Culture

The social science literature has long viewed homophily and network-based job recruitment as crucial drivers of segregation. Researchers at Linköping University and ESADE, Ramon Llull University now show that this view must be revised. In their Science Advances article, they call attention to a previously unidentified factor, the Trojan-horse mechanism, which shows that network-based recruitment can reduce rather than increase segregation levels.

The segregation of labor markets along ethnic and gender lines is an important source of socio-economic inequalities. Therefore, the understanding the mechanisms that drive segregation processes is of utmost importance.

Individuals often find their jobs through friends, colleagues, and acquaintances. Analyses of the role of labor-market networks in segregation processes has usually centered on homophily - the tendency to like and to befriend others who are similar to oneself. If individuals recruit friends or acquaintances, the homophily argument suggests that labor markets are likely to become more segregated, because individuals with similar characteristics then tend to agglomerate at certain workplaces.

What previous research has overlooked is the importance of restricted opportunities. Both females and males prefer to form ties with individuals of the same gender, but if an individual works in a workplace where most employees are of the opposite gender, the individual is likely to form ties to those of the opposite gender.

"The Trojan-horse mechanism shows how constraints on the formation of same-gender ties within workplaces affect mobility patterns between workplaces and thereby the gender segregation of the labor market. When an individual changes job and moves from one workplace to another, colleagues are likely to subsequently follow the same path", says Professor Peter Hedstrom at the Institute for Analytical Sociology, Linkoping University.

The Trojan-horse mechanism predicts that when an individual leaves a workplace in which he/she is in a minority, he/she is likely to be followed by majority-group individuals. This implies, in turn, that an initially segregating move can set in motion a chain of desegregating moves. In other words, the mechanism shows how networks can counteract the segregating impact of a mobility event.

To test this prediction, a large-scale longitudinal register dataset is used with rich demographic and socioeconomic information, as well as detailed mobility records, for every individual and every workplace that ever resided in the Stockholm metropolitan area during the years 2000-2017. The number of workplaces included in the analyses ranges from 20,000 to 30,000 each year, and the number of individuals is about 700,000 at every given point in time. The analyses offer strong empirical support for the Trojan-horse prediction.

The results presented provide important pieces of the larger causal puzzle that, once solved, will allow of us to steer segregation processes in more desirable directions. In and of itself, the Trojan-horse mechanism is also of importance for everyday organizational practices.

"For efficiency as well as affirmative-action reasons, workplaces often want to hire individuals of the underrepresented gender. What these results suggest is that recruiters who want to increase diversity or change the gender balance of the workforce should pay attention not only to the gender of the recruited individual but also to the gender composition of the workplace from which the individual is recruited", says Professor Peter Hedstrom at The Institute for Analytical Sociology, Linkoping University.

Although antibodies induced by SARS-CoV-2 infection are largely protective, they do not completely protect against reinfection in young people, as evidenced through a longitudinal, prospective study of more than 3,000 young, healthy members of the US Marines Corps conducted by researchers at the Icahn School of Medicine at Mount Sinai and the Naval Medical Research Center, published April 15 in The Lancet Respiratory Medicine.

"Our findings indicate that reinfection by SARS-CoV-2 in health young adults is common" says Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology at the Icahn School of Medicine at Mount Sinai and senior author of the paper. "Despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. This is an important point to know and remember as vaccine rollouts continue. Young people should get the vaccine whenever possible, since vaccination is necessary to boost immune responses, prevent reinfection, and reduce transmission."

The study, conducted between May and November 2020, revealed that around 10 percent (19 out of 189) of participants who were previously infected with SARS-CoV-s (seropositive) became reinfected, compared with new infections in 50 percent (1.079 out of 2,247) of participants who had not been previously infected (seronegative). While seronegative study participants had a five times greater risk of infection than seropositive participants, the study showed that seropositive people are still at risk of reinfection.

The study population consisted of 3,249 predominantly male, 18-20-year-old Marine recruits who, upon arrival at a Marine-supervised two-week quarantine prior to entering basic training, were assessed for baseline SARS-CoV-2 IgG seropositivity (defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent [ELISA] assays.) The presence of SARS-CoV-2 was assessed by PCR at initiation, middle and end of quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, the study team performed three bi-weekly PCR tests in both seronegative and seropositive groups once recruits left quarantine and entered basic training.

Recruits who tested positive for a new second COVID-19 infection during the study were isolated and the study team followed up with additional testing. Levels of neutralising antibodies were also taken from subsequently infected seropositive and selected seropositive participants who were not reinfected during the study period.

Of the 2,346 Marines followed long enough for this analysis of reinfection rate, 189 were seropositive and 2,247 were seronegative at the start of the study. Across both groups of recruits, there were 1,098 (45%) new infections during the study. Among the seropositive participants, 19 (10%) tested positive for a second infection during the study. Of the recruits who were seronegative, 1,079 (48%) became infected during the study.

To understand why these reinfections occurred, the authors studied the reinfected and not infected participants' antibody responses. They found that, among the seropositive group, participants who became reinfected had lower antibody levels against the SARS-CoV-2 virus than those who did not become reinfected. In addition, in the seropositive group, neutralising antibodies were less common (neutralising antibodies were detected in 45 (83%) of 54 uninfected, and in six (32%) of 19 reinfected participants during the six weeks of observation).

Comparing new infections between seropositive and seronegative participants, the authors found that viral load (the amount of measurable SARS-CoV-2 virus) in reinfected seropositive recruits was on average only 10 times lower than in infected seronegative participants, which could mean that some reinfected individuals could still have a capacity to transmit infection. The authors note that this will need further investigation.

