India's tiger population rises above 3,000

India's wild tiger population—by far the largest in the world—has risen above 3,000, according to a census released Sunday, boosting efforts to conserve the endangered species.

The largest of all cats, tigers once roamed throughout central, eastern and southern Asia.

But in the past 100 years the tiger has lost more than 93 percent of its historic range and now only survives in scattered populations in 13 countries, according to the International Union for Conservation of Nature (IUCN).

The Indian census estimated there were 3,167 tigers in the wild across the country, up from 2,967 reported in the last such exercise.

Surveys are conducted every four years, using camera traps and computer programmes to individually identify each creature.

The rate of increase has slowed to less than seven percent over the period, down from more than 30 percent in the previous four years.

Deforestation, poaching and human encroachment on habitats have devastated tiger populations across Asia .

India is now home to 75 percent of the global tiger population and also the "largest tiger range country in the world".

In 1900, more than 100,000 tigers were estimated to roam the planet. But that fell to a record low of 3,200 in 2010.

That year, India and 12 other countries with tiger populations signed an agreement to double their big cat numbers by 2022.

India is believed to have had a tiger population of around 40,000 at the time of independence from Britain in 1947.

That fell over subsequent decades to about 3,700 in 2002 and an all-time low of 1,411 four years later, but numbers have since risen steadily.

On the other hand it also tells us that each of us now need to work harder to restore degraded habitats, ensure safe movement of tigers through corridors and promote coexistence.

Source: News agencies

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 Link between youthful gut microbiota and potential centenarians

With a growing body of scientific evidence illustrating the influence of gut microbiota on human health, researchers investigated the microflora inhabiting the guts of the world's healthiest people—centenarians.

In the paper, "Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures," published in Nature Aging, the researchers studied the microbiomes of 1,575 individuals aged 20 up to 117, with 297 of them reported to be 100 years old or older. A Research Briefing on the study, titled "Youth-associated signatures in the gut microbiome of centenarians," has been published in the same journal issue.

Participants were evaluated in five age-related groups. Young adults (n = 314, 20–44 years), a middle-aged group (n = 277, 45–65 years), old adults (n = 386, 66–85 years), a nonagenarian group (n = 301, 90–99 years), and a centenarian cohort (n = 297, 100–117 years).

The researchers discovered that the gut microbiome signature in centenarians resembles that of young adults with an overrepresentation of Bacteroides spp., an increase in species evenness (species have a similar abundance), an enrichment of potentially beneficial species from the Bacteroidetes phylum and depletion of potential pathobionts (harmless but can become pathogenic under certain circumstances).

A smaller group of 45 centenarians was tested twice over a year and a half. Results from the group indicated that as centenarians age, the signature species evenness and low pathobionts continued to develop and were enhanced or conserved.

The researchers propose that this microbiome signature is associated with longevity, as they observed in their study, and state that this may counteract the senescence or chronic diseases that generally accompany aging, which this study could not have observed.

The researchers are currently isolating thousands of bacteria strains from the centenarians and testing their benefits on animal models in search of microorganisms that are able to extend the human lifespan. 

Shifu Pang et al, Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures, Nature Aging (2023). DOI: 10.1038/s43587-023-00389-y

Youth-associated signatures in the gut microbiome of centenarians, Nature Aging (2023). DOI: 10.1038/s43587-023-00395-0

Evidence found of possible interdomain horizontal gene transfer leading to development of the eye in vertebrates

A group of molecular and chemical biologists,  has found possible evidence of interdomain horizontal gene transfer leading to the development of the eye in vertebrates. In their study, reported in Proceedings of the National Academy of Sciences researchers used the IQ-TREE software program to trace the evolutionary history of genes associated with vision.

Ever since scientists proved that humans, along with other animals, developed due to evolutionary processes, one problem has stood out—how could evolution possibly account for the development of something as complicated as the eyeball? Even Charles Darwin was said to be stumped by the question. In recent times, this seeming conundrum has been used by some groups as a means to discredit evolutionary theory altogether. In this new effort, researchers sought to answer the question once and for all.

Their work began with the idea that vision in vertebrates may have got its start by using light-sensitive genes transferred from microbes. To find out if that might be the case, the team submitted likely human gene candidates to the IQ-TREE program to look for similar genetic sequences in other creatures, most specifically, microbes.

They found a promising candidate, a gene called IRBP. In humans, it encodes for a protein that is used in the eye as part of a process that converts light into electrical pulses that are eventually sent to the brain via the optic nerve. The research team notes that the gene is an essential component of vision in all vertebrates. IRBP is also found in microbes, most specifically in bacterial peptidases, a class of enzymes that is known for recycling proteins.

The researchers note that while IRBP and the protein that it encodes exists in all vertebrates, it does not exist in most invertebrates. This, they suggest, indicates that the IRBP gene may have been transferred from a microbe over 500 million years ago to an ancient vertebrate, leading to the development of light sensitivity, and over time, to organs such as eyeballs.

Geoscientist discovers new phosphorus material after lightning strike

After lightning struck a tree in a New Port Richey neighborhood, a University of South Florida professor discovered the strike led to the formation of a new phosphorus material. It was found in a rock—the first time in solid form on Earth—and could represent a member of a new mineral group.

Minerals similar to it can be found in meteorites and space, but can't be  seen this exact material anywhere on Earth.

High-energy events, such as lightning, can cause unique chemical reactions, and in this instance, result in a new material—one that is transitional between space minerals and minerals found on Earth.

When lightning strikes a tree, the ground typically explodes out and the surrounding grass dies, forming a scar and sending electric discharge through nearby rock, soil and sand, forming fulgurites, also known as 'fossilized lightning'.

In wet environments, such as in Florida,  iron will often accumulate and encrust tree roots. In this case, not only did the lightening strike combust the iron on the tree roots, but it combusted the naturally occurring carbon in the tree as well. The two elements led to a chemical reaction that created a fulgurite that looked like a metal 'glob.'

Inside the fulgurite, a colorful, crystal-like matter revealed a material never before discovered.

The experiment, when repeated in a lab,  was unsuccessful and indicates the material likely forms quickly under precise conditions, and if heated too long, will turn into the mineral found in meteorites.

This research may reveal other forms of reduced minerals are plausible and many could have been important in the development of life on Earth.

Luca Bindi et al, Routes to reduction of phosphate by high-energy events, Communications Earth & Environment (2023). DOI: 10.1038/s43247-023-00736-2

A day and night difference: Molecular composition of aerosols diffe...

Tiny aerosols particles in the atmosphere have a significant effect on the climate. They affect the climate directly by interacting with solar radiation. Depending on the type of particle, they can block sunlight, cooling the atmosphere, or absorb sunlight, warming the atmosphere. They also affect climate indirectly by acting as seeds for warm and cold cloud formation. But scientists lack information on these aerosols' molecular composition. This is especially true of aerosols during the day and night above agricultural fields.

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How air pollution causes lung cancer

Air pollution might cause lung cancer by creating inflammation that encourages proliferation of cells with e... — not by mutating DNA itself. The results provide a mechanism that could apply to other cancers caused by environmental exposure and might one day lead to ways to prevent them. “The idea is that exposures to carcinogens could promote cancer without actually doing anything to the DNA,” says medical geneticist Serena Nik-Zainal. “Not every carcinogen is a mutagen.”

Environmental particulate matter measuring ≤2.5 μm (PM_2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue.

https://www.nature.com/articles/s41586-023-05874-3?utm_source=Natur...

