. Scientific Frontline

Friday, December 9, 2022

Prostate cancer risk prediction algorithm could help target testing at men at greatest risk

Prostate cancer is the most common type of cancer in men
Photo Credit: Shawnee D

Cambridge scientists have created a comprehensive tool for predicting an individual’s risk of developing prostate cancer, which they say could help ensure that those men at greatest risk will receive the appropriate testing while reducing unnecessary – and potentially invasive – testing for those at very low risk.

CanRisk-Prostate, developed by researchers at the University of Cambridge and The Institute of Cancer Research, London, will be incorporated into the group’s CanRisk web tool, which has now recorded almost 1.2 million risk predictions. The free tool is already used by healthcare professionals worldwide to help predict the risk of developing breast and ovarian cancers.

Prostate cancer is the most common type of cancer in men. According to Cancer Research UK, over 52,000 men are diagnosed with the disease each year and there are more than 12,000 deaths. Over three-quarters (78%) of men diagnosed with prostate cancer survive for over ten years, but this proportion has barely changed over the past decade in the UK.

Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. According to the NHS website, around three in four men with a raised PSA level will not have cancer. Further tests, such as tissue biopsies or MRI scans, are therefore required to confirm a diagnosis.

Aging is driven by unbalanced genes


Northwestern University researchers have discovered a previously unknown mechanism that drives aging.

In a new study, researchers used artificial intelligence to analyze data from a wide variety of tissues, collected from humans, mice, rats and killifish. They discovered that the length of genes can explain most molecular-level changes that occur during aging.

All cells must balance the activity of long and short genes. The researchers found that longer genes are linked to longer lifespans, and shorter genes are linked to shorter lifespans. They also found that aging genes change their activity according to length. More specifically, aging is accompanied by a shift in activity toward short genes. This causes the gene activity in cells to become unbalanced.

Surprisingly, this finding was near universal. The researchers uncovered this pattern across several animals, including humans, and across many tissues (blood, muscle, bone and organs, including liver, heart, intestines, brain and lungs) analyzed in the study.

The new finding potentially could lead to interventions designed to slow the pace of — or even reverse — aging.

How a viral toxin may exacerbate severe COVID-19

In a new study, University of California, Berkeley, researchers find that portions of the SARS-CoV-2 “spike” protein, shown in the foreground, can damage the cell barriers that line the inside of blood vessels, contributing to some of COVID-19’s most dangerous symptoms, including acute respiratory distress syndrome (ARDS).
Image Credit: National Institutes of Health

In a new study, University of California, Berkeley, researchers find that portions of the SARS-CoV-2 “spike” protein, shown in the foreground, can damage the cell barriers that line the inside of blood vessels, contributing to some of COVID-19’s most dangerous symptoms, including acute respiratory distress syndrome (ARDS). (National Institutes of Health photo via Flickr)

A study published today in the journal Nature Communications reveals how a viral toxin produced by the SARS-CoV-2 virus may contribute to severe COVID-19 infections.

The study shows how a portion of the SARS-CoV-2 “spike” protein can damage cell barriers that line the inside of blood vessels within organs of the body, such as the lungs, contributing to what is known as vascular leak. Blocking the activity of this protein may help prevent some of COVID-19’s deadliest symptoms, including pulmonary edema, which contributes to acute respiratory distress syndrome (ARDS).

“In theory, by specifically targeting this pathway, we could block pathogenesis that leads to vascular disorder and acute respiratory distress syndrome without needing to target the virus itself,” said study lead author Scott Biering, a postdoctoral scholar at the University of California, Berkeley. “In light of all the different variants that are emerging and the difficulty in preventing infection from each one individually, it might be beneficial to focus on these triggers of pathogenesis in addition to blocking infection altogether.”