In the study, most new COVID-19 cases were asymptomatic - 84% (16 out of 19 participants) in the seropositive group vs 68% (732 out of 1,079 participants) in the seronegative group - or had mild symptoms and none were hospitalised.

The authors note some limitations to their study, including that it likely underestimates the risk of reinfection in previously infected individuals because it does not account for people with very love antibody levels following their past infection. They strongly suggest that even young people with previous SARS-CoV-2 infection be a target of vaccination since efforts must be made to prevent transmission and prevent infection amongst this group.

In recent years there has been an exhaustive study of red dwarf stars to find exoplanets in orbit around them. These stars have effective surface temperatures between 2400 and 3700 K (over 2000 degrees cooler than the Sun), and masses between 0.08 and 0.45 solar masses. In this context, a team of researchers led by Borja Toledo Padrón, a Severo Ochoa-La Caixa doctoral student at the Instituto de Astrofísica de Canarias (IAC), specializing in the search for planets around this type of stars, has discovered a super-Earth orbiting the star GJ 740, a red dwarf star situated some 36 light years from the Earth.

The planet orbits its star with a period of 2.4 days and its mass is around 3 times the mass of the Earth. Because the star is so close to the Sun, and the planet so close to the star, this new super-Earth could be the object of future researches with very large diameter telescopes towards the end of this decade. The results of the study were recently published in the journal Astronomy & Astrophysics.

"This is the planet with the second shortest orbital period around this type of star. The mass and the period suggest a rocky planet, with a radius of around 1.4 Earth radii, which could be confirmed in future observations with the TESS satellite", explains Borja Toledo Padrón, the first author of the article. The data also indicate the presence of a second planet with an orbital period of 9 years, and a mass comparable to that of Saturn (close to 100 Earth masses), although its radial velocity signal could be due to the magnetic cycle of the star (similar to that of the Sun), so that more data are needed to confirm that the signal is really due to a planet.

The Kepler mission, recognised at one of the most successful in detecting exoplanets using the transit method (which is the search for small variations in the brightness of a star caused by the transit between it and ourselves of planets orbiting around it), has discovered a total of 156 new planets around cool stars. From its data it has been estimated that this type of stars harbours an average of 2.5 planets with orbital periods of less than 200 days. "The search for new exoplanets around cool stars is driven by the smaller difference between the planet's mass and the star's mass compared with stars in warmer spectral classes (which facilitates the detection of the planets' signals), as well as the large number of this type of stars in our Galaxy", comments Borja Toledo Padrón.

Cool stars are also an ideal target for the search for planets via the radial velocity method. This method is based on the detection of small variations in the velocity of a star due to the gravitational attraction of a planet in orbit around it, using spectroscopic observations. Since the discovery in 1998 of the first radial velocity signal of an exoplanet around a cool star, until now, a total of 116 exoplanets has been discovered around this class of stars using the radial velocity method. "The main difficulty of this method is related to the intense magnetic activity of this type of stars, which can produce spectroscopic signals very similar to those due to an exoplanet", says Jonay I. González Hernández, an IAC researcher who is a co-author of this article.

LA JOLLA, CALIF. - April 16, 2021 - Scientists at Sanford Burnham Prebys have identified a set of human genes that fight SARS-CoV-2 infection, the virus that causes COVID-19. Knowing which genes help control viral infection can greatly assist researchers' understanding of factors that affect disease severity and also suggest possible therapeutic options. The genes in question are related to interferons, the body's frontline virus fighters.

The study was published in the journal Molecular Cell.

"We wanted to gain a better understanding of the cellular response to SARS-CoV-2, including what drives a strong or weak response to infection," says Sumit K. Chanda, Ph.D., professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and lead author of the study. "We've gained new insights into how the virus exploits the human cells it invades, but we are still searching for its Achille's heel so that we can develop optimal antivirals."

Soon after the start of the pandemic, clinicians found that a weak interferon response to SARS-CoV-2 infection resulted in some of the more severe cases of COVID-19. This knowledge led Chanda and his collaborators to search for the human genes that are triggered by interferons, known as interferon-stimulated genes (ISGs), which act to limit SARS-CoV-2 infection.

Based on knowledge gleaned from SARS-CoV-1, the virus that caused a deadly, but relatively brief, outbreak of disease from 2002 to 2004, and knowing that it was similar to SARS-CoV-2, the investigators were able to develop laboratory experiments to identify the ISGs that control viral replication in COVID-19.

"We found that 65 ISGs controlled SARS-CoV-2 infection, including some that inhibited the virus' ability to enter cells, some that suppressed manufacture of the RNA that is the virus's lifeblood, and a cluster of genes that inhibited assembly of the virus," says Chanda. "What was also of great interest was the fact that some of the ISGs exhibited control across unrelated viruses, such as seasonal flu, West Nile and HIV, which leads to AIDS".

"We identified eight ISGs that inhibited both SARS-CoV-1 and CoV-2 replication in the subcellular compartment responsible for protein packaging, suggesting this vulnerable site could be exploited to clear viral infection," says Laura Martin-Sancho, Ph.D., a senior postdoctoral associate in the Chanda lab and first author of this study. "This is important information, but we still need to learn more about the biology of the virus and investigate if genetic variability within these ISGs correlates with COVID-19 severity."

As a next step, the researchers will look at the biology of SARS-CoV-2 variants that continue to evolve and threaten vaccine efficacy. Martin-Sancho notes that they have already started gathering variants for laboratory investigation,

"It's vitally important that we don't take our foot off the pedal of basic research efforts now that vaccines are helping control the pandemic," concludes Chanda. "We've come so far so fast because of investment in fundamental research at Sanford Burnham Prebys and elsewhere, and our continued efforts will be especially important when, not if, another viral outbreak occurs."

