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Comment by Dr. Krishna Kumari Challa on December 11, 2021 at 9:24am

Inching closer towards "living biotherapeutics"

The human gut is home to thousands of species of bacteria, and some of those bacteria have the potential to treat a variety of gastrointestinal diseases. Some species may help to combat colon cancer, while others could help treat or prevent infections such as C. difficile.

One of the obstacles to developing these "living biotherapeutics" is that many of the species that could be beneficial are harmed by oxygen, making it difficult to manufacture, store, and deliver them. Chemical engineers have now shown that they can protect those bacteria with a coating that helps them to survive the manufacturing process.

In a study appearing today in the Journal of the American Chemical Society, the researchers showed they could use the coating on a strain of E. coli as well as another species that may aid in digestion of plant starches. The coating could be applied to many other species as well, they say. They think this coating could be used to protect pretty much any microbe of interest.

Most of the microbes that live in the human gut are anaerobic, and they have varying degrees of sensitivity to oxygen. Some can tolerate a little bit of oxygen, while for others, oxygen is deadly.

This makes it difficult to test their potential as treatments for human disease, because bacteria need to be freeze-dried and formulated as capsules in order to be used therapeutically. In this study, researchers decided to try protecting anaerobic bacteria by coating them with a material made from metal ions and organic compounds called polyphenols.

When polyphenols and metal ions are put into a solution, they form a two-dimensional, grid-like sheet. For this study, the researchers used iron, which is safe for human consumption, and three polyphenols that are all classified as GRAS (generally regarded as safe) : gallic acid, tannic acid, and epigallocatechin (EGCG), all of which are found in tea and other plant products.

If bacteria are also added to the solution, the material self-assembles into a coating on individual bacterial cells. This coating protects bacteria during the freeze-drying and manufacturing process. The researchers showed that the coated cells were healthy and able to perform normal cellular activities, although their growth was temporarily inhibited.

When exposed to an acidic environment, such as that of the stomach, the coating breaks down and releases the bacteria. Coating the bacteria with a protective layer could eliminate the need for cold storage and make distribution easier. This would make a lot of therapeutics more widely available.

Gang Fan et al, Protection of Anaerobic Microbes from Processing Stressors Using Metal–Phenolic Networks, Journal of the American Chemical Society (2021). DOI: 10.1021/jacs.1c09018

https://phys.org/news/2021-12-biotherapeutics.html?utm_source=nwlet...

Comment by Dr. Krishna Kumari Challa on December 11, 2021 at 9:09am

To edit even larger sequences, the researchers used their twin prime editing system to install "landing sites" in the genome for enzymes called site-specific recombinases, which catalyze the integration of DNA at specific sites in the genome. The team then treated the cells with a recombinase enzyme and introduced the long pieces of DNA they wanted to insert into the genome. Combining twinPE and recombinase enzymes allowed the scientists to edit sequences thousands of base pairs long—the length of entire genes.

 Andrew V. Anzalone et al, Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing, Nature Biotechnology (2021). DOI: 10.1038/s41587-021-01133-w

https://phys.org/news/2021-12-prime-inserts-entire-genes-human.html...

Comment by Dr. Krishna Kumari Challa on December 11, 2021 at 9:08am

New prime editing system inserts entire genes in human cells

Researchers  have developed a new version of prime editing that can install or swap out gene-sized DNA sequences. First developed in 2019, prime editing is a precise method of making a wide diversity of gene edits in human cells, including small substitutions, insertions, and deletions.

In a study published recently in Nature Biotechnology, the team describes twin prime editing (twinPE), a technique that makes two adjacent prime edits to introduce larger sequences of DNA at specific locations in the genome with few unwanted byproducts. With further development, the technology could potentially be used as a new form of gene therapy to insert therapeutic genes in a safe and highly targeted manner to replace mutated or missing genes.

The researchers demonstrated the therapeutic potential of twinPE by editing, in human cells, a gene linked to Hunter syndrome, a rare genetic disorder. This disease is caused by an inversion of a specific 40,000 base pair long stretch of DNA. The team used twinPE to introduce an inversion of a similar length at the same site in the genome, showing how the method could be used to correct the disease-causing mutation. The team also used twin PE to precisely insert gene-sized DNA cargo of thousands of base pairs into therapeutically relevant sites in the genome.

