Comment

Comment by Dr. Krishna Kumari Challa on December 20, 2023 at 9:22am

Now researchers have pinpointed a promising small molecule called N6F11, which not only triggers ferroptotic cell death, it also selectively causes the degradation of glutathione peroxidase-4, also known as GPX4, a notorious blocker of ferroptosis.

With N6F11 in the mix, ferroptosis can be triggered and GPX4 is no longer in the way to prevent this specialized form of cell death from annihilating tumors. Even more eye-opening, N6F11 degraded GPX4 in human pancreatic, bladder, breast, and cervical cancer cells without affecting GPX4 in that vital trio of the immune system: dendritic cells, T cells and neutrophils. They also also found that N6F11 slowed the growth of active tumors in mouse models inoculated with pancreatic cancer cells. The animals endured the treatment without severe side effects—an effect the authors tied to N6F11's ability to stimulate T cells.

In summary, researchers now identified a small molecule, N6F11, that induces the selective degradation of GPX4 in malignant, but not immune cells in small tumours, N6F11-induced ferroptosis and initiates a powerful antitumour immune system.

Jingbo Li et al, Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.adg3049

Part 2

Comment by Dr. Krishna Kumari Challa on December 20, 2023 at 9:17am

Massive drug search uncovers infinitesimal molecule that kills cancers while sparing immune cells

Scientists have found an experimental small molecule that induces a form of cell death to kill a variety of cancers while enhancing the power of the immune system and leaving healthy cells totally unscathed.

The molecule triggers ferroptosis, a unique form of cell death that is increasingly being tested as an anti-cancer strategy. The international team of scientists reported their findings in the journal Science Translational Medicine.

All biologists know that the three major forms of cell death are  apoptosis, or type 1 cell death; autophagy, type 2 cell death; and cell necrosis, or type 3. Ferroptosis, by contrast, is a distinct form of cell death that relies on a buildup of iron and the generation of reactive oxygen species, which ultimately cause a doomed cell to self-destruct.

Turning to a different form of cell death is vital because most forms of cancer treatment today trigger cell death by enzyme-dependent apoptosis. Unfortunately, a key hallmark of human cancers is their capacity to develop resistance to treatment, and many tumor types have shockingly developed resistance to apoptosis, hence the hunt for a different way to kill tumour cells.

Even though ferroptosis is being actively pursued as a potential cancer treatment, other researchers are studying the process for its pathological role in a variety of disparate diseases that range from Alzheimer's, cardiovascular disease to even various forms of cancer. Ferroptosis is intimately involved in the disease processes of these conditions, studies have shown.

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In terms of harnessing this form of cell death as a therapeutic, teams worldwide are racing to overcome a number of conundrums, especially what's known as the "non-selective" activities of ferroptotic cell death. It doesn't just kill cancer cells, it kills a multitude of cells in the immediate micro-environment, particularly the Big Three: dendritic cells, T cells and neutrophils, which seemingly defeats the promise that ferroptosis holds as a cancer fighter.

That means most compounds capable of inducing ferroptosis in cancer cells may also inflict the same fate on various immune cells, weakening the immune system's ability to swoop in and wage war on deadly tumours.

Part 1

Comment by Dr. Krishna Kumari Challa on December 19, 2023 at 1:17pm

When exposed to PFOS and PFOA, the cells showed increased movement and a higher tendency of spreading. In a different test with CRC cells grown in a flat layer, a line was scratched down the middle to split them. When the chemicals were introduced, the cells grew and moved toward each other again.

To dig deeper, the researchers examined the chemicals' effects on the cell's metabolism. PFAS exposure altered various metabolites crucial for cell function, like amino acids and fatty acids, as well as signaling proteins associated with metastasis.

Substances that are usually anti-inflammatory and protective against cancer were reduced in the CRC cells after exposure, too. Some differences were more noticeable in the mutated cells, which could mean that cancers with this mutation may be more likely to spread with exposure to PFAS.

These results in the lab indicate that exposure to high levels of PFOS and PFOA could potentially increase the risk of CRC spreading in real-life conditions. This is crucial information for those in jobs with potential high exposure, the team says, and monitoring these chemicals is key to safeguarding their health, as are future clinical studies.

