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Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 11:40am

The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication. After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.

By further optimizing the identified molecules, for which extremely high-resolution cryo-electron microscopic imaging was used, the researchers were able to synthesize agonists that produced high concentrations in the brain and reduced the sensation of pain effectively in investigations with animal models.

The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication , especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients.

Elissa A. Fink et al, Structure-based discovery of nonopioid analgesics acting through the α 2A -adrenergic receptor, Science (2022). DOI: 10.1126/science.abn7065

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Part 2

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 11:39am

Pain relief without side effects and addiction

New substances that activate adrenalin receptors instead of opioid receptors have a similar pain relieving effect to opiates, but without the negative aspects such as respiratory depression and addiction.

This is the result of research carried out by an international team of researchers. 

Opiates cause addiction, new substances do not

They are a blessing for patients suffering from severe pain, but they also have serious side effects: Opioids, and above all morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure. In addition, opiates are addictive—a high percentage of the drug problem  is caused by pain medication, for example.

In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics.

They are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances. It is only when researchers understand these on the atomic level that they can develop effective and safe active substances. They have now turned their attention to a new receptor that is responsible for binding adrenaline—the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine.

Part 1

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 11:30am

Far-ultraviolet LED can kill bacteria and viruses efficiently without harming humans

Ultraviolet germicidal lamps are extremely effective at exterminating bacteria and viruses, and they are routinely used in hospitals to sterilize surfaces and medical instruments.

Such lamps can be made with LEDs, making them energy efficient. But these LEDs use ultraviolet light in a range that damages DNA and thus cannot be used around people. The hunt is on to develop efficient LEDs that shine light within a narrow band of far-ultraviolet light that appears to be both good at disinfecting and safe for people.

A highly efficient LED that is deadly to microbes and viruses but safe for people has been engineered by  physicists. It could one day help countries emerge from the shadows of pandemics by killing pathogens in rooms full of people.

Germicidal LED lamps that operate in the absence of humans are often made from aluminum, gallium and nitrogen. By increasing the amount of aluminum they contain, these LEDs can be modified to work in a wavelength region that is safe for humans. But traditionally this has dramatically reduced their power.

To get around this, Masafumi Jo, Yuri Itokazu and Hideki Hirayama, all at the RIKEN Quantum Optodevice Laboratory, created an LED with a more complex design. They sandwiched together multiple layers, each containing slightly different proportions of aluminum, while in some layers they also added tiny amounts of silicon or magnesium.

This effectively created an obstacle course for electrons, hampering their movement across the material and trapping them for longer in certain areas. This, in turn, increased the amount of light emitted by the device and reduced the amount it absorbed.

To help pin down the best design, the team used  computer simulations to model all possible effects and came up with the best. They will still strive to improve their LED's performance even further, according to their research paper.

 Masafumi Jo et al, Milliwatt-power far-UVC AlGaN LEDs on sapphire substrates, Applied Physics Letters (2022). DOI: 10.1063/5.0088454

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 10:24am

Study finds the mechanism used by metastatic cancer cells to infiltrate the liver

Metastasis—when cancer spreads to form new tumors—causes approximately 90% of cancer-related deaths. Because metastatic cancer cells circulate in the blood, the liver—which filters the blood—is considered the most vulnerable organ, so treatments that prevent liver metastasis are urgently needed. A team of  researchers discovered a mechanism that allows metastatic cancer cells to infiltrate the liver, and how that infiltration can be blocked by inhibiting a related protein.

Approximately 90% of cancer-related deaths are due to metastasis when cancer spreads and forms new tumors. The liver is considered the most vulnerable organ to metastatic cancer: the 5-year survival rate after surgery to remove liver metastases is as low as 30–50%, so developing treatments to prevent liver metastasis is urgently needed.

A group of researchers has identified an alternative pathway for liver metastasis, showing that cancer cells invade via intracellular gap formation in endothelial cells, and clarified the molecular mechanism involved. The results of their research are expected to lead to the development of drugs to prevent and treat metastatic liver cancer.

