Culture

Sociodemographic characteristics, inequities associated with access to in-person, remote elementary schooling during pandemic in New York State

What The Study Did: Among the few New York state public school districts providing full-time in-person elementary school instruction during the COVID-19 pandemic, most districts served predominately white students, rural/suburban students and children who were not disadvantaged (children who were not from a low-income family, were not English language learners, did not have homelessness, and did not have a disability).

Authors: Ashley M. Fox, Ph.D., M.A., of the University at Albany, State University of New York (SUNY), is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2021.17267)

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

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

Credit: 
JAMA Network

Scientists create rechargeable swimming microrobots using oil and water

By combining oil drops with water containing a detergent-like substance, the scientists found they could produce artificial swimmers that are able to swim independently and even harvest energy to recharge.

The oil droplets use fluctuating temperature changes in their surrounding environment to store energy and to swim. When cooled, the droplets release thin 'tail-like' threads into the environment. The friction generated between the tails and surrounding fluid, pushes the droplet causing them to move. On heating, the droplets then retract their tails returning to their original state, and harness the heat from their environment to recharge.

The researchers show that the droplets recharge multiple times and are able to swim for periods of up to 12 minutes at a time.

Dr Stoyan Smoukov, Reader in Chemical Engineering at Queen Mary University of London and author of the study, said: "In biology, research shows that to create even the simplest artificial cells we need over 470 genes. However, through this international collaboration, we show that just by using a few simple and inexpensive components we can create a new type of active matter that can change shape and move just like a living thing."

"We hope that this study will open up the opportunity for people to engage in cutting-edge science. As the only equipment needed is a simple optical microscope, people could create these microswimmers with the most basic laboratory set-ups, or even at home. With thousands of swimmers per drop of water, it's a world in a drop situation. And when it costs 7p per teaspoon, there's plenty for everyone."

Other types of artificial swimmers exist however their movements are either driven by chemical reactions, which create bubbles that propel the swimmers through fluids, or by physical forces such as magnetic or electric fields. Instead, this new class of swimmers, which are around the size of a red blood cell, are able to spontaneously assemble and move without using external forces.

As the swimmers are not harmful to other living things, the scientists hope they could be used to study the basic interactions between living organisms such as bacteria and algae.

"In nature we often see large numbers of organisms such as bacteria, grouping together but our understanding of how these organisms interact with each other is incomplete. By mixing our simple artificial swimmers with groups of living organisms we could develop a clearer picture of how biological microswimmers communicate with each other. For example, do they only communicate due to the physical act of 'bumping' into each other, or are there other chemicals or signals released into the environment essential for their interaction."

Credit: 
Queen Mary University of London

T-cell 'training grounds' behind robust immune system response seen in adenovirus vaccines

Adenovirus vaccine vectors, such as the ChAdOx1 nCov-19 construct which has risen to prominence as a major vaccine for COVID-19, may generate robust long-term immune system responses, according to scientists from the Universities of Oxford and the Cantonal Hospital St.Gallen, Switzerland.

Writing in the journal Nature Immunology, they detail an investigation into one of the key features of adenovirus vaccines - their ability to generate strong and sustained populations of the 'killer' T-cell element of the immune system.

In an animal model, they observed that adenoviruses are able to get into long-lived tissue cells, known as fibroblastic reticular cells, which in turned formed small, well organised clusters, acting as 'training grounds' for these T-cells, appearing to explain how these vaccines sustain robust immune system responses.

Paul Klenerman, Sidney Truelove Professor of Gastroenterology at the University of Oxford's Nuffield Department of Medicine, and one of the lead authors of the paper, said:

'Millions of people will have received adenovirus vaccines around the world, not only the Oxford-AstraZeneca vaccine, but the J&J vaccine, and also the Chinese and Russian versions. The ultimate goal with these vaccines is the induction of long-term immune system protection using both antibodies and T-cells. This research helps us to understand more on the process of vaccination, and why the effects on killer T-cells are so prolonged.'

The researchers show that adenovirus vectors can target specific cells - known as stromal cells in tissues such as the lung - generating antigen 'depots' in these long-lived cells. These stromal cells were originally thought just to provide an inert scaffold for the tissues, but it appears that they are very dynamic cells with a major role in immune control. The long lived nature of the cells means that the antigen can be 'shown' to the immune system many times, effectively boosting the response, a critical element of generation of protective T-cells.

They were also able to investigate other mechanisms which may explain the particular efficacy of adenovirus vectors, including the key chemical messenger involved in signalling to T cells. This is a factor called IL-33 - a so-called "alarmin" released when the stromal cells receive signals of distress. IL-33 acts to strongly boost to the metabolism of the T cells, resulting in effectively more energetic cells and a highly protective immune response.

Burkhard Ludewig, Professor at the University of Zurich, and Head of the Medical Research Center, Cantonal Hospital St. Gallen, Switzerland, also a lead author of the paper, said:

'Adenoviruses have co-evolved with humans over a very long time, and learned a lot about the human immune system in the process. Viruses are always the best teachers, and here they have taught us an important lesson about how best to boost killer T cell responses. The T cells that come from these cellular training camps appear to have a very high level of "fitness". Hopefully we can put this to good use in designing new vaccines - vaccines that we still desperately need for diseases such as TB, HIV, hepatitis C and cancers.'

The researchers will now continue to investigate these particular pathways for immunization against emerging pathogens, both in pre-clinical models, and clinical studies, with the goal of helping to accelerate further development of crucial vaccines.

