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Comment by Dr. Krishna Kumari Challa on December 9, 2023 at 10:35am

Catalyst makes drugs inside the body to minimize side effects

A highly active catalyst capable of synthesizing drug molecules within the body has been developed by  chemists. In mice, an anticancer drug assembled near tumors using the injected catalyst suppressed tumour growth.

In conventional medicines delivered by injection or pill, the active drug molecule circulates throughout the body, flooding not only the target site but also healthy tissues. The resulting side effects can be so serious that they can cause permanent damage and force treatment to be stopped. Assembling drug molecules at target sites within the body could make them more effective while minimizing their side effects.

The direct synthesis of drugs in the body would enable drugs to treat diseases without causing side effects in healthy tissues. That's why we need a biocompatible biocatalysis system to perform drug synthesis near target sites in the body.

The team targeted drug assembly in the body using a catalytic chemical reaction called olefin metathesis. Olefin metathesis is one of the most efficient methods for constructing carbon–carbon double bonds for synthesizing drugs. If it could be worked out in the body, it should enable us to synthesize many different types of drugs.

Most chemical catalysts are rapidly deactivated by biomolecules in the bloodstream. To overcome this problem, the team wrapped a ruthenium-based olefin metathesis catalyst inside a protective protein called human serum albumin.

Tanaka's team had previously shown that a ruthenium chloride complex embedded inside human serum albumin—forming a catalytic assembly called an artificial metalloenzyme—was somewhat active in blood. Now, they have shown that switching to a ruthenium iodide complex produces a far superior artificial metalloenzyme.

At low catalyst concentrations, the new albumin-based ruthenium iodide (AlbRuI) catalyst catalyzed three types of olefin metathesis reactions in blood at high yield.

AlbRuI also showed robust stability for 24 hours in blood.This expands the biocompatibility of artificial metalloenzymes and opens the door for developing general, metal-based artificial metalloenzymes for catalytic reactions in blood.

The team also showed that a low dose of cancer-targeting AlbRuI significantly inhibited tumour growth in mice through localized synthesis of an antitumour drug.

 Igor Nasibullin et al, Catalytic olefin metathesis in blood, Chemical Science (2023). DOI: 10.1039/D3SC03785A

Comment by Dr. Krishna Kumari Challa on December 9, 2023 at 10:27am

Rich nations need to ditch fossil fuels by 2040: scientists

Rich countries need to stop using coal by 2030 and oil and gas by 2040, with poorer nations following a decade behind, to give the world a chance of limiting warming to 1.5C, climate scientists told the UN this week.

In a note to the UN Secretary-General Antonio Guterres and UN Climate Change body, shared with AFP, climate scientists said there was very little room for anything but a total phase-out of fossil fuels.

The steep timeline they laid out comes as climate negotiators at the COP28 talks in Dubai are tussling over the future of oil, gas and coal, responsible for the lion's share of humanity's planet-heating emissions.

The UN climate negotiations are tasked with helping the world meet the Paris deal goal of limiting global warming to 1.5 degrees Celsius from pre-industrial levels, but have often been vague on how that target will be achieved.

The discussions should be around serious and fair efforts to start implementing a phase out plan: scientists

Source: AFP

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Israel's AI can produce 100 bombing targets a day in Gaza. Is this ...

Last week, reports emerged that the Israel Defense Forces (IDF) are using an artificial intelligence (AI) system called Habsora (Hebrew for "The Gospel") to select targets in the war on Hamas in Gaza. The system has reportedly been used to find more targets for bombing, to link locations to Hamas operatives, and to estimate likely numbers of civilian deaths in advance.

https://theconversation.com/israels-ai-can-produce-100-bombing-targ...