Researchers leverage cell self-destruction to treat brain tumours

Glioblastoma is the most common type of brain tumor in adults. The disease is 100% fatal and there are no cures, making it the most aggressive type of cancer. Such a poor prognosis has motivated researchers and neurosurgeons to understand the biology of tumors with the goal of creating better therapies.

A team of researchers have found that glioblastoma tumor cells are particularly sensitive to ferroptosis—a type of cell death that can be triggered by removing certain amino acids from the diet.

First, the researchers found that when they take away certain amino acids in animal models that the glioblastoma cells are more likely to die by ferroptosis. Secondly, they found that removing these amino acids makes the drugs a lot more effective at inducing ferroptosis in cancer cells.

Ferroptosis is an iron-dependent type of "programmed cell death" or a biological process that causes cells to "self-destruct" on command. Our bodies don't need to kill cells unless absolutely necessary, so the process is tightly controlled by certain biological mechanisms. However, researchers are only now beginning to comprehend the process because ferroptosis was recognized only a decade ago.

Every cell has certain safety features to keep it from going through ferroptosis in an unpredictable way. Two amino acids, cysteine and methionine, are critical for preventing the process from starting in cells. We typically pick up these amino acids through our diet.

By depriving animal models of cysteine and methionine through a customized diet, they found that the glioblastoma cells were significantly more likely to die via ferroptosis. They also found that the diet made their chemotherapy drugs more apt at initiating programmed cell death, meaning that very low doses were able to achieve a more potent effect than before. Ultimately, the animal models had improved survival after going on the diet.

This type of diet has also shown to be very effective in sarcoma, lung cancers, and pancreatic cancers, so there is hope that this diet can be used to put some extra umph behind chemotherapy and/or surgery to remove tumors throughout the body.

Pavan S. Upadhyayula, Dominique M. Higgins, Angeliki Mela, Matei Banu, Athanassios Dovas, Fereshteh Zandkarimi, Purvi Patel, Aayushi Mahajan, Nelson Humala, Trang T. T. Nguyen, Kunal R. Chaudhary, Lillian Liao, Michael Argenziano, Tejaswi Sudhakar, Colin P. Sperring, Benjamin L. Shapiro, Eman R. Ahmed, Connor Kinslow, Ling F. Ye, Markus D. Siegelin, Simon Cheng, Rajesh Soni, Jeffrey N. Bruce, Brent R. Stockwell, Peter Canoll. Dietary restriction of cysteine and methionine sensitizes gliomas to ferroptosis and induces alterations in energetic metabolism. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-36630-w

New 'AI scientist' combines theory and data to discover scientific equations

In 1918, the American chemist Irving Langmuir published a paper examining the behavior of gas molecules sticking to a solid surface. Guided by the results of careful experiments, as well as his theory that solids offer discrete sites for the gas molecules to fill, he worked out a series of equations that describe how much gas will stick, given the pressure.

Now, about a hundred years later, an "AI scientist" developed by researchers at IBM Research, Samsung AI, and the University of Maryland, Baltimore County (UMBC) has reproduced a key part of Langmuir's Nobel Prize-winning work. The system—artificial intelligence (AI) functioning as a scientist—also rediscovered Kepler's third law of planetary motion, which can calculate the time it takes one space object to orbit another given the distance separating them, and produced a good approximation of Einstein's relativistic time-dilation law, which shows that time slows down for fast-moving objects.

A paper describing the results is published in Nature Communications on April 12.

Combining Data and Theory for Derivable Scientific Discovery with AI-Descartes, Nature Communications (2023). DOI: 10.1038/s41467-023-37236-y

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Time-restricted fasting could cause fertility problems

Time-restricted fasting diets could cause fertility problems according to new research.

Time-restricted fasting is an eating pattern where people limit their food consumption to certain hours of the day. It's a popular health and fitness trend and people are doing it to lose weight and improve their health.

 A new study published recently in Proceedings of the Royal Society B: Biological Sciences shows that time-restricted fasting affects reproduction differently in male and female zebrafish. It is titled, "Fasting increases investment in soma upon refeeding at the cost of gamete quality in zebrafish."

Importantly, some of the negative effects on eggs and sperm quality can be seen after the fish returned to their normal levels of food consumption.

The research team say that while the study was conducted in fish, their findings highlight the importance of considering not just the effect of fasting on weight and health, but also on fertility.

The way organisms respond to food shortages can affect the quality of eggs and sperm, and such effects could potentially continue after the end of the fasting period.

Fasting increases investment in soma upon refeeding at the cost of gamete quality in zebrafish, Proceedings of the Royal Society B: Biological Sciences (2023). DOI: 10.1098/rspb.2022.1556. royalsocietypublishing.org/doi … .1098/rspb.2022.1556

Mitochondria power supply failure may cause age-related cognitive impairment

Brains are like puzzles, requiring many nested and co-dependent pieces to function well. The brain is divided into areas, each containing many millions of neurons connected across thousands of synapses. These synapses, which enable communication between neurons, depend on even smaller structures: message-sending boutons (swollen bulbs at the branch-like tips of neurons), message-receiving dendrites (complementary branch-like structures for receiving bouton messages), and power-generating mitochondria. To create a cohesive brain, all these pieces must be accounted for.

The team found that adherence to the ultrastructural size principle was essential for avoiding working memory impairment with age. By viewing violation of the ultrastructural size principle and mitochondria-related failures as the key to age-related cognitive impairment, the study ushers in a new era for aging research.

 Violation of the ultrastructural size principle in the dorsolateral prefrontal cortex underlies working memory impairment in the aged common marmoset (Callithrix jacchus), Frontiers in Aging Neuroscience (2023). DOI: 10.3389/fnagi.2023.1146245

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Predictive power of climate models may be masked by volcanoes

Simulated volcanic eruptions may be blowing up our ability to predict near-term climate, according to a new study published in Science Advances.

The research, led by the National Center for Atmospheric Research (NCAR), finds that the way volcanic eruptions are represented in climate models may be masking the models' ability to accurately predict variations in sea surface temperatures in the tropical Pacific that unfold over multiple years to a decade. These decadal variations in sea surface temperatures in the tropical Pacific are linked to climate impacts across the globe, including variations in precipitation and severe weather. Accurate predictions, therefore, could provide community leaders, farmers, water managers, and others with critical climate information that allows them to plan years in advance.

Because it is well established that large volcanic eruptions can have significant, long-term cooling effects on the climate, researchers expected that the collection of simulations that included the volcanic eruptions would produce more accurate multiyear and decadal climate predictions. Instead, they found that the inclusion of the eruptions degraded the model's predictive capabilities, at least in the tropical Pacific, an area that is especially important because of the connections between sea surface temperatures and near-term climate events.

For example, the simulations that included the volcanoes predicted a subsequent cooling of the sea surface temperatures in the tropical Pacific after the eruptions. In reality, that region of the ocean warmed, a change that was well predicted by the simulations that did not include the volcanic eruptions.

These findings highlight the difficulty of accurately representing the complex climate impacts that follow a volcanic eruption  in a model, a task made more challenging because researchers only have a few real-life examples in the observational record. Scientists know that volcanoes can loft sulfur gases high into the stratosphere where they can transform into sunlight-reflecting aerosols. But how the resulting cooling ultimately affects the entire Earth system, including sea surface temperatures, is not well understood.

Xian Wu, Volcanic forcing degrades multiyear-to-decadal prediction skill in the tropical Pacific, Science Advances (2023). DOI: 10.1126/sciadv.add9364. www.science.org/doi/10.1126/sciadv.add9364

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Viruses: How avian influenza viruses spill over to mammals

Picture your local lake covered with migrating geese, ducks or other waterfowl. Even though you don’t hear any coughing, you might well be witnessing ‘flu season’ for birds. Influenza viruses cause gastrointestinal infections in birds, and are spread when birds defecate in water that other birds then drink .Sometimes, however, avian influenza viruses make their way into mammals, including humans, and cause respiratory infections: how does this happen?

