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Comment by Dr. Krishna Kumari Challa on August 31, 2023 at 9:37am

Newly-engineered versions of bacterial enzyme reveal how antibiotics could be more potent

Modern medicine depends on antibiotics to treat infections by disabling targets inside bacterial cells. Once inside these cells, antibiotics bind to certain sites on specific enzyme targets to stop bacterial growth. Randomly occurring changes (mutations) in the genes for these targets occur naturally, in some cases making the target harder for the antibiotic to attach to, and that bacterial version resistant to treatment.

For this reason, the more antibiotics have been used over time, the greater the chances that bacterial populations will evolve to have mutants resistant to existing antibiotics, and the more urgent the call for new approaches to keep the treatments from becoming obsolete.

Researchers have for decades studied resistant mutants in hopes that related mechanisms would guide the design of new treatments to overcome resistance. The effort has been limited, however, because naturally occurring resistant mutants represent a small fraction of the mutations that could possibly occur (the complete mutational space), with most drug binding-site mutations to date having been overlooked.

To address this challenge, a new study by researchers to generate the full inventory of mutations in the bacterial species Escherichia coli where the antibiotic rifampicin attaches to and disables an essential bacterial enzyme known as RNA polymerase (RNAP).

The study authors created 760 unique RNAP mutants by replacing each of the 38 amino acid building blocks that make up the rifampicin binding site on E. coli with each of the 20 amino acid options present in nature. Growth of this mutant pool was then tested under different conditions, including treatment with rifampicin.

Published online August 30 in the journal Nature, the study found two mutants, L521Y and T525D, that are hyper-sensitive to rifampicin. Not only does the antibiotic prevent these mutants from growing, it nearly obliterates the mutant bacterial populations. This is a remarkable finding, say the authors, because rifampicin normally does not kill E. coli, or many other bacterial pathogens, but only stops their growth.

This work provides a map of antibiotic-bacterial RNAP interactions that will be of value to chemists working to build on the study effects by changing, not bacterial binding site residues, but instead the structure of rifampicin and other antibiotics so that they bind tighter for increased potency.

These techniques could be applied to map the binding sites of other drug types, and especially to those vulnerable to resistance.

Evgeny Nudler, High-resolution landscape of an antibiotic binding site, Nature (2023). DOI: 10.1038/s41586-023-06495-6. www.nature.com/articles/s41586-023-06495-6

Comment by Dr. Krishna Kumari Challa on August 31, 2023 at 8:52am

Sea sponge tissue found to hold bits of DNA from fish living around them

A team of environmental and marine biologists  has found that studying sea sponge tissue can reveal the nature of the fish community living around them. 

Sea sponges live on the ocean floor—once they pick a spot to call home, they anchor themselves to a base and remain fixed in that place for the rest of their existence. They survive by filtering nutrients and oxygen from ocean water as it moves through their porous tissue. They also emit waste.

In this new effort, the researchers  found that the water passing through sea sponge pores also carries DNA from fish that live in the area and that it becomes trapped in the sea sponges' tissues. This DNA provides a record of local biodiversity.

By classifying the fish that shed the DNA via sequencing, researchers were able to create a map of a given underwater ecosystem. They were able to discriminate assemblages by region of the ocean (from Svalbard to Western Greenland, for example) and the depth of the habitat and even the level of protection.

The researchers note that there is generally a high cost associated with conducting ocean biodiversity studies—collecting and studying sea sponges could offer a much cheaper option.

Trapped DNA fragments in marine sponge specimens unveil north Atlantic deep-sea fish diversity, Proceedings of the Royal Society B: Biological Sciences (2023). DOI: 10.1098/rspb.2023.0771. royalsocietypublishing.org/doi … .1098/rspb.2023.0771

Comment by Dr. Krishna Kumari Challa on August 30, 2023 at 12:11pm

Enhancing cancer therapy using functionalized photosynthetic bacteria

Targeting malignant tumors with high precision is challenging for biomedical researchers. However, this scenario is likely to witness a paradigm shift in the near future through the use of specially engineered bacteria that can eliminate malignant cells efficiently.