Scientists have figured out how to modify CRISPR's basic architecture to extend its reach beyond the genome and into what's known as the epigenome -- proteins and small molecules that latch onto DNA and control when and where genes are switched on or off.

In a paper published April 9, 2021, in the journal Cell, researchers at UC San Francisco and the Whitehead Institute describe a novel CRISPR-based tool called "CRISPRoff," which allows scientists to switch off almost any gene in human cells without making a single edit to the genetic code. The researchers also show that once a gene is switched off, it remains inert in the cell's descendants for hundreds of generations, unless it is switched back on with a complementary tool called CRISPRon, also described in the paper.

Because the epigenome plays a central role in many diseases, from viral infection to cancer, CRISPRoff technology may one day lead to powerful epigenetic therapies. And since this approach doesn't involve any DNA edits, it's likely to be safer than conventional CRISPR therapeutics, which have been known to cause unwanted and potentially harmful changes to the genome.

"Though genetic and cellular therapies are the future of medicine, there are potential safety concerns around permanently changing the genome, which is why we're trying to come up with other ways to use CRISPR to treat disease," said Luke Gilbert, PhD, a professor at UCSF's Helen Diller Family Comprehensive Cancer Center and co-senior author of the new paper.

Transforming CRISPR From Genome to Epigenome Editor

Conventional CRISPR is equipped with two pieces of molecular hardware that make it an effective gene-editing tool. One component is a DNA-snipping enzyme, which gives CRISPR the ability to alter DNA sequences. The other is a homing device that can be programmed to zero in on any DNA sequence of interest, imparting precise control over where edits are made.

To build CRISPRoff, the researchers dispensed with conventional CRISPR's DNA-snipping enzyme function while retaining the homing device, creating a stripped-down CRISPR capable of targeting any gene, but not editing it. Then they tethered an enzyme to this barebones CRISPR. But rather than splicing DNA, this enzyme acts on the epigenome.

The new tool targets a particular epigenetic feature known as DNA methylation, which is one of many molecular parts of the epigenome. When DNA is methylated, a small chemical tag known as a methyl group is affixed to DNA, which silences nearby genes. Although DNA methylation occurs naturally in all mammalian cells, CRISPRoff offers scientists unprecedented control over this process. Another tool described in the paper, called CRISPRon, removes methylation marks deposited by CRISPRoff, making the process fully reversible.

"Now we have a simple tool that can silence the vast majority of genes," said Jonathan Weissman, PhD, Whitehead Institute member, co-senior author of the new paper and a former UCSF faculty member. "We can do this for multiple genes at the same time without any DNA damage, and in a way that can be reversed. It's a great tool for controlling gene expression."

"Major Surprise" Upends A Basic Tenet of Epigenetics

Based on previous work by a group in Italy, the researchers were confident that CRISPRoff would be able to silence specific genes, but they suspected that some 30 percent of human genes would be unresponsive to the new tool.

DNA consists of four genetic letters -- A, C, G, T -- but, in general, only Cs next to Gs can be methylated. To complicate matters, scientists have long believed that methylation could only silence genes at sites in the genome where CG sequences are highly concentrated, regions known as "CpG islands."

Since nearly a third of human genes lack CpG islands, the researchers assumed methylation wouldn't switch these genes off. But their CRISPRoff experiments upended this epigenetic dogma.

"What was thought before this work was that the 30 percent of genes that do not have CpG islands were not controlled by DNA methylation," said Gilbert. "But our work clearly shows that you don't require a CpG island to turn genes off by methylation. That, to me, was a major surprise."

Epigenetic Inheritance Enhances CRISPRoff's Therapeutic Potential

Easy-to-use epigenetic editors like CRISPRoff have tremendous therapeutic potential, in large part because, like the genome, the epigenome can be inherited.

When CRISPRoff silences a gene, not only does the gene remain off in the treated cell, it also stays off in the descendants of the cell as it divides, for as many as 450 generations.

To the researchers' surprise, this held true even in maturing stem cells. Though the transition from stem cell to differentiated adult cell involves a significant rewiring of the epigenome, the methylation marks deposited by CRISPRoff were faithfully inherited in a significant fraction of cells that made this transition.

These findings suggest that CRISPRoff would only need to be administered once to have lasting therapeutic effects, making it a promising approach for treating rare genetic disorders -- including Marfan syndrome, which affects connective tissue, Job's syndrome, an immune system disorder, and certain forms of cancer -- that are caused by the activity of a single damaged copy of a gene.

The researchers noted that although CRISPRoff is exceptionally promising, further work is needed to realize its full therapeutic potential. Time will tell if CRISPRoff and similar technologies are indeed "the future of medicine."

Look deep inside the brain of someone with Alzheimer's disease, most forms of dementia or the concussion-related syndrome known as chronic traumatic encephalopathy (CTE) and you'll find a common suspected culprit: stringy, hairball-like tangles of a protein called tau.

Such conditions, collectively known as "tauopathies" strike scores of people across the globe, with Alzheimer's alone affecting six million people in the United States.

But more than a century after German psychiatrist Alois Alzheimer discovered tau tangles, scientists still have much to learn about them.

A University of Colorado Boulder study, published this week in the journal Neuron, shows for the first time that tau aggregates gobble up RNA, or ribonucleic acid, inside cells and interfere with an integral mechanism called splicing, by which cells ultimately produce needed proteins.

"Understanding how tau leads to neurodegeneration is the crux of not just understanding Alzheimer's disease but also multiple other neurological diseases," said senior author Roy Parker, a professor of biochemistry and director of the BioFrontiers Institute at CU Boulder. "If we can understand what it does and how it goes bad in disease we can develop new therapies for conditions that now are largely untreatable."

