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Comment by Dr. Krishna Kumari Challa on November 18, 2024 at 8:33am

'Moonlighting' enzymes may lead to new cancer therapies

Researchers at the Center for Genomic Regulation (CRG) reveal that metabolic enzymes known for their roles in energy production and nucleotide synthesis are taking on unexpected "second jobs" within the nucleus, orchestrating critical functions like cell division and DNA repair.

The discovery, reported in two separate research papers in Nature Communications, not only challenges longstanding biological paradigms in cellular biology but also opens new avenues for cancer therapies, particularly against aggressive tumors like triple-negative breast cancer (TNBC).

For decades, biology textbooks have neatly compartmentalized cellular functions. Mitochondria are the powerhouses of the cell, the cytoplasm is a bustling factory floor for protein synthesis, and the nucleus a custodian of genetic information. However, scientists have now discovered that the boundaries between these cellular compartments are less defined than previously thought.

Metabolic enzymes are moonlighting outside of their traditional neighborhood. There's an overlap in the skillset, but they're doing entirely different jobs for entirely different purposes. Surprisingly, their secondary roles in the nucleus are just as critical as their primary metabolic functions.

In one of the studies, researchers  focused on the metabolic enzyme MTHFD2. Traditionally, MTHFD2 is found in the mitochondria, where it plays a key role in synthesizing the building blocks of life and contributing to cell growth. Others research  work reveals that MTHFD2 also moonlights within the nucleus, where it plays a pivotal role in ensuring proper cell division.

The study is the first to demonstrate that the nucleus relies on metabolic pathways to maintain the integrity and stability of the human genome. The nucleus isn't just a passive storage space for DNA; it has its own metabolic needs and processes.

Part 1

Comment by Dr. Krishna Kumari Challa on November 18, 2024 at 8:21am

Blood vessel-like coating could make medical devices safer for patients

Researchers have developed a coating that could make medical devices safer for millions of patients, reducing the risks associated with blood clots and dangerous bleeding. The work has been published in Nature Materials.

The new material, designed to mimic the natural behavior of blood vessels, could allow for safer use of blood-contacting devices like catheters, stents, blood-oxygenation machines and dialysis machines—especially in cases where blood clots are a significant concern.

This discovery could be a transformative step in the development of safer medical devices. By designing a coating that mimics the body's natural approach to preventing clots, researchers have created a solution that could dramatically reduce the need for risky blood thinners before and after patients use these devices.

Thrombosis, or clot formation, is a major challenge when blood-contacting devices are used. Unlike natural blood vessels, these devices can trigger clotting by activating specific proteins in the blood. Blood clots can obstruct the device, disrupting treatment, or lead to severe complications such as stroke and heart attack.

Doctors often prescribe high doses of blood thinners to prevent clots on these devices, but this approach increases the risk of dangerous bleeding—a trade-off that many patients and clinicians would rather avoid.

The newly developed coating offers a promising alternative. It's engineered to imitate how blood vessels function—encouraging normal blood flow without triggering clot formation. Imagine the coating as a "soft barrier" on a device that attracts a key blood protein but keeps it from activating the clotting process.

By interacting with this protein in a controlled way, the coating prevents it from sparking a cascade of events that lead to clot formation.

In lab and animal studies, the coating demonstrated significant reductions in clot formation on device surfaces, without the use of blood thinners and without affecting the normal clotting functions elsewhere in the body.

One of the most surprising insights was that controlling the interaction between the coating and specific blood proteins could prevent clotting without disrupting the body's natural balance. This shows us that mimicking the body's own mechanisms, rather than simply repelling blood components, is key to truly biocompatible device design.

The innovation comes as demand for blood-contacting devices continues to rise. 

Additionally, the team is interested in understanding whether this approach could eventually be adapted to address other blood-related complications, such as inflammation or infection, in long-term medical implants.

Antithrombotic coating with sheltered positive charges prevents contact activation by controlling factor XII–biointerface binding, Nature Materials (2024). DOI: 10.1038/s41563-024-02046-0

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 1:51pm

The first experiments were conducted on board a Convair C-131 Samaritan, and yes, there is absolutely video of the proceedings. A similar experiment involved releasing pigeons inside the C-131 during parabolic flight.

It's fascinating to watch. The narration for the video says the cats' "automatic reflex action is almost completely lost under weightlessness". Almost – but not quite. Although the cats seem disoriented, they are still able to twist and turn their bodies around as they try to figure out where they are going to fall.
Part 2

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 1:48pm

Scientists Put Cats in Microgravity to See What Would Happen

There is, perhaps, no animal on this planet as lithe as the simple domestic cat. And not least in their bag of acrobatic tricks is one for which they are well-known: the ability to land, safely, on their velvet paws, when subjected to a tumble.

