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Comment by Dr. Krishna Kumari Challa on January 9, 2024 at 9:19am

Bottled water can contain hundreds of thousands of previously uncounted tiny plastic bits, study finds

In recent years, there has been rising concern that tiny particles known as microplastics are showing up basically everywhere on Earth, from polar ice to soil, drinking water and food. Formed when plastics break down into progressively smaller bits, these particles are being consumed by humans and other creatures, with unknown potential health and ecosystem effects.

One big focus of research: bottled water, which has been shown to contain tens of thousands of identifiable fragments in each container.

Now, using newly-refined technology, researchers have entered a whole new plastic world: the poorly known realm of nanoplastics, the spawn of microplastics that have broken down even further.

For the first time, they counted and identified these minute particles in bottled water. They found that on average, a liter contained some 240,000 detectable plastic fragments—10 to 100 times greater than previous estimates, which were based mainly on larger sizes.

The study was published in the journal Proceedings of the National Academy of Sciences.

Nanoplastics are so tiny that, unlike microplastics, they can pass through intestines and lungs directly into the bloodstream and travel from there to organs including the heart and brain. They can invade individual cells, and cross through the placenta to the bodies of unborn babies. Medical scientists are racing to study the possible effects on a wide variety of biological systems.

Unlike natural organic matter, most plastics do not break down into relatively benign substances; they simply divide and redivide into smaller and smaller particles of the same chemical composition. Beyond single molecules, there is no theoretical limit to how small they can get.

Microplastics are defined as fragments ranging from 5 millimeters (less than a quarter inch) down to 1 micrometer, which is 1 millionth of a meter, or 1/25,000th of an inch. (A human hair is about 70 micrometers across.) Nanoplastics, which are particles below 1 micrometer, are measured in billionths of a meter.

Plastics in bottled water became a public issue largely after a 2018 study detected an average of 325 particles per liter; later studies multiplied that number many times over. Scientists suspected there were even more than they had yet counted, but good estimates stopped at sizes below 1 micrometer—the boundary of the nano world.

The new study uses a technique called stimulated Raman scattering microscopy .This involves probing samples with two simultaneous lasers that are tuned to make specific molecules resonate. Targeting seven common plastics, the researchers created a data-driven algorithm to interpret the results. It is one thing to detect, but another to know what you are detecting .

The researchers tested three popular brands of bottled water sold in the United States (they declined to name which ones), analyzing plastic particles down to just 100 nanometers in size.
They spotted 110,000 to 370,000 particles in each liter, 90% of which were nanoplastics; the rest were microplastics. They also determined which of the seven specific plastics they were, and charted their shapes—qualities that could be valuable in biomedical research.

Part 1

Comment by Dr. Krishna Kumari Challa on January 9, 2024 at 9:06am

Harnessing haywire cells: The implications of these insights expanded in January 2020. They thought of programming macrophages to eat cancer cells as a novel treatment for the disease, an approach called CAR-M.
They found that adding a CAR receptor to macrophages promoted this behavior. But it was also clear that inducing the macrophages to eat more would make the approach more effective—especially if they would specifically consume, and kill, entire cancer cells.
There is a current cancer treatment called CAR-T, which uses the CAR receptor and a patient's own T-cells to attack and destroy cancers. It is highly effective against some cancers, but there are many that do not respond. CAR-M, a newer cousin to CAR-T, has recently entered into clinical trials in humans and so far seems safe.
Researchers now are interested in harnessing Rac-enhanced CAR macrophages to increase the efficacy of CAR-M treatments. They've filed a provisional patent for the technique—which they call Race CAR-M—and are inviting biotech companies to partner in further developing the approach.
This new multifaceted paper raises both basic science and practical questions, which the lab has begun to tackle. They're investigating whether the technique, which is so effective in the lab, will also work in freshly collected human immune cells and in animal cancer models, in mice and zebrafish. The team is also exploring how Rac2 is making this all happen at the molecular level, deep inside the cells.

