. Scientific Frontline

Thursday, November 24, 2022

SARS-CoV-2 detection in 30 minutes using gene scissors

Multiplex chip of a Freiburg research team: On this chip, the viral load in the nasal swab and, if necessary, the antibiotic concentration in the blood of COVID-19 patients could be measured simultaneously.
Photo Credit: AG Disposable Microsystems/University of Freiburg

Researchers of the University of Freiburg introduce biosensor for the nucleic acid amplification-free detection of SARS-CoV-2 RNA

CRISPR-Cas is versatile: Besides the controversial genetically modified organisms (GMOs), created through gene editing, various new scientific studies use different orthologues of the effector protein ‘Cas’ to detect nucleic acids such as DNA or RNA.

In its most recent study, the research group headed by microsystems engineer Dr. Can Dincer of the Department of Microsystems2 Engineering, University of Freiburg introduces a microfluidic multiplexed chip for the simultaneous measurement of the viral load in nasal swabs and (if applicable) the blood antibiotic levels of COVID-19 patients.

Rapid test or PCR?

The market launch of rapid antigen test kits has significantly changed the way in which society handles the effects of the pandemic: Individuals suspecting an infection with SARS-CoV-2 can now test themselves at home with kits that are readily available at most drug stores, pharmacies and supermarkets, instead of making an, oftentimes difficult to acquire, appointment for PCR testing, that requires 1 to 3 additional days to receive the result. This convenience is, however, paid for with test sensitivity. This issue became flagrantly apparent during the wave of infections last winter, when the ‘lateral flow devices’ frequently failed to detect infections with the Omicron-variant until after the onset of symptoms. “The trade-off between sensitivity and sample-to-result time could potentially be bridged using our method,” says Midori Johnston, first author of the study, that is now being published in the journal Materials Today.

Wednesday, November 23, 2022

Pocket feature shared by deadly coronaviruses could lead to pan-coronavirus antiviral treatment

Spike glycoprotein structure of SARS-CoV, the coronavirus causing the 2002 outbreak. When linoleic acid is bound, the structure is locked in a non-infectious form. The cryo-EM density, calculated by cloud computing, is shown (left) along with the protein structure (middle). Linoleic acid molecules are colored orange. A zoom-in of the pocket (boxed), conserved in all deadly coronaviruses, is shown
 Illustration Credit: Christiane Schaffitzel and Christine Toelzer, University of Bristol

Scientists have discovered why some coronaviruses are more likely to cause severe disease, which has remained a mystery, until now. Researchers of the University of Bristol-led study, published in Science Advances today [23 November], say their findings could lead to the development of a pan-coronavirus treatment to defeat all coronaviruses—from the 2002 SARS-CoV outbreak to Omicron, the current variant of SARS-CoV-2, as well as dangerous variants that may emerge in future.

In this new study, an international team, led by Bristol's Professor Christiane Schaffitzel, scrutinized the spike glycoproteins decorating all coronaviruses. They reveal that a tailor-made pocket feature in the SARS-CoV-2 spike protein, first discovered in 2020, is present in all deadly coronaviruses, including MERS and Omicron. In striking contrast, the pocket feature is not present in coronaviruses which cause mild infection with cold-like symptoms.

The team say their findings suggest that the pocket, which binds a small molecule, linoleic acid—an essential fatty acid indispensable for many cellular functions including inflammation and maintaining cell membranes in the lungs so that we can breathe properly—could now be exploited to treat all deadly coronaviruses, at the same time rendering them vulnerable to a linoleic acid-based treatment targeting this pocket.

Spin correlation between paired electrons demonstrated

Electrons leave a superconductor only as pairs with opposite spins. If both electron paths are blocked for the same type of spin by parallel spin filters, paired electrons from the superconductor are blocked and the currents decrease.
Image Credit: University of Basel, Department of Physics/Scixel

Physicists at the University of Basel have experimentally demonstrated for the first time that there is a negative correlation between the two spins of an entangled pair of electrons from a superconductor. For their study, the researchers used spin filters made of nanomagnets and quantum dots, as they report in the scientific journal Nature.

The entanglement between two particles is among those phenomena in quantum physics that are hard to reconcile with everyday experiences. If entangled, certain properties of the two particles are closely linked, even when far apart. Albert Einstein described entanglement as a “spooky action at a distance”. Research on entanglement between light particles (photons) was awarded this year's Nobel Prize in Physics.