The study was led by Evan Lester, an M.D./PhD candidate in the Medical Scientist Training Program, which enables students to simultaneously work toward a medical degree from the University of Colorado Anschutz Medical Campus and a PhD from CU Boulder.

For part of his medical training, Lester worked alongside doctors and patients at the CU Alzheimer's and Cognition Center in Aurora.

"There is nothing we can do for these patients right now - no disease modifying-treatments for Alzheimer's or most of the other tauopathies," Lester said, noting that 70% of neurodegenerative diseases are believed to be at least partially related to tau aggregates.

For the study, the researchers isolated tau aggregates from cell lines and from the brains of mice with an Alzheimer's-like condition. Then they used genetic sequencing techniques to determine what was inside.

They confirmed for the first time that tau aggregates contain RNA, or ribonucleic acid, a single-stranded molecule key for synthesizing proteins in cells. They identified what kind of RNA it is, specifically snRNA, or small nuclear RNA, and snoRNA, or small nucleolar RNA.

They also discovered that tau interacts with pieces of cellular machinery known as nuclear speckles, sequestering and displacing proteins inside them and disrupting a process called RNA splicing in which the cell weeds out unneeded material to generate new, healthy RNA.

"The tau aggregates appear to be sequestering splicing-related RNA and proteins, disrupting their normal function and impairing the cell's ability to make proteins," said Lester.

Notably, scientists examining the brains of Alzheimer's patients after death have discovered evidence of splicing-related defects in cells.

The paper is the first in a series out of Parker's lab to explore the mechanism of action by which tau aggregates gum up the works inside brain cells.

Already, several companies have clinical trials underway testing drugs that would do away with tau entirely in patients with neurodegenerative diseases. But that could potentially have unintended consequences, said Lester.

"A big problem in the field is that no one really knows what tau does in healthy people and It likely has important functions when not in tangles," he said.

By better understanding precisely what it does to harm and kill cells, Parker and Lester hope to bring a different approach to the table.

"The idea would be to intervene in the abnormal functions while preserving the normal functions of tau," Lester said.

 Aging entails a loss of muscle mass and strength, which in some cases impairs mobility, hinders walking or performance of day-to-day tasks, and exposes the elderly to the risk of falls and hospitalizations.

In clinical practice, handgrip measurement is the most widely used method to identify loss of overall muscular strength in older people. Values below 26 kg for men and 16 kg for women have for some time been considered an indication of risk-associated weakness, but these parameters are being revised.

Researchers at the Federal University of São Carlos (UFSCar) in the state of São Paulo, Brazil, collaborating with colleagues at other institutions in the same state such as the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP), Nursing School (EE-USP) and School of Public Health (FSP-USP), as well as University College London (UCL), have suggested higher handgrip cutoff values than those typically used by physicians, physical therapists and nutritionists. A higher cutoff permits early diagnosis and intervention to avert clinical progression.

“Our study argues against the prevailing view of mobility loss. Based on an analysis of demographic data and appropriate statistical methods, we tested the usual cutoffs and found higher values, such as 32 kg for men and 21 kg for women, to be more accurate markers of mobility impairment,” Tiago da Silva Alexandre, a professor at UFSCar’s Department of Gerontology, told Agência FAPESP. Alexandre coordinates the International Collaboration of Longitudinal Studies of Aging (InterCoLAging), a consortium of longitudinal studies that includes epidemiological data from Brazil and the UK. 

In this latest study, which was supported by FAPESP, the researchers analyzed data for 5,783 people aged 60 and more, all of whom were participants in the English Longitudinal Study of Ageing (ELSA) and the SABE study in São Paulo City. 

The principal investigator for ELSA is Andrew Steptoe, a professor at UCL, assisted by Cesar de Oliveira, a researcher at the same institution. SABE (the Portuguese-language acronym for Health, Wellbeing, and Aging) is supported by FAPESP and led by Yeda Duarte and Jair Licio Ferreira Santos. 

Early diagnosis

In an article on the study published in Archives of Gerontology and Geriatrics, the researchers report that mobility impairment is 88% more likely in older men with a handgrip of less than 32 kg and 89% more likely in women with less than 21 kg, regardless of socio-economic conditions, lifestyle, existing diseases and anthropometric measurements. 

“The increase is considerable. The most widely used cutoffs include 26 kg for men and 16 kg for women, although values vary between studies and countries,” Alexandre said.

The study also discusses previous research in which handgrip measured with a dynamometer is correlated with walking speed among the more than 5,000 older people involved in SABE and ELSA.

“We raised the cutoffs a lot so that subjects most likely to have impaired mobility could be identified and action taken sooner. The cause of the problem can be investigated and treatment designed in order to avoid all the consequences of muscle weakness and mobility impairment. This preserves the individual’s functional capacity, facilitates social interaction and enhances quality of life while aging. For society as a whole, using higher cutoffs helps reduce the cost of healthcare,” Alexandre said.

Preventing is better than curing

Muscle strength is extremely important to mobility. A classic example is lower-limb muscle weakness, which prevents people from walking. However, both loss of muscle mass and weakness are natural age-related processes and become a serious problem only when they cross a certain threshold.

According to the researchers, while loss of muscle mass and strength are known to contribute significantly to mobility impairment, the exact point at which low muscle mass entails loss of strength and mobility is not entirely understood. “Loss of strength depends on loss of mass, but other drivers of the process include neurological factors, hormones and vitamin deficiencies. On the other hand, muscle strength can be recouped, so it’s very important to have a metric that tells us when it’s best to start preventive treatment that avoids loss of mobility,” said Maicon Delinocente, a researcher at UFSCar and first author of the article.

