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.

Part 1

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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How Do Greenhouse Gases Actually Work?

Chandra X-ray Observatory identifies new stellar danger to planets

Astronomers using data from NASA's Chandra X-ray Observatory and other telescopes have identified a new threat to life on planets like Earth: a phase during which intense X-rays from exploded stars can affect planets over 100 light-years away. This result has implication for the study of exoplanets and their habitability.

This newly found threat comes from a supernova's blast wave striking dense gas surrounding the exploded star. When this impact occurs it can produce a large dose of X-rays that reaches an Earth-like planet months to years after the explosion and may last for decades. Such intense exposure may trigger an extinction event on the planet.

A new study reporting this threat is based on X-ray observations of 31 supernovae and their aftermath—mostly from NASA's Chandra X-ray Observatory, Swift and NuSTAR missions, and ESA's XMM-Newton—show that planets can be subjected to lethal doses of radiation located as much as about 160 light-years away. Four of the supernovae in the study (SN 1979C, SN 1987A, SN 2010jl, and SN 1994I) are shown in composite images containing Chandra data in the supplemental image.

If a torrent of X-rays sweeps over a nearby planet, the radiation could severely alter the planet's atmospheric chemistry. For an Earth-like planet, this process could wipe out a significant portion of ozone, which ultimately protects life from the dangerous ultraviolet radiation of its host star. It could also lead to the demise of a wide range of organisms, especially marine ones at the foundation of the food chain, leading to an extinction event.

 Ian R. Brunton et al, X-Ray-luminous Supernovae: Threats to Terrestrial Biospheres, The Astrophysical Journal (2023). DOI: 10.3847/1538-4357/acc728

How electricity can heal wounds three times faster

Chronic wounds are a major health problem for diabetic patients and the elderly—in extreme cases they can even lead to amputation. Using electric stimulation, researchers have developed a method that speeds up the healing process, making wounds heal three times faster.

For most people, a small wound does not lead to any serious complications, but many common diagnoses make wound healing far more difficult. People with diabetes, spinal injuries or poor blood circulation have impaired wound healing ability. This means a greater risk of infection and chronic wounds—which in the long run can lead to such serious consequences as amputation.

Electric guidance of cells for faster healing
The researchers worked from an old hypothesis that electric stimulation of damaged skin can be used to heal wounds. The idea is that skin cells are electrotactic, which means that they directionally "migrate" in electric fields. This means that if an electric field is placed in a petri dish with skin cells, the cells stop moving randomly and start moving in the same direction.

The researchers investigated how this principle can be used to electrically guide the cells in order to make wounds heal faster. Using a tiny engineered chip, the researchers were able to compare wound healing in artificial skin, stimulating one wound with electricity and letting one heal without electricity. The differences were striking.

Researchers were able to show that the old hypothesis about electric stimulation can be used to make wounds heal significantly faster. In order to study exactly how this works for wounds, they developed a kind of biochip on which they cultured skin cells, which they then made tiny wounds in. Then they stimulated one wound with an electric field, which clearly led to it healing three times as fast as the wound that healed without electric stimulation.

In the study, the researchers also focused on wound healing in connection with diabetes, a growing health problem worldwide. One in 11 adults today has some form of diabetes according to the World Health Organization (WHO) and the International Diabetes Federation.

The researchers have also looked at diabetes models of wounds and investigated whether this method could be effective even in those cases. They saw that when they mimicked diabetes in the cells, the wounds on the chip healed very slowly. However, with electric stimulation they could increase the speed of healing so that the diabetes-affected cells almost corresponded to healthy skin cells.

Sebastian Shaner, Anna Savelyeva, Anja Kvartuh, Nicole Jedrusik, Lukas Matter, José Leal, Maria Asplund. Bioelectronic microfluidic wound healing: a platform for investigating direct current stimulation of injured cell collectives. Lab on a Chip, 2023; 23 (6): 1531 DOI: 10.1039/D2LC01045C

Mosquito Saliva Can Actually Suppress Our Immune System, Study Finds

We know mosquitoes are a serious threat to our health as human beings– in fact, they're the world's deadliest animal, with mosquito-borne diseases responsible for more than a million deaths a year.

