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Comment by Dr. Krishna Kumari Challa on June 2, 2023 at 10:54am

We are exceeding most of Earth’s limits

In 2009, a seminal paper in Nature showed that humanity had crossed three of nine ‘Earth-system boundaries’: the limits of what the planet can support before human activities make it uninhabitable. Now, there’s a reboot of the extraordinarily influential concept that takes into account how changes to climate, ecosystems and other factors disproportionately affect vulnerable communities. We have crossed seven of the eight safe and just boundaries. Only air pollution was inside dangerous limits globally, despite it causing an estimated 4.2 million deaths annually. If our planet got a check-up, “our doctor would say that the Earth is really quite sick right now, and it is sick in terms of many different areas or systems, and this sickness is also affecting the people living on Earth”, says climate-policy researcher and co-author Joyeeta Gupta.

https://apnews.com/article/earth-environment-climate-change-nature-...

Comment by Dr. Krishna Kumari Challa on June 2, 2023 at 10:51am

Brain’s wrinkles help to drive how it works

Our brains’ walnut-like wrinkles have a large effect on brain activity, in much the same way that the shape of a bell determines how it sounds. The discovery challenges the paradigm that brain function emerges from the intricate web of connections between specialized brain-cell populations, called the connectome. Researchers used mathematical models that predict how waves travel across surfaces, and found that the shape of the brain’s outer surface was a better predictor of brainwave data than was the model of the connectome.

Comment by Dr. Krishna Kumari Challa on June 2, 2023 at 9:57am

The researchers experimentally induced DNA damage in human cell lines using a common chemotherapy medication known as etoposide. Etoposide works by breaking DNA strands and blocking an enzyme that helps repair the damage. Surprisingly, inducing DNA damage resulted in reactive oxygen species being generated and accumulating inside the nucleus. The researchers observed that cellular respiratory enzymes, a major source of reactive oxygen species, relocated from the mitochondria to the nucleus in response to DNA damage.

The findings represent a paradigm shift in cellular biology because it suggests the nucleus is metabolically active. Where there's smoke there's fire, and where there's reactive oxygen species there are metabolic enzymes at work. Historically, scientists have thought of the nucleus as a metabolically inert organelle that imports all its needs from the cytoplasm, but this study demonstrates that another type of metabolism exists in cells and is found in the nucleus.

The researchers also used CRISPR-Cas9 to identify all the metabolic genes that were important for cell survival in this scenario. These experiments revealed that cells order the enzyme PRDX1, an antioxidant enzyme also normally found in mitochondria, to travel to the nucleus and scavenge reactive oxygen species present to prevent further damage. PRDX1 was also found to repair the damage by regulating the cellular availability of aspartate, a raw material that is critical for synthesizing nucleotides, the building blocks of DNA.

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The findings can guide future lines of cancer research. Some anti-cancer drugs, such as the etoposide used in this study, kill tumor cells by damaging their DNA and inhibiting the repair process. If enough damage accumulates, the cancer cell initiates a process where it autodestructs.

During their experiments, the researchers found that knocking out metabolic genes critical for cellular respiration—the process that generates energy from oxygen and nutrients—made normal healthy cells become resistant to etoposide. The finding is important because many cancer cells are glycolytic, meaning that even in the presence of oxygen they generate energy without doing cellular respiration. This means etoposide, and other chemotherapies with a similar mechanism, is likely to have a limited effect in treating glycolytic tumors.

The authors of the study call for the exploration of new strategies such as dual treatment combining etoposide with drugs that also boost the generation of reactive oxygen species to overcome drug resistance and kill cancer cells faster. They also hypothesize that combining etoposide with inhibitors of nucleotide synthesis processes could potentiate the effect of the drug by preventing the repair of DNA damage and ensuring cancer cells self-destruct correctly.

"A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability", Molecular Systems Biology (2023). DOI: 10.15252/msb.202211267

Part 2

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Comment by Dr. Krishna Kumari Challa on June 2, 2023 at 9:53am

Study examines how DNA damage is repaired by antioxidant enzymes

A typical human cell is metabolically active, roaring with chemical reactions that convert nutrients into energy and useful products that sustain life. These reactions also create reactive oxygen species, dangerous by-products like hydrogen peroxide which damage the building blocks of DNA in the same way oxygen and water corrode metal and form rust. Similar to how buildings collapse from the cumulative effect of rust, reactive oxygen species threaten a genome's integrity.