Waterfowl are the main natural reservoir for influenza viruses, and influenza viruses that infect humans and other mammals originally came from birds. This spillover can happen in two ways. The first way involves special mammalian hosts (like pigs) that can be infected by both avian and mammalian influenza viruses . Occasionally, an individual from one of these species becomes simultaneously infected with both types of virus, and the two viruses exchange gene segments to form a novel virus that retains the ability to infect mammals. This process – which is known as gene reassortment – is what happened to start human influenza pandemics in 1957 and 1968 .

The second way that spillover can happen involves a mammal getting directly infected with a bird virus . This individual then transmits this bird virus to others in its same species. If infection of the new species is sustained over time and within many individuals, the avian virus will experience natural selection for genetic mutations that make it more and more compatible with the mammalian species.

 https://elifesciences.org/articles/86051?utm_source=content_alert&a...

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Study unveils neural processes underpinning the re-emergence of consciousness after anesthesia

Before undergoing surgeries and other invasive medical procedures, patients typically undergo anesthesia. Anesthesia consists in giving patients a class of drugs (i.e., anesthetics) that cause them to lose feeling in specific areas of the body (i.e., local anesthesia) or fully lose awareness during a procedure (i.e., general anesthesia). These anesthetics can be administered to patients via injection, inhalation, skin-numbing lotions, and other means.

In the past, doctors and medical researchers viewed general anesthesia as a passive process that could not be influenced or interrupted once anesthetic drugs were administered. More recently, however, studies showed that it is in fact an active brain process that can be experimentally controlled and acted on. A research team  recently carried out a study investigating the processes underpinning brain states while under general anesthesia and those associated with the subsequent re-emergence of awareness. Their findings, published in Nature Neuroscience, highlight possible strategies that could help anesthesiologists to extend and deepen or shorten periods of anesthesia.

In the experiments with mice , when the brain is forced into a minimum responsive state by diverse anesthetics, a rapid downregulation of K⁺/Cl⁻ cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) serves as a common mechanism by which the brain regains consciousness.

To examine the neural processes linked to the re-emergence of consciousness after anesthesia, the researchers carried out a series of experiments on adult mice. They gave the mice one of three different anesthetic drugs (i.e., ketamine, propofol and pentobarbital) and then looked at the molecular mechanisms that emerged while they were re-gaining awareness.

To assess the mice's levels of consciousness they measured the so-called loss of righting reflex (LORR), a point in which animals no longer act on their instinct to avoid laying with their stomach facing up. In addition, they observed the animals' behavioral responses to external stimuli.

Part 1

The team's experiments yielded interesting results, identifying a new neuronal and molecular mechanism through which the brain re-gains consciousness after general anesthesia. They also showed that the ventral posteromedial nucleus (VPN), part of the thalamus, is a key brain region associated with re-emergence of consciousness.

Ubiquitin-proteasomal degradation is responsible for KCC2 downregulation, which is driven by ubiquitin ligase Fbxl4. Phosphorylation of KCC2 at Thr1007 promotes interaction between KCC2 and Fbxl4. KCC2 downregulation leads to γ-aminobutyric acid type A receptor-mediated disinhibition, enabling accelerated recovery of VPM neuron excitability and emergence of consciousness from anesthetic inhibition. This pathway to recovery is an active process and occurs independent of anesthetic choice.

Overall, the recent work by this team of researchers shows that the degradation of KCC2 transporter neurons located in the VPM, through the means of ubiquitin, a compound in living cells that contributes to the degradation of superfluous or faulty proteins in the brain, is a key step in the mice's emergence of consciousness after general anesthesia. This key finding could potentially inform the development of strategies to wake patients who are in a  vegetative state or minimally conscious state, which is a long-standing medical challenge.

Jiang-Jian Hu et al, Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01290-y

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Preventing dangerous blood clots

Hibernating bears, paralyzed humans, and pigs kept in small enclosures all avoid dangerous blood clots, despite being immobile for extremely long periods. Recent research shows that reduction of a key protein prevents the formation of blood clots in all three mammal species when they are still for days, weeks, months, or even years at a time. The study is published recently (April 13, 2023), in Science.

If you've ever taken a long haul flight, you might have taken advice to prevent a dangerous blood clot—deep vein thrombosis—from forming in one or both of your legs, while you sit still for multiple hours. Perhaps you set a reminder to get up and walk around, and you wore compression socks to keep the blood from pooling in your legs.

Most people won't experience a clot if they take care on a flight, but there is a serious risk for some people who are pre-disposed to blood clots due to genetic factors.

The discovery that a protein known as Hsp47 is dramatically reduced—by 55 times—when someone is immobilized for a much longer period than a flight, could lead to new medicines to help those who have inherited blood clotting disorders that put them at risk for pulmonary embolism, heart attack, and stroke.

It seems counterintuitive that people who have severe paralysis don't appear to be at higher risk of blood clots. This tells us that something interesting is happening. And it turns out that reducing levels of Hsp47 plays a key role in preventing clots, not just in humans, but in other mammals, including bears and pigs.

"When we see something like this in multiple species, that reinforces its importance. Having Hsp47 must have been an evolutionary advantage."

Hsp47 is released by platelets—the sticky blood cells that trigger blood clotting. Usually clotting is an important response to an injury, to prevent blood loss, and Hsp47 is one of the necessary ingredients to enable platelets to do their job. Examining the role of Hsp47 in clotting function the team found that when released into the blood of bears, mice and humans that it promoted conditions that may give rise to deep vein thrombosis.

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It appears that there is something about movement that keeps Hsp47 at an appropriate level. It could be that the mechanical forces involved in moving around actually have an impact on gene expression, dramatically increasing the amount of Hsp47 that circulates in the blood.
Now we know that Hsp47 is so important, we can begin to look for new or existing medicines that might be able to inhibit the function of this protein in blood clotting and protect mobile people who are prone to clots.

Manuela Thienel et al, Immobility-associated thromboprotection is conserved across mammalian species from bear to human, Science (2023). DOI: 10.1126/science.abo5044. www.science.org/doi/10.1126/science.abo5044

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Significant association found between all-cause mortality and weight loss in the elderly

An international team of researchers  has examined the associations of changes in body weight and waist circumference with all-cause and cause-specific mortality. In the paper, "Associations of Change in Body Size With All-Cause and Cause-Specific Mortality Among Healthy Older Adults," published in JAMA Network Open, the team highlights the startling connection between weight loss and increased risk of death.

The researchers used data from a past study looking at aspirin use in 16,703 Australian participants aged 70 and above. They focused on weight recordings, waist circumference measurements and mortality information over time. The cohort consisted of 7,510 men and 9,193 women. All the individuals were without evident cardiovascular disease, dementia, physical disability, or life-limiting chronic illnesses.

Both body weight and waist circumference changes were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by more than 10%, increase by 5% to 10%, and increase by more than 10%.

Using men with stable weight as a control, men with a 5% to 10% weight loss had a 33% higher risk of all-cause mortality, and those with more than a 10% decrease in body weight had a 289% higher risk.

Compared to women with stable weight, women with a 5% to 10% weight loss had a 26% higher risk of all-cause mortality, and those with more than a 10% decrease in body weight had a 114% higher risk.

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A more than 10% decrease in waist circumference was associated with a 2.14-fold higher risk of all-cause mortality for men and a 34% higher risk of all-cause mortality for women.