And it's not just their bites that we need to worry about. New research shows how the saliva of a mosquito carrying the  dengue virus is loaded with a substance that may suppress our immune system response and increase the risk of infection.

Through three separate analysis methods, scientists identified a specific type of viral RNA, or chemical messenger, called sfRNA in the infected mosquito saliva. It essentially blocks the defense mechanisms the human body puts up against infection.

It's incredible that the virus can hijack these molecules so that their co-delivery at the mosquito bite site gives it an advantage in establishing an infection.

These findings provide new perspectives on how we can counteract dengue virus infections from the very first bite of the mosquito.

The sfRNA is loaded in membrane compartments called extracellular vesicles, ready for delivery. The dengue virus appears to "subvert mosquito biology", in the words of the researchers, to give it a better chance of spreading. In tests on immortalized cell lines, the team confirmed that this sfRNA payload did indeed increase virus infection levels – laying the groundwork so that the human body isn't quite so well prepared for attack. These sfRNAs have been spotted before in insect-borne viruses, including Zika and yellow fever. Their role, more generally, seems to be to get in the way of the chemical signaling used by the body as the virus replicates.

Right now, there's no way of treating the virus, only methods for managing the symptoms. While we're still some way from a drug to treat dengue, understanding more about it and how it spreads is essential in fighting it.

https://journals.plos.org/plospathogens/article?id=10.1371/journal....

A First-of-Its-Kind Signal Has Been Detected in The Human Brain

Scientists have recently identified a unique form of cell messaging occurring in the human brain that's not been seen before.

Excitingly, the discovery hints that our brains might be even more powerful units of computation than we realized.

In 2020, researchers  reported a mechanism in the brain's outer cortical cells that produces a novel 'graded' signal all on its own, one that could provide individual neurons with another way to carry out their logical functions.

By measuring the electrical activity in sections of tissue removed during surgery on epileptic patients and analyzing their structure using fluorescent microscopy, the neurologists found individual cells in the cortex used not just the usual sodium ions to 'fire', but calcium as well.

This combination of positively charged ions kicked off waves of voltage that had never been seen before, referred to as a calcium-mediated dendritic action potentials, or dCaAPs.

Brains – especially those of the human variety – are often compared to computers. The analogy has its limits, but on some levels they perform tasks in similar ways.

Both use the power of an electrical voltage to carry out various operations. In computers it's in the form of a rather simple flow of electrons through intersections called transistors.

In neurons, the signal is in the form of a wave of opening and closing channels that exchange charged particles such as sodium, chloride, and potassium. This pulse of flowing ions is called an action potential.

Instead of transistors, neurons manage these messages chemically at the end of branches called dendrites.

"The dendrites are central to understanding the brain because they are at the core of what determines the computational power of single neurons.

Part 1

Dendrites are the traffic lights of our nervous system. If an action potential is significant enough, it can be passed on to other nerves, which can block or pass on the message.

This is the logical underpinnings of our brain – ripples of voltage that can be communicated collectively in two forms: either an AND message (if x and y are triggered, the message is passed on); or an OR message (if x or y is triggered, the message is passed on).

Arguably, nowhere is this more complex than in the dense, wrinkled outer section of the human central nervous system; the cerebral cortex. The deeper second and third layers are especially thick, packed with branches that carry out high order functions we associate with sensation, thought, and motor control.

It was tissues from these layers that the researchers took a close look at, hooking up cells to a device called a somatodendritic patch clamp to send active potentials up and down each neuron, recording their signals.

There was a 'eureka' moment when  scientists saw the dendritic action potentials for the first time.

To ensure any discoveries weren't unique to people with epilepsy, they double checked their results in a handful of samples taken from brain tumors.

While the team had carried out similar experiments on rats, the kinds of signals they observed buzzing through the human cells were very different.

