Culture

One of the marks of a successful idea in science is how quickly it can develop and evolve. In the case of the Anthropocene, the conceptual evolution has taken place with extraordinary speed. The strikingly influential hypothesis launched by the late Nobel laureate Paul Crutzen (Obituary, 24th Feb 2021) in 2000, was that the actions of an industrialised humanity has impacted the Earth so greatly as to trigger a new geological epoch. Originally developed within the Earth System science community in charting global environmental change, the Anthropocene then began to be analysed by geologists to see whether it really could be accepted, formally, on to the Geological Time scale--ongoing work steered from the outset by a University of Leicester team (Professors Zalasiewicz, Waters, Williams) and other UK and international scholars. "It quickly spread widely across the sciences, humanities and arts, including to become a central framing concept of the IPCC, the UN Environment Programme and in international law", Waters explains. With such profound influence across so many different communities, of such different backgrounds and perspectives, though, came large questions about what the Anthropocene is, and when it started.

Originally Crutzen suggested it began as the Industrial Revolution commenced in the late 18th century, but subsequent analysis by the Anthropocene Working Group (AWG), has refined this estimate. "The greatest changes, of population, industrialization, globalization have taken place with the 'Great Acceleration' of the boom post-WWII years of the mid-20th century", Zalasiewicz explained. "In that brief spell--a little less than one average human lifetime--humanity has burned through more energy than in the previous 12 millennia and more", Williams said. This is driving the physical, chemical and biological changes to Earth that are now destabilizing the biosphere and climate, leaving records in modern-day strata, including plastics, concrete and supermarket chicken bones that justify the Anthropocene in geology.

But look at the Anthropocene from more human-based perspectives, and one can foreground human impacts on the environment that go back thousands of years. So should the beginning of the Anthropocene be pushed back to these earliest impacts, of the felling of forests, or the domestication of animals, or the spread of farmland soils, or of the linking of the New World with the Old? "All these ideas, and more, have emerged, in intense discussions that have erupted around this vivid and powerful new concept--each of which puts it in a different light", new AWG member Jens Zinke (UofL) adds. What, then, is the Anthropocene?

A new paper from the AWG, representing a wide range of academic disciplines, faces up to this conundrum, the playing out of which will determine how the Anthropocene will survive in human thinking. "Dissecting the many interpretations of the Anthropocene suggests that a range of quite distinct, but variably overlapping, concepts are in play", Waters noted. The debate has broken many barriers between academic disciplines--but also led to the risk of confusion of different meanings of the term. How should this be resolved? The authors encourage more debate across various disciplines--and suggest that eventual formalization of the Anthropocene in geology would help stabilize its interpretation and use, including to help societies to navigate the many challenges of the emerging Anthropocene world.

April 19, 2021 -- Ensuring COVID-19 vaccine access for refugee and displaced populations, and addressing health inequities, is vital for an effective pandemic response. Yet, vaccine allocation and distribution has been neither equitable nor inclusive, despite that global leaders have stressed this as a critical aspect to globally overcoming the pandemic, according to a paper published by Columbia University Mailman School of Public Health. Read "Leave No-one Behind: Ensuring Access to COVID-19 vaccines for Refugee and Displaced Populations" in the journal Nature Medicine.

As of April 1st, high and upper-middle-income countries received 86 percent of the vaccine doses delivered worldwide, while only 0.1 percent of doses have been delivered in low-income countries. Worldwide, over 80 percent of refugees and nearly all internally displaced persons are hosted by low and middle-income countries - nations at the end of the line for COVID-19 vaccine doses.

"As the world grapples with supply challenges and inequitable vaccine access on local and global scales, marginalized groups, particularly refugees, internally displaced persons and stateless persons, face a double burden of access, even within countries that are themselves marginalized on the global stage," said Monette Zard, MA, Allan Rosenfield Associate Professor of Forced Migration and Health and director of the forced migration and health program at Columbia Mailman School. "Legal status should have no place in decisions about vaccine access, and relying on regularization as a route to vaccination will unacceptably delay the protective effects for migrants and refugees, particularly in higher risk groups."

