ribs moving to prevent being bunched together as the animals bended. At some point, early amniotes evolved the ability to express these rib movements on both sides simultaneously, which allowed for the expansion and contraction of the trunk that support inhalation and exhalation.

"Aspiration breathing was one of the key innovations that allowed amniotes to diversify on land. We were surprised and thrilled to find clues to how it evolved from a study on locomotion," co-author Brainerd said.

A collaboration between scientists at the Medical University of South Carolina and clinicians at the Greenwood Genetic Center has yielded new findings about how a particular gene might regulate brain development.

A paper published in Biological Psychiatry showcases how the researchers connected problems in mice with a defective copy of the MEF2C gene to issues suffered in real life by patients seen at the Greenwood Genetic Center who also have a defective copy of that gene.

Those patients have a rare form of autism called MEF2C haploinsufficiency syndrome. Basically, one of their two MEF2C genes in each cell is nonfunctioning, and the one non-mutated copy of the gene isn't powerful enough to regulate brain development the way it should, said Christopher Cowan, Ph.D., chairman of the Department of Neuroscience, whose lab conducted the study. The result in humans includes an inability to use language to communicate, epilepsy, repetitive movements, low muscle tone and breathing problems.

Cowan said the results of the study raise new prospects for treatment.

"We know the problem. The individuals have half as much MEF2C as they need. So, from a therapy standpoint, I think it opens a lot of interesting doors. We can think about ways to introduce more MEF2C into the brain during critical periods of development," he said.

It's not yet clear when interventions could be effective or if there is a developmental point of no return, he said. However, he noted that most children with this syndrome experience seizures by 20 months old, which could be a trigger for genetic testing and then potential treatment.

Cowan has been studying MEF2C for more than a decade. He'd previously found the MEF2 family is involved in synaptic pruning, the process by which the brain becomes more efficient as it prunes away redundant or irrelevant synaptic connections; this process occurs through young adulthood but is most active in the preschool and elementary school years. He'd also observed a connection to fragile X syndrome, the most common inherited form of autism.

When Cowan moved to South Carolina in 2016, he gave a talk at the Greenwood Genetic Center about his latest research findings, including information about MEF2C. More recently, the paper's joint lead authors, Adam Harrington, a postdoctoral scholar, and Catherine Bridges, an MUSC medical scientist training program student, both made presentations at a South Carolina Autism and Neurodevelopmental Disorders Consortium conference about their work on MEF2C in mice.

There to hear the talks was Steve Skinner, M.D., director of the Greenwood Genetic Center. As he listened, Skinner realized he'd just seen a patient with this gene dysfunction. Cowan and his team were excited about the opportunity to connect and interested in meeting human patients, Skinner said.

From there, the collaboration blossomed.

Cowan said that when they first created a mouse model of MEF2C haploinsufficiency syndrome, they looked to the scientific literature to see what gene mutations had already been found. They realized that nearly all the mutations were in the DNA binding region, affecting the most highly conserved portion of the protein MEF2C. Highly conserved protein regions have barely changed through millions of years of evolution - they remain nearly identical whether in yeast, flies or humans, strongly suggesting they serve a very important function.

And this particular protein is a transcription factor, which sits in the nucleus of the cell, binds to DNA and turns on hundreds of other genes, Cowan said. Those other genes must be activated at just the right time for neurons to mature, form appropriate connections and change in response to experiences, he said. That the mutations were occurring in this "hub" gene hinted that the mutations were causing problems for the protein to bind to DNA.

Indeed, the mouse model that was given one good copy and one inactive copy of MEF2C showed social deficits, hyperactivity, repetitive behavior and a significant reduction in ultrasonic vocalizations, Cowan said.

"We don't know for sure what mouse ultrasonic vocalization means to another mouse, but they generate them in social contexts," Cowan said. Researchers consider vocalizations a "species-appropriate communication mode," and this communication problem in mice mirrors the communication problems of the children in the study, he said.

When the team analyzed the genes in the mouse brains that were abnormally expressed and compared them to the human genome, two areas pinged. The first was excitatory neurons, and the second was the microglia, what Cowan calls "the brain's resident immune cell." Microglia eat up dead cells after an injury or a stroke and also physically remove synaptic material to help with pruning during normal brain development.

The scientists then removed MEF2C from just the neuronal cells or just the microglia, which produced different subsets of autism-like behaviors.

