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Comment by Dr. Krishna Kumari Challa on March 28, 2023 at 11:56am

The researchers found that in countries where antibiotics are taken more regularly, their populations also have higher numbers of resistance genes in their gut microbiome.

The reason this collateral damage is such a major problem is that microbes are constantly sharing genes with each other. Known as horizontal gene transfer, this process helps AMR genes to spread back and forth between species. Our bodies are continually importing and exporting microbes and pathogen strains. These strains are themselves passing genes back and forth, which means the challenge of AMR has to be tackled at both the micro and macro level. Given our complex relationship with microbes, we need to do more research to understand how we maximize the benefits and minimize the risks when it comes to guiding treatment decisions and developing new medicines.

We've known for some years that antimicrobial resistance genes can spread incredibly fast between gut bacteria. This study is so important because it can, for the first time, quantify the impact national antibiotic usage has on our commensal bacteria, as well as giving us insights into the common types of resistance we can expect to evolve.

Kihyun Lee et al, Population-level impacts of antibiotic usage on the human gut microbiome, Nature Communications (2023). DOI: 10.1038/s41467-023-36633-7

Part 2

Comment by Dr. Krishna Kumari Challa on March 28, 2023 at 11:53am

Human body is a breeding ground for antimicrobial resistance genes, shows new study

The community of microbes living in and on our bodies may be acting as a reservoir for antibiotic resistance, according to new research.

The use of antibiotics leads to "collateral damage" to the microbiome, ramping up the number of resistance genes being passed back and forth between strains in the microbiome. The findings also suggest these genes spread so easily through a population, that regardless of your own health and habits, the number of resistance genes in your gut is heavily influenced by national trends in antibiotic consumption.

The rise of antimicrobial resistance (AMR) among human pathogens is widely seen as one of the most serious threats to global health in the coming decades. AMR is already believed to be contributing to tens of thousands of deaths in the world each year.

Tracking the emergence and spread of genes that help these pathogens to shrug off antibiotics has generally been limited to samples taken from infected individuals. The majority of microbes living in the human body, however, are not pathogenic.

The human microbiome is a complex and dynamic community of millions of species of microbes, primarily living in the gut and coexisting with us. Microbiomes play an important role in health and disease, with the gut microbiome known to help with the digestion of food and the development of our immune system.

Even a healthy individual who hasn't taken antibiotics recently is constantly bombarded by microbes from people or even pets they interact with, which leads to resistance genes becoming embedded in their own microbiota. If they exist in a population with a heavy burden of antibiotic consumption, it leads to more resistance genes in their microbiome.

To better understand the impact of antimicrobials on the gut microbiome, researchers analyzed over 3,000 gut microbiome samples, collected from healthy individuals across 14 countries. They then compared the resistance genes identified in samples to those found in large genome collections in order to understand the movement of AMR genes between microbe and pathogen species.

They carefully catalogued and recorded the number of antimicrobial resistance genes found in the samples by comparing data to the Comprehensive Antibiotic Resistance Database, a public health resource where resistance genes are documented.

The team identified a median of 16 AMR genes per stool sample analyzed. They also found that the median number of genes varied across the 14 countries for which they had data. For example, they saw a five-fold variation in median resistance levels between the lowest in the Netherlands and the highest in Spain.

Using World Health Organization and ResistanceMap data, the team were able to show a strong correlation between the frequency of resistance genes present in a country and national antibiotic consumption levels.

Part 1

Comment by Dr. Krishna Kumari Challa on March 28, 2023 at 11:42am

The reaction produces different isomers—molecules that all have the same mass, but slightly different structures. With standard mass spectrometry, all these variants produce the same signal. But the outcome is different when using photoelectron photoion coincidence spectroscopy, the method adopted by the team. With this technique, the structure of the measurement curve allows conclusions to be drawn about each individual isomer.

The universe contains a wild jungle of molecules and chemical reactions—not all of them can be distinctly classified in the signals from telescopes.

Scientists already know from models that both corannulene and vinylacetylene exist in the universe. Now it has been possible to confirm that these molecules actually form the building blocks to fullerene.

 The researchers want to conduct more experiments in order to understand how the classic buckyballs form in the universe, along with the football-shaped fullerene molecules with 60 carbon atoms and the minute nanotubes with even more atoms.