In fragile settings with weak governance, competition for scarce COVID-19 vaccines may heighten tensions and exacerbate conflict, while unequal access raises the prospect of populations moving in an effort to access vaccines that are not available in their country or region, according to the authors.

The COVAX facility allocates around 5 percent of total available vaccine doses for humanitarian use, including vaccinating refugees, yet the total 2 billion vaccine doses targeted by the end of 2021 will only cover 20 percent of participating countries' populations, at most. Poorer countries may not be able to widely vaccinate their populations until 2023.

To create an equitable and inclusive COVID-19 vaccination strategy, Zard and co-authors believe lessons can also be drawn from experience managing conditions such as HIV and TB among mobile populations, as well as previous large-scale vaccination campaigns in humanitarian settings. They point out how the global community approaches COVID-19 vaccinations may further entrench the inequities and distrust experienced by refugees and displaced populations around the world or is a chance to build stronger, fairer health systems that are better prepared to respond to COVID-19 and future health emergencies. "Engage, listen, and mobilize trusted community and religious leaders -- involving the community, including displaced populations, in vaccine activities is vital,"noted Zard.

"Policy makers need to seize the opportunity of the pandemic to strengthen health systems more broadly and sustainably, to better respond to the challenges of COVID-19, while addressing the comprehensive health needs of refugees and host populations," observes one of the authors S. Patrick Kachur, MD, professor of population and family health at Columbia Mailman School. "As the world confronts one of the most formidable public health challenges in recent history, how we respond today will not only determine the course of this pandemic, but also who benefits from public health advances for years to come."

Tools that allow neuroscientists to record and quantify functional activity within the living brain are in great demand. Traditionally, researchers have used techniques such as functional magnetic resonance imaging, but this method cannot record neural activity with high spatial resolution or in moving subjects. In recent years, a technology called optogenetics has shown considerable success in recording neural activity from animals in real time with single neuron resolution. Optogenetic tools use light to control neurons and record signals in tissues that are genetically modified to express light-sensitive and fluorescent proteins. However, existing technologies for imaging light signals from the brain have drawbacks in their size, imaging speed, or contrast that limit their applications in experimental neuroscience.

A technology called light-sheet fluorescence imaging shows promise for imaging brain activity in 3D with high speed and contrast (overcoming multiple limitations of other imaging technologies). In this technique, a thin sheet of laser light (light-sheet) is directed through a brain tissue region of interest, and fluorescent activity reporters within the brain tissues respond by emitting fluorescence signals that microscopes can detect. Scanning a light sheet in the tissue enables high-speed, high-contrast, volumetric imaging of the brain activity.

Currently, using light-sheet fluorescence brain imaging with nontransparent organisms (like a mouse) is difficult because of the size of the necessary apparatus. To make experiments with nontransparent animals and, in the future, freely moving animals feasible, researchers will first need to miniaturize many of the components.

A key component for the miniaturization is the light-sheet generator itself, which needs to be inserted into the brain and thus must be as small as possible to avoid displacing too much brain tissue. In a new study reported in Neurophotonics, an international team of researchers from the California Institute of Technology (USA), University of Toronto (Canada), University Health Network (Canada), the Max Planck Institute of Microstructure Physics (Germany), and Advanced Micro Foundry (Singapore) developed a miniature light-sheet generator, or a photonic neural probe, that can be implanted into a living animal's brain.

The researchers used nanophotonic technology to create ultrathin silicon-based photonic neural probes that emit multiple addressable thin sheets of light with thicknesses

Describing the significance of his team's work, the study's lead author, Wesley Sacher, says, "This new implantable photonic neural probe technology for generating light sheets within the brain circumvents many of the constraints that have limited the use of light-sheet fluorescence imaging in experimental neuroscience. We predict that this technology will lead to new variants of light-sheet microscopy for deep brain imaging and behavior experiments with freely moving animals."

Such variants would be a boon to neuroscientists seeking to understand the workings of the brain.

Below please find link(s) to new coronavirus-related content published today in Annals of Internal Medicine. All coronavirus-related content published in Annals of Internal Medicine is free to the public. A complete collection is available at https://annals.org/aim/pages/coronavirus-content.