"For the field, I think it's important because it's starting to help us appreciate that neurodevelopmental disorders are probably a convergence of dysfunction or altered development of multiple different cell types. This has treatment implications as well because you can't just target the neuronal population. You can't just target microglia. You're probably going to have to think about the cluster of different cooperating cell types in the brain that lead to a typically functioning brain,"' Cowan said.

Research is continuing with cooperation from families across the world with children with this disorder. They're a small group, relatively speaking, but the internet and social media have given patients with rare disorders the opportunity to combine forces in looking for answers and even charting a path for research, Skinner said. For example, parents of children with Rett syndrome, another rare neurodevelopmental disorder, noted that their children often suffered from gallbladder diseases at a young age. Nowhere was this described in the scientific literature, but the parents saw the common thread among their children. As they began pressing for confirmation, Skinner said, researchers began looking at the question and found the connection the parents had intuited.

"Parents want to drive research to eventually find a treatment for their children," Skinner said.

The parents of children with MEF2C haploinsufficiency syndrome deeply appreciate the opportunity to talk to a researcher like Cowan, he said. The online support and information group, which consists of a few hundred families from across the world, is participating in further research, too. The research team recruited a Clemson University graduate student who developed a questionnaire that she sent to these families. It covers topics like when symptoms appeared, which symptoms appeared and treatments they have tried.

Skinner said the cooperative effort with MUSC has been rewarding.

"It's been a very collegial and collaborative relationship," he said. "Dr. Cowan has been very receptive to fielding questions from us, from the patients and families."

Cowan, for his part, said the relationship has been helpful in providing real-world context for his lab's work.

"Right in our own backyard, here in South Carolina, there are the tools and the research capabilities to be able to attack these really complex problems in biology. It's been a really great collaboration," he said.

BLOOMINGTON, Ind. -- As millions continue working from home during the pandemic or are required to report to jobs as essential employees, many have raised questions about how these work conditions impact our health -- and not just as they relate to COVID-19.

A new study from the Indiana University Kelley School of Business finds that our mental health and mortality have a strong correlation with the amount of autonomy we have at our job, our workload and job demands, and our cognitive ability to deal with those demands.

"When job demands are greater than the control afforded by the job or an individual's ability to deal with those demands, there is a deterioration of their mental health and, accordingly, an increased likelihood of death," said Erik Gonzalez-Mulé, assistant professor of organizational behavior and human resources at the Kelley School and the paper's lead author.

"We examined how job control -- or the amount of autonomy employees have at work -- and cognitive ability -- or people's ability to learn and solve problems -- influence how work stressors such as time pressure or workload affect mental and physical health and, ultimately, death," he said. "We found that work stressors are more likely to cause depression and death as a result of jobs in which workers have little control or for people with lower cognitive ability."

On the other hand, Gonzalez-Mulé and his co-author, Bethany Cockburn, assistant professor of management at Northern Illinois University, found that job demands resulted in better physical health and lower likelihood of death when paired with more control of work responsibilities.

"We believe that this is because job control and cognitive ability act as resources that help people cope with work stressors," Gonzalez-Mulé said. "Job control allows people to set their own schedules and prioritize work in a way that helps them achieve their work goals, while people that are smarter are better able to adapt to the demands of a stressful job and figure out ways to deal with stress."

The study, "This Job Is (Literally) Killing Me: A Moderated-Mediated Model Linking Work Characteristics to Mortality," appears in the current issue of the Journal of Applied Psychology. It is a follow-up to previous research the pair published in 2017, which was the first study in the management and applied psychology fields to examine the relationship between job characteristics and mortality.

The researchers used data from 3,148 Wisconsin residents who participated in the nationally representative, longitudinal Midlife in the United States survey. Of those in their sample, 211 participants died during the 20-year study.

"Managers should provide employees working in demanding jobs more control, and in jobs where it is unfeasible to do so, a commensurate reduction in demands. For example, allowing employees to set their own goals or decide how to do their work, or reducing employees' work hours, could improve health," Gonzalez-Mulé said. "Organizations should select people high on cognitive ability for demanding jobs. By doing this, they will benefit from the increased job performance associated with more intelligent employees, while having a healthier workforce.

"COVID-19 might be causing more mental health issues, so it's particularly important that work not exacerbate those problems," Gonzalez-Mulé said. "This includes managing and perhaps reducing employee demands, being aware of employees' cognitive capability to handle demands and providing employees with autonomy are even more important than before the pandemic began."

