Culture

Social distancing - from mobility restrictions to complete lockdowns -- can take many weeks, possibly even months, a potentially devastating outcome for social and economic stability. One of the challenges is that the sick cannot be selectively isolated, since many of the spreaders remain pre-symptomatic for a period ranging from several days to as much as two weeks - invisible spreaders who continue to be socially active. Hence, it seems that without a population-wide lockdown isolating the carriers cannot be achieved effectively.

To bypass this challenge, researchers from Israel's Bar-Ilan University, led by Prof. Baruch Barzel, devised a strategy based on alternating lockdowns: first splitting the population into two groups, then alternating these groups between lockdown and routine activity in weekly succession. Together with isolation of the symptomatic spreaders and the adoption of everyday prophylactic behaviors, this strategy can help defeat the virus, while sustaining socio-economic activity at a 50% level. This strategy was recently published in the journal Nature Communications.

In the alternating lockdown routine, society is partitioned into two groups, with little interaction between them -- one half active this week, and the other active only the next. This will already slow the spread, but its main advantage is that it helps isolate the invisible spreaders, such as those who are pre-symptomatic carriers still in the incubation period. "Consider an individual who became infected during their active week. They are now in their pre-symptomatic period - the most dangerous stage, in which they are invisible spreaders. The crucial point is that, according to the alternating lock-down routine they are now scheduled to enter their lockdown phase," explains Prof. Barzel, of Bar-Ilan's Department of Mathematics. "Staying at home for another week, they will most likely begin to exhibit symptoms, and therefore remain in isolation until full recovery. Indeed, if following a week of lockdown they show no symptoms, they are most likely uninfected and can partake in social and professional activities during their active week. Therefore, alternating lockdown with full isolation of symptomatic spreaders ensures that at all times, the majority of invisible spreaders are inactive, as their incubation period is naturally directed towards their lockdown phase."

Most people are extremely cautious, and will refrain from any contact with someone showing symptoms. "Therefore, we believe that it is the invisible spreaders that are the main contributors to the proliferating case count. Our strategy is precisely directed at this challenge -- placing each person on weekly lockdown after they were potentially exposed during their active week. Hence, we effectively isolate not just the sick, but also the majority of the pre-symptomatic carriers," says Barzel.

To examine this Barzel and team simulated the spread of COVID-19 using a detailed epidemiological model. This model tracks the number of individuals as they transition between the different stages of the disease, from the pre-symptomatic phase to the onset of symptoms and, down the disease cycle, to potential hospitalization, ventilation or even mortality. They found that employing their strategy significantly reduces the spread and helps flatten the curve, with effectiveness comparable to that of an 80% lockdown, all the while sustaining continuous socioeconomic activity at 50% capacity.

"We can achieve more if we also adopt responsible behavior. Specifically, we expect that even during their active week, people will continue to interact with caution: avoid physical contact, increase personal space and practice hygienic behavior. These additional measures, when coupled with our alternating lockdown strategy, can help inhibit the spread, allowing us to overcome COVID-19 with reasonable economic consequences," he says.

Sustaining restrictive measures such as lockdowns is always a challenge, since some percentage of the population may not cooperate, especially in democratic and individualistic societies. The researchers therefore allowed for a fraction of defectors who continue to be active even during their lockdown phase in their simulation. This can also represent exempt individuals who hold essential positions and cannot be under lockdown. They found that even under 20% of non-cooperators their strategy would still overcome the viral spread.

The proposed weekly succession is aimed to sustain a functional economy in these challenging times. The researchers believe that, providing an outlet for people to continue their social and professional activity, at least at 50% capacity, will, in and of itself encourage cooperation, as it relaxes some of the individual stress endured under lockdown.

In the first few months of their lives, babies cry, babble, gurgle and make a variety of other peculiar sounds. It can be difficult to imagine that they are actually laying the foundations for later speech with these utterances. However, there is a determining element that proves that even their cries can be assigned to a particular language: the speech melody - or, more accurately: prosody.

"Every language is characterised by specific musical elements, which we call prosody," says Kathleen Wermke. Prosody, in simple terms, is the combination of intonation (melody) and rhythm. Earlier studies have shown that even newborns are able to distinguish different languages, like German or French, using prosodic cues, particularly melody. With the help of these musical elements, infants recognise the respective language long before they are able to perceive its special features such as consonants, vowels or syllables.

Study with more than 67,000 baby sounds

Kathleen Wermke is a Professor at the Würzburg University Hospital at the Department of Orthodontics and Head of the Center for Pre-speech Development and Developmental Disorders. Together with scientists from the USA and New Zealand, she has now examined the vocalisations of a total of 277 infants over the first six months of life in more detail. In total, the team analysed more than 67,500 cry vocalisations - the so-called hungry-crying -, cooing and babbling sounds.

"We have found a clear developmental pattern towards more complexity," Wermke summarises the result of the study, which has now been published in the journal Scientific Reports. According to the study, this increasing degree of complexity is an important building block on the way to language development. According to the research team, these findings do not only significantly improves our understanding of the early preparatory processes for language acquisition, it also makes it possible to identify potential signs of a language development disorder.

Complexity increases over the course of the first six months

In their study, the team distinguished between two types of vocalisations in babies: cry and non-cry vocalisations in technical language. Or, to put it another way, the "communicative" crying uttered in the presence of the mother, which results from discomfort such as hunger and when there is a desire for contact. And, on the other hand, the sounds a baby makes when it feels comfortable and interacts vocally. "The aim of the study was to conduct an objective developmental analysis of prosodic antecedents in the form of melodies in healthy infants from birth to 6 months of age in all their vocalisations," says Wermke. Her hypothesis was: both types of vocalisation show a characteristic developmental increase in complex melodies.