1. Liver transplant recipient reinfected with SARS-CoV-2 infection 3 months after initial diagnosis

Viral genomic sequencing used to distinguish between relapse and reinfection

Free full text: https://www.acpjournals.org/doi/10.7326/L21-0108

A liver transplant recipient was reinfected with SARS-CoV-2 111 days after his initial diagnosis. Researchers from the University of Massachusetts Medical School and The Broad Institute of MIT and Harvard used viral genomic sequencing to distinguish whether the later positive samples were due to SARS-CoV-2 relapse or reinfection. The case report is published in Annals of Internal Medicine.

A 61-year-old man with a history of liver transplant reported to the emergency department (ED) complaining of fever, nausea, vomiting, and cough. The patient tested positive for SARS-CoV-2 infection with a RT-qPCR swab taken at the time of his visit. Swabs taken 48 and 53 days after his visit were negative for the virus. On day 111, the patient returned to the ED reporting several days of increasing confusion, hallucinations, unstable gait, and frequent falls. Once again, the patient tested positive for SARS-CoV-2 infection.

According to the study authors, the patient may have been susceptible to reinfection due to a lack of antibody response after the first infection. This case shows that genomic sequencing offers the ability to discern whether subsequent infections may be reinfection. In addition, genomic sequence data can also identify variants circulating in the population that are of high risk because of infectivity, disease severity, or resistance to treatment.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Stuart M. Levitz, MD, can be reached at Stuart.Levitz@umassmed.edu.

2. People of color have substantially higher risk for hospitalization, intensive-level care for COVID-19 than White persons

Authors say pandemic response must be adjusted to be culturally appropriate, address mistrust in health care system

Free full text: https://www.acpjournals.org/doi/10.7326/M20-8283

Even after adjustment for known COVID-19 risk factors, such as comorbidities and body mass index, persons of color continue to have a substantially higher risk for hospitalization and requiring intensive-level care than White persons. These results confirm findings from earlier in the pandemic suggesting that COVID-19 affects Hispanic, Black or African American, and Asian persons disproportionately. Further, they provide evidence of the disproportionate effect of COVID-19 on Pacific Islanders. A brief research report is published in Annals of Internal Medicine.

Researchers from Kaiser Permanente Southern California (KPSC) studied electronic health records from KPSC to compare age- and sex-adjusted relative risk (RR) of COVID-19 testing, cases, hospitalizations, and intensive-level care among Hispanic, Black or African American, Asian, and Pacific Islander populations versus White populations before and after adjusting for comorbidities and body weight status. The researchers observed disparities across race/ethnicity for all outcomes regardless of adjustment. Patients of color were slightly more likely to be tested than White patients but were substantially more likely to be hospitalized and to receive intensive-level care. Hispanic patients had the highest RRs of being tested and testing positive or being diagnosed with COVID-19 compared with White patients; however, Pacific Islander, Black or African American, and Asian patients had higher RRs for severe COVID-19 outcomes than White patients.

According to the authors, inequities in COVID-19 outcomes are a call to action for a culturally appropriate pandemic response and vaccination strategies that go beyond addressing comorbidities and account for factors like distrust in the medical system, resource constraints, language proficiency, and health literacy.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Claudia Nau, PhD, can be reached through Maureen McInaney at Maureen.McInaney@kp.org or Kerry Sinclair at KSinclair@webershandwick.com.

LOS ALAMOS, N.M., April 19, 2021 -- A recent series of experiments at the National High Magnetic Field Laboratory (National MagLab) at Los Alamos National Laboratory leveraged some of the nation's highest-powered nondestructive magnets to reveal an exotic new phase of matter at high magnetic fields. The experiments studied the unusual Kondo insulator ytterbium dodecaboride (or YbB12) and were the first results from the new 75-tesla duplex magnet housed at the National MagLab's Pulsed Field Facility at Los Alamos.

"This magnet and the resulting experiments are the first fruits of the National Science Foundation-supported pulsed magnet surge," said Michael Rabin, director of the Pulsed Field Facility at Los Alamos. "The surge is creating new science capabilities in the 75-85 tesla range -- leading eventually to an expanded portfolio of some of the most powerful nondestructive magnetic fields in the world."

Researchers from the University of Michigan, Kyoto University and Los Alamos conducted the research, published last week in Nature Physics.