Researchers in the Ludwig Center at the Johns Hopkins Kimmel Cancer Center report they have identified a drug treatment that could--if given early enough--potentially reduce the risk of death from the most serious complication of Coronavirus disease 2019 (COVID-19), also known as SARS-CoV-2 infection.

Prazosin, a U.S. Food and Drug Administration-approved alpha blocker that relaxes blood vessels, may specifically target an extreme inflammatory process often referred to as cytokine storm syndrome (CSS) that disproportionately affects older adults with underlying health conditions, and is associated with disease severity and increased risk of death in COVID-19 infection. Using it pre-emptively to address COVID-19-associated hyperinflammation of the lungs and other organs has the potential to reduce deaths in the most vulnerable populations, they say.

In a report of their findings published April 30 in the Journal of Clinical Investigation, the researchers caution that although they believe if given early enough after viral exposure, the drug could prevent some deaths, it would not work in patients with advanced stages of the disease. They also emphasize that controlled clinical trials for this novel use of prazosin are needed before it can be safely recommended.

The investigators published the letter, they said, in hopes of stimulating rapid efforts to conduct such trials.

In the letter, the researchers described how they have been working in collaboration with researchers in the Johns Hopkins Divisions of Rheumatology and Infectious Diseases, and Departments of Neurology and Neurosurgery, to identify chemical ways of safely blocking the actions of catecholamines and cytokine responses. Together, catecholamines and cytokines enhance the inflammatory process that leads to severe COVID-19 symptoms, explains Chetan Bettegowda, M.D., Ph.D., Jennison and Novak Families Professor of Neurosurgery, who is senior author of the paper.

"The purpose of our article is to make the biomedical community aware of the potential of this approach and to stimulate additional basic and clinical research. Although, we are excited about this idea, we stress that a clinical trial is necessary to know if this intervention will help COVID patients, and that is where we are focusing all of our attention," says Bettegowda.

In mouse models of CSS, they found that prazosin--commonly used to treat blood pressure, prostate gland enlargement and other conditions--blocked catecholamines (hormones released by the adrenal glands when the body is under stress), reduced cytokine levels, and increased survival after exposure to agents that trigger cytokine storm responses similar to those observed in COVID-19.

Drugs that target CSS have been found to reduce the risk of death from other viral illnesses by up to 55%, according to preliminary results from a retrospective clinical study.

Prazosin is taken by mouth, costs less than $25 per month in the United States, and has been safely taken by millions of people over the last two decades. This should enable highly expedited clinical trials in people early after exposure to the SARS-CoV-2 virus, say the researchers.

"All drugs can have unanticipated side effects when used in new situations, so it is critical to evaluate the effectiveness and side effects of this drug in controlled clinical trials before it can be safely recommended for public use. This is particularly important for drugs like prazosin, which are already sold in pharmacies," says Bettegowda.

Maximilian Konig, M.D., research fellow and lead author of the report, says a vaccine remains the best long-term hope to prevent deaths from COVID-19 but notes, at present, there are hundreds of individuals throughout the world who are dying every day. "Prazosin is already widely available, known to be safe and inexpensive, and the regulatory path for use in individuals exposed to the virus is straightforward," he says.

The CSS treatment was granted Food and Drug Administration approval to be studied in a clinical trial for individuals with COVID-19.

Sometimes proteins misfold. When that happens in the human brain, the pileup of misfolded proteins can lead to neurodegenerative diseases like Alzheimer's, Parkinson's and ALS.

Proteins do not misbehave and misfold out of the blue. There is a delicate ecosystem of biochemical interactions and environments that usually let them twist, unfold, refold and do their jobs as they're meant to.

However, as researchers from Michigan Technological University explore in an article published in ACS Chemical Neuroscience, even a small change may cause long-term consequences.

For amyloid beta peptides -- considered a major hallmark of Alzheimer's disease -- a common chemical modification at a particular location on the molecule has a butterfly effect that leads to protein misfolding, aggregation and cellular toxicity.

Ashutosh Tiwari, associate professor of chemistry at Michigan Tech, explains that misfolded amyloid beta proteins tend to pile up and form aggregates, which can form stringy fibrils or balled-up amorphous shapes.

To understand what causes the different shapes and to assess their toxicity, Tiwari's team looked at acetylation.

