A Bacterial Culprit for Rheumatoid Arthritis

Scientists identified a species of Subdoligranulum that may drive disease.

heumatoid arthritis (RA) is a debilitating autoimmune condition that affects millions of people across the globe (1). The ultimate cause of RA is largely mysterious. While researchers have long suspected that the microbiome influenced development of the disease, the specific microbe (or microbes) has eluded identification.

Now, in a recent Science Translational Medicine paper, researchers reported a strain of Subdoligranulum bacteria that may drive RA development . Some people at risk for the disease have antibodies against this bacteria, and Subdoligranulum activation of T cells was more prevalent in people with RA than in healthy controls. Perhaps even more intriguingly, mice given this bacterium developed a condition similar to human RA.

Identifying this bacterium was no simple task. First, the research team, a collaboration between scientists at the University of Colorado, Stanford University, and the Benaroya Research Institute, screened blood donated by people at risk for RA or with early-stage RA for RA-related autoantibodies.

Then researchers tested whether any of these autoantibodies also targeted human intestinal bacteria. They mixed the antibodies with bacteria from stool samples donated by healthy people and people with RA. They then sequenced the bacterial species to which the autoantibodies attached. These RA antibodies cross-reacted with many species of bacteria, largely from Lachnospiraceae or Ruminococcaceae, two closely related families.

To study these species in more detail, researchers cultured bacteria from the stool of an individual who had high levels of these two bacterial families present. Two types of Subdoligranulum bacteria, which they called isolates 1 and 7, emerged as potential candidates for driving RA development. Compared to isolate 1, isolate 7 was a more potent activator of T cells in blood from RA patients.

To find out if isolate 7 bacteria actually caused disease, scientists fed the bacteria to mice. After a couple of weeks,  the mice got swollen paws. This is similar to the swollen hand and finger joints experienced by people with RA.

The similarities between the mice and human RA patients extended beyond what could be seen with the naked eye. There were antibodies getting into the joints, much like we see in rheumatoid arthritis.

1. Chriswell, M. E. et al. Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Science Translational Medicine  14, eabn5166 (2022).
2. Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife  2, e01202 (2013).

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CRISPR Protects Bacteria From Invading Viruses in a Completely Unexpected Way

The acronym CRISPR has become synonymous with editing DNA in recent years, taking center stage in the molecular geneticist's toolbox as a means of identifying genetic codes and then cutting into them with uncanny precision.
In its original function as a means of immunity in bacteria, the CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated endonuclease) system seeks out known genes of invading viruses and renders them dysfunctional.

Scientists  have discovered that the famous gene-editing tool does more in bacteria than just spot DNA for chopping up; it coordinates with other proteins to bulk up defenses against invading viruses as well.

Activating the funnel-shaped proteins – called Csx28 – scrambles the permeability of the bacteria's membrane, making it difficult for invading viral DNA to hijack the cell's machinery and replicate.

The study involved a series of experiments where Escherichia coli bacteria were infected with a virus that infects bacteria, or bacteriophage, called enterobacteria phage λ. This phage latches onto the bacteria cell surface like a lunar module and injects its DNA into the cell to create copies of itself. The E. coli fight back, using CRISPR to identify the threat by matching repetitive DNA sections from previously encountered phages, and then using an enzyme called Cas13b to snip the invading DNA into pieces.

The researchers found that the virus replicated sluggishly when Csx28 was present inside the bacteria.

part1

This protein only worked in conjunction with Cas13b, which suggested the two were coordinating with each other to disarm the virus.

When both Cas13b and Csx28 were present, the proportion of infected bacteria that released infectious viral particles decreased from around 19 percent to roughly 3 percent, and there was a significant reduction of phage numbers per milliliter. In other words, the virus wasn't able to replicate as much as it usually would.

The researchers examined the structure of the Csx28 protein using a technique called cryogenic electron microscopy and found that it resembled a funnel with a hole in the center.

This raised the possibility that the protein formed a membrane pore and was disrupting the metabolism of the cell to make it an inhospitable environment for the virus.

The researchers tested this hypothesis using a technique that makes cells fluorescent after they have lost their membrane potential, a small electrical charge caused by the difference in the concentration of ions inside and outside the cell.

They found that the two proteins together caused the membrane to depolarize, sending in a rush of charged atoms that radically altered the cell's internal environment. After 90 minutes, 40 percent of the bacterial population was depolarized in this fashion.

It is really impressive that the research team identified this pore-like protein that doesn't resemble anything else we've seen before.

https://www.science.org/doi/10.1126/science.abm1184

Part 2

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'Deletions' from the human genome may be what made us human

 What the human genome is lacking compared with the genomes of other primates might have been as crucial to the development of humankind as what has been added during our evolutionary history, according to a new study led by researchers.

The new findings, published April 28 in the journal Science, fill an important gap in what is known about historical changes to the human genome. While a revolution in the capacity to collect data from genomes of different species has allowed scientists to identify additions that are specific to the human genome — such as a gene that was critical for humans to develop the ability to speak — less attention has been paid to what’s missing in the human genome.

For the new study researchers used an even deeper genomic dive into primate DNA to show that the loss of about 10,000 bits of genetic information — most as small as a few base pairs of DNA — over the course of our evolutionary history differentiate humans from chimpanzees, our closest primate relative. Some of those “deleted” pieces of genetic information are closely related to genes involved in neuronal and cognitive functions, including one associated with the formation of cells in the developing brain.

These 10,000 missing pieces of DNA — which are present in the genomes of other mammals — are common to all humans, the researchers found.

The fact that these genetic deletions became conserved in all humans, the authors say, attests to their evolutionary importance, suggesting that they conferred some biological advantage.

Often we think new biological functions must require new pieces of DNA, but this work shows us that deleting genetic code can result in profound consequences for traits make us unique as a species.

Researchers found that some genetic sequences found in the genomes of most other mammal species, from mice to whales, vanished in humans. But rather than disrupt human biology, they say, some of these deletions created new genetic encodings that eliminated elements that would normally turn genes off.

The deletion of this genetic information had an effect that was the equivalent of removing three characters — “n’t” — from the word “isn’t” to create a new word, “is.”
Such deletions can tweak the meaning of the instructions of how to make a human slightly, helping explain our bigger brains and complex cognition.

The researchers used a technology called Massively Parallel Reporter Assays (MPRA), which can simultaneously screen and measure the function of thousands of genetic changes among species.

“These tools have the capability to allow us to start to identify the many small molecular building blocks that make us unique as a species.

https://news.yale.edu/2023/04/27/deletions-human-genome-may-be-what...,'Deletions'%20from%20the%20human%20genome%20may%20be%20what%20made%20us,team%20of%20Yale%20researchers%20found.

The functional and evolutionary impacts of human-specific deletions in conserved elements. Science, 2023; 380 (6643) DOI: 10.1126/science.abn2253

cUSP - Conformable Ultrasound Sonophoresis Patch

Using bubbles, instead of needles to penetrate skin

Untangling Worm Blobs
Tiny California blackworms tangle themselves by the thousands to form ball-shaped blobs that allow them to execute a wide range of biological functions. But, while the worms tangle over a period of several minutes, they can untangle in milliseconds, escaping at the first sign of a threat from a predator.

Even Clouds Are Carrying Drug-Resistant Bacteria

For  researchers dark clouds on the horizon are potentially ominous not because they signal an approaching storm – but because they were found in a recent study to carry drug-resistant bacteria over long distances.

These bacteria usually live on the surface of vegetation like leaves, or in soil. It was found now that they are carried by the wind into the atmosphere and can travel long distances – around the world – at high altitudes in clouds.

https://www.sciencedirect.com/science/article/abs/pii/S004896972208...

