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Comment by Dr. Krishna Kumari Challa on October 26, 2024 at 10:53am

There are hundreds of these retrotransposon sequences in our genome. Why not permanently inactivate them, like some species have done? They must have some adaptive value for us, the scientists thought.
They used reverse transcriptase inhibiting drugs, commonly used to suppress HIV replication in patients, to inhibit the replication of retrotransposons in mice. These drugs did not alter blood cell production in normal mice but blocked the increase in blood-forming stem cells and red blood cell production during pregnancy, leading to anemia.
As researchers further explored mechanisms activating blood cell production, they found retrotransposons were being detected by the immune sensors, cGAS and STING. These sensors induce interferon production after viral infection or replication of retrotransposons.

They found the retrotransposons turned on just enough interferon to activate blood cell production.
What these scientists discovered in mice is also true in humans, they found.
Earlier they also found that estrogen contributes to blood-forming stem cell activation during pregnancy.

Julia Phan et al, Retrotransposons are co-opted to activate hematopoietic stem cells and erythropoiesis, Science (2024). DOI: 10.1126/science.ado6836

Part2

Comment by Dr. Krishna Kumari Challa on October 26, 2024 at 10:46am

Ancient viral DNA activates blood cell production during pregnancy and after significant bleeding, researchers discover

Ancient viral remnants in the human genome are activated during pregnancy and after significant bleeding in order to increase blood cell production, an important step toward defining the purpose of "junk DNA" in humans, according to research published in Science.

These scientists set out to discover how hematopoietic, or blood-forming, stem cells—which typically divide infrequently—are activated during pregnancy and after blood loss. 

When they compared activated genes in stem cells from pregnant versus nonpregnant mice, they found retrotransposons had switched on in stem cells from pregnant mice.
Retrotransposons are ancient viral gene sequences now permanently part of our genome and sometimes called "junk DNA" because they don't encode proteins that contribute to cellular function. They use an enzyme called reverse transcriptase, just like the human immunodeficiency virus (HIV), to replicate themselves.

Humans have evolved mechanisms to keep retrotransposons turned off most of the time, because retrotransposons have the ability to damage DNA when they replicate and reinsert into other parts of the genome.

Comment by Dr. Krishna Kumari Challa on October 26, 2024 at 9:46am

The preparation makes the poison: How muscarine in mushrooms becomes toxic

Mushrooms exist in a breathtaking variety of shapes, colors and sizes. Especially in autumn, mushroom hunters go into the forests to find the tastiest of them, prepare them in multiple ways and eat them with relish. However, it is well known that there are also poisonous mushrooms among them and it is life-saving to distinguish between them. But are these mushrooms really poisonous?

Researchers have investigated this question and recently published the results of a study about muscarine in Angewandte Chemie International Edition.

This toxin is found in various mushrooms, the best known of which is the fly agaric mushroom (Amanita muscaria), which also gave the toxin its name. However, considerably higher concentrations of muscarine are found in fiber cap mushrooms and fool's funnel mushrooms.

Researchers have now been able to show that muscarine is not only present in mushrooms as such, but it can also be stored as a harmless precursor and only be released when mushrooms got injured.

Muscarine was discovered 150 years ago as the first fungal toxin. The current study was able to prove that it is stored, for example, in the fool's funnel mushroom Clitocybe rivulosa as 4phosphomuscarin, which is less toxic.

There are indications that other substances are also present because pure muscarine apparently has a different effect than a mushroom containing muscarine.

The fool's funnel mushroom is also known as the false champignon and can easily be confused with the real champignon. Only when the mushroom is damaged by cutting, cooking or digestion, an enzyme releases the poisonous muscarine from this precursor molecule.

In other mushrooms however, muscarine is already present in its active form. It is not uncommon for organisms to show defense and protective reactions when they are damaged, for example by being eaten by animals.