Comment by Dr. Krishna Kumari Challa on December 9, 2023 at 10:05am

Credit: Molecular Cell (2023). DOI: 10.1016/j.molcel.2023.10.036

Comment by Dr. Krishna Kumari Challa on December 9, 2023 at 10:03am

Researchers discover a mechanism that controls the identity of stem cells

Researchers  discovered a mechanism that controls the identity of stem cells. When this mechanism fails, embryonic stem cells revert back in time and become totipotent (totipotent embryo cells can differentiate into a hundred different cell types specialized to form such tissues as skin, marrow, and muscle).

When a cell becomes totipotent, this rare change enables the cells to differentiate into hundreds of cell types, and then go on to form every part of our body. This contrasts with pluripotent stem cells, which can divide into various cell types but are unable to become an entire organism solely on their own.

In a dish of embryonic stem cells, the majority of stem cells are pluripotent. However, 1 out of 1,000 cells are different from the rest, and are totipotent. Totipotent cells are the only cells that have unlimited potential and can give rise to all parts of our body. Scientists now discovered the mechanism that allows this change from pluripotent to totipotent.

Denis Torre et al, Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation, Molecular Cell (2023). DOI: 10.1016/j.molcel.2023.10.036

Comment by Dr. Krishna Kumari Challa on December 9, 2023 at 9:58am

In genetics, the concept of pleiotropy posits that a single mutation can influence multiple traits. The idea that the same mutation can be both beneficial and harmful, depending on the situation, is known as antagonistic pleiotropy and was proposed by Williams to underlie the origin of aging in a paper titled "Pleiotropy, natural selection, and the evolution of senescence."

To a biologist, senescence refers specifically to a gradual decline of bodily functions that manifests as a decline in reproductive performance and an increase in the death rate with age.

Compared with environmental factors, genetic factors play a minor role in the human phenotypic changes studied here.

Erping Long et al, Evidence for the role of selection for reproductively advantageous alleles in human aging, Science Advances (2023). DOI: 10.1126/sciadv.adh4990. www.science.org/doi/10.1126/sciadv.adh4990

Part 2

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Comment by Dr. Krishna Kumari Challa on December 9, 2023 at 9:56am

Genetic mutations that promote reproduction tend to shorten human lifespan, study shows

A  study based on a review of genetic and health information from more than 276,000 people finds strong support for a decades-old evolutionary theory that sought to explain aging and senescence.

In 1957, evolutionary biologist George Williams proposed that genetic mutations that contribute to aging could be favored by natural selection if they are advantageous early in life in promoting earlier reproduction or the production of more offspring.

Now known as the antagonistic pleiotropy theory of aging, remains the prevailing evolutionary explanation of senescence, the process of becoming old or aging. 

This theory was tested now. 

The researchers found reproduction and lifespan to be genetically strongly negatively correlated, meaning that genetic mutations that promote reproduction tend to shorten lifespan.

In addition, individuals carrying mutations that predispose them to relatively high reproductive rates have lower probabilities of living to age 76 than those carrying mutations that predispose them to relatively low reproductive rates, according to the study.

However, the authors caution that reproduction and lifespan are affected by both genes and the environment. And compared with environmental factors—including the impacts of contraception and abortion on reproduction and medical advances on lifespan—the genetic factors discussed in the study play a relatively minor role, according to the authors. These results provide strong support for the Williams hypothesis that aging arises as a byproduct of natural selection for earlier and more reproduction. Natural selection cares little about how long we live after the completion of reproduction, because our fitness is largely set by the end of reproduction.

Fitness is a concept biologists use to describe the degree to which an organism's characteristics increase its number of offspring.

The researchers now  found that when you control for the genetically predicted amount and timing of reproduction, having two kids corresponds to the longest lifespan. Having fewer or more kids both lower the lifespan. That result supports the findings of several previous studies.

Part 1

Comment by Dr. Krishna Kumari Challa on December 9, 2023 at 9:47am

Six-million-year-old groundwater pool discovered deep under Sicilian mountains

A multi-institutional team of geoscientists has discovered a deep, ancient underground pool of fresh water underneath part of the Sicilian mountains. In their study, reported in the journal Communications Earth & Environment, the group used publicly available data gathered from oil discovery efforts to study the groundwater in and around the Gela formation beneath the mountains on the island of Sicily.

