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Comment by Dr. Krishna Kumari Challa on April 14, 2023 at 12:29pm

It appears that there is something about movement that keeps Hsp47 at an appropriate level. It could be that the mechanical forces involved in moving around actually have an impact on gene expression, dramatically increasing the amount of Hsp47 that circulates in the blood.
Now we know that Hsp47 is so important, we can begin to look for new or existing medicines that might be able to inhibit the function of this protein in blood clotting and protect mobile people who are prone to clots.

Manuela Thienel et al, Immobility-associated thromboprotection is conserved across mammalian species from bear to human, Science (2023). DOI: 10.1126/science.abo5044. www.science.org/doi/10.1126/science.abo5044

part 2

Comment by Dr. Krishna Kumari Challa on April 14, 2023 at 12:27pm

Preventing dangerous blood clots

Hibernating bears, paralyzed humans, and pigs kept in small enclosures all avoid dangerous blood clots, despite being immobile for extremely long periods. Recent research shows that reduction of a key protein prevents the formation of blood clots in all three mammal species when they are still for days, weeks, months, or even years at a time. The study is published recently (April 13, 2023), in Science.

If you've ever taken a long haul flight, you might have taken advice to prevent a dangerous blood clot—deep vein thrombosis—from forming in one or both of your legs, while you sit still for multiple hours. Perhaps you set a reminder to get up and walk around, and you wore compression socks to keep the blood from pooling in your legs.

Most people won't experience a clot if they take care on a flight, but there is a serious risk for some people who are pre-disposed to blood clots due to genetic factors.

The discovery that a protein known as Hsp47 is dramatically reduced—by 55 times—when someone is immobilized for a much longer period than a flight, could lead to new medicines to help those who have inherited blood clotting disorders that put them at risk for pulmonary embolism, heart attack, and stroke.

It seems counterintuitive that people who have severe paralysis don't appear to be at higher risk of blood clots. This tells us that something interesting is happening. And it turns out that reducing levels of Hsp47 plays a key role in preventing clots, not just in humans, but in other mammals, including bears and pigs.

"When we see something like this in multiple species, that reinforces its importance. Having Hsp47 must have been an evolutionary advantage."

Hsp47 is released by platelets—the sticky blood cells that trigger blood clotting. Usually clotting is an important response to an injury, to prevent blood loss, and Hsp47 is one of the necessary ingredients to enable platelets to do their job. Examining the role of Hsp47 in clotting function the team found that when released into the blood of bears, mice and humans that it promoted conditions that may give rise to deep vein thrombosis.

Part 1

Comment by Dr. Krishna Kumari Challa on April 14, 2023 at 12:00pm

The team's experiments yielded interesting results, identifying a new neuronal and molecular mechanism through which the brain re-gains consciousness after general anesthesia. They also showed that the ventral posteromedial nucleus (VPN), part of the thalamus, is a key brain region associated with re-emergence of consciousness.

Ubiquitin-proteasomal degradation is responsible for KCC2 downregulation, which is driven by ubiquitin ligase Fbxl4. Phosphorylation of KCC2 at Thr1007 promotes interaction between KCC2 and Fbxl4. KCC2 downregulation leads to γ-aminobutyric acid type A receptor-mediated disinhibition, enabling accelerated recovery of VPM neuron excitability and emergence of consciousness from anesthetic inhibition. This pathway to recovery is an active process and occurs independent of anesthetic choice.

Overall, the recent work by this team of researchers shows that the degradation of KCC2 transporter neurons located in the VPM, through the means of ubiquitin, a compound in living cells that contributes to the degradation of superfluous or faulty proteins in the brain, is a key step in the mice's emergence of consciousness after general anesthesia. This key finding could potentially inform the development of strategies to wake patients who are in a  vegetative state or minimally conscious state, which is a long-standing medical challenge.

Jiang-Jian Hu et al, Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01290-y

Part 2

Comment by Dr. Krishna Kumari Challa on April 14, 2023 at 12:00pm

Study unveils neural processes underpinning the re-emergence of consciousness after anesthesia

Before undergoing surgeries and other invasive medical procedures, patients typically undergo anesthesia. Anesthesia consists in giving patients a class of drugs (i.e., anesthetics) that cause them to lose feeling in specific areas of the body (i.e., local anesthesia) or fully lose awareness during a procedure (i.e., general anesthesia). These anesthetics can be administered to patients via injection, inhalation, skin-numbing lotions, and other means.