The approach addresses a limitation of the original prime editing system, which can edit only several dozen base pairs. However, the study or treatment of some genetic diseases could require larger edits. Like the original prime editing method, twinPE also does not completely sever the DNA double helix by cutting both strands simultaneously at the same location, which can induce poorly controlled editing outcomes and harmful chromosomal abnormalities.

TwinPE could be a potentially safer and more precise way to insert whole genes of therapeutic interest into positions we specify, such as the location of the native gene in healthy individuals or 'safe harbor' sites thought to minimize the risk of side-effects.

Prime editing, developed by Liu's lab, enables DNA substitutions, insertions, and deletions, and promises to correct the majority of known disease-causing genetic variations. Recent improvements to prime editing technology increased its efficiency, edging it closer to therapeutic applications. But editing sequences longer than 100 base pairs remained inefficient.

Twin prime editing fills this gap. The system uses a prime editor protein and two prime editing guide RNAs, which guide the editing machinery and encode the edits. Each of the two guide RNAs direct the editing protein to make a single-stranded nick in the DNA at different targeted sites in the genome, avoiding the kind of double-strand break that creates unwanted byproducts in other methods. The system then synthesizes two new complementary DNA strands containing the desired sequence in between the two nicks. Using this approach, the researchers were able to insert, substitute, or delete sequences up to about 800 base pairs long.

Part 1

Comment by Dr. Krishna Kumari Challa on December 10, 2021 at 12:53pm

Why global tech turns to Indian talent

Twitter's new CEO Parag Agrawal is the latest alumnus of India's prestigious technical universities appointed to head a multi-billion-dollar US tech firm.

Google-parent Alphabet's 49-year-old CEO Sundar Pichai. Other Indians at the highest corporate tech echelons include IBM's Arvind Krishna and Palo Alto Networks' Nikesh Arora—both IIT alumni—along with Satya Nadella of Microsoft and Shantanu Narayen at Adobe.

If you ask why Indians are succeeding like hell, here is what the experts say:

beyond the South Asian nation's sheer size, the phenomenon is due to multiple push-pull factors and skillsets including a culture of problem-solving, the English language, and relentless hard work. 

after growing up with multiple communities, customs and languages, Indians have the ability to "navigate complex situations".

"Educational competition in India and societal chaos helps hone their skills in addition to the rigorous technical education at the IITs.

Silicon Valley demands technical expertise, managing diverse communities, and entrepreneurship in the face of uncertainty from its top executives.

"In innovation, you have to be able to break the rules, you're fearless. And... you can't survive a day in India without having to break one rule or the other or dealing with incompetent bureaucracy or corruption. Those skills are very useful when you're innovating in Silicon Valley, because you have to constantly challenge authority. The contest for such prizes begins early in a country of more than 1.3 billion people with a longstanding focus on education.

Agrawal, Pichai and Nadella spent a decade or more working their way through the ranks of their respective companies, building up insider knowledge while gaining the trust of the firms' American founders.

And for years, more than half the applicants for US H1-B skilled immigrant visas have been from India, and mostly from the tech sector.

The phenomenon may wane in time as India's own tech sector thrives, offering the country's best and brightest minds greater domestic opportunities.

https://techxplore.com/news/2021-12-global-tech-indian-talent.html?...

Comment by Dr. Krishna Kumari Challa on December 10, 2021 at 12:42pm

Scientists solve the grass leaf conundrum

Grass is cut regularly by our mowers and grazed on by cows and sheep, yet continues to grow back. The secret to its remarkable regenerative powers lies in part in the shape of its leaves, but how that shape arises has been a topic of longstanding debate. 

The debate is relevant to our staple crops wheat, rice and maize, because they are members of the grass family with the same type of leaf.

The mystery of grass leaf formation has now been unraveled by a research team.

