Common medications accumulate in gut bacteria, which may reduce drug effectiveness and alter the gut microbiome

Common medications can accumulate in gut bacteria, a new study has found, altering bacterial function and potentially reducing the effectiveness of the drug. These interactions—seen for a variety of medications, such as depression, diabetes, and asthma drugs—could help researchers to better understand individual differences in drug effectiveness and side-effects, according to the study published in Nature.

It is known that bacteria can chemically modify some drugs, a process known as biotransformation. This study is the first to show that certain species of gut bacteria accumulate human drugs.

This could change the effectiveness of the drug both directly, as the accumulation could reduce the availability of the drug to the body, and indirectly, as altered bacterial function and composition could be linked to side-effects.

The human gut naturally contains communities of hundreds of different species of bacteria, which are important in health and disease, called the gut microbiome. The composition of bacterial species varies significantly between people and has previously been shown to be associated with a wide range of conditions including obesity, immune response, and mental health.

In this study, the researchers grew 25 common gut bacteria and studied how they interacted with 15 drugs that are taken orally. The drugs were chosen to represent a range of different types of common drugs, including antidepressant medications, which are known to affect individuals dissimilarly and cause side effects such as gut problems and weight gain.

The researchers tested how each of the 15 drugs interacted with the selected bacterial strains—a total of 375 bacteria-drug tests.

They found 70 interactions between the bacteria and the drugs studied—of which 29 had not been previously reported.

While earlier research has shown bacteria can chemically modify drugs, when the scientists studied these interactions further, they found that for 17 of the 29 new interactions, the drug accumulated within the bacteria without being modified.

 Bioaccumulation of therapeutic drugs by human gut bacteria, Nature (2021). DOI: 10.1038/s41586-021-03891-8 , www.nature.com/articles/s41586-021-03891-8

https://medicalxpress.com/news/2021-09-common-medications-accumulat...

COVID, vaccine misinformation spread by hundreds of websites, analysis finds

More than 500 websites have promoted misinformation about the coronavirus—including debunked claims about vaccines, according to a firm that rates the credibility of websites.

NewsGuard announced Wednesday that, of the more than 6,700 websites it has analyzed, 519 have published false information about COVID-19. Some of the sites publish dubious health information or political conspiracy theories, while others were "created specifically to spread misinformation about COVID-19," the company says on its website.

It's become virtually impossible for people to tell the difference between a generally reliable site and an untrustworthy site. And that is why there is such a big business in publishing this information. They're all hoaxes that have gained traction, and we know that because we see them spreading from website to website. Some of the websites NewsGuard identified have become more popular online than trustworthy sources of information about COVID-19.

https://techxplore.com/news/2021-09-covid-vaccine-misinformation-hu...

Tea made with impure water tastes better

Chemical impurities in tap water can cause a thin film to form on the surface of a cup of tea, and these make it taste better than a drink made with pure water, according to researchers at ETH Zurich in Switzerland.

Pour yourself a cup of tea and leave it to cool slightly, and you may see a film on the surface that cracks like sea ice when you disturb the cup. There are many factors that affect the formation of this film, the researchers say, but the primary one is calcium carbonate in the water. When tap water contains a high amount of minerals such as calcium carbonate, it is called hard water.

“Tap water in many regions comes from limestone aquifers, where calcium carbonate, a harmless compound that can make water taste ‘crisper’, is found.

Other factors that affect the formation of this film include milk, sugar or lemon added to the tea, the brewing temperature, and the concentration of the tea.

The team studied how the strength of the film changed with water hardness by placing a metal device on the surface of the tea and rotating it. “The rotation of that device is carefully controlled, and the resistance to rotation that the film applies is what allows us to determine its strength.

They found that the more calcium carbonate in the water, the stronger the film woul.... “If you were to make a cup of tea in perfectly pure water, it would not form a film at all, but the tea would taste quite bitter

The team’s findings could be useful in industrial settings, where creating conditions to form a strong film could improve the shelf life in packaged tea drinks.

https://aip.scitation.org/doi/10.1063/5.0059760

https://www.sciencefocus.com/science/put-down-the-filter-tea-made-w...

Exposure to traffic noise linked to higher dementia risk

Exposure to noise from traffic on roads and railways over a long period is associated with a higher risk of developing dementia, especially Alzheimer's disease, suggests a study published in The BMJ recently.

The researchers estimate that as many as 1,216 out of the 8,475 cases of dementia registered in Denmark in 2017 could be attributed to these noise exposures, indicating a great potential for dementia prevention through reduction in traffic related noise.

Worldwide, the number of people with dementia is expected to exceed 130 million by 2050, making it a costly and growing global health crisis. Besides well established risk factors, such as cardiovascular diseases and unhealthy lifestyle, environmental exposures may also play a role in the development of dementia.

Transportation noise is considered the second worst environmental risk factor for public health in Europe after air pollution, and around a fifth of the European population is exposed to transportation noise above the recommended level of 55 dB (decibels).

Studies have consistently linked transportation noise to various diseases and health conditions, such as coronary heart disease, obesity, and diabetes. There is, however, little research on transportation noise and dementia and findings are inconsistent.

To address this, researchers investigated the association between long term residential exposure to road traffic and railway noise and risk of dementia among two million adults aged over 60 and living in Denmark between 2004 and 2017.

The researchers estimated road traffic and railway noise at the most and least exposed sides (or façades) of all residential addresses in Denmark.

They then analyzed national health registers to identify cases of all-cause dementia and different types of dementia (Alzheimer's disease, vascular dementia, and Parkinson's disease related dementia) over an average of 8.5 years.

They found 103,500 new cases of dementia during the study period.

After taking account of potentially influential factors related to residents and their neighborhoods, the researchers found that a 10-year average exposure to road traffic and railway noise at the most and least exposed sides of buildings was associated with a higher risk of all-cause dementia.

These associations showed a general pattern of higher risk with higher noise exposure, but with a leveling off or even small declines in risk at higher noise levels.

Further analysis by type of dementia showed both road traffic and railway noise were associated with a higher risk of Alzheimer's disease—up to 27% higher for exposure to road traffic noise of 55 dB and up to 24% higher for exposure to railway noise of 50 dB compared with less than 40 dB.

However, only road traffic noise was associated with an increased risk of vascular dementia, and not railway noise.

 Residential exposure to transportation noise in Denmark and incidence of dementia: national cohort study, BMJ (2021). www.bmj.com/content/374/bmj.n1954

Editorial: Noise exposure and dementia: a rising concern in ageing populations, www.bmj.com/content/374/bmj.n2120

https://medicalxpress.com/news/2021-09-exposure-traffic-noise-linke...

Scientists solve mystery of icy plumes that may foretell deadly supercell storms

The most devastating tornadoes are often preceded by a cloudy plume of ice and water vapor billowing above a severe thunderstorm. New research reveals the mechanism for these plumes could be tied to 'hydraulic jumps' -- a phenomenon Leonardo Da Vinci observed more than 500 years ago.

When a cloudy plume of ice and water vapor billows up above the top of a severe thunderstorm, there's a good chance a violent tornado, high winds or hailstones bigger than golf balls will soon pelt the Earth below.