 Abhinava K. Mishra et al, Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2310221120

Part 3

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Comment by Dr. Krishna Kumari Challa on January 9, 2024 at 9:02am

Around the time that they made their breakthrough, these researchers caught wind of an intriguing study in the journal Blood. This paper found that three unrelated people suffering from recurrent infections had the exact same mutation, which hyperactivates Rac2, a Rac protein produced in blood cells. They suspected their lab's recent revelation in fruit flies might shed light on this enigma.

The patients' mutation was just mildly activating, and yet it was enough that they all suffered from multiple infections and ultimately needed bone marrow transplants. Blood tests revealed that these patients had nearly no T cells, a specialized kind of white blood cells crucial to the immune system. The team at the National Institutes of Health inserted the Rac2 mutation into mice and found the same mysterious loss of T cells. They also found that the T cells with hyperactive Rac developed normally in the animals' bone marrow, and migrated to the thymus, where they continued to mature without incident. But then they just seemed to disappear. So, the paper ended with a mystery: what was causing the T cells to disappear?

The authors of that journal study had noticed that many of the patients' neutrophils—another type of white blood cell—were enlarged. They seemed to be consuming quite a lot of material, unusual behavior in an otherwise healthy person.
The researchers wondered if the patients' T cells were disappearing because their innate immune cells like neutrophils with active Rac2 were eating them, much like the fruit fly border cells with active Rac were eating the egg chamber. So they turned their attention to macrophages—the neutrophil's more voracious counterpart—to investigate. They cultured human macrophages with and without hyperactive Rac2 together with T cells. They observed that macrophages with hyperactive Rac consumed more cells, confirming the group's hypothesis from their work with fruit flies.

To test whether this might cause the observed immunodeficiency, co-author Melanie Rodriguez (a graduate student in Montell's lab) took bone marrow samples from mice with the same hyperactive Rac2 mutation found in the patients. She then grew the marrow stem cells into macrophages, and performed a similar experiment to earlier researchers' work , but this time mixing both macrophages and T cells with and without the Rac2 mutation.

She found that macrophages with active Rac2 consumed significantly more T-cells than their normal counterparts. However, T-cells with active Rac2 were also more vulnerable to consumption from either kind of macrophage. So the most likely explanation for the patients' missing T cells was a combination of increased consumption by macrophages as well as increased vulnerability of the T cells themselves. A human medical mystery was solved based on fundamental observations in fruit flies.
part 2

Comment by Dr. Krishna Kumari Challa on January 9, 2024 at 8:58am

When bad cells go good: Harnessing cellular cannibalism for cancer treatment

Scientists have solved a cellular murder mystery nearly 25 years after the case went cold. Following a trail of evidence from fruit flies to mice to humans revealed that cannibalistic cells likely cause a rare human immunodeficiency. Now the discovery shows promise for enhancing an up-and-coming cancer treatment.

This paper takes us from very fundamental cell biology in a fly, to explaining a human disease and harnessing that knowledge for a cancer therapy.

The primary character in this story is a gene, Rac2, and the protein it encodes. Rac2 is one of three Rac genes in humans. Rac is very ancient in evolution, so it must serve a fundamental function.

Rac proteins help build a cell's scaffolding, called the cytoskeleton. The cytoskeleton is made of dynamic filaments that allow cells to maintain their shape or deform, as needed. In 1996, while studying a small group of cells in the fruit fly ovary, scientists determined that Rac proteins are instrumental in cell movement. Since then, it has become clear that Rac is a nearly universal regulator of cell motility in animal.

In nineties, they also noticed that a hyperactive form of the Rac1 protein, expressed in only a few cells in a fly's egg chamber, destroyed the whole tissue. Just expressing this active Rac in six to eight cells kills the entire tissue, which is composed of about 900 cells.

A few years ago, evidence began to mount implicating cell eating, also known as cannibalism, in tissue destruction. There's a step in normal fly egg development where certain cells similar to the border cells consume their neighbors because they are no longer needed. Indeed, cellular cannibalism is not as rare as you might expect: Millions of old red blood cells are eliminated from the human body this way every second.

Rac2 is one component of the complex eating process. Rac helps the eating cell to envelop its target. The researchers were curious if a hyperactive form of the protein was causing border cells to prematurely consume their neighbours.