Using bacteria to target cancer cells, or bacterial therapy, can be further enhanced through genetic engineering and nanotechnology. However, its efficacy may be hindered due to technical constraints and the potential development of antibiotic resistance. Hence, it is crucial to achieve the moderate yet effective chemical modification of bacteria for improved biocompatibility and functionality, such that their medical abilities are not compromised.

Recently, certain types of purple photosynthetic bacteria (PPSB) have come into limelight for their potential to address the challenges of bacterial therapy. Exploring this further, researchers published a study in Nano Today that reports the use of chemically modified PPSB for detecting and eliminating hard-to-eradicate cancerous cells in a mouse model.

Researchers selected Rhodopseudomonas palustris (RP) as the optimal bacterium for conducting the studies. "RP demonstrated excellent properties, such as near-infrared (NIR) fluorescence, photothermal conversion, and low cytotoxicity. It absorbs NIR light and produces free radicals—a property that can be utilized to kill cancer cells.

In an attempt to improve the therapeutic efficacy of the isolated strain, the team sought chemical modifications to alter the bacterial membranes. First, they performed membrane PEGylation, or the attachment of polyethylene glycol derivatives to the bacterial cell walls. Prior research indicates that bacterial PEGylation helps in evading host immune response and converts light energy into heat, which can then be utilized to selectively eliminate cancerous cells.

Initial results were encouraging.

 Sheethal Reghu et al, Cancer immunotheranostics using bioactive nanocoated photosynthetic bacterial complexes, Nano Today (2023). DOI: 10.1016/j.nantod.2023.101966

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Comment by Dr. Krishna Kumari Challa on August 30, 2023 at 12:06pm

Watch this cosmic spectacle:

The cosmic curtain rises Wednesday night with the second full moon of the month - the reason it's considered blue. It's dubbed a super-moon because it's closer to Earth than usual, appearing especially big and bright.

This will be the closest full moon of the year, just 222,043 miles (357,344 kilometers) or so away. That's more than 100 miles (160 kilometers) closer than the Aug. 1 supermoon.

As a bonus, Saturn will be visible as a bright point 5 degrees to the upper right of the moon at sunset in the east-southeastern sky. The ringed planet will appear to circle clockwise around the moon as the night wears on.

If you missed the month's first spectacle, better catch this one. There won't be another blue super-moon until 2037. The first super-moon of 2023 was in July. The fourth and last will be in September.

Comment by Dr. Krishna Kumari Challa on August 30, 2023 at 11:24am

India's moon rover confirms sulfur and detects several other elements near the lunar south pole

India's moon rover confirmed the presence of sulfur and detected several other elements near the lunar south pole as it searches for signs of frozen water nearly a week after its historic moon landing, India's space agency said recently. 

The rover's laser-induced spectroscope instrument also detected aluminum, iron, calcium, chromium, titanium, manganese, oxygen and silicon on the lunar surface, the Indian Space Research Organization, or ISRO, said in a post on its website.

The lunar rover had come down a ramp from the lander of India's spacecraft after last Wednesday's touch down near the moon's south pole. The Chandrayan-3 Rover is expected to conduct experiments over 14 days, the ISRO has said.

The rover "unambiguously confirms the presence of sulfur," ISRO said. It also is searching for signs of frozen water that could help future astronaut missions, as a potential source of drinking water or to make rocket fuel.

The rover also will study the moon's atmosphere and seismic activity.

Source: ISRO

Comment by Dr. Krishna Kumari Challa on August 29, 2023 at 11:10am

How much heat can a human body bear?
There is a fundamental limit to the body's coping ability: it is a fixed goalpost.

Research in 2010 demonstrated that a 'wet-bulb' temperature of 35° Celsius or higher would make it impossible for humans to exhaust metabolic heat, due to our fixed core body temperature.

It proposed this was an effective survivability limit.

The wet-bulb temperature measures the ability to cool by evaporation; it equals normal temperature if relative humidity is 100 percent, and otherwise is lower. 35C is extreme—most places on Earth never experience wet bulbs above 30°C.