In fact, the evaluation shows that the melodies of spontaneous cries become increasingly complex during the first 180 days of life; complex meaning that simple melodies (single-arc) are increasingly replaced by multiple-arc melodies, i.e. the foundation for the richness of variants of later intonation patterns in speech is already laid during crying. The development was comparable for phonetic utterances that fall under the category of "comfort vocalisations". The degree of complexity also increased in these, but with a temporary decline at around 140 days of age.

Rapid brain growth is the foundation

"Already at the end of the first month of life, the cry repertoire of the babies studied shows a complex melody in more than half of the cases," says Wermke. From single-arc to multiple-arc melodies in 30 days: this developmental programme is based on an early maturity of the neurophysiological mechanisms underlying melody production. In fact, the brains of newborns also grow tremendously fast during this time, and newborns show amazing coordination between breathing and phonation. Furthermore, the scientists believe that the early occurrence of complex cry melodies indicates that infants have already undergone a kind of training, a "preparatory" intrauterine development before birth, in order to start with the development of melodies immediately after or at the starting signal "birth".

Wermke and her co-authors have an explanation for this slight decrease in complexity between the ages of four and five months: "During this time, infants expand their repertoire of vocalic utterances to include new components that interact with the overall melodic contour, namely vowel- and consonant-like elements," says Kathleen Wermke. At the same time, the larynx and vocal tract are changing, which entails a series of adaptation processes in sound production. In addition to this, infants also begin to produce their first syllable combinations in babbling during this phase. "This new developmental period evidently causes a temporary 'regression' in melody development to establish vocal development on a higher hierarchical level. Thereafter, the infant begins to intentionally imitate intonation patterns of the surrounding language(s) in consonant-vowel syllable sequences in babbling.

Prerequisite for innovative therapies

According to those involved, the developmental model now presented can contribute to a better understanding of why the human infant acquires such a complex skill as language so quickly and seemingly effortlessly. What sounds like rather dry basic research in the field of spoken language acquisition nevertheless has a very practical relevance. "Knowledge of this developmental process will enable us to identify clinically robust risk markers for language development disorders," says Wermke. This, she says, is the crucial prerequisite for developing new and innovative therapies for young children at risk for language disorders.

Extreme weather driven by climate change is making power outages more commonplace even as the need for electricity-dependent home health equipment grows. In this context, battery storage can help protect medically vulnerable households, according to researchers at Columbia University Mailman School of Public Health. The article is published in the journal Futures.

For the millions reliant on electricity for home medical equipment, even short-term power outages can lead to a potentially life-threatening situation. Society's most vulnerable populations--elders, the ill, and the poor--face the greatest risks. Only a fraction of individuals who rely on medical equipment like oxygen concentrators, nebulizers, ventilators, dialysis, and sleep apnea machines has an alternative source of power to use in the event of an outage. During outages related to the 2019 Camp Fire in Northern California, vulnerable residents reported complications, including one man who awoke when his sleep apnea breathing machine failed in the middle of the night and he couldn't breathe. One woman had to spend the night in her wheelchair because her special mattress required electricity to remain inflated.

The researchers call for policies to support resilient power systems--ideally, battery storage paired with solar photovoltaics--that provide clean, reliable emergency backup power by storing electricity for use when grid power is unavailable. One model is the California Self-Generation Incentive Program, which provides incentives for residential battery storage, and includes energy storage incentives for low-income residents. Additional lessons come from a study in Puerto Rico after Hurricane Maria, which found that residents preferred solar-powered battery backups to diesel generators due to ease of use, low cost, and an elimination of fumes that exacerbate asthma and other lung conditions.

Community facilities like senior centers, public schools, and health centers often lack backup power, too. During an emergency, vulnerable residents typically turn to these facilities for heating/cooling, refrigeration to store perishable items and temperature-regulated medicines, lighting, and outlets to charge cell phones and medical equipment. Without backup power, critical facilities ultimately must limit operations or close entirely.

"Climate change coupled with an aging energy infrastructure is driving extreme weather-related power outages, as we've seen recently in Texas," says co-author Diana Hernández, PhD, associate professor of sociomedical sciences. "The technology to improve resiliency and energy independence exists, and it needs to be made more accessible to those who could most benefit. Battery storage units, particularly those powered by the sun, are a critical tool to help vulnerable individuals and communities survive the climate crisis."

In a separate review of scientific literature published in Current Environmental Health Reports, researchers found that power outages have important health consequences ranging from carbon monoxide poisoning, temperature-related illness, gastrointestinal illness, and mortality to cardiovascular, respiratory, and renal disease hospitalizations, especially for individuals relying on electricity-dependent medical equipment. Evidence from the U.S. suggests older adults, poorer families, and individuals of non-Hispanic Black and Hispanic race/ethnicity are least likely to have a three-day supply of food, drinking water, and medication, a preparedness measure for power outages.

Overall, the researchers found that more work is needed to better define and capture the relevant exposures and outcomes. "There is urgent need for data to inform disaster mitigation, preparedness, and response policies (and budgets) in an increasingly energy-reliant world," said first author Joan Casey, PhD, assistant professor of environmental health sciences at Columbia Mailman School.

COVID-19, the disease caused by the pandemic coronavirus SARS-CoV-2, is primarily regarded as a respiratory infection. Yet the virus has also become known for affecting other parts of the body in ways not as well understood, sometimes with longer-term consequences, such as heart arrhythmia, fatigue and "brain fog."

