Culture

Fusarium Head Blight (FHB), also known as scab, is a significant disease of small grain cereals, such as wheat and barley, that impacts farmers around the world. The disease has been reducing acreage and increasing the price of wheat production in the United States since the early 1990s, which in turn increases costs for downstream producers, such as millers and brewers.

The disease is caused by a fungus that produces heat-stable trichothecene mycotoxins, which help the disease spread. To stop the spread, plant breeders are working to develop cultivars with improved resistance to FHB. A team of plant pathologists primarily based at Rutgers University recently generated wheat overexpressing two non-specific lipid transfer proteins and found that this enhanced protection against the fungus and led to a reduction of one of the major mycotoxins.

"We found that the AtLTp4.4 protein, from the large gene family of nsLTPs, had both antifungal and antioxidant properties," said John McLaughlin. "This is the first study to show that nsLTPs have dual functions and the first study to explore how these functions contribute to FHB-resistance in wheat."

The discovery that genes like nsLTPs can improve FHB-resistance in wheat adds to the catalog of genes that plant breeders can use in their breeding programs. This discovery also opens new research avenues for McLaughlin and his colleagues.

"We are exploring if nsLTP overexpression in barley can impact FHB resistance and if the increase of nsLTPs in the grain improves the antioxidant properties of malt," said McLaughlin. "Additionally, nsLTPs are predicted to improve beer shelf life and flavor stability, and we will be testing that."

Their research also highlights the need to better understand the connection between the induction of reactive oxygen species and mycotoxin production/accumulation in small grain cereals as the scientists found that application of trichothecenes to wheat leaf tissue and the accumulation of reactive oxygen species, independent of the fungus, can be significantly impacted by the overexpression of nsLTPs.

"Our research shows that gain-of-function mutants can be used to enhance plant disease resistance, and our article shows some of the techniques involved to explore the mechanisms of disease resistance," McLaughlin added.

What started as the preliminary analysis of routine laboratory data has since evolved into the largest-ever study of viral load levels in patients with SARS-CoV-2. A team of researchers from Charité - Universitätsmedizin Berlin have now analyzed the PCR samples of more than 25,000 persons with COVID-19. Working under the leadership of Prof. Dr. Christian Drosten, the team determined the viral loads of each individual sample and used their results to estimate levels of infectiousness. The research, which has been published in Science*, provides a clear idea of the infectiousness of the disease in different age groups and at different levels of disease severity. It also provides new insights into the B.1.1.7 variant.

According to the reproductive number (R 0), a person infected with SARS-CoV-2 will, on average, transmit their infection to three to five other people. While it is a useful metric in an epidemiological setting, 'R 0' does not lend itself to estimating the risk of transmission at the individual or group level. Once normal social and environmental factors are removed from the equation, individuals can differ markedly in terms of their infectiousness and the length of time during which they actively shed the virus.

To better understand and estimate infectiousness in specific groups of individuals, a team led by Prof. Dr. Christian Drosten, Director of Charité's Institute of Virology and a researcher at the German Center for Infection Research (DZIF), analyzed the PCR samples of more than 25,000 COVID-19 cases in order to determine their 'viral loads'. A sample's viral load - the total number of copies of the SARS-CoV-2 genome contained in the sample - provides a rough estimate of the quantity of virus present in a patient's throat and, as such, is a useful metric for estimating an individual's infectiousness. To further improve their estimates, the researchers also applied findings regarding the minimum viral load threshold typically required for the successful isolation of SARS-CoV-2 in cell culture (where isolation indicates the presence of infectious virus). Sequential samples were available for more than 4,300 of the cases studied. Using these to track throat viral load data over time, the researchers were able to model the typical development of viral loads over the course of the infection. The researchers then looked for significant differences in their data, specifically in relation to different age groups, disease severity and virus variants.

No notable differences in viral load levels were recorded among SARS-CoV-2-positive individuals aged between 20 and 65 years, the average throat swab sample containing approximately 2.5 million copies of the SARS-CoV-2 genome. Viral loads were found to be lowest in very young children (0 to 5 years). Levels started at approximately 800,000 copies of the viral genome, increased with age, and approached adult levels in older children and adolescents.

"While these numbers look very different at first glance, it is crucial to remember that viral load results are shown on a logarithmic scale," says Prof. Drosten. "The differences in viral loads found in the youngest children are, in fact, barely below the threshold at which we would normally consider them clinically relevant. Crucially, one also has to understand how we arrive at these values and take this into account when interpreting them." Highlighting the differences in the methodology of sample collection between children and adults, the virologist adds: "Children's swabs are significantly smaller in size and collect less than half the sample quantity normally available for PCR testing. Moreover, the level of discomfort involved with the procedure means that deep nasopharyngeal swabs are often replaced with simple throat swabs. This of course further reduces the amount of viral material collected. For this reason, we fully expect that, in children, the same level of viral replication will produce lower viral load results during PCR testing."

When comparing peak viral loads in laboratory samples, the researchers estimated levels of infectivity in the youngest children (0 to 5 years) to be at approximately 80 percent of that found in adults. As previously, values for school-aged children and adolescents were found to be approaching adult values. "This shows that viral loads are not directly proportional to infectivity and cannot be converted directly," explains Prof. Drosten. He adds: "Even these data-based estimates of infectivity have to be corrected upwards because of the different methods of sample collection used in children. All of this forms part of a clinical virologist's overall assessment. My initial assumption, that all age groups have roughly the same level of infectivity, has been confirmed, both by this and by other studies."

A symptom-based comparison confirmed observations previously made in COVID-19 cases, namely that even asymptomatic individuals can have very high viral loads. Individuals who required hospitalization were found to have higher viral loads than others over the entire course of the disease. Based on their new models of viral load courses over time, the researchers estimate that individuals infected with SARS-CoV-2 reach peak viral load levels in their throats as early as 1 to 3 days before the onset of symptoms.