More importantly, when they dosed the cells with a sodium channel blocker called tetrodotoxin, they still found a signal. Only by blocking calcium did all fall quiet.

Finding an action-potential mediated by calcium is interesting enough. But modelling the way this sensitive new kind of signal worked in the cortex revealed a surprise.

In addition to the logical AND and OR-type functions, these individual neurons could act as 'exclusive' OR (XOR) intersections, which only permit a signal when another signal is graded in a particular fashion.

More work needs to be done to see how dCaAPs behave across entire neurons, and in a living system. Not to mention whether it's a human-thing, or if similar mechanisms have evolved elsewhere in the animal kingdom.

https://www.science.org/doi/10.1126/science.aax6239

Part 2

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Stuck stem cells cause grey hair

Hair turns grey when melanocyte stem cells in the hair follicle fail to mature into thei... — at least that’s true in mice, and humans have similar cells. Scientists had thought that hair greys because the follicle runs out of melanocytes. A team tracked individual cells in mice over two years, which revealed that melanocytes travel up and down the hair follicle and switch back and forth between mature and young states. When the cells become stuck and stop making this journey, they stop receiving the signal to produce pigment.

Unlike embryonic stem cells, which develop into all sorts of different organs, adult stem cells have a more set path. The melanocyte stem cells in our hair follicles are responsible for producing and maintaining the pigment in our hair.

Each hair follicle keeps immature melanocyte stem cells in storage. When they’re needed, those cells travel from one part of the follicle to another, where proteins spur them to mature into pigment-producing cells, giving hair its hue.

Scientists assumed that gray hair was the result of that pool of melanocyte stem cells running dry. However, previous studies with mice made  scientists wonder if hair could lose its pigment even when stem cells are still present.

To learn more about stem cell behavior throughout different phases of hair growth, the researchers spent two years tracking and imaging individual cells in mouse fur. To their amazement, the stem cells traveled back and forth within the hair follicle, transitioning into their mature, pigment-producing state and then out of it again.

But as time wore on, the melanocyte cells couldn’t keep up the double act. A hair falling out and growing back takes a toll on the follicle, and eventually, the stem cells stopped making their journey, and thus, stopped receiving protein signals to make pigment. From then on, the new hair growth didn’t get its dose of melanin.

The researchers further explored this effect by plucking hairs from mice, simulating a faster hair growth cycle. This “forced aging” led to a buildup of melanocyte stem cells stuck in their storage place, no longer producing melanin. The mice’s fur went from dark brown to salt-and-pepper.

While the study was conducted with rodents, the researchers say their findings should be relevant to how human hair gets and loses its color. What’s more, they hope their findings could be a step toward preventing or reversing the graying process.

https://www.nature.com/articles/s41586-023-05960-6.epdf?sharing_tok...

eHighway - solution for electrified road freight transport

It's not as difficult as you think to shout upwind, shows study

For years, people have been wondering why it feels so difficult to shout upwind. The sensation is common enough to have found its way into an idiom about not being understood. But a scientific explanation for the phenomenon is  - there wasn't been one!

A research team showed that our common sense understanding of this situation is wrong. It isn't harder to shout into the wind; it's just harder to hear yourself.

In fact, acousticians have long known that sound carries better within the first 100 meters upwind. Many people have noticed that a siren sounds louder as it approaches and then quieter as it moves away. The mechanics behind this is similar to the Doppler effect, in which a sound changes frequency as it moves.

Research had confirmed that wind doesn't affect the emanation pattern of speech, so there was no reason why shouting into the wind would be difficult.

Their results were surprising but simple: it's harder for people to hear themselves when shouting upwind.

When someone shouts upwind, their ears are situated downwind from their mouth, which means that their ears receive less sound—it's harder from them to hear their shout than when there's no wind.

The same thing happens when someone is moving quickly even if there's no wind blowing—if you're cycling, for example. As a person bikes, their motion generates a wind around their head even in stationary air, and they end up shouting because they can't hear their own voice well.