There was no significant association between weight gain and increases in waist circumference and all-cause mortality.

The researchers state it is likely that weight loss is an early indicator of the presence of various life-shortening diseases. While weight loss may precede a cancer diagnosis, the study revealed that weight loss also precedes increased mortality from all causes, including deaths from cardiovascular disease, trauma, dementia, Parkinson's disease, and other less common causes.

The weight loss was primarily associated with reduced appetite, leading to reduced food intake. The paper describes appetite as a complex process governed by both the central nervous system and various circulating hormones, any of which might be disrupted ahead of more pronounced disease presentation.

The researchers conclude that physicians and their patients should be aware of the significant association between mortality and elder weight loss.

Bladder ‘Memory’ Influences Urinary Tract Infection Recurrence in Mice

Urinary tract infections leave permanent epigenetic marks in the mouse bladder epithelium, reprogramming its response to subsequent infections, a study finds.

One of the main challenges for treating urinary tract infections is their high recurrence, especially in women. The underlying mechanisms of this high recurrence rate are not well understood, but having suffered from a previous UTI is a significant risk factor. A study in mice published April 10 in Nature Microbiology proposes that this may be partially explained because an initial urinary infection with Escherichia coli—the culprit of most UTI cases—modifies the host’s epithelial epigenome in such a way that it alters the morphology of the bladder in the long term, influencing the response to future infections by the same bacteria.

When people think about how our body fights pathogens, they focus on the immune system. However, this work shows “clear evidence that changes that occur to epithelial cells . . . have long-term consequences for how we react to infections". 

Some of the researchers behind the new study had already reported in 2016 that mice infected with an initial E. coli UTI resulted in either spontaneous resolution or a chronic cystitis, respectively reducing or increasing susceptibility to future infections. The researchers found then that, in each scenario, the E. coli UTI had differentially modified the bladder epithelium in terms of architecture, morphology, and molecular signatures. 

Translating these findings to humans—for instance, to treat recurrent UTIs—is still a distant goal, all sources agree. A lot of other technologies would need to be in place and we need a “better understanding of how you can manipulate the epigenome in a very directed way” in order to develop such therapies.

https://www.nature.com/articles/s41564-023-01346-6

Researchers use skin-colonizing bacteria to create a topical cancer therapy in mice

While studying a type of bacteria that lives on the healthy skin of every human being, researchers  may have stumbled on a powerful new way to fight cancer.

After genetically engineering the bacteria, called Staphylococcus epidermidis, to produce a tumor antigen (a protein unique to the tumor that's capable of stimulating the immune system), they applied the live bacteria onto the fur of mice with cancer. The resulting immune response was strong enough to kill even an aggressive type of metastatic skin cancer, without causing inflammation.

Millions of bacteria, fungi and viruses live on the surface of healthy skin. These friendly colonists play a crucial role in maintaining the skin barrier and preventing infection, but there are many unknowns about how the skin microbiota interacts with the host immune system. For instance, unique among colonizing bacteria, staph epidermidis triggers the production of potent immune cells called CD8 T cells—the "killer" cells responsible for battling severe infections or cancer.

The researchers showed that by inserting a tumor antigen into staph epidermidis, they could trick the mouse's immune system into producing CD8 T cells targeting the chosen antigen. These cells traveled throughout the mice and rapidly proliferated when they encountered a matching tumor, drastically slowing tumour growth or extinguishing the tumours altogether.

Even when melanoma had metastasized to the lungs, treatment with the bacteria drastically shrank the size of tumors or eliminated them, significantly improving survival times for the mice. 

When the researchers combined the new treatment with a second type of immunotherapy designed to bolster T cell activity, called "checkpoint blockade," the benefit was even more pronounced: 15 out of 16 established tumors disappeared. When the mice were re-injected with more cancer cells 30 days later, tumors still didn't grow.

"This appears to be evidence of a memory immune response, similar to what happens after a vaccine."

The researchers now think that the host organism produces these T cells to essentially vaccinate itself against the colonists, protecting against inevitable cuts and scrapes that could allow bacteria to breach the skin barrier.

In these experiments, they have basically tricked the host into thinking that the tumour is bacterially infected and then the host is going after that tumour aggressively.

The researchers have discovered that the host is vaccinating itself, day in and day out, against organisms that live at barrier surfaces. If they can direct even a bit of this immune attention toward specific cancers—or potentially infectious diseases—they will have a very effective, low-cost therapy that can simply be applied to the skin.

Will this therapy work in human beings? This has to be tested now.

Sex of blood donor has no effect on recipient survival, finds clinical trial

A large clinical trial of more than 8,700 patients published in the New England Journal of Medicine concluded that the sex of a donor has no effect on the survival of recipients of red blood cell transfusions.

The possible impact of the sex of a blood donor on recipient survival has been an unanswered question in transfusion medicine since 2015, when the American National Heart, Lung and Blood Institute identified it as a research priority. Some evidence suggested that sex-related differences such as hormone levels in male and female blood might affect recipient survival, but the results of observational studies have been conflicting.

"To answer this question definitively, researchers needed a large, randomized clinical trial, but those studies are incredibly expensive. By embedding this trial in real-world practice and using practical methods, they answered this question for a fraction of what a trial would normally cost.

And most importantly, the study found no statistically significant differences in overall survival between recipients of male donor blood and recipients of female donor blood.

 The effect of donor sex on recipient mortality in transfusion, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2211523

How a virus causes chromosomal breakage, leading to cancer

The Epstein-Barr virus (EBV) is easily spread through bodily fluids, primarily saliva, such as kissing, shared drinks or using the same eating utensils. Not surprisingly then, EBV is also among the most ubiquitous of viruses: More than 90% of the world’s population has been infected, usually during childhood.

EBV causes infectious mononucleosis and similar ailments, though often there are no symptoms. Most infections are mild and pass, but the virus persists in the body, becoming latent or inactive, sometimes reactivating. Long-term latent infections are associated with several chronic inflammatory conditions and multiple cancers.

In a new paper, published April 12, 2023 in the journal Nature, researchers describe for the first time how the virus exploits genomic weaknesses to cause cancer while reducing the body’s ability to suppress it.

These findings show “how a virus can induce cleavage of human chromosome 11, initiating a cascade of genomic instability that can potentially activate a leukemia-causing oncogene and inactivate a major tumor suppressor”.

It’s the first demonstration of how cleavage of a ‘fragile DNA’ site can be selectively induced.

Throughout every person’s genome or full set of genes are fragile sites, specific chromosomal regions more likely to produce mutations, breaks or gaps when replicating. Some are rare, some are common; all are associated with disorders and disease, sometimes heritable conditions, sometimes not, such as many cancers.

In the new study, the researchers focused on EBNA1, a viral protein that persists in cells infected with EBV. EBNA1 was previously known to bind at a specific genomic sequence in the EBV genome at the origin of replication. The researchers found that EBNA1 also binds a cluster of EBV-like sequences at a fragile site on human chromosome 11 where increasing abundance of the protein triggers chromosomal breakage.

Other prior research has shown that EBNA1 inhibits p53, a gene that plays a key role in controlling cell division and cell death. It also suppresses tumor formation when normal. Mutations of p53, on the other hand, are linked to cancer cell growth.

When the scientists examined whole-genome sequencing data for 2,439 cancers across 38 tumor types from the Pan-Cancer Analysis of Whole Genomes project, they found that cancer tumors with detectable EBV revealed higher levels of chromosome 11 abnormalities, including 100% of the head and neck cancer cases.

