Culture

What The Study Did: Researchers examined the association of closures of childcare facilities with the employment status of women and men with children in the United States during the COVID-19 pandemic.

Authors: Yevgeniy Feyman, B.A., of the Boston University School of Public Health, 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/jamahealthforum.2021.1297)

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

What The Study Did: This analysis describes the use of a multifaceted COVID-19 control plan to reduce spread of SARS-CoV-2 at a large urban university during the second wave of the pandemic.

Authors: Davidson H. Hamer, M.D., of the Boston University School of Public Health, 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.2021.16425)

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

Effective diagnostics, therapies and treatments for diseases and infections could increasingly involve re-engineering the body’s internal biomechanisms at their most basic chemical and molecular foundations.

Growing knowledge about the body’s biological processes is increasing the possibilities for restoring human health, says Xiao Wang, an associate professor of biomedical engineering in Arizona State University’s Ira A. Fulton Schools of Engineering. He and a team of researchers are exploring ways to trigger and control cell differentiation and transition to unlock properties that may change bioengineers’ approach to diagnostics, vaccine development and therapeutic treatments.

Recent research led by Wang and Alexander Green, an assistant professor of biomedical engineering at Boston University, reveals more about the potential for designing small add-on structures for biomolecules that can enhance their properties.

“There could be new and better kinds of applications for diagnostics, therapeutics and treatments, and for genome engineering,” Wang says. “These could be big contributions to biomedicine.”

The details about what the research may yield appear in the paper Predictable control of RNA lifetime using engineered degradation-tuning RNAs, published this week in the research journal Nature Chemical Biology.

Wang and Green’s focus is on messenger RNA, or mRNA, which carries genetic information from DNA, the molecule that contains the genetic blueprint needed to develop and maintain organisms — including humans.

Within cells, mRNA transmits messages from DNA to the protein-producing ribosomes, informing them of which proteins need to be synthesized at a given time. While DNA’s status as the information repository of the cell means that it is very stable, mRNA’s message-carrying role means it rapidly degrades. This degradation has made it harder to implement RNA-based therapies and diagnostics.

Wang, Green and their research team are devising methods of controlling degradation to produce predictable, precise and stable results. The new research paper describes how they are attempting to fine-tune the speed of mRNA degradation to boost the ability to perform biotechnological functions. To do this, they have identified specific RNA structural features to build a library of RNA components called degradation-tuning RNAs, or dtRNAs.

Attaching the dtRNAs to an RNA of interest through genetic engineering enables them to increase or decrease the RNA’s degradation rate, and fine-tune gene expression levels in vivo and in vitro — either inside a living organism or in a laboratory setting.

“We found that dtRNAs could be used with a variety of different types of RNAs and modify gene expression levels over a very wide range. These capabilities can increase the speed and sensitivity of medical diagnostics and give us better control over cell function,” says Green, who was an assistant professor in ASU’s Biodesign Institute and School of Molecular Sciences from 2015 to 2020 and is currently an adjunct professor with the school.

One of the more impactful results of these refining processes could be the development of mRNA-based vaccines that would be especially effective against viruses, Wang says.

“We can actually engineer the structure of RNA molecules in faster and more systematic ways that make them more efficient in how they behave,” he says.

These behavior changes will inform how effective Wang and Green’s bioengineering process will be at boosting the efficacy of diagnostics, vaccines, therapies and treatments.

Tokyo, Japan - A cell is composed of numerous organelles, each with a unique role that helps contribute to its overall functionality. The lysosome is an organelle that contains digestive enzymes and functions as a molecular garbage disposal and recycling center. Since the role of lysosome is crucial to maintain the cellular homeostasis, the lysosomal dysfunction causes neurodegenerative and metabolic diseases, cancer, as well as lysosomal storage disorders.

In a new article published in Autophagy, researchers at Tokyo Medical and Dental University (TMDU) performed a novel type of structural analysis to demonstrate how a certain molecular interaction is crucial for one lysosomal membrane protein to perform effectively.

LAMP1 (lysosomal-associated membrane protein 1) and LAMP2 the most abundant protein components of lysosome membranes. Both LAMP1 and LAMP2 are composed of a large lumenal domain, a transmembrane domain, and a short C-terminal cytoplasmic tail (Fig. 1). The lumenal domains of LAMPs are composed of two domains (N-domain and C-domain, which are membrane-distal and -proximal, respectively). Each domain has the unique ?-prims fold structure (a triangular prism). On the other hand, genetic experiments have shown that mice embryos without both LAMP-1 and 2 die a little more than two weeks after fertilization. Mice without LAMP-1 are born and can thrive, while those without LAMP-2 often die a few weeks after birth, suggesting that LAMP-2 is more important for lysosome activity. The research of the TMDU group further investigates this protein's biological role.

