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Comment by Dr. Krishna Kumari Challa on February 15, 2023 at 10:29am

We really need this : New AI tool guides users away from vitriol

To help identify when tense online debates are inching toward irredeemable meltdown,  researchers have developed an artificial intelligence tool that can track these conversations in real-time, detect when tensions are escalating and nudge users away from using incendiary language.

Detailed in two recently published papers that examine AI's effectiveness in moderating online discussions, the research shows promising signs that conversational forecasting methods within the field of natural language processing could prove useful in helping both moderators and users proactively lessen vitriol and maintain healthy, productive debate forums.

The tool, named ConvoWizard, is a browser extension powered by a deep neural network. That network was trained on mountains of language-based data pulled from the subreddit Change My View, a forum that prioritizes good faith debates on potentially heated subjects related to politics, economics and culture.

When participating Change My View users enable ConvoWizard, the tool can inform them when their conversation is starting to get tense. It can also inform users, in real-time as they are writing their replies, whether their comment is likely to escalate tension. The study suggests that AI-powered feedback can be effective in guiding the user toward language that elevates constructive debate, researchers say.

Jonathan P. Chang et al, Thread With Caution: Proactively Helping Users Assess and Deescalate Tension in Their Online Discussions, Proceedings of the ACM on Human-Computer Interaction (2022). DOI: 10.1145/3555603

Charlotte Schluger et al, Proactive Moderation of Online Discussions: Existing Practices and the Potential for Algorithmic Support, Proceedings of the ACM on Human-Computer Interaction (2022). DOI: 10.1145/3555095

Comment by Dr. Krishna Kumari Challa on February 15, 2023 at 9:48am

In the experiments now published, a special detection was used. "The energy released during the decay of the state is sufficient to release other electrons from the nanostructure.

The triggered electrons could then be captured in an image using a photoemission electron microscope and a resolution of a few nanometers. Because of the fast decay times, sequences of ultrashort laser pulses were used to obtain the "fingerprint" of the superposition states of the light.

This is a first step toward the goal of analyzing the full quantum physical state of coupled photon and electrons directly at the nanoscale. 

Sebastian Pres et al, Detection of a plasmon-polariton quantum wave packet, Nature Physics (2023). DOI: 10.1038/s41567-022-01912-5

Part 2

Comment by Dr. Krishna Kumari Challa on February 15, 2023 at 9:47am

The weird world of Quantum Mechanics: When the light is neither 'on' nor 'off' in the nanoworld!

Whether the light in our living spaces is on or off can be regulated in everyday life simply by reaching for the light switch. However, when the space for the light is shrunk to a few nanometers, quantum mechanical effects dominate, and it is unclear whether there is light in it or not. Both can even be the case at the same time, as scientists show in the journal Nature Physics.

The technology of our digital world is based on the principle that either a current flows or it does not: one or zero, on or off. Two clear states exist. In quantum physics, on the other hand, it is possible to disregard this principle and create an arbitrary superposition of the supposed opposites. This increases the possibilities of transmitting and processing information many times over. Such superposition states have been known for some time, especially for the particles of light, so-called photons, and are used in the detection of gravitational waves.

A team of physicists and physical chemists from Bielefeld and Würzburg has now succeeded in detecting such superposition states of light directly in a nanostructure. Light is captured in a nanostructure in a very small space and couples to electronic oscillations: so-called plasmons. This allows the energy of the light to be held in place on the nanoscale.

In the experiment, the researchers investigated how many photons from a light pulse couple to the nanostructure. The result: simultaneously no photon and three photons.

Detecting this signature was an enormous challenge. Photons can be detected very well with sensitive detectors; however, in the case of single photons, which are also in a quantum mechanical superposition state, suitable methods did not exist in the nanoworld." In addition, the coupled states of photons and electrons survive for less than a millionth of a millionth of a second and then decay again, leaving hardly any time for their detection.

Part 1

Comment by Dr. Krishna Kumari Challa on February 15, 2023 at 8:51am

Kangaroo fecal microbes could reduce methane from cows

Baby kangaroo feces might help provide an unlikely solution to the environmental problem of cow-produced methane. A microbial culture developed from the kangaroo feces inhibited methane production in a cow stomach simulator in a recent study.

After researchers added the baby kangaroo culture and a known methane inhibitor to the simulated stomach, it produced acetic acid instead of methane. Unlike methane, which cattle discard as flatulence, acetic acid has benefits for cows as it aids muscle growth.