This discovery suggests that susceptibility to EBNA1-induced fragmentation of chromosome 11 depends on the control of EBNA1 levels produced in latent infection, as well as the genetic variability in the number of EBV-like sequences present on chromosome 11 in each individual. Going forward, this knowledge paves the way for screening risk factors for the development of EBV-associated diseases. Moreover, blocking EBNA1 from binding at this cluster of sequences on chromosome 11 can be exploited to prevent the development of EBV-associated diseases.

https://www.nature.com/articles/s41586-023-05923-x

What Is an Annular Eclipse?

Link between a vitamin deficiency and  'double-jointedness' and hypermobile Ehlers-Danlos  syndrome

Researchers have discovered a possible genetic cause for hypermobility (commonly known as double-jointedness) and a range of associated connective tissue disorders such as hypermobile Ehlers-Danlos syndrome, according to preliminary findings published in the journal Heliyon.

You may know someone with overly flexible joints, a friend or family member who can easily slide into a split or bend limbs to impossible angles. But hypermobility is a more serious condition than being "double-jointed."

For those with hypermobile Ehlers-Danlos syndrome (EDS), the same conditions that create fragile connective tissue can cause a range of symptoms that, on the surface, can seem unrelated: physical conditions such as joint pain, chronic fatigue, thin tooth enamel, dizziness, digestive trouble and migraines; and psychiatric disorders, such as anxiety and depression. Women with hypermobile EDS may also be at increased risk for endometriosis or uterine fibroids.

Researchers have long struggled to find the cause of hypermobility and hypermobile EDS. Of the 13 subtypes of EDS, hypermobile EDS comprises more than 90% of the cases. But until this study, hypermobile EDS was the only subtype without a known genetic correlate. As a result, symptoms have often been treated individually rather than as the result of a single cause.

Researchers now have linked hypermobility to a deficiency of folate—the natural form of vitamin B9—caused by a variation of the MTHFR gene.

Those with this genetic variant can't metabolize folate, which causes unmetabolized folate to accumulate in the bloodstream. The folate deficiency may prevent key proteins from binding collagen to the extracellular matrix. This results in more elastic connective tissue, hypermobility, and a potential cascade of associated conditions.

The discovery could help doctors more accurately diagnose hypermobility and hypermobile EDS by looking for elevated folate levels in blood tests as well as the MTHFR genetic variant.

Jacques Courseault et al, Folate-dependent hypermobility syndrome: A proposed mechanism and diagnosis, Heliyon (2023). DOI: 10.1016/j.heliyon.2023.e15387

How drugs get into the blood

Computer simulations have helped researchers understand in detail how pharmaceutically active substances cross cell membranes. These findings can now be used to discover new drug candidates more efficiently.

There is a need for new drugs. For example, many of the antibiotics that we have been using for a long time are becoming less effective. Chemists and pharmaceutical scientists are frantically searching for new active substances, especially those that can penetrate cell membranes, as these are the only ones that patients can take orally in the form of a tablet or syrup. Only these active ingredients pass through the intestinal wall in the small intestine and enter the bloodstream to reach the affected area in the body. For active ingredients that cannot penetrate the cell membrane, physicians have no choice but to inject them directly into the bloodstream.

That is why researchers are trying to understand which molecules can penetrate cell membranes and how exactly they do this. For one important and promising class of substances – cyclic peptides – chemists  have now decoded additional details of the relevant mechanism. 

Only modelling allows researchers such detailed, high-​resolution insights.

Cyclic peptides are ring-​shaped molecules that are much larger than the small molecules that make up the majority of today’s drugs. In some areas of application, however, chemists and pharmaceutical scientists are coming up against their limits with small molecules, which is why they are turning to larger molecules like the cyclic peptides. This substance class includes many pharmaceutically active natural substances, such as cyclosporine, an immunosuppressant that for decades has been used after organ transplants, and many antibiotics.

Using computer modelling and a lot of supercomputer power, researchers were able to elucidate how cyclic peptides similar to cyclosporine cross a membrane.

Part 1 

To understand the mechanism, one must know how cyclic peptides are structured: they consist of a central ring structure to which side chains are attached. The molecules are flexible and can dynamically change their structure to adapt to their environment.

 simulations reveal in detail how a cyclic peptide penetrates the membrane: First, the molecule anchor itself to the membrane’s surface, before penetrating it perpendicular to the membrane. It then changes its three-​dimensional shape while passing through, rotating once about its longitudinal axis before reaching the other side of the membrane, where it exits again.

These changes in shape have to do with the different environments the molecule experiences as it moves through the membrane: The body consists largely of water. Both inside and outside of cells, biochemical molecules are mostly present in aqueous solution. Cell membranes, on the other hand, are made up of fatty acids, so water-​repellent conditions prevail within them. To enable it to cross the membrane, the cyclic peptide changes its three-​dimensional shape to briefly become as hydrophobic as possible.

For the present study, the researchers investigated eight different cyclic peptides. These are model peptides with no medicinal effect – scientists at pharmaceutical giant Novartis developed them for basic research.

The new findings can now be used in discovering cyclic peptides as new drug candidates. However, the researchers point out a certain trade-​off: there are side chains that provide ideal conditions for cyclic peptides to anchor to the membrane surface, but that make it difficult for the peptides to cross the membrane. This new knowledge helps researchers to give advance thought to which side chains they want to use and where on the molecule they are most helpful. All of this could speed up drug discovery and development by ensuring right from the outset that researchers are investigating potential active ingredients that can eventually be taken as a tablet.

https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c01837

Linker SM, Schellhaas C, Kamenik AS, Veldhuizen MM, Waibl F, Roth HJ, Fouché M, Rodde S, Riniker S: Lessons for Oral Bioavailability: How Conformationally Flexible Cyclic Peptides Enter and Cross Lipid Membranes, Journal of Medicinal Chemistry 2023, 66: 2773, doi: external page10.1021/acs.jmedchem.2c01837call_made

Part 2

The Fight Against Misinformation with Dr. Sander van der Linden

Income rank linked to experience of physical pain, irrespective of whether in a rich or poor country, study suggests

A new study of worldwide polling data suggests that a person's income rank relative to their peers is linked to their experience of physical pain, with a lower income rank linked to a higher likelihood of experiencing pain. It is the first time such a relationship has been shown.

The study found the link to persist, to the same degree, irrespective of whether the person lives in a rich country or a poor country. Income rank is the position of an individual's absolute personal income amount in a list of those amounts ordered from lowest to highest. The higher the position in the list, the higher the income rank.

 Having less than others is physically painful: Income rank and pain around the world, Social Psychological and Personality Science (2023). DOI: 10.1177/19485506231167928

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Dark Matter Matters

Researchers develop carbon-negative concrete

A viable formula for a carbon-negative, environmentally friendly concrete that is nearly as strong as regular concrete has been developed by researchers.

In a proof-of-concept work, the researchers infused regular cement with environmentally friendly biochar, a type of charcoal made from organic waste, that had been strengthened beforehand with concrete wastewater. The biochar was able to suck up to 23% of its weight in carbon dioxide from the air while still reaching a strength comparable to ordinary cement.

The research could significantly reduce carbon emissions of the concrete industry, which is one of the most energy- and carbon-intensive of all manufacturing industries.

Zhipeng Li et al, Towards sustainable industrial application of carbon-negative concrete: Synergistic carbon-capture by concrete washout water and biochar, Materials Letters (2023). DOI: 10.1016/j.matlet.2023.134368

Quantum liquid becomes solid when heated!

