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Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 10:24am

Study finds the mechanism used by metastatic cancer cells to infiltrate the liver

Metastasis—when cancer spreads to form new tumors—causes approximately 90% of cancer-related deaths. Because metastatic cancer cells circulate in the blood, the liver—which filters the blood—is considered the most vulnerable organ, so treatments that prevent liver metastasis are urgently needed. A team of  researchers discovered a mechanism that allows metastatic cancer cells to infiltrate the liver, and how that infiltration can be blocked by inhibiting a related protein.

Approximately 90% of cancer-related deaths are due to metastasis when cancer spreads and forms new tumors. The liver is considered the most vulnerable organ to metastatic cancer: the 5-year survival rate after surgery to remove liver metastases is as low as 30–50%, so developing treatments to prevent liver metastasis is urgently needed.

A group of researchers has identified an alternative pathway for liver metastasis, showing that cancer cells invade via intracellular gap formation in endothelial cells, and clarified the molecular mechanism involved. The results of their research are expected to lead to the development of drugs to prevent and treat metastatic liver cancer.

Truong Huu Hoang et al, Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms, Science Advances (2022). DOI: 10.1126/sciadv.abo5525

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 10:06am

Nobel prize: physicists share prize for insights into the spooky world of quantum mechanics

The 2022 Nobel prize for physics has been awarded to a trio of scientists for pioneering experiments in quantum mechanics, the theory covering the micro-world of atoms and particles.

Alain Aspect from Université Paris-Saclay in France, John Clauser from J.F. Clauser & Associates in the US, and Anton Zeilinger from University of Vienna in Austria, will share the prize sum of 10 million Swedish kronor (US$915,000) “for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science”.

https://www.nobelprize.org/

Comment by Dr. Krishna Kumari Challa on October 4, 2022 at 8:47am

Scientists discover dual-function messenger RNA

For the very first time, a study has discovered an unprecedented pathway producing telomerase RNA from a protein-coding messenger RNA (mRNA).

The central dogma of molecular biology specifies the order in which genetic information is transferred from DNA to make proteins. Messenger RNA molecules carry the genetic information from the DNA in the nucleus of the cell to the cytoplasm where the proteins are made. Messenger RNA acts as the messenger to build proteins.

Actually, there are many RNAs (ribonucleic acids) that are not used to make proteins. 

About 70 percent of the human genome is used to make noncoding RNAs that don't code for protein sequences but have other uses."

Telomerase RNA is one of the noncoding RNAs that assembles along with telomerase proteins to form the enzyme telomerase. Telomerase is crucial for cellular immortality in cancer and stem cells. In this study, scientists show that a fungal telomerase RNA is processed from a protein-coding mRNA, instead of being synthesized independently.

Most RNA molecules are synthesized independently and here scientists uncovered a dual function mRNA that can be used to produce a protein or to make a noncoding telomerase RNA, which is really unique.

 Logeswaran, Dhenugen et al, Biogenesis of telomerase RNA from a protein-coding mRNA precursor, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2204636119. doi.org/10.1073/pnas.2204636119

Comment by Dr. Krishna Kumari Challa on October 4, 2022 at 8:40am

Water droplets hold the secret ingredient for building life

Chemists have uncovered a mechanism for peptide-forming reactions to occur in water—something that has puzzled scientists for decades.

This is essentially the chemistry behind the origin of life. This is the first demonstration that primordial molecules, simple amino acids, spontaneously form peptides, the building blocks of life, in droplets of pure water. This water-based chemistry, which leads to proteins and so to life on Earth, could also lead to the faster development of drugs to treat humanity's most debilitating diseases.

Water isn't wet everywhere. On the margins, where the water droplet meets the atmosphere, incredibly rapid reactions can take place, transforming abiotic amino acids into the building blocks of life. Places where sea spray flies into the air and waves pound the land, or where fresh water burbles down a slope, were fertile landscapes for life's potential evolution.

The chemists have spent more than 10 years using mass spectrometers to study chemical reactions in droplets containing water.

The rates of reactions in droplets are anywhere from a hundred to a million times faster than the same chemicals reacting in bulk solution. The rates of these reactions make catalysts unnecessary, speeding up the reactions and, in the case of early Earth chemistry, making the evolution of life possible.

 Holden, Dylan T. et al, Aqueous microdroplets enable abiotic synthesis and chain extension of unique peptide isomers from free amino acids, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2212642119. doi.org/10.1073/pnas.2212642119

Comment by Dr. Krishna Kumari Challa on October 4, 2022 at 8:32am

Nobel win for  unlocking secrets of Neanderthal DNA 

Scientist Svante Paabo won the Nobel Prize in medicine this year for his discoveries on human evolution that provided key insights into our immune system and what makes us unique compared with our extinct cousins.

