Researchers at Karolinska Institutet in Sweden have developed a technology for cost-effective surveillance of the global spread of new SARS-CoV-2 variants. This could help low- and middle-income countries monitor variants in their own borders.
From the beginning of the pandemic, thousands of viral genomes have been sequenced in order to reconstruct the evolution and global spread of the coronavirus. Dependent on these is the identification of particularly concerning variants.
To achieve global surveillance of the SARS-CoV-2 genome, the sequencing and analysis of numerous samples cost-effectively is key. Therefore, researchers in the Bienko-Crosetto laboratory at Karolinska Institutet and Science for Life Laboratory (SciLifeLab) in Sweden have developed a new method, COVseq, that can be used for surveillance of the viral genome on a massive scale at a low cost.
Multiplex PCR (polymerase chain reaction) is used to make more copies of the virus. The samples are then labeled and pooled together in the same sequencing library, using a previous method developed in their laboratory and now adapted for SARS-CoV-2 analysis.
“By performing reactions in very small volumes and pooling together hundreds of samples into the same sequencing library, we can sequence potentially thousands of viral genomes per week at a cost of less than 15 dollars per sample,” said co-first author Ning Zhang, postdoctoral researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
Comparative analyses of 29 SARS-CoV-2 positive samples revealed that COVseq could detect small changes in the genome as well as standard methods. Analysing 245 additional samples, they showed that COVseq could also detect emerging variants of concern well. COVseq’s key advantage over existing methods is cost-effectiveness.
“Our inexpensive method could immediately be used for SARS-CoV-2 genomic surveillance by public health agencies and could also be easily adapted to other RNA viruses, such as influenza and dengue viruses,” said last author Nicola Crosetto, senior researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
Journal information: COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance. Nature Communications, 23 June 2021, DOI: 10.1038/s41467-021-24078-9
Researchers have discovered that failing to dispose of old photoreceptor cells leads to age-related macular degeneration.
The estimated number of people worldwide with age-related macular degeneration in 2020 was 196 million, increasing to 288 million in 2040. Though more than 50 genes are associated with the condition, the precise mechanism is unknown. Most people have a form of the condition, for which there are no known effective treatments.
In order to develop new therapies to treat the disease, University of Maryland School of Medicine (UMSOM) researchers are starting to understand what goes wrong in the disease. Using human and mice tissue, researchers showed that the process which removes the eye’s old, damaged light sensors is disrupted in macular degeneration.
Previously, the lead researcher had found out that many families with hearing disorders had genetic mutations in the gene for the CIB2 protein, and later work also showed that CIB2 was needed for vision in a large human family, as well as in zebrafish. Now, in this latest study, his team built on that previous work to dissect the intricate cell mechanisms behind retinal degeneration.
The team compared healthy mouse eyes to those from a mouse with the CIB2 protein genetically deleted. These CIB2 mutant mice were not disposing of their old light sensor proteins, called photoreceptors, like healthy mouse eyes did.
“Photoreceptors continue growing in tiny columns in the eye, but over time, light damages the photoreceptors. To combat this, support cells in the eye slowly munch on the old, damaged photoreceptors, keeping the columns the correct length,” explained first author Saumil Sethna, PhD, at the University of Maryland School of Medicine. “If the photoreceptors are not removed, or if the process is backed up due to slow digestion by the support cells, like in the CIB2 mutant mice, the undigested material builds up over time, which may contribute to blindness.”
The researchers then identified several components in this photoreceptor recycling process, including a group of proteins collectively called mTORC1, which is involved in many human diseases, including cancer, obesity, and epilepsy.
Since mTORC1 (part of a family called mTOR) is a decision-maker for many cellular functions including cleaning up cellular debris, the researchers examined mTORC1’s activity in the CIB2 mutant mice and saw that it was overactive. mTORC1 was also found to be overactive in eye tissue of people with a form of age-related macular degeneration. The findings therefore indicate that drugs against mTORC1 may be effective treatments for the most common type of age-related macular degeneration, according to the researcher. “Researchers have tested many small molecules directed at mTORC1 to treat various diseases, but the problem is that mTOR is needed for so many other cell functions that there are major side-effects when you tinker with it,” said senior author Zubair M Ahmed, PhD, Professor of Otorhinolaryngology-Head & Neck Surgery and Ophthalmology at the University of Maryland School of Medicine. “In our study, we found a backdoor way to regulate mTORC1, which may bypass many of the unpleasant side-effects that normally occur with suppressing mTORC1. We think we may be able to use our new knowledge of this mechanism to develop treatments for age-related macular degeneration and other diseases as well.”