According to Delinocente, when the problem is diagnosed, its cause must be identified and treated by resistance training and an appropriate high protein/calorie diet, for example.

Tarantulas are among the most notorious spiders, due in part to their size, vibrant colors and prevalence throughout the world. But one thing most people don't know is that tarantulas are homebodies. Females and their young rarely leave their burrows and only mature males will wander to seek out a mate. How then did such a sedentary spider come to inhabit six out of seven continents?

An international team of researchers, including Carnegie Mellon University's Saoirse Foley, set out on an ancestry.com-like investigation to find the answer to this question. They looked to the transcriptomes, the sum of all the transcripts from the mRNA, of many tarantulas and other spiders from different time periods. Their findings were published online by PeerJ on April 6.

They used the transcriptomes to build a genetic tree of spiders and then time-calibrated their tree with fossil data. Tarantula fossils are extremely rare, but the software used in the study managed to estimate the ages of older tarantulas relative to the ages of fossils from other spiders.

They found that tarantulas are ancient, first emerging in the piece of land now considered the Americas about 120 million years ago during the Cretaceous period. At that time South America would have been attached to Africa, India and Australia as part of the Gondwana supercontinent. The spiders ultimately reached their present destinations due to continental drift, with a few interesting departures.

For example, the nature of their entry into Asia suggests tarantulas may also be surprisingly proficient dispersers. The researchers were able to establish two separate lineages of tarantulas that diverged on the Indian subcontinent before it crashed into Asia, with one lineage being predominantly ground dwelling and the other predominantly arboreal. They found that these lineages colonized Asia about 20 million years apart. Surprisingly, the first group that reached Asia also managed to cross the Wallace Line, a boundary between Australia and the Asian islands where many species are found in abundance on one side and rarely or not at all on the other.

"Previously, we did not consider tarantulas to be good dispersers. While continental drift certainly played its part in their history, the two Asian colonization events encourage us to reconsider this narrative. The microhabitat differences between those two lineages also suggest that tarantulas are experts at exploiting ecological niches, while simultaneously displaying signs of niche conservation," said Foley.

JUPITER, FL--Making memories involves more than seeing friends or taking photos. The brain constantly adapts to new information and stores memories by building connections among neurons, called synapses. How neurons do this--reaching out arm-like dendrites to communicate with other neurons--requires a ballet of genes, signaling molecules, cellular scaffolding and protein-building machinery.

A new study from scientists at Scripps Research and the Max Planck Florida Institute for Neuroscience finds a central role for one signaling molecule, a long, noncoding RNA that the scientists named ADEPTR.

Using a variety of technologies, including confocal and two-photon microscopy, they track ADEPTR's moves, watching as it forms, travels, amasses at the synapse and activates other proteins upon a neuron's stimulation.

Its journey to the far reaches of a brain cell is made possible by a cellular carrier that that tiptoes along a dendrite's microtubule scaffolding. Called a kinesin motor, it deposits ADEPTR near the synapse junction, where it activates other proteins.

The team also found that if ADEPTR is silenced, new synapses don't form during stimulation.

The study, "Activity regulated synaptic targeting of lncRNA ADEPTR mediates structural plasticity by localizing Sptn1 and AnkB in dendrites," is published online April 16 in the journal Science Advances.

Long noncoding RNAs have often been described as "genomic dark matter," because their role in cells has yet to be fully characterized, especially in neurons, says the study's lead author, Scripps Research neuroscientist Sathyanarayanan Puthanveettil, PhD. Puthanveettil's team is finding that they play a signaling role in neural plasticity--how neurons adapt and change with experience.

"Here we report activity-dependent dendritic targeting of a newly transcribed long noncoding RNA for modulating synapse function, and describe its underlying mechanisms," Puthanveettil says. "These studies bring novel insights into the functions of long noncoding RNAs at the synapse."

The first author is Eddie Grinman, a graduate student in Puthanveettil's lab.

A long noncoding RNA is a type of RNA that exceeds 200 nucleotides, and does not get translated into protein. There are thousands of these long noncoding RNA in our cells, but in most cases, their function isn't yet known. What is known is that usually, they tend to stay within the cell nucleus. Some regulate the transcription of genes.

"It was surprising to see a long noncoding RNA move from nucleus to the synapse so rapidly and robustly," Grinman says.

The hippocampus is the part of the brain where learning, memory and emotions reside. Working in hippocampal neurons from mice, the team stimulated the neurons with pharmacological activators of learning-related signaling. They found through molecular and high-resolution imaging techniques that the ADEPTR long noncoding RNA was rapidly expressed and transported to the outer arms of the cell. There, the ADEPTR molecules interact with proteins that play a role in structural organization of synapses, proteins called spectrin 1 and ankyrin B.

They found that ADEPTR became downregulated if exposed to an inhibitory neurotransmitter, GABA.

"These findings add another layer of complexity in synapse modulation and plasticity," Puthanveettil says. "Synaptically localized long noncoding RNA are important regulators of adaptive neuronal function."

Going forward, the team intends to continue characterizing how stimulation affects neuronal plasticity. Also, the authors hope to learn more about the role of ADEPTR in vivo.

"It would be interesting to learn what role ADEPTR plays in forming new memories in living organisms," says Grinman.

The work is revealing one of the most fundamental processes of learning and memory, adaptation to changing information and circumstances.

"Neural plasticity is what allows us to learn, respond to stimuli, and lay down long-term memories," Puthanveettil says. "There is still much to learn about the magnificent complexity of this fundamental biological process."

Research shows that a new telescope could detect a potential signature of life on other planets in as little as 60 hours.