Lotefa B. Tuli et al, Gas phase synthesis of the C₄₀ nano bowl C₄₀H₁₀, Nature Communications (2023). DOI: 10.1038/s41467-023-37058-y

Part 2

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Comment by Dr. Krishna Kumari Challa on March 28, 2023 at 11:40am

How football-shaped molecules occur in the universe

For a long time it has been suspected that fullerene and its derivatives could form naturally in the universe. These are large carbon molecules shaped like a football, salad bowl or nanotube. An international team of researchers using the Swiss SLS synchrotron light source at PSI has shown how this reaction works. The results have just been published in the journal Nature Communications.

The planets and  human beings and all the life forms  are actually made up of dust from burnt-out supernovae and carbon compounds billions of years old. The universe is a giant reactor and understanding these reactions means understanding the origins and development of the universe—and where life - especially humans come from.

In the past, the formation of fullerenes and their derivatives in the universe has been a puzzle. These carbon molecules, in the shape of a football, bowl or small tube, were first created in the laboratory in the 1980s. In 2010 the infrared space telescope Spitzer discovered the C₆₀ molecules with the characteristic shape of a soccer ball, known as buckyballs, in the planetary nebula Tc 1. They are therefore the biggest molecules to have been discovered to date known to exist in the universe beyond our solar system.

But how do they actually form there? A team of researchers has now completed an important reaction step in the formation of the molecules, with active support from PSI and the vacuum ultraviolet (VUV) beamline of the synchrotron light source Swiss SLS.

Scientists working on the VUV beamline at PSI, has built a mini reactor for observing the formation of fullerene in real time. A corannulene radical (C₂₀H₉) is created in a reactor at a temperature of 1,000 degrees Celsius. This molecule looks like a salad bowl, as if it had been dissected from a C₆₀ buckyball. This radical is highly reactive. It reacts with vinyl acetylene (C₄H₄), which deposits a layer of carbon onto the rim of the bowl.

By repeating this process many times, the molecule would grow into the end cap of a nanotube. We have managed to demonstrate this phenomenon in computer simulations.

Part 1

Comment by Dr. Krishna Kumari Challa on March 27, 2023 at 9:44am

From mutation to arrhythmia: Desmosomal protein breakdown as an underlying mechanism of cardiac disease

Mutations in genes that form the desmosome are the most common cause of the cardiac disease arrhythmogenic cardiomyopathy (ACM), which affects one in 2,000 to 5,000 people worldwide. Researchers  now discovered how a mutation in the desmosomal gene plakophilin-2 leads to ACM. They found that the structural and functional changes in ACM hearts caused by a plakophilin-2 mutation are the result of increased desmosomal protein degradation. The findings of this study, published in Science Translational Medicine on March 22, 2023, further our understanding of ACM and could contribute to the development of new therapies for this disease.

ACM is a progressive and inheritable cardiac disease for which currently no treatments exist to halt its progression. Although patients initially do not experience any symptoms, they are at a higher risk of arrhythmias and resulting sudden cardiac arrest. As the disease progresses, patches of fibrotic and fat tissue form in the heart which can lead to heart failure. At this stage, patients require a heart transplantation as treatment.

More than 50% of all ACM cases are caused by a mutation in one of the desmosomal genes, which together form complex protein structures known as desmosomes. Desmosomes form "bridges" between individual heart muscle cells, allowing the cells to contract in a coordinated manner. Most of the desmosomal mutations that cause ACM occur in a gene called plakophilin-2.

The researchers used the genetic tool  CRISPR/Cas9 to introduce the human plakophilin-2 mutation in mice to mimic ACM. This allowed them to study progression of the disease in more detail. They observed that old ACM mice carrying this mutation had lower levels of desmosomal proteins and heart relaxation issues, similar to ACM patients.

Strikingly, the researchers discovered that the mutation lowered levels of desmosomal proteins even in young, healthy mice of which the heart contracted normally. From this they concluded that a loss of desmosomal proteins could underlie the onset of ACM caused by a plakophilin-2 mutation.

The researchers then moved on to explain the loss of desmosomal proteins. For this they studied both RNA and protein levels in their ACM mice. "The levels of desmosomal proteins were lower in our ACM mice compared to healthy control mice. However, the RNA levels of these genes were unchanged. They discovered that these surprising findings are the result of increased protein degradation in ACM hearts.

When the researchers treated their ACM mice with a drug that prevents protein degradation, the levels of desmosomal proteins were restored. More importantly, the restored levels of desmosomal proteins improved calcium handling of heart muscle cells, which is vital for their normal function.