"Mice lacking LAMP-2 also display issues with autophagy progression," says one of the lead authors of the study Kazue Terasawa. "Expanding our knowledge of how LAMP-2 interacts and operates at the molecular level will ultimately help us understand autophagy better."

The researchers demonstrated LAMP2 molecules assemble by facing each other with one side the ?-prism (defined as side A, as shown in Fig. 1) of the C-domain (Fig. 2). The N-domain truncation permitted the nonspecific involvement of both sides of the ?-prims (side A and side B). In combination with some biochemical studies, "we believe that the homophilic interaction we demonstrated is crucial for function of LAMP-2, via ensuring a proper arrangement of the cytoplasmic tails, which is crucial for the function of LAMP2, on the lysosome membrane," says Miki Hara-Yokoyama, senior author.

Scientists of Tomsk Polytechnic University jointly with their colleagues have synthetized a unique molecule of verdazyl-nitronyl nitroxide triradical. Only several research teams in the world were able to obtain molecules with similar properties. The molecule is stable. It is able to withstand high temperatures and obtains promising magnetic properties. It is a continuation of scientists' work on the search for promising organic magnetic materials. The research findings are published in the Journal of the American Chemical Society (IF: 14.612, Q1).

Magnetoresistive random-access memory (MRAM) is one of the most promising technologies for storage devices. Nowadays, the MRAM development is limited due to the fact it is impossible to create a smaller memory cell because of spontaneous magnetization reversal. Single-molecular magnets based on organic compounds are free from this disadvantage: few molecules are already capable to operate as a memory storage unit.

"At a certain temperature, a magnetic phase transition occurs, the consistent orientation of the magnetic vectors of molecules is observed, as a result, the matter becomes a united magnet. Thus, 20-40 molecules are quite enough to form a micromagnet.

Our task in the research laid in creation such a molecule that could be capable to give its magnetic properties at high temperatures, would be crystalline and would possess a small distance between radical centers,"

Pavel Petunin, Associate Professor of the TPU Research School of Chemistry and Applied Biomedical Sciences, an article author, explains.

When creating the molecule, the scientists worked with three radical centers in one molecule combined them in one conjugated structure. To synthetize the molecule, the scientists used a palladium-catalyzed reaction of a verdazyl radical with a gold complex of a nitronyl-nitroxyl radical. The course of the reaction was complicated due to the presence of unpaired electrons in starting compounds, as well as the combination of three radical centers in one molecule, which affects its stability. According to the scientists, there are no other ways to synthesize the molecule.

The research teams from TPU, the Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of Russian Academy of Sciences, the Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, the Voevodsky Institute of Chemical Kinetics and Combustion of the Siberian Branch of the Russian Academy of Sciences and International Tomography Center of the Siberian Branch of the Russian Academy of Sciences took part in the molecule synthesis. The research work was conducted within the project of the Russian Science Foundation No. 20-73-00236 "Stable Organic Radicals as Promising Building Blocks for New Materials".

"The published research not only makes a significant contribution to the development of stable verdazyl radicals but it is also a meaningful publication for TPU. Research teams of the TPU Research School of Chemistry and Applied Biomedical Sciences perfectly complete the mission, which was determined at the moment of the School creation. The Journal of the American Chemical Society is the most peer-reviewed chemical journal. Research teams around the globe are intending to publish their articles in this journal. It should be noted that it is a cycle of the research works of the research team. The authors have recently published their research work in the equally top-rated Angewandte Chemie academic journal (IF: 12.959, Q1)," Marina Trusova, Director of the TPU Research School of Chemistry and Applied Biomedical Sciences, says.

At the moment, the researchers have approached complicated molecules and are planning to synthetize almost impossible molecules: heterospin and high-spin dendrimers.

What does it take for people to commit to take action to promote social equality? And how might this differ for people from advantaged and disadvantaged groups?

An international team, including Linda Tropp at the University of Massachusetts Amherst and researchers in 23 countries, finds more mutual support for social change among advantaged and disadvantaged groups when inequality is actively addressed and the psychological needs of each group are met. The new research, led by the University of Zurich (UZH), was published in the Journal of Personality and Social Psychology.

"What this research is showing is that people on both sides really need to acknowledge that they have different motivations and concerns when they interact with each other," says co-author Tropp, the lead researcher in the U.S. who has examined how members of different groups experience intergroup contact for more than 20 years.

Prior research has shown that advantaged groups prefer to discuss commonalities among groups rather than differences between groups, at the same time as they desire to feel accepted and not be labeled as biased. But if members of socially disadvantaged groups simply have pleasant, positive exchanges with people who are not themselves targets of discrimination, they may emerge from those contact experiences even less committed to fighting for social justice and improving their own group's social position.

As first author Tabea Hässler of UZH says, "They get the deceptive impression that their own group no longer suffers so much discrimination... It is therefore important that social inequalities and discrimination between different social groups are actively addressed and named." This helps to meet the needs of disadvantaged group members, such as racial minorities and LGBTIQ+ individuals, who are motivated to have a voice and feel empowered in their relations with advantaged groups.