Cannabis use among young adults was associated with increased risks of thoughts of suicide (suicidal ideation), suicide plan, and suicide attempt, according to a population analysis.
These associations remained regardless of whether someone was also experiencing depression, and the risks were greater for women than for men. The study was conducted by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.
“While we cannot establish that cannabis use caused the increased suicidality we observed in this study, these associations warrant further research, especially given the great burden of suicide on young adults,” said senior author NIDA Director Nora Volkow, MD. “As we better understand the relationship between cannabis use, depression, and suicidality, clinicians will be able to provide better guidance and care to patients.”
The number of cannabis-using adults in the US more than doubled from 22.6 million in 2008 to 45.0 million in 2019. Over the same period the number of adults with depression also increased, as did those reported suicidal ideation or who committed suicide. However the link between cannabis and suicidality is not well understood.
Setting out to address, NIDA researchers examined data from the 2008-2019 National Surveys on Drug Use and Health (NSDUH). NSDUH collects nationally representative data among the US civilian population age 12 or older on cannabis use and use disorder, depression, suicidality, and other behavioural health indicators. In addition to determining the associations between these factors, the researchers examined whether the associations varied by gender. They examined data from 281 650 young adults ages 18 to 35 years, the age range where most mood and substance use disorders emerge.
Four levels of past-year cannabis use were compared: no cannabis use; nondaily cannabis use; daily cannabis use (use on at least 300 days per year); and presence of cannabis use disorder, assessed on specific criteria for a pattern of continued cannabis misuse. The prevalence of major depressive episodes based on specific diagnostic criteria measured through the survey was used to measure depression. To identify suicidality trends, the tean separately assessed the trends in the prevalence of past-year suicidal ideation, plan, and attempt as reported in the 2008-2019 NSDUH surveys.
The study found that even nondaily cannabis users were more likely to have suicidal ideation and to plan or attempt suicide than complete non-users. These associations remained regardless of comorbid depression. In people without a major depressive episode, about 3% of those who did not use cannabis had suicidal ideation, compared with about 7% of those with nondaily cannabis use, about 9% of those with daily cannabis use, and 14% of those with a cannabis use disorder. In people with depression, 35% of non-users had suicidal ideation, compared to 44% of nondaily cannabis users, 53% of daily cannabis users, and 50% of those with cannabis use disorder. Similar trends existed for the associations between different levels of cannabis use and suicide plan or attempt.
Additionally, the researchers found that women with any cannabis use were more likely to have suicidal ideation or report a suicide plan or attempt than men with the same levels of cannabis use. For example, among individuals without major depressive episode, the prevalence of suicidal ideation for those with vs without a cannabis use disorder was 13.9% vs. 3.5% among women and 9.9% vs. 3.0% among men. In individuals with both cannabis use disorder and major depressive episode, the prevalence of past-year suicide plan was 52% higher for women (23.7%) than men (15.6%).
“Suicide is a leading cause of death among young adults in the United States, and the findings of this study offer important information that may help us reduce this risk,” explained lead author Beth Han, MD. PhD, MPH, from NIDA. “Depression and cannabis use disorder are treatable conditions, and cannabis use can be modified. Through better understanding the associations of different risk factors for suicidality, we hope to offer new targets for prevention and intervention in individuals that we know may be at high-risk. These findings also underscore the importance of tailoring interventions in a way that take sex and gender into account.”
Researchers have discovered that albumin (Alb), one of the most abundant proteins in the body, activates a proton channel (hHv1), also widespread in the body, giving sperm the ability to penetrate and fertilise an egg, and also allowing white blood cells to produce inflammatory mediators to fight infection.
The study explored the physiological connection between Alb and human voltage-gated proton channels (hHv1), which are both essential to cell biology in health and diseases. Researchers also demonstrated the mechanism by which Alb binds directly to hHv1 to activate the channel. This research explains how sperm are triggered to fertilise, and neutrophils are stimulated to release mediators in the innate immune response, describing a new role for Alb in physiology that will operate in the many tissues expressing hHv1.