"Many in vitro studies can't be translated into humans but  understanding first the mechanisms of how they can actually affect cancer cell growth is important."

https://pubs.acs.org/doi/10.1021/acs.est.3c04844

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Part 2

Comment by Dr. Krishna Kumari Challa on December 19, 2023 at 1:16pm

Common Forever Chemicals May Trigger Cancer Cells to Spread

When colorectal cancer cells are exposed to two different types of 'forever chemicals' in the lab, the chemicals can potentially accelerate cancer progression, new research suggests.

A new study conducted an analysis of exposure levels comparable to those found in firefighters and other people who come into regular contact with per- and poly-fluoroalkyl substances (PFAS). Firefighters' blood levels of PFAS tend to be higher than the general population's because of their frequent exposure to firefighting foam, which contains PFAS chemicals for its flame retardant properties. Firefighters are more likely than the general population to develop and die from a variety of cancers that include colorectal cancer. Environmental factors are believed to be related to about 80 percent of CRC cases. In the new research, PFAS exposure in the lab induced CRC cells to migrate to new positions, implying a potential role in cancer spreading (metastasis) in living organisms. It doesn't prove it's metastasis, but they have increased motility, which is a feature of metastasis, according to researchers.

PFAS are human-made chemicals based on carbon-fluorine bonds, and as the nickname 'forever chemicals' suggests, these bonds are very strong and resistant to degradation, which makes PFAS popular for use in many kinds of products. Unfortunately, it also allows them to survive in the environment for years in ever-increasing concentrations.

They have been frequently detected in the environment, such as in drinking water, indoor dust, cleaning products, and coatings.

Many of these 'forever chemicals' are still present in everyday items, though the hazards of PFAS are largely unclear – partially because of the many different compounds involved. Research has shown that these long-lasting chemicals spread throughout the environment, and exposure to high levels has been linked to harmful health effects in people and animals. Perfluorooctanoic acid (PFOA), a widely used PFAS, was classified as carcinogenic to humans by the International Agency for Research on Cancer in November 2023, and perfluorooctanesulfonic acid (PFOS), another common PFAS, was classified as possibly carcinogenic to humans.

Part 1

Comment by Dr. Krishna Kumari Challa on December 19, 2023 at 9:57am

A framework to train multi-skilled robots for domestic use

Roboticists have been trying to develop robots that can tackle various everyday house chores, such as washing dishes or tidying up, for several years. However, so far none of the robots created has been commercialized adopted on a large scale.

Researchers  recently introduced Dobb-E, a new framework specifically designed to effectively train mobile robots on domestic tasks, ultimately contributing to their future widespread use. This framework, outlined in a paper pre-published on the server arXiv, could be applied to various robots designed to assist humans in their homes.

We already have specialist 'robots' in our homes, such as a dishwasher or a laundry machines, but a generalist robot that can learn how to complete each home-work and how it can help best in that situation has been a distant goal for all too long now.

So researchers developed an ergonomic demonstration collection tool, enabling us to gather task-specific demonstrations in unfamiliar homes without direct robot operation.

The Dobb-E framework has four key components, namely a data collection tool, a pre-trained model, a diverse data set and a deployment scheme. 

Remarkably, the robot was taught to complete 109 different household tasks. For each of these tasks, the researchers fine-tuned their model with five minutes of new video data on average.

The most exciting result of this paper is the confirmation that with our current level of technology we can build learned robotic agents that can address a wide range of tasks in a similarly large range of homes.

Now I want to buy one!

Nur Muhammad Mahi Shafiullah et al, On Bringing Robots Home, arXiv (2023). DOI: 10.48550/arxiv.2311.16098

Comment by Dr. Krishna Kumari Challa on December 18, 2023 at 11:17am

The connection to cats has to do with T. gondii's affinity for reproducing only in domestic cats. This affinity may be related to the lack of a single enzyme in feline guts, delta-6-desaturase.

While any mammal can become infected by the parasite, the digestive enzyme delta-6-desaturase prevents the parasite from getting high enough levels of linoleic acid the parasite requires to fuel reproduction.

Unlike all other mammals, cats are full of linoleic acid due to not producing the data-6-desaturase enzyme that would convert linoleic acid to oleic acid. So, the parasite only reproduces in cat intestines.