Each group's psychological needs are therefore an important part of the equation. "If contact situations are structured where members of disadvantaged groups or minority groups feel empowered, that they have a voice and are being listened to and heard, that's the time when contact with members of advantaged groups may support their interest in collective action to challenge the status quo," says Tropp, professor of social psychology at UMass Amherst.

Similarly, when members of majority groups "feel welcome as allies in that cause and not presumed to be racist, then that can bolster their willingness to use some of their time and energy to try to promote social equality," she says.

To gather their data, 43 researchers around the world conducted a survey with more than 11,000 individuals from a range of identity groups, including heterosexual individuals and members of sexual or gender minorities, migrants and members of their respective host societies, as well as indigenous groups and religious minorities.

"Overall, our findings suggest that contact across group boundaries fosters social change when it meets the targeted needs of disadvantaged and advantaged groups," says Johannes Ullrich, professor of social psychology at UZH.

Tropp says one next step is to help prepare members of advantaged groups to engage in difficult conversations about power relations and discrimination.

"To the extent that the advantaged engage in those conversations with disadvantaged groups, talking about the structural inequalities that do exist and need to be addressed, then it's likely that both members of disadvantaged groups as well as advantaged groups will be more prepared to engage in efforts to challenge the inequalities that we have in our society," she says.

COLUMBUS, Ohio - Although the United States is the only wealthy nation that doesn't guarantee paid leave to mothers or fathers after the arrival of a new child, Americans endorse providing paid time off for parents nearly as much as people from other countries.

About 82% of Americans support paid maternity leave, just slightly less than the 86% who support it in 26 wealthy nations, a new study shows.

Where Americans differ from the rest of the world is that they are less supportive of government funding for paid leaves, prefer shorter leave times and are less supportive of paid leave for fathers.

"We find marked differences in how Americans want paid leave administered compared to the rest of the world - but very similar desires to have leave available," said Chris Knoester, co-author of the study and associate professor of sociology at The Ohio State University.

Knoester conducted the study with Richard Petts, professor of sociology at Ball State University, and Amelia Li, a doctoral student in sociology at Ohio State. Their findings were published this week in the International Journal of Comparative Sociology.

The researchers analyzed data from 35,488 people who participated in the International Social Survey Programme 2012. The participants come from 26 wealthy countries, including the United States, that belong to the OECD, the Organisation for Economic Co-Operation and Development.

Overall, the study found high levels of support for paid leave across the developed world, as well as support for relatively long paid leave periods and government funding for the time off, Knoester said.

Worldwide, about 75% of people wanted government support for paid maternity leave. In a previous study the authors published in Social Science Research, they found that about half wanted it for paternity leave.

Support for government funding was much lower in the United States - about half endorsed it for maternity leave, and only a third wanted it for paternity leave. And very few Americans wanted government funding leave by itself, Knoester said. Most wanted the government and private employers to share the costs.

"This may be a major reason why we don't have more widespread and generous leave offered in the United States, even though most people support it," he said.

"If we don't have leave provided through the federal government, we get what we have now, which is a patchwork of states and employers offering different leave policies."

Americans also didn't want as much paid leave as did those from other countries in the survey. People in the United States wanted about four months of leave allocated to new parents. Worldwide, people supported close to 13 months.

Support for paid leave for fathers is lower than for maternity leave, both in the United States and in the rest of the countries surveyed.

Overall, about 60% of people surveyed wanted paid paternity leave, compared to just over half of Americans.

While a lack of support for government funding may be one reason why the U.S. is the only major country without paid maternity leave, there are other reasons, the researchers said.

In another new study by the researchers, forthcoming in Sociological Focus, findings showed that older white people with more conservative political views in the United States were least supportive of paid parental leave.

"These tend to be the people in the elite positions in our society who make those policy decisions about paid leave," Li said. "That makes it difficult to enact leave policies."

Petts noted another reason why political elites in the United States may be less supportive of government-supported leave.

"These are the people who already largely have access to paid leave through their employers. They would not directly benefit from it, because they already have it," Petts said.

"It is a story of the haves and the have-nots."

The international study also showed other factors that affect people's support of paid leave.

As expected, women were generally more likely to support paid leave and wanted longer time off.

Also, people who were strong supporters of traditional gender roles, in which men focus on paid work and women focus on the home and family, were less supportive of paid leave than people who advocated more egalitarian gender roles.

"Relatedly, when people endorse both members of a couple working, they are more supportive of paid leave and this shows up particularly for support of paid leave for fathers in the U.S.," Knoester said.

In addition, individuals who felt more conflict between their home and job responsibilities were more likely to endorse paid leave.

While the survey that this study was based on was done 10 years ago, the researchers said more recent surveys suggest people's views have not changed much. If anything, people may have become slightly more supportive of paid leave, particularly in the United States.

