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Comment by Dr. Krishna Kumari Challa on July 30, 2023 at 11:43am

Who are scientists on whom experiments were performed?

Here is the story of a Doctor Who Jammed a Catheter Into His Heart to help humanity…

Werner Theodor Otto Forßmann : (29 August 1904 – 1 June 1979) was a German researcher and physician from Germany who shared the 1956 Nobel Prize in Medicine (with Andre Frederic Cournand and Dickinson W. Richards) for developing a procedure that allowed cardiac catheterization. In 1929, he put himself under local anesthesia and inserted a catheter into a vein of his arm. Not knowing if the catheter might pierce a vein, he put his life at risk. Forssmann was nevertheless successful; he safely passed the catheter into his heart.

Comment by Dr. Krishna Kumari Challa on July 29, 2023 at 8:14am

The result is that the mitochondria send two chemical signals to the cell when protein misfolding stress occurs: They release reactive oxygen compounds and block the import of protein precursors, which are produced in the cell and are only folded into their functional shape inside the mitochondrion, causing these precursors to accumulate in the cell. Among other things, the reactive oxygen compounds lead to chemical changes in a protein called DNAJA1. Normally, DNAJA1 supports a specific chaperone (folding assistant) in the cell, which molds the cell's newly formed proteins into the correct shape.

As a consequence of the chemical change, DNAJA1 now increasingly forces itself on the folding assistant HSP70 as its helper. HSP70 then takes special care of the misfolded protein precursors that accumulate around the mitochondrion because of the blocked protein import. By doing so, HSP70 reduces its interaction with its regular partner HSF1. HSF1 is now released and can migrate into the cell nucleus, where it can trigger the anti-stress mechanism for the mitochondrion.

It was very exciting to discover how the two mitochondrial stress signals are combined into one signal in the cell, which then triggers the cell's response to mitochondrial stress. Moreover, in this complex process, which is essentially driven by tiny local changes in concentration, the stress signaling pathways of the cell and the mitochondrion dovetail very elegantly with each other—like the cogs in a clockwork.

F. X. Reymond Sutandy et al, A cytosolic surveillance mechanism activates the mitochondrial UPR, Nature (2023). DOI: 10.1038/s41586-023-06142-0

Part 2

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Comment by Dr. Krishna Kumari Challa on July 29, 2023 at 8:13am

Researchers discover how mitochondria call for help when under stress

As life propagated across Earth in the form of the widest variety of single-celled organisms, sometime between 3.5 and 1 billion years ago one such organism managed an evolutionary coup: Instead of devouring and digesting bacteria, it encapsulated its prey and used it as a source of energy. As a host cell, it offered protection and nutrition in return.

This is referred to as the endosymbiotic theory, according to which that one single-celled organism was the primordial mother of all higher cells, out of which all animals, fungi and plants developed. Over the course of billions of years, the encapsulated bacterium became the cell's powerhouse, the mitochondrion, which supplies it with the cellular energy currency ATP.

It lost a large part of its genetic material—its DNA—and exchanged smaller DNA segments with the mother cell. However, now as in the past, mitochondria divide independently of the cell and possess some genes of their own.

How closely the cell and the mitochondrion work together in human cells today is what some researchers are investigating. They have now discovered how the mitochondrion calls for help from the cell when it is under stress. Triggers for such stress can be infections, inflammatory diseases or genetic disorders, for example, but also nutrient deficiencies or cell toxins. The study has been published in the journal Nature.

A certain type of mitochondrial stress is caused by misfolded proteins that are not quickly degraded and accumulate in the mitochondrion. The consequences for both the mitochondrion and the cell are dramatic: Misfolded proteins can, for example, disrupt energy production or lead to the formation of larger amounts of reactive oxygen compounds, which attack the mitochondrial DNA and generate further misfolded proteins. In addition, misfolded proteins can destabilize the mitochondrial membranes, releasing signal substances from the mitochondrion that activate apoptosis, the cell's self-destruction program. The mitochondrion responds to the stress by producing more chaperones (folding assistants) to fold the proteins in order to reduce the misfolding, as well as protein shredding units that degrade the misfolded proteins. Until now, how cells trigger this protective mechanism was unknown.