Approximately 9 percent of the COVID-19 cases tested showed extremely high viral loads of one billion copies per sample or higher. More than a third of these potentially highly infectious individuals had either no symptoms or only mild symptoms. "These data provide a virological foundation for the notion that a minority of infected individuals cause the majority of all transmissions," explains Prof. Drosten. He adds: "The fact that this includes so many people without any relevant symptoms underlines the importance of pandemic control measures such as social distancing and mandatory mask-wearing."

In samples collected from individuals infected with the B.1.1.7 ('UK' or 'British') variant, average viral loads were found to be increased by a factor of ten, while laboratory-based estimates of infectivity were increased by a factor of 2.6. To arrive at these data, the researchers took viral load data from approximately 1,500 cases infected with B.1.1.7 and compared them with data from approximately 1,000 people infected with other variants who had been tested at the same testing centers, outpatient departments and clinical wards around the same time. Prof. Drosten adds: "Laboratory studies may not as yet be in a position to provide a definitive explanation, but one thing is clear: B.1.1.7 is more infectious than other variants."

The researchers plan to continue their work on viral loads throughout the course of the pandemic. They hope to gain insights into the changes which occur as new variants arise as the virus adapts to increasing levels of population immunity.

LA JOLLA--(May 25, 2021) One of the many effects of aging is loss of muscle mass, which contributes to disability in older people. To counter this loss, scientists at the Salk Institute are studying ways to accelerate the regeneration of muscle tissue, using a combination of molecular compounds that are commonly used in stem-cell research.

In a study published on May 25, 2021, in Nature Communications, the investigators showed that using these compounds increased the regeneration of muscle cells in mice by activating the precursors of muscle cells, called myogenic progenitors. Although more work is needed before this approach can be applied in humans, the research provides insight into the underlying mechanisms related to muscle regeneration and growth and could one day help athletes as well as aging adults regenerate tissue more effectively.

"Loss of these progenitors has been connected to age-related muscle degeneration," says Salk Professor Juan Carlos Izpisua Belmonte, the paper's senior author. "Our study uncovers specific factors that are able to accelerate muscle regeneration, as well as revealing the mechanism by which this occurred."

The compounds used in the study are often called Yamanaka factors after the Japanese scientist who discovered them. Yamanaka factors are a combination of proteins (called transcription factors) that control how DNA is copied for translation into other proteins. In lab research, they are used to convert specialized cells, like skin cells, into more stem-cell-like cells that are pluripotent, which means they have the ability to become many different types of cells.

"Our laboratory previously showed that these factors can rejuvenate cells and promote tissue regeneration in live animals," says first author Chao Wang, a postdoctoral fellow in the Izpisua Belmonte lab. "But how this happens was not previously known."

Muscle regeneration is mediated by muscle stem cells, also called satellite cells. Satellite cells are located in a niche between a layer of connective tissue (basal lamina) and muscle fibers (myofibers). In this study, the team used two different mouse models to pinpoint the muscle stem-cell-specific or niche-specific changes following addition of Yamanaka factors. They focused on younger mice to study the effects of the factors independent of age.

In the myofiber-specific model, they found that adding the Yamanaka factors accelerated muscle regeneration in mice by reducing the levels of a protein called Wnt4 in the niche, which in turn activated the satellite cells. By contrast, in the satellite-cell-specific model, Yamanaka factors did not activate satellite cells and did not improve muscle regeneration, suggesting that Wnt4 plays a vital role in muscle regeneration.

According to Izpisua Belmonte, who holds the Roger Guillemin Chair, the observations from this study could eventually lead to new treatments by targeting Wnt4.

"Our laboratory has recently developed novel gene-editing technologies that could be used to accelerate muscle recovery after injury and improve muscle function," he says. "We could potentially use this technology to either directly reduce Wnt4 levels in skeletal muscle or to block the communication between Wnt4 and muscle stem cells."

The investigators are also studying other ways to rejuvenate cells, including using mRNA and genetic engineering. These techniques could eventually lead to new approaches to boost tissue and organ regeneration.

Extra funding should be made available for early years care in the wake of the pandemic, researchers say.

Experts at the University of Leeds, University of Oxford and Oxford Brookes University have made the call after assessing the benefits of early childhood education and care (ECEC) for children under three during COVID-19.

They found children who attended childcare outside the home throughout the first UK lockdown made greater gains in language and thinking skills, particularly if they were from less advantaged backgrounds.

And now they are making several policy recommendations including

- A sustainable funding model for nursery provision

- Promotion of funded places in target areas where take-up is low

- Removal of administrative barriers to the take-up of places

Dr Catherine Davies, Associate Professor in Language Development in the School of Languages, Cultures and Societies, who co-authored the study, said: "Our data clearly show that children from all backgrounds benefit from attending childcare for all or part of the week. Their cognitive skills become stronger, which will help them in their later learning and development, too. Government investment in sustainable, high-quality early years education and care is crucial so that all families can access this support."

Part of a nationally-funded project on Social Distancing and Development, the aim of the study was to analyse the impact of attending childcare - and of missing out - on children from different backgrounds, and to provide evidence for policymakers planning for further lockdowns and disruptions to early education and care.

The researchers worked with 189 UK families with children aged 8 to 36 months old during spring and winter 2020, when nurseries were closed to all children except those of critical workers or those classed as vulnerable. Between March and June 2020, nursery attendance dropped to less than 10% of usual levels. This was followed by an extended period of quarantine measures, reduced attendance, and disruption to sessions.

The families answered questions about their use of formal childcare such as nursery and childminders before, during and between lockdowns, informal childcare from family members or friends, and about their income, level of education, occupation and neighbourhood. Parents completed surveys about the number of words that their child said or understood, and their child's early thinking skills, or executive functions - the control of attention, behaviour and emotion. They followed up six months later, reporting again on their child's language ability and thinking skills.

Parents were asked to record their child's understanding and use of words across categories such as animals, vehicles and food. They were also asked how often their child exhibited different behaviours, and then played games designed to elicit skills such as waiting, finding, and sorting.

The team then explored associations between time spent at ECEC, the families' socioeconomic background, and children's growth in language and thinking skills.

