Comment

Comment by Dr. Krishna Kumari Challa on December 20, 2023 at 10:24am

The research team explained that they suggest this path because other studies have shown women to be very responsive to exercise countermeasures during (simulated) weightlessness. In addition, future space missions are likely to be much longer than the current study and information in this area is needed for longer durations of weightlessness.

More information: Todd A. Trappe et al, Microgravity-induced skeletal muscle atrophy in women and men: implications for long-duration spaceflights to the Moon and Mars, Journal of Applied Physiology (2023). DOI: 10.1152/japplphysiol.00412.2023

Part 2

Comment by Dr. Krishna Kumari Challa on December 20, 2023 at 10:24am

Research suggests women lose more muscle than men in spaceflight

New research published ahead of print in the Journal of Applied Physiology suggests women lose more muscle than men in a microgravity environment such as spaceflight. The study "represent[s] the longest bed rest study on a large cohort of women" and underscores the need for more sex-specific studies on physiological responses to microgravity, the research team wrote.

Historically, only about 2 out of every 10 astronauts sent into space have been women. With NASA's decision to diversify crewmembers in future spaceflight missions, including the agency's intention to send the first woman to the moon in 2024, scientists are more interested than ever in discovering how biological sex plays a role in the physiological response to microgravity. However, existing literature on the female response to low-gravity environments is sparse.

The current study explored muscle loss (atrophy) in men and women during two extended bed rest trials. The men spent 90 days, and the women spent 60 days in a 6-degree head-down tilt position, where their head was below their feet. This simulated a weightless condition similar to what crewmembers experience during spaceflight. Both volunteer groups ate, slept, performed personal hygiene, and all other activities in either the head-down tilt or a horizontal position.

The research team conducted magnetic resonance imaging tests on the volunteers' thigh and calf muscles before and after the trial as well as at the one-month mark of bed rest. These muscles were chosen "because they are critical for ambulation and extravehicular activities that likely will be required of space crews visiting the moon or Mars," the researchers said.

The researchers found that all participants lost a significant amount of muscle mass in both areas of the leg throughout their bed rest period compared to before bed rest. The women lost more muscle from the quadriceps at one month compared to the men, and the women lost more muscle mass at two months than the men lost at three months. This trend is concerning not only because of the impact on typical muscle function but also because "it is now established that muscle serves as an endocrine organ, communicating with numerous other organs," the research team explained.

The current findings from two spaceflight simulation studies suggest that women are more susceptible to weightlessness-induced muscle atrophy," the researchers wrote. "Therefore, a more appropriate path to understand sex-specific responses to microgravity (including the muscle atrophy issue) and to obtain data to better protect the health of future crewmembers may be through well-controlled long-duration bed rest studies with only exercise countermeasure groups."

Part 1

Comment by Dr. Krishna Kumari Challa on December 20, 2023 at 9:59am

Scientists construct a synthetic yeast genome

Chromosomes are long DNA molecules that collectively form a genome, containing all the genetic material of an organism. Advances in technology have allowed scientists to redesign and construct different chromosomal sequences, facilitating the study of the link between gene variations and traits.

Notably, yeast is an important model organism for the understanding of basic cellular processes, owing to its similarity to plants and animals at the cellular level while being considerably simpler to manipulate and study. Therefore, redesigning and synthesizing a yeast genome can help scientists to understand the impact of genetic variations on individual traits, potentially elucidating the mechanisms of genetic diseases.

With this goal in mind, scientists 

have synthesized a redesigned yeast—chromosome XV, that comprises 1.05 million base pairs—the largest synthesized chromosome in Asia.

The work is published in Cell Genomics. It is seen as a major milestone in the field of synthetic biology. 

In creating the synthetic Chromosome XV (synXV), the Medicine team extensively redesigned the original DNA to incorporate various changes that resulted in a sequence which is distinctively unique and different from the natural one.

In order to streamline the assembly process of synXV, the team developed a groundbreaking technology, called CRISPR/Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE). This innovative technology significantly speeds up the exchange of large chromosomal DNA segments at specific sites, hence enabling multiple synthetic chromosome segments to be assembled concurrently and stitched together into a complete synthetic Chromosome XV.

Upon generating the synthetic yeast chromosome, CRIMiRE further allows for the intentional mixing and matching of synXV with another yeast chromosome. This generates different genetic combinations for studies, which illuminates the association between genetic variations and individual traits.

Given the challenges of working with extremely long DNA sequences, the traditional approaches are unable to change the sequences efficiently. However, the use of CRIMiRE has simplified the process, shortening it tenfold, potentially revolutionizing the way larger synthetic chromosomes are built for more complex organisms. This achievement opens the door to understanding basic questions about biological processes.

 Jee Loon Foo et al, Establishing chromosomal design-build-test-learn through a synthetic chromosome and its combinatorial reconfiguration, Cell Genomics (2023). DOI: 10.1016/j.xgen.2023.100435

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.

--

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

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