The researchers artificially triggered misfolding stress in the mitochondria of cultured human cells and analyzed the result. What makes it difficult to unravel such signaling processes is that an incredibly large number take place simultaneously and at high speed in the cell.

The research team therefore availed itself of methods (transcriptome analyses) that can be used to measure over time to what extent genes are transcribed. In addition, the researchers observed, among other things, which proteins bind to each other at which point in time, at which intervals the concentrations of intracellular substances change, and what effects there are when individual proteins are systematically deactivated.

Part 1

Comment by Dr. Krishna Kumari Challa on July 29, 2023 at 8:03am

Microorganisms ward off parasites: Potential new function of CRISPR-Cas system discovered

Microorganisms use the CRISPR-Cas system to fight viral attacks. In genetic engineering, the microbial immune system is used for the targeted modification of the genetic make-up. A research team has now discovered another function of this specialized genomic sequence: archaea—microorganisms that are often very similar to bacteria in appearance—also use them to fight parasites. 

They analyzed the genetic material of microbes in the Earth's deep crust. More than 70% of the Earth's microorganisms are housed in the deep biosphere. If we want to understand diversity on our planet, it is worth taking a look into the deep.

The microbiologists have analyzed the water that a geyser in the U.S. spits to the surface from the depths, as well as samples from the Horonobe underground laboratory in Japan. The research team focused on archaea, which live in the ecosystem as hosts and parasites. The tiny microbes are highly similar to bacteria in cell size but have substantially different physiological properties. The result of their genomic analysis provided new insights: there were conspicuously few parasites in the vicinity of the hosts, and the hosts showed genetic resistance to the parasites. The researchers discovered the reason for this in the genetic scissors in the genome of the microorganisms.

In the course of evolution, the archaea have incorporated the parasitic DNA. If a parasite with the same DNA now attacks the organism, the foreign genetic material is probably recognized by the CRISPR system and presumably decomposed.

In order to rule out the possibility that they have only come across isolated cases, the researchers have extended the analysis to more than 7,000 genomes and observed the phenomenon very frequently.

Sarah P. Esser et al, A predicted CRISPR-mediated symbiosis between uncultivated archaea, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01439-2

Comment by Dr. Krishna Kumari Challa on July 29, 2023 at 7:57am

How a gut microbe causes flies to live fast and die young

Researchers have uncovered how one species of gut bacteria causes fruit flies to perish early. This discovery illuminates the complex interactions between the microbes in our guts and our health.

The human gut is home to somewhere between 200 and 1,000 species of bacteria. The vast majority of these species are beneficial, converting food into useful compounds that the human body cannot make by itself. But some bacterial species have a negative impact on health.

The sheer number of bacterial species in the human gut makes it extremely challenging to untangle their individual effects on our health. Researchers find it much simpler to look at the gut microbiome of fruit flies since they only have about two to five bacterial species in their guts.

In a previous study, researchers have found that one of these species, Acetobacter persici, accelerated aging in flies, causing them to die early. A. persici has a drastic impact on fly lifespan, curtailing it by about 20%–30%.

Now, by feeding flies with a diet of dead A. persici, scientists have discovered the connection between A. persici and shortened fly lifespans.

To their surprise, the researchers found that the shortened lifespan is not due to a compound produced by A. persici. Rather, a component in the bacterium's cell wall triggers a receptor in the fly's gut, which stimulates the immune system, boosting the production of antimicrobial compounds and activating intestinal stem cells. It's this enhanced immunity that causes the flies to die young. In an intriguing twist, the team discovered that these effects also boost a fly's resistance to infection by a harmful bacterium that can kill flies. It thus provides flies with a short-term advantage in exchange for an early death—a tradeoff that the researchers dubbed a "live fast, die young" lifestyle.

This increased resistance to infection explains why the vast majority of flies in the wild have A. persici or other Acetobacter species in their guts. It's better to have a strong resistance to stressors such as infection rather than to live to a ripe old age.

The finding raises the possibility that "postbiotics"—food and drinks that contain dead gut microbes (rather than prebiotics containing live ones)—with health benefits could be developed.

The team now aims to determine the genes involved in the immune signaling that leads to shorter lifespans. They also want to see if the same mechanism occurs in other animals such as mice and humans.