Researchers at University of California San Diego School of Medicine are using stem cell-derived organoids -- small balls of human cells that look and act like mini-organs in a laboratory dish -- to study how the virus interacts with various organ systems and to develop therapies to block infection.

"We're finding that SARS-CoV-2 doesn't infect the entire body in the same way," said Tariq Rana, PhD, professor and chief of the Division of Genetics in the Department of Pediatrics at UC San Diego School of Medicine and Moores Cancer Center. "In different cell types, the virus triggers the expression of different genes, and we see different outcomes."

Rana's team published their findings February 11, 2021 in Stem Cell Reports.

Like many organs, the team's lung and brain organoids produce the molecules ACE2 and TMPRSS2, which sit like doorknobs on the outer surfaces of cells. SARS-CoV-2 grabs these doorknobs with its spike protein as a means to enter cells and establish infection.

Rana and team developed a pseudovirus -- a noninfectious version of SARS-CoV-2 -- and labeled it with green fluorescent protein, or GFP, a bright molecule derived from jellyfish that helps researchers visualize the inner workings of cells. The fluorescent label allowed them to quantify the binding of the virus' spike protein to ACE2 receptors in human lung and brain organoids, and evaluate the cells' responses.

The team was surprised to see approximately 10-fold more ACE2 and TMPRSS2 receptors and correspondingly much higher viral infection in lung organoids, as compared to brain organoids. Treatment with viral spike protein or TMPRSS2 inhibitors reduced infection levels in both organoids.

"We saw dots of fluorescence in the brain organoids, but it was the lung organoids that really lit up," Rana said.

Besides differences in infectivity levels, the lung and brain organoids also differed in their responses to the virus. SARS-CoV-2-infected lung organoids pumped out molecules intended to summon help from the immune system -- interferons, cytokines and chemokines. Infected brain organoids, on the other hand, upped their production of other molecules, such as TLR3, a member of the toll-like receptor family that plays a fundamental role in pathogen recognition and activation of innate immunity

Rana explained that, while it might seem at first like the brain organoid reaction is just another form of immune response, those molecules can also aid in programmed cell death. Rana's team previously saw a similar brain cell response to Zika virus, an infection known to stunt neonatal brain development.

"The way we are seeing brain cells react to the virus may help explain some of the neurological effects reported by patients with COVID-19," Rana said.

Of course, organoids aren't exact replicas of human organs. They lack blood vessels and immune cells, for example. But they provide an important tool for studying diseases and testing potential therapies. According to Rana, organoids mimic the real-world human condition more accurately than cell lines or animal models that have been engineered to over-express human ACE2 and TMPRSS2.

"In animals over-expressing ACE2 receptors, you see everything light up with infection, even the brain, so everyone thinks this is the real situation," Rana said. "But we found that's likely not the case."

In addition to their work with the pseudovirus, the team validated their findings by applying live, infectious SARS-CoV-2 to lung and brain organoids in a Biosafety Level-3 laboratory -- a facility specially designed and certified to safely study high-risk microbes.

Now Rana and collaborators are developing SARS-CoV-2 inhibitors and testing how well they work in organoid models derived from people of a variety of racial and ethnic backgrounds that represent California's diverse population. They were recently awarded new funding from the California Institute for Regenerative Medicine to support the work.

ROCKVILLE, MD - Coronaviruses exploit our cells so they can make copies of themselves inside us. After they enter our cells, they use our cell machinery to make unique tools of their own that help them generate these copies. By understanding the molecular tools that are shared across coronaviruses, there is potential to develop treatments that can not only work in the current COVID-19 pandemic, but in future coronavirus outbreaks as well. Rockefeller University researchers in the labs of Tarun Kapoor and Shixin Liu, including postdoctoral associate Keith Mickolajczyk, recently published their study of one of these molecular tools, which is a potential drug target. They will present their research on Tuesday, February 23 at the 65th Annual Meeting of the Biophysical Society.

During a viral infection, viruses make copies of themselves inside their host, and viruses carry genetic instructions for several tools in order to do so. One of those tools is called a helicase--all organisms have helicases that unwind the genetic information so it can be read or copied. Mickolajczyk had been studying helicases and other molecular motors when the COVID-19 pandemic hit and turned his attention to a helicase encoded in the genome of SARS-CoV-2 (the virus that causes COVID-19), called nsp13.

Mickolajczyk and colleagues investigated the mechanism that individual nsp13 molecules use to unwind genetic material, and their study marks the first single-molecule unwinding experiments to ever be done on a coronavirus helicase. They found that nsp13 is a relatively weak helicase, meaning it needs assisting mechanical forces to be activated, and other viral molecules may help it. They also found that nsp13 did not act like a Hepatitis C virus helicase with a similar shape, and instead acted more like ring-shaped helicases found in bacteriophages (viruses that infect bacteria).

Because coronaviruses have helicases that are very similar to nsp13, it is valuable to understand how this molecule works. "If we can come up with viral therapeutics that hit nsp13, we can have a first line of defense when new coronaviruses potentially erupt and cause new epidemics or pandemics in the future. Understanding this mechanism now can help us design inhibitors that can be treatments against coronaviruses," Mickolajczyk says.

Their results, Mickolajczyk says, can provide insights that can be leveraged for drug discovery efforts. By inhibiting nsp13, a drug could prevent coronaviruses from making copies of themselves, thereby halting infections and stopping or preventing a pandemic.