Paabo spearheaded the development of new techniques that allowed researchers to compare the genome of modern humans and that of other hominins—the Neanderthals and Denisovans. He and his team also surprisingly found that gene flow had occurred from Neanderthals to Homo sapiens, demonstrating that they had children together during periods of co-existence.

This transfer of genes between hominin species affects how the immune system of modern humans reacts to infections, such as the coronavirus. People outside Africa have 1-2% of Neanderthal genes.

Paabo and his team also managed to extract DNA from a tiny finger bone found in a cave in Siberia, leading to the recognition of a new species of ancient humans they called Denisovans.

www.nobelprize.org/prizes/medi … dvanced-information/

Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 12:41pm

First-ever mycobiome Atlas describes associations between cancers and fungi

An international team of scientists has created the first pan-cancer mycobiome atlas — a survey of 35 types of cancer and their associated fungi.
Cancer cells and microbes have a long and enduring association. Both have coevolved within the ecosystems of the human body, often relying on the same resources. Competition for these resources often affects the replication and survival of cancer cells, microbes and the human host.

The association between cancer and individual microbes has long been studied case-by-case, but much recent attention focuses on the whole human microbiome, particularly in the gut, which houses more — and more diverse — communities of bacteria, viruses and fungi than anywhere else in or on the human body.
However, the roles and influence of cancer-associated fungi remain largely unstudied. Fungi are more complicated organisms than viruses and bacteria. They are eukaryotes — organisms with cells containing nuclei. Their cells are much more similar to animal cells than to bacteria or viruses.

The existence of fungi in most human cancers is both a surprise and to be expected. It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.

Fungi found on the human body come in two main types: environmental fungi, such as yeasts and mold that generally pose no harm to most healthy people, and commensal fungi, which live on or inside the human body and may be harmless, provide a benefit such as improving gut health or contribute to disease, such as yeast infections or liver disease. Fungi also play a role in shaping host immunity, for better or worse, which looms large in immunocompromised persons, including cancer patients.

The new study characterizes the cancer mycobiome — fungi linked to cancers — in 17,401 samples of patient tissues, blood and plasma across 35 types of cancer in four independent cohorts. The researchers found fungal DNA and cells in low abundances across many major human cancers, with differences in community compositions that differed among cancer types.

The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens.

Analyses that compared fungal communities with matched bacteriomes (the bacterial component of the microbiome) and immunomes (genes and proteins constituting the immune system) revealed that the associations between them were often “permissive,” rather than competitive.

For example, one species of fungi was found to be enriched in breast cancer tumors of patients older than 50 years while another species was notably abundant in lung cancer samples.

The researchers said there were significant correlations between specific fungi and age, tumor subtypes, smoking status, response to immunotherapy and survival measures. Whether the fungi are simply correlated or causally associated remains to be determined.

These findings validate the view that the microbiome in its entirety is a key piece of cancer biology.

Ravid Straussman, Pan-cancer analyses reveal cancer type-specific fungal ecologies and bacteriome interactions, Cell (2022). DOI: 10.1016/j.cell.2022.09.005. www.cell.com/cell/fulltext/S0092-8674(22)01127-8

Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 11:27am

Researchers reveal new strategy to prevent blood clots without increasing the risk of bleeding

A nanoparticle therapy developed by investigators  targets overactive neutrophils, a specific kind of white blood cell, to prevent almost all types of blood clots while causing no increased risk for bleeding. The preclinical findings, published in Science Translational Medicine, may lead to safer ways to care for patients impacted by blood clots. 

According to the researchers, neutrophils are key drivers of both arterial and venous thrombosis. And when you target a neutrophil, you do not increase bleeding risk, you only decrease clotting risk. 

Earlier arterial and venous thrombosis have been thought of as distinct molecular events that require separate treatment paradigms. Arterial thrombosis (an artery clot), which can cause heart attack or stroke, is commonly treated with antiplatelet agents like aspirin, while anticoagulants are used to treat venous thrombosis (a vein clot), a cause of pain or swelling in the legs or clots in the lungs.

More recently, however, experts have begun to suspect commonalities between the two events that could be leveraged as novel therapeutic targets.

In the new study, researchers used animal models to show that overactive neutrophils participate in both arterial and venous thrombosis through an increased capacity to migrate and adhere to sites of injury. They also showed that overactive neutrophils increase the production of key factors used as building blocks for clots. In seeking to halt the process, the researchers identified a cluster of receptors unique to activated neutrophils and developed antibody-coated nanoparticles that specifically target those clusters.