So be careful what you shout upwind, for others might hear you just fine, even if you don't. This information is particularly useful for people who work with sound, such as musicians.

Ville Pulkki et al, Perceived difficulty of upwind shouting is a misconception explained by convective attenuation effect, Scientific Reports (2023). DOI: 10.1038/s41598-023-32306-z

Using superconductors to move people, cargo and energy through one combined system

The promise of superconductivity for electrical power transmission and transportation has long been held back by high costs. Now researchers  have demonstrated a way to cut the cost and upend both the transit and energy transport sectors by using superconductors to move people, cargo and energy along existing highway infrastructure.

The combined system would not only lower the cost of operating each system but would also provide a way to store and transport liquified hydrogen, an important future source of clean energy. The liquified hydrogen would be used to cool the superconductor guideway as it is stored and transported, reducing the need for a separate specialized pipeline system capable of cooling the fuel to 20 degrees Kelvin, or minus 424 Fahrenheit. The concept, described in a paper published on April 24, 2023 in the journal APL Energy, suggests a future in which air travel and traditional freight transport could become obsolete, replaced by a "super system" allowing personal and commercial vehicles to travel at speeds up to 400 miles an hour—maybe even twice that fast.

Researchers built a model to demonstrate the key technical aspect of the concept—levitating a magnet above a superconductor guideway. Liquified nitrogen was used to cool the superconductors in the model; Researchers say future models will use hydrogen.

Vehicles with magnetized undercarriages—trains, cargo trucks, even personal vehicles—would enter the superconductor guideway, levitating and moving at high speed to reach their destinations. After leaving the guideway, vehicles would continue their trips powered by traditional electric or internal combustion motors.

People would be able to travel at their own convenience while enjoying the time-saving benefits of high-speed trains and air travel.

Fuel or electrical power consumption would drop dramatically while the car or truck was on the superconductor guideway, reducing both the cost and the environmental footprint.

Oleksii Vakaliuk et al, A multifunctional highway system incorporating superconductor levitated vehicles and liquefied hydrogen, APL Energy (2023). DOI: 10.1063/5.0139834. pubs.aip.org/aip/ape/article/1/1/016107/2884934

Population growth is the main driver of increased carbon emissions, study finds

The richest countries emit more carbon dioxide than the rest of the world combined, while population is only growing in the poorest countries. These are two widespread notions that argue for focusing on reducing emissions per capita in order to mitigate climate change. But this is not entirely true on the light of data from the last 30 years, new research published in the journal Sustainability shows.

A dominant narrative in the climate change debate is that addressing population is not relevant for mitigation. This is because the population is only growing in the poorest countries, whose contribution to global carbon emissions is negligible, the reasoning goes. The largest emissions come instead from rich countries where the population no longer grows.

"This way of reasoning is not correct. Our thorough analysis suggests that climate change mitigation strategies should address population along with per capita consumption and technological innovation. A comprehensive approach to the problem is needed," says Giangiacomo Bravo, professor at Linnaeus University.

Part 1

The World Bank's four income groups

The World Bank has four classifications of income for the world's countries: low, lower-middle, upper-middle and high income. These are based on the respective country's gross national income (GNI) per capita.

The current figures apply to the year 2021, when 28 countries are defined as low-income countries, 54 as lower-middle, 54 as upper-middle and 81 as high-income countries.

Analysis of 30 years of emission data

The basis for Giangiacomo Bravo's statement is the analysis of 30 years of emission data for all the world's countries that he and two research colleagues have carried out. By splitting the countries into four income groups according to the World Bank's standard classification, the researchers were able to confirm that the contribution of low-income countries to emission increase is indeed limited. However, they also found that:

• Population is growing in all four income groups.
• The largest contribution to global carbon emissions comes from the upper-middle group.
• Population growth is the main driver of increased emissions in all income groups except the upper-middle one.
• The successful reduction in per capita emissions that occurred in high-income countries was nullified by the parallel increase in population in the same group.