Credit: 
University of Oxford

Sperm migration in the genital tract: computer simulations identify factors for success

image: Frozen bovine sperm

Image: 
wikipedia, Uwe Muell

During mating in wildlife species, males transfer millions of sperm into the female genital tract. On the way to the egg cell the sperm have to pass through the genital tract. Very few of the sperm cells actually succeed in passing through and reaching the vicinity of the egg cell. Those that do will then be conditioned for fertilisation. Mechanisms underlying sperm selection and, therefore, reproductive success are largely unknown, as their experimental study in the living organism is very difficult for both ethical and practical reasons. A deeper understanding of the factors which favour successful sperm migration and selection in the context of species-specific reproductive systems would be of great fundamental as well as of applied interest, since for threatened wildlife species this will help recognise reproductive problems and optimise assisted reproduction techniques such as artificial insemination.

The scientist team developed a spatio-temporal computer simulation model of the mammalian female genital tract, in which individual sperm cells were treated as independent agents equipped with a set of biophysical characteristics specifying concrete properties and subjected to specific rules for motion and interaction with the female genital tract. The first implementation used data on bovine genital tract geometry and the biophysical properties and principles of sperm motion of bovine sperm as observed in test tubes. Thus, sperm preferentially swam against a fluid stream (positive rheotaxis) and moved along wall structures (thigmotaxis).

In order to ensure that the model was reasonably realistic in depicting salient features of the interaction between sperm and the female genital tract, the simulation results were compared with published data derived from cattle. The simulation results demonstrated a close match with the observed timing and number of sperm actually reaching the entry of the oviducts.

"As expected, we found that physical sperm characteristics such as velocity and directional stability are essential for successful sperm. In addition, the ability to swim against the mucus flow of cervical secretions as well as the ability of sperm to align to epithelial walls of the genital tract turned out to have a tremendous impact on the chances of a successful transit of sperm to the oviduct," explains Jorin Diemer, doctoral student at the Humboldt-Universität zu Berlin. Karin Müller, leader of the andrology lab at Leibniz-IZW, concludes, "that these identified characteristics of sperm should be considered in future attempts to condition sperm in artificial selection procedures since natural selection processes are normally bypassed in reproductive test tube technologies." This is of particular importance because a species-specific optimal time window for sperm accumulation in the oviduct exists in relation to the timing of ovulation when the oocyte is liberated for fertilisation. "The big advantage of our model is its flexibility, it can be extended and generalised to other systems," highlights Edda Klipp, leader of the Theoretical Biophysics department at Humboldt-Universität zu Berlin. Predictions from this computer simulation system have the potential to improve assisted reproduction in endangered species, livestock and perhaps humans without using animal experiments.

Credit: 
Leibniz Institute for Zoo and Wildlife Research (IZW)

Repairs using light signals

Repairing complex electrical appliances is time consuming and rarely cost-effective. The working group led by Prof. Dr. Karl Mandel, Professorship of Inorganic Chemistry at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), has now developed a smart microparticle that enables defective components in these appliances to be identified more quickly and easily by using light signals. In the long-term, this could make repairs easier and extend the operating life of devices. The results have been published in the journal Advanced Functional Materials.

To identify defective components in a device, particles known as supraparticles are applied to the individual parts. These particles measure between one and ten micrometres and under black light they provide information about the component's identity and temperature history (the temperatures the specific component was recently subjected to) by emitting blue, green and red light. This allows the device to be checked for defects while it is still assembled. The signal ratio between building blocks emitting green and red light determines the identity of the component. The maximum temperature can be read from the signal ratio of blue and green particles. If a specific temperature limit is exceeded, the blue signal irreversibly loses intensity. An overheated and therefore usually damaged micro-component can be detected by the weaker blue light signal it emits. The developed particles make it easier and faster to repair complex electrical devices and extend their operating life.

The supraparticles themselves consist of organic and anorganic nanoparticle building blocks that communicate information only when they are combined. The structure and quantity ratios of the nanoparticles determine the identity signals and temperature sensitivity. By changing the composition of the smart microparticles, the temperature sensitivity and the identity signal can be adapted to a specific product.

Credit: 
Friedrich-Alexander-Universität Erlangen-Nürnberg

Biomolecular bonsai: Controlling the pruning and strengthening of neuron branches

image: Like a bonsai, neurons called mitral cells also grow multiple branches. In the beginning, mitral cells branch into many glomeruli, but as development progresses, a single branch is strengthened and the others are pruned away. Kyushu University researchers studying mouse olfactory neurons found that BMPR-2 is one of the key regulators of selective stabilization of neuron branching and that strengthening of that input only happens in the presence of neuron signaling.

Image: 
Kyushu University, bonsai provided by @h.h.rockkraft on Instagram

Fukuoka, Japan--At this very moment, the billions of neurons in your brain are using their trillions of connections to enable you to read and comprehend this sentence.

Now, by studying the neurons involved in the sense of smell, researchers from Kyushu University's Faculty of Medical Sciences report a new mechanism behind the biomolecular bonsai that selectively strengthens these connections.

How neuronal circuits remodel themselves over time, especially during early development, is an open question in neurobiology. At the start of neuronal development, neurons form excessive amounts of connections that are gradually eliminated as others are strengthened.

Studying a type of olfactory neuron known as a mitral cell in mice, the research team found that the protein BMPR-2 is one of the key regulators of selective stabilization of neuron branching and that the strengthening only happens when the branch receives signals from other neurons.

"A main reason we use olfactory neurons is because they are easy to access and study, and mitral cells develop only a single branch," explains Shuhei Aihara, first author of the study published in Cell Reports.

"When an olfactory neuron detects a specific molecule that we smell, it sends the signal to a specific 'way station' in the brain's olfactory bulb called a glomerulus. That signal is then relayed to the brain through mitral cells. One mitral cell receives signals for one specific smell."

At a very early stage in development, these mitral cells send branches into many glomeruli. As time progresses, these branches--known as dendrites--are pruned away to leave only a single, strong connection. The research team set out to uncover what kind of molecular cues caused one branch to be favored over others.

After analyzing candidate factors known to control dendritic growth and remodeling from extrinsic signals, the team focused on the protein BMPR-2.