"We are still seeing very high support of paid maternity leave, and there are some indications that support for paternity leave has increased since 2012," Knoester said.

In addition, signs point toward more Americans being in favor of government support of parental leave. Nine states and Washington, D.C., have enacted paid parental leave programs. Last November, Colorado voters passed a ballot measure that allows for up to 12 weeks of leave.

"I would never have guessed that the kind of measure enacted in Colorado would pass in the U.S. It suggests Americans are becoming more open to government support," Petts said.

Singularities such as those at the centre of black holes, where density becomes infinite, are often said to be places where physics 'breaks down'. However, this doesn't mean that 'anything' could happen, and physicists are interested in which laws could break down, and how.

Now, a research team from Imperial College London and the Cockcroft Institute and Lancaster University have proposed a way that singularities could violate the law of conservation of charge. Their theory is published in Annalen der Physik.

Co-author Professor Martin McCall, from the Department of Physics at Imperial, said: "'Physics breaks down at a singularity' is one of the most famous statements in pop-physics. But by showing how this might actually happen, we take aim at one of the most cherished laws of physics: the conservation of charge."

The conservation of charge says that the total electric charge of any isolated system - including the Universe as a whole - never changes. This means that if negatively or positively charged particles move into one area, the same amount of respectively charged particles must move out.

This has been shown at the very smallest scales: when different particles are created or eliminated in experiments such as the Large Hadron Collider, the same amount of negatively and positively charged particles are always produced or destroyed, respectively.

Now, by modifying classic physics equations to include axions, a candidate for dark matter, the team have been able to show that temporary singularities - such as black holes that appear and then later evaporate - could destroy charge when they come to the end of their life.

Axions are hypothetical particles that may explain dark matter - the 'missing' 85 percent of the matter of the Universe. Their predicted properties could form a field that would interact with the kind of fields physicists have known about for centuries - electromagnetic fields, which are described by a set of equations called Maxwell's equations.

Using a branch of mathematics called differential geometry, the team found out how to create or destroy charge, violating the charge conservation of the Universe.

Co-author Jonathan Gratus said: "You can imagine creating an 'axion bomb' that holds charge by combining coupled axion and magnetic fields; and then dropping it into an evaporating black hole. As the construction shrinks and disappears into the singularity, it takes electrical charge with it. It is the combination of a temporary singularity and a newly proposed type of axion field that is crucial to its success."

Co-author Dr Paul Kinsler, from the Department of Physics at Imperial, said: "There are also philosophical implications. Although people often like to say that physics 'breaks down', here we show that although exotic phenomena might occur, what actually happens is nevertheless constrained by the still-working laws of physics around the singularity."

The team say the axion phenomenon would only occur under extreme conditions that currently cannot be created in a lab, but that future advances in intense laser fields might allow the theory to be tested in a terrestrial environment.

"Fit for 55": under this heading, the EU Commission will specify the implementation of the European Green Deal on 14 July. This refers to the more ambitious climate policy announced, with 55 instead of 40 percent emission reduction by 2030 (relative to 1990), and net-zero emissions in 2050. Coordination between the 27 EU states is expected to be difficult since unanimity is usually required here for sweeping changes. An economic model study by the Berlin-based climate research institute MCC (Mercator Research Institute on Global Commons and Climate Change) and the Potsdam Institute for Climate Impact Research (PIK) examines how to achieve good results under such conditions. The study has just been published in the renowned Journal of Environmental Economics and Management.

In a model based on so-called game theory, the researchers mathematically depict the main features of such negotiations. This includes a coexistence of climate policy at the federal and state levels, the need for coordination between rich and poor as well as large and small countries and, as an anchor point, the assumption that there is zero idealism involved in the tug-of-war over climate protection. Focusing on maximising national welfare, governments veto any action they perceive as excessive at the federal level, generating more costs than benefits.

"We expand the economic theory on fiscal federalism to include climate policy and consensus-building," explains Christina Roolfs, researcher in the joint MCC-PIK Future Lab on Public Economics and Climate Finance and lead author of the study. "We were interested in how we could achieve as much climate protection as possible under such circumstances. It is about smart policy design that should set the right incentives, so that common plus national policy together render climate emissions as costly as appropriately, and accordingly cause them to decline."

The decisive factor is how the revenues from joint emissions pricing are being distributed within the states. Up to a certain point, rich countries accept the role of net donor, making transfers to poorer countries to support climate policy. Given their prosperity, the effect of climate damage on their economy is likely to be large, and countermeasures are therefore particularly worthwhile. Only when the transfers become too high will they switch from being the driver to putting on the brakes. The researchers model the behaviour of individual governments under different forms of revenue distribution, and for different decision processes: if the countries anticipate that they will benefit from the revenues generated from federal emissions pricing, they will agree to a higher common price. The key finding of the study is that the revenues from emissions pricing should be distributed between countries not according to population, and not according to current emissions, but according to historical emissions before the start of the pricing system. This principal will provide the greatest leeway for a consensual ambitious climate policy.