The mixture of free active and "hidden" inactive muscarine, which only becomes active poison when eaten, increases the danger of certain types of mushrooms such as the funnel mushrooms. These results could help doctors and toxicologists to better assess the actual danger of certain types of fungi and treat poisoning more efficiently.

Muscarine interferes with the transmission of signals by the neurotransmitter acetylcholine and leads to permanent excitation. The consequences are increased salivation and lacrimation, sweating, vomiting, diarrhea, circulatory collapse and even fatal cardiac paralysis.

It is irrelevant whether the poison has already been ingested in free form or as a precursor that is only activated in the body. The correct identification of edible mushrooms is therefore still an important prerequisite for an enjoyable and carefree mushroom meal.

Sebastian Dörner et al, The Fatal Mushroom Neurotoxin Muscarine is Released from a Harmless Phosphorylated Precursor upon Cellular Injury, Angewandte Chemie International Edition (2024). DOI: 10.1002/anie.202417220

Comment by Dr. Krishna Kumari Challa on October 26, 2024 at 9:40am

Study shows that LLMs could maliciously be used to poison biomedical knowledge graphs

In recent years, medical researchers have devised various new techniques that can help them to organize and analyze large amounts of research data, uncovering links between different variables (e.g., diseases, drugs, proteins, etc.). One of these methods entails building so-called biomedical knowledge graphs (KGs), which are structured representations of biomedical datasets.

Researchers  recently showed that large language models (LLMs), machine learning techniques which are now widely used to generate and alter written texts, could be used by malicious users to poison biomedical KGs. Their paper, published in Nature Machine Intelligence, shows that LLMs could be used to generate fabricated scientific papers that could in turn produce unreliable KGs and adversely impact medical research.

Junwei Yang et al, Poisoning medical knowledge using large language models, Nature Machine Intelligence (2024). DOI: 10.1038/s42256-024-00899-3.

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Comment by Dr. Krishna Kumari Challa on October 25, 2024 at 11:52am

Plastic chemical phthalate causes DNA breakage and chromosome defects in sex cells, new study finds

A new study conducted on roundworms finds that a common plastic ingredient causes breaks in DNA strands, resulting in egg cells with the wrong number of chromosomes.

Benzyl butyl phthalate (BBP) is a chemical that makes plastic more flexible and durable, and is found in many consumer products, including food packaging, personal care products and children's toys. Previous studies have shown that BBP interferes with the body's hormones and affects human reproduction and development. In the new study, researchers tested a range of doses of BBP on the nematode Caenorhabditis elegans and looked for abnormal changes in egg cells. They saw that at levels similar to those detected in humans, BBP interferes with how newly copied chromosomes are distributed into the sex cells. Specifically, BBP causes oxidative stress and breaks in the DNA strands, which lead to cell death and egg cells with the wrong number of chromosomes.
Based on these findings, the researchers propose that BBP exposure alters gene expression in ways that cause significant damage to the DNA, ultimately leading to lower quality egg cells with abnormal chromosomes. The study also showed that C. elegans metabolizes BBP in the same way as mammals, and is impacted at similar BBP levels that occur in humans, suggesting that C. elegans is an effective model for studying the impacts on people. Overall, the study underscores the toxic nature of this very common plastic ingredient and the damage it causes to animal reproduction.

 Henderson AL, Karthikraj R, Berdan EL, Sui SH, Kannan K, Colaiácovo MP (2024) Exposure to benzyl butyl phthalate (BBP) leads to increased double-strand break formation and germline dysfunction in Caenorhabditis elegans, PLoS Genetics (2024). DOI: 10.1371/journal.pgen.1011434

Comment by Dr. Krishna Kumari Challa on October 25, 2024 at 10:28am

How microbes feed on iron

Pipelines, sprinklers, and other infrastructure in oxygen-free environments are vulnerable to microbially induced corrosion (MIC)—a process where microorganisms degrade iron-based structures, potentially leading to costly damages or even collapses.