"When we disrupted BMPR-2, mitral cells would fail in the selective stabilization and form multiple connections to multiple glomeruli," explains Aihara. "In our next step, we found that BMPR-2 is bound to a protein called LIMK, and only when BMPR-2 is activated by the cell-signaling protein called BMP does it release LIMK into the cell."

LIMK is known to activate the process to assemble actin, the cell's 'skeleton.' Once activated, actin begins to build long fibers that stabilize dendrites.

However, this still did not explain how this mechanism strengthens specific dendrites. The team's next step was to find the elements that activate LIMK. Their investigation led them to identify a well-known neurotransmitter, glutamic acid, as one of the factors that kicks off the process.

"Glutamic acid is required for signals to be transmitted between neurons. Taken together, this means that both BMP and neural signals are necessary to form actin, thereby inducing the construction of a stable dendrite," states Aihara.

"It's like the brake and accelerator in your car. You need to release the brake, in this case BMPR-2 releasing LIMK, and then press on the accelerator--the neurotransmitter signal--for your machinery to move forward. The necessity of simultaneous control, or inputs, is the basis of selective branch stabilization."

Takeshi Imai, who led the team, concludes, "Hopefully these new insights into neural development can lead to further understanding of the fundamental mechanisms behind critical brain functions and possible treatments into pathologies underlined by synaptic dysfunction."

"Our next step is to find the factors that promote dendrite pruning, and we also want to see if this mechanism in the olfactory bulb is fundamental throughout the neocortex."

Credit: 
Kyushu University

Study IDs risk factors for irregular heartbeats in hypertrophic cardiomyopathy patients

image: Christopher Kramer, MD, is the chief of the Division of Cardiovascular Medicine at UVA Health, Virginia's only designated Center of Excellence by the Hypertrophic Cardiomyopathy Association.

Image: 
UVA Health

New research will help doctors identify, treat and prevent potentially dangerous irregular heartbeats in patients with hypertrophic cardiomyopathy (HCM), a common heart condition in which the heart thickens and strains to pump blood.

These chaotic heart rhythms are known as atrial fibrillation. Atrial fibrillation can be asymptomatic, but it can lead to blood clots, stroke or even heart failure. The new research, from an international team of doctors and scientists, identifies risk factors for major atrial fibrillation outcomes, such as the need for procedures or hospitalization for more than 24 hours, in patients with hypertrophic cardiomyopathy.

Age was the dominant predictor, the researchers found. But they also identified a list of other predictors, including obesity as measured by body mass index (BMI). Obesity was particularly important in younger patients, the researchers conclude.

"The latter finding points out the importance of weight loss and exercise in HCM patients," said researcher Christopher Kramer, MD, the chief of the Division of Cardiovascular Medicine at UVA Health, Virginia's only designated Center of Excellence by the Hypertrophic Cardiomyopathy Association. "Until only recently, exercise was thought to be contraindicated in HCM. This is no longer the case based on recent studies."

Atrial Fibrillation in Hypertrophic Cardiomyopathy

Like atrial fibrillation, hypertrophic cardiomyopathy often goes undiagnosed. It is, however, the most common inheritable heart disease, and it is the most common cause of sudden cardiac death in young athletes.

Atrial fibrillation is a common complication among patients with hypertrophic cardiomyopathy. Previous studies have focused on detecting atrial fibrillation, as patients may require blood thinners to prevent stroke. But Kramer and his colleagues wanted to look at atrial fibrillation outcomes to better identify those who need early or tailored interventions.

The researchers examined data from 2,631 patients, identifying 127 major end- points, such as needing hospitalization or catheter ablation, in 96 of the patients. Key risk factors for reaching an endpoint included age; BMI; size and function of the heart's left atrium; moderate or severe failure of the heart's mitral valve to close completely; and history of arrhythmia (irregular heartbeat).

Obesity was a stronger risk factor in younger patients than older ones. The remaining risk factors were greater risk factors for middle-aged and older patients.

The researchers say their findings can be used to create a risk-assessment tool for patients, to identify those at risk and help keep them out of the hospital.

"These findings will help physicians who treat HCM patients, as they can target the risk factors that lead to atrial fibrillation," Kramer said.

Credit: 
University of Virginia Health System

A rapid method to quantify antibodies against SARS-CoV-2

image: The principle behind FPIA for detection of antibodies against SARS-CoV-2. When free fluorescently-labelled recombinant SARS-CoV-2 spike proteins (F-RBD) are exposed to a specific wavelength of polarized light, they emit depolarized light. However, if F-RBD are bound to anti-RBD antibodies, they emit polarized light instead, which can be measured (Keine Nishiyama, et al. Biosensors and Bioelectronics. June 5, 2021).

Image: 
Keine Nishiyama, et al. Biosensors and Bioelectronics. June 5, 2021

Scientists have developed a rapid, highly accurate test to detect antibodies against the spike protein of SARS-CoV-2 in human serum, opening a new avenue for understanding the full extent of the pandemic and evaluating the effectiveness of vaccines.

In the 18 months since the emergence of Covid-19 pandemic, great strides have been made in discovering and inventing various approaches to track and control the spread of the SARS-CoV-2 virus. Rapid and accurate diagnosis has always been vital in this regard. The gold standard since the beginning of the pandemic has been the RT-PCR method; however, it is time-consuming, labor-intensive, and requires sophisticated equipment, and can only detect the presence of viral RNA in the samples.

A team of scientists from Japan, including Professor Manabu Tokeshi of Hokkaido University's Faculty of Engineering, have developed a 20-minute test to detect and quantify antibodies against SARS-CoV-2 in human serum. Their findings were published in the journal Biosensors and Bioelectronics.