Their findings showed that a child who regularly attended ECEC one day per week during the pandemic could be expected to understand an average of 24 more new words over the Spring-Winter 2020 period compared with their peers, while a child regularly attending two days could be expected to understand 48 more new words than their peers over the same period, and so on. This effect was greater among children from less affluent backgrounds. Overall, the results suggest that those children who could not attend nursery were disadvantaged by the social distancing measures.

In addition, children from all backgrounds who continued to attend nursery displayed boosted growth in thinking skills.

Study co-author Dr Alexandra Hendry, a research fellow at the University of Oxford, said: "Lower-income families have been disproportionately impacted by infections, deaths, unemployment, and mental ill-health during the pandemic - all stressors which are likely to negatively affect home interactions with children. We have demonstrated that early childhood education and care boosts these children's vocabulary skills, and all children's thinking skills.

"Solid abilities in these areas are likely to have cascading positive effects as children move through their preschool years and beyond. To maintain these benefits for child development and for levelling inequalities, properly-funded, high-quality early childhood education and care is crucial."

The project lead for the Social Distancing and Development Study, Dr Nayeli Gonzalez-Gomez, Senior Lecturer in Psychology at Oxford Brookes University, noted "Our findings add to the evidence base that providing access to properly-funded, safe, and high-quality early childhood education and care may be a way to level some of the inequalities experienced by children from less privileged background, while still benefiting all children."

The paper, Early Childhood Education and Care (ECEC) during COVID-19 boosts growth in language and executive function, is published in Infant and Child Development.

The research was funded by the Economic and Social Research Council as part of its rapid response to COVID-19.

Royal College of Speech and Language Therapists' chief executive Kamini Gadhok MBE says: "This important research provides clear evidence that young children from disadvantaged backgrounds have been disproportionately affected by the COVID-19 pandemic, with a worrying impact on their language development.

"Given the importance of language skills for young people's life chances, it's imperative that governments across all four nations put support for children's communication and language development at the centre of education recovery plans. This must include action and funding in the early years which supports pre-school settings to work in partnership with speech and language therapists."

Research Study Key Takeaways:

Ridesharing can reduce a passenger's risk of being a target of sexual assault by providing a more reliable and timely transportation option for traveling to a safer place.

The entry of Uber into a city contributes to a 6.3% reduction in rape incidents.

A 1% increase in Uber pickups in a neighborhood translates to a more than 3% decrease in the likelihood of sexual assaults.

CATONSVILLE, MD, May 24, 2021 - Contrary to portraits painted in popular media, new research involving ridesharing services shows they provide an additional level of protection for potential sexual assault victims, particularly in neighborhoods with inadequate public transportation or in circumstances that are more prone to sex crimes.

The study, "The Deterrent Effect of Ride-sharing on Sexual Assault and Investigation of Situational Contingencies," published in the INFORMS journal Information Systems Research, found the entry of Uber into a city in the United States contributes to a 6.3% reduction in rape incidents.

"Even a 1% increase in Uber pickups in a neighborhood translates to a more than 3% decrease in the likelihood of sexual assaults," said Jiyong Park of the University of North Carolina at Greensboro.

The study was conducted by Park alongside Min-Seok Pang of Temple University, Junetae Kim of the National Cancer Center Korea and Byungtae Lee of the Korea Advanced Institute of Science and Technology.

This research investigates the relationship between ridesharing and sexual assault, which has been a controversial, but underexplored topic in public debates on the sharing economy and ridesharing. This study is the first to present systematic empirical evidence that a ridesharing platform can provide a viable means to prevent sexual crimes under certain circumstances.

"Ridesharing can reduce a passenger's risk of being a target of sexual assault by providing a more reliable and timely transportation option for traveling to a safer place," said Park. "Moreover, ridesharing contributes to a more significant reduction in the likelihood of rape occurrences in neighborhoods with limited transportation accessibility, such as the city's outskirts and neighborhoods where a higher percentage of the population is non-Caucasian."

The study also found that ridesharing is more effective in deterring sexual crime in riskier circumstances, such as around alcohol-serving establishments on weekend nights or when the probability of crime occurrences increases.

"Despite the common misconception due to popular media stories, our work proves that digital platforms can be leveraged to solve societal challenges by matching supply and demand closely for relevant services, which calls for spatiotemporal investigations of granular-level data in designing platform businesses and devising policy instruments," concluded Park.

Has your heart ever started to race at the thought of an upcoming deadline for work? Or has the sight of an unknown object in a dark room made you jump? Well, you can probably thank your amygdala for that.

The small almond-shaped brain structure is central to how we perceive and process fear. As we start to learn to associate fear with cues in our environment, neuronal connections within the amygdala are dynamically altered in a process called synaptic plasticity. Although this physiological mechanism is important for facilitating fear learning, it has mostly been studied in the context of excitatory neurons within the amygdala. Far less is known about the role inhibitory cells play.

In a recent publication in Cell Reports, MPFI scientists from the Bolton Lab delve deeper into a specialized portion of inhibitory circuitry in the amygdala, known as the apical intercalated cell cluster (apITC). Characterizing this small but distinctive cluster of cells, the Bolton Lab has discovered rich connectivity and a rather unique ability to modulate plasticity in the amygdala.

"What really grabbed our attention was the fact that relatively little was known about apITC function or connective circuitry," explains Douglas Asede, Ph.D., first author and former postdoc in the Bolton Lab. "When working with a relatively unknown brain area, it's a game of inputs and outputs. First, you have to identify what connects with the neuron cluster and what it connects to, then evaluate what functional role that circuitry plays."

The Bolton Lab began its investigation by characterizing and functionally testing the incoming connections to the apITC. First, the team utilized a highly specialized technique called monosynaptic tracing to selectively identify the upstream presynaptic partners. Once identified, the researchers used a combination of presynaptic optogenetic stimulation (light activation) and postsynaptic electrophysiology to verify that the connections were functional.

"We were able to unravel a number of diverse inputs for this unique cell cluster, ranging from areas important for memory such as the entorhinal cortex to sensory processing regions such as the thalamus," explains Dr. Asede. "Among this diversity, two notable inputs from the thalamus stood out because of their relative strength compared to other connections we tested as well as their origin in thalamic regions known for their involvement in fear learning."