In the past, doctors and medical researchers viewed general anesthesia as a passive process that could not be influenced or interrupted once anesthetic drugs were administered. More recently, however, studies showed that it is in fact an active brain process that can be experimentally controlled and acted on. A research team  recently carried out a study investigating the processes underpinning brain states while under general anesthesia and those associated with the subsequent re-emergence of awareness. Their findings, published in Nature Neuroscience, highlight possible strategies that could help anesthesiologists to extend and deepen or shorten periods of anesthesia.

In the experiments with mice , when the brain is forced into a minimum responsive state by diverse anesthetics, a rapid downregulation of K⁺/Cl⁻ cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) serves as a common mechanism by which the brain regains consciousness.

To examine the neural processes linked to the re-emergence of consciousness after anesthesia, the researchers carried out a series of experiments on adult mice. They gave the mice one of three different anesthetic drugs (i.e., ketamine, propofol and pentobarbital) and then looked at the molecular mechanisms that emerged while they were re-gaining awareness.

To assess the mice's levels of consciousness they measured the so-called loss of righting reflex (LORR), a point in which animals no longer act on their instinct to avoid laying with their stomach facing up. In addition, they observed the animals' behavioral responses to external stimuli.

Part 1

Comment by Dr. Krishna Kumari Challa on April 13, 2023 at 12:14pm

Viruses: How avian influenza viruses spill over to mammals

Picture your local lake covered with migrating geese, ducks or other waterfowl. Even though you don’t hear any coughing, you might well be witnessing ‘flu season’ for birds. Influenza viruses cause gastrointestinal infections in birds, and are spread when birds defecate in water that other birds then drink .Sometimes, however, avian influenza viruses make their way into mammals, including humans, and cause respiratory infections: how does this happen?

Waterfowl are the main natural reservoir for influenza viruses, and influenza viruses that infect humans and other mammals originally came from birds. This spillover can happen in two ways. The first way involves special mammalian hosts (like pigs) that can be infected by both avian and mammalian influenza viruses . Occasionally, an individual from one of these species becomes simultaneously infected with both types of virus, and the two viruses exchange gene segments to form a novel virus that retains the ability to infect mammals. This process – which is known as gene reassortment – is what happened to start human influenza pandemics in 1957 and 1968 .

The second way that spillover can happen involves a mammal getting directly infected with a bird virus . This individual then transmits this bird virus to others in its same species. If infection of the new species is sustained over time and within many individuals, the avian virus will experience natural selection for genetic mutations that make it more and more compatible with the mammalian species.

 https://elifesciences.org/articles/86051?utm_source=content_alert&a...

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Comment by Dr. Krishna Kumari Challa on April 13, 2023 at 12:08pm

Predictive power of climate models may be masked by volcanoes

Simulated volcanic eruptions may be blowing up our ability to predict near-term climate, according to a new study published in Science Advances.

The research, led by the National Center for Atmospheric Research (NCAR), finds that the way volcanic eruptions are represented in climate models may be masking the models' ability to accurately predict variations in sea surface temperatures in the tropical Pacific that unfold over multiple years to a decade. These decadal variations in sea surface temperatures in the tropical Pacific are linked to climate impacts across the globe, including variations in precipitation and severe weather. Accurate predictions, therefore, could provide community leaders, farmers, water managers, and others with critical climate information that allows them to plan years in advance.

Because it is well established that large volcanic eruptions can have significant, long-term cooling effects on the climate, researchers expected that the collection of simulations that included the volcanic eruptions would produce more accurate multiyear and decadal climate predictions. Instead, they found that the inclusion of the eruptions degraded the model's predictive capabilities, at least in the tropical Pacific, an area that is especially important because of the connections between sea surface temperatures and near-term climate events.

For example, the simulations that included the volcanoes predicted a subsequent cooling of the sea surface temperatures in the tropical Pacific after the eruptions. In reality, that region of the ocean warmed, a change that was well predicted by the simulations that did not include the volcanic eruptions.

These findings highlight the difficulty of accurately representing the complex climate impacts that follow a volcanic eruption  in a model, a task made more challenging because researchers only have a few real-life examples in the observational record. Scientists know that volcanoes can loft sulfur gases high into the stratosphere where they can transform into sunlight-reflecting aerosols. But how the resulting cooling ultimately affects the entire Earth system, including sea surface temperatures, is not well understood.

Xian Wu, Volcanic forcing degrades multiyear-to-decadal prediction skill in the tropical Pacific, Science Advances (2023). DOI: 10.1126/sciadv.add9364. www.science.org/doi/10.1126/sciadv.add9364

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Comment by Dr. Krishna Kumari Challa on April 13, 2023 at 11:48am

The team found that adherence to the ultrastructural size principle was essential for avoiding working memory impairment with age. By viewing violation of the ultrastructural size principle and mitochondria-related failures as the key to age-related cognitive impairment, the study ushers in a new era for aging research.