"This is of practical importance for the European Green Deal," emphasises Ottmar Edenhofer, Director of MCC and PIK and one of the study's co-authors." Money from the EU Emissions Trading System in the energy and industry sectors is already distributed primarily according to historical emissions. But the revenue base is currently riddled with holes because about half of the emission rights are allocated for free. There is a need for a harmonised and consistent design. This also applies to the intended expansion of pricing to the transport and heat sectors." According to Edenhofer, the study is relevant to international cooperation in general: "The theoretical analysis shows that large differences in size and wealth are obstacles. That is why, for example, linking carbon pricing systems might initially be a sensible thing to undertake between similarly strong partners, for example between the EU and the USA."

LA JOLLA, CA--Researchers at La Jolla Institute for Immunology (LJI) have shed light on a process in immune cells that may explain why some people develop cardiovascular diseases.

Their research, published recently in Genome Biology, shows the key role that TET enzymes play in keeping immune cells on a healthy track as they mature. The scientists found that other enzymes do play a role in this process--but TET enzymes do the heavy lifting.

"If we can figure out what's going on with these enzymes, that could be important for controlling cardiovascular disease," says Atsushi Onodera, Ph.D., a postdoctoral researcher at LJI and first author of the new Genome Biology study.

LJI Professor Anjana Rao, Ph.D., co-discovered TET enzymes while working at Harvard University alongside Mamta Tahiliani, Ph.D., and L. Aravind, Ph.D. Their work showed that this family of three enzymes alters how our genes are expressed.

TET enzymes control gene expression by triggering a process called demethylation, where a molecule called a methyl group is removed from where it sits in the genetic code. Demethylation is important because it alters how a cell "reads" DNA.

Over the last decade, Rao has shown the importance of TET activity in cancer development. Her work has revealed that TET enzymes are key to proper gene expression in immune cells--and they can actually protect against cancerous mutations.

For the new study, Rao and Onodera investigated how immune cell DNA can be altered by either TET enzymes (a process called passive demethylation) or by a DNA repair enzyme called TDG (active demethylation).

The researchers aimed to uncover which demethylation pathway has a bigger role in determining the gene expression--the very fate--of immune cells.

The researchers started with two immune cell models: CD4 "helper" T cells and monocytes. Both cell types must proliferate and mature into more specific cell types to help fight off pathogens. However, once monocytes are differentiated into macrophages and stimulated with a molecule called LPS, they stop proliferating. By taking a close look at these CD4 helper T cells and macrophages the researchers could better understand proliferating and non-proliferating models.

The proliferation process is very quick, making it a prime time to witness how demethylation occurs and how it affects gene expression. Onodera used CD4 helper T cells to analyze the demethylation process using a cutting-edge computational analysis program developed for this study. This tool gives scientists an unprecedented look at which regions of DNA within a cell are methylated.

"We found that in immune cells, most demethylation happens through the passive pathway," explains Onodera.

Using a new technique called pyridine borane sequencing, the researchers showed that "active" demethylation--through TDG--is working in immune cells. Onodera says TDG's role is minor: it does the job of removing two molecules generated by TET enzyme activity.

This discovery is important because TET mutations can be life-threatening. Previous studies have shown that mutations in the TET2 enzyme disable (or interfere with) some of the normal restraints on healthy monocytes. The monocytes go rogue and mature into inflammatory macrophages. People bearing TET2 mutations in macrophages have a 40 percent increase in their risk of developing cardiovascular disease.

A deeper understanding of how TET enzymes work could help researchers know where to intervene and help patients with this kind of mutation.

Onodera's new analysis program for identifying changes in DNA modification may also prove useful for understanding how TET mutations in immune cells can lead to blood cancers. He explains that researchers could potentially use the program to identify patients who may have different treatment outcomes based on where their DNA has been demethylated.

"Hopefully we can apply this technique to disease diagnoses," says Onodera.

In fact, Onodera says the new sequencing and analysis program from this study can be applied to many immune cell types and many disease models.

"At this point, we can make significant progress in understanding the molecular mechanisms behind DNA demethylation," Onodera says.

A study from UCLA neurologists challenges the idea that the brain recruits existing neurons to take over for those that are lost from stroke. It shows that in mice, undamaged neurons do not change their function after a stroke to compensate for damaged ones.

A stroke occurs when the blood supply to a certain part of the brain is interrupted, such as by a blood clot. Brain cells in that area become damaged and can no longer function.

A person who is having a stroke may temporarily lose the ability to speak, walk, or move their arms. Few patients recover fully and most are left with some disability, but the majority exhibit some degree of spontaneous recovery during the first few weeks after the stroke.