While the researchers have tested their system in the simulated rumen, they hope to try it on real cows  in the future.

 Supriya C. Karekar et al, Reducing methane production from rumen cultures by bioaugmentation with homoacetogenic bacteria, Biocatalysis and Agricultural Biotechnology (2022). DOI: 10.1016/j.bcab.2022.102526

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Reducing the burps and farts of methane emissions from cattle is no laughing matter. Methane is the second largest greenhouse gas contributor and is about 30 times more potent at heating up the atmosphere than carbon dioxide. More than half of the methane released to the atmosphere is thought to come from the agricultural sector, and ruminant animals, such as cattle and goats, are the most significant contributors. Furthermore, the process of producing methane requires as much as 10% of the animal's energy.

Researchers have tried changing cows' diets as well as giving them chemical inhibitors to stop methane production, but the methane-producing bacteria soon become resistant to the chemicals. They also have tried to develop vaccines, but a cow's microbiome depends on where it's eating, and there are far too many varieties of the methane-producing bacteria worldwide. The interventions can also negatively affect the animals' biological processes. 

Comment by Dr. Krishna Kumari Challa on February 15, 2023 at 8:40am

How eyeless centipedes are able to detect sunlight

Researchers have  uncovered the means by which the Chinese red-headed centipede is able to detect sunlight despite having no eyes or even photoreceptors.

Venomous Chinese red-headed centipedes have long, black segmented bodies, yellow legs and a large, eyeless head with long antennae and a mouth capable of biting and injecting venom into prey, predators and humans that happen to step on them. Prior research has shown that the centipede actively avoids sunlight, though it is not known if this is to avoid predators or prevent overheating. Prior research has also shown that in addition to having no eyes, the pencil-size bugs also have no photoreceptors, raising the question of how they know when the sun is shining on them. To find out, the researchers conducted experiments that involved placing specimens in clear containers, some of which were covered with black tape. They then studied how the centipedes moved when exposed to differing amounts of light. They also used thermal cameras to record changes in body temperature during sunlight exposure. They found that the temperature of the antennae rose almost immediately when exposed to sunlight, and did so rapidly. Readings showed temperature increases of up to 9°C within seconds.

To confirm that the antennae were alerting the centipedes to sunlight, the researchers covered the curly red, segmented structures of several specimens and then retested the bugs to see how they responded to sudden bursts of light. The covering made the creatures far less averse to sunlight. The researchers then took a closer look at the antennae to find out how they were working as sunlight heat sensors and found thermal receptors called BRTNaC1 that served as ion channels. They were triggered by temperature increases.

 Zhihao Yao et al, A thermal receptor for nonvisual sunlight detection in myriapods, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2218948120

Comment by Dr. Krishna Kumari Challa on February 14, 2023 at 10:18am

Time of day may determine the amount of fat burned by exercise

Physical activity at the right time of the day seems able to increase fat metabolism, at least in mice. A new study shows that mice that did exercise in an early active phase, which corresponds to morning exercise in humans, increased their metabolism more than mice that did exercise at a time when they usually rest. The results are published in the journal PNAS.

Physical activity at different times of the day can affect the body in different ways since the biological processes depend on the circadian rhythms of the cells. To ascertain how the time of day at which exercise is done affects the burning of fat, researchers studied the adipose tissue of mice after a session of high-intensity exercise performed at two points of the daily cycle, an early active phase and early rest phase (corresponding to a late morning and late evening session, respectively, in humans). The researchers studied various markers for fat metabolism and analyzed which genes were active in adipose tissue after exercise.

Independent of food intake

The researchers found that physical activity at an early active phase increased the expression of genes involved in the breakdown of adipose tissue, thermogenesis (heat production) and mitochondria in the adipose tissue, indicating a higher metabolic rate. These effects were observed only in mice that exercised in the early active phase and were independent of food intake.

These results suggest that late morning exercise could be more effective than late evening exercise in terms of boosting the metabolism and the burning of fat, and if this is the case, they could prove of value to people who are overweight.

The right timing seems to be important to the body's energy balance and to improving the health benefits of exercise. This has to to be ascertained in human beings now.

Pendergrast, Logan A. et al, Time of day determines postexercise metabolism in mouse adipose tissue, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2218510120. doi.org/10.1073/pnas.2218510120

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Comment by Dr. Krishna Kumari Challa on February 14, 2023 at 10:10am

Study reveals how drug resistant bacteria secrete toxins, suggesting targets to reduce virulence

Antimicrobial resistance represents one of the top 10 global public health threats according to the World Health Organization, and scientists have been scrambling to find new tools to cure the most deadly drug-resistant infections.