Supercell storms and exploding turbulence

The thunderstorms that spawn most tornadoes are known as supercells, a rare breed of storm with a rotating updraft that can hurtle skyward at speeds faster than 150 miles an hour, with enough power to punch through the usual lid on Earth's troposphere, the lowest layer of our atmosphere.

In weaker thunderstorms, rising currents of moist air tend to flatten and spread out upon reaching this lid, called the tropopause, forming an anvil-shaped cloud. A supercell thunderstorm's intense updraft presses the tropopause upward into the next layer of the atmosphere, creating what scientists call an overshooting top. "It's like a fountain pushing up against the next layer of our atmosphere," O'Neill said.

As winds in the upper atmosphere race over and around the protruding storm top, they sometimes kick up streams of water vapor and ice, which shoot into the stratosphere to form the tell-tale plume, technically called an Above-Anvil Cirrus Plume, or AACP.

The rising air of the overshooting top soon speeds back toward the troposphere, like a ball that accelerates downward after cresting aloft. At the same time, air is flowing over the dome in the stratosphere and then racing down the sheltered side.

Using computer simulations of idealized supercell thunderstorms, O'Neill and colleagues discovered that this excites a downslope windstorm at the tropopause, where wind speeds exceed 240 miles per hour. "Dry air descending from the stratosphere and moist air rising from the troposphere join in this very narrow, crazy-fast jet. The jet becomes unstable and the whole thing mixes and explodes in turbulence," O'Neill said. "These speeds at the storm top have never been observed or hypothesized before."

part2

We Asked a NASA Scientist – Do Aliens Exist?

COVID advances win Breakthrough prizes

Techniques that have helped scientists to understand COVID-19 have scooped two out of five of the most lucrative awards in science and.... “These two awards are for research that has had such an impact on the world that they elevate the stature of the Breakthrough Prize,” says chemical biologist Yamuna Krishnan. “They have been saving lives by the millions.” This year’s US$3-million Breakthrough prizes went to:

• Biochemists Katalin Karikó and Drew Weissman, who discovered how to smuggle genetic material called messenger RNA into cells, leading to the development of a new class of vaccine. Karikó recalls the scepticism surrounding her work in the 1990s that led to numerous grant-proposal and paper rejections (including the 2005 paper for which she is now being recognized), and forced her to take a demotion and a pay cut.
• Chemists Shankar Balasubramanian, David Klenerman and Pascal Mayer, who developed the next-generation sequencing technique that has been used to rapidly track variants of the SARS-CoV-2 coronavirus.
• Chemical biologist Jeffrey Kelly, for working out the part that protein misfolding plays in amyloidosis, a disease that can affect the heart and other organs and cause neurodegeneration — and for developing an effective treatment.
• Optical physicists Hidetoshi Katori and Jun Ye, for inventing the optical lattice clock — a device that would lose less than one second over 15 billion years, improving the precision of time measurements by 10,000 times.
• Mathematician Takuro Mochizuki, for extending the understanding of algebraic structures called ‘holonomic D-modules’ — which are related to certain types of differential equation — to deal with points at which the equations under study are not well defined.

https://www.nature.com/articles/d41586-021-02449-y?utm_source=Natur...

Sim shows how COVID virus infects cells

How Volcanic Eruptions Can Cool Earth? -- Explained!

Climate change includes both global warming driven by human-induced emissions of greenhouse gases and the resulting large-scale shifts in weather patterns.

Research on beards, wads of gum wins 2021 Ig Nobel prizes

Beards aren't just cool and trendy—they might also be an evolutionary development to help protect a man's delicate facial bones from a punch to the face.

That's the conclusion of a trio of scientists from the University of Utah who are among the winners of this year's Ig Nobel prizes, the Nobel Prize spoofs that honor—or maybe dishonor, depending on your point of view—strange scientific discoveries.

The winners of the 31st annual Ig Nobels being announced Thursday included researchers who figured out how to better control cockroaches on U.S. Navy submarines; animal scientists who looked at whether it's safer to transport an airborne rhinoceros upside-down; and a team that figured out just how disgusting that discarded gum stuck to your shoe is.

These sound like  silly studies, but as usual, there was some method to the madness. These findings have implications for a wide range of disciplines, including forensics, contagious disease control, or bioremediation of wasted chewing gum residues.

https://www.improbable.com/2021-ceremony/winners/

https://phys.org/news/2021-09-beards-wads-gum-ig-nobel.html?utm_sou...

New programmable gene editing proteins found outside of CRISPR systems

Within the last decade, scientists have adapted CRISPR systems from microbes into gene editing technology, a precise and programmable system for modifying DNA. Now, scientists at MIT's McGovern Institute and the Broad Institute of MIT and Harvard have discovered a new class of programmable DNA modifying systems called OMEGAs (Obligate Mobile Element Guided Activity), which may naturally be involved in shuffling small bits of DNA throughout bacterial genomes.

These ancient DNA-cutting enzymes are guided to their targets by small pieces of RNA. While they originated in bacteria, they have now been engineered to work in human cells, suggesting they could be useful in the development of gene editing therapies, particularly as they are small (~30% the size of Cas9), making them easier to deliver to cells than bulkier enzymes. The discovery, reported in the journal Science, provides evidence that natural RNA-guided enzymes are among the most abundant proteins on earth, pointing toward a vast new area of biology that is poised to drive the next revolution in genome editing technology.

Han Altae-Tran et al, The widespread IS200/605 transposon family encodes diverse programmable RNA-guided endonucleases, Science (2021). DOI: 10.1126/science.abj6856

https://phys.org/news/2021-09-programmable-gene-proteins-crispr.htm...

New technology designed to genetically control disease-spreading mosquitoes

Leveraging advancements in CRISPR-based genetic engineering, researchers have created a new system that restrains populations of mosquitoes that infect millions each year with debilitating diseases.

The new precision-guided sterile insect technique, or pgSIT, alters genes linked to male fertility—creating sterile offspring—and female flight in Aedes aegypti, the mosquito species responsible for spreading wide-ranging diseases including dengue fever, chikungunya and Zika.

pgSIT is a new scalable genetic control system that uses a CRISPR-based approach to engineer deployable mosquitoes that can suppress populations. Males don't transmit diseases so the idea is that as you release more and more sterile males, you can suppress the population without relying on harmful chemicals and insecticides.

pgSIT differs from "gene drive" systems that could suppress disease vectors by passing desired genetic alterations indefinitely from one generation to the next. Instead, pgSIT uses CRISPR to sterilize male mosquitoes and render female mosquitoes, which spread disease, as flightless. The system is self-limiting and is not predicted to persist or spread in the environment, two important safety features that should enable acceptance for this technology.

Suppressing mosquito populations with precision guided sterile males, Nature Communications (2021). DOI: 10.1038/s41467-021-25421-w

https://phys.org/news/2021-09-technology-genetically-disease-spread...

Study: AI can make better clinical decisions than humans

There's no harm in getting a second opinion. But what if that second opinion could be generated by a computer, using artificial intelligence? Would it come up with better treatment recommendations than your professional proposes?