Acetylation is one of the most common chemical modifications proteins undergo, but one of the least researched in terms of how it affects amyloid beta toxicity. On amyloid beta proteins, acetylation can occur at two sites: lysine 16 and lysine 28.

The team found that acetylation at lysine 16 led to the disordered aggregates that formed sticky but flexible amorphous structures and showed high levels of toxicity. They also found the aggregates showed higher free radical formation.

"No one has done a systematic study to show if you acetylate amyloid beta it changes how the aggregate looks, then it changes its biophysical properties and hence toxicity," Tiwari said. "What we're saying is that the shape, stickiness and flexibility of the aggregated protein structure can play a vital role in the cellular toxicity and may also affect the mechanism of toxicity."

In Alzheimer's, these aggregates accumulate in the part of the brain that affects memory. It's a disease that the Alzheimer's Organization reports is the sixth leading cause of death in the US and will cost the nation about $305 billion in 2020. Tiwari says what we truly need to understand about the disease is that there is no single cause, no single trigger, and probably no silver bullet because of the chemistry involved.

"This is how a subtle change on a single position can affect a whole protein's aggregation," Tiwari said, adding that the effect of acetylation on tau, another protein aggregation, has been far more studied than amyloid beta. Also, many researchers still think a misfolded protein has to look a certain way to become problematic, and that other misfolded forms are less of an issue.

Tiwari agrees some of the proteins' changes are subtle, and compares discerning the differences and their effects to snow tires. Snow tires have deeper treads and a more flexible material to handle winter roads, but it's hard to point out those features at highway speeds. Like different kinds of tires, protein shapes can appear indistinguishable at a distance.

"This is not something that can be viewed from afar -- it's a touch-and-feel property," Tiwari said. "We have to interrogate these properties. We have to look at these structures more deeply from both morphology and biophysical perspectives."

When we do, we may better understand the complexity of the misfolded proteins and amyloid beta toxicity that can cause neurodegenerative diseases like Alzheimer's.

COLD SPRING HARBOR, NEW YORK -- In an important, comprehensive, and timely review, an expert team from the University of California Berkeley details the methodologies used in nucleic acid-based tests for detecting the presence of SARS-CoV-2, the virus that causes COVID-19. They show that these tests vary widely in applicability to mass screening and urge further improvements in testing technologies to increase speed and availability.

Testing for the presence of the SARS-CoV-2 virus has been extensively discussed during the COVID-19 pandemic. The most sensitive tests measure the presence of the virus' genetic material, RNA, in a patient's sample, suggesting an ongoing infection. A huge effort is needed to scale up COVID-19 testing to a level required to ensure public safety. Many tests take several hours to complete and require extensive human labor as well as materials and equipment that are not universally available. There is a pressing need for alternatives, and the research community worldwide has provided a large number of them in journal articles and preprints (papers that have not yet been peer reviewed). The Berkeley scientists have assessed these approaches and show that some tests take minutes, some take hours, many are done in different ways, and they vary in cost and potential for mass use. The authors are "hopeful that the explosion of creative and multifaceted approaches to COVID-19 nucleic-acid testing will continue to seed solutions as society addresses the COVID-19 pandemic."

According to a UC Davis study, adolescents and young adults with autism spectrum disorder (ASD) and those with typical development show similar proactive cognitive control. However, symptoms of depression in individuals with autism were linked to less proactive control.

Cognitive control refers to a set of mental processes that coordinate thoughts and behaviors to fit one's goals and intentions. One type of cognitive control is proactive control, characterized by being actively ready and prepared by focusing on goal-relevant information ahead of time.

"Proactive control is a very important cognitive function that allows you to plan and prepare how to direct your attention. It allows you to follow directions or achieve certain goals without getting distracted," said Marie Krug, assistant project scientist in the Solomon Lab at the UC Davis MIND Institute and lead author of the study.

Autism, depression symptoms and cognitive control

In this study, published May 14 in the Journal of Abnormal Psychology, the researchers examined whether proactive control is different in adolescents and young adults with ASD than in individuals with typical development. They also studied how repetitive behaviors (a symptom of ASD) and psychological disorders (such as depression, anxiety and attention-deficit/hyperactivity disorder) are related to proactive control.

The study consisted of 88 participants (44 with ASD and 44 with typical development) between the ages of 12 and 22. The participants were enrolled in the Cognitive Control in Autism (CoCoA) Study at the UC Davis MIND Institute.