Brain activity decoder can reveal stories in people's minds

A new artificial intelligence system called a semantic decoder can translate a person's brain activity—while listening to a story or silently imagining telling a story—into a continuous stream of text. The system developed by researchers might help people who are mentally conscious yet unable to physically speak, such as those debilitated by strokes, to communicate intelligibly again.

The work relies in part on a transformer model, similar to the ones that power Open AI's ChatGPT and Google's Bard.

Unlike other language decoding systems in development, this system does not require subjects to have surgical implants, making the process noninvasive. Participants also do not need to use only words from a prescribed list. Brain activity is measured using an fMRI scanner after extensive training of the decoder, in which the individual listens to hours of podcasts in the scanner. Later, provided that the participant is open to having their thoughts decoded, their listening to a new story or imagining telling a story allows the machine to generate corresponding text from brain activity alone.

The result is not a word-for-word transcript. Instead, researchers designed it to capture the gist of what is being said or thought, albeit imperfectly. About half the time, when the decoder has been trained to monitor a participant's brain activity, the machine produces text that closely (and sometimes precisely) matches the intended meanings of the original words.

 Semantic reconstruction of continuous language from non-invasive brain recordings, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01304-9

A protein hidden in plain sight helps cells time their escape

When a cell is getting ready to divide, it needs to duplicate its DNA, which is divided among its chromosomes, and arrange the chromosomes so that each new cell gets one complete set. If the chromosomes get sorted incorrectly, the resulting cells with the wrong number or set can become dysfunctional, or even cancerous.

Because the risks are so severe, cells have evolved strong controls to ensure that upon division, each of the daughter cells has the correct chromosomes. If a cell's machinery detects errors while the cell is preparing to divide, division is paused until those errors are corrected.

However, if division gets paused for too long, a state called being in arrest, the cell will eventually die. To escape this fate, every type of cell has a different timer for how long it will stay in arrest before escaping. When the timer runs out, cells exit the process of cell division without completing it, and resume life with double the normal number of chromosomes.

Researchers have wondered what mechanisms determine how long a cell will remain in arrest and how they manage to escape it. The question is particularly important in the context of cancer cells, which can use early escapes from arrest to evolve—changing their sets of chromosomes—and resist common cancer drugs.

New research identifies a way in which cells set their timers for arrest. The key player is a previously undiscovered variant of a known protein, CDC20.

What they discovered, as published in Nature on April 26, is that cells produce both full-length and shortened, alternative versions of CDC20, and that the shifting ratio of these versions determines when cells will escape arrest.

Alternative proteins like these are very hard to find, because cells don't make them in the way that researchers and common analytic tools typically look for, but researchers are coming to appreciate their prevalence and importance to biology.

CDC20—the full-length protein, that is—has a well-known role in cell division. If no issues are detected at the checkpoint before chromosomes are pulled apart, then CDC20 binds to and activates a molecular complex called the anaphase-promoting complex (APC/C), which in turn initiates the end stages of cell division. If an issue is detected, then a mechanism called the spindle assembly checkpoint (SAC) inhibits CDC20, arresting cell division.

The researchers discovered that CDC20 plays another important role at this checkpoint, thanks to its previously undetected alternatives. As a protein, CDC20 is assembled according to a genetic sequence contained in messenger RNA. 

Part 1

However, they found that sometimes the machinery translating the CDC20 RNA into protein skips the normal starting point, and begins following the instructions from one of two unofficial starting points farther down the RNA sequence, which causes it to create alternative short versions of the molecule. These short versions vary from the full-length protein in one crucial way: they are not inhibited by the SAC. This means that the cell cannot stop them from activating the APC/C, even in the presence of errors that should arrest cell division.

This difference between versions of CDC20 enables cells to set a timer for arrest. Early in cell division, the APC/C is most likely to be bound by full-length CDC20, because cells produce more of the full-length protein than the alternatives. This keeps the cells responsive to the signal to enter arrest.

As cells spend more time in arrest, they continue to produce all versions of CDC20, but they break down full-length CDC20 faster than the shorter versions. The ratio of full-length to short CDC20 shifts in favor of the short versions. Eventually, the ratio shifts enough that the APC/C is most likely to be bound by short CDC20, which means that the SAC can no longer inhibit it. At this point, the timer runs out: the cells activate the APC/C and escape arrest.

A cell's arrest timer is therefore determined by factors that affect its starting levels of full-length and short CDC20 and the speed at which it makes and breaks them down, such as what machinery the cell has active for translating RNA. These factors vary from cell type to cell type, so different cell types have different length timers.

Understanding how cells set their timers helps to explain why some cancer cells are better at resisting certain cancer drugs.

Tsang, MJ., Cheeseman, I.M. Alternative CDC20 translational isoforms tune mitotic arrest duration. Nature (2023). https://doi.org/10.1038/s41586-023-05943-7

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'Zero plant extinction' is possible

Like animals, many plant species are struggling to adapt to a human-dominated planet. However, plants are often overlooked in conservation efforts, even though they are cheaper and easier to protect than animals and play a pivotal role in bolstering our food, fuel and medical systems. In a review published in the journal Trends in Plant Science on May 2,  ecologists suggest an approach for preventing all future land plant extinctions across the globe which includes training more plant experts, building an online "metaherbarium," and creating "microreserves."

An estimated 21%–48% of vascular plant species—which includes flowering plants and trees—could go extinct, primarily due to changes in land use and unsustainable harvesting practices. While it's potentially possible to prevent the extinction of all 382,000 currently known plant species, no single solution works for all species.

Conservation plans can take many forms and can be carried out either in a plant's natural habitat, often in the form of a nature reserve, or in a curated environment like a botanical garden. Sometimes a combination works best. For example, a microreserve—a tiny piece of protected land designed to get around space constraints—could be coupled with a supply of frozen seeds to fall back on if necessary.

Conservation of self-sustaining wild populations in protected areas is the ideal. This allows continued evolution in response to ongoing environmental change (such as climate change, and new pests and diseases) and the continued support of mutualists, herbivores, and pathogens, some of which may face extinction without their only plant hosts.

 Richard T. Corlett, Achieving zero extinction for land plants, Trends in Plant Science (2023). DOI: 10.1016/j.tplants.2023.03.019

'Explainable AI' can efficiently detect AR/VR cybersickness

Exposure to an augmented reality (AR) or virtual reality (VR) environment can cause people to experience cybersickness—a special type of motion sickness with symptoms ranging from dizziness to nausea—and existing research to mitigate the severity of the symptoms often relies upon a one-size-fits-all approach.

However, a team of researchers are working to develop a personalized approach to identifying cybersickness by focusing on the root causes, which can be different for every person.

Cybersickness is not generic. For instance, one simulation could trigger cybersickness in me while the same simulation may not cause cybersickness for someone else. 

One of the problems people typically face when wearing virtual reality or augmented reality headsets is the user experience can get bad after some time, including symptoms of nausea and vomiting, especially if the user is immersed in a virtual environment where a lot of motion is involved. It can depend on many factors, including a person's gender, age and experience.

Explainable AI is a great tool to help with this because typically machine learning or deep learning algorithms  can tell you what the prediction and the decision may be, whereas explainable AI can also tell the user how and why the AI made the decision. So, instead of imposing a static mitigation technique for all users, it will be more effective if we know why a particular person is developing cybersickness and give that person the right mitigation that they need. Explainable AI can help us do that without hindering the user experience.

This research was recently presented at three conferences for AR/VR research:

• "LiteVR: Interpretable and Lightweight Cybersickness Detection using Explainable AI" was presented at the IEEE Virtual Reality Conference on March 25-29, 2023.
• "VR-LENS: Super Learning-based Cybersickness Detection and Explainable AI-Guided Deployment in Virtual Reality" was presented at the ACM Conference on Intelligent User Interfaces on March 27-31, 2023.
• "TruVR: Trustworthy Cybersickness Detection using Explainable Machine Learning" was presented at the International Symposium on Mixed and Augmented Reality (ISMAR) Conference on October 17-21, 2022.

