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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+...

Comment by Dr. Krishna Kumari Challa on December 8, 2023 at 2:03pm

Study reveals genes that set humans apart from other primates in cognitive ability

An international team of researchers has uncovered over 100 genes that are common to primate brains but have undergone evolutionary divergence only in humans – and which could be a source of our unique cognitive ability.

They found the genes are expressed differently in the brains of humans compared to four of our relatives – chimpanzees, gorillas, macaques and marmosets.

The findings, published in Nature Ecology & Evolution, suggest that reduced selective pressure, or tolerance to loss-of-function mutations, may have allowed the genes to take on higher-level cognitive capacity. The study is part of the Human Cell Atlas, a global initiative to map all human cells to better understand health and disease.
This research contributes to our understanding of differences in the brain between humans and other primates at the cellular level, but it has also resulted in a database that can be used to further characterize genetic similarities and differences across primates.

In all, the team found 139 genes that are common across the primate groups but highly divergent in their expression in human brains. These genes displayed a stronger ability to withstand mutations without impacting their function, suggesting they may have evolved under more relaxed selective pressure.

The genes that have diverged in humans must be tolerant to change. This manifests as tolerance to loss-of-function mutations, and seems to allow for rapid evolutionary change in the human brain.

Our higher cognitive function may have resulted from the adaptive evolution of human brain cells to a multitude of less threatening mutations over time. It’s also worth noting that around a quarter of the human-divergent genes identified in the study are associated with various brain disorders.

The divergent genes the researchers identified are found in 57 brain cell types, grouped by inhibitory neurons, excitatory neurons and non-neurons. A quarter of the genes were only expressed differently in neuronal cells, also known as grey matter, and half were only expressed differently in glial cells, which are white matter.

Grey matter in the brain consists of neurons, while white matter consists of other cell types, including those responsible for vasculature and immune function.

 Hamsini Suresh et al, Comparative single-cell transcriptomic analysis of primate brains highlights human-specific regulatory evolution, Nature Ecology & Evolution (2023). DOI: 10.1038/s41559-023-02186-7

Comment by Dr. Krishna Kumari Challa on December 8, 2023 at 1:56pm

Scientists create 'cloaked' donor cell, tissue grafts that escape immune system rejection

Immune rejection poses a major challenge in donor cell therapy. Transplant and cell therapy patients are required to take immunosuppressive drugs – sometimes for the rest of their lives – to prevent their bodies from rejecting the transplant. The extended use of these drugs can lead to serious health issues, including recurring infections and an elevated cancer risk.

Scientists worldwide have been exploring various solutions, including creating therapeutic cells from the patient’s own cells or encapsulating donor cells in inorganic material for protection.

But these methods face challenges such as high costs, long preparation times and foreign body immune response, complicating their widespread and cost-effective application.

Researchers now have developed a technology that may one day eliminate the need for immunosuppressive drugs in transplant patients.
Through genetic modification of donor cells, the researchers successfully created transplants that persisted long-term in pre-clinical testing without the need for immune suppression.
The findings raise hope that a similar strategy could be employed in human patients, potentially making transplantation safer and more widely available.

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Stem cells have the unique ability to divide indefinitely and give rise to specialized cells that form our organs. They make an ideal source for cell therapies as large numbers of cells can be obtained and converted into desired cell types to replace those lost to disease or injury.

But there are major safety concerns: in addition to addressing immune-matching, scientists must ensure that no unwanted dividing cells remain in the transplant that could cause cancer in the future.

Researchers  selected eight key genes that regulate how the immune system responds to threats, including foreign cells. Forced overexpression of these genes in mouse embryonic stem cells prevented the immune system from recognizing them as foreign.

The modification effectively created an immune cloak around the cells following their injection under the skin of genetically unmatched hosts.

This study demonstrates the combined potential of FailSafe and immune cloaking for the creation of a universal source of cells that could be applied to a multitude of diseases.

Uncloaked cells are typically rejected within 10 days of transplantation. In contrast, the cloaked cells persisted for more than nine months at the endpoint of the experiment. This is the first time that  scientists have been able to achieve this length of time without rejection in a fully functional immune system.

In another key finding, the researchers showed that unmodified cells can escape rejection when embedded into the tissue created by the cloaked donor cells below the skin surface. The protection extended to cells from another species, as shown by the ability of unmodified human cells to survive within a cloaked mouse graft.

This suggests that modified cells also act as an immune-privileged implantation site for unmodified cells, with implications for interspecies transplants. Researchers at other institutions are exploring the potential of pigs as donors because their organs are very similar in size and function to humans.

https://www.nature.com/articles/s41551-023-01133-y

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