Medical and educational professionals frequently disagree on the effectiveness of behavioral interventions, which may cause people to receive inadequate treatment.

To find a better way, researchers compiled simulated data from 1,024 individuals receiving treatment for behavioral issues. The researchers then compared the treatment conclusions drawn in each case by five doctoral-level behavior analysts with those produced by a computer model the two academics developed using machine learning.

The five professionals only came to the same conclusions approximately 75 percent of the time. More importantly, machine learning produced fewer decision-making errors than did all the professionals.

Given these very positive results, the next step would be to "integrate these models in an app that could automatically make decisions or provide feedback about how treatment is progressing". 

The goal, the researchers think, should be to use machine learning to facilitate the work of professionals, not actually replace them, while also making treatment decisions more consistent and predictable.

 Marc J. Lanovaz et al, Machine learning to analyze single‐case graphs: A comparison to visual inspection, Journal of Applied Behavior Analysis (2021). DOI: 10.1002/jaba.863

https://techxplore.com/news/2021-09-ai-clinical-decisions-humans.ht...

Drugs that mimic effects of cigarette smoke reduce SARS-CoV-2's ability to enter cells

Researchers have identified a potential reason why lower numbers of COVID cases have appeared amongst smokers compared to non-smokers, even as other reports suggest smoking increases severity of the disease.

Researchers have identified two drugs that mimic the effect of chemicals in cigarette smoke to bind to a receptor in mammalian cells that inhibits production of ACE2 proteins, a process that appears to reduce the ability of the SARS-CoV-2 virus to enter the cell.

The findings appear in the journal Scientific Reports on 17 August.

Something of a paradox exists with respect to smoking cigarettes and COVID-19. Active smoking is associated with increased severity of disease, but at the same time, many reports have suggested lower numbers of COVID cases amongst smokers than amongst non-smokers.

Something strange was going on here. We must stress the presence of strong evidence showing that smoking increases the severity of COVID-19. But the mechanism now discovered  is worth further investigation as a potential tool to fight SARS-CoV-2 infections.

--

It is known that cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs). These can bind to and activate aryl hydrocarbon receptors (AHRs). A receptor is any structure of the surface or inside of a cell that is shaped to receive and bind to a particular substance. AHRs are a type of receptor inside of mammalian cells that is in turn a transcription factor—something that can induce a wide range of cellular activities through its ability to increase or decrease the expression of certain genes.

Knowing this about the relationship between PAHs and AHRs, the researchers wanted to investigate the effect of drugs that activate AHR on expression of the genes that control production of the ACE2 protein—the infamous receptor protein on the surface of many cells types that works like a lock that the SARS-CoV-2 virus is able to pick. After binding the virus to the ACE2 protein, it can then enter and infect the cell.

Part 1

First, the scientists investigated various cell lines to examine their gene expression levels of ACE2. They found that those cells originating in the oral cavity, lungs and liver had the highest ACE2 expression.

These high-ACE2-expression cells were then subjected to various doses of cigarette-smoke extract (CSE) for 24 hours. After this, the rate of expression of the CYP1A1 gene, which is known to be inducible by CSE, was evaluated. The CSE treatment had induced increased expression of CYP1A1 gene in liver and lung cells in a dose-dependent manner—the greater the dose, the greater the effect. However, this effect was not as pronounced in oral cavity cells. In other words, greater activity of the CYP1A1, less production of the ACE2 receptors—the route that the virus is able to enter cells.

In order to explain why this was happening in the presence of cigarette smoke, the researchers then used RNA sequencing analysis to investigate what was happening with gene expression more comprehensively. They found that CSE increased the expressions of genes related to a number of key signaling processes within the cell that are regulated by AHR.

To more directly observe this mechanism by which AHR acts on ACE2 expression, the effects of two drugs that can activate AHR were evaluated on the liver cells. The first, 6‑formylindolo(3,2‑b)carbazole (FICZ) is derivative of the amino acid tryptophan, and the second, omeprazole (OMP), is a medication already widely used in the treatment of acid reflux and peptic ulcers.

RNA sequencing data suggested that the CYP1A1 gene was strongly induced in liver cells by these AHR activators, and expression of the ACE2 gene was strongly inhibited, again in a dose-dependent manner.

In other words, the cigarette smoke extract and these two drugs—all of which act as activators of AHR—are able to suppress the expression of ACE2 in mammalian cells, and by doing so, reduce the ability of the SARS-CoV-2 virus to enter the cell.

Keiji Tanimoto et al, Inhibiting SARS-CoV-2 infection in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl-hydrocarbon receptor signal, Scientific Reports (2021). DOI: 10.1038/s41598-021-96109-w

https://medicalxpress.com/news/2021-09-drugs-mimic-effects-cigarett...

Part 2

A new gold standard for detecting cancer mutations

An international research collaboration has identified a new gold standard for detecting cancer mutations using genomic pathology.

This research set out to understand why there has been a history of low reproducibility of genomic testing results between different labs when detecting cancers.

Scientists found factors like sample and library preparation, differing sequencing technology and bioinformatic tools were affecting the reproducibility and performance of the genomic analytical techniques.

The research team have now developed a set recommendations and guidelines on how to improve the reproducibility and precision of the tumor mutation detection in clinical practice.

All stages of mutation detection are interdependent and this dependency is complex.

There is no 'one way' to detect cancerous tumor mutations. For example, the amount of DNA sequencing needed to detect a cancer mutation will vary based on the amount of tumor content.

Every person is different and should be treated differently. And our research provides a new tool to improve precision medicine.

Wenming Xiao et al, Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing, Nature Biotechnology (2021). DOI: 10.1038/s41587-021-00994-5

https://medicalxpress.com/news/2021-09-gold-standard-cancer-mutatio...

 Study reveals that immune cells cooperate to trap and kill bacteria

Like a spider trapping its prey, our immune system cells cooperate to capture and "eat" bacteria.

The newly identified antibacterial mechanism, reported Sept. 10 in Science Advances, could inspire novel strategies for combating Staphylococcus aureus (staph) and other extracellular bacterial pathogens.

It was known that neutrophils—first responder immune cells that migrate to sites of infection—can self-destruct and release their protein and DNA contents to generate neutrophil extracellular traps (NETs). Now, Vanderbilt researchers led by postdoctoral fellow Andrew Monteith, Ph.D., have discovered that NETs boost the bacterial killing power of another type of immune cell: macrophages.

Neutrophils produce the spider webs that immobilize the bacteria, and macrophages are the spiders that engulf and kill the bacteria. Neutrophils and macrophages are both phagocytic cells known for ingesting bacteria and producing antimicrobial peptides, reactive oxygen species and other enzymes to fight infection. NET generation (NETosis), thought to be a form of programmed cell death, is a more recently discovered neutrophil antibacterial strategy. The released neutrophil DNA creates a sticky trap that is also studded with antimicrobial peptides.

The macrophages end up with not only their own antibacterial arsenal, but also the neutrophils' antibacterial arsenal, all in the same compartment killing the bacteria.

 Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens, Science Advances (2021). DOI: 10.1126/sciadv.abj2101

https://phys.org/news/2021-09-caught-web-reveals-immune-cells.html?...

Why do some plants track the sun?

Heliotropism,  literally means moving in relation to the sun.

Sunflowers track the course of the sun spectacularly on warm and sunny, spring or summer days. Sometimes they move through an arc of almost 180⁰ from morning to evening.

A number flowering species display heliotropism, including alpine buttercups, arctic poppies, alfalfa, soybean and many of the daisy-type species. So why do they do it?

Flowers are really in the advertising game and will do anything they can to attract a suitable pollinator, as effectively and as efficiently as they can. There are several possible reasons why tracking the sun might have evolved to achieve more successful pollination.

By tracking the sun, flowers absorb more solar radiation and so remain warmer. The warmer temperature suits or even rewards insect pollinators that are more active when they have a higher body temperature.

Optimum flower warmth may also boost pollen development and germination, leading to a higher fertilization rate and more seeds.

So, the flowers are clearly moving. But how?

For many heliotropic flowering species, there's a special layer of cells called the pulvinus just under the flower heads. These cells pump water across their cell membranes in a controlled way, so that cells can be fully pumped up like a balloon or become empty and flaccid. Changes in these cells allow the flower head to move.

When potassium from neighboring plant cells is moved into the cells of the pulvinus, water follows and the cells inflate. When they move potassium out of the cells, they become flaccid.

These potassium pumps are involved in many other aspects of plant movement, too. This includes the opening and closing of stomata (tiny regulated leaf apertures), the rapid movement of mimosa leaves, or the closing of a fly trap.

In 2016, scientists discovered that the pin-up example of heliotropism—the sunflower—had a different way of moving.

They found sunflower movement is due to significantly different growth rates on opposite sides of the flowering stem.

On the east-facing side, the cells grow and elongate quickly during the day, which slowly pushes the flower to face west as the daylight hours go by—following the sun. At night the west-side cells grow and elongate more rapidly, which pushes the flower back toward the east over night.

Everything is then set for the whole process to begin again at dawn next day, which is repeated daily until the flower stops growing and movement ceases.

While many people are aware of heliotropism in flowers, heliotropic movement of leaves is less commonly noticed or known. Plants with heliotropic flowers don't necessarily have heliotropic leaves, and vice versa.

Part1

Heliotropism evolves in response to highly specific environmental conditions, and factors affecting flowers can be different from those impacting leaves.

For example, flowers are all about pollination and seed production. For leaves, it's for maximizing photosynthesis, avoiding over-heating on a hot day or even reducing water loss in harsh and arid conditions.

Some species, such as the Queensland box, arrange their leaves so they're somewhat horizontal in the morning, capturing the full value of the available sunlight. But there are also instances where leaves align vertically to the sun in the middle of the day to minimize the risks of heat damage.

It's easy to think of plants as static organisms. But of course, they are forever changing, responding to their environments and growing. They are dynamic in their own way, and we tend to assume that when they do change, it will be at a very slow and steady pace.

Heliotropism shows us this is not necessarily the case. Plants changing daily can be a little unsettling in that we sense a change but may not be aware of what is causing our unease.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

https://phys.org/news/2021-09-daily-tracking-sun-fascinating.html?u...

Part2

What happens when two very different respiratory viruses infect the same cell

We know that several viruses infect us. A recent study from the University of Glasgow has discovered what happens when you get infected with some of these viruses at the same time, and it has implications for how they make us sick and how we protect ourselves from them.

For many reasons, respiratory viruses are often found during winter in the temperate regions of the world, or the rainy season of equatorial regions. During these periods, you'll probably be infected with more than one virus at any one time in a situation called a "co-infection."

Research shows that up to 30% of infections may harbor more than one virus. What this means is that, at some point two different viruses are infecting the cells that line your nose or lungs.

We know that co-infection can be important if we look at a process called "antigenic shift" in influenza viruses, which is basically caused by virus "sex." This sometimes occurs when two different influenza strains meet up inside the same cell and exchange genes, allowing a new variant to emerge.

Co-infection can create a predicament for viruses when you consider that they need to compete for the same resource: you. Some viruses appear to block other viruses, while some viruses seem to like each other. What is driving these positive and negative interactions during co-infections is unknown, but animal studies suggest that it could be critical in determining how sick you get.

The University of Glasgow study investigated what happens when you infect cells in a dish with two human respiratory viruses. For their experiments, they chose IAV and RSV, which are both common and cause lots of disease and death each year. The researchers looked at what happens to each virus using high-resolution imaging techniques, such as cryo-electron microscopy, that their labs have perfected over the years.

They found that some of the human lung cells in the dish contained both viruses. And, by looking closely at those co-infected cells, they found that the viruses that were emerging from the cell had structural characteristics of both IAV and RSV. The new "chimeric" virus particles had proteins of both viruses on their surface and some even contained genes from the other. This is the first evidence of this occurring from co-infection of distinct respiratory viruses.

Follow-up experiments in the same paper showed that these new chimeric viruses were fully functional and could even infect cells that were rendered resistant to influenza, presumably gaining access using the RSV proteins could even get into a broader range of human cells than either virus alone could. Potentially, this could be happening during natural co-infections during the winter.

https://www.biorxiv.org/content/10.1101/2021.08.16.456460v2

https://theconversation.com/heres-what-happens-when-two-very-differ...

Animals shape shifting as climate warms

Some animals are "shape-shifting" and have developed bigger tails, beaks and ears to regulate their body temperatures as the planet warms, according to a new study. From Australian parrots to European rabbits, researchers found evidence that a host of warm-blooded animals have evolved bigger body parts, which could allow them to lose body heat more effectively. Climate change is heaping "a whole lot of pressure" on animals. It's high time we recognised that animals also have to adapt to these changes, but this is occurring over a far shorter timescale than would have occurred through most of evolutionary time. The study, published on recently  in the journal Trends in Ecology and Evolution, reviewed previous research "where climatic warming is a potential hidden explanatory variable for the occurrence of shape-shifting" and found trends particularly noticeable in birds.

The Australian parrot, for example, had shown an average 4-10 percent increase in the size of its bill since 1871 and the authors said this positively correlated with the summer temperature each year.

Other birds, like North American dark-eyed juncos, thrushes and Galapagos finches also saw bill size increases.

Meanwhile, the wings of the great roundleaf bat grew, the European rabbit developed bigger ears, while the tails and legs of masked shrews were found to be larger.

Shape-shifting does not mean that animals are coping with climate change and that all is 'fine'. It just means they are evolving to survive it -- but we're not sure what the other ecological consequences of these changes are, or indeed that all species are capable of changing and surviving.

It's well known that animals use their appendages to regulate their internal temperature. African elephants, for example, pump warm blood to their large ears, which they then flap to disperse heat.

The beaks of birds perform a similar function – blood flow can be diverted to the bill when the bird is hot. This heat-dispersing function shows the beak is warmer than the rest of the body. All this means there are advantages to bigger appendages in warmer environments.

warm-blooded animals – also known as endotherms – tended to have smaller appendages while those in warmer climates tend to have larger ones.