It is estimated that between 40% to 45% of individuals infected with SARS-CoV-2 are asymptomatic -- despite being infected, they do not develop any symptoms of the disease. Identifying individuals who may have had asymptomatic Covid-19 is important to understanding the full extent of the pandemic. RT-PCR can only detect the presence of the viral RNA in samples; individuals who have recovered from the pandemic will only have antibodies to the virus, which RT-PCR cannot detect.

There are commercially available tests to detect the presence of antibodies against SARS-CoV-2; however, the majority of these tests are inaccurate. Lateral flow immunoassay is one of the most common tests for diagnosis of Covid-19 based on antibody detection. While rapid, it is a qualitative method, and cannot be used for the quantification of antibodies. Further, the method does not scale well, resulting in a low cost efficiency.

The scientists developed a method of detecting antibodies against SARS-CoV-2 in human serum using a method called non-competitive fluorescence polarization immunoassay (FPIA). This method is not just rapid, but can also be used to quantify the antibodies. FPIA has been used in the food and medical industry; the team has previously made many innovations to the method and associated equipment, including the development of a portable fluorescence polarization analyzer.

FPIA requires fluorescently-labelled recombinant SARS-CoV-2 spike proteins (F-RBD) and human serum to be mixed together for the test. Individuals who have been infected with or vaccinated against SARS-CoV-2 will have anti-spike protein antibodies in their serum. When these antibodies bind to F-RBD, polarised light is emitted, while F-RBD alone emits depolarized light. By measuring the degree of polarisation using a fluorescence polarization analyser, the concentration of antibodies can be determined. The scientists optimised the test and evaluated it using samples of human serum from individuals diagnosed with Covid-19 and from those who had not been infected by SARS-CoV-2.

The test was demonstrated to be highly accurate, quick and easy to perform, with high throughput. This test requires about 20 minutes to complete, compared to about 2 hours for other tests; furthermore, the equipment required for the test is highly portable, weighing only 4.3 kg. Taken all together, these features make the test an excellent option for detecting and quantifying antibodies against SARS-CoV-2. The test can now be used for two purposes: screening large populations to determine the exact extent of the pandemic, and from evaluating the effectiveness of SARS-CoV-2 vaccines based on the antibody response.

Credit: 
Hokkaido University

The cells combating a deadly lung disease

image: Fibroblasts positive for meflin in idiopathic pulmonary fibrosis (IPF)

Image: 
Nakahara Y, Hashimoto N, Sakamoto K, et al. ERJ 2021

Single-cell RNA sequencing has revealed a subset of cells that could provide protection from a rare, but severely debilitating and fatal, lung disease. The findings were published by Nagoya University researchers and colleagues in the European Respiratory Journal. Further research could lead to new therapeutic strategies for the disease, called idiopathic pulmonary fibrosis (IPF).

Approximately 15 in every 100,000 people worldwide develop IPF. Its prognosis and five-year survival rate can be worse than many types of cancer. It involves the development of scar tissue on the lung, impairing gas exchange and making it difficult to breath. The disease currently has no cure and scientists do not know exactly what causes it.

"Our research, led by a collaborative team from Nagoya University in Japan and Yale University in the US, found a special cell population of protective fibroblasts in lungs of people with IPF," says Nagoya University's Naozumi Hashimoto, who specializes in respiratory medicine.

The team examined around 250,000 cells from lung tissue belonging to 29 normal and 32 IPF lungs. The examinations involved sequencing the RNA of each individual cell to find which genes they expressed. The analysis pinpointed one specific subset of fibroblast cells that were significantly more prevalent in IPF lungs than in normal ones. Fibroblasts are the most common type of cell in the supportive tissue in and around organs. This particular subset of fibroblasts produced a protein called meflin.

Interestingly, these meflin-producing fibroblasts were mainly found within acute focal lung lesions on the edges of dense scarring. The surrounding dense scar tissue contained very few of these cells.

Turning off meflin and inducing lung fibrosis in mice triggered cell aging, which led to more extensive pulmonary fibrosis than would have been expected. This process was counteracted in laboratory-studied cells by inserting the gene that codes for meflin.

"We anticipate that our discovery will promote better understanding of the unsolved disease mechanisms of IPF and ultimately lead to the development of novel therapies for lung fibrosis," says Hashimoto.

The team next plans to further investigate how meflin protects lungs from fibrosis and if meflin-positive cells can be used to diagnose and treat IPF.

Credit: 
Nagoya University

Looking beyond the numbers to see pandemic's effect on nursing home residents

video: Regenstrief Institute Research Scientist Kathleen Unroe, M.D. discusses pandemic's effect on nursing home residents.

Image: 
Regenstrief Institute

INDIANAPOLIS -- Nursing homes throughout the United States have been devastated by the COVID-19 pandemic with many perceptions and misperceptions but little documentation about what has happened on a day-by -day basis to residents in these facilities. A study from Regenstrief Institute and Indiana University School of Medicine research scientists is one of the first to describe and identify patterns in the course of COVID-19 in the typically frail individuals who reside in nursing homes.

Much has been written about number of deaths, vaccine uptake and other topics related to the impact of COVID on nursing homes, yet prior to the Regenstrief-IU School of Medicine study, there has been little known about how the disease has clinically affected individuals residing in nursing homes. A full understanding of the disease burden and trajectories of COVID-19 in nursing home residents - those who died and those who survived COVID - will aid medical and public health professionals immediately, will help them prepare for outbreaks of variants and may inform efforts to confront outbreaks of other diseases.

"When the COVID outbreak occurred, we [physicians who care for nursing home residents] didn't know, because we weren't armed with knowledge or clinical experience, what to expect - who would do well and who wouldn't," said Regenstrief Institute Research Scientist Kathleen Unroe, M.D., senior author of the study. "This is a population that by their very need to reside in a nursing home, has complex medical conditions and is at high risk. And it's a different population than younger adults. For example, some older adults may not experience fever in response to infection; persons with dementia may be unable to report symptoms."