But enough global warming could push heat waves in many areas past 35° C. This upended the widely held assumption at the time that humans could adapt to any amount of increased heat, i.e., that the goalposts would move. This goalpost will not.

Wet-bulb temperature is used by meteorologists and climatologists to quantify heat stress. It is a combination of heat and humidity: a high wet bulb can occur in humid places at lower temperatures, as well as in dry places at extremely high temperatures.

New studies are beginning to chart out the road to 35° C.

One study in the US last year found that young, healthy subjects exposed to very hot conditions started to enter hyperthermia (inability to regulate core body temperature) well below 35°C wet bulb, closer to 32° C or less.

This is an important reminder that 35° C was a theoretical upper limit, not a practical one.

On the other hand they would undoubtedly have found a higher tolerance had they done the study in India or Brazil, because physiology does adjust to heat over time (up to a point).

The heat will force us to change how we live, for example shifting outdoor summertime activities to nighttime or just eliminating them.

It remains challenging to measure or predict extreme heat's overall cost to the community in terms of health, work and quality of life.

To do this, climate and health researchers need to develop models that factor in human behavior and adaptation along with physiology, weather, and climate information. We also need to understand what will happen to nature, and seek ways to protect wildlife.

Above all we need to reach net zero carbon emissions as soon as we possibly can to arrest the continuing rise in heat.

Provided by University of New South Wales 

Originally published under Creative Commons by 360info.

Comment by Dr. Krishna Kumari Challa on August 29, 2023 at 10:17am

Researchers find key for transforming cancer cells to muscle in rhabdomyosarcoma

For six years,  some researchers  have been on a mission to transform sarcoma cells into regularly functioning tissue cells. Sarcomas are cancers that form in connective tissues such as muscle. Treatment often involves chemotherapy, surgery, and radiation—procedures that are especially tough on kids. If doctors could transform cancer cells into healthy cells, it would offer patients a whole new treatment option—one that could spare them and their families a great deal of pain and suffering.

A devastating and aggressive type of pediatric cancer, rhabdomyosarcoma (RMS) resembles children's muscle cells. No one knew whether this proposed treatment method, called differentiation therapy, might ever work in RMS. It could still be decades out. But now, thanks to some scientists, it seems like a real possibility.

To carry out their mission, these researchers created a new genetic screening technique. Using genome-editing technology, they hunted down genes that, when disrupted, would force RMS cells to become muscle cells. That's when a protein called NF-Y emerged. With NF-Y impaired, the scientists witnessed an astonishing transformation.

The cells literally turn into muscle. The tumor loses all cancer attributes. They're switching from a cell that just wants to make more of itself to cells devoted to contraction. Because all its energy and resources are now devoted to contraction, it can't go back to this multiplying state. The research is published in the journal Proceedings of the National Academy of Sciences.

This newfound relationship between NF-Y and RMS may set off the chain reaction needed to bring differentiation therapy to patients. And the mission doesn't stop at RMS. The technology could be applicable to other cancer types. If so, scientists may someday work out how to turn other tumors into healthy cells.

 Sroka, Martyna W. et al, Myo-differentiation reporter screen reveals NF-Y as an activator of PAX3–FOXO1 in rhabdomyosarcoma, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2303859120. doi.org/10.1073/pnas.2303859120

Comment by Dr. Krishna Kumari Challa on August 29, 2023 at 9:58am

The first observation of neutrinos at CERN's Large Hadron Collider

Neutrinos are tiny and neutrally charged particles accounted for by the Standard Model of particle physics. While they are estimated to be some of the most abundant particles in the universe, observing them has so far proved to be highly challenging, as the probability that they will interact with other matter is low.

To detect these particles, physicists have been using detectors and advanced equipment to examine known sources of neutrinos. Their efforts ultimately led to the observation of neutrinos originating from the sun, cosmic rays, supernovae and other cosmic objects, as well as particle accelerators and nuclear reactors. A long-standing goal in this field of study was to observe neutrinos inside colliders, particle accelerators in which two beams of particles collide with each other. Two large research collaborations, namely FASER (Forward Search Experiment) and SND (Scattering and Neutrino Detector)@LHC, have observed these collider neutrinos for the very first time, using detectors located at CERN's Large Hadron Collider (LHC) in Switzerland. The results of their two studies were recently published in Physical Review Letters.