This pattern became known as Allen's rule, which has since been supported by studies of birds  and mammals.

Biological patterns such as Allen's rule can also help make predictions about how animals will evolve as the climate warms.

https://www.cell.com/trends/ecology-evolution/fulltext/S0169-5347(21)00197-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS016953472100197X%3Fshowall%3Dtrue

https://researchnews.cc/news/8818/Animals--shape-shifting--as-clima...

Cannibalistic butterflies chow down on live caterpillars

For the first time, milkweed butterflies have been seen harassing, subduing and then slurping up the juices of caterpillars.

We generally think of butterflies s as beautiful, harmless, nectar-drinking insects. But new research carried out by the University of Sydney may change all that, as milkweed butterflies have been spotted scratching at caterpillars with their sharp claws to suck up their juices.

Milkweed butterflies are a group of butterflies in the Nymphalidae family, with one well-known species being the monarch butterfly.

As caterpillars, milkweed butterflies feed on toxic plants, using the chemicals as self-defence to make them unpalatable to birds and other predators. When the caterpillars turn into butterflies, they retain these toxins and advertise that they are poisonous with their bright colours.

Male butterflies will also use these toxic substances to produce mating pheromones. In order to boost their supplies of these love drugs, they’ll seek out extra sources of the chemicals.

Generally, they get these through plants, but in North Sulawesi, Indonesia, they have developed a taste for caterpillars – and they don’t care whether they are alive or dead.

“This is the first time the behaviour has been reported.

https://esajournals.onlinelibrary.wiley.com/doi/10.1002/ecy.3532

https://www.sciencefocus.com/news/cannibalistic-butterflies-chow-do...

An Alternative to Injection

Research on microneedle patches for vaccine delivery has grown in popularity in recent years, due to their exceptional compliance and low invasiveness.

Several researchers, including ourselves, are working on a technology that aims to provide the advantages of injectable vaccines without the drawbacks—and without the traditional needle stick: microneedles. While the technology still has a long road to the clinic, having entered human trials less than 10 years ago, we believe this it is the future of vaccine delivery, and the ongoing pandemic has highlighted the need to accelerate its development.

Basically, an array of tiny needles measuring just hundreds of microns is attached to a backing, permitting bandage-like application. Drugs can be encapsulated within water-soluble microneedles that dissolve when the patch is placed on the skin, allowing the drug to be released. Importantly, the microneedles pierce the outermost layer of tissue to allow greater absorption of the drugs compared to creams or other kinds of medical patches such as nicotine patches, but they do not penetrate deep enough to stimulate pain receptors. The patch can be self-administered and is as easy and painless as taking a pill. 

The patch has its limitations. Being such a small medical device, for example, the maximum drug dose is less than 1 mg. But for treatments that do not require a high dosage, including vaccines (both antigen-based ones and nanoparticle ones, such as those used for mRNA vaccines against COVID-19), hormones, and drugs with elevated potency, microneedles are ideal. In addition to being user friendly, microneedles could elicit a more robust immunological response. 

Conventional vaccine injection bypasses the skin’s immune system and introduces the antigen into the muscle or subcutaneous tissue, thereby inducing a systemic immune response. Yet, the skin, our biggest organ, also has a superb immunogenicity capacity due to the presence of many antigen-presenting cells. By delivering antigens there, microneedles could capitalize on this local response to boost the protection provided by vaccines. Indeed, animal studies suggest that microneedles elicit higher antibody production and better cellular response.

part 1

Moreover, because microneedles are a dry formulation, they allow drugs to maintain their activity even without storing them at the low temperatures required of many injectable vaccines. For example, one study has shown that a vaccine for influenza can be stable for six months at 25 °C and at least a few weeks at 40 °C if incorporated into microneedles. This is critical for ensuring vaccinations reach far-flung corners of the world that do not have the resources to maintain the cold chain. 

Another issue is vaccine wastage. For example, in some cases only a portion of the dose is used before a vaccine expires. It can also happen that healthcare personnel decide not to vaccinate a patient when there are not enough patients to use the whole vial. According to estimates, the wastage rates for 10-dose vials may be as high as 25 percent for liquid vaccines and 40 percent for freeze-dried vaccines. With microneedle patches, there is no wasted drug. And there are no needles that require special disposal procedures.

There are plenty of hurdles yet to be overcome. We need further clinical studies in human volunteers to demonstrate safety and efficacy of this vaccine approach, and the scale-up of production is still in its infancy. On a lab scale, usually we fill molds with the polymer solutions via vacuum or centrifugation. Once dried, the final formulation is demolded and secured to a backing. This is tedious and not practical for mass production.

Additionally, the majority of vaccinations are sterilized by filtering, which is not feasible for solid microneedle patches. While the solution may be sterilized before being placed in the molds, the final product will also need to undergo sterilization by some alternative technique not yet developed. 

The recent pandemic and the possibility of others is a wake-up call to focus on these challenges. In the last year and a half, several institutions and biotech companies announced preclinical studies for a SARS-CoV-2 vaccine utilizing microneedle patches. Big pharmaceutical companies will certainly step up and invest more over the coming years in microneedle-based products. Injections have been used for centuries, but the necessity for a worldwide immunization effort is a persuasive reason to try to move forward. 

https://www.the-scientist.com/news-opinion/opinion-an-alternative-t...

part3

Researchers  discover river of dust around the sun

A team of researchers has discovered a dusty mystery in a newly explored region around Earth’s sun.  They noticed a new and unexplained stream of microscopic particles that seemed to be spraying out from around the star.

Dust can come from asteroids and comets or can be left over from the original formation of the planets. It can show us how our solar system has formed and continues to evolve and even how other solar systems may be evolving.

There are two basic types of dust around the sun. Dust that is in bound orbits around the sun that will eventually spiral into the sun. Then there’s unbound dust that is flung away and out of the solar system.

No one had seen anything like this third type before—dust flying away from the sun usually spreads out in every direction. It doesn’t tend to cluster together like this one. 

https://iopscience.iop.org/article/10.3847/PSJ/ac0bb9

https://researchnews.cc/news/8866/Researchers-led-by-undergraduate-...

How Old Are Stars? An  Astrophysicist Unlocks the Secrets of Age-Dating

Black holes found to exert a pressure on their environment

Physicists have discovered that black holes exert a pressure on their environment, in a scientific first.

In 1974 Stephen Hawking made the seminal discovery that black holes emit thermal radiation. Previous to that, black holes were believed to be inert, the final stages of a dying heavy star.

Now scientists have shown that they are in fact even more complex thermodynamic systems, with not only a temperature but also a pressure.

 Quantum gravity  can lead to a pressure in black holes. This  finding that Schwarzschild black holes have a pressure as well as a temperature is more surprising. 

Xavier Calmet et al, Quantum gravitational corrections to the entropy of a Schwarzschild black hole, Physical Review D (2021). DOI: 10.1103/PhysRevD.104.066012

https://phys.org/news/2021-09-black-holes-exert-pressure-environmen...

Ancient marsupial ‘junk DNA’ might be useful after all, scientists say

CDC finds unvaccinated 11 times more likely to die of COVID

New U.S. studies released Friday show the COVID-19 vaccines remain highly effective against hospitalizations and death even as the extra-contagious delta variant swept the country.