Cells are thought to delicately balance their energy needs and avoid damaging DNA by containing metabolic activity outside the nucleus and within the cytoplasm and mitochondria. Antioxidant enzymes are deployed to mop up reactive oxygen species at their source before they reach DNA, a defensive strategy that protects the roughly 3 billion nucleotides from suffering potentially catastrophic mutations. If DNA damage occurs anyway, cells pause momentarily and carry out repairs, synthesizing new building blocks and filling in the gaps.

Despite the central role of cellular metabolism in maintaining genome integrity, there has been no systematic, unbiased study on how metabolic perturbations affect the DNA damage and repair process. This is particularly important for diseases like cancer, characterized by their ability to hijack metabolic processes for unfettered growth.

A research team has now addressed this challenge by carrying out various experiments to identify which metabolic enzymes and processes are essential for a cell's DNA damage response. The findings are published today in the journal Molecular Systems Biology.

Part 1

Comment by Dr. Krishna Kumari Challa on June 2, 2023 at 9:20am

The lead risk variant at the MTHFR–CLCN6 locus has been previously associated with reduced levels of circulating N-terminal pro-BNP43. A recent analysis found that first-trimester levels of N-terminal pro-BNP were unexpectedly lower among female individuals who subsequently developed hypertensive disorders of pregnancy later in pregnancy. These findings suggest that genetic network-driven deficiency in endogenous natriuretic peptide signaling may predispose individuals to hypertensive disorders of pregnancy.

Synthetic natriuretic peptides have been developed, and the authors suggest that natriuretic peptides may represent a future therapeutic target for direct or indirect modulation toward hypertensive disorders of pregnancy prevention and treatment.

 Michael C. Honigberg et al, Polygenic prediction of preeclampsia and gestational hypertension, Nature Medicine (2023). DOI: 10.1038/s41591-023-02374-9

Part 2

Comment by Dr. Krishna Kumari Challa on June 2, 2023 at 9:20am

From genes to gestation, researchers probe predictive markers for pregnancy complications

A new study has identified genetic markers associated with preeclampsia and gestational hypertension in a large cohort study. In the paper, "Polygenic prediction of preeclampsia and gestational hypertension," published in Nature Medicine, the researchers detail how these genetic markers could be used as a predictive risk assessment and offers mechanistic insights into pregnancy disorders.

Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse outcomes, including substantial morbidity and mortality for both mother and child. Current tools for prediction, prevention and treatment are limited.

The team examined the associations of maternal DNA variants in 20,064 preeclampsia cases compared to 703,117 control individuals and gestational hypertension in 11,027 cases compared with 412,788 controls. Polygenic risk scores were tuned to a UK Biobank and then tested against other data sets for validation.

The analysis identified 18 independent loci associated with preeclampsia and gestational hypertension, 12 of which were previously unknown, and an additional two genes were implicated in a follow-up meta-analysis. The genes associated highlight potential roles of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation.

Interestingly, almost none of the associated genes reside on the same chromosome, making them less likely to be inherited together.

Low-dose aspirin starting after week 12 gestation is an evidence-based but underused strategy to reduce risk of preeclampsia. To probe the potential clinical impact of incorporating PRS to guide aspirin allocation, researchers examined aspirin eligibility according to current US Preventive Service Task Force major criteria. Those with polygenic risk scores in the top 10% were shown to increase identification as low-dose aspirin-eligible by 30.4%, offering a potential preemptive intervention.

Part 1

Comment by Dr. Krishna Kumari Challa on June 1, 2023 at 10:16am

Darker skies are disappearing:

Light pollution can have negative consequences for the well-being of many living things—plants, animals and even humans. Between 2011 and 2022 light pollution increased globally by 9.6 percent a year. “This might not sound like much, but it reflects an exponential growth rate,” writes Phil Plait, astronomer and science communicator. 

Why this matters: Light pollution disrupts the migrations of birds, the blossoming of flowers and even the courtship of fireflies. For humans, more light might mean more insomnia or other health impacts. 

What the experts say: To help, you can: Use smarter streetlights that concentrate light downward (which are cheaper, too); turn off your own outdoor lighting at night; use targeted illumination rather than flood lighting; choose lightbulbs and LEDs that shine more red than blue to reduce how much light scatters across the sky. 

Comment by Dr. Krishna Kumari Challa on June 1, 2023 at 9:35am

Biological cleanup discovered for certain 'forever chemicals'

Chemical and environmental engineering scientists have identified two species of bacteria found in soil that break down a class of stubborn "forever chemicals," giving hope for low-cost biological cleanup of industrial pollutants.