In Kondo insulators, there is an unusual quantum-mechanical mixing of mobile electrons and magnetic atoms, making these materials attractive as model systems for basic science, electronic devices, and possibly quantum computing. Unlike simple metals and insulators, YbB12 exhibits properties of both -- its electrical resistance behaves like that of an insulator, but it also clearly shows quantum oscillations at high magnetic fields that are a fundamental metallic property.

"A plethora of theories has emerged to account for such behavior," said John Singleton, a fellow at the MagLab's Los Alamos campus and co-author on the paper. "Some physicists believe this is a condensed-matter incarnation of neutral Majorana fermions, entities normally explored in particle physics."

To test these theories, the research team wanted to observe how the neutral fermions that they found in YbB12 responded to extreme conditions. The high magnetic fields in the new 75-tesla duplex magnet available at the National MagLab's Pulsed Field Facility were used to suppress the insulating properties of YbB12 and measure quantum oscillations and various properties that are affected by the presence of the neutral fermions.

"The extra 10 tesla above our standard pulsed magnets provided by the duplex magnet enabled this new state of matter -- exotic fermions gradually being drowned in a sea of normal electrons -- to be tracked across a wide range of magnetic fields for the first time," said Singleton. This confirmed that the phenomena observed were definitely associated with the neutral fermions and provided a test of the various theoretical models.

The duplex magnet is a result of a Pulsed Field Facility "magnet surge" supported by the National Science Foundation. The purpose of the surge is to create new and expanded science capabilities in the 75-85 tesla range. The duplex magnet system is available to researchers from around the world to conduct their own experiments, and an 85-tesla duplex magnet and necessary supporting technology are under development.

These new pulsed magnets are powered solely by capacitor banks without relying on the Los Alamos generator that powers the much larger 100 tesla magnet. The generator is currently offline for repairs and maintenance, so magnets from the surge fill an important gap for condensed-matter physics in high magnetic fields.

The new magnets are called duplex magnets because they are made from two concentric electromagnet coils (solenoids) that are powered independently from separate capacitor-bank modules. When the generator is back online, technology developed by the pulsed magnet surge will be combined with Los Alamos' largest magnets to further expand the MagLab's science capabilities.

CORVALLIS, Ore. - Four decades after their capture more than a half-mile below the ocean's surface, three snailfish species have received their scientific names, two of them from school children on Guam in the island's native Chamorro language.

The rare specimens of liparids were collected in the early 1980s in traps set in the Mariana Archipelago in the western Pacific Ocean, deposited with NOAA's Pacific Islands Fisheries Science Center in Hawaii and did not get examined until recently, when they were noticed during the center's move to a new location.

Oregon State alumnus Bruce Mundy, retired from the National Marine Fisheries Service, learned of the liparid specimens from Robert Moffitt, the Pacific Islands Fisheries Science Center biologist who collected them.

Mundy and fellow OSU alum David Stein of the OSU College of Agricultural Sciences describe the new species, Paraliparis echongpachot, P. kadadakaleguak and P. marianae, in a paper published today in Ichthyological Research.

"David Stein came to Hawaii to assist with the description of another snailfish species from the depths of the Mariana Trench and visited PIFSC to examine the snailfish specimens," Mundy said. "That's when he found that three distinct, undescribed species were among them."

The specimens have been deposited in the Oregon State University Ichthyology Collection, curated by Brian Sidlauskas and Peter Konstantinidis in the Department of Fisheries, Wildlife, and Conservation Sciences. OSU was selected as the archive for the specimens because the Pacific Islands Fisheries Science Center does not maintain permanent biological collections.

Captured in traps as a byproduct of assessments of deepwater shrimp populations, the species are the first of the snailfish family to be described from the Mariana Islands bathyal zone - between 200 and 2,000 meters deep.

There are more than 400 species of snailfishes known from about 30 genera; they have tadpole-like bodies without scales and range from 2 inches to 30 inches in length.

Needing cool or cold water, snailfish are most abundant and diverse in temperate and polar areas; in the tropics and subtropics, suitable water temperatures occur only at bathyal depths or deeper.