Truong Huu Hoang et al, Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms, Science Advances (2022). DOI: 10.1126/sciadv.abo5525

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 10:06am

Nobel prize: physicists share prize for insights into the spooky world of quantum mechanics

The 2022 Nobel prize for physics has been awarded to a trio of scientists for pioneering experiments in quantum mechanics, the theory covering the micro-world of atoms and particles.

Alain Aspect from Université Paris-Saclay in France, John Clauser from J.F. Clauser & Associates in the US, and Anton Zeilinger from University of Vienna in Austria, will share the prize sum of 10 million Swedish kronor (US$915,000) “for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science”.

https://www.nobelprize.org/

Comment by Dr. Krishna Kumari Challa on October 4, 2022 at 8:47am

Scientists discover dual-function messenger RNA

For the very first time, a study has discovered an unprecedented pathway producing telomerase RNA from a protein-coding messenger RNA (mRNA).

The central dogma of molecular biology specifies the order in which genetic information is transferred from DNA to make proteins. Messenger RNA molecules carry the genetic information from the DNA in the nucleus of the cell to the cytoplasm where the proteins are made. Messenger RNA acts as the messenger to build proteins.

Actually, there are many RNAs (ribonucleic acids) that are not used to make proteins. 

About 70 percent of the human genome is used to make noncoding RNAs that don't code for protein sequences but have other uses."

Telomerase RNA is one of the noncoding RNAs that assembles along with telomerase proteins to form the enzyme telomerase. Telomerase is crucial for cellular immortality in cancer and stem cells. In this study, scientists show that a fungal telomerase RNA is processed from a protein-coding mRNA, instead of being synthesized independently.

Most RNA molecules are synthesized independently and here scientists uncovered a dual function mRNA that can be used to produce a protein or to make a noncoding telomerase RNA, which is really unique.

 Logeswaran, Dhenugen et al, Biogenesis of telomerase RNA from a protein-coding mRNA precursor, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2204636119. doi.org/10.1073/pnas.2204636119

Comment by Dr. Krishna Kumari Challa on October 4, 2022 at 8:40am

Water droplets hold the secret ingredient for building life

Chemists have uncovered a mechanism for peptide-forming reactions to occur in water—something that has puzzled scientists for decades.

This is essentially the chemistry behind the origin of life. This is the first demonstration that primordial molecules, simple amino acids, spontaneously form peptides, the building blocks of life, in droplets of pure water. This water-based chemistry, which leads to proteins and so to life on Earth, could also lead to the faster development of drugs to treat humanity's most debilitating diseases.

Water isn't wet everywhere. On the margins, where the water droplet meets the atmosphere, incredibly rapid reactions can take place, transforming abiotic amino acids into the building blocks of life. Places where sea spray flies into the air and waves pound the land, or where fresh water burbles down a slope, were fertile landscapes for life's potential evolution.

The chemists have spent more than 10 years using mass spectrometers to study chemical reactions in droplets containing water.

The rates of reactions in droplets are anywhere from a hundred to a million times faster than the same chemicals reacting in bulk solution. The rates of these reactions make catalysts unnecessary, speeding up the reactions and, in the case of early Earth chemistry, making the evolution of life possible.

 Holden, Dylan T. et al, Aqueous microdroplets enable abiotic synthesis and chain extension of unique peptide isomers from free amino acids, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2212642119. doi.org/10.1073/pnas.2212642119

Comment by Dr. Krishna Kumari Challa on October 4, 2022 at 8:32am

Nobel win for  unlocking secrets of Neanderthal DNA 

Scientist Svante Paabo won the Nobel Prize in medicine this year for his discoveries on human evolution that provided key insights into our immune system and what makes us unique compared with our extinct cousins.

Paabo spearheaded the development of new techniques that allowed researchers to compare the genome of modern humans and that of other hominins—the Neanderthals and Denisovans. He and his team also surprisingly found that gene flow had occurred from Neanderthals to Homo sapiens, demonstrating that they had children together during periods of co-existence.

This transfer of genes between hominin species affects how the immune system of modern humans reacts to infections, such as the coronavirus. People outside Africa have 1-2% of Neanderthal genes.