ROCKVILLE, MD - A tenth of all intensive care unit patients worldwide, and many critical patients with COVID-19, have acute respiratory distress syndrome (ARDS). Therapeutic hypothermia, an intentional cooling of the body, has been suggested as a way to improve ARDS. New research by Chiara Autilio and colleagues in the lab of Jesus Perez-Gil at the Complutense University of Madrid shows not only how therapeutic hypothermia works in the lungs at the molecular level, but also why it could be successfully applied to ARDS. Autilio and her colleagues' work was published in Nature Scientific Reports in January 2021 and will be presented on Tuesday, February 23 at the 65th Annual Meeting of the Biophysical Society to be held virtually.

Inside our lungs, surfactant is a molecular mixture that is essential for breathing. Premature babies are sometimes born without yet having developed surfactant and require emergency surfactant replacement treatments in order to breathe. But surfactant is also inactivated and broken up in adults with lung injuries or inflammation.

Because therapeutic hypothermia, a cooling of the body to about 33°C (or 91°F), has been used to improve breathing for some premature babies and for some kinds of cardiac arrest in adults, and some early studies have shown a benefit for ARDS, Autilio and colleagues wanted to know if cooling could impact surfactant. They looked at the physics of isolated surfactant in their lab, and Autilio said, "unexpectedly, we found an improvement in surfactant activity at 33°C."

The team found that at 33°C, the surfactant had lower surface tension, which could make it easier for oxygen to enter the lungs. They also found that the lower tension changed the activity of the molecules in the surfactant, which prevented surfactant from being disrupted by blood molecules, which can occur during lung injury. Their results indicate that "using therapeutic hypothermia could help people with acute respiratory distress syndrome to breathe."

There are currently clinical trials underway in other labs, testing therapeutic hypothermia as a treatment for severe breathing problems associated with COVID-19, according to Autilio. And in the Perez-Gil lab at the Complutense University, "we are working to create a surfactant for adults, a surfactant that could work in the context of acute respiratory distress syndrome," says Autilio.

HSE University researchers have become the first in the world to discover genetic predisposition to severe COVID-19. The results of the study were published in the journal Frontiers in Immunology.

T-cell immunity is one of the key mechanisms used by the human body to fight virus infections. The staging ground for cell immunity development is the presentation of virus peptides on the surface of infected cells. This is followed by activation of T lymphocytes, which start to kill the infected cells.
The ability to successfully present virus peptides is largely determined by genetics. In human cells, human leukocyte antigen class I (HLA-I) molecules are responsible for this presentation. The set of six such molecules is unique in every human and is inherited from an individual's parents. In simple terms, if the set of alleles detects the virus well, then the immune cells will detect and destroy the infected cells fast; if a person has a set that is bad at such detection, a more severe case of disease is more likely to be observed.

Researchers from the HSE Faculty of Biology and Biotechnology - Maxim Shkurnikov, Stepan Nersisyan, Alexei Galatenko and Alexander Tonevitsky -together with colleagues from Pirogov Russian National Research Medical University and Filatov City Clinical Hospital (Tatjana Jankevic, Ivan Gordeev, Valery Vechorko) studied the interconnection between HLA-I genotype and the severity of COVID-19.

Using machine learning, they built a model that provides an integral assessment of the possible power of T-cell immune response to COVID-19: if the set of HLA-I alleles allows for effective presentation of the SARS-CoV-2 virus peptides, those individuals received low risk score, while people with lower presentation capability received higher risk scores (in the range from 0 to 100). To validate the model, genotypes of over 100 patients who had suffered from COVID-19 and over 400 healthy people (the control group) were analysed. It turned out that the modelled risk score is highly effective in predicting the severity of COVID-19.

In addition to analysing the Moscow population, the researchers used their model on a sample of patients from Madrid, Spain. The high precision of prediction was confirmed on this independent sample as well: the risk score of patients suffering severe COVID-19 was significantly higher than in patients with moderate and mild cases of the disease.

'In addition to the discovered correlations between the genotype and COVID-19 severity, the suggested approach also helps to evaluate how a certain COVID-19 mutation can affect the development of T-cell immunity to the virus. For example, we will be able to detect groups of patients for whom infection with new strains of SARS-CoV-2 can lead to more severe forms of the disease,' Alexander Tonevitsky said.

New compound targets neurons that initiate voluntary movement

After 60 days of treatment, diseased brain cells look like healthy cells

More research needed before clinical trial can be initiated

CHICAGO and EVANSTON--- Northwestern University scientists have identified the first compound that eliminates the ongoing degeneration of upper motor neurons that become diseased and are a key contributor to ALS (amyotrophic lateral sclerosis), a swift and fatal neurodegenerative disease that paralyzes its victims.

In addition to ALS, upper motor neuron degeneration also results in other motor neuron diseases, such as hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS).

In ALS, movement-initiating nerve cells in the brain (upper motor neurons) and muscle-controlling nerve cells in the spinal cord (lower motor neurons) die. The disease results in rapidly progressing paralysis and death.

So far, there has been no drug or treatment for the brain component of ALS, and no drug for HSP and PLS patients.

"Even though the upper motor neurons are responsible for the initiation and modulation of movement, and their degeneration is an early event in ALS, so far there has been no treatment option to improve their health," said senior author Hande Ozdinler, associate professor of neurology at Northwestern University Feinberg School of Medicine. "We have identified the first compound that improves the health of upper motor neurons that become diseased."

The study will be published in Clinical and Translational Medicine on February 23.

Ozdinler collaborated on the research with study author Richard B. Silverman, the Patrick G. Ryan/Aon Professor of Chemistry at Northwestern.

The study was initiated after Silverman identified a compound, NU-9, developed in his lab for its ability to reduce protein misfolding in critical cell lines. The compound is not toxic and crosses the blood brain barrier.