Cats then shed oocytes (protozoan parasite eggs) by the millions when they defecate, trapping them on fur and paw used to dutifully cover up their deposit, tracking them wherever a cat's paw may wander.

With the parasite completing its lifecycle, it may not affect the rest of cat biology. In humans and other animals, the failure to turn into the larger reproductive form allows the tiny parasite to migrate past the blood-brain barrier, where the disruption occurs.

The missing enzyme and the independent social lives of outdoor cats, mingling in shared sandboxes and loose garden soils around the world, make cat contact the primary vector for the infection. The secondary vector would be anything that has been in contact with a cat, such as a kitchen counter or any surface a cat has walked on or rubbed against.

While social media has clearly made the case that society would crumble without cats, it is important for all cat owners never to allow their cats outdoors to prevent the continued spread of the T. gondii parasite.

It is even more important that parents, with or without cats, understand the danger cat-borne parasites can pose to the long-term mental health of their children.

More information: John J McGrath et al, Cat Ownership and Schizophrenia-Related Disorders and Psychotic-Like Experiences: A Systematic Review and Meta-Analysis, Schizophrenia Bulletin (2023). DOI: 10.1093/schbul/sbad168

E. F. Torrey et al, Toxoplasma gondii and Other Risk Factors for Schizophrenia: An Update, Schizophrenia Bulletin (2012). DOI: 10.1093/schbul/sbs043

Part 3

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Comment by Dr. Krishna Kumari Challa on December 18, 2023 at 11:16am

Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that causes toxoplasmosis, an infection that around 25% of the world population has gotten at some point.

It is the reason kitty litter bags have a warning label for pregnant women to avoid contact with cat feces, as toxoplasmosis infection is the leading cause of newborn blindness globally, as well as later vision loss, mental disability, and seizures.

Toxoplasmosis can be a significant cause of death among people with severely weakened immune systems. A daily drug is taken by patients with AIDS, undergoing organ transplant, or with intense chemotherapy treatments just to counter the effects of this one parasite.

T. gondii has previously been linked with all sorts of neurological impairments and behavioural changes, from guilt issues to novelty seeking and increased car accidents. Some presentations of schizophrenia can be reversed by antiprotozoal drugs, suggesting that a T. gondii infection may have been the root cause of those case symptoms.

A 2012 meta-analysis of 38 studies, "Toxoplasma gondii and Other Risk Factors for Schizophrenia," also published in Schizophrenia Bulletin, found that patients with schizophrenia were nearly three times more likely to have toxoplasma antibodies in their blood, suggesting past infections were far more prevalent with the pathology.

A striking find in that study, while comparing risk factors for schizophrenia, was the discrepancy between the risk associated with having a first-degree relative with schizophrenia (RR 6.99–9.31) and the risk associated with specific genetic polymorphisms (OR 1.09–1.24). While a family disease pattern can suggest the involvement of shared genes, it can also point to nongenetic factors like environmental exposure to an infectious agent, like a chemical superfund site, or cats.

Toxoplasmosis has also been linked to various wildlife illnesses, as behavioral changes in wild animals often result in poor survival strategies. Rats, for example, become unafraid of cats while infected. It is a common comorbidity for most California sea lions found distressed or dead to have a toxoplasma infection. If anyone is wondering how a sea lion has contact with a cat, try to see a sandy beach from a cat's perspective. That and the human habit of flushing cat litter have created a massive problem for marine mammals.

Part 2

Comment by Dr. Krishna Kumari Challa on December 18, 2023 at 11:14am

Kids with cats have more than double the risk of developing schizophrenia, researchers find

Researchers  have added to the growing body of evidence that cat ownership is a major risk factor for schizophrenia and quantified the risk at more than double.

In a paper, "Cat Ownership and Schizophrenia-Related Disorders and Psychotic-Like Experiences: A Systematic Review and Meta-Analysis," published in Schizophrenia Bulletin, the team details the connections between youth cat ownership and later-in-life schizophrenia-related diagnosis.

The researchers conducted an extensive study search across various databases and gray literature from January 1, 1980, to May 30, 2023, without geographical or language limitations. They included studies reporting original data on cat ownership and schizophrenia-related outcomes. Out of 1,915 identified studies, 17 were used from 11 different countries.

