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Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 11:04am

Research pinpoints how early-life antibiotics turn immunity into allergy

Researchers  have shown for the first time how and why the depletion of microbes in a newborn's gut by antibiotics can lead to lifelong respiratory allergies.

In a study published recently in the Journal of Allergy and Clinical Immunology, a research team from the school of biomedical engineering (SBME) has identified a specific cascade of events that lead to allergies and asthma. In doing so, they have opened many new avenues for exploring potential preventions and treatments.

This new research  finally shows how the gut bacteria and antibiotics shape a newborn's immune system to make them more prone to allergies.

Allergies are a result of the immune system reacting too strongly to harmless substances like pollen or pet dander, and a leading cause for emergency room visits in kids. Normally, the immune system protects us from harmful invaders like bacteria, viruses and parasites. In the case of allergies, it mistakes something harmless for a threat—in this case, parasites—and triggers a response that causes symptoms like sneezing, itching or swelling.

The stage for our immune system's development is set very early in life. Research over the past two decades has pointed toward microbes in the infant gut playing a key role. Babies often receive antibiotics shortly after birth to combat infections, and these can reduce certain bacteria. Some of those bacteria produce a compound called butyrate, which is key to halting the processes uncovered in this research.

The same researchers had previously shown that infants with fewer butyrate-producing bacteria become particularly susceptible to allergies. They had also shown that this could be mitigated or even reversed by providing butyrate as a supplement in early life.

Now, by studying the process in mice, they have discovered how this works.
Mice with depleted gut bacteria who received no butyrate supplement developed twice as many of a certain type of immune cell called ILC2s. These cells, discovered less than 15 years ago, have quickly become prime suspects in allergy development.

The researchers showed that ILC2s produce molecules that 'flip a switch' on white blood cells to make them produce an abundance of certain kinds of antibodies. These antibodies then coat cells as a defense against foreign invaders, giving the allergic person an immune system that is ready to attack at the slightest provocation.

Ahmed Kabil et al, Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell–innate IgE axis., Journal of Allergy and Clinical Immunology (2024). DOI: 10.1016/j.jaci.2024.07.023

Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 10:36am

Gut microbial pathway identified as target for improved heart disease treatment

 Researchers have made a significant discovery about how the gut microbiome interacts with cells to cause cardiovascular disease. The study published in Nature Communications found that phenylacetylglutamine (PAG), produced by gut bacteria as a waste product, then absorbed and formed in the liver, interacts with previously undiscovered locations on beta-2 adrenergic receptors on heart cells once it enters the circulation.

PAG was shown to interact with beta-2 adrenergic receptors to influence how forcefully the heart muscle cells contract—a process that investigators think contributes to heart failure. Researchers showed mutating parts of the beta-2 adrenergic receptor that were previously thought to be unrelated to signaling activity in preclinical models prevented PAG from depressing the function of the receptor.

The same researchers earlier demonstrated that elevated circulating levels of PAG in subjects are associated with heightened risk for developing heart failure, and lead to worse outcomes for patients with heart failure.

They also showed that the gut microbial PAG signaling pathway was mechanistically linked to numerous heart failure-related features and cardiovascular disease risks. The new findings bring us one step closer to therapeutically targeting this pathway to develop an improved treatment for the prevention of heart failure.

 Prasenjit Prasad Saha et al, Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors, Nature Communications (2024). DOI: 10.1038/s41467-024-50855-3

Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 9:52am

Like many conspiracies, no researcher could come up with a mechanism. If dark matter and stars could interact in this way, then we would need to change our understanding of how galaxies form and evolve. But they also couldn't find an alternate reason to explain what they were seeing, until now.

Present research work found that the similarity in density might not be due to the galaxies themselves but in how astronomers were measuring and modeling them.

The team which made this observation observed 22 middle-aged galaxies (looking back some four billion years in the past due to their great distance) in extraordinary detail, using the European Southern Observatory's Very Large Telescope in Chile. It enabled them to create more complex models that better captured the diversity of galaxies in the universe.
In the past, people built simple models that had too many simplifications and assumptions. Galaxies are complicated, and researchers have to model them with freedom or they're going to measure the wrong things. The new models ran on the OzStar supercomputer at Swinburne University, using the equivalent of about 8,000 hours of desktop computing time.

C Derkenne et al, The MAGPI Survey: Evidence against the bulge-halo conspiracy, Monthly Notices of the Royal Astronomical Society (2024). DOI: 10.1093/mnras/stae1836

Part 2

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Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 9:49am

A galactic theory disproven: Dark matter and stars not interacting as previously thought

A longstanding theory in astronomy—that stars and dark matter are interacting in inexplicable ways—has been overturned by an international team of astronomers, in a paper in Monthly Notices of the Royal Astronomical Society.