Part 2

"Our analysis does not support the widespread belief that increased affluence is the main driver of increased carbon emissions at the global level. It is definitely an important factor, but neglecting population growth leads to a skewed and misleading vision of reality."

"Developed nations with stable or declining populations should hence quit fighting these trends and instead embrace them. Just as a small population growth in rich countries can drive big emission increases, a population decrease in rich countries could have big emission-related benefits going forward," says Giangiacomo Bravo.

Study examines the potential of edible cutlery

Plastic waste is an increasing problem the world over, with food packaging and single-use items such as plastic knives and forks representing a significant component of the waste stream. There have been efforts to replace disposable cutlery with implements crafted from wood or bamboo, but work in the International Journal of Mathematical Modelling and Numerical Optimisation has looked at a radical alternative—edible cutlery.

Researchers think that creating edible cutlery from millet is one possibility. However, as they explain the production of such items from this unusual source material requires a lengthy step-by-step process.

the researchers recognized that such step-by-step processes lend themselves to being defined by a scientific queuing model that can be solved using supplementary variable queuing technology. They have thus developed a conceptual approach to queue theory that might be implemented in the creation of edible cutley and is displayed through a numerical and complex visual analysis.

Millet is a nutritious, gluten-free, and easily cultivable crop that is widely grown in many parts of the world, particularly in Africa and Asia. It is a general term for are small-grained, annual, warm-weather cereals in the grass family of crops. These plants are fast-growing and highly drought-tolerant. They could therefore be useful as a sustainable and accessible source material in the developing world.

If such edible cutlery were to become a sustainable alternative to plastic or wooden products, then there is a cradle-to-grave assessment to be made of energy and resource costs as well as a need for health and safety considerations. The team has surveyed potential users and found the concept largely acceptable. All that said, chewing and swallowing a millet knife and fork at the end of one's meal may not be to everyone's taste.

Mitochondrial DNA: Are some mutations more equal than others?

The team studied eight different tissues – ranging from the kidney, to the brain and the heart – in young and old mice which were 4.5 and 26 months old. This resulted in an unprecedently large dataset consisting of around 80,000 somatic mtDNA mutations, showing that the rate of accumulation and the composition of mutations vary between different tissues. The highest accumulation rate was in the kidney, where mutations reached the level of one in five mtDNA molecules.

In agreement with previous studies, Sanchez-Contreras et al. observed a high proportion of transition mutations, in which purine (adenine and guanine) and pyrimidine (thymine and cytosine) nucleotide bases are only exchanged for other purines or pyrimidines, respectively. An unusually high proportion of transversion mutations – where a purine changes to a pyrimidine, or vice versa – were also detected. However, unlike the transition mutations, these transversions did not clonally expand and did not accumulate with age in any of the tissues studied. Because new transversions are constantly being generated (mostly through damage caused by reactive oxygen species), lack of accumulation with age implies that these mutations are excluded from being propogated in somatic cells.

Intriguingly, another study also found a high proportion of transversion mutations in the mtDNA of mouse egg cells , which was surprising given that the proportion of inherited mutations that are transversions is usually very low. This suggests that transversion mutations are excluded from being propagated in germ cells as well.

Part 2

Why do transversions not expand and accumulate with age? And why do transversion and transition mutations behave differently?

Despite using a duplex sequencing approach, it is possible that the transversions they detect might have been potentially generated in vitro from real in vivo DNA damage.

The researchers built a model to understand this: there are two broad classes of mtDNA molecules (Figure 1): a ‘stem subpopulation’ of actively replicating mtDNAs which are responsible for renewing the mtDNA pool, and a ‘worker subpopulation’ which are located in actively respiring mitochondria. ‘Stem’ mtDNAs reside in mitochondria that respire less and are therefore protected from reactive oxygen species. Consequently, transversions primarily occur on ‘worker’ mtDNA molecules which rarely replicate, which prevents these mutations from being able to clonally expand and accumulate with age. 

https://elifesciences.org/articles/87194?utm_source=content_alert&a...

Part 3