"What really surprised me about the results is that we may realistically find signs of life on other planets in the next 5 to 10 years," said Caprice Phillips, a graduate student at The Ohio State University, who will share preliminary findings at a press conference during the 2021 APS April Meeting.

Gas dwarf planets have the potential to foster life. But because none of these super-Earths or mini-Neptunes exist within our solar system, scientists struggle to determine whether their atmospheres contain ammonia and other potential signs of living things.

Phillips calculated that when the James Webb Space Telescope launches this October, it could feasibly detect ammonia around six gas dwarf planets after just a few orbits.

She and her team modeled how JWST instruments would respond to varying clouds and atmospheric conditions, then produced a ranked list of where the telescope should search for life.

"Humankind has contemplated the questions, 'Are we alone? What is life? Is life elsewhere similar to us?'" said Phillips. "My research suggests that for the first time, we have the scientific knowledge and technological capabilities to realistically begin to find the answers to these questions."

FEATURED TALK

Detecting Biosignatures in the Atmospheres of Gas Dwarfs With JWST (K05.2)
2:06 p.m. - 2:42 p.m. CDT, Sunday, April 18, 2021
Caprice Phillips, phillips.1622@buckeyemail.osu.edu
Livestream: Access here
Abstract: https://meetings.aps.org/Meeting/APR21/Session/K05.2

PRESS CONFERENCE

Register for the press conference to be held on Zoom at 12:00 p.m. CDT, Sunday, April 18, 2021.

Speaker:

Caprice Phillips (Ohio State)

From engineered pandemics to city-toppling cyber attacks to nuclear annihilation, life on Earth could radically change, and soon. Scientists will forecast the fate of the planet at a press conference during the 2021 APS April Meeting.

"Our Earth is 45 million centuries old. But this century is the first when one species--ours--can determine the biosphere's fate," said Martin Rees, the United Kingdom's Astronomer Royal and a founder of the Centre for the Study of Existential Risks at Cambridge University.

"Our globally-linked society is vulnerable to the unintended consequences of powerful new technologies--not only nuclear, but (even more) biotech, cyber, advanced AI, space technology," he added.

Royal astronomer predicts the world in 2050 and beyond

Rees thinks biohackers pose a particularly underappreciated threat to humanity. In the near future, simple equipment will enable people to reengineer the human genome irrevocably or build a superspreading influenza. Like drug laws, regulations could never prevent all such actions--and in a world more interconnected than ever before, the consequences would spread globally.

He will discuss other dangers: population rise leading to plummeting biodiversity, disastrous climate change, uncontrollable cybercriminals, plans for artificial intelligence that erodes privacy, security, and freedom.

But Rees is an optimist. He will offer a path toward avoiding these risks and achieving a sustainable future better than the world we live in today.

"If all of us passengers on 'spaceship Earth' want to ensure that we leave it in better shape for future generations we need to promote wise deployment of new technologies, while minimizing the risk of pandemics, cyberthreats, and other global catastrophes," he said.

Scaling back missile defense could prevent a nuclear attack

A single nuclear weapon could kill millions and destroy a city instantaneously. Hundreds of weapons could wipe out functioning society in a large nation. Even a limited nuclear war could cause a climate catastrophe, leading to the starvation of hundreds of millions of people.

Recently, Russia, China, and North Korea have deployed new types of nearly unstoppable missiles.

"Missile defense is an idea that can sound appealing at first--doesn't defense sound like the right thing to do?" said Frederick Lamb, astrophysicist at the University of Illinois at Urbana-Champaign, cochair of the 2003 APS Study of Boost-Phase Missile Defense, and chair of the current APS Panel on Public Affairs Study of Missile Defense and National Security.

"But when the technical challenges and arms race implications are considered, one can see that deploying a system that is intended to defend against intercontinental ballistic missiles is unlikely to improve the security of the United States," he said.

Lamb points to the United Kingdom's decision to increase its nuclear arsenal by 44%, possibly motivated by Russia's new missile defense system around Moscow. He sees the move as yet another sign that existing limits on nuclear weapons are unraveling. Even missile defenses that would never work in practice can catalyze the development of new nuclear weapons and increase global risk.

Lamb will share what may happen if the United States ramps up new missile defense systems.

"What is done about nuclear weapons and missile defenses by the United States and other countries affects the safety and survival of every person on the planet," he said.

FEATURED TALKS

The World in 2050--and Beyond (X06.1)

10:45 a.m. - 11:21 a.m. CDT, Tuesday, April 20, 2021
Martin Rees, mjr36@cam.ac.uk
Livestream: Access here
Abstract: http://meetings.aps.org/Meeting/APR21/Session/X06.1

Nuclear Weapons and Missile Defense (Y05.2)

2:06 p.m. - 2:42 p.m. CDT, Tuesday, April 20, 2021
Frederick Lamb, fkl@illinois.edu
Livestream: Access here
Abstract: http://meetings.aps.org/Meeting/APR21/Session/Y05.2

PRESS CONFERENCE

Register for the press conference to be held on Zoom at 11:00 a.m. CDT, Monday, April 19, 2021.

Speakers:

Martin Rees (Cambridge)

Frederick Lamb (University of Illinois at Urbana-Champaign)

The composition of the street drugs heroin and cocaine has dramatically changed at alarming speeds across the globe. No longer are these street drugs cut with benign materials such as lactose but now cut with up to 17 or more pharmaceutically active and potentially toxic adulterants.

A drug user may buy cocaine today but may end up with a drug cocktail more dangerous then what was bought and assumed was cocaine. This has a profound effect on public health and safety as well as on the individual street drug users during the COVID-19 pandemic.