“We found that the interaction of Alb and hHv1 activates sperm when they leave semen and enter the female reproductive tract because Alb is low in semen and high in the reproductive tract. We now understand why albumin supplementation improves IVF,” explained first author Ruiming Zhao, PhD, from the Department of Physiology & Biophysics at UCI School of Medicine. “We also found the same Alb/hHv1 interaction allows the white blood cells called neutrophils to produce and secrete the inflammatory mediators that kill bacteria and fight infection. However, it’s important to note that the inflammatory response itself can lead to disease.”
Alb’s stimulating role in the physiology of sperm and neutrophils via hHv1 pointed to its having other enhancing or deleterious roles in the other tissues, including the central nervous system, heart and lungs, and influencing cancers of the breast and gastrointestinal tract.
“It is exciting to discover that a common protein has the power to activate the proton channel. This finding suggests new strategies to block or enhance fertility, and to augment or suppress the innate immune response and inflammation,” said senior author Steve A. N. Goldstein, MD, PhD, vice chancellor of Health Affairs at UCI.
hHv1 is involved in many biological processes in addition to the capacitation of sperm and the innate immune responses included in the study. The channels have notable roles in proliferation of cancer cells, tissue damage during ischaemic stroke, and hypertensive kidney injury. Because Alb’s presence and involvement varies, the potentiation of hHv1 by Alb can be either beneficial or detrimental in different diseases or conditions.
“We have modeled the structural basis for binding of Alb to the channel that leads to activation and changes in cellular function, and we are now conducting in vivo studies of viral and bacterial infections. Our next steps include studies of the effects of inhibitors of the Alb-hHv1 interaction on infection, inflammation and fertility,” said Goldstein.
Journal information: Ruiming Zhao et al, Direct activation of the proton channel by albumin leads to human sperm capacitation and sustained release of inflammatory mediators by neutrophils, Nature Communications (2021). DOI: 10.1038/s41467-021-24145-1
Researchers have found that having no audience present made men run slower, but helped women run faster.
The new study by Martin Luther University Halle-Wittenberg (MLU) examined the effect of an audience on performance of athletes at the 2020 Biathlon World Cup. According to the new analysis, women also performed better in complex tasks, such as shooting, when an audience was present while men did not.
According to social facilitation theory, a person’s performance is impacted if other people watch them. Merely having an audience improves the performance of simple tasks, especially those requiring stamina: and it is surprisingly hard to circumvent. One study showed that ‘virtual’ bystanders did not have the same effect as having real bystanders in firefighter’s performance in training tasks.
“The studies have been relatively clear so far, but the results are more heterogeneous when it comes to more complex coordinative tasks,” explains Amelie Heinrich from the Institute of Sports Science at MLU. Generally the assumption is that performance tends to drop when an audience is present.
Heinrich is a sports psychology expert who coaches Germany’s junior biathlon squad, and took advantage of the unique conditions created by COVID. “The pandemic offers a unique opportunity to study an audience’s influence outside of experimental conditions in the real world,” said Heinrich, who compared the running times and shooting successes of male and female biathletes from the 2018/2019 season with their performances in the 2020 season in the sprint and mass start events.
“The men’s results were as expected: they ran faster with an audience present, but performed more poorly in shooting,” noted Heinrich. Cross-country skiing mainly requires stamina while shooting is a coordinative task.
“Interestingly, it was the other way around for women.” With spectators present they ran slower, but on average, it took them an entire second less to make their shot and, at least in the sprint, their scoring performance was five per cent higher. The researchers argue that it is not just due to fluctuation in the athletes’ performance; with 83 (sprint) and 34 (mass start) World Cup biathletes, the study has a good basis for evidence, and the same tendency was seen in both disciplines.
“To our knowledge, this is the first time that a study was able to show a different effect of the audience on men and women,” noted Professor Oliver Stoll, head of the sports psychology section at MLU. Most previous research focused on men. “Our study raises questions about the generalisability of the social facilitation theory and indicates there might be a previously unknown difference between men and women,” said Heinrich, adding that more research in sports with coordination and stamina is needed.
Thus far, the researchers can only speculate about the reasons for the possible gender-specific performance differences in response to audiences or the lack of. “It is possible that gender-specific stereotypes play a role,” said Heinrich. Men have a stereotype that they should be strong, while studies have shown that women are more sensitive to feedback. In any case, Heinrich concluded, this underscores the need to account for gender in studying psychological effects.