The  theory emerged to explain a phenomenon that had puzzled astronomers for a quarter of a century. The density of matter in different galaxies appeared to be decreasing at the same rate from their center to outer edges. This was perplexing because galaxies are diverse, with many different ages, shapes, sizes, and numbers of stars. So why would they have the same density structure?

This homogeneity suggested that dark matter and stars must somehow compensate for each other in order to produce such regular mass structures.

Part 1

Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 9:18am

Over the last 15 years, genomic surveillance has become a powerful tool for tracking pathogen evolution and transmission, giving critical insights to help manage the spread of disease.

However, current methods involve culturing a single strain of bacteria in a sample at a time and then conducting whole genome sequencing for all of them separately. This is a labor-intensive process, which can easily take several days and only provides a partial snapshot of all the clinically relevant bacteria found in a sample.

In this new study the research team developed a new approach that captured whole genome sequencing data across multiple pathogens at once. This is known as a 'pan-pathogen' deep sequencing approach and can provide genomic data as rapidly as hospitals can process the samples.

Pan-pathogen deep sequencing of nosocomial bacterial pathogens during the early COVID-19 pandemic, spring 2020: A prospective cohort study, The Lancet Microbe (2024). DOI: 10.1016/S2666-5247(24)00113-7

Part 2

Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 9:17am

Genomic surveillance method tracks multiple superbugs in hospitals

Researchers have developed a new genomic technique that can track the spread of multiple superbugs in a hospital simultaneously, which could help prevent and manage common hospital infections quicker and more effectively than ever before.

The proof-of-concept study details a new deep sequencing approach that captures all the common infectious bacteria in a hospital at once. Current methods culture and sequence all pathogens separately, which takes longer and requires more work.

Published 20 August in the Lancet Microbe, the study captured the whole population of pathogenic bacteria found in multiple hospital intensive care units (ICUs) and ordinary wards during the first wave of the 2020 COVID-19 pandemic. Researchers could see the type of bacteria patients had, including any well-known antibiotic-resistant pathogens found in hospitals.

They discovered that each ICU patient tested in the study was colonized by at least one such treatment-resistant bacteria, while the majority were colonized by several of them simultaneously.

Researchers think their approach could be integrated with existing hospital clinical surveillance systems. As drug resistance is a widespread issue in hospitals and other clinical settings, this system could identify, track and limit the spread of common multiple treatment-resistant bacteria at the same time.

Bacteria are commonly found in or on the body without causing harm, known as colonization. However, if certain strains get into the bloodstream due to a weakened immune system, they can cause severe and life-threatening infections, unless they can be effectively treated with antibiotics.

As an added challenge for health care providers, some of these bacteria are antibiotic-resistant (AMR). Infections caused by AMR bacteria are a major issue in hospitals, with these treatment-resistant bacteria predicted to cause more deaths than cancer by 2050. While some hospitals test for AMR bacteria on arrival, no system effectively tracks all multi-drug resistant bacteria throughout a hospital.

Part 1

Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 9:08am

How air pollution increases thunderstorm danger

Air pollution is increasing the severity of summertime thunderstorms, according to a recent study conducted by researchers at James Madison University and published in the journal Atmospheric Research.

Pollution acts as cloud nuclei. It gets brought into the cloud through the updraft; the updraft and downdraft then separate the pollution particles, which divides the electrical charges in the cloud and leads to more lightning production.

The three-year study examined nearly 200,000 thunderstorms.

Using 12 years of lightning data from the National Lightning Detection Network, US, and data from hundreds of air pollution stations, the researchers were able to determine that in environments with high instability, adding more pollution increases cloud-to-ground lightning strikes.

Similar research on Bangkok, a megacity with more pollution than most US cities and located in a hot, tropical climate, show similar results, albeit with lightning rates even higher in those storms.

It looks like no matter where you go in the world, urban pollution is capable of enhancing thunderstorms and lightening, the researchers conclude.

Mace Bentley et al, Toward untangling thunderstorm-aerosol relationships: An observational study of regions centered on Washington, DC and Kansas City, MO, Atmospheric Research (2024). DOI: 10.1016/j.atmosres.2024.107402

Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 8:38am

Aside from cosmic ice, the present research into low-energy electrons and radiation chemistry also has potential applications on Earth. The researchers studied the radiolysis of water, finding evidence of electron-stimulated release of hydrogen peroxide and hydroperoxyl radicals, which destroy stratospheric ozone and act as damaging reactive oxygen species in cells.