Two electrons can be entangled as well – for example in their spins. In a superconductor, the electrons form so-called Cooper pairs responsible for the lossless electrical currents and in which the individual spins are entangled.

For several years, researchers at the Swiss Nanoscience Institute and the Department of Physics at the University of Basel have been able to extract electron pairs from a superconductor and spatially separate the two electrons. This is achieved by means of two quantum dots – nanoelectronic structures connected in parallel, each of which only allows single electrons to pass.

A Radical New Approach in Synthetic Chemistry

The Laser Electron Accelerator Facility (LEAF) generates intense high-energy electron pulses that allow scientists to add or subtract electrons from molecules to make chemically reactive species and monitor what happens as a reaction proceeds.
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Photo Credit: Courtesy of Brookhaven National Laboratory

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory helped measure how unpaired electrons in atoms at one end of a molecule can drive chemical reactivity on the molecule’s opposite side. As described in a paper recently published in the Journal of the American Chemical Society, this work, done in collaboration with Princeton University, shows how molecules containing these so-called free radicals could be used in a whole new class of reactions.

“Most reactions involving free radicals take place at the site of the unpaired electron,” explained Brookhaven Lab chemist Matthew Bird, one of the co-corresponding authors on the paper. The Princeton team had become experts in using free radicals for a range of synthetic applications, such as polymer upcycling. But they’ve wondered whether free radicals might influence reactivity on other parts of the molecule as well, by pulling electrons away from those more distant locations.

“Our measurements show that these radicals can exert powerful ‘electron-withdrawing’ effects that make other parts of the molecule more reactive,” Bird said.

The Princeton team demonstrated how that long-distance pull can overcome energy barriers and bring together otherwise unreactive molecules, potentially leading to a new approach to organic molecule synthesis.

Genome studies uncover a new branch in fungal evolution

In a class of their own: The earth tongue is one of 600 “oddball” fungi that were found to share a common ancestor dating back 300 million years, according to U of A researchers.
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Photo Credit: Alan Rockefeller, CC-BY-SA-4.0

About 600 seemingly disparate fungi that never quite found a fit along the fungal family tree have been shown to have a common ancestor, according to a University of Alberta-led research team that used genome sequencing to give these peculiar creatures their own classification home.

“They don't have any particular feature that you can see with the naked eye where you can say they belong to the same group. But when you go to the genome, suddenly this emerges,” says Toby Spribille, principal investigator on the project and associate professor in the Department of Biological Sciences.

“I like to think of these as the platypus and echidna of the fungal world.”

Spribille, Canada Research Chair in Symbiosis, is referring to Australia’s famed Linnaean classification system-defying monotremes — which produce milk and have nipples, but lay eggs — that were the source of debate as to whether they were even real.

Major discovery about mammalian brains surprises researchers

Illustration shows vacuolar-type adenosine triphosphatases (V-ATPases, large blue structures) on a synaptic vesicle from a nerve cell in the mammalian brain.
Illustration Image: C. Kutzner, H. Grubmüller and R. Jahn/Max Planck Institute for Multidisciplinary Sciences.

Major discovery about mammalian brains surprises researchers, University of Copenhagen researchers have made an incredible discovery. Namely, a vital enzyme that enables brain signals is switching on/off at random, even taking hours-long “breaks from work”. These findings may have a major impact on our understanding of the brain and the development of pharmaceuticals. 

Millions of neurons are constantly messaging each other to shape thoughts and memories and let us move our bodies at will. When two neurons meet to exchange a message, neurotransmitters are transported from one neuron to another with the aid of a unique enzyme.

This process is crucial for neuronal communication and the survival of all complex organisms. Until now, researchers worldwide thought that these enzymes were active at all times to convey essential signals continuously. But this is far from the case.

Using a groundbreaking method, researchers from the University of Copenhagen’s Department of Chemistry have closely studied the enzyme and discovered that its activity is switching on and off at random intervals, which contradicts our previous understanding.

Machine learning gives nuanced view of Alzheimer’s stages


A Cornell-led collaboration used machine learning to pinpoint the most accurate means, and timelines, for anticipating the advancement of Alzheimer’s disease in people who are either cognitively normal or experiencing mild cognitive impairment.

The modeling showed that predicting the future decline into dementia for individuals with mild cognitive impairment is easier and more accurate than it is for cognitively normal, or asymptomatic, individuals. At the same time, the researchers found that the predictions for cognitively normal subjects are less accurate for longer time horizons, but for individuals with mild cognitive impairment, the opposite is true.