The researchers analyzed maps and data from prior surveys looking for oil deposits. They discovered what they believe to be a previously unknown aquifer thousands of feet below the Hyblaean Mountains. They made 3D models of the aquifer to validate their findings and found evidence suggesting that not only is it an aquifer, but it holds approximately 17.5 cubic kilometers of water.
The team then set out to explain how so much fresh water could have come to reside, locked in, beneath a mountain range. They suggest it was trapped there during the Messinian salinity crisis millions of years ago—the 700,000-year period saw a blockage at the Strait of Gibraltar that allowed many parts of the Mediterranean Sea to dry up, exposing the seafloor to rainwater.
The research team suggests that this rainwater trickled down into the crust. Such rainwater, the researchers note, could have accumulated underground as it was soaked up by carbonate rock acting as a sponge. When sea levels returned to normal, the underground fresh water was locked in due to seawater pressure.

Lorenzo Lipparini et al, Extensive freshened groundwater resources emplaced during the Messinian sea-level drawdown in southern Sicily, Italy, Communications Earth & Environment (2023). DOI: 10.1038/s43247-023-01077-w

Comment by Dr. Krishna Kumari Challa on December 8, 2023 at 2:47pm

The zebrafish larvae and a DNA solution were put into a small container and placed inside the tank where the electric eel produces electric pulses when it is fed by the experimenter.

Part 2

Comment by Dr. Krishna Kumari Challa on December 8, 2023 at 2:43pm

Electricity from electric eels may transfer genetic material to nearby animals

 The electric eel is the biggest power-making creature on Earth. It can release up to 860 volts, which is enough to run a machine. In a recent study, a research group  found electric eels can release enough electricity to genetically modify small fish larvae. They published their findings in PeerJ.

The researchers' findings add to what we know about electroporation, a gene delivery technique. Electroporation uses an electric field to create temporary pores in the cell membrane. This lets molecules, like DNA or proteins, enter the target cell.

To test this, they exposed the young fish in their laboratory to a DNA solution with a marker that glowed in the light to see if the zebrafish had taken the DNA. Then, they introduced an electric eel and prompted it to bite a feeder to discharge electricity.

Electroporation might happen in nature.  Researchers realized that electric eels in the Amazon River could well act as a power source, organisms living in the surrounding area could act as recipient cells, and environmental DNA fragments released into the water would become foreign genes, causing genetic recombination in the surrounding organisms because of electric discharge.

The researchers discovered that 5% of the larvae had markers showing gene transfer. "This indicates that the discharge from the electric eel promoted gene transfer to the cells, even though eels have different shapes of pulse and unstable voltage compared to machines usually used in electroporation. Electric eels and other organisms that generate electricity could affect genetic modification in nature.

Other studies have observed a similar phenomenon occurring with naturally occurring fields, such as lightning, affecting nematodes and soil bacteria. 

Shintaro Sakaki et al, Electric organ discharge from electric eel facilitates DNA transformation into teleost larvae in laboratory conditions, PeerJ (2023). DOI: 10.7717/peerj.16596

Comment by Dr. Krishna Kumari Challa on December 8, 2023 at 2:31pm

Self-copying RNA vaccine wins approval
Japanese regulators have approved a COVID-19 vaccine constructed using a form of RNA that can make copies of itself inside cells. It’s the first ‘self-amplifying’ RNA (saRNA) vaccine platform to be granted full regulatory approval anywhere in the world. Because it could be used at a lower dose, it might have fewer side effects than other messenger RNA (mRNA) treatments have. When used as a booster in clinical testing, the newly authorized vaccine, ARCT-154 — developed by US biotechnology firm Arcturus Therapeutics and Australia-based CSL — triggered higher levels of virus-fighting antibodies that circulated the body for longer than did a standard mRNA COVID-19 vaccine.

https://www.nature.com/articles/d41586-023-03859-w?utm_source=Live+...

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