The FASER and SND@LHC collaboration are two distinct research efforts, both utilizing the LHC at CERN. Recently, these two efforts independently observed the first collider neutrinos, which could open important new avenues for experimental particle physics research.

The FASER collaboration is a large research effort established with the goal of observing light and weakly interacting particles. FASER was the first research group to observe neutrinos at the LHC, using the FASER detector, which is positioned over 400m away from the renowned ATLAS experiment, in a separate tunnel. FASER (and SND@LHC) observe neutrinos produced in the same "interaction region" inside the LHC as ATLAS.

Henso Abreu et al, First Direct Observation of Collider Neutrinos with FASER at the LHC, Physical Review Letters (2023). DOI: 10.1103/PhysRevLett.131.031801

R. Albanese et al, Observation of Collider Muon Neutrinos with the SND@LHC Experiment, Physical Review Letters (2023). DOI: 10.1103/PhysRevLett.131.031802

Comment by Dr. Krishna Kumari Challa on August 28, 2023 at 8:04am

New ancient ape from Türkiye challenges the story of human origins

A new fossil ape from an 8.7-million-year-old site in Türkiye is challenging long-accepted ideas of human origins and adding weight to the theory that the ancestors of African apes and humans evolved in Europe before migrating to Africa between nine and seven million years ago.

Analysis of a newly identified ape named Anadoluvius turkae recovered from the Çorakyerler fossil locality near Çankırı with the support of the Ministry of Culture and Tourism in Türkiye, shows Mediterranean fossil apes are diverse and are part of the first known radiation of early hominines—the group that includes African apes (chimpanzees, bonobos and gorillas), humans and their fossil ancestors.

The findings are described in a study published today in Communications Biology authored by an international team of researchers.

These findings further suggest that hominines not only evolved in western and central Europe but spent over five million years evolving there and spreading to the eastern Mediterranean before eventually dispersing into Africa, probably as a consequence of changing environments and diminishing forests.

The members of this radiation to which Anadoluvius belongs are currently only identified in Europe and Anatolia. The conclusion is based on analysis of a significantly well-preserved partial cranium uncovered at the site in 2015, which includes most of the facial structure and the front part of the brain case.

Ayla Sevim-Erol et al, A new ape from Türkiye and the radiation of late Miocene hominines, Communications Biology (2023). DOI: 10.1038/s42003-023-05210-5

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Comment by Dr. Krishna Kumari Challa on August 28, 2023 at 7:04am

Teeth Can Preserve The Signal of Pathogens For Hundreds of Years, Study Finds

An analysis of antibodies extracted from 800-year-old teeth has provided a new way to identify pathogens our ancestors contended with. The process could potentially help us understand how human antibodies – proteins naturally produced by our bodies in self-defense – have developed through history.

Building on previous research, a team of researchers conducted a process called affinity purification to identify molecules through the way they bind to other molecules. These kinds of bindings are a crucial part of how the human immune system works, and they can help researchers retroactively identify antibodies and what they were designed to fight against.

Intact antibodies from teeth recovered from an English grave dated to between 1285 and 1470 CE had their protein sequences read and their reactivity tested against potential antigens. Crucially, the antibodies recovered from the teeth retained a large part of their original structure, and were still biologically active, enabling the scientists to measure their response against current viruses. The researchers found that antibodies from medieval teeth were able to recognize the Epstein-Barr virus, which causes glandular fever.

Although this study only involved three teeth, it demonstrates how viable this type of analysis is – and how it could be scaled up in the future.

This emerging field of research is known as paleoproteomics, where the latest chemical analysis techniques are used to identify proteins on ancient remains – proteins that are typically more resilient than any DNA fragments that might also be recovered.

https://www.cell.com/iscience/fulltext/S2589-0042(23)01652-8

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