 TruVR: Trustworthy Cybersickness Detection using Explainable Machin...

When your house spreads gossip about you

More and more of the devices that we surround ourselves with on a daily basis are connected to the internet. This makes them not only smart, but also vulnerable to cyberattacks and criminal acts.

Before long, we might have smart fridges that help us keep track of what foods are about to expire and when to shop. How could this be harmful? Who would be interested in the expiry date of your milk or monitoring your food inventory?

When you think about it, everyday objects in a modern smart home process a lot of data that you probably don't wish to share with all and sundry.

Your thermostat, for example, could give clues about when you are away from home. Your fitness equipment often stores health information about you and your family.

And as an American software developer recently demonstrated—your smart speaker may have security holes that allow eavesdropping on your private conversations.

In the wrong hands, this is information can be misused for everything from burglary to identity theft and extortion. Smart devices are increasingly finding their way into large companies and government institutions, a trend that does not exactly make the situation any less serious.

 Fartein Færøy et al, Automatic Verification and Execution of Cyber Attack on IoT Devices, Sensors (2023). DOI: 10.3390/s23020733

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Cybersickness more likely to affect women

 Researchers in psychology and engineering found women experience cybersickness with virtual reality headsets more often than men. Their ongoing work explores why this difference exists and options to help individuals adapt.

Gender discrepancies in cybersickness may not seem that important when it's related to video games and other forms of entertainment.

But it's still a problem, and when VR gets to the point where it's a bigger part of job training or education in a classroom, it's even more important to make sure people can access this technology. If not, a lot of people are going to get left out, and there could be a backlash.

Like motion sickness, cybersickness can occur when there's a mismatch between visual motion and body motion. Symptoms, including nausea, dizziness, headaches and eye fatigue, usually resolve quickly after removing the headset. But in severe cases, they sometimes last for hours.

Women reported experiencing more motion sickness and screen-based sickness than men, and this increased susceptibility is part of the reason that women experience more cybersickness.

The  researchers will continue to investigate the causes of cybersickness and methods to help individuals have a positive experience with VR.

Jonathan W. Kelly et al, Gender differences in cybersickness: Clarifying confusion and identifying paths forward, 2023 IEEE Conference on Virtual Reality and 3D User Interfaces Abstracts and Workshops (VRW) (2023). DOI: 10.1109/VRW58643.2023.00067

Taylor A. Doty et al, Does interpupillary distance (IPD) relate to immediate cybersickness?, 2023 IEEE Conference on Virtual Reality and 3D User Interfaces Abstracts and Workshops (VRW) (2023). DOI: 10.1109/VRW58643.2023.00173

‘Remarkable’ AI tool designs mRNA vaccines

An artificial-intelligence (AI) software tool optimizes the gene sequences found in mRNA vaccines. The new methodology was developed by the California branch of Baidu Research, the AI-research arm of Beijing-based search-engine behemoth Baidu. It could help to create jabs that are more potent and stable than standard ones. The software borrows techniques from computational linguistics to design mRNA sequences with more-intricate shapes and structures than those used in current vaccines. Already, the tool has been used to optimize at least one authorized vaccine: a COVID-19 shot called SW-BIC-213.

https://www.nature.com/articles/s41586-023-06127-z?utm_source=Natur...

How menopause reshapes the brain

Oestrogen does a lot for the brain: it stimulates glucose uptake and energy production. Once the transition to menopause is complete, neurons grow accustomed to its absence. But in the perimenopausal period, levels of the hormone can crash one week only to soar the next. The result can be a period of neuronal discord in which brain cells are periodically deprived of oestrogen, but not for long enough to forge the pathways needed to adapt to life without it.

Perimenopause is also when many of the characteristic symptoms of menopause occur. Hot flushes are the hallmark of perimenopause; other symptoms include irregular periods, anxiety, high blood pressure and the dreaded ‘brain fog’ that impedes concentration. 

It could also be a key time to intervene using treatments that ease the transition into menopause, and which could slow the pace of age-related diseases that seem to accelerate afterwards.

But perimenopause does not have a clear start and end, making it difficult to study. Large clinical trials of treatments such as hormone-replacement therapy have often focused on women who are post-menopausal, sometimes years beyond their last period.

Some women have a short duration of perimenopausal symptoms, and others continue to be symptomatic for years or decades.

Now researchers are taking these changes in the brain seriously and are working to find solutions.

https://www.nature.com/articles/d41586-023-01474-3?utm_source=Natur...

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How to solve the biggest climate challenges

In a special issue dedicated to climate solutions, The New Yorker explores the breakthroughs that can make the most difference.

• Satellites in development aim to pinpoint the illicit sources of the potent greenhouse gas methane and map carbon in the atmosphere in unprecedented detail. (16 min read)
• People hoping to reduce the carbon emissions from cargo ships — which is on par with the aviation industry — are turning to a time-tested technology: sails. (17 min read)
• Pavagada Ultra Mega Solar Park in southern India is one of the largest solar-generating solar farms in the world — but the people whose livelihoods relied on the land it covers say that not everyone receives a fair share in the fruits of a cleaner economy. (18 min read)

Scientists find link between photosynthesis and 'fifth state of matter'

Inside a lab, scientists marvel at a strange state that forms when they cool down atoms to nearly absolute zero. Outside their window, trees gather sunlight and turn them into new leaves. The two seem unrelated—but a new study suggests that these processes aren't so different as they might appear on the surface.

The study, published in PRX Energy on April 28, found links at the atomic level between photosynthesis and exciton condensates—a strange state of physics that allows energy to flow frictionlessly through a material. The finding is scientifically intriguing and may suggest new ways to think about designing electronics, the researchers say.

Modeling the complicated interactions of atoms and molecules as they display interesting properties is not possible to see  with the naked eye, so computer modeling can give scientists a window into why the behaviour happens—and can also provide a foundation for designing future technology.

When a photon from the sun strikes a leaf, it sparks a change in a specially designed molecule. The energy knocks loose an electron. The electron, and the "hole" where it once was, can now travel around the leaf, carrying the energy of the sun to another area where it triggers a chemical reaction to make sugars for the plant.

Together, that traveling electron-and-hole-pair is referred to as an "exciton." When the researchers took a birds-eye view and modeled how multiple excitons move around, they noticed something odd. They saw patterns in the paths of the excitons that looked remarkably familiar.

In fact, it looked very much like the behavior in a material that is known as a Bose-Einstein condensate, sometimes known as "the fifth state of matter." In this material, excitons can link up into the same quantum state—kind of like a set of bells all ringing perfectly in tune. This allows energy to move around the material with zero friction. (These sorts of strange behaviors intrigue scientists because they can be the seeds for remarkable technology—for example, a similar state called superconductivity is the basis for MRI machines). According to the models created by the researchers, the excitons in a leaf can sometimes link up in ways similar to exciton condensate behaviour.

Photosynthetic light harvesting is taking place in a system that is at room temperature and what's more, its structure is disordered—very unlike the pristine crystallized materials and cold temperatures that you use to make exciton condensates.

This effect isn't total—it's more akin to "islands" of condensates forming, the scientists say. But that's still enough to enhance energy transfer in the system.

 Anna O. Schouten et al, Exciton-Condensate-Like Amplification of Energy Transport in Light Harvesting, PRX Energy (2023). DOI: 10.1103/PRXEnergy.2.023002

Dead rivers, flaming lakes: India's sewage failure

India at the end of April was projected to have overtaken China as the world's most populous country, according to the United Nations, with almost 1.43 billion people.

Its urban population is predicted to explode in the coming decades, with over 270 million more people forecast to live in its cities by 2040.