Doctors and scientists don't fully understand how this happens, because the brain does not grow new cells to replace the ones damaged by the stroke. Neurologists have generally assumed that the brain instead recruits existing neurons to take over for those that are lost.

Now, new results from neurologists William Zeiger and Carlos Portera-Cailliau from the David Geffen School of Medicine at UCLA challenge that idea. In their paper, published June 25 in the journal Nature Communications, they show that in mice, undamaged neurons do not change their function after a stroke to compensate for damaged ones.

Neurologists have been "mapping" the brain since the mid-1800s, when the French physician Paul Broca realized that patients who sustained damage to a certain part of the frontal lobe lost the ability to speak. Over the years, scientists have created increasingly detailed maps of which brain regions control various functions. Still, the resolution of the map has been limited by the precision of the tools available to study the living brain.

Studies in animals and humans that recorded activity across different brain regions have found that activity patterns change after a stroke, suggesting that the damaged brain can "re-map" functions from one area to another. In the last few years, innovative new tools have enabled researchers to start looking at individual neuron activation in real-time. By using a technique called two-photon fluorescence microscopy that causes neurons to light up when they are activated, researchers can observe which neurons in the animal brain are called upon during certain activities and determine if neurons that survived a stroke can assume the function of those that were lost.

"We thought, now that we have this tool where we can record the activity of neurons in the brain, we could directly test this question," says Zeiger. By learning the functions of individual neurons, then causing a targeted stroke, the researchers could use the new technique to observe how the neighboring neurons responded.

Mice gather information about their environment primarily through their whiskers, and each whisker transmits sensory signals to a specific group of neurons. By destroying the neurons coded to a specific whisker, the researchers could look at whether neurons for a different whisker took over for their lost neighbors.

Think of a departmental office, says Portera-Cailliau. "Imagine that several admin staff in human resources for the Department of Neurology suddenly quit their jobs one day. Instantly, the department would suffer their absence, but would try to make up for it." The department might do this by asking HR employees from other departments to do some of the missing employees' work on top of their own.

That's what the re-mapping hypothesis predicts would happen in the brain. "If the hypothesis were true, we would see cells that survived the stroke start to respond to that whisker that had the stroke," Zeiger says. "What we found was that that didn't happen."

Adjacent to the main column of neurons that respond to a given whisker are neurons called "surround-responsive" cells. These are located in the column for one whisker, but they react to the stimulation of a neighboring whisker. Using the office analogy, these neurons would be like employees that work on HR but happen to have their desks in a different physical office.

Logically, then, the team thought that the surround-responsive neurons would be good candidates to take over when the primary responding neurons were destroyed by the stroke. "If the HR office suddenly shut down, you might think more people in these other offices would start doing human resource jobs," Portera-Cailliau says. Yet not only did these other neurons fail to step up, the activity of the surround-responsive neurons themselves decreased after the stroke.

"That was pretty strong evidence against this remapping hypothesis," Zeiger says. "It did not seem like there was bulk recruitment to take over the function which had been lost to stroke."

More studies will be needed to gain a full understanding of what happens in the human brain after a stroke, including why spontaneous recovery happens. Zeiger says that future studies could also explore various ways to induce the surviving cells to compensate for the lost neurons.

"I think it gives the field more of a direction," Zeiger says. "Rather than assuming the brain can remap on its own, now we know that to achieve full recovery, we're going to need a way to get cells to do things they are not already doing."

A new study by UC Davis researchers confirms the low likelihood that SARS-CoV-2 contamination on hospital surfaces is infectious. The study, published June 24 in PLOS ONE, is the original report on recovering near-complete SARS-CoV-2 genome sequences directly from surface swabs.

"Our team was the first to demonstrate that SARS-CoV-2 virus sequences could be identified from environmental swabs collected from hospital surfaces," said Angela Haczku, a respiratory immunologist and senior author on the study.

Changing cleaning and ICU protocols linked to lower SARS-CoV-2 contamination

In April 2020, a COVID-19 outbreak among hospital staff led an interdisciplinary team of UC Davis researchers to investigate if there was virus contamination of frequently used surfaces in patient serving ICU and staff meeting areas at the UC Davis Medical Center. At that time the role of fomites (surfaces) in spreading the disease was highly debated. They collected multiple samples during the first (April 2020) and the second (August 2020) waves of COVID-19 from surfaces and HVAC filters in the hospital.

The researchers analyzed the surface swabs for SARS-CoV-2 RNA and infectivity and assessed the suitability of the RNA for sequencing.

Despite a significant increase in the number of hospital patients with COVID-19 during the second surge, the team found that only 2% of swabs tested positive in August, compared to 11% of samples collected in April.

"The reduction in the virus contamination was likely due to improved ICU patient management and cleaning protocols," Haczku said. Haczku is a professor of medicine, director at the UC Davis Lung Center and associate dean for translational research at the UC Davis School of Medicine.