For this to occur, the border cells need to recognize their targets, which requires a particular receptor. Indeed, when  this receptor was blocked by scientists, the border cells expressing activated Rac didn't consume their neighbors, and the egg chamber remained alive and healthy.

Part 1

Comment by Dr. Krishna Kumari Challa on January 9, 2024 at 8:45am

Renal macrophages observed playing crucial role in preventing kidney stones

Researchers have investigated how the body's innate immune system of renal macrophages works to prevent kidney stones. In a paper, "Renal macrophages monitor and remove particles from urine to prevent tubule obstruction," published in Immunity, the authors detail their findings of mechanistic actions and strategic positioning of macrophages to surveil epithelial cells and intratubular environments.

When urine passes through the tubular system of the kidneys, it generates various microscopic sediment particles, including mineral crystals, from the concentrated urine. Pathological conditions can lead to the presence of proteins and inflammatory cells. These particles can become lodged in the tubules, blocking urine flow and causing renal dysfunction.

The researchers observed renal macrophages adjacent to the tubules in real-time, using high-resolution microscopy, live recordings and two-photon microscopy techniques. They were able to record macrophages extending transepithelial protrusions and interacting with intratubular particles, as well as their migration to assist in the excretion of urine particles.

These techniques captured the association of macrophages with particles in urine and demonstrated the role of macrophages in particle removal. Renal macrophages located near medullary tubules display specific behaviors, extending transepithelial protrusions and constantly sampling urine contents. The macrophages were then seen to migrate and surround intratubular particles, aiding in their removal from the tubular system.

To confirm the role of the macrophages, the latex bead experiment was repeated with mice lacking renal macrophages. Macrophage-depleted mice showed increased retention of the fluorescent beads even after 36 hours despite the more prolonged exposure to natural urine flushing.

This result suggests that normal urine flushing alone could not efficiently remove big particles in the renal tubule system without the macrophage pre-disposal assistance.

 Jian He et al, Renal macrophages monitor and remove particles from urine to prevent tubule obstruction, Immunity (2023). DOI: 10.1016/j.immuni.2023.12.003

Comment by Dr. Krishna Kumari Challa on January 8, 2024 at 11:59am

Study Discovers Novel Biomarker for Vascular Aging and Neurodegeneration

Comment by Dr. Krishna Kumari Challa on January 8, 2024 at 11:46am

They found that some gene families never turned up in a genome when a particular other gene family was already there, and on other occasions, some genes were very much dependent on a different gene family being present.
In effect, the researchers discovered an invisible ecosystem where genes can cooperate or can be in conflict with one another.

"These interactions between genes make aspects of evolution somewhat predictable and furthermore, we now have a tool that allows us to make those predictions
The implications of the research are far-reaching and could lead to:

Novel Genome Design—allowing scientists to design synthetic genomes and providing a roadmap for the predictable manipulation of genetic material.
Combating Antibiotic Resistance—Understanding the dependencies between genes can help identify the 'supporting cast' of genes that make antibiotic resistance possible, paving the way for targeted treatments.
Climate Change Mitigation—Insights from the study could inform the design of microorganisms engineered to capture carbon or degrade pollutants, thereby contributing to efforts to combat climate change.
Medical Applications—The predictability of gene interactions could revolutionize personalized medicine by providing new metrics for disease risk and treatment efficacy.

Alan Beavan et al, Contingency, repeatability, and predictability in the evolution of a prokaryotic pangenome, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2304934120

Part 2

Comment by Dr. Krishna Kumari Challa on January 8, 2024 at 11:45am

Evolution is not as random as previously thought, finds new study

A new study has found that evolution is not as unpredictable as previously thought, which could allow scientists to explore which genes could be useful to tackle real-world issues such as antibiotic resistance, disease, and climate change.

The study, which is published in the Proceedings of the National Academy of Sciences (PNAS), challenges the long-standing belief about the unpredictability of evolution and has found that the evolutionary trajectory of a genome may be influenced by its evolutionary history, rather than determined by numerous factors and historical accidents.

By demonstrating that evolution is not as random as scientists once thought, they've opened the door to an array of possibilities in synthetic biology, medicine, and environmental science.