One study tracked over 600,000 COVID-19 cases in 13 states from April through mid-July. As delta surged in early summer, those who were unvaccinated were 4.5 times more likely than the fully vaccinated to get infected, over 10 times more likely to be hospitalized and 11 times more likely to die, according to the Centers for Disease Control and Prevention.

Vaccination works! But ...

But as earlier data has shown, protection against coronavirus infection is slipping some: It was 91% in the spring but 78% in June and July, the study found.

So-called "breakthrough" cases in the fully vaccinated accounted for 14% of hospitalizations and 16% of deaths in June and July, about twice the percentage as earlier in the year.

An increase in those percentages isn't surprising: No one ever said the vaccines were perfect.

Source: Agence France-Presse

https://medicalxpress.com/news/2021-09-cdc-unvaccinated-die-covid.h...

https://researchnews.cc/news/8872/Covid-vaccines-hold-up-against-se...

Self‐care tooling innovation in a disabled kea (Nestor notabilis)

Situs inversus totalis involves complete transposition (right to left reversal) of the thoracic and abdominal organs. 

The heart is not in its usual position in the left chest, but is on the right. Specifically related to the heart, this is referred to as dextrocardia (literally, right-hearted).The stomach, which is normally in the left upper abdomen, is on the right. In patients with situs inversus totalis, all of the chest and abdominal organs are reversed and appear in mirror image when examined or visualized by tests such as X-ray filming. Situs inversus totalis has been estimated to occur once in about 6-8,000 births. Situs inversus occurs in a rare abnormal condition that is present at birth (congenital) called Kartagener's syndrome.

Gut flora composition may impact susceptibility to konzo, a neurological disease caused by world staple crop cassava

Konzo is a severe, irreversible neurologic disease that results in paralysis. It occurs after consuming poorly processed cassava -- a manioc root and essential crop for DRC and other low-income nations. Poorly processed cassava contains linamarin, a cyanogenic compound. While enzymes with glucosidase activity convert starch to simple sugars, they also break down linamarin, which then releases cyanide into the body.

 Differences between gut flora and genes from konzo-prone regions of the Democratic Republic of Congo (DRC) may affect the release of cyanide after poorly processed cassava is consumed, according to a study with 180 children. Cassava is a food security crop for over half a billion people in the developing world. Children living in high-risk konzo areas have high glucosidase (linamarase) microbes and low rhodanese microbes in their gut, which could mean more susceptibility and less protection against the disease, suggest  researchers who led the study published in Nature Communications.

Knowing who is more at risk could result in targeted interventions to process cassava better or try to diversify the diet. An alternative intervention is to modify the microbiome to increase the level of protection. This is, however, a difficult task which may have unintended consequences and other side effects.

While the gut microbiome is not the sole cause of disease given that environment and malnourishment play a role, it is a required modulator. "Simply stated, without gut microbes, linamarin and other cyanogenic glucosides would pose little to no risk to humans."

1. Matthew S. Bramble, Neerja Vashist, Arthur Ko, Sambhawa Priya, Céleste Musasa, Alban Mathieu, D’ Andre Spencer, Michel Lupamba Kasendue, Patrick Mamona Dilufwasayo, Kevin Karume, Joanna Nsibu, Hans Manya, Mary N. A. Uy, Brian Colwell, Michael Boivin, J. P. Banae Mayambu, Daniel Okitundu, Arnaud Droit, Dieudonné Mumba Ngoyi, Ran Blekhman, Desire Tshala-Katumbay, Eric Vilain. The gut microbiome in konzo. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-25694-1

A Clever 'Gene Silencing' Injection Has Been Approved For Treating High Cholesterol

cholesterol-busting jab to save thousands of lives in UK

The revolutionary new treatment, Inclisiran, is delivered as an injection twice a year and can be used alongside statins, adding to the options available to patients to help control their cholesterol levels.

It has been estimated that Inclisiran could prevent 55,000 heart attacks and strokes, saving 30,000 lives within the next decade.

It will mainly be prescribed to patients who suffer with a genetic condition that leads to high cholesterol, those who have already suffered a heart attack or stroke, or those who haven't responded well to other cholesterol-lowering drugs, such as statins.

This is an emerging therapeutic technique that works by targeting the underlying causes of a disease, rather than the symptoms it causes. It does this by targeting a particular gene, and preventing it from making the protein that it produces.

Until now, most treatments using gene silencing technology have been used to treat rare genetic diseases. This means the cholesterol jab will be one of the first gene silencing drugs used to treat people on a wider scale.

Researchers are also currently investigating whether gene silencing could be used to treat a wide variety of health conditions, including Alzheimer's disease and cancer.

Gene silencing drugs work by targeting a specific type of RNA (ribonucleic acid) in the body, called "messenger" RNA. RNAs are found in every cell of the body, and play an important role in the flow of genetic information.

But messenger RNA (mRNA) is one of the most important types of RNA our body has, as it copies and carries genetic instructions from our DNA and makes specific proteins depending on the instructions.

In the case of the cholesterol jab, gene silencing works by targeting a protein called PCSK9 and degrading it. This protein is involved in regulating cholesterol in our bodies, but occurs in excess in people with high levels of LDL cholesterol (the "bad" cholesterol). Preventing this protein from being produced in the first place will reduce cholesterol levels.

https://www.england.nhs.uk/2021/09/nhs-cholesterol-busting-jab-to-s...

In this case, the siRNA is designed to specifically target the mRNA which carries instructions for the PCSK9 protein. It binds to its target mRNA and destroys the instructions, which significantly reduces the amount of these proteins that are produced.

Gene therapies are usually delivered using a viral vector – a virus-like vehicle that delivers genes to our cells in the same way a virus might infect them. So far, viral vector therapies have been used to treat rare genetic blood disorders, genetic blindness and spinal muscular atrophy.

Although viral vectors are very effective with one treatment, it may be impossible to deliver a second dose if needed due to adverse immune reactions. These drugs are also extremely costly.

Because of this, many of the gene silencing drugs currently being investigated are delivered using a different technique. Known as non-viral vector gene therapies, these deliver the drug using a nanoparticle which protects it from degradation in the blood so it can be delivered specifically to the target – such as the liver, which is the target of the cholesterol jab.

https://www.sciencealert.com/this-gene-silencing-injection-was-just...

Part 2

Our mobile phones are covered in bacteria and viruses… and we never wash them

Mechanical buckling of petals produces iridescent patterns visible to bees

People only pay attention to new information when they want to

A new paper in the Journal of the European Economic Association, published by Oxford University Press, indicates that we tend to listen to people who tell us things we'd like to believe and ignore people who tell us things we'd prefer not to be true. As a result, like-minded people tend to make one another more biased when they exchange beliefs with one another.

While it would reasonable to think that people form decisions based on evidence and experience alone, previous research has demonstrated that decision makers have "motivated beliefs;" They believe things in part because they would like such things to be true. Motivated beliefs (and the reasoning that leads to them) can generate serious biases. Motivated beliefs have been speculated to explain the proliferation of misinformation on online forums.