The NU-9 compound addresses two of the important factors that cause upper motor neurons to become diseased in ALS: protein misfolding and protein clumping inside the cell. Proteins fold in a unique way to function; when they misfold they become toxic to the neuron. Sometimes proteins aggregate inside the cell and cause pathology as in the TDP-43 protein pathology. This happens in about 90% of all ALS patient brains and is one of the most common problems in neurodegeneration.

The research team began to investigate whether NU-9 would be able to help repair upper motor neurons that become diseased due to increased protein misfolding in ALS. The results in mice were positive. Scientists next performed experiments to reveal how and why the diseased upper motor neurons regained their health.

New compound restores neurons to robust health

After administering NU-9, both the mitochondria (the cell's energy producer) and the endoplasmic reticulum (the cell's protein producer) began to regain their health and integrity resulting in improved neuron health. The upper motor neurons were more intact, their cell bodies were larger and the dendrites were not riddled with holes. They stopped degenerating so much that the diseased neurons became similar to healthy control neurons after 60 days of NU-9 treatment.

Commanders-in-chief of movement

"Improving the health of brain neurons is important for ALS and other motor neuron diseases," Ozdinler said.

Upper motor neurons are the brain's commanders-in-chief of movement. They carry the brain's input to spinal cord targets to initiate voluntary movement. The degeneration of these neurons impairs the connection from the brain to the spinal cord and leads to paralysis in patients.

Lower motor neurons have direct connections with the muscle, contracting muscle to execute movement. Thus, the lower motor neuron activity is in part controlled by the upper motor neurons.

Ozdinler and colleagues will now complete more detailed toxicology and pharmacokinetic studies prior to initiating a Phase 1 clinical trial.

COLUMBUS, Ohio - Scientists from around the world have published more than 87,000 papers about coronavirus between the start of the COVID-19 pandemic and October 2020, a new analysis shows.

Even given the importance of the pandemic, researchers were surprised by the huge number of studies and other papers that scientists produced on the subject in such a short time.

"It is an astonishing number of publications - it may be unprecedented in the history of science," said Caroline Wagner, co-author of the study and associate professor in the John Glenn College of Public Affairs at The Ohio State University.

"Nearly all of the scientific community around the world turned its attention to this one issue."

Wagner conducted the analysis with Xiaojing Cai from Zhejiang University in China and Caroline Fry of the University of Hawai'i. The study was published online this month in the journal Scientometrics.

The researchers searched for coronavirus-related articles in several scientific databases and found that 4,875 articles were produced on the issue between January and mid-April of 2020. That rose to 44,013 by mid-July and 87,515 by the start of October.

Wagner compared research on coronavirus to the attention given to nanoscale science, which was one of the hottest topics in science during the 1990s.

It took more than 19 years to go from 4,000 to 90,000 scientific articles on that topic, she said.

"Coronavirus research reached that level in about five months," she said.

This new study was an update to one the researchers published in July in PLOS ONE.

In the earlier study, the researchers found that China and the United States led the world in coronavirus research during the early months of the pandemic.

This new study showed that China's contributions dropped off significantly after infection rates in the country fell. From Jan. 1 to April 8, Chinese scientists were involved in 47% of all worldwide publications on coronavirus. That dropped to only 16% from July 13 to Oct. 5.

Similar results were found in other countries when infection levels dropped among their populations.

"That surprised us a bit," Wanger said.

It may be that government funding for research on the issue dropped dramatically in countries like China when the pandemic no longer posed as large of a threat.

"At the beginning of the pandemic, governments flooded scientists with funding for COVID research, probably because they wanted to look like they were responding," she said. "It may be that when the threat went down, so did the funding."

In China, the work was also slowed by a government requirement that officials approve all articles related to COVID-19, Wagner said. Political leaders were concerned about how China, as the source of the virus, appeared to the rest of the world.

Scientists in the United States were involved in 23% of all worldwide coronavirus studies at the beginning of the pandemic and about 33% from July to October, the last period covered in this study.

The new study found that the size of teams on coronavirus research projects, which had already started to get smaller in the first study, continued to drop.

That was unexpected, Wagner said. She and colleagues had anticipated team sizes would slowly get larger as the pandemic continued and researchers had more time to plan and figure out what was happening.

"We attribute this continued decline to the need for speedy results as pandemic infections grew rapidly," Wagner said. "Smaller teams make it easier to work quickly."

The rate of international collaborations also continued to drop, the study found. Part of the reason was practical: Travel bans made it impossible for researchers to meet. This particularly hurt the formation of new collaborations among scientists, which almost always begin face-to-face, Wagner said.

But there may have also been a political component, she said, particularly in U.S.-China collaborations.

The Chinese government's requirement of study review probably hurt. In addition, the U.S. government has given more scrutiny to Chinese researchers in the United States, which may have led some scientists to forgo partnerships.

"We need to figure out a way to restart these collaborations as we move into the post-COVID period," Wagner said. "International cooperation is crucial for the scientific enterprise."

Luxembourg, 23 February 2021 - At an online European Parliament workshop hosted by Deirdre Clune MEP (Ireland), Alzheimer Europe launched a new report "Data Sharing in Dementia Research", which reviews recent changes in EU research policy and sets out recommendations to improve data sharing in dementia research.

In this report, Alzheimer Europe evaluates the legal and policy landscapes that dementia researchers have had to navigate since the launch of Horizon 2020 in 2013. The report identifies key barriers and enablers for data sharing. It maps the Horizon 2020 dementia research portfolio, assessing the scale of EU investment in dementia research and the use of clinical research data. Finally, it reviews recent surveys of researchers, research participants and patients, collating their perceptions and concerns regarding data sharing.