The results of this study raise new insights into ACM development and indicate that protein degradation could be an interesting target for future therapies.

 Desmosomal protein degradation as an underlying cause of arrhythmogenic cardiomyopathy. Science Translational Medicine, 2023; 15 (688) DOI: 10.1126/scitranslmed.add4248

Comment by Dr. Krishna Kumari Challa on March 25, 2023 at 12:13pm

ARTEMIS: Advanced Robotic Technology for Enhanced Mobility and Improved Stability

Comment by Dr. Krishna Kumari Challa on March 25, 2023 at 12:04pm

Research team finds indirect evidence for existence of dark matter surrounding black holes

Dark matter does not emit or reflect light, nor does it interact with electromagnetic forces, making it exceptionally difficult to detect. Nevertheless, a research team has proven that there is a substantial amount of dark matter surrounding black holes. The study results are published in the journal The Astrophysical Journal Letters.

The team selected two nearby black holes (A0620-00 and XTE J1118+480) as research subjects, with both considered as binary systems. That is, each of the black holes has a companion star orbiting it. Based on the orbits of the companion stars, observations indicate that their rates of orbital decay are approximately one millisecond (1ms) per year, which is about 50 times greater than the theoretical estimation of about 0.02ms annually.

To examine whether dark matter exists around black holes, the team applied the "dark matter dynamical friction model"—a theory widely held in academia—to the two chosen binary systems, through computer simulations. The team found that the fast orbital decay of the companion stars precisely matches the data observed.

Notably, this is indirect evidence that dark matter around black holes can generate significant dynamical friction, slowing down the orbital speed of the companion stars.

Man Ho Chan et al, Indirect Evidence for Dark Matter Density Spikes around Stellar-mass Black Holes, The Astrophysical Journal Letters (2023). DOI: 10.3847/2041-8213/acaafa

The findings, which verified a theoretical hypothesis formulated in the late 20th century, represent a breakthrough in dark matter research. According to the hypothesis, dark matter close enough to black holes would be swallowed, leaving the remnants to be redistributed. The process ends up forming a "density spike" around the black holes.

Comment by Dr. Krishna Kumari Challa on March 25, 2023 at 11:21am

The fast and the fibrous: Developing the muscles you need for speed

Different types of exercise encourage the formation of different types of muscle fibers, or the cells that make up your muscles. Slow twitch muscle fibers support endurance activities like long-distance running, while fast twitch fibers are needed for short, powerful movements such as those involved in heavy weight lifting. Now, researchers in Japan have shed new light on a family of proteins involved in the development of these muscle fiber types.

Comment by Dr. Krishna Kumari Challa on March 25, 2023 at 9:26am

Tiny nanoparticle could have big impact on patients receiving corneal transplants

Corneal transplants can be the last step to returning clear vision to many patients suffering from eye disease. Each year  more than 184,000 corneal transplantation surgeries are performed annually in the world.

However, rejection rates for the corneal grafts can be as high as 10%. This is largely due to poor patient compliance to the medications, which require frequent administrations of topical eyedrops over a long period of time.

This becomes especially acute when patients show signs of early rejection of the transplanted corneas. When this occurs, patients need to apply topical eyedrops hourly to rescue the corneal grafts from failure.

The tedious process of eyedrop dosing causes a tremendous burden for patients. The resulting noncompliance to medical treatment can lead to even higher graft-rejection rates.

Research by a team  may make the corneal grafts more successful by using nano particles to encapsulate the medication. The novel approach could significantly improve patient compliance, according to a paper recently published in Science Advances titled "Six-month effective treatment of corneal graft rejection."

Each nanoparticle encapsulates a drug called dexamethasone sodium phosphate, one of the most commonly used corticosteroids for various ocular diseases treatment such as ocular inflammation, non-infectious uveitis, macular edema and corneal neovascularization. By using the nanoparticles to control the release of the medicine over time, patients would require only one injection right after the corneal transplantation surgery without the frequent eye drops. These studies have shown that using this method the medication maintains its efficacy for six months on a corneal graft rejection model.

In addition, because the medicine is released slowly and directly where it is most needed, the approach requires much lower doses than current standard eyedrop treatment while providing better efficacy and safety profiles.

Tuo Meng et al, Six-month effective treatment of corneal graft rejection, Science Advances (2023). DOI: 10.1126/sciadv.adf4608

Comment by Dr. Krishna Kumari Challa on March 25, 2023 at 7:32am

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