These bacteria destroy a subgroup of per- and poly-fluoroalkyl substances, or PFAS, that have one or more chlorine atoms within their chemical structure.

Unhealthful forever chemicals persist in the environment for decades or much longer because of their unusually strong carbon-to-fluorine bonds. Remarkably, the researchers found that the bacteria cleave the pollutant's chlorine-carbon bonds, which starts a chain of reactions that destroy the forever chemical structures, rendering them harmless.

What they discovered is that bacteria can do carbon-chlorine bond cleavage first, generating unstable intermediates. And then those unstable intermediates undergo spontaneous defluorination, which is the cleavage of the carbon-fluorine bond.

Bosen Jin et al, Substantial defluorination of polychlorofluorocarboxylic acids triggered by anaerobic microbial hydrolytic dechlorination, Nature Water (2023). DOI: 10.1038/s44221-023-00077-6

Comment by Dr. Krishna Kumari Challa on June 1, 2023 at 9:32am

Scientists' report world's first X-ray of a single atom

A team of scientists has taken the world's first X-ray SIGNAL (or SIGNATURE) of just one atom. This groundbreaking achievement could revolutionize the way scientists detect the materials.

An important usage of X-rays in science is to identify the type of materials in a sample. Over the years, the quantity of materials in a sample required for X-ray detection has been greatly reduced thanks to the development of synchrotron X-rays sources and new instruments. To date, the smallest amount one can X-ray a sample is in attogram, that is about 10,000 atoms or more. This is due to the X-ray signal produced by an atom being extremely weak so that the conventional X-ray detectors cannot be used to detect it. It is a long-standing dream of scientists to X-ray just one atom, which is now being realized by the research team .

Atoms can be routinely imaged with scanning probe microscopes, but without X-rays one cannot tell what they are made of. Scientists can now detect exactly the type of a particular atom, one atom-at-a-time, and can simultaneously measure its chemical state.

Once they are able to do that, they can trace the materials down to ultimate limit of just one atom. This will have a great impact on environmental and medical sciences and maybe even find a cure that can have a huge impact for humankind. This discovery will transform the world.

Saw-Wai Hla, Characterization of just one atom using synchrotron X-rays, Nature (2023). DOI: 10.1038/s41586-023-06011-w. www.nature.com/articles/s41586-023-06011-w

Comment by Dr. Krishna Kumari Challa on June 1, 2023 at 9:26am

Sleep deprivation is a risk factor for Alzheimer's, say scientists

Scientists have long explored the link between disturbances in sleep patterns and neurodegenerative diseases. Powerful evidence has emerged in recent years linking disrupted sleep to Parkinson's, and a massive body of research has explored the serious sleep disturbances associated with chronic traumatic encephalopathy—CTE—a condition linked with repeated head injuries, such as the trauma sustained in boxing, football and other aggressive sports.

Of equal concern has been sleep impairments associated with Alzheimer's disease, a condition that is increasing globally as the world's population inexorably ages. According to data from the Mayo Clinic, an estimated 25% of people with mild to moderate forms of the disorder have disturbed sleep and 50% are estimated to have sleep problems when the condition is deemed severe.

Now, scientists have posed a series of provocative questions about the impact of poor sleep and the development of Alzheimer's disease. Chronic sleep disturbances, these scientists say, are an inescapable Alzheimer's risk factor.

The scientists have also demonstrated in a series of experiments that sleep deprivation prevents immune cells known as microglia from properly cleaning up deposits of amyloid protein during the sleep cycle, a finding that helps explain the long-observed connection between sleep loss and neurodegeneration. Amyloid proteins are the building blocks of gooey amyloid plaques, a key hallmark of Alzheimer's disease.

In their research, which is reported in Science Translational Medicine, the team turned to multiple mouse models to show how disrupted sleep patterns allow deposits of amyloid to accumulate. Sleep is biologically beneficial to the brain because that's when an elaborate network flushes away excess amyloid as well as cellular and metabolic debris. Without that daily clean-up cycle, the brain can pay an enormous price, according to these scientists.

These findings highlight that sleep deprivation directly affects microglial reactivity, for which TREM2 is required, by altering the metabolic ability to cope with the energy demands of prolonged wakefulness, leading to further amyloid-β deposition, and underlines the importance of sleep modulation as a promising future therapeutic approach.

Samira Parhizkar et al, Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2 -dependent manner in mice, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.ade6285

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