Paabo and his team also managed to extract DNA from a tiny finger bone found in a cave in Siberia, leading to the recognition of a new species of ancient humans they called Denisovans.

www.nobelprize.org/prizes/medi … dvanced-information/

Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 12:41pm

First-ever mycobiome Atlas describes associations between cancers and fungi

An international team of scientists has created the first pan-cancer mycobiome atlas — a survey of 35 types of cancer and their associated fungi.
Cancer cells and microbes have a long and enduring association. Both have coevolved within the ecosystems of the human body, often relying on the same resources. Competition for these resources often affects the replication and survival of cancer cells, microbes and the human host.

The association between cancer and individual microbes has long been studied case-by-case, but much recent attention focuses on the whole human microbiome, particularly in the gut, which houses more — and more diverse — communities of bacteria, viruses and fungi than anywhere else in or on the human body.
However, the roles and influence of cancer-associated fungi remain largely unstudied. Fungi are more complicated organisms than viruses and bacteria. They are eukaryotes — organisms with cells containing nuclei. Their cells are much more similar to animal cells than to bacteria or viruses.

The existence of fungi in most human cancers is both a surprise and to be expected. It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.

Fungi found on the human body come in two main types: environmental fungi, such as yeasts and mold that generally pose no harm to most healthy people, and commensal fungi, which live on or inside the human body and may be harmless, provide a benefit such as improving gut health or contribute to disease, such as yeast infections or liver disease. Fungi also play a role in shaping host immunity, for better or worse, which looms large in immunocompromised persons, including cancer patients.

The new study characterizes the cancer mycobiome — fungi linked to cancers — in 17,401 samples of patient tissues, blood and plasma across 35 types of cancer in four independent cohorts. The researchers found fungal DNA and cells in low abundances across many major human cancers, with differences in community compositions that differed among cancer types.

The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens.

Analyses that compared fungal communities with matched bacteriomes (the bacterial component of the microbiome) and immunomes (genes and proteins constituting the immune system) revealed that the associations between them were often “permissive,” rather than competitive.

For example, one species of fungi was found to be enriched in breast cancer tumors of patients older than 50 years while another species was notably abundant in lung cancer samples.

The researchers said there were significant correlations between specific fungi and age, tumor subtypes, smoking status, response to immunotherapy and survival measures. Whether the fungi are simply correlated or causally associated remains to be determined.

These findings validate the view that the microbiome in its entirety is a key piece of cancer biology.

Ravid Straussman, Pan-cancer analyses reveal cancer type-specific fungal ecologies and bacteriome interactions, Cell (2022). DOI: 10.1016/j.cell.2022.09.005. www.cell.com/cell/fulltext/S0092-8674(22)01127-8

Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 11:27am

Researchers reveal new strategy to prevent blood clots without increasing the risk of bleeding

A nanoparticle therapy developed by investigators  targets overactive neutrophils, a specific kind of white blood cell, to prevent almost all types of blood clots while causing no increased risk for bleeding. The preclinical findings, published in Science Translational Medicine, may lead to safer ways to care for patients impacted by blood clots. 

According to the researchers, neutrophils are key drivers of both arterial and venous thrombosis. And when you target a neutrophil, you do not increase bleeding risk, you only decrease clotting risk. 

Earlier arterial and venous thrombosis have been thought of as distinct molecular events that require separate treatment paradigms. Arterial thrombosis (an artery clot), which can cause heart attack or stroke, is commonly treated with antiplatelet agents like aspirin, while anticoagulants are used to treat venous thrombosis (a vein clot), a cause of pain or swelling in the legs or clots in the lungs.

More recently, however, experts have begun to suspect commonalities between the two events that could be leveraged as novel therapeutic targets.

In the new study, researchers used animal models to show that overactive neutrophils participate in both arterial and venous thrombosis through an increased capacity to migrate and adhere to sites of injury. They also showed that overactive neutrophils increase the production of key factors used as building blocks for clots. In seeking to halt the process, the researchers identified a cluster of receptors unique to activated neutrophils and developed antibody-coated nanoparticles that specifically target those clusters.

Lalitha Nayak et al, A targetable pathway in neutrophils mitigates both arterial and venous thrombosis, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abj7465

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