Unlike rust, which is caused by a chemical reaction with oxygen, MIC occurs in oxygen-free environments. The microbes responsible thrive on the iron itself, producing a destructive reaction that damages the material. This kind of corrosion costs industries billions of dollars annually, particularly in sectors such as oil and gas. Identifying and preventing the microbial activity behind the corrosion is therefore of importance.

Now microbiologists have uncovered new details about how one microbial strain of the species Methanococcus maripaludis corrodes iron in an extremely efficient way. The study is  published in npj Biofilms and Microbiomes.

The study refutes the long-standing belief that these microbes release enzymes into the environment to corrode iron and have them produce nutrients for the microbe's growth. Instead, the researchers show that the microbes cling directly to the iron surface, using sticky enzymes on their cell walls to extract what they need without wasting energy on releasing enzymes that may not reach the iron surface.

Once attached to the iron surface, the microbe initiates corrosion, quickly developing a black film on the material's surface.

The microbes will quickly create pits under this black film, and within a few months, significant damage will occur. 

According to the researchers, microbial adaptation like this is an example of how microbes can learn to thrive in human-made environments. In this case, Methanococcus maripaludis, has learned to survive on and efficiently get energy from iron structures.

Such microbial adaptation poses not only a financial burden but also an environmental one. These microbes are methanogenic, meaning they produce methane. Methane is a potent greenhouse gas, so it does cause some concern that microbes adapting to human-made, built environments produce methane more effectively. These new adaptations may spur increases in methane emissions.

Satoshi Kawaichi et al, Adaptation of a methanogen to Fe⁰ corrosion via direct contact, npj Biofilms and Microbiomes (2024). DOI: 10.1038/s41522-024-00574-w

Methane-producing microbes also thrive on a variety of mineral particles that are being released to the natural environment by climate change and other anthropogenic activities. Such particles come from industry, agriculture, forest fires, river runoffs, melting glaciers, etc., and they may promote the activity of certain methane-producing microbes.

Comment by Dr. Krishna Kumari Challa on October 25, 2024 at 10:21am

The smart 3D printer that can upgrade your home instantly

If someone wants to add 3D-printed elements to a room—a footrest beneath a desk, for instance—the project gets more difficult. A space must be measured. The objects must then get scaled, printed elsewhere and fixed in the right spot. Handheld 3D printers exist, but they lack accuracy and come with a learning curve.

Researchers now created Mobiprint, a mobile 3D printer that can automatically measure a room and print objects onto its floor. The team's graphic interface lets users design objects for a space that the robot has mapped out. The prototype, which the team built on a modified consumer vacuum robot, can add accessibility features, home customizations or artistic flourishes to a space.

The team presented its work Tuesday, Oct. 15, at the ACM Symposium on User Interface Software and Technology

https://programs.sigchi.org/uist/2024/program/content/170934

Comment by Dr. Krishna Kumari Challa on October 25, 2024 at 8:56am

Unique mRNA delivery method could fix faulty genes before birth

A new study shows that a biomedical tool can successfully deliver genetic material to edit faulty genes in developing fetal brain cells. The technology, tested in mice, might have the potential to stop the progression of genetic-based neurodevelopmental conditions, such as Angelman syndrome and Rett syndrome, before birth.

The implications of this tool for treating neurodevelopmental conditions are profound. We can now potentially correct genetic anomalies at a foundational level during critical periods of brain development, say the researchers associated with the study.

 The research team hopes to develop this technology into treatments for genetic conditions that can be diagnosed during prenatal testing. The treatments can be given in the womb to avoid more damage as cells develop and mature.

Proteins have a crucial role in the way our bodies function. They are assembled in cells based on instructions from messenger RNA (mRNA). In certain genetic conditions, the genes express (produce) more or fewer proteins than the body needs. In such cases, the body might get dysregulated and need to silence an overactive gene or supplement the low protein levels.

Proteins have large and complex structures, which makes them hard to deliver. Their delivery remains a huge challenge and a dream for treating diseases.