The researchers studied the electronic medical records (EMRs) of 74 nursing home residents infected with COVID of whom half were women, 57 percent were Caucasian and 43 percent were African American. One third (25) died; with 23 of the deaths considered related to COVID-19 infection. Hypertension was the most common comorbidity (81 percent) followed by dementia (51 percent), diabetes (50 percent) and non-dementia mental illness (43 percent). The most common symptoms were fever, hypoxia (low oxygen level in the blood), anorexia, and fatigue/malaise. None reported headaches. The duration of symptoms was extended, with an average of more than three weeks.

The 74 nursing home residents with COVID-19 infection appeared to fall into four disease trajectory categories:

minimal to no symptoms (17)

residents who survived but experienced significant symptoms (32),

residents who died after a rapidly progressive course (less than seven days) (5)

residents who died after a prolonged course with significant symptom burden (20)

"For many of nursing home residents who survive COVID-19, the duration of symptoms is long and arduous; most will survive the disease but may not get back to baseline," said Dr. Unroe. "The effect of COVID on nursing home residents goes beyond the mortality numbers we saw."

Credit: 
Regenstrief Institute

The virus trap

video: For the DNA plates to assemble into larger geometrical structures, the edges must be slightly beveled. The correct choice and positioning of binding points on the edges ensure that the panels self-assemble to the desired objects. The video shows a cryo-EM 3D reconstruction of an open nano-shell.

Image: 
Christian Sigl / DietzLab / TUM

To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origami method. The strategy has already been tested against hepatitis and adeno-associated viruses in cell cultures. It may also prove successful against corona viruses.

There are antibiotics against dangerous bacteria, but few antidotes to treat acute viral infections. Some infections can be prevented by vaccination but developing new vaccines is a long and laborious process.

Now an interdisciplinary research team from the Technical University of Munich, the Helmholtz Zentrum München and the Brandeis University (USA) is proposing a novel strategy for the treatment of acute viral infections: The team has developed nanostructures made of DNA, the substance that makes up our genetic material, that can trap viruses and render them harmless.

DNA nanostructures

Even before the new variant of the corona virus put the world on hold, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team were working on the construction of virus-sized objects that assemble themselves.

In 1962, the biologist Donald Caspar and the biophysicist Aaron Klug discovered the geometrical principles according to which the protein envelopes of viruses are built. Based on these geometric specifications, the team around Hendrik Dietz at the Technical University of Munich, supported by Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a concept that made it possible to produce artificial hollow bodies the size of a virus.

In the summer of 2019, the team asked whether such hollow bodies could also be used as a kind of "virus trap". If they were to be lined with virus-binding molecules on the inside, they should be able to bind viruses tightly and thus be able to take them out of circulation. For this, however, the hollow bodies would also have to have sufficiently large openings through which viruses can get into the shells.

"None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus - they were simply too small," says Hendrik Dietz in retrospect. "Building stable hollow bodies of this size was a huge challenge."

The kit for a virus trap

Starting from the basic geometric shape of the icosahedron, an object made up of 20 triangular surfaces, the team decided to build the hollow bodies for the virus trap from three-dimensional, triangular plates.

For the DNA plates to assemble into larger geometrical structures, the edges must be slightly beveled. The correct choice and positioning of binding points on the edges ensure that the panels self-assemble to the desired objects.

"In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates," says Hendrik Dietz. "We can now produce objects with up to 180 subunits and achieve yields of up to 95 percent. The route there was, however, quite rocky, with many iterations."

Viruses are reliably blocked

By varying the binding points on the edges of the triangles, the team's scientists can not only create closed hollow spheres, but also spheres with openings or half-shells. These can then be used as virus traps.

In cooperation with the team of Prof. Ulrike Protzer, head of the Institute for Virology at TUM and director of the Institute for Virology at the Helmholtz Zentrum München, the team tested the virus traps on adeno-associated viruses and hepatitis B virus cores.

"Even a simple half-shell of the right size shows a measurable reduction in virus activity," says Hendrik Dietz. "If we put five binding sites for the virus on the inside, for example suitable antibodies, we can already block the virus by 80 percent, if we incorporate more, we achieve complete blocking."

To prevent the DNA particles from being immediately degraded in body fluids, the team irradiated the finished building blocks with UV light and treated the outside with polyethylene glycol and oligolysine. The particles were thus stable in mouse serum for 24 hours.

A universal construction principle

Now the next step is to test the building blocks on living mice. "We are very confident that this material will also be well tolerated by the human body," says Dietz.

"Bacteria have a metabolism. We can attack them in different ways, " says Prof. Ulrike Protzer. "Viruses, on the other hand, do not have their own metabolism, which is why antiviral drugs are almost always targeted against a specific enzyme in a single virus. Such a development takes time. If the idea of simply mechanically eliminating viruses can be realized, this would be widely applicable and thus an important breakthrough, especially for newly emerging viruses.

The starting materials for the virus traps can be mass-produced biotechnologically at a reasonable cost. "In addition to the proposed application as a virus trap, our programmable system also creates other opportunities," says Hendrik Dietz. "It would also be conceivable to use it as a multivalent antigen carrier for vaccinations, as a DNA or RNA carrier for gene therapy or as a transport vehicle for drugs."

Credit: 
Technical University of Munich (TUM)

Study highlights how resilience is dynamic, not a static character trait

A new study finds that resilience is a dynamic process, rather than a fixed trait - and suggests this may have significant ramifications for the business world.

"Organizations are interested in cultivating a resilient workforce, because they want people who are able to remain committed to an organization and its goals over time," says Patrick Flynn, corresponding author of the study and an assistant professor of human resources management at North Carolina State University's Poole College of Management.

