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Comment by Dr. Krishna Kumari Challa on September 28, 2023 at 9:52am

Ultrasound enables gene delivery throughout the brain

Researchers tested the safety and feasibility of gene delivery to multiple brain regions using a noninvasive, ultrasound-based technique in rodents, and their findings suggest that the efficiency of gene delivery improves within each targeted site when more sites are opened.

The work used focused ultrasound energy to safely make the blood-brain barrier permeable. The technique is known as focused ultrasound blood-brain barrier opening (FUS-BBBO). 

The procedure also permits the passage of proteins and other small molecules in the other direction—that is, from the brain into the bloodstream—where they can be readily sampled.

Many disorders affect large brain regions or the entire brain, but delivery of gene therapy to these regions is difficult. 

When a gene-delivery vector is injected into the brain with a needle, it often only diffuses a few millimeters. To treat the entire brain, one would need to perform thousands of injections, which would be difficult and possibly harmful. With FUS-BBBO, such surgical delivery could be circumvented.

Researchers now tested the efficiency and safety of opening 105 sites simultaneously with positive results in most regions of the brain. Surprisingly, their findings suggest that the efficiency of gene delivery improves within each targeted site when more sites are opened.

 Shirin Nouraein et al, Acoustically targeted noninvasive gene therapy in large brain volumes, Gene Therapy (2023). DOI: 10.1038/s41434-023-00421-1

Comment by Dr. Krishna Kumari Challa on September 28, 2023 at 9:35am

 Why our skin feels 'tight' after washing

When we wash our face with a cleanser, our skin can start to feel tight. With the application of a favorite moisturizer, that feeling often goes away. This perception of our skin might seem subjective, but researchers recently revealed the mechanism behind these feelings.

Their work, published in PNAS Nexus, demonstrates how mechanical changes at the outer surface of our skin translate into sensations and provides a quantitative approach for determining how people will perceive their skin after using a moisturizer or cleanser.

Our skin is the largest organ in our body and it's constantly exposed to the environment around us. The outermost layer of our skin—the stratum corneum—acts as a barrier to keep out unwanted chemicals and bacteria and to keep in moisture. When we use a harsh cleanser, it strips away some of the lipids that hold in moisture, causing the stratum corneum to contract. A good moisturizer increases the water content of the stratum corneum, causing it to swell.

 The mechanical forces created by this shrinking or swelling propagate through the skin to reach mechanoreceptors—sensory receptors that turn mechanical force into neurological signals—below the epidermis, which then fire off signals to the brain that we interpret as a feeling of skin tightness.

The researchers studied the effects of nine different moisturizing formulas and six different cleansers on donor skin samples from three locations on the human body—cheek, forehead, and abdomen. They measured changes in the stratum corneum in the lab and then fed that information into a sophisticated model of human skin to predict the signals that the mechanoreceptors would send.

Ross Bennett-Kennett et al, Sensory neuron activation from topical treatments modulates the sensorial perception of human skin, PNAS Nexus, (2023) DOI: 10.1093/pnasnexus/pgad292. academic.oup.com/pnasnexus/art … /2/9/pgad292/7278834

Comment by Dr. Krishna Kumari Challa on September 28, 2023 at 9:19am

An artist's conceptual rendering of the antihydrogen atoms contained within the magnetic trap of the ALPHA-g apparatus. As the field strength at the top and bottom of the magnetic trap is reduced, the antihydrogen atoms escape, touch the chamber walls and annihilate. Most of the annihilations occur beneath the chamber, showing that gravity is pulling the antihydrogen down.

Jeffrey Hangst, Observation of the effect of gravity on the motion of antimatter, Nature (2023). DOI: 10.1038/s41586-023-06527-1. www.nature.com/articles/s41586-023-06527-1

Anna Soter, Free-falling antihydrogen reveals the effect of gravity on antimatter, Nature (2023). DOI: 10.1038/d41586-023-02930-w , www.nature.com/articles/d41586-023-02930-w

Part 2

Comment by Dr. Krishna Kumari Challa on September 28, 2023 at 9:18am

Antimatter falls downward like normal matter: Study reveals gravity's effect on matter's elusive twin

Physicists studying antihydrogen—an anti-proton paired with an antielectron, or positron—have conclusively shown that gravity pulls it downward and does not push it upward. At least for antimatter, antigravity doesn't exist.

