Comment

Comment by Dr. Krishna Kumari Challa on January 4, 2022 at 11:57am

One of the reasons why a clearer understanding of the channel protein's natural structure is important is to advance the development of treatments for genetic disorders for which there is no known cure, such as retinitis pigmentosa. With this disease, photoreceptors gradually die off, leaving people blind. One possible cause is that the body is unable to correctly produce the CNG channel protein due to a genetic defect. As a result, the ion channel does not close completely when light hits the eye, disrupting the cell's electrochemical balance and causing the cells to die.

If we could find molecules that affect the protein in such a way that the channel would completely close, we could prevent the cells from dying—and thus stop people going blind.

 Now that researchers have identified the precise structure of the protein they are able to search specifically for such molecules.

The protein comprises four parts: three lots of subunit A, and one lot of subunit B. A correctly functioning ion channel is only possible in this combination. In their study, PSI scientists show why the B subunit seems to play such an important role: a side arm of the protein—a single amino acid—protrudes from the rest of the protein, like a barrier across a gateway. This narrows the passage in the channel to the point where no ions can pass through.

 It is interesting to note that the additional barrier is found not only in the protein from the cow's eye, but seems to apply to all types of animal, as the scientists showed. Whether crocodiles, eagles or humans—all living creatures with an ion channel in their eye have the same protruding amino acid at this position in the protein. As it has been preserved so consistently during evolution, it must be essential for the functioning of the channel.

Diane C. A. Barret et al, The structure of the native CNGA1/CNGB1 CNG channel from bovine retinal rods, Nature Structural & Molecular Biology (2021). DOI: 10.1038/s41594-021-00700-8

https://phys.org/news/2022-01-newly-discovered-protein-rod-cells-re...

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Comment by Dr. Krishna Kumari Challa on January 4, 2022 at 11:55am

Newly-discovered protein in the rod cells of the retina helps us see in dim light

 scientists have shed light on an important component of the eye: a protein in the rod cells of the retina which helps us see in dim light. Acting as an ion channel in the cell membrane, the protein is responsible for relaying the optical signal from the eye to the brain. If a genetic disorder disrupts the molecular function in a person, they will go blind. Scientists have deciphered the protein's three-dimensional structure, preparing the way for innovative medical treatments. The study is published in the scientific journal Nature Structural & Molecular Biology.

It's thanks to the rod cells in our eye that we can observe the stars in the night sky.

These photo cells are so sensitive to light that they can detect even a single photon reaching us from a very remote part of the universe—a truly incredible feat." The ability of our brain to eventually translate these light beams into a visual impression is partly down to the cyclic nucleotide-gated (CNG) ion channels whose three-dimensional structure has now been illuminated by a  research group.

The ion channel acts as a gatekeeper controlling whether specific particles are allowed through to the interior of the receptor cell. It is embedded in the protein-rich shell—the cell membrane—of the rod cells. In darkness, the ion channel, and thus the gate to the cell, is completely open. But when light hits the eye, it triggers a cascade of processes in the rod cells. This ultimately causes the gate to close, with the result that positively charged particles, such as calcium ions, can no longer enter into the cell.

This electrochemical signal continues via the nerve cells into the brain's visual cortex, where a visual impression—such as a flash of light—is created. The scientists  used cryo-electron microscopy to reveal the three-dimensional structure of the ion channel.

Part 1

Comment by Dr. Krishna Kumari Challa on January 4, 2022 at 11:51am

How To Kick A Pulsar Out Of The Galaxy

The Baseline #10 - How To Kick A Pulsar Out Of The Galaxy from NRAO Outreach on Vimeo.

Comment by Dr. Krishna Kumari Challa on January 4, 2022 at 11:38am

Scientists discover emergency pathway to help human cells with protein damage survive

Cell proteins damaged by oxygen radicals can be chemically "tagged" for elimination, but an "emergency pathway" bypasses strict protocol and can eliminate even without the need for prior tagging.

An international research team headed by Technion scientists has found an alternative manner for eliminating damaged proteins when the cells are impaired by "oxygen radicals," as can happen in failing human hearts where there is poor cell respiration and cells become oxygen depleted, or suffer "hypoxia," because of poor oxygen uptake.

Significantly, the researchers discovered that there can be a shift from the tightly controlled process of eliminating proteins in the cells to a less strict mechanism when cells enter an "emergency protocol." This shift can "clear up" the toxic proteins before their toxicity levels get too high.