"Our work here does a couple things," Flynn says. "First it finds that resilience is more of a process than a characteristic. Second, it identifies some of the characteristics that can contribute to that process in a meaningful way. Taken together, we think the findings can inform recruitment, hiring, operations and training practices."

At the heart of the study is the idea that resilience fluctuates, because it encompasses the way that an individual responds to a variety of circumstances over time.

"It's impossible to assess dynamic resilience at any given moment," Flynn says. "Dynamic resilience is demonstrated across time. How does people's behavior change over time? What influences that? Those are the sorts of questions we wanted to answer with this study."

To that end, researchers worked with 314 members of a university marching band. Study participants were surveyed weekly for 12 weeks. The surveys were designed to collect data on individual participants and their emotional and personal characteristics. To assess how resilience is functioning in individuals over time, the researchers also asked study participants about their commitment to the marching band as an organization, as well as their feelings of "burnout" - specifically, emotional exhaustion related to their work in the organization.

"Tracking the trajectories of commitment and burnout helped us see how resilience played out in real world terms," Flynn says.

The researchers found that, on average, emotional exhaustion increased over time and commitment decreased over time. However, there were factors that influenced those effects.

For example, experience within the organization exacerbated the effects of emotional exhaustion and decreased commitment. In other words, newcomers appeared to be more resilient over the study period.

The researchers also found that people who scored higher on assessments of emotional stability were better able to maintain higher levels of commitment.

Lastly, the researchers also looked at the trajectory of each individual's commitment to the organization to see if it predicted "retention." They found that positive commitment trajectories were associated with a greater likelihood of both planning to return to the organization for another year and then subsequently doing so.

"One takeaway here is that annual employee surveys may not be the best way to assess employee resilience and commitment to an organization," Flynn says.

That's because annual surveys provide snapshots, while resilience is a dynamic process that fluctuates.

"Since resilience affects things like employee retention, which are important to a company's bottom line, we really need to be touching base with employees more often," Flynn says.

The work also shows that resilience can wear down over time, even if people are only exposed to mild stressors.

"Chronic stress can wear down resilience, with ramifications for employee retention and, in all likelihood, job performance," Flynn says.

"However, we also feel that thinking about resilience as a dynamic process creates opportunities to foster resilience in employees not only through recruitment, but through training, and even job design. In short, it's not as simple as hiring the right person and assuming things will work out. Fostering resilience is going to be an ongoing task for management and human resources professionals."

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North Carolina State University

Researcher creates cell lines to help treat mitochondrial diseases in children

image: A visualization of the CRISPR-Cas9 process, which involves a 6-well plate with cloned guide RNA which has been introduced to humans cells (top), harvested cells in a 96-well plate, (middle) and successfully grown clone cells sitting in big flasks (bottom). Next, the cells will be ready to undergo testing. Images courtesy of Abey Bandara. Illustration courtesy of Alex Crookshanks.

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Virginia Tech

The mitochondrion has garnered quite the reputation for its role as the "powerhouse of the cell." These tiny, but mighty organelles play various life-sustaining roles, from powering our own cells and organs to fueling chemical and biological processes. But when they aren't working properly, a number of rare diseases can occur.

Mitochondrial diseases are a group of debilitating genetic disorders that affect one in 5,000 people throughout the world, most of them being children. Along with these diseases come a variety of health concerns including, but not limited to, heart disease, developmental and cognitive disabilities, respiratory issues, poor growth, and even premature death. As of this moment, there is no cure.

But recent work published in the journals Mitochondrion and BMC Molecular and Cell Biology by Aloka Abey Bandara, a research associate professor in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine, and his team offers mitochondrial disease patients and their parents a glimmer of hope.

Along with a team of Virginia Tech researchers across Blacksburg and Roanoke, Bandara has successfully created live cell models that mimic mitochondrial disease cells. These cells will lay the groundwork for drug studies and future studies into mitochondrial diseases.

"Our cell models will allow us to see what exactly happens to the cells and its processes when a child develops mitochondrial disease. In addition to these factors, we will be able to conduct further study into the toxicity and effectiveness of novel drug candidates," said Bandara, who is also an affiliated faculty member of the Fralin Life Sciences Institute.

Our bodies produce life-sustaining energy from the food we eat and the air we breathe. Oxygen and nutrients, like glucose, travel throughout the body's organs, tissues, and cells until they arrive at their final destination: the mitochondria. When the nutrients reach the inner membrane of the mitochondria, a unique series of protein complexes, called the electron transport chain, kicks into gear.

Through a series of reactions, the electron transport chain is able to remove electrons from the nutrients and push them through the mitochondrial membrane, which forms a gradient of protons. When this happens, the body generates adenosine triphosphate, better known as ATP, a molecule that carries energy within cells.

"Sometimes, you can see disruptions or mutations within the electron transport chain proteins," said Bandara. "As a result, the protein complexes cannot transport electrons, and then energy production is disrupted. Almost all organs of the organism will be affected - heart, eyes, and muscles - and they will not be able to function correctly."

The electron transport chain is composed of five protein complexes, or groups of proteins. Complex I and Complex II are two protein complexes that are primarily responsible for removing electrons from the nutrients. If they fail to do their duty, the whole electron transport chain fails, and the body cannot produce ATP.

Mitochondrial disease patients can have defects in either Complex I or Complex II. Patients who have Complex I disruptions typically have neurological problems, such as seizures and abnormal brain functions. Those with Complex II disruptions can develop many other diseases and are more likely to develop several cancers.

Although researchers are able to pinpoint where exactly the defects are located, creating treatments for these mitochondrial diseases has been a challenge. Therapies, vitamins, and dietary adjustments have been able to help alleviate symptoms and slow down the progression of disease; but, mitochondrial disease, itself, does not have a cure. Therefore, new drugs need to be created, tested, and refined.

Bandara hopes that his cell lines will not only support upcoming research, but also the patients and their families, who are experiencing the mitochondrial disease and all of its impacts firsthand.