Taro Onuma et al, Recognition of commensal bacterial peptidoglycans defines Drosophila gut homeostasis and lifespan, PLOS Genetics (2023). DOI: 10.1371/journal.pgen.1010709

Comment by Dr. Krishna Kumari Challa on July 29, 2023 at 7:27am

Scientists discover secret of virgin birth, and switch on the ability in female flies

For the first time, scientists have managed to induce virgin birth in an animal that usually reproduces sexually: the fruit fly Drosophila melanogaster.

Once induced in this fruit fly, this ability is passed on through the generations: The offspring can reproduce either sexually if there are males around, or by virgin birth if there aren't.

For most animals, reproduction is sexual—it involves a female's egg being fertilized by a male's sperm. Virgin birth, or "parthenogenesis," is the process by which an egg develops into an embryo without fertilization by sperm—a male is not needed. The offspring of a virgin birth are not exact clones of their mother but are genetically very similar, and are always female.

This work 's the first to show that you can engineer virgin births to happen in an animal—it was very exciting to see a virgin fly produce an embryo able to develop to adulthood, and then repeat the process.

In the genetically manipulated flies, the females waited to find a male for half their lives—about 40 days—but then gave up and proceeded to have a virgin birth.

In the experiments, only 1–2% of the second generation of female flies with the ability for virgin birth produced offspring, and this occurred only when there were no male flies around. When males were available, the females mated and reproduced in the normal way.

Switching to a virgin birth can be a survival strategy: A one-off generation of virgin births can help to keep the species going.

To achieve their results, researchers first sequenced the genomes of two strains of another species of fruit fly, called Drosophila mercatorum. One strain needs males to reproduce, the other reproduces only through virgin birth. The researchers identified the genes that were switched on or switched off when the flies were reproducing without fathers.

With the candidate genes for virgin birth ability identified in Drosophila mercatorum, the researchers altered what they thought were the corresponding genes in the model fruit fly, Drosophila melanogaster. It worked: Drosophila melanogaster suddenly acquired the ability for virgin birth.

The research involved over 220,000 virgin fruit flies and took six years to complete.

More information: Alexis L Sperling, A genetic basis for facultative parthenogenesis in Drosophila, Current Biology (2023). DOI: 10.1016/j.cub.2023.07.006. www.cell.com/current-biology/f … 0960-9822(23)00913-2

Comment by Dr. Krishna Kumari Challa on July 28, 2023 at 12:42pm

Long Hot July
Science articles have had their own recurring theme in recent weeks: extreme heat. An expert recently said,  “I’m feeling like a broken record about heat breaking records.” As if to further her point, today she gathered a list of the latest all-time high temps–ALL set in 2023. To cap it off, this July is set to be the hottest month ever recorded on Earth—and likely the hottest in about 120,000 years—preliminary analyses show.

What's causing this: Breaking high-temperature records is a hallmark of climate change. With more and more heat being trapped in the atmosphere by the greenhouse gases emitted when humans burn fossil fuels, heat records are now set increasingly more often than cold ones.

The solution is to ditch fossil fuels as soon as possible and to build up our use of renewable energy. Easier said than done, yes, but if extreme weather is the sweltering, flooding, hurricaning canary in the coal mine we know it to be, the urgency to make change is ramping up.

Then follow all that experts say. 

Comment by Dr. Krishna Kumari Challa on July 28, 2023 at 10:17am

However, not all vegetarian diets are alike

Vegetarian meals marketed for convenience may be high in calories, refined carbohydrates, hydrogenated oils, high-fructose corn syrup, sucrose or artificial sweeteners and salt.

A higher risk of CVD and diabetes is possible on a vegetarian diet if the veggies pass through a deep fryer first. Foods rich in trans fatty acids and salt are associated with a 32% higher risk of coronary heart disease and a high risk of type 2 diabetes.

While a meta-analysis of 20 past trials cannot control for the wide range of diets included in those studies, which ranged from vegan to vegetarian (allowing for eggs and dairy), the overall signal from these diverse vegetarian diets was clear.

The vegetarian diet is associated with significant improvements in LDL-C, HbA1c (glucose level) and body weight in individuals with type 2 diabetes or at high risk of CVDs.

The data suggests that vegetarian diets might have a synergistic (or at least nonantagonistic) use in potentiating the effects of optimal drug therapy in the prevention and treatment of a range of cardiometabolic diseases.