The modeling also demonstrated that magnetic resonance imaging (MRI) is a useful prognostic tool for people in both stages, whereas tools that track molecular biomarkers, such as positron emission tomography (PET) scans, are more useful for people experiencing mild cognitive impairment.

The team’s paper, “Machine Learning Based Multi-Modal Prediction of Future Decline Toward Alzheimer’s Disease: An Empirical Study,” published in PLOS ONE. The lead author is Batuhan Karaman, a doctoral student in the field of electrical and computer engineering.

Vitamin D fails to reduce statin-associated muscle pain

Study is the first placebo-controlled, randomized clinical trial to study this
Photo Credit: PublicDomainPictures

Patients who take statins to lower high cholesterol levels often complain of muscle pains, which can lead them to stop taking the highly effective medication and put them at greater risk of heart attack or stroke.

Some clinicians have recommended vitamin D supplements to ease the muscle aches of patients taking a statin, but a new study from scientists at Northwestern University, Harvard University and Stanford University shows the vitamin appears to have no substantial impact.

The study was published Nov. 23 in JAMA Cardiology.

Although non-randomized studies have reported vitamin D to be an effective treatment for statin-associated muscle symptoms, the new study, which is the first randomized clinical trial to look at the effect of vitamin D on statin-associated muscle symptoms, was large enough to rule out any important benefits.

In the randomized, double-blind trial, 2,083 participants ingested either 2,000 units of vitamin D supplements daily or a placebo. The study found participants in both categories were equally likely to develop muscle symptoms and discontinue statin therapy.

Human evolution wasn’t just the sheet music, but how it was played

The fluorescent glow of mouse brain cells on the right indicates the effectiveness of a human-derived gene enhancer, HAQER0059, versus a 6-million-year-old version of the enhancer at left.
Image Credit: Riley Mangan, Duke University

A team of Duke researchers has identified a group of human DNA sequences driving changes in brain development, digestion and immunity that seem to have evolved rapidly after our family line split from that of the chimpanzees, but before we split with the Neanderthals.

Our brains are bigger, and our guts are shorter than our ape peers.

“A lot of the traits that we think of as uniquely human, and human-specific, probably appear during that time period,” in the 7.5 million years since the split with the common ancestor we share with the chimpanzee, said Craig Lowe, Ph.D., an assistant professor of molecular genetics and microbiology in the Duke School of Medicine.

Specifically, the DNA sequences in question, which the researchers have dubbed Human Ancestor Quickly Evolved Regions (HAQERS), pronounced like hackers, regulate genes. They are the switches that tell nearby genes when to turn on and off. The findings appear Nov.23 in the journal Cell.

The rapid evolution of these regions of the genome seems to have served as a fine-tuning of regulatory control, Lowe said. More switches were added to the human operating system as sequences developed into regulatory regions, and they were more finely tuned to adapt to environmental or developmental cues. By and large, those changes were advantageous to our species.

Physicist Errando helps NASA solve black hole jet mystery

Illustration Credit: NASA courtesy of IXPE team

Some of the brightest objects in the sky are called blazars. They consist of a supermassive black hole feeding off material swirling around it in a disk, which can create two powerful jets perpendicular to the disk on each side. A blazar is especially bright because one of its powerful jets of high-speed particles points straight at Earth. For decades, scientists have wondered: How do particles in these jets get accelerated to such high energies?

NASA’s Imaging X-Ray Polarimetry Explorer, or IXPE, has helped astronomers get closer to an answer. In a new study in the journal Nature, authored by a large international collaboration, astronomers find that the best explanation for the particle acceleration is a shock wave within the jet.

Manel Errando, an assistant professor of physics in Arts & Sciences at Washington University in St. Louis, and a faculty fellow of the McDonnell Center for the Space Sciences, is part of the team that analyzed the IXPE data.

Young lives under pressure as global crises hits mental health and well-being

Photo Credit: Marco Torrazzina

The well-being and mental health of young people in low - and middle - income countries have been dramatically affected by the series of crises hitting the world.

As the international community continues to struggle with the impact of COVID-19, conflict and climate change, the latest report from the Young Lives project shows a long-running upward trend in young people’s well-being has been sharply reversed alongside widespread anxiety and depression. Young people are less confident about their futures for the first time in their 20-year study.

Before the pandemic, there had been a steady but notable upward trend in young people’s sense of well-being across all four countries in the Young Lives study - Peru, Vietnam, India and Ethiopia. But new data from the most recent survey, collected during the pandemic, shows young people reported a significant decline in well-being - and high levels of anxiety and depression.