New research work  suggests that reducing virulence in drug resistant infections rather than trying to kill bacteria  outright may offer an alternative approach to treatment.

The study revealed how two proteins enable the methicillin-resistant Staphylococcus aureus (MRSA) bacterium to secrete the toxins that make people sick. The research suggests that therapies targeting these two proteins could disable MRSA, making it less deadly and possibly even harmless. Such an approach would also reduce the risk of promoting antibiotic resistance.

The paper, which was published on February 13, 2023, in the Proceedings of the National Academy of Science suggests that similar mechanisms may exist in other bacteria, pointing to the potential for a new approach to treating other bacterial infections.

 Dickey, Seth W. et al, Two transporters cooperate to secrete amphipathic peptides from the cytoplasmic and membranous milieus, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2211689120. doi.org/10.1073/pnas.2211689120

Comment by Dr. Krishna Kumari Challa on February 13, 2023 at 11:39am

The nucleolus within the cell nucleus is also a condensate, which appears as a diffuse dark speck under the microscope. This is where many proteins with positively charged tails like to linger. Many of these provide the machinery required for protein synthesis, making this condensate essential for cellular functions.

The mutant protein HMGB1 with its positively charged molecular tail is attracted to the nucleolus as well, as the team observed from experiments with isolated protein and with cell cultures.

But since the mutated protein region has also gained an oily, sticky part, it tends to clump. The nucleolus loses its fluid-like properties and increasingly solidifies, which Niskanen was able to observe under the microscope. This impaired the vital functions of the cells – with the mutated protein, more cells in a culture died compared to a culture of cells without the mutation.

What scientists discovered in this one disease might apply to many more disorders. It is likely not a rare unicorn that exists only once.

The research team then searched databases of genomic data from thousands of individuals looking for similar incidents. In fact, the scientists were able to identify more than six hundred similar mutations in 66 proteins, in which the reading frame had been shifted by a mutation in the protein tail, making it both more positively charged and more “greasy”. Of the mutations, 101 had previously been linked to several different disorders.

For a cell culture assay, the team selected 13 mutant genes. In 12 out of 13 cases, the mutant proteins had a preference to localize into the nucleolus. About half of the tested proteins impaired the function of the nucleolus, resembling the disease mechanism of BPTA syndrome.

1. Martin A. Mensah, Henri Niskanen, Alexandre P. Magalhaes, Shaon Basu, Martin Kircher, Henrike L. Sczakiel, Alisa M. V. Reiter, Jonas Elsner, Peter Meinecke, Saskia Biskup, Brian H. Y. Chung, Gregor Dombrowsky, Christel Eckmann-Scholz, Marc Phillip Hitz, Alexander Hoischen, Paul-Martin Holterhus, Wiebke Hülsemann, Kimia Kahrizi, Vera M. Kalscheuer, Anita Kan, Mandy Krumbiegel, Ingo Kurth, Jonas Leubner, Ann Carolin Longardt, Jörg D. Moritz, Hossein Najmabadi, Karolina Skipalova, Lot Snijders Blok, Andreas Tzschach, Eberhard Wiedersberg, Martin Zenker, Carla Garcia-Cabau, René Buschow, Xavier Salvatella, Matthew L. Kraushar, Stefan Mundlos, Almuth Caliebe, Malte Spielmann, Denise Horn, Denes Hnisz. Aberrant phase separation and nucleolar dysfunction in rare genetic diseases. Nature, 2023; DOI: 10.1038/s41586-022-05682-1

Part 2

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Comment by Dr. Krishna Kumari Challa on February 13, 2023 at 11:38am

Protein droplets may cause many types of genetic disease

Most proteins localize to distinct protein-rich droplets in cells, also known as “cellular condensates”. Such proteins contain sequence features that function as address labels, telling the protein which condensate to move into. When the labels get screwed up, proteins may end up in the wrong condensate. According to an international team of researchers from clinical medicine and basic biology, this could be the cause of many unresolved diseases.

Patients with BPTA syndrome have characteristically malformed limbs featuring short fingers and additional toes, missing tibia bones in their legs and reduced brain size. As the researchers found out, BPTAS is caused by a special genetic change that causes an essential protein to migrate to the nucleolus, a large proteinaceous droplet in the cell nucleus. As a result, the function of the nucleolar condensate is inhibited and developmental disease develops.