But of the 72 billion liters of sewage currently generated in urban centers every day, 45 billion liters—enough to fill 18,000 Olympic-sized swimming pools—aren't treated, according to government figures for 2020-21.

India's sewerage system does not connect to about two-thirds of its urban homes, according to the National Faecal Sludge and Septage Management Alliance (NFSSM).

Many of the sewage treatment plants in operation don't comply with standards— according to media reports.

Coupled with huge volumes of industrial effluent, the sewage is causing disease, polluting India's waterways, killing wildlife and seeping into groundwater.

Part 1

Although India has made major progress in reducing child mortality, diarrhea—caused mostly by contaminated water and food—remains a leading killer.

More than 55,000 children under five died of diarrhea across India in 2019, according to a study published last year in the scientific journal BMC Public Health.

The Yamuna in Delhi is one of the world's filthiest rivers and is considered ecologically dead in places, although people still wash clothes and take ritual baths in it.

It often billows with white foam, and facilities processing drinking water from the river for Delhi's 20 million people regularly shut down because of dangerous ammonia levels.

Despite some bright spots, as well as efforts to plant more trees alongside rivers, the situation elsewhere is often no better in big cities including Mumbai and Chennai.

In Bengaluru, massive Bellandur Lake has on occasion caught fire when methane, generated by bacteria feasting on sewage in the oxygen-depleted water, ignited.

According to the World Bank, India is one of the most "water-stressed" countries in the world, with plummeting water tables and increasingly erratic monsoon rains. India is headed for a water crisis. Sewage can so easily be co-opted to fight that and help us to a very large extent solve the problem in our cities.

India's water is so seasonal. Many cities in India get 50 rain days... but sewage is available every day because you go to the bathroom every day... It's such a powerful weapon.

Children keep falling sick... If they don't get treatment and medicine, the children will die.

Source: 2023 AFP

https://phys.org/news/2023-05-dead-rivers-flaming-lakes-india.html?...

Part 2

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'Gluing' soft materials without glue!

You're likely familiar with the messy, sticky, frustration-inducing nature of liquid glues. But researchers reporting in ACS Applied Materials & Interfaces now have a brand-new way to weld squishy stuff together without the need for glue at all. They've demonstrated a universal, "electroadhesion" technique that can adhere soft materials to each other just by running electricity through them.

Electroadhesion, in which an electric field is used to hold oppositely charged materials together, forming attachments between the materials' components. This can involve chemical bonds, like ionic bonds, or more physical connections, like ensnaring polymer chains together. Plus, it works with little more than a household battery and pencil lead..

To explore the phenomenon, the team tested a gel in addition to three types of capsules made of alginate or chitosan—both naturally occurring polymers—that were either positively or negatively charged. When attached to graphite electrodes and exposed to a 10-V electric field for around 10 seconds, the oppositely charged materials stuck together.

This bond was strong enough to withstand gravity, and evidence from previous experiments suggests it could last for years. By reversing the flow of electricity, however, the bond was easily broken. .

The researchers also used electroadhesion to sort capsules by their charges, either by laying a charged gel on top of several capsules, or by touching them with a fingertip "robot" that adhered the capsules to themselves. The researchers say that this work demonstrates the universality of electroadhesion and could one day be used in robotics and tissue engineering.

 Leah K. Borden et al, Universal Way to "Glue" Capsules and Gels into 3D Structures by Electroadhesion, ACS Applied Materials & Interfaces (2023). DOI: 10.1021/acsami.2c20793

Birds of a Feather Video-Flock Together: Design and Evaluation of an Agency-Based Parrot-to-Parrot...

Scientists discover the dynamics of an 'extra' chromosome in fruit flies

Most chromosomes have been around for millions of years. Now, researchers  have revealed the dynamics of a new, very young chromosome in fruit flies that is similar to chromosomes that arise in humans and is associated with treatment-resistant cancer and infertility. The findings may one day lead to developing more targeted therapies for treating these conditions.

A new study published in Current Biology on May 4, 2023, reveals how this small chromosome that arose less than 20 years ago has persisted in a single, lab-reared strain of the fruit fly, Drosophila melanogaster, and is correlated with supernumerary (extra) chromosomes in humans.

Supernumerary chromosomes in humans are found in cancer cells and frequently interfere with drugs designed to target tumors, making these types of cancers, like osteosarcoma, difficult to treat. In addition, the presence of supernumerary chromosomes in men can disrupt normal chromosome segregation during sperm production, which can cause infertility.

Being able to understand how supernumerary chromosomes arise and what their structures are can potentially illuminate their vulnerabilities. This may enable the development of potential therapeutic targets.

Called B chromosomes—as opposed to the standard "A" set of essential chromosomes—these genetic elements naturally appeared in a single laboratory stock of fruit flies.

Now, the researchers are witnessing chromosome birth and evolution in less than two decades.

How does something like this new chromosome apparently arise from nothing? More important, as these newly born B chromosomes do not possess any known essential genes for fruit fly function, how do they persist in a genome? In short, by cheating. They do not follow the rules.

Researchers discovered that the fruit fly B chromosomes are maintained by a mechanism called "meiotic drive" that enables the them to rebel against the usual rules of inheritance. The B chromosomes drive their way into the next generation during the formation of the egg to ensure their own persistence in more than half of the next generation.

Part 1

Their genetic background—meaning the unique features in the B chromosome flies' genetic make-up—supports their preferential transmission to the next generation. That buys these  evolutionary time to become a new chromosome, whether that's picking up an essential gene or acquiring something that enables them to better cheat.

Importantly, meiotic drive is a powerful force that can shape how genomes evolve. 

Researchers are also examining how specific mutations can lead to chromosome breakage and new chromosome formation, revealing the mechanism of how supernumeraries arise and become requisite components of a genome.

Stacey L. Hanlon et al, B chromosomes reveal a female meiotic drive suppression system in Drosophila melanogaster, Current Biology (2023). DOI: 10.1016/j.cub.2023.04.028

Part 2

Study finds doctors prescribing untested drug combinations with high addiction potential

The Center for Drug Safety and Effectiveness at Johns Hopkins University has led a study into prescription drug use of multiple concurrent central nervous system (CNS)-active drugs. They found widespread combination prescribing of drugs classified as Schedule II controlled substances with a high potential for psychological or physical dependence and with limited combined clinical trial testing.

The paper, "Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis," published in BMJ Open, examined patterns of medical amphetamine and methylphenidate stimulant drug use, both substances considered to have a high potential for psychological or physical addiction.

Utilizing prescription drug claims for US adults aged 19 to 64 from a commercial insurance claims database with over 9.1 million continuously enrolled adults, stimulant use was defined as adults filling one or more stimulant prescriptions in a single year.

The study identified 276,223 individuals (3.0%) using Schedule II stimulants in 2020. They filled a median of eight prescriptions that provided 227 days of exposure. Among this group, 125,781 (45.5%) combined use of one or more additional CNS active drugs for a median of 213 days. Also, 66,996 (24.3%) stimulant users used two or more additional CNS-active medications for a median of 182  days. Among stimulants users, 131,485 (47.6%) used an antidepressant, 85,166 (30.8%) filled prescriptions for anxiety/sedative/hypnotic medications and 54,035 (19.6%) received opioid prescriptions.

Many adults using Schedule II stimulants simultaneously use one or more additional CNS-active drugs. As these can have tolerance and withdrawal effects or potential recreational abuse, the authors suggest that "discontinuation may be challenging," which is another way of stating that these individuals have likely formed a habitual dependence or addiction possibly requiring intervention or rehabilitation.

Once treatment has started, 75% of patients become long-term users. This underscores the possible risks of non-medical guideline use, noting the issues that warranted the classification of these drugs as having a high potential for psychological or physical dependence and their prominent appearance in toxicology drug rankings of fatal overdose cases.