Key findings:

To date, over EUR 570 million has been invested through Horizon 2020 in dementia research projects, many of which involve the use of clinical data

Although Open Access principles have been widely adopted, the uptake of Open Data practices varies between sectors and Member States

The General Data Protection Regulation (GDPR) has not yet fully delivered on its aim of facilitating research data sharing, due to a perceived lack of clarity and regulatory divergence between Member States

Researchers face technical, financial and motivational obstacles to data sharing, with the loss of privacy being the most frequently-cited concern for research participants.

Key recommendations to improve data sharing:

Developing pathways for faster, secure sharing of research data between sectors and across borders, including GDPR codes of conduct and standard contract clauses

Supporting researchers to maintain datasets and platforms after projects end, and embedding academic reward systems that place a greater value on data sharing and transparency

Increasing digital literacy in the general population, ensuring that older adults and vulnerable groups are not left behind

Involving people with dementia in the design and conduct of research, as well as in data governance.

Commenting on the launch of the report, Alzheimer Europe's Executive Director, Jean Georges, stated:

"The number of people with dementia in Europe is likely to double by 2050, increasing from 9.78 to 18.8 million in the wider European region. Unfortunately, research on dementia has historically received proportionately less funding than other disease areas. As a result, there is an urgent need to maximise the utility of data from dementia research. Data sharing represents an important step towards meeting this need, and could help increase our understanding of the causes, treatment, prevention and care of dementia. However, there is still much to do to improve data sharing in dementia research. To ensure people with dementia benefit from the progress made in recent years, we need to work together to overcome the remaining obstacles to data sharing, and maintain dementia research as a priority for EU research programmes."

Helsinki, Finland--Technology helps humans maintain connections, get work done, and relax after a long day. How it can best improve the lives of animals, particularly those in captivity, however, has remained an open question.

Scientists from Aalto University, in collaboration with Korkeasaari Zoo, have designed and built an on-demand video device for white-faced saki monkeys to activate as and when they like. While enrichment systems for zoo animals have been around for some time, very few offer animals the ability to choose when and how they use the device, even though choice and control are known to promote animal welfare.

'We were very much interested in how we can give animals control over their environment and especially how they can control technology. Typically, when we use technology with animals, we use it on them, so we play them sounds or video, rather than giving them the option of controlling the technology themselves,' says Ilyena Hirskyj-Douglas, lead author and visiting researcher at Aalto University.

The device, a tunnel built of plywood and acrylic and equipped with a monitor, camera and sensors to monitor the use of space, was placed in the saki habitat at Korkeasaari Zoo, located in the Finnish capital of Helsinki. It was up to the animals to decide whether they wanted to step inside the device - the equivalent of pressing play - to see the video of the week. During the study, the device played five different kinds of scenes: sealife like fish and jellyfish, wiggly worms, other zoo animals like zebras, makis and dear, abstract art, or lush forests.

'We got interesting results. First of all, we learned that the monkeys do pay attention to the screen; they watch it and touch it. We also suspect they recognize objects on the screen. One of the videos we had featured meal worms - an everyday meal for them. They actually tried to lick the screen and even went around the tunnel to see if the worms were behind it,' explains Vilma Kankaanpää, co-author of the paper and Master's student at Aalto University.

Despite keen observation, it's difficult to say with certainty which video the monkeys liked the most. They spent most of their time watching slithering worms or underwater scenes but these were also the videos accessible at the middle of the study, when they were accustomed to using the device, but it was still fairly new.

The researchers, however, found that, in comparison to the no-video control condition, the sakis scratched themselves significantly less often when presented with video content. For monkeys in captivity, scratching can be a sign of stress.

While a causal link between specific activities and animals' stress levels cannot be made, one thing is sure: different types of stimuli gives them new things to do, which is important for their wellbeing.

The researchers based the video device on their previous research published in autumn 2020, in which they used the same tunnel-shaped device to play the sakis different sounds and music. At the time, researchers found that monkeys listened more to the sounds of traffic than to the sounds of rain, music, or silence.

Kirsi Pynnönen-Oudman, research coordinator at Korkeasaari Zoo, believes that both audio and video can be used to enrich the lives of primates and possibly some birds, such as parrots and crows, living at their facilities also in the future.

'The equipment must, of course, withstand the handling of animals, and those which have, for example, sharp teeth must have their own equipment. The advantage is that the availability of video and audio content is almost unlimited, so the use of the device is not expensive,' Pynnönen-Oudman says.

The study has been published in the scientific journal Animals.

U.S. policies in the Middle East are built on outdated "legacy" aid packages, massive arms sales and a disproportionate focus on the Iranian threat that fail to advance American interests - or help the region's people - and need to be rethought, according to a new RAND Corporation report.

The United States devotes an overwhelming share of foreign military financing to just three countries - Israel, Egypt and Jordan, which received 81% of the $6 billion spent globally in 2019. If policymakers were to pursue an alternative strategy outlined by RAND researchers, they would rebalance America's support by prioritizing non-security investments in development and improved governance, which could enhance regional stability.

"This imbalance limits the depth of cooperation the U.S. can realize with other Middle Eastern countries outside of the Big 3," said Linda Robinson, co-author of the report and director of the Center for Middle East Public Policy (CMEPP) at nonprofit, nonpartisan RAND. "We propose continuing to engage in the region but doing so at a more measured rate and with a smarter approach."

The report reimagines a U.S. strategy in the Middle East with a positive vision of outcomes rather than one focused solely on threats. "We need to start thinking about what we are for in this region, not just what we're against," said Dalia Dassa Kaye, lead author of the report, former CMEPP director at RAND and now a fellow at the Wilson Center.