The strong connections to the apITC originated from two areas of the thalamus, the medial geniculate nucleus (MGm) and the posterior intralaminar nucleus (PIN). Previous work has shown the MGm and PIN to be important processing centers for auditory and somatosensory information, respectively. In the context of fear learning, inputs from the thalamus send fear-related sensory information to the amygdala, which then integrates and associates fear with particular cues from the environment.

To examine whether this sensory information flow through the apITC was important for fear learning, MPFI scientists studied the changes in these synaptic connections in mice directly after behavioral training. A group of mice underwent classical fear conditioning and behavior-driven changes and were then evaluated using pre and post-synaptic markers for plasticity. Interestingly, the team found significant signs of synaptic strengthening in the sensory inputs to the apITC after fear learning when compared to control animals.

"Typically, when synapses are important to a particular behavior, their connections are strengthened during learning, so our results really highlighted the importance of these sensory connections in fear learning," notes Dr. Asede.

The LA is a region of the amygdala that is strongly associated with fear learning, fear-related sensory integration, and the formation of fear-based memories. The Bolton Lab used simultaneous electrical stimulation of thalamic sensory inputs and optogenetic stimulation of apITC cell inputs to the LA to reveal that activation of apITC acts as a gate to reduce incoming sensory-driven responses in the LA.

"Armed with the understanding that apITC is important for sensory gating and fear learning, we next looked at what type of downstream connections the apITC makes to give us a clue about possible functions the cluster has in the amygdala fear circuitry."

Classically it's been thought that inhibitory cells within the brain make very short-range, downstream connections, acting to dynamically modify circuits within their own local environments. Using axonal reconstruction, the Bolton Lab identified that while most apITC connections are local axon collaterals to neighboring apITCs or project to a close region within the amygdala called the lateral amygdala (LA). Surprisingly, they also identified a subset of relatively long-range connections to more distant brain structures, challenging classical thinking on inhibitory circuits.

"The apITC is one of several clusters of inhibitory neurons that surround the amygdala like a
net. Each cluster has a unique role in regulating emotional processing in the amygdala by gating specific inputs," notes Mclean Bolton, Ph.D. and Research Group Leader at MPFI. "The ITCs have receptors for many neuromodulators such as dopamine, opiates, and oxytocin so they may function as a barometer for sensing internal state and modifying emotions accordingly. This makes them a potential target for therapies to treat anxiety and PTSD, so understanding how each cluster contributes to amygdala function is important."

CHICAGO, May 24, 2021--More than a year after COVID-19 appeared in the U.S., dentists continue to have a lower infection rate than other front-line health professionals, such as nurses and physicians, according to a study published online ahead of the June print issue in the Journal of the American Dental Association. The study, "COVID19 among Dentists in the U.S. and Associated Infection Control: a six-month longitudinal study," is based on data collected June 9 - Nov. 13, 2020.

According to the study, based on the number of dentists with confirmed or probable COVID-19 infections over more than six months, the cumulative infection rate for U.S. dentists is 2.6%. The monthly incidence rate varied, ranging from 0.2% to 1.1% per month. By comparison, in June 2020, the cumulative COVID-19 prevalence rate for other U.S. health professionals ranged from 3.3% (Chicago-based hospital physicians) to 35.3% (U.S. based emergency medicine services).

"We're pleased to see that dentists have demonstrated continued low monthly incidence of disease despite several regional and national COVID-19 rate spikes during the study period," said American Dental Association (ADA) Science and Research Institute Chief Executive Officer Marcelo Araujo, D.D.S., M.S., Ph.D., the senior author of the report.

Dr. Araujo added, "This study shows high rates of pre-appointment screening of patients and appropriate infection control measures throughout the study period, demonstrating that adhering to very strict protocols for enhanced infection control helps protect their patients, their dental team and themselves."

In addition to Dr. Araujo, other authors of the report include researchers from the ADA Science and Research Institute and Health Policy Institute based in Chicago, as well as Maria L Geisinger, D.D.S., M.S. with University of Alabama at Birmingham in Birmingham, Ala., and Effie Ioannidou, D.D.S., M.D.S., with the University of Connecticut in Farmington, Conn., and a member of the ADA Council on Scientific Affairs.

This study is a continuation of the first large-scale report of incidence rates of COVID-19 among dentists in the U.S published in October 2020. The present six-month longitudinal study aimed to:

Determine the cumulative prevalence rate of COVID-19 among dentists;

Calculate the monthly incidence rate for the same population over the course of the study; and

Assess the level of engagement in specific infection control practices among dentists over a six-month period of time.

The results of this present study, as well as the earlier study, show that prevalence and incidence rates among dentists continue to be very low when compared to the population as a whole and to other health care professionals.

"This study reinforces that the dental care sector is up and running safely," said Chief Economist and Vice President of the ADA Health Policy Institute Marko Vujicic, Ph.D. "Nowhere is this proof point more evident than by the fact that more than 90% of patients surveyed indicate they have already visited the dentist or soon will."

The authors plan future research projects on the barriers and facilitators to wearing Personal Protective Equipment (PPE) according to CDC recommendations, and levels of protection against COVID-19 provided by different levels of PPE use and infection control procedures.

Researchers at Lund University in Sweden have developed an algorithm that combines data from a simple blood test and brief memory tests, to predict with great accuracy who will develop Alzheimer's disease in the future. The findings are published in Nature Medicine.

Approximately 20-30% of patients with Alzheimer's disease are wrongly diagnosed within specialist healthcare, and diagnostic work-up is even more difficult in primary care. Accuracy can be significantly improved by measuring the proteins tau and beta-amyloid via a spinal fluid sample, or PET scan. However, those methods are expensive and only available at a relatively few specialized memory clinics worldwide. Early and accurate diagnosis of AD is becoming even more important, as new drugs that slow down the progression of the disease will hopefully soon become available.

A research group led by Professor Oskar Hansson at Lund University have now shown that a combination of relatively easily acccessible tests can be used for early and reliable diagnosis of Alzheimer's disease. The study examined 340 patients with mild memory impairment in the Swedish BioFINDER Study, and the results were confirmed in a North American study of 543 people.