In the 1950s, humans discovered parabolic flight: the ability to simulate zero-G conditions using specially-designed aircraft plummeting along a precise flight trajectory. And with that came a devilish thought. What would happen to a cat's ability to land on its feet if they can't tell the difference between up and down?
So, this is what the bright minds at the US Air Force Aerospace Medical Research Lab decided to find out.

Parabolic flight is not true microgravity, but a brief experience of its effect. Just as a rapid descent in an elevator can make you feel lighter in your loafers, passengers on an aircraft will experience weightlessness while rapidly descending from a high altitude to a lower one. It's pretty disorienting, earning parabolic flight the nickname 'vomit comet' for good reason.

https://spacemedicineassociation.org/download/history/history_files...

Part 1

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 1:29pm

The researchers found the incorporation of trans fats through SPT increased lipoprotein secretion from the liver, which then promoted the formation of atherosclerotic plaques.
In the end, they saw mice consuming a high trans fat diet were producing trans fat-derived sphingolipids that promoted the secretion of VLDL from the liver into the bloodstream. This, in turn, accelerated the buildup of atherosclerotic plaques and the development of fatty livers and insulin dysregulation. High cis-fat diet mice, on the other hand, experienced shorter-term, less harmful effects like weight gain.

Jivani M. Gengatharan et al, Altered sphingolipid biosynthetic flux and lipoprotein trafficking contribute to trans-fat-induced atherosclerosis, Cell Metabolism (2024). DOI: 10.1016/j.cmet.2024.10.016

Part 2

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 1:27pm

Cholesterol may not be the only lipid involved in trans fat-driven cardiovascular disease
Excess cholesterol is known to form artery-clogging plaques that can lead to stroke, arterial disease, heart attack, and more, making it the focus of many heart health campaigns. Fortunately, this attention to cholesterol has prompted the development of cholesterol-lowering drugs called statins and lifestyle interventions like dietary and exercise regimens. But what if there's more to the picture than just cholesterol?
New research from Salk Institute scientists describes how another class of lipids, called sphingolipids, contributes to arterial plaques and atherosclerotic cardiovascular disease (ASCVD). Using a longitudinal study of mice fed high-fat diets—with no additional cholesterol—the team tracked how these fats flow through the body and found the progression of ASCVD induced by high trans fats was fueled by the incorporation of trans fats into ceramides and other sphingolipids. Knowing that sphingolipids promote atherosclerotic plaque formation reveals another side of cardiovascular disease in addition to cholesterol.

The findings, published in Cell Metabolism, open an entirely new avenue of potential drug targets to address these diseases and adverse health events like stroke or heart attacks.

When dietary fats enter the body through the foods we eat, they must be sorted and processed into compounds called lipids, such as triglycerides, phospholipids, cholesterol, or sphingolipids. Lipoproteins—like the familiar HDL, LDL, and VLDL—are used to transport these lipids through the blood.

Sphingolipids have become useful biomarkers for diseases like ASCVD, non-alcoholic fatty liver disease, obesity, diabetes, peripheral neuropathy, and neurodegeneration. However, it is unclear exactly how the incorporation of different dietary fats into sphingolipids leads to the development of ASCVD.

The fate of dietary fat is often determined by the protein that metabolizes it. 

The team suspected that trans fats were being incorporated into sphingolipids by SPT, which, in turn, would promote the excess lipoprotein secretion into the bloodstream that causes ASCVD.

To test their theory, they compared the processing of two different fats, cis fats and trans fats. The difference between these two comes down to the placement of a hydrogen atom; cis fats, found in natural foods like fish or walnuts, have a kink in their structure caused by two side-by-side hydrogen atoms, whereas trans fats, found in processed foods like margarine or anything fried, have a straight-chain structure caused by two opposing hydrogen atoms. Importantly, the kink in cis fats means they cannot be tightly packed—a positive feature for avoiding impenetrable clogs.

The researchers combined mouse model dietary manipulation with metabolic tracing, pharmacological interventions, and physiological analyses to answer their question—what is the link between trans fats, sphingolipids, and ASCVD?

Part 1

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 1:21pm

How does the brain keep calm? Insight into brain stability and the key role of NMDA receptors

Researchers  have made a fundamental discovery: the NMDA receptor (NMDAR)—long studied primarily for its role in learning and memory—also plays a crucial role in stabilizing brain activity.

By setting the "baseline" level for activity in neural networks, the NMDAR helps maintain stable brain function amidst continuous environmental and physiological changes. This discovery may lead to innovative treatments for diseases linked to disrupted neural stability, such as depression, Alzheimer's disease, and epilepsy.

In recent decades, brain research has mainly focused on processes that allow information encoding, memory, and learning, based on changes in synaptic connections between nerve cells. But the brain's fundamental stability, or homeostasis, is essential to support these processes.