The experimental results have been reported in the Sept. 28 issue of the journal Nature by a team representing the Antihydrogen Laser Physics Apparatus (ALPHA) collaboration at the European Center for Nuclear Research (CERN) in Geneva, Switzerland.

The gravitational acceleration of antimatter that the team comes up with is close to that for normal matter on Earth: 1 g, or 9.8 meters per second per second (32 feet per second per second). More precisely, it was found to be within about 25% (one standard deviation) of normal gravity.

It surely accelerates downwards, and it's within about one standard deviation of accelerating at the normal rate.

Albert Einstein's theory of general relativity, though conceived before antimatter was discovered in 1932, treats all matter identically, implying that antimatter and matter respond the same to gravitational forces. All normal matter, such as protons, neutrons and electrons, have anti-particles that bear the opposite electrical charge and, when they encounter their normal matter counterpart, annihilate completely.

Part 1

Comment by Dr. Krishna Kumari Challa on September 27, 2023 at 12:15pm

AI predicts sea surface temperature cooling during tropical cyclones

Tropical cyclones are extreme weather events, characterized by a circular form and formation over warm tropical oceans experiencing low atmospheric pressure, high winds and heavy rain. Tropical storms exceed 39 miles per hour (mph), while hurricanes experience sustained winds of 74mph and above.

The warm waters fuel the continuation of the cyclone, consequently cooling the surface of the ocean, and high wind speeds increase currents. The latter results in mixing of the layers of the ocean, bringing deeper and cooler water to the surface. In doing so, this can help to reduce the warm water fuel to cyclones, causing them to slow down or even cease altogether.

New research published in Geophysical Research Letters has turned towards technology to model the effects of tropical cyclones on oceans, in particular sea surface temperatures. This is important as the temperature can impact wider ecosystem responses, as well as the organisms that call the oceans home.

The machine learning-based random forest method used data from a 20-year period beginning in 1998 to train the system and help predict the evolution of sea surface temperature over time and space within the northwest Pacific Ocean (equator to 30°N, 100–160°E), one of the most active zones for tropical cyclones.

The research work showed that stronger intensity, larger and slower-moving tropical cyclones in areas with a shallow mixed ocean layer tend to have a greater cooling effect on the surface waters. Storm intensity and speed have a greater local effect, while the overall size of the cyclone, pre-storm ocean mixed layer depth and sea surface temperature impact the cooling effect over a larger area. 

Hongxing Cui et al, Predicting Tropical Cyclone‐Induced Sea Surface Temperature Responses Using Machine Learning, Geophysical Research Letters (2023). DOI: 10.1029/2023GL104171

Comment by Dr. Krishna Kumari Challa on September 26, 2023 at 11:44am

Scam awareness found to be best defense for older adults facing fraudster phone calls

Research  has looked into the susceptibility of older adults to scammers. In a paper, "Vulnerability of Older Adults to Government Impersonation Scams," published in JAMA Network Open, researchers tested 644 older adults with an experiment designed to mimic a government impersonation scam.

Participants averaged age 85.6 and were part of the Rush Memory and Aging Project (MAP), an ongoing cohort study of common chronic conditions related to aging. As part of the experiment, they were exposed to deceptive materials through mailers, emails, and phone calls by a live agent, mimicking a government impersonation scam.

Results were classified by three engagement groups: no engagement, engagement with skepticism, and conversion (those who engaged without skepticism).

Of the 644 participants, 441 (68.5%) did not engage, 97 (15.1%) engaged but raised skepticism, and 106 (16.4%) comprised the conversion group. Of those converted, nearly three-quarters provided personal information.