The experiment conducted supports a lot of popular suspicions about why biased beliefs might be getting worse in the age of the internet. We now get a lot of information from social media and we don't know much about the quality of the information we're getting. As a result, we're often forced to decide for ourselves how accurate various opinions and sources of information are and how much stock to put in them. Our results suggest that people resolve this quandary by assigning credibility to sources that are telling us what we'd like to hear and this can make biases due to motivated reasoning a lot worse over time.

Ryan Oprea et al, Social Exchange of Motivated Beliefs, Journal of the European Economic Association (2021). DOI: 10.1093/jeea/jvab035

https://phys.org/news/2021-09-people-attention.html?utm_source=nwle...

Study links severe COVID-19 to increase in self-attacking antibodies

Hospitalized COVID-19 patients are substantially more likely to harbor autoantibodies—antibodies directed at their own tissues or at substances their immune cells secrete into the blood—than people without COVID-19, according to a new study.

Autoantibodies can be early harbingers of full-blown autoimmune disease.

If you get sick enough from COVID-19 to end up in the hospital, you may not be out of the woods even after you recover.

The scientists looked for autoantibodies in blood samples drawn during March and April of 2020 from 147 COVID-19 patients at the three university-affiliated hospitals and from a cohort of 48 patients at Kaiser Permanente in California. Blood samples drawn from other donors prior to the COVID-19 pandemic were used as controls.

The researchers identified and measured levels of antibodies targeting the virus; autoantibodies; and antibodies directed against cytokines, proteins that immune cells secrete to communicate with one another and coordinate their overall strategy.

Upward of 60% of all hospitalized COVID-19 patients, compared with about 15% of healthy controls, carried anti-cytokine antibodies, the scientists found. This could be the result of immune-system overdrive triggered by a virulent, lingering infection. In the fog of war, the abundance of cytokines may trip off the erroneous production of antibodies targeting them.

If any of these antibodies block a cytokine's ability to bind to its appropriate receptor, the intended recipient immune cell may not get activated. That, in turn, might buy the virus more time to replicate and lead to a much worse outcome.

Part1

In some cases, the presence of those newly detected autoantibodies may reflect an increase, driven by the immune response, of antibodies that had been flying under the radar at low levels, Utz said. It could be that inflammatory shock to the systems of patients with severe COVID-19 caused a jump in previously undetectable, and perhaps harmless, levels of autoantibodies these individuals may have been carrying prior to infection.

In other cases, autoantibody generation could result from exposure to viral materials that resemble our own proteins.

--

It's possible that, in the course of a poorly controlled SARS-CoV-2 infection—in which the virus hangs around for too long while an intensifying immune response continues to break viral particles into pieces—the immune system sees bits and pieces of the virus that it hadn't previously seen," he said. "If any of these viral pieces too closely resemble one of our own proteins, this could trigger autoantibody production."

The finding bolsters the argument for vaccination. Vaccines for COVID-19 contain only a single protein—SARS-CoV-2's so-called spike protein—or the genetic instructions for producing it. With vaccination, the immune system is never exposed to—and potentially confused by—the numerous other novel viral proteins generated during infection.

In addition, vaccination is less intensely inflammatory than an actual infection, so there's less likelihood that the immune system would be confused into generating antibodies to its own signaling proteins or to the body's own tissues.

Patients who, in response to vaccination, quickly mount appropriate antibody responses to the viral spike protein should be less likely to develop autoantibodies.

Indeed, a recent study in Nature showed that, unlike SARS-CoV-2 infection, the COVID-19 vaccine produced by Pfizer doesn't trigger any detectable generation of autoantibodies among recipients.

1. Sarah Esther Chang, Allan Feng, Wenzhao Meng, Sokratis A. Apostolidis, Elisabeth Mack, Maja Artandi, Linda Barman, Kate Bennett, Saborni Chakraborty, Iris Chang, Peggie Cheung, Sharon Chinthrajah, Shaurya Dhingra, Evan Do, Amanda Finck, Andrew Gaano, Reinhard Geßner, Heather M. Giannini, Joyce Gonzalez, Sarah Greib, Margrit Gündisch, Alex Ren Hsu, Alex Kuo, Monali Manohar, Rong Mao, Indira Neeli, Andreas Neubauer, Oluwatosin Oniyide, Abigail E. Powell, Rajan Puri, Harald Renz, Jeffrey Schapiro, Payton A. Weidenbacher, Richard Wittman, Neera Ahuja, Ho-Ryun Chung, Prasanna Jagannathan, Judith A. James, Peter S. Kim, Nuala J. Meyer, Kari C. Nadeau, Marko Radic, William H. Robinson, Upinder Singh, Taia T. Wang, E. John Wherry, Chrysanthi Skevaki, Eline T. Luning Prak, Paul J. Utz. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-25509-3

https://medicalxpress.com/news/2021-09-links-severe-covid-self-atta...

part 2

Researchers find immune cells that guard frequent site of cancer spread

In the progressing field of immunotherapy, surprisingly little is known about immunity to metastatic tumors in locations such as lymph nodes, a frequent place where cancers first spread. Not only do lymph nodes act as a gateway for cancer cells to travel throughout the body, but they are also home to infection-fighting white blood cells called T cells. In some cases, T cells in lymph nodes activate to kill invading cancer cells. In other cases, that process clearly fails.

While T cells can freely travel from lymph nodes into the bloodstream and back to the lymph nodes, researchers in Turk's lab have discovered a novel population of tumor-fighting T cells that do not circulate, but rather stay in lymph nodes where they provide protection against melanoma. "These T cells, for whatever reason, have changed their program and stay in the lymph nodes where they persist and kill tumor cells for many months while never entering circulation," says Turk.

These long-lived T cells, called "lymph node resident memory T cells," were shown to counteract melanoma spreading in mice. Turk's team found that when melanoma cells were put back into mice that had been cured of cancer with immunotherapy a month earlier, the lymph nodes were still resistant to the cancer—the melanoma would not grow.

Researchers identified T cells with similar characteristics in melanoma-invaded patient lymph nodes, showing that similar populations exist in humans.

Computational analysis of melanoma specimen data from The Cancer Genome Atlas revealed that the presence of T cells with this gene signature predicted better outcomes and improved survival for human melanoma patients with lymph node metastases. "These studies reveal a new population of T cells that is vital for counteracting the earliest stages of cancer metastasis.

Resident memory T cells in regional lymph nodes mediate immunity to metastatic melanoma, Immunity, DOI: 10.1016/j.immuni.2021.08.019

https://medicalxpress.com/news/2021-09-immune-cells-frequent-site-c...

**

Scientists pinpoint the uncertainty of our working memory

The human brain regions responsible for working memory content are also used to gauge the quality, or uncertainty, of memories, a team of scientists has found. Its study uncovers how these neural responses allow us to act and make decisions based on how sure we are about our memories.

Access to the uncertainty in our working memory enables us to determine how much to 'trust' our memory in making decisions.

This research is the first to reveal that the neural populations that encode the content of working memory also represent the uncertainty of memory.