The researchers assessed proactive control using a picture-word Stroop test. They asked participants to name animals depicted in drawings with a superimposed word. They calculated "interference effects" by measuring the difference in the participants' reaction time between difficult incongruent trials (with nonmatching animal pictures and words) and simpler congruent trials (with matching animal pictures and words). They used two versions of the Stroop task: a mostly congruent block and a mostly incongruent block.

The researchers calculated proactive control as the reduction in the participant's interference effect for the mostly incongruent block compared to the mostly congruent block.

The study did not find any association between proactive control and repetitive behaviors, anxiety or attention-deficit/hyperactivity problems in the ASD group. Participants with autism who had more symptoms of depression showed less ability to implement proactive control.

People with autism experience depression four times more often than their neurotypical peers. One key symptom of depression is rumination, the act of dwelling on negative thoughts. Rumination may drain or limit cognitive resources needed to exercise proactive control. This was especially true in mostly incongruent blocks where cognitive resources are needed the most.

"This study helps us better understand the cognitive strengths and challenges in persons with autism," said Marjorie Solomon, professor of psychiatry and behavioral sciences at UC Davis and senior author of the study. "It also provides clues on the impact of co-existing conditions such as depression on these persons with autism, and thereby aids researchers with treatment development."

Researchers at the Beckman Institute at the University of Illinois at Urbana-Champaign have developed a new technique that can determine the specific molecular form, location, and the amount of lipids in samples of rat brain tissue. The technique provides more information than previous methods.

The paper "Quantitative Imprint Mass Spectrometry Imaging of Endogenous Ceramides in Rat Brain Tissue with Kinetic Calibration" was published in Analytical Chemistry.

"The brain is like a bar of butter. The most common molecules are water and lipids," said Jonathan Sweedler, James R. Eiszner Family Endowed Chair in Chemistry and the director of the School of Chemical Sciences. "Unfortunately, we don't fully understand the chemical complexity of lipids in the brain, which makes it hard to know their functions and how they are affected by different diseases."

Previous research in the field determined the lipid composition in a brain region, but not the localization or amount. The Sweedler Research Group refined a new technique called mass spectroscopy imaging that measures all three. "The technique allows us to look at a slice of a rat brain and figure out the locations of specific and unusual lipids," Sweedler said.

Members of the Sweedler Research Group imprinted the tissues onto slides containing chemicals that could diffuse into the tissues and vice versa. "It's like taking a piece of paper with ink and putting silly putty on it and seeing the image on the silly putty," Sweedler said. Using this technique, the researchers were able to determine the distribution and amount of ceramides, which are important in learning and memory, in the tissue samples.

However, there are disadvantages to the technique. "Although it works well for certain categories of lipids, we haven't shown that it works for the molecules found in the brain," Sweedler said. "Additionally, it requires more steps because you have to prepare the brain sample and the surfaces that have the chemical coating."

The researchers hope that this technique will help them look at how the lipid composition changes in response to pain medicines and drugs of abuse. This may help in the search for alternatives to existing treatments for chronic pain.

Medical personnel treating coronavirus cases in China have higher rates of anxiety and other mental health symptoms than the general population, according to a new study in the open-access journal PLOS ONE by Ning Sun of Ningbo College of Health Science in Ningbo China, and colleagues.

During the height of China's COVID-19 outbreak this year, more than 30,000 medical personnel from around China provided direct support to critically ill COVID-19 patients in Hubei province, the epicenter of the pandemic. These healthcare providers were confronted by stressors not typical to their usual jobs. Anecdotal evidence has suggested that the psychological toll of being on the front line of this pandemic may lead to an uptick in mental health disorders among healthcare providers.

In the new study, 560 medical personnel from 12 hospitals in eight provinces and cities across China completed an online questionnaire regarding their mental health status. The survey, carried out in January and February 2020, collected demographic information, information about COVID-19 exposure and work, and used the well-established Symptom-Checklist-90 (SCL-90) to quantify mental health symptoms. The subjects were 75 percent nurses and 25 percent doctors, with 72 percent being female.

The healthcare providers surveyed scored higher on scales of somatization (experiencing physical symptoms of psychiatric conditions), obsessive-compulsive symptoms, anxiety, phobic anxiety and psychoticism compared to a national average (p

The authors add: "The overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China."