The research revealed that factors like cognition, financial literacy, and awareness of fraud scams were associated with the type of engagement. Those in the skeptical engagement group had the highest cognitive scores and financial literacy, while the conversion group had the lowest scam awareness.

According to the Federal Trade Commission, phone calls are the most common and most effective method used by fraudsters for targeting older adults.

Lei Yu et al, Vulnerability of Older Adults to Government Impersonation Scams, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.35319

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Comment by Dr. Krishna Kumari Challa on September 26, 2023 at 11:39am

Cross-species virus transmission found in several species of small furry animals

Research led by multiple institutions in China has examined how small, furry, viral vectors affect the spread and evolution of viruses. They report the identification of 669 viruses, including 534 novel viruses, greatly expanding our knowledge of the mammalian virome, including previously unknown coronaviruses and orthorubulaviruses.

In their paper, "Host traits shape virome composition and virus transmission in wild small mammals," published in Cell, the team used meta-transcriptomic sequencing of internal organ and fecal samples from 2,443 wild bats, rodents, and shrews from four Chinese habitats. Viruses were identified in nearly all animals studied.

Researchers identified viruses related to known human or domestic animal pathogens (e.g., Rotavirus A, Seoul virus, Wenzhou mammarenavirus), including coronaviruses, which have caused diseases like SARS and COVID-19. There were also newly identified viruses from the orthorubulaviruses, porcine epidemic diarrhea virus (PEDV), swine acute diarrhea syndrome coronaviruses (SADS-CoVs), and SARS-related coronaviruses.

The study provided robust evidence of cross-species virus transmission. For instance, viruses were found in multiple species of wild small mammals, indicating that these viruses can move between different animal species, potentially including humans.

The team observed cross-species virus transmission at taxonomic levels across species, genus, family, and order, where the same virus was found in three or more mammalian species. Viruses with multi-organ distributions within hosts were more likely to be found in other host species. This suggests that if a virus is present in multiple internal organs, it has a higher chance of spreading to other species.

Bats are often considered to harbor more viruses than rodents. Of the animals sampled in the study, bats did have the highest richness, followed by rodents and shrews. While the total number of viruses identified in bats was more than that in rodents, the average number of viruses identified per species of bats and rodents was similar.

Yan-Mei Chen et al, Host traits shape virome composition and virus transmission in wild small mammals, Cell (2023). DOI: 10.1016/j.cell.2023.08.029

Comment by Dr. Krishna Kumari Challa on September 25, 2023 at 8:39am

RNA has been recovered from an extinct species for the first time

A new study shows the isolation and sequencing of more than a century-old RNA molecules from a Tasmanian tiger specimen preserved at room temperature in a museum collection. This resulted in the reconstruction of skin and skeletal muscle transcriptomes from an extinct species for the first time.

The researchers note that their findings have relevant implications for international efforts to resurrect extinct species, including both the Tasmanian tiger and the wooly mammoth, as well as for studying pandemic RNA viruses.

The Tasmanian tiger, also known as the thylacine, was a remarkable apex carnivorous marsupial that was once distributed all across the Australian continent and the island of Tasmania. This extraordinary species found its final demise after European colonization, when it was declared as an agricultural pest and a bounty of £1 per each full-grown animal killed was set by 1888. The last known living Tasmanian tiger died in captivity in 1936 at the Beaumaris Zoo in Hobart, Tasmania. Recent efforts in de-extinction have focused on the Tasmanian tiger, as its natural habitat in Tasmania is still mostly preserved, and its reintroduction could help recovering past ecosystem equilibriums lost after its final disappearance. However, reconstructing a functional living Tasmanian tiger not only requires a comprehensive knowledge of its genome (DNA) but also of tissue-specific gene expression dynamics and how gene regulation worked, which are only attainable by studying its transcriptome (RNA). Resurrecting the Tasmanian tiger or the wooly mammoth is not a trivial task, and will require a deep knowledge of both the genome and transcriptome regulation of such renowned species, something that only now is starting to be revealed.