A combination of a simple blood test (measuring a variant of the tau protein and a risk gene for Alzheimer's) and three brief cognitive tests that only take 10 minutes to complete, predicted with over 90% certainty which patients would develop Alzheimer's dementia within four years. This simple prognostic algorithm was significantly more accurate than the clinical predictions by the dementia experts who examined the patients, but did not have access to expensive spinal fluid testing or PET scans, said Oskar Hansson.

"Our algorithm is based on a blood analysis of phosphylated tau and a risk gene for Alzheimer's, combined with testing of memory and executive function. We have now developed a prototype online tool to estimate the individual risk of a person with mild memory complaints developing Alzheimer's dementia within four years", explains Sebastian Palmqvist, first author of the study and associate professor at Lund University.

One clear advantage of the algorithm is that it has been developed for use in clinics without access to advanced diagnostic instruments. In the future, the algorithm might therefore make a major difference in the diagnosis of Alzheimer's within primary healthcare.

"The algorithm has currently only been tested on patients who have been examined in memory clinics. Our hope is that it will also be validated for use in primary healthcare as well as in developing countries with limited resources", says Sebastian Palmqvist.

Simple diagnostic tools for Alzheimer's could also improve the development of drugs, as it is difficult to recruit the suitable study partcipants for drug trials in a time- and cost-effective manner.

"The algorithm will enable us to recruit people with Alzheimer's at an early stage, which is when new drugs have a better chance of slowing the course of the disease", concludes Professor Oskar Hansson.

MIAMI - Scientists from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science analyzed ground movements measured by Interferometric Synthetic Aperture Radar (InSAR) satellite data and GPS stations to precisely model where magma intruded and how magma influx changed over time, as well as where faults under the flanks moved without generating significant earthquakes. The GPS network is operated by the U.S. Geological Survey's Hawaii Volcano Observatory.

"An earthquake of magnitude-6 or greater would relieve the stress imparted by the influx of magma along a sub-horizontal fault under the western flank of the volcano," said Bhuvan Varugu, a Ph.D. candidate at the UM Rosenstiel School and lead author of the study. "This earthquake could trigger an eruption."

The researchers found that during 2014-2020 a total of 0.11 kilometers3 of new magma intruded into a dike-like magma body located under and south of the summit caldera, with the upper edge at 2.5 - 3 kilometers depth beneath the summit. They were able to determine that in 2015 the magma began expanding southward, where the topographic elevation is lower and the magma had less work to do against the topographic pressure. After the magma flux waned in 2017, the inflation center returned to its previous 2014-2015 horizontal position. Such changes of a magma body have never been observed before.

"At Mauna Loa, flank motion and eruptions are inherently related," said Varugu. "The influx of new magma started in 2014 after more than four years of seaward motion of the eastern flank - which opened up space in the rift zone for the magma to intrude."

The researchers also found that there was movement not associated with an earthquake along a near-horizontal fault under the eastern flank, however, no movement was detected under the western flank. This led the researchers to conclude that an earthquake under the western flank is due. Motions along near-horizontal faults under the flanks are essential features of long-term volcano growth.

Will the volcano erupt in the near future? "If magma influx continues it is likely, but not required," says Varugu. "The topographic load is pretty heavy, the magma could also propagate laterally through the rift zone".

"An earthquake could be a game changer," said Falk Amelung, a professor at the UM Rosenstiel School's Department of Marine Geosciences and senior author of the study. "It would release gases from the magma comparable to shaking a soda bottle, generating additional pressure and buoyancy, sufficient to break the rock above the magma."

According to the researchers there are many uncertainties. Though the stress that was exerted along the fault is known, the magnitude of the earthquake will also depend on the size of the fault patch that will actually rupture. Additionally, there are no satellite data available to determine movements prior to 2002.

"It is a fascinating problem," said Amelung, "We can explain how and why the magma body changed during the past six years. We will continue observing and this will eventually lead to better models to forecast the next eruption site."

Standing 9 kilometers tall from the base on the seafloor to the summit, Mauna Loa is the largest volcano on Earth. In the 1950 eruption, it took only three hours for the lava to reach the Kona coast. Such rapid flows would leave very little time to evacuate people in the path of its lava. Another large eruption of Mauna Loa occurred in 1984.

The combination of earthquakes and eruptions is nothing unusual. The 1950 eruption was preceded by a magnitude 6.3 earthquake three days prior, and was followed by a magnitude 6.9 earthquake more than a year later. The 1984 eruption was preceded by a magnitude 6.6 earthquake 5 months prior.

The satellite data were acquired by the Italian Cosmo-Skymed satellites in the framework of the Geohazard Supersites and Natural Laboratories (GSNL) initiative of the Group on Earth Observation (GEO), an international umbrella organization to enhance the use of Earth Observation for societal benefits. Several space agencies pool their satellite resources to enable new studies of hazardous volcanoes. Other volcano supersites include the Icelandic, Ecuadorian and New Zealand volcanoes as well as Italy's Mt. Etna.

A research group from Osaka University led by Professor Hisashi Arase and consisting of researchers from the Research Institute for Microbial Diseases, the Institute for Protein Research, the Immunology Frontier Research Center, the Center for Infectious Diseases, and the Graduate School of Medicine has discovered for the first time that both neutralizing antibodies that protect against infection as well as infection-enhancing antibodies that increase infectivity are produced after infection with SARS-CoV-2 by analyzing antibodies derived from COVID-19 patients.

Antibodies against the receptor binding site (RBD) of the SARS-CoV-2 spike protein play an important function as neutralizing antibodies that suppress SARS-CoV-2 infection by inhibiting its binding to the human receptor, ACE2. On the other hand, the function of antibodies against other sites of the spike protein was unknown.

"We found that when infection-enhancing antibodies bind to a specific site on the spike protein of SARS-CoV-2, the antibodies directly cause a conformational change in the spike protein, resulting in the increased infectivity of SARS-CoV-2. Neutralizing antibodies recognize the RBD, whereas infection-enhancing antibodies recognize specific sites of the N-terminal domain (NTD)," explains Professor Hisashi Arase. "Furthermore, the production of infection-enhancing antibodies attenuated the ability of neutralizing antibodies to prevent infection."