A lot of their water radiolysis research findings could be used in medical applications and medical simulations.
Humans are basically bags of water. So scientists are investigating how low-energy electrons produced in water affect our DNA molecules.
In attempting to better understand prebiotic molecule synthesis, the researchers didn't limit their efforts to mathematical modeling; they also tested their hypothesis by mimicking the conditions of space in the lab. They use an ultrahigh-vacuum chamber containing an ultrapure copper substrate that they can cool to ultralow temperatures, along with an electron gun that produces low-energy electrons and a laser-driven plasma lamp that produces low-energy photons. The scientists then bombard nanoscale ice films with electrons or photons to see what molecules are produced.
Although researchers have previously focused on how this research is applicable to interstellar submicron ice particles, it is also relevant to cosmic ice on a much larger scale, like that of Jupiter's moon Europa, which has a 20-mile-thick ice shell.
The research team's results will be presented at the fall meeting of the American Chemical Society (ACS). ACS Fall 2024
Source: American Chemical Society
https://www.acs.org/meetings/acs-meetings/fall.html
Part 2
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Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 8:32am

Extraterrestrial chemistry with earthbound possibilities

Who are we? Why are we here? We are stardust, the result of chemistry occurring throughout vast clouds of interstellar gas and dust. To better understand how that chemistry could create prebiotic molecules—the seeds of life on Earth and possibly elsewhere—researchers have investigated the role of low-energy electrons created as cosmic radiation traverses through ice particles. Their findings may also inform medical and environmental applications on our home planet.

The first detection of molecules in space was made by Wellesley College alum Annie Jump Cannon more than a hundred years ago. Since Cannon's discovery, scientists have been interested in finding out how extraterrestrial molecules form.

A new work's   goal is to explore the relative importance of low-energy electrons versus photons in instigating the chemical reactions responsible for the extraterrestrial synthesis of these prebiotic molecules. 

The few studies that previously probed this question suggested that both electrons and photons can catalyze the same reactions. Recent Studies , however, hint that the prebiotic molecule yield from low-energy electrons and photons could be significantly different in space.

Their calculations suggest that the number of cosmic-ray-induced electrons within cosmic ice could be much greater than the number of photons striking the ice. Therefore, electrons likely play a more significant role than photons in the extraterrestrial synthesis of prebiotic molecules

Part 1

Comment by Dr. Krishna Kumari Challa on August 21, 2024 at 8:19am

When a foe turns a friend: Deadly sea snail toxin could be key to making better medicines

Scientists are finding clues on how to treat diabetes and hormone disorders in an unexpected place: a toxin from one of the most venomous animals on the planet.

A multinational research team led by University of Utah scientists has identified a component within the venom of a deadly marine cone snail, the geography cone, that mimics a human hormone called somatostatin, which regulates the levels of blood sugar and various hormones in the body. The hormone-like toxin's specific, long-lasting effects, which help the snail hunt its prey, could also help scientists design better drugs for people with diabetes or hormone disorders, conditions that can be serious and sometimes fatal.

The somatostatin-like toxin the researchers characterized could hold the key to improving medications for people with diabetes and hormone disorders. Somatostatin acts like a brake pedal for many processes in the human body, preventing the levels of blood sugar, various hormones, and many other important molecules from rising dangerously high.

The cone snail toxin, called consomatin, works similarly, the researchers found—but consomatin is more stable and specific than the human hormone, which makes it a promising blueprint for drug design.

By measuring how consomatin interacts with somatostatin's targets in human cells in a dish, the researchers found that consomatin interacts with one of the same proteins that somatostatin does. But while somatostatin directly interacts with several proteins, consomatin only interacts with one. This fine-tuned targeting means that the cone snail toxin affects hormone levels and blood sugar levels but not the levels of many other molecules.

In fact, the cone snail toxin is more precisely targeted than the most specific synthetic drugs designed to regulate hormone levels, such as drugs that regulate growth hormone. Such drugs are an important therapy for people whose bodies overproduce growth hormone. Consomatin's effects on blood sugar could make it dangerous to use as a therapeutic, but by studying its structure, researchers could start to design drugs for endocrine disorders that have fewer side effects.

Consomatin is more specific than top-of-the-line synthetic drugs—and it also lasts far longer in the body than the human hormone, thanks to the inclusion of an unusual amino acid that makes it difficult to break down. This is a useful feature for pharmaceutical researchers looking for ways to make drugs that will have long-lasting benefits.

 Disruption of Glucose Homeostasis in Prey: Combinatorial Use of Weaponized Mimetics of Somatostatin and Insulin by a Fish-Hunting Cone Snail, Nature Communications (2024). DOI: 10.1038/s41467-024-50470-2. www.nature.com/articles/s41467-024-50470-2

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