The researchers behind this study have sequenced, for the first time, the transcriptome of the skin and skeletal muscle tissues from a 130-year-old desiccated Tasmanian tiger specimen preserved at room temperature in the Swedish Museum of Natural History in Stockholm. This led to the identification of tissue-specific gene expression signatures that resemble those from living extant marsupial and placental mammals. The recovered transcriptomes were of such good quality that it was possible to identify muscle- and skin-specific protein coding RNAs, and led to the annotation of missing ribosomal RNA and microRNA genes, the later following MirGeneDB recommendations.

Emilio Marmol-Sanchez et al, Historical RNA expression profiles from the extinct Tasmanian tiger, Genome Research (2023). DOI: 10.1101/gr.277663.123

Comment by Dr. Krishna Kumari Challa on September 24, 2023 at 1:49pm

So why is it only mom's mtDNA that gets passed down?

One hypothesis has to do with the mitochondrial genome's relatively high mutation rate compared to the nuclear genome. Each cell in the body contains numerous mitochondria, which get separated into daughter cells the parent cell splits.

The way this split happens is fairly disorganized, all things considered, which means the daughter cells sometimes don't get enough mitochondria to meet their needs. Making the few mitochondria they do receieve work harder only makes splits and mutations more likely.

Because sperm cells rapidly churn through their energy trying to reach a human egg for fertilization, their mtDNA – if it did exist – would probably accumulate a bunch of mutations.

An egg cell, on the other hand, doesn't rely on its own mitochondria for energy. It saves those recipes for the future and instead sucks energy from the mitochondria of neighboring cells.

Eggs pass on really good mtDNA at least partly because they don't use mitochondria as a source of energy.

The findings do not explain why, in rare circumstances, scientists have found mtDNA transmission in some humans that looks as though it came from both the father and the mother. But it might help experts better understand some fertility disorders, which can be passed down through eggs or sperm. In recent years, scientists have started to find ways to target specific mutations in mitochondrial DNA so they aren't inherited by offspring. Worldwide, in fact, several children have been born with DNA from three different people, after their parents sought cutting-edge mitochondrial replacement therapy. The incredibly unique babies have nuclear DNA that derives from the fertilization of a sperm and an egg, like any other child, but their mitochondrial DNA comes from the egg of a separate female donor. "Maternal inheritance of mtDNA is a major paradigm that guides the existence and evolution of the vast majority of species," the authors of the recent study conclude, "however, the molecular basis of this phenomenon and its benefits have remained unclear."

For such a foundational part of life, it's incredible we don't know more about where our genes come from.

https://www.nature.com/articles/s41588-023-01505-9

Part 2

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Comment by Dr. Krishna Kumari Challa on September 24, 2023 at 1:46pm

Why You Didn't Get Your Dad's Mitochondria

Virtually every animal on Earth can thank their mother for the energy that fuels each of their cells. The power is generated in a part of the cell known as the mitochondria, and this organelle is made entirely from a genetic recipe laid out in your mother's DNA.

A father's mitochondrial DNA, or mtDNA, plays no part. Yet the precise point at which dad's mitochondrial genes are given the heave-ho isn't a clear-cut story, with different studies supporting a breakdown in the egg's cytoplasm, and a severe edit in the sperm as it's being formed. A recent study that sequenced the genes in human sperm cells could detect no intact mtDNA before fertilization, lending support to an early chop. While each sperm cell contained about 100 mitochondria of its own, a team of researchers  found no trace of male mtDNA within the mitochondria. The sperm also lacked the transcription factors needed to maintain mtDNA. "We conclude," the authors write, "that the mature human spermatozoa are essentially devoid of mtDNA, consistent with maternal inheritance of the mitochondrial genome in mammals."

Of course, male sex cells still contribute nuclear DNA to their offspring, and the human nuclear genome is billions of times larger than the mitochondrial genome. Even still, mutations in the latter genome are associated with a diversity of diseases and aging processes, which suggests it is quite important for health and function.

So why is it only mom's mtDNA that gets passed down?

Part 1

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