 Thomas J Moore et al, Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis, BMJ Open (2023). DOI: 10.1136/bmjopen-2022-069668

Deep sleep may mitigate Alzheimer's memory loss, research shows

As the most prevalent form of dementia, Alzheimer's disease destroys memory pathways and, in advanced forms, interferes with a person's ability to perform basic daily tasks. Roughly one in nine people over age 65 have the progressive disease—a proportion that is expected to grow rapidly as the baby boomer generation ages.

In recent years, scientists have probed the ways that deposits of beta-amyloid associate with Alzheimer's disease and how such deposits also affect memory more generally. In addition to sleep being a foundational part of memory retention, the team at UC Berkeley previously discovered that the declining amount of a person's deep sleep could act as a 'crystal ball' to forecast a faster rate of future beta-amyloid buildup in the brain, after which dementia is more likely set in.

A deep slumber might help buffer against memory loss for older adults facing a heightened burden of Alzheimer's disease, new research suggests.

Deep sleep, also known as non-REM slow-wave sleep, can act as a "cognitive reserve factor" that may increase resilience against a protein in the brain called beta-amyloid that is linked to memory loss caused by dementia. Disrupted sleep has previously been associated with faster accumulation of beta-amyloid protein in the brain. However, the new research  reveals that superior amounts of deep, slow-wave sleep can act as a protective factor against memory decline in those with existing high amounts of Alzheimer's disease pathology—a potentially significant advance that experts say could help alleviate some of dementia's most devastating outcomes.

Zsófia Zavecz et al, NREM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology, BMC Medicine (2023). DOI: 10.1186/s12916-023-02811-z

Technology enables conversion of mobile phone cameras into high-resolution microscopes

Researchers have developed the world's smallest LED (light-emitting diode) that enables the conversion of existing mobile phone cameras into high-resolution microscopes. Smaller than the wavelength of light, the new LED was used to build the world's smallest holographic microscope, paving the way for existing cameras in everyday devices such as mobile phones to be converted into microscopes via only modifications to the silicon chip and software. This technology also represents a significant step forward in the miniaturization of diagnostics for indoor farmers and sustainable agriculture.

This breakthrough was supplemented by the researchers' development of a revolutionary neural networking algorithm that is able to reconstruct objects measured by the holographic microscope, thus enabling enhanced examination of microscopic objects such as cells and bacteria without the need for bulky conventional microscopes or additional optics. The research also paves the way for a major advancement in photonics—the building of a powerful on-chip emitter that is smaller than a micrometer, which has long been a challenge in the field.

Zheng Li et al, A sub-wavelength Si LED integrated in a CMOS platform, Nature Communications (2023). DOI: 10.1038/s41467-023-36639-1

Iksung Kang et al, Simultaneous spectral recovery and CMOS micro-LED holography with an untrained deep neural network, Optica (2022). DOI: 10.1364/OPTICA.470712

Study finds female astronauts more efficient, suggesting future space missions with all-female crews

As humans contemplate life on other planets, we are immediately confronted with two choices. One is a journey to another solar system that would take tens of thousands of years (with current technology), requiring around 2,000 generations to live out their existence in the cramped confines of a spacecraft while adhering to a strict population control scheme. The other choice is Mars.

Mars has several advantages, not the least of which is proximity, eliminating the need to push people out of airlocks when the spacecraft is at capacity. It would also allow an advance team to set up basic infrastructure and to be the most efficient—the team should all be female.

Researchers from the Space Medicine Team, European Space Agency in Germany have conducted a study published in Scientific Reports that found female astronauts have lower water requirements for hydration, total energy expenditure, oxygen (O₂) consumption, carbon dioxide (CO₂) and metabolic heat production during space exploration missions compared to their male counterparts.

In the study, "Effects of body size and countermeasure exercise on estimates of life support resources during all-female crewed exploration missions," the team utilized an approach developed to estimate the effects of body "size" on life support requirements in male astronauts. For all parameters at all statures, estimates for females were lower than for comparable male astronauts.

When considering the limited space, energy, weight, and life support systems packed into a spacecraft on a long mission, the study finds that the female form is the most efficient body type for space exploration.

Compared to a previous study of theoretical male astronauts, the effect of body size on total energy expenditure was markedly less in females, with relative differences ranging from 5% to 29% lower. Compared at the 50th percentile stature for US females (1.6m), the reductions were even more significant at 11% to 41%. This translates into reduced use of oxygen, production of CO₂, metabolic heat, and water use.

Part 1

When exposed to the prolonged microgravity of space, bad things happen to astronaut bodies. Physiological changes induce muscle atrophy, bone loss, and reduced aerobic and sensorimotor capacity, potentially affecting crewmember health and ability to perform mission tasks.

Exercise in space is called "countermeasure exercise" as it is designed to counter the physiological effects of being weightless. During these exercises (two 30-min aerobic exercises, six days a week), astronauts have higher rates of O₂ consumption, production of CO₂, metabolic heat production, and require more water to rehydrate.

While body size alone correlates to energy metrics (smaller stature, less energy used), missions requiring countermeasure exercise increase this disparity as larger bodies use more energy, need more oxygen, produce more CO₂ and create more heat. Additionally, the study found that females had 29% less water loss through sweating during a single bout of aerobic countermeasure exercise and so required less water to rehydrate.

The theoretical differences between female and male astronauts result from lower resting and exercising O₂ requirements of female astronauts, who are lighter than male astronauts at equivalent statures and have lower relative VO₂max (the rate at which the heart, lungs, and muscles can effectively use oxygen during exercise) values.

The study data, combined with the move towards smaller diameter habitat space for currently proposed mission modules, suggest that there may be several operational advantages to all-female crews during future human space exploration missions, with the most significant improvement coming from shorter females.

Jonathan P. R. Scott et al, Effects of body size and countermeasure exercise on estimates of life support resources during all-female crewed exploration missions, Scientific Reports (2023). DOI: 10.1038/s41598-023-31713-6

Part 2

Fruit fly gut research leads to discovery of new phosphate-storing organelle

Scientists  have discovered something remarkable while studying phosphate transport in fruit fly intestines—a never before seen organelle. Their results are published in the journal Nature, and a News and Views piece in the same journal discusses their findings.

Organelles are the structures performing specific functions within the cell and form the basis for most introductory biology courses. Major organelles include the nucleus, where DNA is kept and translated into RNA; the endoplasmic reticulum, where RNA is translated into proteins; and the Golgi apparatus, where enzymatic processing of proteins takes place; and the mitochondrion, which powers the cell and is involved in monitoring and regulating the cell as well as some intercellular communication.

A few dozen other minor organelles exist within animal cells, and it might have been assumed that every organelle had been discovered after so many years of research. But not so, as detailed in the researchers' new paper, "A phosphate-sensing organelle regulates phosphate and tissue homeostasis."

Immunostaining and ultrastructural analyses showed that PXo specifically appeared in a previously unknown multilamellar membrane—a newly discovered organelle the researchers named PXo bodies. The PXo was essentially storing phosphate in the PXo bodies. When PXo was downregulated or missing, the PXo bodies degraded, releasing the backup storage of phosphate into the cell.

Future investigations will be required to map this new organelle's full functions and interactions and could search for PXo bodies in other life forms.

 Chiwei Xu et al, A phosphate-sensing organelle regulates phosphate and tissue homeostasis, Nature (2023). DOI: 10.1038/s41586-023-06039-y

Emily Strachan et al, Phosphate-storing organelle discovered in fruit flies, Nature (2023). DOI: 10.1038/d41586-023-01410-5

Mobile phone calls linked with increased risk of high blood pressure

Talking on a mobile for 30 minutes or more per week is linked with a 12% increased risk of high blood pressure compared with less than 30 minutes, according to research published recently in European Heart Journal—Digital Health.