Selected by the Editor-in-Chief, Dr. Kenneth Blum as the Editor's Choice in the May 2021 issue of Current Psychopharmacology (CPSP), this work examined the alarming addition of multiple pharmaceutically active substances collectively referred to as "toxic adulterants" and their pathophysiological effects, especially on street drug using patients, in light of the COVID-19 pandemic

Additional pharmaceutically active and potentially toxic compounds have been found in routine street drug seizures at startling amounts. These toxic adulterants include, but are not limited to, ethical pharmaceuticals such as cardiac medications, veterinary pharmaceuticals such as levamisole, industrial chemicals, fungicides, new psychoactive substances all of which have profound effects on the substance user health and COVID-19 risk.

"Never before in the history of addiction medicine have there been so many combinations of drugs and pharmacologically active compounds in a single dose of cocaine or heroin" Stated Dr. David M. Martin, Science Team Director of the project, he continued "Although the reason for this is unclear, it may be to create new product lines for an increasingly overcrowded street drug market and this trend seems to be continuing."

The report concluded that this dangerous new trend in world street drug supply is unprecedented and maybe the undetected cause of many psychostimulant and opioid overdose deaths. This is because many toxic adulterants are not routinely tested in post-mortem or street drug seizure cases. Public health and treatment officials need to know of this new dangerous trend evaluating and treating patients.

To get the full-text article, please visit: https://www.eurekaselect.com/node/190669/article/the-rapidly-changing-composition-of-the-global-street-drug-supply-and-its-effects-on-high-risk-groups-for-covid-19

WASHINGTON, April 16, 2021 -- Early in the COVID-19 pandemic, doctors recognized that patients who developed a "cytokine storm" -- a surge of pro-inflammatory immune proteins -- were often the sickest and at highest risk of dying. But a cytokine storm can also occur in other illnesses, such as influenza. Today, scientists report preliminary results on a sweat sensor that acts as an early warning system for an impending cytokine storm, which could help doctors more effectively treat patients.

The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2021 is being held online April 5-30. Live sessions will be hosted April 5-16, and on-demand and networking content will continue through April 30. The meeting features nearly 9,000 presentations on a wide range of science topics.

A video on the research is available at http://www.acs.org/acsspring2021cytokinesensor.

"Especially now in the context of COVID-19, if you could monitor pro-inflammatory cytokines and see them trending upwards, you could treat patients early, even before they develop symptoms," says Shalini Prasad, Ph.D., the project's principal investigator, who is presenting the work at the meeting.

Early detection is important because once a cytokine storm has been unleashed, the excessive inflammation can damage organs, causing severe illness and death. In contrast, if doctors could administer steroidal or other therapies as soon as cytokine levels begin to rise, hospitalizations and deaths could be reduced.

Although blood tests can measure cytokines, they are difficult to perform at home, and they can't continuously monitor the proteins' levels. Cytokines are excreted in sweat at lower levels than in blood. To collect enough sweat for testing, scientists have asked patients to exercise, or they have applied a small electrical current to patients' skin. However, these procedures can themselves alter cytokine levels, Prasad notes. "When it comes to cytokines, we found that you have to measure them in passive sweat. But the big challenge is that we don't sweat much, especially in air-conditioned environments," she says. Prasad, who is at the University of Texas at Dallas, estimates that most people produce only about 5 microliters, or one-tenth of a drop, of passive sweat in a 0.5-inch square of skin in 10 minutes.

So the researchers wanted to develop an extremely sensitive method to measure cytokine levels in tiny amounts of passive sweat. They drew on their previous work on a wearable sweat sensor to monitor markers of inflammatory bowel disease (IBD). The wristwatch-like device, which is being commercialized by EnLiSense LLC (a company co-founded by Prasad), measures the levels of two proteins that spike during IBD flare-ups. When the device is worn on the arm, passive sweat diffuses onto a disposable sensor strip that is attached to an electronic reader. The sensor strip, which contains two electrodes, is coated with antibodies that bind to the two proteins. Binding of the proteins to their antibodies changes the electrical current flowing through the e-reader. The reader then wirelessly transfers these data to a smartphone app that converts electrical measurements to protein concentrations. After a few minutes, the old sweat diffuses out, and newly excreted sweat enters the strip for analysis.

For their new cytokine sensor (called the SWEATSENSER Dx), the researchers made sensor strips with antibodies against seven pro-inflammatory proteins: interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), TNF-related apoptosis-inducing ligand, IL-10, interferon-γ-induced protein-10 and C-reactive protein. They inserted the strips into their device and, in a small observational study, they tested them on six healthy people and five people with influenza. Two of the sick people showed elevated cytokine levels, and in all participants, cytokines in passive sweat correlated with levels of the same proteins in serum.

The SWEATSENSER Dx was even sensitive enough to measure cytokines in patients taking anti-inflammatory drugs, who excrete cytokines in the low-picogram-per-milliliter concentration range. The device tracked cytokine levels for up to 168 hours before the sensor strip needed to be replaced.

EnLiSense, in partnership with the researchers, is now planning clinical trials of the cytokine sensor in people with respiratory infections. "Access to COVID-19 patients has been a challenge because healthcare workers are overwhelmed and don't have time to test investigational devices," Prasad says. "But we're going to continue to test it for all respiratory infections because the disease trigger itself doesn't matter -- it's what's happening with the cytokines that we're interested in monitoring."

Vitamin D deficiency may impair muscle function due to a reduction in energy production in the muscles, according to a mouse study published in the Journal of Endocrinology. Vitamin D deficient mice were found to have impaired muscle mitochondrial function, which may have implications for muscle function, performance and recovery. This may suggest that preventing vitamin D deficiency in older adults could help maintain better muscle strength and function and reduce age related muscle deterioration, but further studies are needed to confirm this.