Higher production of infection-enhancing antibodies was found in patients with severe COVID-19. It was also found that non-infected individuals may have small amounts of infection-enhancing antibodies.

Although the production of infection-enhancing antibodies may be involved in the development of severe disease, further analysis is required to ascertain whether they are actually involved in the exacerbation of infection in the body.

By analyzing the antibody titer of infection-enhancing antibodies, it may be possible to check for people who are prone to severe disease. The results of this research are also important for the development of vaccines that do not induce the production of infection-enhancing antibodies.

"It is important to analyze not only neutralizing antibodies but also infection-enhancing antibodies. In the future, it may be necessary to develop vaccines that do not induce the production of infection-enhancing antibodies, because infection-enhancing antibodies may be more effective against mutant strains in which neutralizing antibodies are not sufficiently effective," says Professor Hisashi Arase.

UNIVERSITY PARK, Pa. -- A new map of dark matter in the local universe reveals several previously undiscovered filamentary structures connecting galaxies. The map, developed using machine learning by an international team including a Penn State astrophysicist, could enable studies about the nature of dark matter as well as about the history and future of our local universe.

Dark matter is an elusive substance that makes up 80% of the universe. It also provides the skeleton for what cosmologists call the cosmic web, the large-scale structure of the universe that, due to its gravitational influence, dictates the motion of galaxies and other cosmic material. However, the distribution of local dark matter is currently unknown because it cannot be measured directly. Researchers must instead infer its distribution based on its gravitational influence on other objects in the universe, like galaxies.

"Ironically, it's easier to study the distribution of dark matter much further away because it reflects the very distant past, which is much less complex," said Donghui Jeong, associate professor of astronomy and astrophysics at Penn State and a corresponding author of the study. "Over time, as the large-scale structure of the universe has grown, the complexity of the universe has increased, so it is inherently harder to make measurements about dark matter locally."

Previous attempts to map the cosmic web started with a model of the early universe and then simulated the evolution of the model over billions of years. However, this method is computationally intensive and so far has not been able to produce results detailed enough to see the local universe. In the new study, the researchers took a completely different approach, using machine learning to build a model that uses information about the distribution and motion of galaxies to predict the distribution of dark matter.

The researchers built and trained their model using a large set of galaxy simulations, called Illustris-TNG, which includes galaxies, gasses, other visible matter, as well as dark matter. The team specifically selected simulated galaxies comparable to those in the Milky Way and ultimately identified which properties of galaxies are needed to predict the dark matter distribution.

"When given certain information, the model can essentially fill in the gaps based on what it has looked at before," said Jeong. "The map from our models doesn't perfectly fit the simulation data, but we can still reconstruct very detailed structures. We found that including the motion of galaxies--their radial peculiar velocities--in addition to their distribution drastically enhanced the quality of the map and allowed us to see these details."

The research team then applied their model to real data from the local universe from the Cosmicflow-3 galaxy catalog. The catalog contains comprehensive data about the distribution and movement of more than 17 thousand galaxies in the vicinity of the Milky Way--within 200 megaparsecs. The resulting map of the local cosmic web is published in a paper appearing online May 26 in the Astrophysical Journal.

The map successively reproduced known prominent structures in the local universe, including the "local sheet"--a region of space containing the Milky Way, nearby galaxies in the "local group," and galaxies in the Virgo cluster--and the "local void"--a relatively empty region of space next to the local group. Additionally, it identified several new structures that require further investigation, including smaller filamentary structures that connect galaxies.

"Having a local map of the cosmic web opens up a new chapter of cosmological study," said Jeong. "We can study how the distribution of dark matter relates to other emission data, which will help us understand the nature of dark matter. And we can study these filamentary structures directly, these hidden bridges between galaxies."

For example, it has been suggested that the Milky Way and Andromeda galaxies may be slowly moving toward each other, but whether they may collide in many billions of years remains unclear. Studying the dark matter filaments connecting the two galaxies could provide important insights into their future.

"Because dark matter dominates the dynamics of the universe, it basically determines our fate," said Jeong. "So we can ask a computer to evolve the map for billions of years to see what will happen in the local universe. And we can evolve the model back in time to understand the history of our cosmic neighborhood."

The researchers believe they can improve the accuracy of their map by adding more galaxies. Planned astronomical surveys, for example using the James Web Space Telescope, could allow them to add faint or small galaxies that have yet to be observed and galaxies that are further away.

SILVER SPRING, Md.--People who are successful at weight-loss maintenance spend less time sitting during the week and weekends compared to weight-stable individuals with obesity, according to a paper published online in Obesity, The Obesity Society's flagship journal. This is the first study to examine time spent in various sitting activities among weight-loss maintainers.

Prior findings from 2006 in the National Weight Control Registry indicated that weight-loss maintainers watched significantly less television than controls, but other sitting activities were not examined. In the current study, weight-loss maintainers did not significantly differ from controls in reported weekly sitting time spent watching television, but did differ in time spent in non-work-related time using a computer or video game.

Differences between the current study and National Weight Control Registry findings could reflect changes over the past 15 years in available electronic devices, including the rise in availability of computers and video games. Weight-loss maintainers and controls also did not appreciably differ in time spent sitting while reading or studying, traveling; or talking, texting and socializing. These could be considered more mentally active forms of sedentary behavior.

"The findings hopefully will prompt future weight maintenance intervention research testing the effects of and optimal approaches for reducing sedentary behavior, including non-work-related computer and video game usage. Future research should include objective measures of sedentary behavior and activity," said Suzanne Phelan, Department of Kinesiology and Public Health and The Center for Health Research, California Polytechnic State University, in San Luis Obispo. Phelan is the corresponding author of the study.

Participants in the study included 4,305 weight-loss maintainers from WW (formerly Weight Watchers) who had maintained >9.1 kg of weight loss (24.7 kg on average) for 3.3 years and had an average current BMI of 27.6 kg/m2. The group of weight-stable individuals with obesity had an average BMI of 38.9 kg/m2. To gather data, the Multicontext Sitting Time and Paffenbarger physical activity questionnaires were administered.