"The parents are often helpless because they cannot just go to the pharmacy and get a drug," said Bandara. "Hopefully, they can see that Virginia Tech is taking huge leaps to find a cure for these diseases. Maybe they can feel that they are not alone anymore - that the universities, the government, and science are fighting with them."

In order to test drug candidates, researchers must first create cellular models, which act as artificial "sick" cells. Cellular models are an excellent tool for drug discovery because mitochondrial disease can be studied without actually needing to extract cells from patients.

To create cells that mimic mitochondrial disease, Bandara had to "knock-out" portions of the genome that create the coding for Complex I and Complex II using CRISPR/Cas9 technology.

First, researchers identified the portion of the genome that needed to be deleted. Then, they designed a piece of RNA that made that point its "home base." The RNA then "guided" an enzyme called Cas9 to its home base on the gene. Cas9 is then able to bind to that point and "cut" it.

After this process was completed, Bandara ran genomic sequencing to confirm that the portion was successfully deleted from the genome. Over several months of hard work, Bandara and his team created two mutant cell lines, one with Complex I removed, and the other without Complex II.

Bandara is one of the very few researchers on Virginia Tech's Blacksburg campus to use the CRISPR/Cas9 technology to treat mitochondrial disease.

After the mutant cell lines were created, Bandara ran them through a disease model, where he tested the functions of the "sick" cell line against the "parent" cell line, which is composed of healthy cells. Through close analysis, Bandara confirmed that the sick cells consumed far less oxygen, grew very slowly, and did not produce enough ATP for the cells to function properly - the three trademarks of cells with mitochondrial disease.

Once they confirmed that the knockout cell lines properly simulated the cellular dysfunctions of mitochondrial disease, they were able to test a newly developed drug called Idebenone. With this treatment, Bandara showed that cell growth and oxygen consumption can be restored to a certain extent.

These cell lines were the product of a fruitful collaboration of experts from the Department of Human Nutrition, Foods, and Exercise and the Virginia Tech Carilion School of Medicine.

The construction of mutant cell lines was guided and supported by David Brown, a former associate professor in the Department of Human Nutrition, Foods, and Exercise in the Virginia Tech College of Agriculture and Life Sciences, now the senior director of scientific and technical innovation at Stealth BioTherapeutics, a Boston-based biotechnology company.

From this work, the team has received two provisional patents for their cells. One of the cell lines has already been patented and licensed to a pharmaceutical company, which will develop new therapies for individuals suffering from mitochondrial diseases.

These cells have been made available for global use by interested researchers and pharmaceutical companies through Ximbio, the world's largest nonprofit specializing in life science research tools of all types.

"Cell models of mitochondrial Complex I and II defects carry high societal and economic impact as models for testing drug candidates in a cost- and time-effective manner for the treatment of mitochondrial dysfunction," said Justin Perry, a Virginia Tech graduate, and now a business development manager at Ximbio.

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Virginia Tech

Digital assistants created for e-commerce which adapt themselves to each shop's needs

The pandemic has taught us that almost all companies have to sell on the internet. Bots are a technology that facilitates e-commerce. They are digital assistants that can answer customer queries about products that are sold or help to locate them, as well as supporting customers in the purchasing process. "In whatever language; and moreover, chatbots never get tired: They're available 24 hours a day, 365 days a year", said Jordi Cabot, the Universitat Oberta de Catalunya (UOC) researcher who created Xatkit, a company specialized in their development. This technology has existed for some time in big companies and is now also helping improve the digital competitiveness of SMEs. Indeed, the introduction of bots is expanding: this type of artificial intelligence already generates over 40% of the traffic on the internet.

Xatkit is a new UOC spin-off which offers pre-trained bots for e-commerce. Once installed in the shops, they read the products that are sold and are automatically set up to begin to help the customers who arrive. They are also prepared to continue learning by themselves. "Our bots can do any task that a human salesperson would do, from recommending products or showing offers to notifying the shop when clients ask for a product that they are not currently offering", said Cabot.

The pandemic has taught us that almost all companies have to sell on the internet. Bots are a technology that facilitates e-commerce. They are digital assistants that can answer customer queries about products that are sold or help to locate them, as well as supporting customers in the purchasing process. "In whatever language; and moreover, chatbots never get tired: They're available 24 hours a day, 365 days a year", said Jordi Cabot, the Universitat Oberta de Catalunya (UOC) researcher who created Xatkit, a company specialized in their development. This technology has existed for some time in big companies and is now also helping improve the digital competitiveness of SMEs. Indeed, the introduction of bots is expanding: this type of artificial intelligence already generates over 40% of the traffic on the internet.

Xatkit is a new UOC spin-off which offers pre-trained bots for e-commerce. Once installed in the shops, they read the products that are sold and are automatically set up to begin to help the customers who arrive. They are also prepared to continue learning by themselves. "Our bots can do any task that a human salesperson would do, from recommending products or showing offers to notifying the shop when clients ask for a product that they are not currently offering", said Cabot.

Beyond e-commerce: digital assistants using text or the phone

Digital assistants do not just simulate human conversations on chat windows (so-called chatbots), but can also be used to answer telephone calls or comments made on websites or social media in any language. At present, Xatkit creates bots that can understand and speak in English, Spanish and Catalan.

The technological improvement of bots means that these assistants can currently engage in "complex conversations and process management tasks, processing customers' requests", explained Jordi Cabot. This technology allows customer service costs to be optimized. Cabot, a member of the research faculty at ICREA and leader of the research group SOM Research Lab of the UOC's Internet Interdisciplinary Institute (IN3), who developed Xatkit with Gwendal Daniel, a researcher from his group, indicated that the key to the development of digital assistants is that they have a specialized platform to define their functionalities and guarantee the quality of the training of the bot, testing and monitoring the behaviour in order to improve its effectiveness.