"NOAA research vessels made ichthyological collections throughout the Mariana Islands in the 1980s," Mundy said. "A surprising number of snailfishes, unexamined until recently, were captured. Both collection and preservation have been hard on these soft-bodied, fragile fishes, but the condition of some of them remained good enough that description was possible. Among those are the three in this paper."

Students in Guam from elementary through high school age were invited to compete for the right to suggest names for the new species, and two of the student suggestions were chosen by Stein and Mundy. They named the third species, Paraliparis marianae, after the archipelago in which it was found.

Alyssa Roces from Okkodo High School suggested the name Paraliparis kadadakaleguak in recognition of the fish's short ribs; in Chamorro, kadada' kaleguak means short rib bone.

Aydan Charfauros of Tamuning Elementary came up with Paraliparis echongpachot, choosing echong pachot as the species name because that term means crooked mouth in Chamorro; the mouth is a key defining characteristic of this fish.

"Names for new species have traditionally been formed from Greek or Latin words, from the names of people who collected the specimens or from the names of other scientists to honor them," Mundy said. "This has resulted in Euro-American names for species worldwide, a practice that is regarded by some to be colonialist or imperialist. In recent years there has been a movement to form new names from the languages of indigenous people in the areas where new species are found, to reconnect taxonomy to them."

Stein, a globally recognized authority on snailfishes who has described more than 100 liparid species, says a goal when trying to invent a name is for it to be "euphonious."

"You want a name that sounds good, and I particularly enjoy kadadakaleguak," he said. "I just love it."

Stein notes that a gap of four decades between discovery and naming is not unusual.

"Several species have been named that were hundreds of years old," he said. "That's one of the reasons museums exist, and it's very important and largely unappreciated."

"New studies use old material all of the time, and not only for the identification of new species," Sidlauskas added. "People want DNA samples, stomach contents, parasites of fishes, measurements, photographs and skeletons. We're like a regional branch of a worldwide library of biodiversity, of scientific specimens. We send and receive specimens all the time."

Hand, Foot & Mouth Disease (HFMD) is a generally mild, contagious viral infection common in young children. In Singapore, HFMD is endemic and is most commonly caused by intestinal viruses known as coxsackieviruses and enteroviruses.

While most HFMD patients experience common symptoms such as sore throat, fever, ulcers inside the mouth and blisters and lesions on the palms and soles, infection with Enterovirus-A71 (EV-A71) may lead to serious neurological complications that can be potentially fatal or lead to long-term neurological deficits (cognitive and motor deficits). These complicated HFMD cases are mainly seen in young children.

Researchers from NUS Yong Loo Lin School of Medicine's Infectious Diseases Translational Research Programme have identified two new proteins that play a critical role in the ability of EV-A71 to invade the central nervous system. One of these proteins is a druggable target, which means that there are drugs available that target this protein and which could potentially be used to limit the neurological complications associated with this illness.

Since there are currently no antiviral treatments available for HFMD, only symptomatic relief is available to patients. This new discovery could allow for the development of more effective treatment of the disease, particularly for such severe cases. A number of compounds that have been developed to target this discovered protein have mainly been studied in the context of cancer. However, this finding is likely to change the course of the advancement of some of these compounds.

"This exciting finding will bring us one step closer to preventing EV-A71-infected HFMD patients from experiencing potential neurological complications. As this virus is considered to be endemic in Singapore, with cyclical epidemics every two to three years, our discovery is likely to have a significant impact on the country's public health," said Associate Professor Sylvie Alonso, Principal Investigator of the study and Co-Director of the Infectious Diseases TRP at NUS Medicine.

"The new data reported contributes to better understanding of the molecular mechanisms of EV-71 neuroinvasion that may lead to neurological complications of HFMD caused by EV-A71. This is a step towards identifying possible targets for interventions to reduce/prevent EV-A71 complications," shared Dr Chan Si Min, the Head and Senior Consultant of the Division of Paediatric Infectious Diseases at National University Hospital.

The Infectious Diseases TRP aims to provide a holistic, patient-centric approach to infectious diseases that are relevant to Singapore and the region. The Programme focuses on programmatic research areas including pathogen evolution and transmission, host-microbe interactions and vaccine and therapeutics development.

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.