Vitamin D is a hormone well known to be important for maintaining bone health and preventing rickets and osteoporosis. In recent years, vitamin D deficiency has been reported to be as prevalent as 40% in European populations and linked to increased risk for several conditions, including COVID-19, cancer and diabetes. Although these studies report association rather than causation, the benefits of vitamin D supplementation are now a major subject of health debate. Multiple studies have also linked low vitamin D levels to poor muscle strength, particularly in older people. Skeletal muscle enables us to move voluntarily and perform everyday activities. It is essential that they have enough energy to power these movements. Specialised organs in cells, called mitochondria, convert nutrients in to energy to meet this demand. Previous studies indicate that impaired muscle strength in people with vitamin D deficiency may be linked to impaired muscle mitochondrial function. Determining the role of vitamin D in muscle performance of older people is also difficult, as they may suffer from a number of pre-existing health conditions that can also affect their vitamin D status. Therefore, previous studies have been unable to determine how vitamin D may directly affect muscle performance.

Dr Andrew Philp and his team at the Garvan Institute of Medical Research in Australia, and collaborating universities, used a mouse model to determine the effects of diet-induced vitamin D deficiency on skeletal muscle mitochondrial function in young, male mice. Mice were either fed a diet with normal quantities of vitamin D, or with no vitamin D to induce deficiency, for a period of 3 months. A typical vitamin D level for humans is 40-50 nmol.L-1, and acute vitamin D deficiency is diagnosed when levels drop below 12 nmol.L-1. On average, the mice in this study had vitamin D levels of 30 nmol.L1, with diet-induced vitamin D deficiency leading to levels of just 3 nmol.L-1. Although this level was more extreme than typically observed in people, it is still within the clinically-recognised range. Tissue and blood samples were collected monthly to quantify vitamin D and calcium concentrations and to assess markers of muscle mitochondrial function and number. After 3 months of diet-induced vitamin D deficiency skeletal muscle mitochondrial function was found to be impaired by up to 37%. This was not due to a reduced number of mitochondria or a reduction in muscle mass.

"Our results show there is a clear link between vitamin D deficiency and oxidative capacity in skeletal muscle. They suggest that vitamin D deficiency decreases mitochondrial function, as opposed to reducing the number of mitochondria in skeletal muscle." Dr Philp comments. "We are particularly interested to examine whether this reduction in mitochondrial function may be a cause of age related loss in skeletal muscle mass and function."

These findings suggest that vitamin D deficiency may impair mitochondrial function and reduce the amount of energy produced in the muscles, which may lead to poor muscle function. Therefore, preventing vitamin D deficiency in older people may help maintain muscle performance and reduce the risk of muscle related diseases, such as sarcopenia. However, further studies that investigate the direct effect of vitamin D deficiency on muscle function and strength are necessary to confirm this.

Whilst this study indicates that vitamin D deficiency can alter mitochondrial function in skeletal muscle, Dr Philp and his team were unable to determine precisely how this process occurred. Therefore, their future work aims to establish how vitamin D deficiency alters mitochondrial control and function in skeletal muscle.

CHAPEL HILL, NC - A study published today in JAMA Internal Medicine shows that wearing two face coverings can nearly double the effectiveness of filtering out SARS-CoV-2-sized particles, preventing them from reaching the wearer's nose and mouth and causing COVID-19. The reason for the enhanced filtration isn't so much adding layers of cloth, but eliminating any gaps or poor-fitting areas of a mask.

"The medical procedure masks are designed to have very good filtration potential based on their material, but the way they fit our faces isn't perfect," said Emily Sickbert-Bennett, PhD, associate professor of infectious diseases at the UNC School of Medicine and lead author of the study.

To test the fitted filtration efficiency (FFE) of a range of masks, UNC researchers worked with James Samet, PhD, and colleagues in the USEPA Human Studies Facility on the campus of UNC-Chapel Hill. There they filled a 10-foot by 10-foot stainless-steel exposure chamber with small salt particle aerosols, and had researchers don combinations of masks to test how effective they were at keeping particles out of their breathing space.

Each individual mask or layered mask combination was fitted with a metal sample port, which was attached to tubing in the exposure chamber that measured the concentration of particles entering the breathing space underneath the researcher's mask. A second tube measured the ambient concentration of particles in the chamber. By measuring particle concentration in the breathing space underneath the mask compared to that in the chamber, researchers determined the FFE.

"We also had the researchers in the chamber undergo a series of range-of-motion activities to simulate the typical motions a person may do throughout their day - bending at the waist, talking, and looking left, right, up and down," said Phillip Clapp, PhD, an inhalation toxicologist in the UNC School of Medicine who has been testing mask FFE with Sickbert-Bennett since the pandemic began.

According to their findings, the baseline fitted filtration efficiency (FFE) of a mask differs person to person, due to each person's unique face and mask fit. But generally, a procedure mask without altering the fit, is about 40-60% effective at keeping COVID-19-sized particles out. A cloth mask is about 40% effective.

Their recent findings on doubling of face masks, shows that when a cloth mask is placed over a surgical mask, the FFE improved by about 20%, and improved even more with a snug-fitting, sleeve-type mask, such as a gaiter. When layered over procedure masks, cloth masks improve fit by eliminating gaps and holding the procedure mask closer to the face, consistently covering the nose and mouth. When a procedure mask is worn over a cloth mask, FFE improved by 16%.

"We've found that wearing two loosely fitted masks will not give you the filtration benefit that one, snug-fitting procedure mask will," Sickbert-Bennett said. "And with the current data supporting how effective mask-wearing is at preventing the spread of COVID-19, the best kind of double-masking is when you and the person you are interacting with are each correctly wearing a very snug-fitting mask."