Solids can be melted by heating, but in the quantum world it can also be the other way around: In a joint effort, an experimental team show how a quantum liquid forms supersolid structures through heating. The scientists obtained a first phase diagram for a supersolid at finite temperature.

Supersolids are a relatively new and exciting area of research. They exhibit both solid and superfluid properties simultaneously. In 2019, three research groups were able to demonstrate this state for the first time beyond doubt in ultracold quantum gases.

To explore the effect of thermal fluctuation, researchers developed and published in Nature Communications a theoretical model that can explain the experimental results and underlines the thesis that heating the quantum liquid can lead to the formation of a quantum crystal. The theoretical model shows that as the temperature rises, these structures can form more easily.

The surprising behavior, which contradicts our everyday observation, arises from the anisotropic nature of the dipole-dipole interaction of the strongly magnetic atoms of dysprosium.

 J. Sánchez-Baena et al, Heating a dipolar quantum fluid into a solid, Nature Communications (2023). DOI: 10.1038/s41467-023-37207-3

A potential treatment for multidrug-resistant bacteria

A new type of drug could provide a way to treat multidrug-resistant bacteria, according to a study published in Nature Communications. Instead of targeting the bacteria directly, the drug blocks key toxins involved in the infection process. This both reduces inflammation and makes the bacteria more vulnerable to antibiotics.

Antibiotics have been invaluable in the fight against bacterial infections, but bacteria are becoming more and more resistant to them. In the early days of antibiotics, bacteria took about 11 years on average to become resistant, but that figure has dropped to 2-3 years today. Many common bacterial infections are becoming resistant, and new antibiotics aren't being developed quickly enough to keep pace.

In 2019, 1.27 million deaths were directly attributable to antimicrobial resistance, and that number is expected to rise to 10 million per year in 2050. "We urgently need new tools to tackle these resistant infections. Despite this, no new antibiotics have been approved in decades, and there are just six currently under development that might sidestep resistance, only two of which target highly resistant bacteria.

A different approach would be to directly target the toxins and biofilms that pathogens use to establish the infection and cause inflammation, collectively called virulence factors. These virulence factors include small molecules that bacteria use to communicate and larger molecules that are part of their protective membrane. A drug that binds to these molecules could interfere with processes that are vital to the bacteria.

An international team led by researchers at Aalto went looking for drugs that could do just that. They found a good candidate after screening a library to identify molecules that interact with virulence factors but don't affect the bacteria's growth. Because the drug disarms the pathogen instead of killing it or halting its growth, this approach generates much weaker selection pressure for the development of resistant bacteria.

Part 1

The team tested the drug against the pathogenic bacteria Pseudomonas aeruginosa and Acinetobacter baumannii, which feature at the top of the World Health Organization's priority list. The treatment sequestered toxins released by the pathogens and disrupted their ability to communicate, reducing the formation of protective biofilms as explained in this short video:

While these experiments showed that the drug could effectively disarm these pathogens, the researchers also wanted to know if it could make them more vulnerable. Supplementing an antibiotic treatment with the new drug made the antibiotic effective at a lower dose. But more importantly, when the team treated bacteria with a combination of antibiotics and the new drug for two weeks, the bacteria didn't evolve resistance to the antibiotics, although they rapidly became resistant when exposed to the antibiotics alone.

This suggests that the new drug could be used to preserve the efficacy of the antibiotics we have left.

The drug interacts with part of the bacterial outer membrane, which is a strong barrier against antibiotics. The drug loosens the membrane and makes it more permeable. That means it's easier for antibiotics to get into the bacteria and kill them.

Having shown that the drug is effective against bacterial pathogens, the next step was to determine whether it could actually provide protection. To test that, human lung cells were exposed to toxins that cause inflammation and cellular damage. The drug directly sequestered the toxins and protected against inflammation and cellular damage. The researchers found similar protective results when mice were exposed to the toxins.

These findings open the door to an exciting new alternative to antibiotics, one that could potentially break the vicious cycle of antibiotic discovery and resistance. This treatment and others like it could provide the boost we need to keep ahead in our never-ending arms race with bacterial resistance.

 Christopher Jonkergouw et al, Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii, Nature Communications (2023). DOI: 10.1038/s41467-023-37749-6

Part 2

Stab-resistant fabric gains strength from carbon nanotubes, polyacrylate

Fabrics that resist knife cuts can help prevent injuries and save lives. But a sharp enough knife or a very forceful jab can get through some of these materials. Now, researchers report in ACS Applied Nano Materials that carbon nanotubes and polyacrylate strengthen conventional aramid to produce lightweight, soft fabrics that provide better protection. Applications include anti-stabbing clothing, helmets and insoles, as well as cut-resistant packaging.

Soft body armor is typically made from aramid, ultra-high-molecular-weight polyethylene, or carbon and glass fabrics. Their puncture resistance depends, in part, on the friction between yarn fibers within these materials. Up to a point, greater friction means greater protection. Manufacturers can boost friction by roughening the fiber surfaces, but that requires a complicated process, and product yield is low.

Alternatively, the bonding force between yarns can be enhanced by adding another component, such as a sheer thickening fluid (STF) or a polyurethane (PU) coating. But these composite fabrics can't simultaneously satisfy the requirements for thinness, flexibility and light weight. Researchers now  wanted to find another way to improve performance while satisfying these criteria.

The researchers tested a polyacrylate emulsion (PAE), STF and PU as coatings on aramid fabric. In simulated stabbing tests, aramid fabric coated with PAE outperformed the uncoated material used by itself or in combination with STF or PU. Carbon nanotubes are known to make composites tougher, and adding them to aramid/PAE further improved impact resistance. The research team says that's because the nanotubes created bridges between the fibers, thereby increasing friction. The nanotubes also formed a thin, protective network that dispersed stress away from the point of impact and helped prevent fiber disintegration. The new lightweight, flexible, puncture-resistant composite fabric could be useful in military and civilian applications, according to the researchers.

Wen-hua Cai et al, Polyacrylate and Carboxylic Multi-Walled Carbon Nanotube-Strengthened Aramid Fabrics as Flexible Puncture-Resistant Composites for Anti-Stabbing Applications, ACS Applied Nano Materials (2023). DOI: 10.1021/acsanm.3c00738

Nanoparticles provoke immune response against tumors but avoid side effects

Cancer drugs that stimulate the body's immune system to attack tumors are a promising way to treat many types of cancer. However, some of these drugs produce too much systemic inflammation when delivered intravenously, making them harmful to use in patients.

Researchers have now come up with a possible way to get around that obstacle. In a new study, they showed that when immunostimulatory prodrugs—inactive drugs that require activation in the body—are tuned for optimal activation timing, the drugs provoke the immune system to attack tumors without the side effects that occur when the active form of the drug is given.

The researchers designed prodrugs with bottlebrush-like structures based on a class of compounds called imidazoquinolines (IMDs). Mice treated with these bottlebrush prodrugs designed with optimized activation kinetics showed a significant reduction in tumor growth, with no side effects. The researchers hope that this approach could be used to boost immune system responses in cancer patients, especially when combined with other immunotherapy drugs or cancer vaccines.

Sachin Bhagchandani et al, Engineering kinetics of TLR7/8 agonist release from bottlebrush prodrugs enables tumor-focused immune stimulation, Science Advances (2023). DOI: 10.1126/sciadv.adg2239. www.science.org/doi/10.1126/sciadv.adg2239

Climate change may keep India from achieving its sustainable development goals

Heat waves in India are increasing in frequency, intensity and lethality, burdening public health, agriculture, and other socio-economic and cultural systems. A study published in PLOS Climate by  researchers suggests that heat waves made more likely by climate change may impede India's progress toward its sustainable development goals.