Smilodon's saber teeth

Life-size reconstruction of three different species studied with their stress thermal maps at the three different angles for a right lower canine bite. The colder colors on the thermal maps of saber-toothed species indicate lower stress and higher force, especially when biting at larger angles.
Illustration Credit: Massimo Molinero

A team of researchers led by Narimane Chatar, doctoral student at EDDyLab at the University of Liège, tested the bite effectiveness of the Smilodon, an extinct species of carnivore close to current felines. Thanks to high precision 3D scans and simulation methods, the team has just revealed how these animals managed to bite despite the impressive length of their teeth. This study is the subject of a publication in the journal Proceedings of the Royal Society B

ancient carnivorous mammals have developed a wide range of skulls and teeth throughout their evolution. However, few of these developments have yet equaled those of the felidated saber-toothed emblematic Smilodon. Other groups of mammals, such as the now extinct nimravids, have also evolved into a similar morphology, with species with saber teeth but also much shorter canines, similar to those of lions, tigers, caracals, domestic cats, etc. that we know today. This phenomenon of the appearance of similar morphologies in different groups of organisms is known as convergent evolution; felines and nimravids being an astonishing example of convergence. As there are no modern animal equivalents with such saber-shaped teeth, the hunting method. Smilodon and other similar species remained obscure and the subject of heated debate. It was initially suggested that all saber-toothed species hunted in the same way, regardless of the length of their canines, a hypothesis which is today controversial. From then on, the question remained suspended ... How did this variety of "saber-toothed cats" hunt?

SARS-CoV-2 protein caught severing critical immunity pathway

This image shows the SARS-CoV-2 virus's main protease, Mpro, and two strands of a human protein, called NEMO. One NEMO strand (blue) has been cut by Mpro, and the other NEMO strand (red) is in the process of being cut by Mpro. Without NEMO, an immune system is slower to respond to increasing viral loads or new infections. Seeing how Mpro attacks NEMO at the molecular level could inspire new therapeutic approaches. 
Illustration Credit: Greg Stewart/SLAC National Accelerator Laboratory

Over the past two years, scientists have studied the SARS-CoV-2 virus in great detail, laying the foundation for developing COVID-19 vaccines and antiviral treatments. Now, for the first time, scientists at the Department of Energy’s SLAC National Accelerator Laboratory have seen one of the virus’s most critical interactions, which could help researchers develop more precise treatments.

The team caught the moment when a virus protein, called Mpro, cuts a protective protein, known as NEMO, in an infected person. Without NEMO, an immune system is slower to respond to increasing viral loads or new infections. Seeing how Mpro attacks NEMO at the molecular level could inspire new therapeutic approaches.

To see how Mpro cuts NEMO, researchers funneled powerful X-rays from SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) onto crystallized samples of the protein complex. The X-rays struck the protein samples, revealing what Mpro looks like when it dismantles NEMO’s primary function of helping our immune system communicate.

New findings on how to avert excessive weight loss from COVID-19

Professor Yihai Cao.
Photo Credit: Dr. Muyi Yang.

Losing too much weight when infected with COVID-19 has been linked to worse outcomes. Now, researchers at Karolinska Institutet have discovered that SARS-CoV-2 infection fuels blood vessel formation in fat tissues, thus revving up the body’s thermogenic metabolism. Blocking this process by using an existing drug curbed weight loss in mice and hamsters that were infected with the virus, according to the study published in the journal Nature Metabolism.

“Our study proposes a completely new concept for treating COVID-19 associated weight loss by targeting the blood vessels in the fat tissues,” says Yihai Cao, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and the study’s corresponding author.

The researchers examined how different types of fat, including brown fat and visceral and subcutaneous white fat, reacted when exposed to SARS-CoV-2 and how it impacted weight in mice and hamsters. They found that the animals lost significant amounts of weight in four days and that this weight loss was preceded by the activation of brown fat and the browning of both types of white fat. These fat tissues also contained more microvessels and high levels of a signaling protein called vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels.

Neural Network Learned to Create a Molecular Dynamics Model of Liquid Gallium

The melt viscosity determines the choice of casting mode, ingot formation conditions and other parameters.
Photo Credit: Ilya Safarov

Scientists at the Institute of Metallurgy, Ural Branch of the Russian Academy of Sciences, and Ural Federal University have developed a method for theoretically high-precision determination of the viscosity of liquid metals using a trained artificial neural network. The method was successfully tested in the process of building the deep learning potential of the neural network on the example of liquid gallium. Scientists were able to significantly increase the spatiotemporal scale of the simulation. The results of molecular dynamics modeling of liquid gallium are particularly accurate. Previous calculations were notoriously inaccurate, especially in the low temperature range. An article describing the research was published in the journal Computational Materials Science.