This comprehensive project used three primary research methods: electrophysiological recordings from neurons in both cultured cells (in vitro) and living, behaving mice (in vivo) within the hippocampus, combined with computational modeling (in silico). Each approach provided unique insights into how NMDARs contribute to stability in neural networks.

These  findings suggest that ketamine's actions may stem from this newly discovered role of NMDAR: reducing the activity baseline in overactive brain regions seen in depression, like the lateral habenula, without interfering with homeostatic processes. This discovery could reshape our understanding of depression and pave the way for developing innovative treatments.

Antonella Ruggiero et al, NMDA receptors regulate the firing rate set point of hippocampal circuits without altering single-cell dynamics, Neuron (2024). DOI: 10.1016/j.neuron.2024.10.014

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 1:13pm

Living microbes discovered in Earth's driest desert 

The Atacama Desert, which runs along the Pacific Coast in Chile, is the driest place on the planet and, largely because of that aridity, hostile to most living things. Not everything, though—studies of the sandy soil have turned up diverse microbial communities. Studying the function of microorganisms in such habitats is challenging, however, because it's difficult to separate genetic material from the living part of the community from genetic material of the dead.

A new separation technique can help researchers focus on the living part of the community. This week in Applied and Environmental Microbiology, an international team of researchers describes a new way to separate extracellular (eDNA) from intracellular (iDNA) genetic material. The method provides better insights into microbial life in low-biomass environments, which was previously not possible with conventional DNA extraction methods.

The microbiologists used the novel approach on Atacama soil samples collected from the desert along a west-to-east swath from the ocean's edge to the foothills of the Andes mountains. Their analyses revealed a variety of living and possibly active microbes in the most arid areas.

Alexander Bartholomäus et al. Inside the Atacama Desert: uncovering the living microbiome of an extreme environment, Applied and Environmental Microbiology (2024). DOI: 10.1128/aem.01443-24 journals.asm.org/doi/10.1128/aem.01443-24

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 12:52pm

Electric field signals reveal early warnings for extreme weather, study reveals

A new study  has made significant advances in understanding how atmospheric electric field measurements can help predict severe weather events.

The research paper, titled "Understanding heavy precipitation events in southern Israel through atmospheric electric field observations," is now published in Atmospheric Research.

By closely examining low-pressure winter weather systems, known as "Cyprus Lows," in the arid Negev Desert of southern Israel, this research reveals new insights into the role of the electric field in anticipating heavy precipitation.

Focusing on "wet" Cyprus Lows—situations where rain falls as a cold front moves through—researchers observed substantial increases in the potential gradient of the electric field. Minute-by-minute data showed potential gradient values rising sharply from typical fair-weather levels (about 100–200 volts per meter) to hundreds and even thousands of volts per meter during rainfall.

These surges occurred as convective clouds passed overhead, indicating that different cloud types produce unique electric field patterns. The study also highlighted that factors beyond rain intensity, such as cloud structure and the electrical charge of rain droplets, play roles in these electric fluctuations.

Through these findings, the researchers identified how electric field variations correlate with specific weather conditions. This enhanced understanding of electric field responses to weather events could significantly improve nowcasting systems for predicting extreme weather, particularly in regions prone to flash floods and sudden weather changes.

This research demonstrates how electric field variations can serve as indicators of shifting weather patterns, allowing us to anticipate severe weather events in real-time.

Roy Yaniv et al, Understanding heavy precipitation events in southern Israel through atmospheric electric field observations, Atmospheric Research (2024). DOI: 10.1016/j.atmosres.2024.107757

Comment by Dr. Krishna Kumari Challa on November 17, 2024 at 12:48pm

But where is the salt coming from? The explanation: The groundwater from the surrounding aquifers penetrates into the saline lake sediments, leaching out extremely old and thick layers of rock consisting mainly of the mineral halite. It then flows into the lake as brine.

Because the density of this brine is somewhat lower than that of the water in the Dead Sea, it rises upwards like a jet. It looks like smoke, but it's a saline fluid.
Contact with the lake water causes the dissolved salts, especially the halite, to spontaneously crystallize after emerging from the lake bed, where it forms the vents observed for the first time in the world. These can grow by several centimeters within a single day. Many of the slender chimneys were one to two meters high, but they also include giants more than seven meters high, with a diameter of more than 2–3 meters.
These white smokers are especially important because they can serve as an early warning indicator for sinkholes. These are subsidence craters up to 100 meters wide and up to 20 meters deep, thousands of which have formed along the Dead Sea in recent decades.

C. Siebert et al, A new type of submarine chimneys built of halite, Science of The Total Environment (2024). DOI: 10.1016/j.scitotenv.2024.176752

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