India has committed to achieving seventeen United Nations Sustainable Development Goals (SDG), including no poverty, good health and well being, and decent work and economic growth. However, current climate vulnerability assessments may not fully capture how heat waves linked to climate change may impact SDG progress. In order to analyze India's climate vulnerability, and how climate change may impact SDG progress, researchers conducted an analytical evaluation of India's heat index (HI) with its climate vulnerability index, (CVI) a composite index using various indicators to account for socioeconomic, livelihood, and biophysical factors.

They accessed a publicly available dataset on state-level climate vulnerability indicators from the Indian Government's National Data & Analytics Platform to classify severity categories. The researchers then compared India's progress in SDG over 20 years (2001–2021) with extreme weather-related mortality from 2001–2021. The researchers found that heat waves have weakened SDG progress more than previously estimated and that current assessment metrics may not sufficiently capture the nuances of India's vulnerabilities to climate change impacts. For instance, in estimating HI, the study shows that nearly 90% of the country is in danger zone from heat wave impacts.

According to the CVI, about 20% of the country is highly vulnerable to climate change. Similar effects were observed for the national capital, where HI estimates shows almost all of Delhi is threatened by severe heat wave impacts, which is not reflected in its recent state action plan for climate change. However, this study had several limitations, for example the incongruent timeframe for CVI data (2019–2020) and heat index data (2022). Future studies should incorporate more recent data. According to the authors, "This study shows that heat waves make more Indian states vulnerable to climate change than previously estimated with the CVI. The heat waves in India and the Indian subcontinent become recurrent and long-lasting, it is high time that climate experts and policymakers reevaluate the metrics for assessing the country's climate vulnerability. This offers a scope for developing a holistic vulnerability measure through international cooperation and partnership."

Heat waves are getting more intense in India, putting 80% of the country's people in danger, which remains unaccounted for in its current climate vulnerability assessment. If this impact is not addressed immediately, India can slow its progress towards sustainable development goals.

 Lethal heatwaves are challenging India's sustainable development, PLOS Climate (2023). DOI: 10.1371/journal.pclm.0000156

 Uses for Drones on the Farm 

A gun that uses facial recognition can  reduce firearm deaths

 Kai Kloepfer is bringing his smart gun to market in what could be the first weapon to break a decades-old political and manufacturing "log jam" that has kept smart guns from mass production.

Kloepfer's Broomfield-based company, Biofire, on Thursday announced the sale of guns that use both fingerprint and facial recognition to make sure only authorized users can fire the weapon.

His goal is to reduce accidental deaths and suicides and to keep children from accessing their parents' weapons. The gun will allow people to have a weapon at hand but want to make sure children, visitors or criminals can't use it.

The gun is primarily marketed for use as a weapon for home defense, Kloepfer said. Gun owners must balance keeping a weapon easily accessible in case of emergency but also secure enough that others can't access it.

MediaNews Group, Inc.

https://techxplore.com/news/2023-04-gun-facial-recognition-firearm-...

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Earpiece that speeds up recovery after a stroke

researchers have developed a smart earpiece that helps people relearn physical actions faster and more easily after a stroke. By stimulating the brain, the earpiece helps it rewire neural circuits.

Strokes are the number one cause of persistent physical impairment among adults worldwide. Sufferers often find it hard or even impossible to perform everyday physical actions like walking or reaching for something. One reason for this is that the stroke has damaged regions in the brain involved in making the necessary movements.

Initial clinical studies conducted by other scientists have shown that stimulating the vagus nerve plays a crucial role in rehabilitating regions of the brain damaged by a stroke. Such stimulation has allowed stroke patients to regain their movement faster and more effectively.

But until now, this has required patients to undergo an expensive operation, performed under general anaesthetic, to implant a stimulation device below the skin. Since it’s common practice to wait a full year after a stroke to carry out this procedure, patients are losing valuable time.

Now,  researchers  from the Rehabilitation Engineering Laboratory have developed a new system that is set to make vagus nerve stimulation much easier and available much faster: Their earpiece emits subtle electrical impulses to activate the nerve in the outer ear, thus eliminating the need for a surgical procedure.

They ware able to show earlier that stimulating the vagus nerve wasn’t the only factor. The neuroscientist demonstrated that timing is also critical: the electrical impulses are particularly effective if administered while patients are attempting those motions that they have found difficult to perform since their stroke.

This helps the brain rewire motor neural circuits to compensate for malfunctions in regions damaged by the stroke. It’s like we’re reconfiguring the brain’s software: stimulating the nerve promotes neuroplasticity, aids the formation of new synapses and supports the relearning of physical actions.

What the researchers have done now is develop a movement sensor that works a bit like a smartwatch. Stroke patients wear this sensor wherever their motor function is impaired, for instance on their right arm. Using special software,  the sensor analyses the arm’s movements in real time and tells the earpiece when the patient moved their arm particularly well.

This triggers stimulation of the vagus nerve and the brain learns to recall the correct sequence of movements faster and more effectively. The technical term for this process is reinforcement learning.

Unlike previous treatment options, stroke patients can use the technology developed by the  researchers also without professional supervision. What’s more, the movement sensor will make it possible for physical therapists to monitor their patients’ progress conveniently using a smartphone. The  researchers expect this to yield further progress in treatment.

https://ethz.ch/en/news-and-events/eth-news/news/2023/04/earpiece-t...

CAR-T Cells: Engineered Cancer Killers

Yeast gains power to harness light

The first light-powered brewer’s yeast (Saccharomyces cerevisiae) has been engineered. “It is extraordinary,” says biologist Felipe Santiago-Tirado. “To some extent, it’s like turning an animal into a plant.” A protein called rhodopsin was artificially inserted into yeast cells, giving the fungus the ability to use light as an energy source for some of its cellular functions. Under green light, light-powered yeast cells reproduce fast enough to outgrow normal yeast.

https://www.biorxiv.org/content/10.1101/2022.12.06.519405v2

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Scientists uncover the structure of a bacterial toxin which injects itself into human cells and kills them

researchers have revealed the molecular structure of a cell-killing toxin produced by the bacterium Serratia marcescens.

S. marcescens is commonly involved in hospital-acquired infections – including respiratory diseases, bloodstream and urinary tract infections – and has developed resistance to many commonly used antibiotics.

Researchers discovered the toxin is able to inject itself into and kill a wide range of living cells, including in humans and livestock, insects, and plants.

The team determined the three-dimensional structure of Ssp using X-ray crystallography and identified a specific domain that promotes cell entry. It might also break down protein targets within the cell to cause its death – though more research is needed to confirm this.

The finding, published in Nature Communications, could lead to the development of new antimicrobial treatments and circumvent the use of antibiotics.

By understanding what Ssp looks like scientists can now develop targeted inhibitors.

These inhibitors or antimicrobials may be developed to bind to the part of Ssp responsible for injecting itself into cells.

https://www.nature.com/articles/s41467-023-36719-2

New inhibitors of the Ssp toxin, could be used to ‘disarm’ S. marcescens and reduce the sickness during infections. This would circumvent the use of antibiotics.

https://www.latrobe.edu.au/news/articles/2023/release/new-cell-kill...

Defying gravity with the Brazil nut effect

Physicists  have observed—for the first time experimentally—the Brazil nut effect in a mixture of charged colloidal particles.

Until now, it was thought that an influx of external energy was required to create this effect—but the researchers were able to confirm that the process can occur spontaneously. 