Bots created with open-source software

The Xatkit team works with open-source software, making it easy for clients to set up the digital assistants. Its platform is committed to integrating state-of-the-art technology in processing and understanding natural language to optimize the quality of the conversations. In addition to understanding what the client says, Xatkit summarizes and automatically translates texts, and also analyses the feelings of the buyers. "The bot can figure out whether the client is annoyed and adapt its answer to the situation", explained Jordi Cabot.

From research to entrepreneurship

The initiative of the UOC researchers to develop conversation bots began as a research project but, unlike other research, "we thought that, in view of the subject and the innovation behind it, it could help many organizations and have a bigger social impact", indicated Cabot. Thus, the creation of this new spin-off from the UOC's research activity allows the research group's technological expertise on digital assistants to reach the market. "Xatkit takes advantage of the state-of-the-art technology that we generate in the research to develop more innovative solutions and the research team learns from the application of the technology in real cases, thanks to the creation of the company", said the researcher.

"We recommend combining the role of researcher with that of entrepreneur, because this improves the quality and impact of the research", according to Cabot and other researchers in an article published for the 8th International Virtual Workshop on Software Engineering Research and Industrial Practice. Faced with the lack of more investment by industry in R&I, the experts said that as researchers they can "become the partners that companies need, and thus moreover bring the ideas of the research to the market".

The researchers are committed to promoting open resources, strengthening the triangle of collaboration between research, SMEs - as technology suppliers - and end clients - which could be big corporations -, or as a fruitful relationship which provides real cases of technological development. "If as researchers we don't find the appropriate SME to collaborate with our research, we create it, like we did with Xatkit", they concluded.

Spin-offs from UOC research activity

At present the UOC has four spin-offs. Before Xatkit, it created Immersium Studio, specialized in the development of immersive technology (virtual, augmented and mixed reality); Care Respite, with the Universitat Autònoma de Barcelona, specialized in dependent people monitoring technology for carers; and Open Evidence, an international quantitative consultancy that promotes operating strategies and models for decision-making processes through data-based computational intelligence.

The Xatkit project won the jury award at Spin UOC 2021, the UOC's annual entrepreneurship, innovation and knowledge transfer programme, promoted by the Hubbik platform.

The Xatkit project (Massive Generation of chatbots on-demand, ref. 2019 INNOV 00001) is supported by the Department for Universities and Research in the Government of Catalonia's Ministry of Business and Knowledge and receives funding from the European Regional Development Fund (ERDF).

Xatkit supports sustainable development goal (SDG) 9: Build resilient infrastructure, promote sustainable industrialization and foster innovation

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Universitat Oberta de Catalunya (UOC)

RUDN University chemists propose a one-step synthesis of substances for medicine

image: The RUDN University chemists have discovered a reaction for the synthesis of acetimidamides, heterocyclic compounds with biological activity that can be used for the synthesis of hormones, anti-inflammatory and other medical drugs. The reaction goes in one step with an efficiency of up to 96%.

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RUDN University

The RUDN University chemists have discovered a reaction for the synthesis of acetimidamides, heterocyclic compounds with biological activity that can be used for the synthesis of hormones, anti-inflammatory and other medical drugs. The reaction goes in one step with an efficiency of up to 96%. The results are published in the journal Molecules.

Traditional chemical synthesis goes in several stages and requires the isolation and purification of intermediates at each stage. It is not efficient and not environmentally friendly as it increases the loss of substances and the consumption of solvents, and there is a problem of waste disposal. Therefore, modern chemistry is trying to replace multi-stage reactions with multicomponent ones, in which several compounds react to form a product in a single stage. Reactions with isocyanides are the most popular in multicomponent chemistry. Isocyanides are organic compounds with high reactivity. RUDN University chemists have discovered a new three-component reaction with isocyanides that results in a heterocyclic compound with biological activity, acetimidamides. They contain a fragment of indole, which is used for the synthesis of hormones, indomethacin, and other drugs. This work is a development of the famous Ugi reaction.

"Isocyanide-based multicomponent reactions play an outstanding role in the syntheses of heterocycles, biologically relevant compounds and for diversity-oriented synthesis. In the case of the famous Ugi reaction, isocyanide interacts with iminium salt generated in situ. The potency of methods, based on the Ugi reaction, increases with the possibility of subsequent modification or cyclization of obtained products of multicomponent reaction. This is promising from the point of view of medical chemistry", said Nikita Golantsov, PhD, Professor of the Department of Organic Chemistry of the RUDN University.

Apart from isocyanides, the new three-component reaction involves a 3-arylidenindoleninium salt and an amine. In total chemists used 8 salts and 13 amines. To choose the optimal reaction conditions, they tested 6 types of solvents, alternated the reaction time and temperature. After the reaction was completed, the chemists isolated the final product by treatment with a saturated baking soda solution followed by chromatography and studied its composition and structure using various methods, including nuclear magnetic resonance (NMR) spectroscopy.

In total, the RUDN University chemists obtained 16 acetimidamides. When using isocyanoacetic ester, imidamides were further cyclized with the formation of an imidazolone fragment. Thus, a series of 19 imidazolones containing an indole substituent was synthesized. The most suitable solvent was acetonitrile. It allowed to minimize the formation of by-products. After three hours at a temperature of 20?, the reaction yield (the ratio of the actual mass of the product obtained to the theoretical one), was 75%. And after 12 hours, the output reached 96%. Chemists tried to accelerate the reaction by increasing the temperature, but this attempt was unsuccessful due to a tar formation and an increase in the amount of the by-product.

"These reactions furnish a new practical synthetic approach to a series of compounds with a privileged indole scaffold, which are prospective choices for seeking new physiologically active compounds", said Nikita Golantsov, PhD, Professor of the Department of Organic Chemistry of the RUDN University.

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RUDN University