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Comment by Dr. Krishna Kumari Challa on April 27, 2021 at 6:22am

Comment by Dr. Krishna Kumari Challa on April 26, 2021 at 8:45am

part 2 

The team demonstrated the modulator's ability to stimulate the mu-opioid receptor by isolating the purified receptor and measuring how it responds to enkephalins. "If you add the positive allosteric modulator, you need a lot less enkephalin to get the response."

Additional electrophysiology and mouse experiments confirmed that the opioid receptor was more strongly activated by the body's pain-relieving molecules leading to pain relief. In contrast the modulator showed much reduced side effects of depression of breathing, constipation and addiction liability.

Ram Kandasamy et al, Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2000017118

https://medicalxpress.com/news/2021-04-body-natural-pain-killers.ht...

Comment by Dr. Krishna Kumari Challa on April 26, 2021 at 8:45am

Body's natural pain killers can be enhanced

Fentanyl, oxycodone, morphine—these substances are familiar to many as a source of both pain relief and the cause of a painful epidemic of addiction and death.

Scientists have attempted for years to balance the potent pain-relieving properties of opioids with their numerous negative side effects—with mostly mixed results. Now scientists seek to side-step these problems by harnessing the body's own ability to block pain.

All opioid drugs—from poppy-derived opium to heroin—work on receptors that are naturally present in the brain and elsewhere in the body. One such receptor, the mu-opioid receptor, binds to natural pain-killers in the body called endogenous endorphins and enkephalins. Drugs acting on the mu-opioid receptor can cause addiction as well as unwanted side effects like drowsiness, problems with breathing, constipation and nausea.

Normally, when you are in pain, you are releasing endogenous opioids, but they're just not strong enough or long lasting enough. Researchers had long hypothesized that substances called positive allosteric modulators could be used to enhance the body's own endorphins and enkephalins. In a new paper published in PNAS, they demonstrate that a positive allosteric modulator known as BMS-986122 can boost enkephalins' ability to activate the mu-opioid receptor.

What's more, unlike opioid drugs, positive allosteric modulators only work in the presence of endorphins or enkephalins, meaning they would only kick in when needed for pain relief. They do not bind to the receptor in the way that opioids do instead binding in a different location that enhances its ability to respond to the body's pain-relieving compounds.

When you need enkephalins, you release them in a pulsatile fashion in specific regions of the body, then they are metabolized quickly. In contrast, a drug like morphine floods the body and brain and sticks around for several hours.

Contd. part 2

Comment by Dr. Krishna Kumari Challa on April 26, 2021 at 8:20am

'Undruggable' cancer protein becomes druggable, thanks to shrub

A chemist  has found a way to synthesize a compound to fight a previously "undruggable" cancer protein with benefits across a myriad of cancer types.

Inspired by a rare compound found in a shrub native to North America, a scientist  studied the compound and discovered a cost-effective and efficient way to synthesize it in the lab. The compound—curcusone D—has the potential to help combat a protein found in many cancers, including some forms of breast, brain, colorectal, prostate, lung and liver cancers, among others. The protein, dubbed BRAT1, had previously been deemed "undruggable" for its chemical properties. In collaboration with Alexander Adibekian's group at the Scripps Research Institute, they linked curcusone D to BRAT1 and validated curcusone D as the first BRAT1 inhibitor.

Curcusones are compounds that come from a shrub named Jatropha curcas, also called the purging nut. Native to the Americas, it has spread to other continents, including Africa and Asia. The plant has long been used for medicinal properties—including the treatment of cancer—as well as being a proposed inexpensive source of biodiesel.

Researchers tested the compounds on breast cancer cells and found curcusone D to be extremely effective at shutting down cancer cells. The protein they were targeting, BRAT1, regulates DNA damage response and DNA repair in cancer cells. Cancer cells grow very fast and make a lot of DNA. If scientists can damage cancer cells' DNA and keep them from repairing it, they can stop cancer cells from growing.

This compound can not only kill these cancer cells, it can stop their migration.

 Chengsen Cui et al, Total Synthesis and Target Identification of the Curcusone Diterpenes, Journal of the American Chemical Society (2021). DOI: 10.1021/jacs.1c00557

https://phys.org/news/2021-04-undruggable-cancer-protein-druggable-...

Comment by Dr. Krishna Kumari Challa on April 24, 2021 at 10:19am

IceCube Neutrino Observatory Detects New High-Energy Particle

In December 2016, a high-energy particle hurtled to Earth from outer space at close to the speed of light. Deep inside the ice sheet of the South Pole, it smashed into an electron, producing a shower of secondary particles. The interaction was captured by a massive telescope buried in the Antarctic glacier, the IceCube Neutrino Observatory. To enable this discovery, a multinational team of scientists used millions of hours on multiple supercomputers, including SDSC's _Comet_.