Shake an open bag of mixed nuts. Have you noticed that after such a procedure, the largest nuts in the mixture—Brazil nuts—float to the top? The phenomenon of large objects rising to the surface of a mixture of small objects, bearing the professional name of granular convection, is popularly referred to "the Brazil nut effect" and occurs commonly in nature. It can also be observed by shaking, for example, a bucket of sand and pebbles.

This unusual effect contradicts the intuition that heavier objects should sink to the bottom due to gravity and inertia force. This is the case with the phenomenon of sedimentation, common in nature, a process involving the sinking of solid particles dispersed in a liquid, under the influence of gravity or inertia forces. Sedimentation plays a role in processes such as the formation of sedimentary rocks, and is also used to purify water and wastewater or isolate cells from blood.

Until now, it was thought that an influx of external energy, such as shaking the bag, was necessary to create the Brazil nut effect. However, theoretical models being developed suggested that the phenomenon could occur spontaneously, without the supply of external energy. The theoretical calculations were confirmed experimentally for the first time by a group of experimental and theoretical physicists.

They  have shown that the Brazil nut effect can take place in a mixture of charged colloidal particles driven solely by Brownian motions and repulsion of electric charges. 

Part 1

The researchers used charged polymethylmethacrylate particles with different diameters (large and small) to carry out the experiment. A low-polar solvent, cyclohexyl bromide, was used as a dispersing agent.

As the researchers point out, although in both granular (e.g., nut) and colloidal mixtures the "Brazil nut effect" occurs, the mechanisms for its formation are completely different. In the case of a nut mixture, as a result of shaking, smaller nuts fill in the gaps created at the bottom, pushing the larger nuts to the top.

Meanwhile, the charged particles in the colloid make Brownian motion as a result of collisions with the surrounding solvent molecules. "Each particle is positively charged. Heavier but larger particles have a greater charge, so they repel each other more strongly, making them move upward more easily than smaller but lighter particles

The discovery of the "Brazil nut effect" in mixtures of colloidal particles can be used in many fields from geology to soft matter physics. It can also find application in industry such as in the stability of paint and ink.

 Marjolein N. van der Linden et al, Realization of the Brazil-nut effect in charged colloids without external driving, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2213044120

Part 2

Gut bacteria could be behind weaker immune responses to COVID-19 vaccine

Gut bacteria that break down a sugar called fucose could be dampening our immune response to the COVID-19 mRNA vaccine, according to a study  by researchers.

The scientists report that increased fucose digestion by bacteria in the gut before vaccination was associated with lower numbers of T-cells activated by vaccination. T-cells are an important type of blood immune cell that are activated by a specific strain of bacteria or virus, and then multiply to fight the infection.

The findings, published April 20 in Communications Biology, illustrate the important impact that the trillions of bacteria in our gut—collectively called our 'gut microbiome'— have on our immune health and adds a missing piece to the puzzle of why vaccination varies in effectiveness from person to person.

While this research focused on the response to the COVID-19 Pfizer mRNA vaccine, the researchers think their results could also be relevant for other mRNA vaccines in development that protect against other infectious diseases, and even cancer.

The researchers now plans to experimentally manipulate the gut bacteria in mice and investigate the exact mechanism of FOS and ATF3, to further understand the link between the microbiome, blood immune cells and the overall immune response.

Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity, Communications Biology (2023). DOI: 10.1038/s42003-023-04755-9

Part 1

In this study, Prof. Ishikawa and his colleagues took a stool sample and multiple blood samples from 96 healthy participants living in Okinawa, starting before the first dose of the vaccine, and ending a month after the second dose.

They then did a broad analysis, looking at all the genes from immune cells in the blood and bacteria in the gut to see if there was any association with an individual's T-cell and antibody levels.

The researchers did not find a significant link to antibody levels, but they did find that individuals that had a lower T-cell response also had a gut microbiome with a high activity of fucose digestion.

The team also found that individuals with a reduced T-cell response had higher expression of two genes, FOS and ATF3, prior to vaccination. These genes are expressed by blood immune cells, and code for proteins that are part of a larger group, called AP-1 transcription factors. Previous research has shown that different AP-1 transcription factors control T-cell survival and activity, but the exact role and function of these two proteins remains unknown.

Individuals with higher expression of FOS and ATF3 prior to vaccination also had microbiomes with high activity of fucose digestion, suggesting that the gut's impact on the immune system is through a pathway that involves FOS and ATF3.

"The mechanism is not yet proven, but we propose that fucose digestion leads to increased baseline expression of FOS and ATF3 in blood immune cells, which in turn weakens the response to the COVID-19 vaccine," said Masato Hirota, first author and Ph.D. student in the Immune Signal Unit. "It's clear that the gut bacteria have an important impact on the overall health of the immune system."

Part 2

The climate crisis and biodiversity crisis can't be approached separately, says study

Human beings have massively changed the Earth system. Greenhouse-gas emissions produced by human activities have caused the global mean temperature to rise by more than 1.1°C compared to the preindustrial era. And every year, there are additional emissions of carbon dioxide, methane and other greenhouse gases, currently amounting to more than 55 gigatons of carbon dioxide equivalent.

This unprecedented climate crisis has consequences for the entire planet—the distribution of precipitation is shifting, global sea level is rising, extreme weather events are becoming more frequent, the ocean is becoming more acidic, and anoxic zones continue to expand.

The climate crisis they themselves caused is likely the greatest challenge that homo sapiens have faced in their 300,000-year history. 

Yet at the same time another, equally dangerous crisis is unfolding, one that is often overlooked—the dramatic loss of plant and animal species across the planet. The two catastrophes—the climate crisis and biodiversity crisis—are interdependent and mutually amplifying, which is why they should never be seen as two separate things. Consequently, a new review study shows in detail the connections between the climate crisis and biodiversity crisis and presents solutions for addressing both catastrophes and mitigating their social impacts, which are already dramatic.

Part 1

Eighteen international experts contributed to the study. Just published in the journal Science, it is the outcome of a virtual scientific workshop held in December 2020, which 62 researchers from 35 countries attended. 

In their study, the experts describe the rapidly worsening loss of species with the aid of sobering figures: they estimate that human activities have altered roughly 75% of the land surface and 66% of the marine waters on our planet. This has occurred to such an extent that today, approximately 80% of the biomass from mammals and 50% of plant biomass has been lost, while more species are in danger of extinction than at any time in human history. In this regard, global warming and the destruction of natural habitats not only lead to biodiversity loss, but also reduce the capacity of organisms, soils and sediments to store carbon, which in turn exacerbates the climate crisis.

Because each organism has a certain tolerance range for changes to its environmental conditions (e.g., temperature), global warming is also causing species' habitats to shift. Mobile species follow their temperature range and migrate toward the poles, to higher elevations (on land, mountain ranges) or to greater depths (in the ocean). Sessile organisms like corals can only shift their habitats very gradually, in the course of generations: as such, they are caught in a temperature trap, which means that large coral reefs could, in the long term, disappear entirely. And mobile species, too, could run into climatic dead ends in the form of mountain summits, the coasts of landmasses and islands, at the poles and in the ocean's depths, if they can no longer find any habitat with suitable temperatures to colonize. In order to address these multiple crises, the researchers propose an ambitious combination of emissions reduction, restoration and protection measures, intelligent land-use management, and promoting cross-institutional competencies among political actors. Needless to say, a massive reduction of greenhouse-gas emissions and reaching the 1.5-degree target continue to be at the top of the priorities list.

 H.-O. Pörtner, Overcoming the coupled climate and biodiversity crises and their societal impacts, Science (2023). DOI: 10.1126/science.abl4881. www.science.org/doi/10.1126/science.abl4881

Part 2

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