Cat ownership was associated with an increased risk of schizophrenia-related disorders. The unadjusted pooled odds ratio (OR) was 2.35, and the adjusted estimate was 2.24, indicating an over twofold increase in the odds of developing schizophrenia-related disorders among all individuals exposed to cats.

While some studies suggest childhood exposure to cats might be associated with an increased risk of developing schizophrenia-related disorders, the exact age or specific time frame of exposure is not clearly defined across all studies.

One included study from Finland initially reported higher scores on perceptual aberration, schizoid, and social anhedonia scales for those exposed to cats under age seven, though they limited their conclusion to perceptual aberration. Another study from the UK found associations between cat exposure during childhood (at 4 and 10 years) and higher psychotic-like experiences at age 13.

The research suggests that the critical window of exposure needs to be better defined and might be influenced by various factors. More robust investigations are needed to precisely identify the specific period of exposure that might pose the highest risk for schizophrenia-related disorders associated with youth cat exposure.

The overall risk trend focuses on the interaction between the developing brain and feline exposure. But of course, it is not just hanging out with cat personalities that is to blame for the higher risk. There is a causal agent operating unseen in the cat environment that is likely the true culprit—Toxoplasma gondii.

Part1

Comment by Dr. Krishna Kumari Challa on December 18, 2023 at 9:56am

People, not the climate, found to have caused the decline of the giant mammals

For years, scientists have debated whether humans or the climate have caused the population of large mammals to decline dramatically over the past several thousand years. A new study confirms that climate cannot be the explanation.

About 100,000 years ago, the first modern humans migrated out of Africa in large numbers. They were eminent at adapting to new habitats, and they settled in virtually every kind of landscape—from deserts to jungles to the icy taiga in the far north.

Part of the success was human's ability to hunt large animals. With clever hunting techniques and specially built weapons, they perfected the art of killing even the most dangerous mammals.

But unfortunately, the great success of our ancestors came at the expense of the other large mammals.

It is well-known that numerous large species went extinct during the time of worldwide colonization by modern humans. Now, new research reveals that those large mammals that survived also experienced a dramatic decline.

By studying the DNA of 139 living species of large mammals, scientists have been able to show that the abundances of almost all species fell dramatically about 50,000 years ago.

For the past 800,000 years, the globe has fluctuated between ice ages and interglacial periods about every 100,000 years. If the climate was the cause, we should see greater fluctuations when the climate changed prior to 50.000 years ago. But we don't. Humans are, therefore, the most likely explanation.

So far, some of the most important evidence in the debate has been fossils from the past 50,000 years. They show that the strong, selective extinction of large animals in... Therefore, the extinction of animals can hardly be linked to climate.

Juraj Bergman et al, Worldwide Late Pleistocene and Early Holocene population declines in extant megafauna are associated with Homo sapiens expansion rather than climate change, Nature Communications (2023). DOI: 10.1038/s41467-023-43426-5

Comment by Dr. Krishna Kumari Challa on December 18, 2023 at 9:47am

A global biodiversity tipping point as first marine fish extinction declared

A species of ray, so rare it has only ever been recorded once back in the late 1800s, has been declared extinct after an assessment by an international team led by Charles Darwin University (CDU). The loss of the Java Stingaree, a small relative of stingrays, is the first marine fish extinction as a result of human activity.

This news comes as the International Union for Conservation of Nature (IUCN) released its updated Red List of Threatened Species.

The Java Stingaree (Urolophus javanicus) was known only from a single specimen collected in 1862 from a fish market in Jakarta, Indonesia.

The team conducted new modeling encompassing all available information on the species which has revealed the Java Stingaree as extinct.

Intensive and generally unregulated fishing is likely the major threat resulting in the depletion of the Java Stingaree population, with coastal fish catches in the Java Sea already declining by the 1870s.

The northern coast of Java, particularly Jakarta Bay where the species was known to occur, is also heavily industrialized, with extensive, long-term habitat loss and degradation.

These impacts were severe enough to unfortunately cause the extinction of this species.

 www.iucnredlist.org/species/60 … sessment-information

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