Results revealed that weight-loss maintainers versus weight-stable individuals with obesity spent three hours less per day sitting during the week (10.9 versus 13.9) and weekends (9.7 versus 12.6). Weight-loss maintainers compared with controls also spent one hour less per day in non-work-related sitting using a computer or playing a video game during the week (1.4 versus 2.3) and weekends (1.5 versus 2.5). There were no meaningful differences between weight-loss maintainers and weight-stable individuals with obesity in the number of television sets and sedentary-promoting devices in the home (15.8 versus 14.8). Weight-loss maintainers expended significantly more calories per week in physical activity (1,835 versus 785).

"These findings are important for understanding behaviors that may enhance weight loss maintenance, and one of those may be to reduce sitting time and other modes of sedentary behavior. However, this study also showed that physical activity was associated with improved weight-loss maintenance. Thus, this study does not imply that simply standing more rather than sitting will contribute to weight-loss maintenance, but may suggest that less sitting that results in more movement is what is key to weight loss maintenance. Hence, sit less and move more," said John M. Jakicic, PhD, FACSM, FTOS, Distinguished Professor, and Director of the Healthy Lifestyle Institute and the Physical Activity and Weight Management Research Center at the University of Pittsburgh in Pennsylvania. Jakicic was not associated with the research.

Other authors of the study include James Roake, Noemi Alarcon and Sarah Keadle of the Department of Kinesiology and Public Health and The Center for Health Research, California Polytechnic State University, in San Luis Obispo. Chad Rethorst of Texas A&M Agrilife in Dallas, Texas and Gary Foster of WW International, Inc. of New York and the Center for Weight and Eating Disorders, Perelman School of Medicine, University of Pennsylvania, in Philadelphia also co-authored the study.

While many might consider a walk in the woods to be a quiet, peaceful escape from their noisy urban life, we often don't consider just how incredibly noisy some natural environments can be. Although we use soothing natural sounds in our daily lives - to relax or for meditation - the thunder of a mountain river or the crash of pounding surf have likely been changing how animals communicate and where they live for eons. A new experimental study published in the journal Nature Communications finds that birds and bats often avoid habitat swamped with loud whitewater river noise.

Dr. Dylan Gomes, a recent PhD graduate of Boise State University and first author on the paper, summarizes the aims of the work this way, "naturally-loud environments have been largely neglected in ecological research. We aimed to test the hypothesis that intense natural noise can shape animal distributions and behavior by experimentally broadcasting whitewater river noise at a massive scale." In fact, the scientists had to transport literal tons of gear across roadless terrain to place solar-powered speaker arrays in half of their 60 locations in the Pioneer Mountains of Idaho where they monitored bird and bat populations for two summers.

The speaker arrays were arranged along riparian areas, filling each bubbling brook with the auditory experience of a rushing whitewater river. The team took advantage of their experimental approach to broadcast both realistic reproductions of river noise, as well as river noise that had been shifted upwards in frequency to understand how the noise caused changes in animal numbers. "The prevailing hypothesis for why many animals avoid noise is called masking. Masking occurs when noise overlaps in frequency (what we perceive as pitch) with a biological signal or cue. By broadcasting noise of different frequencies, we hoped to assess the role that masking of important sounds, such as birdsong, plays in the avoidance of noisy places", said the senior author of the study, Dr. Jesse Barber of Boise State University. The scientists found that overlap between background noise and song frequency predicted bird declines until acoustic environments became about as loud as a highway, at which point other forces, such as an inability to hear predators and prey, likely become more important.

Understanding how noise drives animals out of otherwise good habitat is clearly important, but what about the animals that stay behind? To study foraging in birds that remained in naturally-loud places the authors set out hundreds of caterpillar decoys made of clay across their study sites. By carefully examining the types of marks predators left in the clay, the scientists found that more noise meant less foraging by birds. This means that, even after controlling for the fact that fewer birds were found in loud places, birds were less efficient at visually hunting for these silent, decoy caterpillars in the presence of noise. This is not unlike the difficulty people can experience when trying to listen to a friend talk while a muted television is on, dividing our attention.

To understand how bats that remained in noise-exposed areas fared, the team deployed two foraging puzzles to solve. The first was a "robo-moth" that lured in bats with its insect-like wing beats. The second was a speaker playing a "mix tape" of cricket and katydid calls and insect walking sounds. After almost 150 nights of data collection the scientists found that, as the world gets louder, some bats switch from listening for prey sounds to using echolocation. Dr. Gomes explains, "this behavioral switch is likely driven by prey calls and footsteps being masked by river noise and this type of problem-solving likely explains why some bats can remain near the ruckus of a raging whitewater river".

When putting all these pieces together, the authors argue that by studying how animals respond to noise sources that they have faced throughout their evolutionary history, we can get a better handle on how animals will deal with human-caused noise. Dr. Clinton Francis from California Polytechnic State University and Co-Principal Investigator of the study says, "our work showing that natural noise can structure where animals live and how they behave only increases the call to manage human-caused noise. The spatial and temporal footprint of anthropogenic noise is far greater than loud natural environments."

Despite a daunting more than 130 million cases of SARS-CoV-2 infections to date worldwide, another global pathogen - the Aedes mosquito-borne dengue virus - saw a record number of over 400 million cases in 2019. But vaccine development has been challenging due to the need to protect equally against all four dengue strains. The discovery of new possible biomarkers to predict clinical and immune responses to dengue virus infection, published today in Nature Communication, could be critical to informing future vaccines.

As with SARS-CoV-2 infection, the effects of dengue virus infection can range from asymptomatic to severe disease that can be fatal. Climate change has expanded the viruses' geographic distribution far beyond tropical areas like Southeast Asia and Latin America to the southern U.S. and Europe. Only one vaccine, Dengvaxia, has been approved for a subset of at-risk individuals in endemic areas.