Lalitha Nayak et al, A targetable pathway in neutrophils mitigates both arterial and venous thrombosis, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abj7465

Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 9:33am

Genetics of longevity are influenced by both gender and age

A team of researchers reports evidence that the genetics of longevity are influenced by both gender and age. In their paper published in the journal Science, the group describes their study of aging in mice and humans. A relevant  perspective piece  has also been published  in the same journal issue outlining the technical challenges to understanding how aging works and the work done by the team on this new effort.

Scientists have been studying the aging process for many years but still do not have a good explanation for why organisms age and why some live longer than others. In this new effort, the researchers wondered if something in the genome plays a role in how long a species lives on average.

Noting that another team had created a very large dataset of information regarding aging in nearly 3,000 mice, the researchers found that it also contained genetic information. After obtaining access to the database, they analyzed that genetic information—more specifically, they conducted quantitative trait locus mapping. They found multiple loci that they could associate with longevity, some that were specific to one or the other gender. They also found that mice who weighed more during their early years or who had small litter sizes tended to die younger. They suggest the same genes that were associated with aging may have also played a role in the other two traits. The researchers also found that the aging-related genes they isolated appeared to remain dormant until the latter stages of a given individual's life.

The researchers then studied data available in public biobanks and found human genes that appeared to play the same role as the age-associated genes in mice. Next, they looked for and found similar genes in a type of worm—disabling those genes influenced their longevity.

Maroun Bou Sleiman et al, Sex- and age-dependent genetics of longevity in a heterogeneous mouse population, Science (2022). DOI: 10.1126/science.abo3191

João Pedro de Magalhães, The genetics of a long life, Science (2022). DOI: 10.1126/science.ade3119

Comment by Dr. Krishna Kumari Challa on September 30, 2022 at 10:42am

Make cooking safe for all, including those in developing countries, say indoor air pollution experts

Developing countries should focus on keeping unnecessary occupants, such as children, out of kitchens during cooking to help reduce their exposure to dangerous levels of air pollution, recommends a study.

Researchers also highlighted the benefits of using cleaner fuels and electric appliances that help reduce carbon dioxide levels within a kitchen by more than 32 percent, compared to the use of polluting fuels.

The GCARE researchers and their partners found that kitchens that regularly had more than two people present during cooking sessions exhibited higher carbon dioxide levels.

The researchers found that cooking resulted in an average increase of 22 percent in carbon dioxide levels across the 60 homes.

Kitchens with their doors and windows open, that also used extractor fans during cooking were found to be the environments with optimal thermal comfort conditions. Having both kitchen doors and windows open during cooking was shown to reduce carbon dioxide levels by 14 percent when compared with environments that only kept their doors open.

Prashant Kumar et al, CO₂ exposure, ventilation, thermal comfort and health risks in low-income home kitchens of twelve global cities, Journal of Building Engineering (2022). DOI: 10.1016/j.jobe.2022.105254

Comment by Dr. Krishna Kumari Challa on September 30, 2022 at 10:29am

Next-generation liquid biopsy detects nano-sized signs of breast cancer in early-stage patients

A team of scientists has found indications that a special blood test called a liquid biopsy could determine whether a patient has breast cancer at its early stage and if that cancer is unlikely to return.

These high-definition comprehensive liquid biopsies are conducted using a standard blood draw from the arm of a patient in a doctor's office. Once in the laboratory, the sample is examined for signs of cancer. The results raise hopes that one day doctors could detect breast cancer in patients with a simple blood draw.

Researchers tested a theory that the high-definition liquid biopsy could detect multiple cancer biomarkers, including the so-called "oncosomes"—nano-sized, membraned cargo carriers that enrich the body's environment for cancer growth. These oncosomes are secreted by cancer cells as the group has shown previously.

They  found the vast majority of early-stage breast cancer patients have these oncosomes at very robust levels. They're about 5-10 microns in diameter. About the size of a cell. They first identified these large vesicles in prostate cancer about a year-and-a-half ago and showed that they are related to the cancer. They are hiding in plain sight.

If further studies produce similar results, this could mean that the next generation high-definition liquid biopsy may become a diagnostic tool for early breast cancer detection and other cancers. The test also could inform patients who have been treated for cancer that they will most likely remain cancer-free.

Sonia Maryam Setayesh et al, Multianalyte liquid biopsy to aid the diagnostic workup of breast cancer, npj Breast Cancer (2022). DOI: 10.1038/s41523-022-00480-4

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