So these things must be understood properly before going for a vegetarian diet.

Tian Wang et al, Vegetarian Dietary Patterns and Cardiometabolic Risk in People With or at High Risk of Cardiovascular Disease, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.25658

Part 2

Comment by Dr. Krishna Kumari Challa on July 28, 2023 at 10:16am

Meta-analysis finds vegetarian diets effective in lowering cholesterol, glucose and weight

Researchers have conducted a metadata analysis on vegetarian diets' effect on people at high risk of cardiovascular diseases (CVDs). They found that the vegetarian diet was associated with significantly improved LDL-cholesterol, HbA1c (glucose level) and body weight.

In their paper, "Vegetarian Dietary Patterns and Cardiometabolic Risk in People With or at High Risk of Cardiovascular Disease: A Systematic Review and Meta-analysis," published in JAMA Network Open, the researchers present a systematic review and meta-analysis of randomized clinical trials (RCTs) on vegetarian diets' effects in individuals with or at high risk of CVDs. It aimed to assess the association of vegetarian diets with outcomes, including LDL-C, HbA1c, SBP, body weight and energy intake.

In analyzing the data from 29 studies on 20 randomized clinical trials over 22 years with 1,878 total participants, the researchers found consistently positive outcomes for participants on vegetarian diets. The studies used were mainly conducted in the U.S. and also included studies from the Czech Republic, Italy, Iran, Korea, New Zealand, and the Republic of China. Within the metadata were subsets of study parameters that all followed a similar result trend. Compared with participants' usual diet, vegetarian intervention diets significantly lowered LDL-C by 12.9 mg/dL. Compared with external control diets, consuming a vegetarian diet was associated with decreased LDL-C by 6.6 mg/dL in a mean of six months.

Vegetarian diets were associated with similar LDL-C reduction in studies with (−7.2 mg/dL) and without (−6.8 mg/dL) energy restriction involved. Vegetarian diets even lowered LDL-C (−5.9 mg/dL) in a subset of studies with no physical activity intervention or requirements.

The most consistent weight reduction was observed in people at high risk of CVDs (−9.1 mg/dL). Among all different vegetarian diets, lacto-ovo (including dairy and egg) vegetarian diets were associated with the greatest reduction in LDL-C.

The most significant weight reduction was observed in people at high risk of CVD (−3.6), followed by people with type 2 diabetes (−2.8 kg). An unexpected signal between restricted and unrestricted caloric studies observed more than twice the weight reduction in vegetarian intervention diets without energy restriction.

Those with unrestricted (vegetarian) calorie intake lost an average of 4.7 kg compared to 1.8 kg for those with energy-restricted vegetarian diets. It is unclear if this indicates additional benefits of an all-you-can-eat vegetarian diet, specific limitations on the type of foods available, or hidden high-calorie deviations from participants on restrictive diets.

Part 1

Comment by Dr. Krishna Kumari Challa on July 27, 2023 at 1:33pm

Man Tests Positive For MERS-CoV in Abu Dhabi, WHO Reports

A man has tested positive for MERS-CoV in Abu Dhabi, the WHO. So far, the 28-year-old is the only case to test positive out of 108 close contacts identified, but the WHO is urging vigilance.

MERS‐CoV is a coronavirus first identified in the Middle East in 2012 after the virus made its way into humans from bats via camels. It's one of a number of zoonotic viruses (those that jump from animals into people) that health authorities keep close tabs on. The WHO was notified of the confirmed case by the United Arab Emirates' health surveillance body on July 10, 17 days after the young man tested positive in hospital on June 23. In light of the case, WHO "re-emphasizes the importance of strong surveillance" for acute respiratory infections and has urged health authorities to "carefully review any unusual patterns."

"No secondary cases have been detected to date," WHO's July 24 statement reads, although the organization expects additional cases will be reported from the Middle East or other countries where the virus circulates in animal hosts.

According to the WHO, the man had not recently traveled outside of the UAE before his diagnosis on June 23, and has no known history of direct contact with dromedary camels, the usual source of MERS infections.

"WHO continues to monitor the epidemiological situation and conducts risk assessments based on the latest available information," the statement reads.

https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON478

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