Genome sequence of coronavirus found on surfaces

The study demonstrated that by genome sequencing, SARS-CoV-2 could be detected even from samples that otherwise tested negative (undetectable) by commonly used PCR tests. The results also confirmed that the SARS-CoV-2 RNA picked up from a surface, although containing near- intact genomic sequence, was not infectious. This finding supports the hypothesis that contaminated surfaces may not be a major way for spreading COVID-19 disease.

"For the first time, to our knowledge, we were able to determine the viral genome sequence from surface swab samples obtained in a hospital environment," said David Coil, project scientist at the UC Davis Genome Center and the first author on the study. "We found SARS-CoV-2 in samples that were tested negative by RT-PCR, suggesting that the sequencing technology is superior for virus detection in environmental samples."

According to Coil, the genome sequencing performed on the hospital surface swab samples is very important. By getting accurate viral genomic sequences, the researchers could track the source and figure out how an infection moves.

"Our data indicated that the sequences determined for the viral RNA from surfaces were identical to the ones derived from the patients hospitalized in the ICU at the time of sample collection. The ability to identify viral genome sequences from environmental samples may have high public health significance in outbreak surveillance and monitoring the spread of new viral variants," Haczku said.

BOSTON - At the recent 2021 Annual Scientific Sessions of the American Diabetes Association, researchers from Massachusetts General Hospital (MGH) presented positive updates on their trials of the bacillus Calmette-Guérin (BCG) vaccine to safely and significantly lower blood sugars.

In type 1 diabetes, an autoimmune disease which currently has no cure, T cells attack the pancreas and destroy its ability to create insulin, a hormone vital in allowing glucose to enter cells to produce energy. In prior work, Denise Faustman, MD, PhD, director of the MGH Immunobiology Laboratory, and colleagues have found that BCG boosts a substance called TNF, which eliminates the harmful T cells and aids development of beneficial ones called regulatory T cells, or Tregs.

Key findings include new understanding in how response to BCG vaccination differs depending on a patient's age of onset and additional support for the role of BCG vaccination to alter glucose transport and change Tregs. Currently 143 type 1 diabetics have received at least two doses of BCG, including 25 patients enrolled in a recently launched trial of adults who had pediatric onset. Pending FDA approval, MGH aims to launch a multi-center pediatric trial later this year.

"More data from randomized double-blinded clinical trials will be reported as we move towards additional readout of the Phase II trial," says Faustman, principal investigator of BCG clinical trials at MGH. "We have continued evidence of BCG's ability to reset and restore the immune system."

In 2018 MGH published results of the follow-up of Phase I trial of BCG-treated long-term diabetic participants, showing lasting clinically and statistically significant drops in HbA1c values that persisted with eight years of follow-up. The new data presented at the ADA include:

Type 1 diabetics with age of onset younger than 21 years have a faster response time and greater change in HbA1c than adult onset type 1 diabetics.

Over a period of three years BCG returns gene expression in Tregs in type 1 diabetics to a pattern consistent with non-type 1 control subjects.

The HbA1c response at two years in juvenile onset subjects is consistent with the three-year response seen in the Phase 1 study.

"BCG is an old vaccine, but it seems to be presenting new gifts," says Nigel Curtis, MD, PhD, of the Murdoch Children's Research Institute in Melbourne, Australia. He directs global clinical trials on the beneficial and off-targets effects of the BCG vaccine but was not involved in the current study. "This new data from MGH adds the growing understanding of how BCG changes the way the body responds to autoimmune and infectious disease."

After suffering a stroke, patients often are unable to use the arm on their affected side. Sometimes, they end up holding it close to their body, with the elbow flexed.

In a new study, Northwestern University and Shirley Ryan AbilityLab researchers have discovered that, in an attempt to adapt to this impairment, muscles actually lose sarcomeres -- their smallest, most basic building blocks.

Stacked end to end (in series) and side to side (in parallel), sarcomeres make up the length and width of muscle fibers. By imaging biceps muscles with three noninvasive methods, the researchers found that stroke patients had fewer sarcomeres along the length of the muscle fiber, resulting in a shorter overall muscle structure.

The research was published today (June 25) in the Proceedings of the National Academy of Arts and Sciences.

This finding is consistent with the common patient experience of abnormally tight, stiff muscles that resist stretching, and it suggests that changes in the muscle potentially amplify existing issues caused by stroke, which is a brain injury. The team hopes this discovery can help improve rehabilitation techniques to rebuild sarcomeres, ultimately helping to ease muscle tightening and shortening.

"This is the most direct evidence yet that chronic impairments, which place a muscle in a shortened position, are associated with the loss of serial sarcomeres in humans," said Wendy Murray, the study's senior author. "Understanding how muscles adapt following impairments is critical to designing more effective clinical interventions to mitigate such adaptations and to improve function following motor impairments."