Human cells—both functional and damaged—are constantly recycled by chemically "tagging" and targeting for removal when they are under stress by the ubiquitin system (2004 Nobel Prize in chemistry). At the same time, a few proteins that are intact and functional can also be dragged into the 20S proteasome "molecular disposal unit" along with the toxic proteins that have be targeted for destruction. Nevertheless, rather than harm cells, this mode of action by 20S proteasome may aid cells in rapidly remove toxic proteins. In their conclusion, the authors raised the interesting speculation that this emergency pathway can help even damaged cells to withstand bouts of stress and allow them to "age gracefully."

Indrajit Sahu et al, The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag, Nature Communications (2021). DOI: 10.1038/s41467-021-26427-0

https://phys.org/news/2022-01-scientists-emergency-pathway-human-ce...

Comment by Dr. Krishna Kumari Challa on January 4, 2022 at 11:34am

Over the course of evolution, some species have developed powerful means of suppressing cancer. Generally, they do this either by trying to prevent mutations from arising in the first place, improving the fidelity of DNA copying mechanisms or by repairing damaged DNA, or some combination of these.

Often, crucial cancer-related genes come into play. One of these, a tumor-suppressing gene known as TP53, can act to repair damaged DNA. Where the sequence can not be repaired, the gene instructs the cell to undergo apoptosis or cell death, preventing the mutation from being duplicated in subsequent cell generations. Elephants, which would otherwise be highly cancer prone due to their size and longevity, carry multiple copies of TP53 and have very low rates of cancer.

Although high radiation caused catastrophic damage to T. adhaerens' DNA, the animal's powers of DNA repair enabled the organism to recover from the assault. Although not all individuals survived the highest doses of radiation, those that did were able to repopulate the culture after 30 days of exposure to 218.6 Gy. A total of 74 genes were significantly overexpressed in T. adhaerens following radiation exposure.

Through a combination of aggressive DNA repair and ejection of damaged cells, T. adhaerens engage in continual bodily renewal, keeping them cancer-free. Understanding such mechanisms may spur new methods of preventing and treating the disease in humans. Other, as -yet-to be discovered genes likely play a role in T. adhaerens' remarkable resistance to cancer, making this tiny creature a treasure chest of information.

 Angelo Fortunato et al, Upregulation of DNA repair genes and cell extrusion underpin the remarkable radiation resistance of Trichoplax adhaerens, PLOS Biology (2021). DOI: 10.1371/journal.pbio.3001471

https://phys.org/news/2022-01-microorganism-cancer-resistance.html?...

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Part 2

Comment by Dr. Krishna Kumari Challa on January 4, 2022 at 11:32am

Microorganism sheds new light on cancer resistance

A simple, marine-dwelling creature known as Trichoplax adhaerens has some remarkable properties. The organism can tolerate unusually high doses of radiation that would kill most other forms of life. T. adhaerens has another intriguing characteristic: the ability to resist cancer.

In a new study scientists found  T. adhaerens' unusual behavior, including its capacity to repair its DNA even after significant radiation damage and to extrude injured cells, which later die.

The findings advance scientific investigations of natural cancer-suppression mechanisms across life. Insights gleaned from these evolutionary adaptations may find their way into new and more effective therapies for this leading killer.

The unusual microorganism observed in the new study is rudimentary in form and easily cultured in the lab. This makes T. adhaerens an attractive model organism, enabling researchers to home in on fundamental processes of radiation tolerance as well as the underlying mechanisms guiding DNA repair, programmed cell death and other natural means of cancer resistance.

Part 1

Comment by Dr. Krishna Kumari Challa on January 3, 2022 at 10:41am

No convincing scientific evidence that hangover cures work, according to new research

A new systematic review has found only very low-quality evidence that substances claiming to treat or prevent alcohol-induced hangover work.

The researchers call for more rigorous scientific exploration of the effectiveness of these remedies for hangovers to provide practitioners and the public with accurate evidence-based information on which to make their decisions.

A team of researchers  conducted a systematic review to consolidate and assess the current evidence for hangover treatments.

The study, published recently by the scientific journal Addiction, assessed 21 placebo-controlled randomized trials of clove extract, red ginseng, Korean pear juice, and other hangover cures. Although some studies showed statistically significant improvements in hangover symptoms, all evidence was of very low quality, usually because of methodological limitations or imprecise measurements. In addition, no two studies reported on the same hangover remedy and no results have been independently replicated.

Of the 21 included studies, eight were conducted exclusively with male participants. The studies were generally limited in their reporting of the nature and timing of alcohol challenge that was used to assess the hangover cures and there were considerable differences in the type of alcohol given and whether it was given alongside food.