Journal information: Heinrich A. et al. Selection bias in social facilitation theory? Audience effects on elite biathletes’ performance are gender-specific. Psychology of Sports and Exercise (2021). Doi: 10.1016/j.psychsport.2021.101943
A new study for the first time provides quantitative evidence linking psychological stress to greying hair in people.
Greying of hair, a phenomenon still poorly understood in humans, first starts in white individuals at 34, while black individuals only start greying around 44. While it may seem intuitive that stress can accelerate greying, the researchers were surprised to discover that hair colour can actually be restored when stress is eliminated, a finding that contrasts with a recent study in mice that suggested that stressed-induced grey hairs are permanent.
The study holds clues to understanding ageing beyond just confirming the old tale about stress and ageing, said the study’s senior author Martin Picard, PhD, associate professor of behavioral medicine (in psychiatry and neurology) at Columbia University Vagelos College of Physicians and Surgeons.
“Understanding the mechanisms that allow ‘old’ grey hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human ageing in general and how it is influenced by stress,” Prof Picard said.
“Our data add to a growing body of evidence demonstrating that human ageing is not a linear, fixed biological process but may, at least in part, be halted or even temporarily reversed.”
Hair can help understand ageing
“Just as the rings in a tree trunk hold information about past decades in the life of a tree, our hair contains information about our biological history,” Picard said. “When hairs are still under the skin as follicles, they are subject to the influence of stress hormones and other things happening in our mind and body. Once hairs grow out of the scalp, they harden and permanently crystallise these exposures into a stable form.”
Though it has long been believed by people that psychological stress can increase grey hairs, it has remained a matter of scientific debate due to a lack of sensitive methods that can precisely correlate times of stress with hair pigmentation at a single-follicle level.
Splitting hairs to document hair pigmentation
Ayelet Rosenberg, first author on the study and a student in Picard’s laboratory, developed a new method for making high resolution images of tiny slices of human hairs to measure the extent of pigment loss — greying — in each of those slices. Each slice, about 1/20th of a millimetre wide, represents about an hour of hair growth.
“If you use your eyes to look at a hair, it will seem like it’s the same color throughout unless there is a major transition,” Picard says. “Under a high-resolution scanner, you see small, subtle variations in color, and that’s what we’re measuring.”
For the study 14 volunteers were asked to review their calendars and rate each week’s level of stress in a stress diary. Analysing individual hair samples, the researchers compared the results with each volunteer’s stress diary.
Right away, it was noticed that some grey hairs naturally regain their original color, which had never been quantitatively documented, Picard said.
When hairs were aligned with stress diaries, it revealed striking associations between stress and hair greying and, in some cases, a reversal of greying with the lifting of stress.
“There was one individual who went on vacation, and five hairs on that person’s head reverted back to dark during the vacation, synchronized in time,” Picard said.
Blame the mind-mitochondria connection
Measuring levels of different proteins in the hairs and how protein levels changed over the length of each hair, the researchers came up with a model showing that mitochondria were responsible for greying.
“We often hear that the mitochondria are the powerhouses of the cell, but that’s not the only role they play,” Picard said. “Mitochondria are actually like little antennas inside the cell that respond to a number of different signals, including psychological stress.”
The mitochondria connection between stress and hair colour is a different mechanism than found in a recent study of mice, where stress-induced greying was caused by an irreversible loss of stem cells in the hair follicle.
“Our data show that greying is reversible in people, which implicates a different mechanism,” said co-author Ralf Paus, PhD, professor of dermatology at the University of Miami Miller School of Medicine. “Mice have very different hair follicle biology, and this may be an instance where findings in mice don’t translate well to people.”
Hair re-pigmentation possible only for some
Stress reduction is a good idea, but it won’t necessarily get rid of your grey hairs.
“Based on our mathematical modeling, we think hair needs to reach a threshold before it turns grey,” Picard said. “In middle age, when the hair is near that threshold because of biological age and other factors, stress will push it over the threshold and it transitions to grey.
“But we don’t think that reducing stress in a 70-year-old who’s been grey for years will darken their hair or increasing stress in a 10-year-old will be enough to tip their hair over the grey threshold.”
Journal information: Ayelet M. Rosenberg et al, Quantitative mapping of human hair greying and reversal in relation to life stress, eLife (2021). DOI: 10.7554/eLife.67437