Instead of delivering proteins, scientists found a way to deliver mRNA to cells that will be translated to functional proteins within the cells. This delivery method uses a unique lipid nanoparticle (LNP) formulation to carry mRNA. The objective is to introduce (transfect) mRNA genetic material into the cells. The mRNA would then translate instructions to build proteins.
Delivery of mRNA using LNP is already transforming disease treatments. It has applications in vaccine development, gene editing and protein replacement therapy. Recently, mRNA delivery has become more popular with its use in Pfizer and Moderna COVID-19 vaccines.

 Kewa Gao et al, Widespread Gene Editing in the Brain via In Utero Delivery of mRNA Using Acid-Degradable Lipid Nanoparticles, ACS Nano (2024). DOI: 10.1021/acsnano.4c05169 Sheng Zhao et al, Acid-degradable lipid nanoparticles enhance the delivery of mRNA, Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01765-4

Comment by Dr. Krishna Kumari Challa on October 25, 2024 at 8:33am

The team validated their database's predictions in the lab, where they made almost 3,000 mutations on over 1,000 proteins and tested their impact on almost 7,000 protein-protein interaction pairs. Preliminary research based on these findings is already underway to develop and test treatments for lung and endometrial cancers. The team also demonstrated that their model's protein-protein interaction mutations can predict:

Survival rates and prognoses for various cancer types, including sarcoma, a rare but potentially deadly cancer.
Anti-cancer drug responses in large pharmacogenomics databases.
The researchers also experimentally validated that protein-protein interaction mutations between the proteins NRF2 and KEAP1 can predict tumor growth in lung cancer, offering a novel target for targeted cancer therapeutic development.

A structurally informed human protein–protein interactome reveals proteome-wide perturbations caused by disease mutations, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02428-4

Part 2

Comment by Dr. Krishna Kumari Challa on October 25, 2024 at 8:32am

New AI tool predicts protein-protein interaction mutations in hundreds of diseases

Scientists have designed a publicly-available software and web database to break down barriers to identifying key protein-protein interactions to treat with medication.

The computational tool is called PIONEER (Protein-protein InteractiOn iNtErfacE pRediction). Researchers demonstrated PIONEER's utility by identifying potential drug targets for dozens of cancers and other complex diseases in a recently published Nature Biotechnology article.

Genomic research is key in drug discovery, but it is not always enough on its own. When it comes to making medications based on genomic data, the average time between discovering a disease-causing gene and entering clinical trials is 10–15 years.

In theory, making new medicines based on genetic data is straightforward: mutated genes make mutated proteins. Scientists try to create molecules that stop these proteins from disrupting critical biological processes by blocking them from interacting with healthy proteins, but in reality, that is much easier said than done.

One protein in our body can interact with hundreds of other proteins in many different ways. Those proteins can then interact with hundreds more, forming a complex network of protein-protein interactions called the interactome.

This becomes even more complicated when disease-causing DNA mutations are introduced into the mix. Some genes can be mutated in many ways to cause the same disease, meaning one condition can be associated with many interactomes arising from just one differently mutated protein.

Drug developers are left with tens of thousands of potential disease-causing interactions to pick from—and that's only after they generate the list based on the affected protein's physical structures.

Some scientists,  especially the drug developers, are taking the help of  artificial intelligence (AI) tools  to  identify the most promising protein-protein interactions more easily and speedily.

Their resulting database allows researchers to navigate the interactome for more than 10,500 diseases, from alopecia to von Willebrand Disease.

Researchers who identified a disease-associated mutation can input it into PIONEER to receive a ranked list of protein-protein interactions that contribute to the disease and can potentially be treated with a drug. Scientists can search for a disease by name to receive a list of potential disease-causing protein interactions that they can then go on to research. PIONEER is designed to help biomedical researchers who specialize in almost any disease across categories including autoimmune, cancer, cardiovascular, metabolic, neurological and pulmonary.

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