Under this alternative strategy, the U.S. would shift from a heavy reliance on military tools to an approach that prioritizes economic investments, governance, diplomacy and programs focused on people. That might entail reducing sales of high-end offensive weaponry in favor of equipment tailored to defensive purposes and closing the gap between the Big 3 aid recipients and other regional partners.

The strategy would also entail a counterterrorism focus on nonmilitary programs to stabilize war-torn countries and counter violent extremism; increased support for domestic reform efforts already underway and supported by leaders across the Arab world; and regular evaluations of all assistance programs. Resources would move to those countries and programs that produce desired outcomes in support of U.S. strategic goals.

The recent announcement by the Biden Administration to withhold support to Saudi Arabia for offensive operations in Yemen "is very much in line with the type of strategic recommendations in our report," said Jeffrey Martini, co-author of the report and a senior Middle East researcher at RAND.

The strategy would favor a long-term time horizon to reduce conflict and support regional growth and development, increasing engagement with Middle Eastern publics on such issues as health, youth unemployment and climate change, for example. It would maintain a spotlight on human rights abuses at the highest levels of government, including consistent pressure for the release of political prisoners.

U.S. policies of maximum pressure and unilateral sanctions have not constrained Iran's nuclear program or curbed its regional activities, the researchers concluded. Along with restraining Iran's nuclear program through multilateral diplomacy, America's longer-term goal should be supporting reforms aimed at changing the environment in which Iran operates to reduce the susceptibility of the region to Iranian influence. Improved governance and stability in Iraq could be particularly important in deflating Iran's reach.

"The strategy we lay out requires a shift from a military to a nonmilitary mindset," the researchers conclude. "It requires recalibrating U.S. military support and reducing arms sales while increasing economic, trade and financial investments. It calls for more diplomatic initiative to break out of the current cycle of conflict and escalation. Our assessment suggests that working toward such a long-term agenda with partners, regionally and globally, is an investment that will pay higher dividends, at lower costs, than continuing on our present path."

A recent genetic study at the University of Helsinki provides new information on the occurrence of a DVL2 gene defect associated with a screw tail and its relevance to canine constitution and health. The variant was found in several Bulldog and Pit Bull type breeds, and it was shown to result in caudal vertebral anomalies and shortening of the muzzle. The DLV2 variant may also affect the development of the heart.

Dog breeding is often focused on appearance. In some breeds, the ideal body shape is bulky, with a broad head and short muzzle, short legs and a very short and kinked tail, also known as a "screw tail". In a previous study in the United States, screw tail was linked to a variant in the DVL2 gene. The variant has become enriched in English Bulldogs, French Bulldogs and Boston Terriers due to inbreeding. In addition to the shape of the tail, the DVL2 variant was suggested to contribute to other features typical of the above breeds, as well as what is known as the Robinow-like syndrome. However, its specific effects on body shape and health remained unclear at the time.

"In this study, we wanted to further investigate the frequency of the DVL2 variant in different dog breeds and determine its effects on skeletal development. The variant was identified in several Bulldog and Pit Bull type breeds, some of which had both the normal form and the genetic variant. This made it possible to investigate the consequences of the variant," says doctoral researcher Julia Niskanen from the University of Helsinki and the Folkhälsan Research Center.

The prevalence of the DVL2 variant varied greatly between breeds. All of the English Bulldogs, French Bulldogs and Boston Terriers in the study were homozygous for the variant, that is, they had inherited the variant from both parents. In other words, the normal form of the gene was not found in these breeds. Both the variant and the normal form were found in the American Staffordshire Terriers, Staffordshire Bull Terriers, Dogues de Bordeaux, Olde English Bulldogges and American Bulldogs.

To determine the effect of the variant on body shape, the researchers analysed the skeletal anatomy of American Staffordshire Bull Terriers of different genotypes through computed tomography scans carried out at the Veterinary Teaching Hospital. The results clearly showed that the DVL2 gene defect results in caudal vertebrae anomalies in homozygous state.

"However, tail abnormalities in the American Staffordshire Terriers were less severe than the screw tails typically seen in English Bulldogs, French Bulldogs and Boston Terriers. In contrast to the previous study, we did not find an association between the DVL2 variant and thoracic vertebral anomalies," says veterinarian and Clinical Instructor Vilma Reunanen from the Faculty of Veterinary Medicine, University of Helsinki.

Another main finding in the study was that the gene defect affects muzzle length in varying degrees. In homozygous dogs, the muzzle is significantly shorter than in heterozygous dogs, who only carry one copy of the gene defect. Similarly, heterozygous dogs have shorter muzzles than dogs that don't have any copies of the gene defect.

"In addition to the effects on the skeletal system, we discovered that several dogs homozygous for the DVL2 variant had a congenital heart defect. However, this is a preliminary finding that requires further study. If confirmed, it could partially explain the prevalence of congenital heart defects in certain breeds," doctoral researcher Niskanen adds.

"Besides the DVL2 gene defect, many breeds also have other genetic variants that affect body shape. Their combined effects may result in serious health problems. For example, a short muzzle predisposes dogs to brachycephalic obstructive airway syndrome (BOAS), whose symptoms include breathing difficulties and low exercise tolerance. The prevalence of the gene defect demonstrates that in certain breeds, DVL2-related health problems can be prevented with gene tests. In some breeds, there is no longer any variation, which makes it impossible to improve the situation with current breeding programmes," explains Docent Marjo Hytönen from the University of Helsinki and the Folkhälsan Research Center.