Murray is a professor of biomedical engineering at Northwestern's McCormick School of Engineering, a professor of physical medicine and rehabilitation at the Northwestern University Feinberg School of Medicine and research scientist at the Shirley Ryan AbilityLab. The research was completed in collaboration with Julius Dewald, professor of physical therapy and human movement sciences and of physical medicine and rehabilitation at Feinberg, professor of biomedical engineering at McCormick, and research scientist at Shirley Ryan AbilityLab.

First demonstration in humans

Measuring just 1.5 to 4.0 microns in length, sarcomeres comprise two main proteins: actin and myosin. When these proteins work together, they enable a muscle to contract and produce force. Although previous animal studies have found that muscles lose serial sarcomeres after a limb is immobilized in a cast, the phenomenon had never before been demonstrated in humans. In the animal studies, muscles that were shorter because they lost serial sarcomeres also became stiffer.

"There is a classic relationship between force and length," said Amy Adkins, a Ph.D. student in Murray's laboratory and the study's first author. "Given that the whole muscle is composed of these building blocks, losing some of them affects how much force the muscle can generate."

To conduct the study in humans, the researchers combined three non-invasive medical imaging techniques: MRI to measure muscle volume, ultrasound to measure bundles of muscle fibers and two-photon microendoscopy to measure the microscopic sarcomeres.

Imaging opens new possibilities

Combining these technologies at Northwestern and Shirley Ryan AbilityLab, the researchers imaged biceps from seven stroke patients and four healthy participants. Because stroke patients are more affected on one side of their body, the researchers compared imaging from the patients' affected side to their unaffected side as well as to images from the healthy participants.

The researchers found that the stroke patients' affected biceps had less volume, shorter muscle fibers and comparable sarcomere lengths. After combining data across scales, they found that affected biceps had fewer sarcomeres in series compared to the unaffected biceps. The differences between stroke patients' arms were greater than in in healthy participants' arms, indicating that the differences were associated with stroke.

By combining medical imaging to better view muscle structure, the study also establishes that it is possible to study muscle adaptations in sarcomere number in humans. Before two-photon microendoscopy, human studies were limited either to examining dissected tissues in anatomy labs, which give imperfect insight into how muscles adapt to injury and impairment, measuring sarcomere lengths during surgery or from a muscle biopsy, which restricts who can participate in the study.

"In almost every facet of our world, there is an important relationship between how something is put together (its structure) and how it works (its function)," the researchers said. "Part of the reason medical imaging is such a valuable resource and clinical tool is that this is also true for the human body, and imaging gives us an opportunity to measure structure."

Three years ago, Arthur Ashkin won the Nobel Prize for inventing optical tweezers, which use light in the form of a high-powered laser beam to capture and manipulate particles. Despite being created decades ago, optical tweezers still lead to major breakthroughs and are widely used today to study biological systems.

However, optical tweezers do have flaws. The prolonged interaction with the laser beam can alter molecules and particles or damage them with excessive heat.

Researchers at The University of Texas at Austin have created a new version of optical tweezer technology that fixes this problem, a development that could open the already highly regarded tools to new types of research and simplify processes for using them today.

The breakthrough that avoids this problem of overheating comes out of a combination of two concepts: the use of a substrate composed of materials that are cooled when a light is shined on them (in this case, a laser); and a concept called thermophoresis, a phenomenon in which mobile particles will commonly gravitate toward a cooler environment.

The cooler materials attract particles, making them easier to isolate, while also protecting them from overheating. By solving the heat problem, optical tweezers could become more widely used to study biomolecules, DNA, diseases and more.

"Optical tweezers have many advantages, but they are limited because whenever the light captures objects, they heat up," said Yuebing Zheng, the corresponding author of a new paper published in Science Advances and an associate professor in the Walker Department of Mechanical Engineering. "Our tool addresses this critical challenge; instead of heating the trapped objects, we have them controlled at a lower temperature."

Optical tweezers do the same thing as regular tweezers -- pick up small objects and manipulate them. However, optical tweezers work at a much smaller scale and use light to capture and move objects.

Analyzing DNA is a common use of optical tweezers. But doing so requires attaching nano-sized glass beads to the particles. Then to move the particles, the laser is shined on the beads, not the particles themselves, because the DNA would be damaged by the heating effect of the light.

"When you are forced to add more steps to the process, you increase uncertainty because now you have introduced something else into the biological system that may impact it," Zheng said.

This new and improved version of optical tweezers eliminates these extra steps.

The team's next steps include developing autonomous control systems, making them easier for people without specialized training to use and extending the tweezers' capabilities to handle biological fluids such as blood and urine. And they are working to commercialize the discovery.

Zheng and his team have much variety in their research, but it all centers on light and how it interacts with materials. Because of this focus on light, he has closely followed, and used, optical tweezers in his research. The researchers were familiar with thermophoresis and hoped they could trigger it with cooler materials, which would actually draw particles to the laser to simplify analysis.