The team carried out an analysis of the pangenome—the complete set of genes within a given species, to answer a critical question of whether evolution is predictable or whether the evolutionary paths of genomes are dependent on their history and so not predictable today.

Using a machine learning approach known as Random Forest, along with a dataset of 2,500 complete genomes from a single bacterial species, the team carried out several hundred thousand hours of computer processing to address the question.

After feeding the data into their high-performance computer, the team first made "gene families" from each of the gene of each genome.

In this way, they could compare like-with-like across the genomes.

Once the families had been identified, the team analyzed the pattern of how these families were present in some genomes and absent in others.

Part 1

Comment by Dr. Krishna Kumari Challa on January 6, 2024 at 12:26pm

HIV vaccine takes step forward with confirmation of neutralizing antibodies

The path to a successful HIV vaccine depends on a critical first step—activating specific immune cells that induce broadly neutralizing antibodies.

Reporting Jan. 4 in the journal Cell, a research team has achieved that requisite initial step in a study using monkeys. The next phase of the work will now move to testing in humans. This study confirms that the antibodies are, at the structural and genetic levels, similar to the human antibody that we need as the foundation for a protective HIV vaccine.

 In earlier work, the research team had isolated naturally occurring broadly neutralizing antibodies from an individual, and then back-tracked through all the changes the antibody and the virus underwent to reach a point of origin for the native antibody and its binding site on the HIV envelope.
With that knowledge, they engineered a molecule that elicits antibodies that mimic the native antibody and its binding site on the HIV envelope.

Four years ago, they published a  study in Science in which they established that monkeys made neutralizing antibodies when vaccinated with the engineered immunogen, but it was uncertain if those antibodies were like the broadly neutralizing antibody that is needed for a human vaccine.

In the current study, the researchers made a new, more potent formulation of the vaccine and delivered it to monkeys. This time, their goal was to determine whether the neutralizing antibodies generated in the animals were structurally and genetically similar to the antibodies needed in humans. They were.

Kevin O. Saunders et al, Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques, Cell (2024). DOI: 10.1016/j.cell.2023.12.002

Comment by Dr. Krishna Kumari Challa on January 6, 2024 at 12:18pm

Scientists discover why chicken farms are a breeding ground for antibiotic resistant bacteria

Scientists  are one step closer to understanding how bacteria, such as E. coli and Salmonella enterica, share genetic material which makes them resistant to antibiotics.

Antimicrobial resistance (AMR), the capability of organisms to be resistant to treatment with antibiotics and other antimicrobials, is now one of the most threatening issues worldwide. Livestock farms, their surrounding environments and food products generated from husbandry, have been highlighted as potential sources of resistant infections for animals and humans.

In livestock farming, the misuse and overuse of broad-spectrum antimicrobials administered to reduce production losses is a major known contribution to the large increase and spread of AMR.

In this latest study, scientists provide a significant contribution to demonstrating that different bacteria species, co-existing within the same microbial community (for example, within the chicken gut), are able to share AMR-associated genetic material and end-up implementing similar resistance mechanisms. The discovery has important implications as it affects our understanding of AMR and poses further challenges to the implementation of solutions for surveillance and treatment/control.

This study, published in Nature Communications, looks at two important bacteria found in food animals—Escherichia coli and Salmonella enterica, which both show high levels of drug resistance, are common in farming settings, have high levels of transmissibility to humans and cause food poisoning.

These species of bacteria can share genetic material both within, and potentially between species, a way in which AMR is spread. That is why understanding the extent to which these bacteria within the same environment, and importantly, the same host, can co-evolve and share their genome could help the development and more efficient treatments to fight AMR.

The insurgence and spread of AMR in livestock farming is a complex phenomenon arising from an entangled network of interactions happening at multiple spatial and temporal scales and involving interchanges between bacteria, animals and humans over a multitude of connected microbial environments.

Michelle Baker et al, Convergence of resistance and evolutionary responses in Escherichia coli and Salmonella enterica co-inhabiting chicken farms in China, Nature Communications (2024). DOI: 10.1038/s41467-023-44272-1

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