It's the number of minutes people spend talking on a mobile that matter for heart health, with more minutes meaning greater risk.

Almost three-quarters of the global population aged 10 and over own a mobile phone. Nearly 1.3 billion adults aged 30 to 79 years worldwide have high blood pressure (hypertension). Hypertension is a major risk factor for heart attack and stroke and a leading cause of premature death globally.

Mobile phones emit low levels of radiofrequency energy, which has been linked with rises in blood pressure after short-term exposure. Results of previous studies on mobile phone use and blood pressure were inconsistent, potentially because they included calls, texts, gaming, and so on.

This study examined the relationship between making and receiving phone calls and new-onset hypertension. The study used data from the UK Biobank. A total of 212,046 adults aged 37 to 73 years without hypertension were included. Information on the use of a mobile phone to make and receive calls was collected through a self-reported touchscreen questionnaire at baseline, including years of use, hours per week, and using a hands-free device/speakerphone.

Participants who used a mobile phone at least once a week to make or receive calls were defined as mobile phone users.

The researchers analyzed the relationship between mobile phone usage and new-onset hypertension after adjusting for age, sex, body mass index, race, deprivation, family history of hypertension, education, smoking status, blood pressure, blood lipids, inflammation, blood glucose, kidney function and use of medications to lower cholesterol or blood glucose levels.

Part 1

The average age of participants was 54 years, 62% were women and 88% were mobile phone users. During a median follow up of 12 years, 13,984 (7%) participants developed hypertension. Mobile phone users had a 7% higher risk of hypertension compared with non-users. Those who talked on their mobile for 30 minutes or more per week had a 12% greater likelihood of new-onset high blood pressure than participants who spent less than 30 minutes on phone calls. The results were similar for women and men.

Looking at the findings in more detail, compared to participants who spent less than 5 minutes per week making or receiving mobile phone calls, weekly usage time of 30-59 minutes, 1-3 hours, 4-6 hours and more than 6 hours was associated with an 8%, 13%, 16% and 25% raised risk of high blood pressure, respectively. Among mobile phone users, years of use and employing a hands-free device/speakerphone were not significantly related to the development of hypertension.

The researchers also examined the relationship between usage time (less than 30 minutes vs. 30 minutes or more) and new-onset hypertension according to whether participants had a low, intermediate or high genetic risk of developing hypertension. Genetic risk was determined using data in the UK Biobank.

The analysis showed that the likelihood of developing high BP was greatest in those with high genetic risk who spent at least 30 minutes a week talking on a mobile—they had a 33% higher likelihood of hypertension compared to those with low genetic risk who spent less than 30 minutes a week on the phone.

These  findings suggest that talking on a mobile may not affect the risk of developing high BP as long as weekly call time is kept below half an hour. More research is required to replicate the results, but until then it seems prudent to keep mobile phone calls to a minimum to preserve heart health.

Ye Z, Zhang Y, Zhang Y, et al, Mobile phone calls, genetic susceptibility and new-onset hypertension: results from 212,046 UK Biobank participants, European Heart Journal—Digital Health (2023). DOI: 10.1093/ehjdh/ztad024.

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Part 2

Can fish catch colds?

The simple answer to the question of whether fish can catch a cold is: no. This is because fish don't have lungs or a respiratory tract—or a nose to breathe through, for that matter. This is why you'll never see a fish with a hacking cough or a runny nose.

This isn't to say that fish cannot get ill, of course. "Fish—as well as bivalves such as mussels and oysters and crustaceans such as shrimp—exchange oxygen and CO2through their gills.

Waterborne viruses have evolved to attack the gills in the same way as airborne viruses have evolved to attack the lungs.

Gills are coated with a kind of mucus that acts as a kind of protective barrier. When this mucus is disrupted, this can create openings for viruses to infect the animal. You wouldn't define this infection as a cough or a sneeze, though.

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Researchers discover a potential cause of Parkinson's disease

In 2021, Professor Per Saris's group published results demonstrating that bacteria of the Desulfovibrio bacterial genus correlate with Parkinson's disease, and that their higher number also correlates with the severity of the symptoms of the disease. Replicating the same study, Chinese researchers came to the same conclusion.

The findings indicate that specific strains of Desulfovibrio bacteria are likely to cause Parkinson's disease. The disease is primarily caused by environmental factors, that is, environmental exposure to the Desulfovibrio bacterial strains that cause Parkinson's disease. Only a small share, or roughly 10%, of Parkinson's disease is caused by individual genes.Vy A. Huynh et al, Desulfovibrio bacteria enhance alpha-synuclein aggregation in a Caenorhabditis elegans model of Parkinson's disease, Frontiers in Cellular and Infection Microbiology (2023). DOI: 10.3389/fcimb.2023.1181315

Stroke: Know the signs and risk factors

To recognize the signs of stroke, remember the acronym FAST:

• Face: Does the face droop on one side when the person tries to smile?
• Arms: Is one arm lower when the person tries to raise both arms?
• Speech: Can the person repeat a simple sentence? Is speech slurred or hard to understand?
• Time: During a stroke, every minute counts. If you observe any of these signs, call 911 or your local emergency number immediately.

Risk factors

Many factors can increase the risk of stroke, including:

• Age: People 55 or older have a higher risk of stroke than younger people.
• Race or ethnicity: People who are African American and Hispanic have a higher risk of stroke than people of other races or ethnicities.
• Sex: Men have a higher risk of stroke than women. Women are usually older when they have strokes, and they're more likely to die of strokes than men, however.
• Hormones: Use of birth control pills or hormone therapies that include estrogen increases risk.

Potentially treatable stroke risk factors include lifestyle and medical factors.

Lifestyle risk factors include:

• Being overweight or obese
• Physical inactivity
• Heavy or binge drinking
• Use of illegal drugs, such as cocaine and methamphetamine

Medical risk factors include:

• High blood pressure
• Cigarette smoking or secondhand smoke exposure
• High cholesterol
• Diabetes
• Obstructive sleep apnea
• Cardiovascular disease, including heart failure, heart defects, heart infection or irregular heart rhythm
• Personal or family history of stroke, heart attack or transient ischemic attack
• COVID-19 infection

Mechanical Force on the Skull May Aid Bone Regeneration

By mechanically inducing the expansion of cranial sutures in young adult mice, researchers stimulated stem cell proliferation that is key to healing bone injuries.

Treatments available to repair damage to the skull as a result of trauma, surgery, or congenital anomalies are limited and sometimes involve risks. A study recently published in PNAS (1) offers an alternative approach inspired by how babies regenerate bone tissue. The researchers expanded on previous studies (2,3) showing that open sutures—the fibrous connective tissue holding bones together—in the skulls of newborn mice and humans are reservoirs of skeletal stem cells. The temporary mechanically-induced expansion of closed sutures in young adult mice resulted in the proliferation of skeletal stem cells and facilitated bone regeneration following an injury.

A major contribution of this study is that it advances our knowledge about the impact of external forces on the structure of cranial sutures and the potential healing properties of such impact.

Researchers first compared the cell composition of the calvarial suture—which joins the bilateral bones in the roof of the skull—in mice of different ages and found that the number of skeletal stem cells is significantly reduced in older mice compared to younger mice. Increased numbers of stem cells correlate with open sutures in newborns, leading them to wonder whether expanding the sutures in adults would increase the number of stem cells enough to harness their regenerative potential.

The team achieved this goal in 2-month-old mice, which the researchers considered the equivalent of young adults in humans. When the researchers mechanically induced calvarial suture expansion, the number of skeletal stem cells increased significantly. Moreover, mice that received an injury to the skull near the suture simultaneous to the mechanical expansion exhibited near complete bone regeneration after 60 days, something that was not achieved in control mice without the expansion device. This mechanically-induced regeneration did not occur in 10-month-old mice, probably due to the limited supply of preexisting skeletal stem cells in the sutures, which is insufficient to achieve successful proliferation.