Comment by Dr. Krishna Kumari Challa on April 24, 2021 at 10:11am

Ingredient in Indian Long Pepper shows promise against brain cancer in animal models

Piperlongumine, a chemical compound found in the Indian Long Pepper plant (Piper longum), is known to kill cancerous cells in many tumor types, including brain tumors. Now an international team including researchers from the Perelman School of Medicine at the University of Pennsylvania has illuminated one way in which the piperlongumine works in animal models — and has confirmed its strong activity against glioblastoma, one of the least treatable types of brain cancer. The researchers, whose findings were published this month in ACS Central Science, showed in detail how piperlongumine binds to — and hinders the activity of — a protein called TRPV2, which is overexpressed in glioblastoma in a way that appears to drive cancer progression. The scientists found that piperlongumine treatment radically shrank glioblastoma tumors and extended life in two mouse models of this cancer, and also selectively destroyed glioblastoma

https://pubs.acs.org/doi/10.1021/acscentsci.1c00070

https://researchnews.cc/news/6316/Ingredient-in-Indian-Long-Pepper-...

Comment by Dr. Krishna Kumari Challa on April 24, 2021 at 8:30am

Climate-friendly microbes chomp dead plants without releasing heat-trapping methane

A team of scientists  has identified an entirely new group of microbes quietly living in hot springs, geothermal systems and hydrothermal sediments around the world. The microbes appear to be playing an important role in the global carbon cycle by helping break down decaying plants without producing the greenhouse gas methane.

The new group, which biologists call a phylum, is named Brockarchaeota.

So far, Brockarchaeota have not been successfully grown in a laboratory or imaged under a microscope. Instead, they were identified by painstakingly reconstructing their genomes from bits of genetic material collected in samples from hot springs in China and hydrothermal sediments in the Gulf of California. The team used high-throughput DNA sequencing and innovative computational approaches to piece together the genomes of the newly described organisms. The scientists also identified genes that suggest how they consume nutrients, produce energy and generate waste.

The Brockarchaeota are part of a larger, poorly studied group of microbes called archaea. Until now, scientists thought that the only archaea involved in breaking down methylated compounds—that is, decaying plants, phytoplankton and other organic matter—were those that also produced the greenhouse gas methane.

They are using a novel metabolism that we didn't know existed in archaea. And this is very important because marine sediments are the biggest reservoir of organic carbon on Earth. These archaea are recycling carbon without producing methane. This gives them a unique ecological position in nature.

In addition to breaking down organic matter, these newly described microbes have other metabolic pathways that scientists speculate might someday be useful in applications ranging from biotechnology to agriculture to biofuels.

Nature Communications (2021). DOI: 10.1038/s41467-021-22736-6

https://phys.org/news/2021-04-climate-friendly-microbes-chomp-dead-...

Comment by Dr. Krishna Kumari Challa on April 23, 2021 at 12:12pm

Widespread lateral gene transfer among grasses

Comment by Dr. Krishna Kumari Challa on April 23, 2021 at 12:09pm

Natural GM: how plants and animals steal genes from other species to accelerate evolution

If species already modify their genes, why shouldn't we?

https://theconversation.com/natural-gm-how-plants-and-animals-steal...

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Most Women at High-Risk of Breast Cancer Are Unaware of Preventative Medicines

Many women who are genetically susceptible to breast cancer have no idea they can take preventative medication to reduce their risk of developing the disease, according to new research from Australia.

https://cancerpreventionresearch.aacrjournals.org/content/14/1/131

https://www.sciencealert.com/many-women-at-high-risk-of-breast-canc...

Comment by Dr. Krishna Kumari Challa on April 23, 2021 at 11:10am

20% of groundwater wells around the world at risk of running dry, study says

If groundwater levels continue to decline as they have over the last several decades, new research suggests approximately one-fifth of groundwater wells around the world will be at risk of running dry.

Groundwater wells are the main source of water for roughly half the globe's population, but over the last half-century, many of the planet's major aquifers have suffered from mismanagement, growing human pressures and prolonged droughts.

The latest analysis, published Thursday in the journal Science, suggests millions of wells could run dry if aquifers continue to be depleted and regional water tables keep declining.

https://science.sciencemag.org/content/372/6540/418

https://www.upi.com/Science_News/2021/04/22/groundwater-wells-globa...

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