This study, led by University of Vermont (UVM) Associate Professor of Microbiology and Molecular Genetics (MMG) Sean Diehl, Ph.D., set out to determine biomarker candidates and predictors for clinical and immunological responses resulting from dengue infection. Previous research published by Diehl and MMG Chair Beth Kirkpatrick, M.D., director of the UVM Vaccine Testing Center, has shown how a dengue vaccine being developed together with Johns Hopkins and the National Institutes of Health activates an immune response that protects against challenge with this dengue virus.

Live, weakened viruses are the basis for the most-effective and longest-lasting vaccines against many viral diseases. This "live attenuated" approach is used in the next-generation dengue vaccine that is being co-developed at UVM. To better understand how live attenuated dengue viruses turn on the immune system, Diehl and colleague John Hanley, Ph.D., a UVM research specialist, in collaboration with Kirkpatrick and the Vaccine Testing Center, investigated which genes are activated or repressed in the immune cells from subjects exposed to a well-characterized and safe live attenuated dengue virus. Hanley developed a new statistical approach to integrate the genomics data with the extensive clinical data collected during the careful monitoring of dengue virus-exposed study participants.

The team found strong correlations between the activation of specific immune genes and the ability of participants' immune systems to turn on early cellular defense mechanisms and make protective antibodies against dengue virus.

"These data offer new potential biomarkers for characterizing dengue virus infection and novel pathways that could be leveraged to combat viral replication," says Diehl. "Our results also gave us some clues about how we might be able to boost protective immune responses, which is the goal of developing effective vaccines."

Diehl adds that for some of the genes identified in this study, little is known about their role in the response against dengue virus.

"This is very exciting, because it could lead to new ways to fight dengue, so we are now investigating these in the lab" says Diehl.

He and Kirkpatrick are also working to determine how long protective immunity lasts after receiving a dengue vaccine and are in the process of identifying volunteers who received the NIH-developed dengue vaccine up to 11 years ago to obtain a current blood sample for further testing.

"A durable protective immune response is the goal of a good vaccine," says Kirkpatrick.

Within the European Union alone, about three million people are affected by an autism spectrum disorder (ASD). Some are only mildly affected and can live independent lives. Others have severe disabilities. What the different forms have in common is difficulty with social interaction and communication, as well as repetitive-stereotypic behaviors. Mutations in a few hundred genes are associated with ASD. One of them is called Cullin 3, and it is a high-risk gene: A mutation of this gene almost certainly leads to a disorder. But how exactly does this gene affect the brain? To learn more about it, Jasmin Morandell and Lena Schwarz, PhD students at Professor Gaia Novarino's research group, turned to mice whose Cullin 3 gene has been partially deactivated and compared them to their healthy siblings. Their results have just been published in the journal Nature Communications.

In a series of behavioral and motoric tests, the team wanted to see if the modified mice mimicked some of the characteristics of patients with this form of autism and could therefore be used as model organisms. In one of these tests, the so-called three-chamber sociability test, a mouse could freely explore three adjacent chambers of a box connected by little doors. Now, the scientists put two other mice in the outer boxes: One was already familiar to the studied mouse, the other mouse it had never met. "Healthy mice usually prefer the new over the already familiar mouse," Jasmin Morandell, co-first author of the study, explains. The mouse with the altered Cullin 3 gene, however, showed no sign of recognition. Furthermore, the mice had motor coordination deficits as well as other ASD-relevant cognitive impairments. With the help of this mouse model, the team was then able to get to the bottom of the mechanisms that bring about these changes.

A Dangerous Accumulation of Proteins

While studying the mouse brain, the researchers noticed a very subtle but consistent change in the position of some brain cells. These so-called neurons or nerve cells originate from a special region in the brain. From there, they migrate toward the uppermost layers until they find their designated place in the cortex. It is a very sensitive process, where even small changes in the speed at which they travel can change the structure of the cortex. By marking the migrating neurons, the scientists could trace their movements. "We could observe migration deficits - the neurons are stranded in the lower cortex layers," Lena Schwarz, the other co-first author of the study, describes. But why are the cells not moving as they should?

The answer lies in the important role Cullin 3 plays at the end of life of proteins. When their time has come, the gene Cullin 3 tags them for degradation - a process that has to be tightly regulated to prevent proteins from accumulating. To find out, which proteins are misregulated when Cullin 3 is defective, Morandell and Schwarz systematically analyzed the protein composition of the mouse brain. "We were looking at proteins that accumulate in the mutant brain and found a protein called Plastin 3. Then Gaia came across a poster describing the work of IST Austria's Schur group in the hallway, and we got very excited," says Jasmin Morandell. "They independently had been working on Plastin 3 as a regulator of cell motility and had complementary results to ours. That's when we started working together," Professor Gaia Novarino remembers.

It turned out that the protein Plastin 3, which was previously unknown in the context of neuronal cell migration, actually plays an important role in this process. "If the Cullin 3 gene is deactivated, the Plastin 3 protein accumulates, causing cells to migrate slower and over shorter distances. This is exactly what we saw happening in the cortex of the Cullin 3 mutant mice," says PhD student Lena Schwarz.

A Risky Pathway?

All this is taking place during a very early stage of brain development around halfway through pregnancy - long before anyone would notice any difference in the fetus. "Determining these critical windows during brain development could be extremely important to fine-tune the treatment of patients with specific forms of ASD," explains Novarino, who is committed to improving diagnosis and treatment options for people with ASD. "Following up with the research on Plastin 3 could pave the way for some therapeutics. Inhibiting the accumulation of this protein could eventually alleviate some of the symptoms patients have," Schwarz says.

"We now know that defective Cullin 3 leads to increased levels of Plastin 3. This tight correlation shows that Plastin 3 protein levels may be an important factor for the control of cell-intrinsic movements," says Jasmin Morandell. She recently graduated and may use her expertise in brain development to study Huntington's disease. Lena Schwarz will next turn to additional high-risk ASD genes to see how other proteins in the degradation pathway may be linked to ASD. For the present study, the Novarino group joined forces with the Danzl and Schur groups and a colleague from the University of Rome. "Finishing this extensive study in around two and a half years despite the pandemic was only possible with the support from our neighbors at IST Austria," Novarino praises the multidisciplinarity at the Institute.