Washington, DC / New Delhi, India - Researchers at CDDEP, in collaboration with leading experts in the field, have produced the "Infectious Diseases in the South-East Asia Region" report, which examines cross-boundary challenges in communicable disease control in countries in the South-and South-East Asia region. The report emphasizes infectious diseases related to other sources of disease burden in the region and communicates overall trends in the health and economic burden they impose.

Despite substantial progress in recent years, which has seen reductions in deaths from HIV and malaria and an increase in tuberculosis treatment coverage, the South-East Asia region continues to bear a significant proportion of the communicable disease burden worldwide. South Asia has the third largest HIV epidemic globally and the highest TB burden, accounting for more than a quarter of the global burden. The second highest incidence of malaria, amongst all WHO regions, occurs in the southeast Asia region, and India bears the third-highest proportion of malaria cases globally.

Malnutrition makes the South-East Asian population particularly vulnerable to neglected tropical diseases (NTDs) alongside emerging infectious diseases from arbovirus infections, dengue, chikungunya, Japanese encephalitis, and the continuing concern of a pandemic influenza outbreak. Furthermore, drug-resistant infections cause 58,000 deaths in newborns every year, in India alone, and continue to threaten the effectiveness of life-saving antibiotics across the region.

Covid-19 has disrupted the control of other infectious diseases in myriad ways, hindering routine vaccination programs, impeding the distribution of bed nets against malaria, and reducing TB services, among others. With the rollout of vaccines against the novel coronavirus and the ebbing of Covid-19, it will be essential to devote our full collective attention to the control of infectious diseases that have long plagued this region and continue to constitute a significant proportion of the avertable disease burden.

"As the battle against the pandemic continues, so too must our progress against communicable diseases, for which WHO will continue to pull out all stops in support of our Member States, partners, and the Region's near 2 billion people.," said Dr. Poonam Khetrapal Singh, Regional Director, WHO SEARO

Huntington's disease is caused by a mutation in the Huntingtin gene (HTT), which appears in adults and features motor, cognitive and psychiatric alterations. The origin of this disease has been associated with the anomalous functioning of the mutated protein: mHTT, but recent data showed the involvement of other molecular mechanisms.

A new study conducted by the University of Barcelona has identified a type of ribonucleic acid (RNA) as a potential therapeutic target for the treatment of the disease. These are the small RNA, or sRNAs, molecules that do not code proteins but have important functions in the regulation of gene expression. According to the study, sRNAs would take part in the development of the disease, results that shed light on the design of new specific drugs to block the activity of these intermediary molecules that help researchers to understand the information in the genes.

The study, published in the journal Acta Neuropathologica, counts on the participation of two teams from the Institute of Neurosciences of the UB, led by the lecturers of the Faculty of Medicine and Health Sciences Eulàlia Martí, also researcher at the Epidemiology and Public Health Networking Biomedical Research Centre (CIBERESP); and Esther Pérez-Navarro, also researcher at the Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED) and the August Pi i Sunyer Biomedical Research Institute (IDIBELL), the Center for Genomic Regulation (CRG) and the University Medical Center Göttingen (Germany).

An innovative technique

The objective of the researchers in the study was to understand the toxic potential of the series of sRNAs that are created in the brain of patients with Huntington's disease. The researchers note that the identification of toxicity mechanisms is important to understand how the disease evolves and to design the right drugs and therapeutic strategies.

In order to solve this question, researchers isolated sRNAs from the brain of patients with Huntington's and from people without this disease, to use them as a comparative model. Then, they administrated these molecules in the brain of normal mice and analyse whether the mice developed anomalies similar to those in the human disease. "This is the first time we use a human-origin RNA injection in mice's brain and this innovative strategy enabled us to understand the importance of these molecules independently from the protein", notes Eulàlia Martí.

The results of this experiment show that sRNAs in patients with Huntington's are enough to cause a similar pathology in normal mice, which includes "motor alterations, transcriptional changes similar to those observed in the human disease and mice models, specific affectation of the most affected neuronal type during the course of the disease, neuronal loss and neuroinflammation", says the researcher.

New perspective on the role of sRNAs in the disease

These results suggest a new view on the role of the different types of sRNAs in the progression of the disease. "To date, researchers showed that both the mHTT protein and the RNA that codes it and which has CAG repeats, contribute to neurotoxicity. However, toxic effects related to RNAs with CAG repeats do not explain certain alterations that are important within the context of the pathology, for instance, the specific neuronal affectation or transcriptional alterations. These results -the researcher continues-, show different types of sRNAs created in the patients' brains would be likely to take part in the pathogenesis".

In this sense, the study shows that derived fragments of RNAs, tRNA fragments (tRFs), are the most altered type of sRNAs in the brain of patients with Huntington's. The study shows that a specific tRF can cause neurotoxicity, suggesting that tRFS could participate in the damaging effects related to sRNAs in the affected patients. After this study, the main objective is to understand the functional relevance of different classes of sRNAs, with special emphasis on tRFs that are abundant in affected human brains. "Understanding the dynamics of the expression of toxic classes in brain regions and in the evolution of the disease is crucial to have a full view of their implication in the pathological process", highlights Eulàlia Martí.

Potential biomarkers

Moreover, these molecules could become potential biomarkers of the disease, since there is multiple evidence to show that changes in the RNAs expression occur before the manifestation of the symptoms. Authors say that "these changes can be reflected in biofluids such as plasma and this fact can grant these types a great value as biomarkers".

Last, these results could have implications in the treatment of other diseases. "Alterations in the sRNAs expression are detected early in many neurodegenerative diseases, and therefore, we can find a broader study field to understand what classes can contribute to specific aspects related to neurodegeneration and neuroinflammation", the researcher concludes.