Finally, the team showed that suture stem cell proliferation and the resulting healing effects depend on Wnt signaling, a pathway that regulates key aspects of animal development.

1. Aldawood, Z.A. et al. (2023) “Expansion of the sagittal suture induces proliferation of skeletal stem cells and sustains endogenous calvarial bone regeneration,” Proceedings of the National Academy of Sciences

2. Zhao, H. et al. (2015) “The suture provides a niche for mesenchymal stem cells of Craniofacial Bones,” Nature Cell Biology, 17(4), pp. 386–396. Available at: https://doi.org/10.1038/ncb3139.

3. Maruyama, T. et al. (2016) “Stem cells of the suture mesenchyme in craniofacial bone development, repair and Regeneration,” Nature Communications, 7(1). Available at: https://doi.org/10.1038/ncomms10526.

Cell Senescence

Each cell in an organism has an average life span. For example, cells lining the surface of the human gut or skin typically live 3-5 days before they die.¹ In contrast, stem cells and neurons can survive for many years.² The process by which a cell arrests their growth after completing its life span is called cell senescence.  

Cell senescence is the expression of aging at the cellular level, and the phenomenon occurs when a cell stops dividing and arrests in the G1 phase of the cell cycle.^3,4 During this phase, the cell undergoes numerous phenotypic and metabolic changes. Some of these phenotypic changes include chromatin remodeling with global demethylation and heterochromatin foci formation, which alters the cell’s gene expression landscape.⁵ Additionally, senescent cells are larger in size and more granular.⁶ Senescent cells are eradicated from the body either through apoptosis or by immune cells such as macrophages.⁵

Although cell senescence is often associated with aging, it is an important process during embryogenesis, wound healing, and maintaining homeostasis.⁷ For instance, during central nervous system development, parts of the neural tube undergo senescence for proper formation of the brain and spinal cord.⁸

Cell senescence was first identified by Leonard Hayflick and Paul Moorhead in 1961, when they serially passaged human fibroblast cells in culture.³ They noticed that the cells stopped dividing after 40-60 passages. The number of cell divisions before cell cycle arrest is now known as the Hayflick limit.³

To detect senescent cells in the laboratory, researchers use markers such as senescence-associated B-galactosidase (SABG), which exists in the lysosome of these cells.⁹

^{Part 1}

What Triggers Cell Senescence? 
Cell senescence is triggered by a variety of internal or external cellular insults. Examples of internal stresses leading to senescence include shortening of the telomeres, DNA damage, mitochondrial dysfunction, nutrient deprivation, oncogenic pathway activation.⁴ Some examples of external stresses are radiation and chemotherapeutic agents.⁴  

Senescence-Associated Secretory Phenotype 
A major characteristic of senescent cells is the senescence-associated secretory phenotype or SASP.¹⁰ SASP encompasses a senescent cell’s secreted components, or secretome, and includes pro-inflammatory cytokines, chemokines, proteases, growth factors, reactive oxygen species (ROS), and extracellular matrix proteins.¹⁰ Senescent cells use these metabolically active components to communicate with surrounding cells and change the environment in either a positive or negative manner. For instance, SASP can recruit immune cells to remove senescent cells, remodel tissue by secreting angiogenic factors, or promote senescence in other cells through paracrine signalling.¹⁰

Senescence and Aging 

Senescence is an important contributor to aging as it depletes various cell pools, including progenitor and stem cells that can replace damaged tissue over time.¹¹ The SASP of senescent cells enhances inflammation, which increases susceptibility to many age-related diseases, such as heart disease, diabetes, and cancer.¹¹ SASP-mediated paracrine signaling can also encourage neighboring cells to undergo senescence.¹¹

Senescence and Cancer 

A major hallmark of cancer progression is cell proliferation.³ As such, researchers previously thought that the senescence pathway suppressed tumors as it eliminated proliferative cells.¹² However, there is increasing evidence that the SASP may contribute to cancer progression by creating an immunosuppressive environment.¹²

^{Part 2}

Anti-senescent Treatments

Researchers have developed drugs called senolytics to selectively target senescent cells that are resistant to apoptosis. These drugs work by upregulating antiapoptotic pathways.⁶ Eliminating these cells is important in diseases such as fibrosis (e.g., pulmonary fibrosis), where tissue is scarred and thickened.¹³ Additionally, patients with obesity or diabetes have high levels of senescent cells in adipose tissue, which contributes to fat cell size.¹⁴ For pulmonary fibrosis and diabetic kidney disease, researchers have conducted clinical trials testing senolytics and observed promising results.⁶

Another class of drugs called senomorphics inhibits SASP.⁶ Reducing SASP is critical for preventing the spread of senescence to neighboring cells or tissues. For example, ruxolitinib reduces inflammation by inhibiting Janus kinases (JAKs), proteins involved in cytokine production.⁹ This drug was shown to be an effective treatment in a chronic obstructive pulmonary disease mouse model.¹⁵

^{Part 3}

Footnotes:

 J. Park et al., "Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids," PLoS ONE, 11(5):e0156334, 2016. 

2. L. Ottoboni et al., "Therapeutic plasticity of neural stem cells," Front Neurol, 11, 2020.  

3. L. Hayflick, P.S. Moorhead, "The serial cultivation of human diploid cell strains," Exp Cell Res, 25(3):585-621, 1961.

4. Kumari R, Jat P. "Mechanisms of cellular senescence: cell cycle arrest and senescence associated secretory phenotype," Front Cell Dev Biol, 2021.

5. V. Gorgoulis et al., "Cellular senescence: defining a path forward," Cell, 179(4):813-27, 2019.  

6. N.S. Gasek et al., "Strategies for targeting senescent cells in human disease," Nat Aging, 1(10):870-79, 2021. 

7. S. Da Silva-Álvarez et al., "The development of cell senescence," Exp Gerontol, 128:110742, 2019. 

8. M. Storer et al., "Senescence Is a developmental mechanism that contributes to embryonic growth and patterning," Cell, 155(5):1119-30, 2013.  

Part 4

9. W. Huang et al., "Cellular senescence: the good, the bad and the unknown," Nat Rev Nephrol, 18(10):611-27, 2022. 

10. D. McHugh, J. Gil, "Senescence and aging: causes, consequences, and therapeutic avenues," J Cell Biol, 217(1):65-77, 2018.  

11. R. Di Micco et al., "Cellular senescence in ageing: from mechanisms to therapeutic opportunities," Nat Rev Mol Cell Biol, 22(2):75-95, 2021.

12. J. Yang et al., "The paradoxical role of cellular senescence in cancer," Front Cell Devl Biol, 9, 2021. 

13. F. Hernandez-Gonzalez et al., "Cellular senescence in lung fibrosis," Int J Mol Sci, 22(13):7012, 2021. 

14. A.K. Palmer et al., "Senolytics: potential for alleviating diabetes and its complications," Endocrinology, 162(8):bqab058, 2021. 

15. D. Beaulieu et al., "Phospholipase A2 receptor 1 promotes lung cell senescence and emphysema in obstructive lung disease. Euro Respir J, 2021. 

Part 5

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The Human Digestive System Varies a lot from person to person

The human digestive system is much more variable than we tend to think, according to a new study, with significant differences in gut anatomy even among healthy individuals.

This includes individual differences from person to person, the researchers report, plus broader differences such as those between women and men.

In one noteworthy example, the researchers found that women tend to have longer small intestines than men, by an average of 30.7 centimeters.

Because having a longer small intestine helps you extract nutrients from your diet, this finding supports the canalization hypothesis, which posits that women are better able to survive during periods of stress.