New data shows young people reported a significant decline in well-being - and high levels of anxiety and depression...at a critical period in [young] lives - because long-term mental health issues often begin in adolescence and early adulthood

New study on morphine treatment in people with COPD and severe, long-term breathlessness

Magnus Ekström, researcher at Lund University and Chief Physician in Pulmonary Medicine at Blekinge Hospital in Karlskrona
Photo Credit: Curtsey of Lund University

Sometimes healthcare professionals treat patients with opioids such as morphine to relieve symptoms, but there has been a lack of evidence as to whether this helps with severe chronic breathlessness. A randomized Phase 3 study conducted by Swedish and Australian researchers now finds that morphine does not reduce worst breathlessness.

The study is published in JAMA.

Long term shortness of breath is a common cause of ongoing suffering that often occurs with advanced serious illness and at the end of life. COPD can cause breathlessness by damaging the lungs and airways and for seriously ill people with severe long-term breathlessness, physical activity is often a challenge.

"Many people live with shortness of breath. It is distressing that no better treatment exists, but based on the results we’ve seen, we cannot generally recommend giving morphine to people with chronic breathlessness", says Magnus Ekström, a researcher in Palliative Medicine and Pulmonary Medicine at Lund University in Sweden and Chief Physician in Pulmonary Medicine at Blekinge Hospital.

World’s oldest meal offers food for thought

Professor Jochen Brocks (left) and Dr Ilya Bobrovskiy
Photo Credit: ANU

The contents of the last meal consumed by the earliest animals known to inhabit Earth more than 550 million years ago has unearthed new clues about the physiology of our earliest animal ancestors, according to scientists from The Australian National University (ANU).

Ediacara biota are the world's oldest large organisms and were first discovered in the Ediacara Hills in South Australia's Flinders Ranges. They date back 575 million years.

ANU researchers found the animals ate bacteria and algae that was sourced from the ocean floor. The findings, published in Current Biology, reveal more about these strange creatures, including how they were able to consume and digest food.

The scientists analyzed ancient fossils containing preserved phytosterol molecules -- a type of fat found in plants -- that remained from the animals' last meal. By examining the molecular remains of what the animals ate, the researchers were able to confirm the slug-like organism, known as Kimberella, had a mouth and a gut and digested food the same way modern animals do. The researchers say it was likely one of the most advanced creatures of the Ediacarans.

Most young people’s well-being falls sharply in first years of secondary school


Most young people in the UK experience a sharp decline in their subjective well-being during their first years at secondary school, regardless of their circumstances or background, new research shows.

Academics from the Universities of Cambridge and Manchester analyzed the well-being and self-esteem of more than 11,000 young people from across the UK, using data collected when they were 11, and again when they were 14.

The adolescents’ overall ‘subjective well-being’ – their satisfaction with different aspects of life (such as friends, school and family) – dropped significantly during the intervening years.

It is widely accepted that young people’s well-being and mental health are influenced by factors such as economic circumstances and family life. The research shows that notwithstanding this, well-being tends to fall steeply and across the board during early adolescence.

That decline is probably linked to the transition to secondary school at age 11. The study identified that the particular aspects of well-being which changed in early adolescence were typically related to school and peer relationships, suggesting a close connection with shifts in these young people’s academic and social lives.

New Omicron subvariant BQ.1.1 resistant to all therapeutic antibodies

The Omicron subvariants BA.1, BA.4, BA.5 as well as Q.1.1 have a high number of mutations in the spike protein. Some of these mutations are escape mutations that allow the virus to escape neutralization by antibodies. In addition, resistance to biotechnologically produced antibodies, which are administered to high-risk patients as a preventive measure or as therapy for a diagnosed SARS-CoV-2 infection, is also developing. Omicron sub-lineage BQ.1.1 is the first variant resistant to all antibody therapies currently approved by the EMA (European Medicines Agency) and/or FDA (US Food and Drug Administration).
Figure Credit: Markus Hoffmann, German Primate Center – Leibniz Institute for Primate Research.

Are the currently approved antibody therapies used to treat individuals at increased risk for severe COVID-19 disease also effective against currently circulating viral variants? A recent study by researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research and Friedrich-Alexander University Erlangen-Nürnberg shows that the Omicron sub-lineage BQ.1.1, currently on the rise worldwide, is resistant to all approved antibody therapies. published in the journal Lancet Infectious Diseases.

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