Working memory, which enables us to maintain information in our minds, is an essential cognitive system that is involved in almost every aspect of human behavior—notably decision-making and learning.

For example, when reading, working memory allows us to store the content we just read a few seconds ago while our eyes keep scanning through the new sentences. Similarly, when shopping online, we may compare, "in our mind," the item in front of us on the screen with previous items already viewed and still remembered.

"It is not only crucial for the brain to remember things, but also to weigh how good the memory is: How certain are we that a specific memory is accurate?

 The study results yielded the first evidence that the human brain registers both the content and the uncertainty of working memory in the same cortical regions.

The knowledge of uncertainty of memory also guides people to seek more information when we are unsure of our own memory.

Joint representation of working memory and uncertainty in human cortex, Neuron (2021). DOI: 10.1016/j.neuron.2021.08.022

https://medicalxpress.com/news/2021-09-scientists-uncertainty-memor...

New immunotherapy method turns activated specifically in tumor

Immunotherapy drugs are promising new weapons in the fight against cancer, but they are so strong that they can be toxic to the rest of the human body. The basic idea behind immunotherapy drugs is simple. Doctors inject special kinds of drugs, especially proteins such as antibodies and cytokines prepared or modified in a lab, into a patient, where they activate the patient’s immune cells –T-cells, NK cells, and so on – and help these cells fight the tumor. In short, immunotherapy drugs work like a powerful cocktail that boosts a patient’s own immune system.

After being prescribed by a doctor, immunotherapy drugs are administered intravenously.

Once inside the body, the drugs spread all over – not just where the tumor or any metastases are located. The problem is that the proteins in the drugs are so strong that they damage healthy tissue. Many of the immunotherapy treatments already out there have proven to be highly effective against cancer in preclinical studies. But they often can’t be used to save people because they’re too toxic to the rest of the body. The treatments that are used in patients today have been toned down so they’re less potent. That makes them safer, but also less effective at destroying tumors. The aim of this new method is to keep all the potency of immunotherapy, because it will be an important treatment option for cancer patients.
Researchers, therefore, developed a method whereby the immunotherapy proteins are activated only when they come into the tumor tissues.  This method draws on techniques from both chemistry and immune engineering.

The tumor microenvironment is different from the rest of the body. The pH is lower, meaning it’s more acidic, and it has a high reducing potential. Researchers used these facts, already known to scientists, to develop a kind of polymer shield for the protein drugs that would let them travel harmlessly through the body until they reach the tumor.

That shield is designed to break down when exposed to the unique chemical environment in the tumor tissue. Chemical reactions in the tumour microenvironment break the bonds at the protein surface, thereby removing the polymer shield. The protein drugs are then free to activate the patient’s cancer-fighting lymphocytes selectively in the tumour tissue.

Zhao, Y. ; Xie, Y.-Q. ; Van Herck, S. ; Nassiri, S. ; Gao, M. ; Guo...

https://actu.epfl.ch/news/new-immunotherapy-becomes-activated-speci...

https://www.myscience.ch/en/news/2021/new_immunotherapy_becomes_act...

https://researchnews.cc/news/8892/New-immunotherapy-method-turns-ac...

Chemically masked cytokines and antibodies turn active selectively in tumors as safer cancer immunotherapies. Credit: Yu Zhao 2021 EPFL

How to modify RNA: Crucial steps for adding chemical tag to transfer RNA revealed

The chemical steps in an important cellular modification process that adds a chemical tag to some RNAs have been revealed in a new study. Interfering with this process in humans can lead to neuronal diseases, diabetes, and cancers. A research team has imaged a protein that facilitates this RNA modification in bacteria, allowing the researchers to reconstruct the process. A paper describing the modification process appears Sept. 15 in the journal Nature.

Transfer RNAs (tRNA) are the RNAs that "read" the genetic code and translate it into a sequence of amino acids to make a protein. The addition of a chemical tag—a methyl sulfur group—to a particular location on some tRNAs improves their ability to translate messenger RNA into proteins. When this modification process—called methylthiolation—doesn't occur properly, mistakes can be incorporated into the resulting proteins, which in humans can lead to neuronal disease, cancer, and increased risk of developing Type 2 diabetes.

Methylthiolation is ubiquitous across bacteria, plants, and animals. In this study, researchers  determined the structure of a protein called MiaB to better understand its role in facilitating this important modification process in bacteria.

Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB, Nature (2021). DOI: 10.1038/s41586-021-03904-6 , www.nature.com/articles/s41586-021-03904-6

https://phys.org/news/2021-09-rna-crucial-adding-chemical-tag.html?...

Differences in cellular signaling offer clues to insulin resistance

In what could be a starting point for new therapeutics to tackle insulin resistance, a major driver of type 2 diabetes and metabolic syndrome present in 20–30 percent of the general U.S. population, researchers recently found that insulin resistance in the general population seems likely to be caused by a series of cell-specific signaling defects, some of which appear to be sex specific.

In addition, only a portion of the defects are shared with those seen in diabetes, pointing towards the existence of novel pathways behind insulin resistance in the general population.

Most people know that insulin is an important hormone for controlling blood glucose, but most people don't realize how important insulin is for all aspects of metabolism—not just sugar, but lipids, amino acids, and proteins

Insulin resistance, that is the failure of the body to respond normally to insulin, is very common in the population, not just in people with diabetes or obesity, and these individuals are at high risk for developing these metabolic disorders.

The research is based on a stem-cell modeling system called iMyos that can be used to investigate cell-specific changes in signaling in combination with a technique called phosphoproteomics.

Specifically, the researchers used stem cells derived from blood cells of individuals without diabetes who were either insulin sensitive or resistant.

The researchers could then investigate differences in cellular signaling, both in the absence and presence of insulin stimulation, to determine how insulin resistance or sensitivity affected signaling in a series of different pathways.

In what emerges as a complex picture, they found large differences in phosphoproteome signatures based on insulin sensitivity status but also based on the sex of the cell donors.

Nida Haider et al, Signaling defects associated with insulin resistance in non-diabetic and diabetic individuals and modification by sex, Journal of Clinical Investigation (2021). DOI: 10.1172/JCI151818

Part 1

**

Researchers identified a comprehensive network of cell signaling defects in non-diabetic individuals and also uncovered critical nodes of signaling changes shared with type 2 diabetic patients.

These critical nodes where signaling was altered go well beyond the classical insulin signaling, opening a whole new view of insulin resistance. One of the most striking and surprising findings was that many of the signaling changes were sex specific.

Thus, even in the absence of adding sex hormones, these male and female cells showed differences in their phosphoproteome fingerprint. This was very unexpected.

Importantly, the investigators also found that the differences and changes did reflect on multiple downstream biological processes, implying that therapeutic interventions at specific points in the signaling cascade will likely affect biological outcomes.

"Further investigation will be needed to identify the regulators that are responsible for the phosphoproteome changes associated with insulin resistance, and for the drastic differences by sex. "Unraveling these critical nodes in insulin resistance will be able to serve as novel targets for the development of future therapies."

https://medicalxpress.com/news/2021-09-differences-cellular-clues-i...

Part 2