"First, liquids are in principle difficult to be described theoretically. The reason, in our opinion, lies in the absence of a simple initial approximation for this class of systems (for example, the initial approximation for gases is the ideal gas model). Secondly, the atomistic calculation of viscosity requires processing of a large volume of statistical data and, at the same time, a large accuracy of description of the potential energy surface and forces acting on atoms. Direct calculations cannot achieve such an effect. Thirdly, gallium in the liquid state is difficult to describe theoretically, because, due to certain features, its structure differs from that of most other metals," explains Vladimir Filippov, Senior Researcher at the Department of Rare Metals and Nanomaterials at UrFU, research participant and co-author of the article.

Very fast, but not a supersonic

The computer model of the dinosaur tail used and a diplodocide
Image Credit: Simone Conti / Zachi Evenor

An international research team with the participation of the Department of Biology at the University of Hamburg has analyzed the mobility of dinosaur tails using computer models and methods from engineering. According to a study published in Scientific Reports, the researchers found that these tails could be moved more than 100 kilometers per hour. Unlike previously assumed, however, they did not reach supersonic speed.

Diplodocids were large herbivorous dinosaurs with long necks and long tails. In a previous study, it was believed that a hypothetical structure at the end of a diplodocid's tail, similar to the end of a whip, could move faster than the speed of sound (340 meters per second) and produce a supersonic bang.

To test this hypothesis, the international research team simulated the movements of the tail of diplodocids using a model based on five fossil diplodocid skeletons. The virtual tail model is over 12 meters long, would weigh 1,446 kilograms in real terms and consists of 82 cylinders, which are supposed to represent vertebrae and are attached to an immovable, virtual basin.

“Research was quite a challenge, because we had to tackle the problem with two methods, that are normally used in aerospace technology: multi-body simulation and the estimation of the resilience of the materials”, reports the first author of the study, Simone Conti from the Universidade NOVA de Lisboa and the Politecnico di Milano.

Corona vaccination also protects people infected with HIV

They represent the study team: Clara Bessen, Carlos Plaza Sirvent, Adriane Skaletz-Rorowski, Anja Potthoff and Agit Simsek (from left).
Photo Credit: RUB, Marquard

A study shows that booster vaccination is particularly useful.

HIV-infected people who receive antiretroviral therapy form antibodies against Sars-Cov-2 after the Corona vaccination with mRNA vaccines. However, your immune response to vaccination is less strong than that of healthy people. The difference is reduced by a third vaccination. These results were achieved by a study with a total of 91 participants, which was carried out by a research team led by Prof. Dr. Ingo Schmitz, head of the Molecular Immunology Department at the Ruhr University in Bochum. The researchers report in the journal Frontiers in Immunology.

Vaccination protection for acquired immunodeficiency

Studies have shown that Sars-Cov-2 vaccines protect otherwise healthy people well against a severe course of Covid-19. It has so far been unclear whether this will also be the case for people with acquired immune deficiency. The research team led by Ingo Schmitz and Dr. Anja Potthoff from the Walk in Ruhr (WIR) Center for Sexual Health and Medicine at the RUB University Hospital included 71 people in her study who are HIV positive and receive antiretroviral therapy. 20 HIV-negative control persons also participated. After the first, second and third vaccinations with the mRNA vaccine from Biontech / Pfizer, they examined the immune response of the participants.

Thursday, December 8, 2022

Intricate ‘snowflakes’ created in liquid metal

A snowflake-like zinc crystal synthesized in liquid gallium by researchers at UNSW Sydney.
Image Credit: Dr Jianbo Tang

Researchers, including those from UNSW Sydney, have synthesized complex symmetrical zinc crystals in liquid gallium which can potentially be used in a range of catalysis applications.

It’s beginning to look a lot like Christmas at UNSW Sydney’s School of Chemical Engineering where researchers have grown crystals made of zinc that look like snowflakes - inside a liquid metal.

The team predominantly used zinc metal dissolved in liquid gallium as the solvent, creating distinctive structures that often resembled those of six-branched snowflake crystals.

Apart from their structural beauty, these liquid metal-grown crystals can enable future processes for making catalytic materials for producing hydrogen from organic fuels. The metallic crystals can also be specially formulated, during their synthesis and extraction, to make semiconductors for electronic and optical devices of computers, mobile phones and solar cells of the future.

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