Common painkillers such as paracetamol or aspirin have not been evaluated in placebo controlled randomized controlled trials for hangover

According to the researchers, future studies should be more rigorous in their methods, for example by using validated scales to assess hangover symptoms. There is also a need to improve the participation of women in hangover research.

The hangover cures assessed in this study included Curcumin, Duolac ProAP4 (probiotics), L-cysteine, N-Acetyl-L-Cysteine (NAC), Rapid Recovery (L-cysteine, thiamine, pyridoxine and ascorbic acid), Loxoprofen (loxoprofen sodium), SJP-001 (naproxen and fexofenadine), Phyllpro (Phyllanthus amarus), Clovinol (extract of clove buds), Hovenia dulcis Thunb. fruit extract (HDE), Polysaccharide rich extract of Acanthopanax (PEA), Red Ginseng, Korean Pear Juice, L-ornithine, Prickly Pear, Artichoke extract, 'Morning-Fit' (dried yeast, thiamine nitrate, pyridoxine hydrochloride, and riboflavin), Propranolol, Tolfenamic acid, Chlormethiazole, and Pyritinol.

Emmert Roberts et al, The efficacy and tolerability of pharmacologically active interventions for alcohol‐induced hangover symptomatology: A systematic review of the evidence from randomised placebo‐controlled trials, Addiction (2022). DOI: 10.1111/add.15786

https://medicalxpress.com/news/2022-01-convincing-scientific-eviden...

Comment by Dr. Krishna Kumari Challa on January 3, 2022 at 10:30am

The new findings join a growing body of work that may eventually lay the groundwork for future pharmaceutical interventions to help the vast majority of HIV patients eliminate the virus based on principles scientists are learning from elite controllers, people who have achieved so-called "sterilizing cures."

"Increasing evidence suggests that durable drug-free control of HIV-1 replication is enabled by effective cellular immune responses. Data from their experimental work suggest that viable human immunodeficiency viruses in elite controllers may face greater pressure from immune system cells. As a result, the viruses are unable to dodge the immune system's formidable army.

 Xiaodong Lian, et al, Signatures of immune selection in intact and defective proviruses distinguish HIV-1 elite controllers, Science Translational Medicine (2021) DOI: 10.1126/scitranslmed.abl4097

https://medicalxpress.com/news/2021-12-hiv-patients-unique-biology-...

Part 2

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Comment by Dr. Krishna Kumari Challa on January 3, 2022 at 10:28am

HIV patients 'cured' by their own unique biology may harbor secrets to end the global scourge

Some people diagnosed with HIV are able to eradicate the virus without antiretroviral medications or even stem cell transplants, possessing the ability to naturally suppress the virus and achieve a medically verifiable cure.

Scientists call this small population elite controllers, a moniker that reflects their unique ability to keep one of the most notorious viruses at bay.

Two of these patients have garnered fame in the scientific literature in recent months, each known mostly by a code name: the San Francisco Patient, and another called the Esperanza Patient. Both are women who have been spotlighted in medical journals and at scientific conferences for having eradicated HIV from their bodies.

Beyond those two celebrated examples, new research from the Ragon Institute in Boston has zeroed in on a larger group of elite controllers—58 altogether—who have also been able to keep the virus at bay by virtue of their distinct biological capabilities. The elite controllers were compared with 42 HIV patients on antiretroviral therapy, people who represent the vast majority of those diagnosed globally with HIV.

Writing in Science Translational Medicine, immunologists at the institute report that they have uncovered a deep well of new clues that point to elite controllers' unusual ability to eradicate the virus. One reason is a powerful immune response, but another centers on where latent viral genetic sequences are stranded in the human genome. These sequences tend to be in tucked into chromosomes in remote regions where they're less likely to replicate, but more likely to be found by immune forces.

The research is opening a new window of understanding into what it means to be infected with HIV, a virus that is estimated to affect 38 million people globally. Millions worldwide have died since the HIV pandemic began 40 years ago.

Most patients take antiretroviral drugs for life to hold the virus in check, but elite controllers can handily subdue HIV for long periods without the need for medications. Although the San Francisco Patient was infected in 1992, she has kept the virus at bay for decades. Her existence—and that of other elite controllers—defies the long-held dogma that HIV infection is invariably for life.

Part 1

Comment by Dr. Krishna Kumari Challa on January 2, 2022 at 10:54am

2021's Breakthroughs in Neuroscience and Other Biology

2021's Biggest Breakthroughs in Physics

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