 Violation of the ultrastructural size principle in the dorsolateral prefrontal cortex underlies working memory impairment in the aged common marmoset (Callithrix jacchus), Frontiers in Aging Neuroscience (2023). DOI: 10.3389/fnagi.2023.1146245

Part 2

Comment by Dr. Krishna Kumari Challa on April 13, 2023 at 11:47am

Mitochondria power supply failure may cause age-related cognitive impairment

Brains are like puzzles, requiring many nested and co-dependent pieces to function well. The brain is divided into areas, each containing many millions of neurons connected across thousands of synapses. These synapses, which enable communication between neurons, depend on even smaller structures: message-sending boutons (swollen bulbs at the branch-like tips of neurons), message-receiving dendrites (complementary branch-like structures for receiving bouton messages), and power-generating mitochondria. To create a cohesive brain, all these pieces must be accounted for.

However, in the aging brain, these pieces can get lost or altered, and no longer fit in the greater brain puzzle. A research team has now published a study in Frontiers in Aging Neuroscience on this topic.

Fifty percent of people experience loss of working memory with old age, meaning their ability to hold and manipulate information in the short-term decreases.

Researchers set out to understand why some individuals maintain healthy working memory as they age, while others do not. In the process, they discovered a novel mechanism for the synaptic basis of cognitive impairment.

Prior studies had found that brains lose synapses as they age, and the researchers saw this pattern in their non-human primate model, too. But when they looked at the synapses that remained, they found evidence of a breakdown in coordination between the size of boutons and the mitochondria they contained.

A fundamental neuroscientific principle, the ultrastructural size principle, explains that whenever one part of the synaptic complex changes in size, so too must all the other parts. The synapse, the mitochondria, the boutons—all these parts must scale in accordance with one another. Before this new study, nobody had asked whether this principle could be violated with age or disease.

Researchers  turned to electron microscopy to examine this. This enabled them to visualize these components across many synapses. They found that synaptic loss occurred with healthy and impaired aging, but what differed was the breakdown in the correlation between the sizes of boutons and their mitochondria.

Part 1

Comment by Dr. Krishna Kumari Challa on April 13, 2023 at 10:58am

Time-restricted fasting could cause fertility problems

Time-restricted fasting diets could cause fertility problems according to new research.

Time-restricted fasting is an eating pattern where people limit their food consumption to certain hours of the day. It's a popular health and fitness trend and people are doing it to lose weight and improve their health.

 A new study published recently in Proceedings of the Royal Society B: Biological Sciences shows that time-restricted fasting affects reproduction differently in male and female zebrafish. It is titled, "Fasting increases investment in soma upon refeeding at the cost of gamete quality in zebrafish."

Importantly, some of the negative effects on eggs and sperm quality can be seen after the fish returned to their normal levels of food consumption.

The research team say that while the study was conducted in fish, their findings highlight the importance of considering not just the effect of fasting on weight and health, but also on fertility.

The way organisms respond to food shortages can affect the quality of eggs and sperm, and such effects could potentially continue after the end of the fasting period.

Fasting increases investment in soma upon refeeding at the cost of gamete quality in zebrafish, Proceedings of the Royal Society B: Biological Sciences (2023). DOI: 10.1098/rspb.2022.1556. royalsocietypublishing.org/doi … .1098/rspb.2022.1556

Comment by Dr. Krishna Kumari Challa on April 13, 2023 at 10:48am

New 'AI scientist' combines theory and data to discover scientific equations

In 1918, the American chemist Irving Langmuir published a paper examining the behavior of gas molecules sticking to a solid surface. Guided by the results of careful experiments, as well as his theory that solids offer discrete sites for the gas molecules to fill, he worked out a series of equations that describe how much gas will stick, given the pressure.

Now, about a hundred years later, an "AI scientist" developed by researchers at IBM Research, Samsung AI, and the University of Maryland, Baltimore County (UMBC) has reproduced a key part of Langmuir's Nobel Prize-winning work. The system—artificial intelligence (AI) functioning as a scientist—also rediscovered Kepler's third law of planetary motion, which can calculate the time it takes one space object to orbit another given the distance separating them, and produced a good approximation of Einstein's relativistic time-dilation law, which shows that time slows down for fast-moving objects.

A paper describing the results is published in Nature Communications on April 12.

Combining Data and Theory for Derivable Scientific Discovery with AI-Descartes, Nature Communications (2023). DOI: 10.1038/s41467-023-37236-y

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