The study also revealed more granular differences, suggesting healthy human digestive systems are far more variable than many experts had appreciated.

If you're talking to four different people, odds are good that all of them have different guts, in terms of the relative sizes of the organs that make up that system.

For example, the cecum is an organ that's found at the nexus of the large and small intestine[s]. One person may have a cecum that is only a few centimeters long, while another may have a cecum the size of a coin purse.

The researchers point out that this has big implications for health care, emphasizing the importance of recognizing individual differences in gastrointestinal systems rather than focusing on typical or "normal" anatomy among humans in general.

The researchers point out, however, that humans stand apart for our high variation in intestinal length compared with other species. One possible explanation, they suggest, is that humans don't eat a "standardized captive diet," unlike many other species .

https://peerj.com/articles/15148/

Why should our PC or laptop  restart to install updates?

Software comprises lots of files and programs all interacting. 

When a computer is running software, it loads much of the program into its memory.

If we managed to update that same software on the hard disk or solid state drive (SSD), then the program may panic as everything will be different – it won’t be able to find the files that were there a moment ago. The version in memory will not be compatible with the version on the hard disk or SSD. Lots of errors will be thrown and your computer may crash.

To prevent this, operating systems usually insist that when major updates are needed, we shut down the software being updated, then restart with the new software installed.

Nightmares Can Be Silenced by a Single Piano Chord, Scientists Find

Using non-invasive techniques to manipulate our emotions, it might be possible to curtail the screaming horrors that plague our sleep.

A study last year conducted on 36 patients diagnosed with a nightmare disorder showed that a combination of two simple therapies reduced the frequency of their bad dreams.

Scientists invited the volunteers to rewrite their most frequent nightmares in a positive light and then played sound associated with positive experiences as they slept.

"There is a relationship between the types of emotions experienced in dreams and our emotional well-being. Based on this observation, sceintists had the idea that they could help people by manipulating emotions in their dreams. In this study, they show that they can reduce the number of emotionally very strong and very negative dreams in patients suffering from nightmares.

Many people suffer from nightmares, which aren't always a simple case of a few bad dreams. Nightmares are also associated with poor-quality sleep, which in turn is linked with a whole plethora of other health issues.

Poor sleep can also increase anxiety, which in turn can result in insomnia and nightmares. Recent studies have shown that nightmares and sleep disturbances have seen an uptick during the ongoing global SARS-CoV-2 pandemic.

Given that we don't really understand why, or even how, our brain creates dreams while we sleep, treating chronic nightmares is something of a challenge.

Part 1

One non-invasive method is imagery rehearsal therapy, in which patients rewrite their most harrowing and frequent nightmares to give them a happy ending. Then, they "rehearse" telling themselves that rewritten story, trying to overwrite the nightmare.

This method can reduce the frequency and severity of nightmares, but the treatment is not effective for all patients.

In 2010 scientists found that playing sounds that people have been trained to associate with a certain stimulus, while those people are sleeping, aids in boosting the memory of that stimulus. This has been named targeted memory reactivation (TMR), and researchers wanted to find out if it could improve the effectiveness of imagery rehearsal therapy (IRT).

After having the study's participants complete a dream and sleep diary for two weeks, the volunteers were all given a single IRT session. At this point, half of the group underwent a TMR session, creating a link between a positive version of their nightmares and a sound.

The other half served as a control group, imagining a less horrific version of a nightmare without being exposed to positive sounds.

Both groups received a sleep headphone headband that would play the sound – the piano chord C69 – while they were sleeping, every 10 seconds during REM sleep when nightmares were most likely to occur.

The groups were evaluated after two weeks of additional diary entries, and then again after three months without any sort of treatment.

At the start of the study, the control group had, on average, 2.58 nightmares per week, and the TMR group had an average of 2.94 weekly nightmares. By the end of the study, the control group was down to 1.02 weekly nightmares, while the TMR group had dropped to just 0.19. Even more promising, the TMR group reported an increase in happy dreams.

Part 2

At the three-month follow-up, nightmares had risen slightly in both groups, to 1.48 and 0.33 per week respectively. However, that is still an impressive reduction in the frequency of nightmares, the researchers said, suggesting that using TMR to support IRT results in a more effective treatment.

Researchers observed a fast decrease of nightmares, together with dreams becoming emotionally more positive. For  researchers and clinicians, these findings are very promising both for the study of emotional processing during sleep and for the development of new therapies.

https://www.cell.com/current-biology/fulltext/S0960-9822(22)01477-4

Part 3

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AI could run a million microbial experiments per year, says study

An artificial intelligence system enables robots to conduct autonomous scientific experiments—as many as 10,000 per day—potentially driving a drastic leap forward in the pace of discovery in areas from medicine to agriculture to environmental science. 

 That artificial intelligence platform, dubbed BacterAI, mapped the metabolism of two microbes associated with oral health—with no baseline information to start with. Bacteria consume some combination of the 20 amino acids needed to support life, but each species requires specific nutrients to grow.

Robots trained by artificial intelligence can conduct autonomous experiments, as many as 10,000 per day, to answer scientific questions. New research from University of Michigan engineers shows how automation can help speed the pace of discovery, with ramifications for a variety of fields of study.

Adam C. Dama et al, BacterAI maps microbial metabolism without prior knowledge, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01376-0

Advanced aliens could soon detect life on Earth, say scientists

Aliens on nearby stars could detect Earth through radio signals leaked from the planet, new research suggests.

Researchers used crowd sourced data to simulate radio leakage from mobile towers to determine what alien civilizations might detect from various nearby stars, including Barnard's star, six light years away from Earth.

The research, published in the Monthly Notices of the Royal Astronomical Society journal, found that only more technologically advanced civilizations would be able to detect the current levels of mobile tower radio leakage from Earth. However, as most alien civilizations are likely to have more sensitive receiving systems and as we move towards more powerful broadband systems on Earth, the detectability of humans from other intelligent beings will become more and more likely.

Although it's true we have fewer powerful TV and radio transmitters today, the proliferation of mobile communication systems around the world is profound. While each system represents relatively low radio powers individually, the integrated spectrum of billions of these devices is substantial, according to them.

Current estimates suggest we will have more than one hundred thousand satellites in low Earth orbit and beyond before the end of the decade. The Earth is already anomalously bright in the radio part of the spectrum; if the trend continues, we could become readily detectable by any advanced civilization with the right technology.

Ramiro C Saide et al, Simulation of the Earth's radio-leakage from mobile towers as seen from selected nearby stellar systems, Monthly Notices of the Royal Astronomical Society (2023). DOI: 10.1093/mnras/stad378

Happy worms have healthy eggs

 Worms might not be depressed, per se. But that doesn’t mean they can’t benefit from antidepressants.

In a new study researchers exposed roundworms (a well-established model organism in biological research) to selective serotonin reuptake inhibitors (SSRIs), a class of drugs used for treating depression and anxiety. Surprisingly, this treatment improved the quality of aging females’ egg cells.

Not only did exposure to SSRIs decrease embryonic death by more than twofold, it also decreased chromosomal abnormalities in surviving offspring by more than twofold. Under the microscope, egg cells also looked younger and healthier, appearing round and plump rather than tiny and misshapen, which is common with aging.

Astounded by the results, the researchers replicated the experiment in fruit flies — another common model organism — and the SSRIs demonstrated the same effect.

Although much more work is needed, the researchers say these findings provide new opportunities to explore pharmacological interventions that might combat infertility issues in humans by improving egg quality and by delaying the onset of reproductive aging.

Erin Z. Aprison, Svetlana Dzitoyeva, Ilya Ruvinsky. Serotonergic signaling plays a deeply conserved role in improving oocyte quality. Developmental Biology, 2023; DOI: 10.1016/j.ydbio.2023.04.008