Affected individuals have complex and striking malformations of the limbs, face, and nervous and bone systems, only partially described by the already-long disease name “brachyphalangy-polydactyly-tibial aplasia/hypoplasia syndrome” (BPTAS).

 To track down the cause,  researchers decoded the genome of five affected individuals and found that the gene for the protein HMGB1 was altered in all patients.

This protein has the task of organizing the genetic material in the cell nucleus and facilitates the interaction of other molecules with the DNA, for example to read genes.

In mice, a complete loss of the gene on both chromosomes is catastrophic and leads to death of the embryo. In some patients with only one copy mutated, however, the cells are using the intact copy on the other chromosome, resulting only in mild neurodevelopmental delay. But the newly discovered cases did not fit this scheme.

A closer look revealed that different mutations of HMGB1 have different consequences. The sequencing data showed that in the affected individuals with the severe malformations, the reading frame for the final third of the HMGB1 gene is shifted.After translation to protein, the corresponding region is now no longer equipped with negative but with positively charged amino acid building blocks. This can happen if a number of genetic letters not divisible by three is missing in the sequence, because exactly three consecutive letters always code for one building block of the protein.

However, the tail part of the protein does not have a defined structure. Instead, this section hangs out of the molecule like a loose rubber band. The purposes of such protein tails (also called “intrinsically disordered regions”) are difficult to study because they often become effective only in conjunction with other molecules. So how might their mutation lead to the observed disease?

To answer this question, the medical researchers approached biochemists  who work with cellular condensates that control important genes. These droplet-like structures behave much like the oil and vinegar droplets in a salad dressing. Composed of a large number of different molecules, they are separated from their surroundings and can undergo dynamic changes.

Researchers think condensates are formed in the cell for practical reasons.

 Molecules for a specific task are grouped together in this way, say to read a gene. For this task alone several hundred proteins need to somehow make their way to the right place.
Intrinsically disordered regions, which tend not to have an obvious biochemical role, are thought to be responsible for forming condensates.

Part1

Comment by Dr. Krishna Kumari Challa on February 13, 2023 at 11:21am

Drugs Hitch a Ride on Algae for Targeted Delivery

A new microrobot uses algae to transport antibiotics into the lungs of mice with pneumonia.

When you swallow a pill, only a fraction of the drug ends up where it’s needed. Active compounds diffuse across the intestinal wall and are diluted in rivers of blood, aimlessly drifting with the currents. For more precise delivery, scientists are recruiting motile, single-celled organisms as vehicles that transport drugs to specific sites in the body.

So far, researchers have harnessed swimming bacteria for targeted drug delivery. In one case, magnetotactic bacteria guided by an external magnetic field carried nanosize liposomes loaded with a chemotherapy drug to mouse tumors. But bacteria are prime targets for the immune system that are often destroyed before they reach their destination.

Now, a team at the University of California, San Diego has built a microscopic robot—or microrobot—using Chlamydomonas reinhardtii, a species of microalgae, which are less likely to elicit an immune response than bacteria.

Researchers attached antibiotic-filled nanoparticles to the microbes’ surfaces using click chemistry, the Nobel Prize-winning
method that uses rapid reactions to connect molecules. Inside the body, modified algae beat their flagella to swim through the blood and dive deep into tissues. Each nanoparticle is wrapped in a neutrophil membrane, which promotes immune evasion and allows the microrobots to latch onto pathogens, depositing the drugs in their vicinity.

The researchers tested the algae in mice with a severe form of pneumonia caused by Pseudomonas aeruginosa bacteria. Known as ventilator-associated pneumonia (VAP), the potentially fatal infection is picked up by human patients during ventilator use in hospitals. Microrobots were delivered directly into mouse lungs through a tube leading into the windpipe. After one week, infections disappeared in all treated mice. Their untreated littermates died within three days.

The researchers then compared the microrobots to intravenous injection, the current standard treatment for VAP. Treatment with microalgae worked despite a dose of antibiotics 3,000 times smaller than was needed intravenously, which could reduce side effects.

Taking advantage of the algae’s natural fluorescence, the researchers dissected and imaged the mouse lungs. Light radiated from the whole organ for over 24 hours and from homogenized lung tissue for three days, indicating that the robots had dispersed throughout the tissue and dodged immune attack long enough for successful drug delivery.

https://www.nature.com/articles/s41563-022-01360-9.epdf?sharing_tok...

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