Flowering plants can be categorized into monocots and eudicots. Monocots, which include the grass family, have leaves that encircle the stem at their base and have parallel veins throughout. Eudicots, which include brassicas, legumes and most common garden shrubs and trees, have leaves that are held away from the stem by stalks, termed petioles, and typically have broad laminas with net-like veins.

In grasses, the base of the leaf forms a tube-like structure, called the sheath. The sheath allows the plant to increase in height while keeping its growing tip close to the ground, protecting it from the blades of lawnmowers or incisors of herbivores. Using recent advances in computational modeling and developmental genetics, the team revisited the problem of grass development. They modeled different hypotheses for how grass leaves grow, and tested the predictions of each model against experimental results. To their surprise, they found that the model based on the 19^th century idea of sheath-petiole equivalence was much more strongly supported than the current view.

The grass study shows how simple modulations of growth rules, based on a common pattern of gene activities, can generate a remarkable diversity of different leaf shapes, without which our gardens and dining tables would be much poorer.

Annis Richardson et al, Evolution of the grass leaf by primordium extension and petiole-lamina remodeling, Science (2021). DOI: 10.1126/science.abf9407. www.science.org/doi/10.1126/science.abf9407

https://phys.org/news/2021-12-scientists-grass-leaf-conundrum.html?...

Comment by Dr. Krishna Kumari Challa on December 9, 2021 at 11:57am

Engineers build in-pipe sewer robot

Scientists from the Division of Mechanical Science and Engineering at Kanazawa University developed a prototype pipe maintenance robot that can unclog and repair pipes with a wide range of diameters. Using a cutting tool with multiple degrees of freedom, the machine is capable of manipulating and dissecting objects for removal. This work may be a significant step forward for the field of sewerage maintenance robots.

Various sewer pipes that are essential to the services of buildings require regular inspection, repair, and maintenance. Current robots that move inside pipes are primarily designed only for visual surveying or inspection. Some robots were developed for maintenance, but they couldn't execute complicated tasks. In-pipe robots that can also clear blockages or perform complex maintenance tasks are highly desirable, especially for pipes that are too narrow for humans to traverse. Now, a team of researchers at Kanazawa University have developed and tested a prototype with these capabilities. 

This robot can help civic and industrial workers by making their job much safer. It can operate in small pipes that humans either cannot access or are dangerous.

Thaelasutt Tugeumwolachot et al, Development of a compact sewerage robot with multi-DOF cutting tool, Artificial Life and Robotics (2021). DOI: 10.1007/s10015-021-00694-y

https://techxplore.com/news/2021-12-in-pipe-sewer-robot.html?utm_so...

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Comment by Dr. Krishna Kumari Challa on December 9, 2021 at 11:54am

A new view of the Universe

Comment by Dr. Krishna Kumari Challa on December 9, 2021 at 11:04am

Plants buy us time to slow climate change—but not enough to stop it

Plants take up carbon dioxide from the atmosphere and convert it into food, forests and other similar ecosystems are considered to be some of the planet's most important carbon sinks.

As human activities cause more carbon dioxide to be emitted into the atmosphere, scientists have debated whether plants are responding by photosynthesizing more and sucking up even more carbon dioxide than they already do—and if so, is it a little or a lot more. Now an international team of researchers led by Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley have used a novel methodology combining remote sensing, machine learning, and terrestrial biosphere models to find that plants are indeed photosynthesizing more, to the tune of 12% higher global photosynthesis from 1982 to 2020. In that same time period, global carbon dioxide concentrations in the atmosphere grew about 17%, from 360 parts per million (ppm) to 420 ppm.

The 12% increase in photosynthesis translates to 14 petagrams of additional carbon taken out of the atmosphere by plants each year, roughly the equivalent of the carbon emitted worldwide from burning fossil fuels in 2020 alone. Not all of the carbon taken out of the atmosphere through photosynthesis is stored in ecosystems, as much is later released back to the atmosphere through respiration, but the study reports a direct link between the increased photosynthesis and increased global carbon storage. The study was published in Nature.

This is a very large increase in photosynthesis, but it's nowhere close to removing the amount of carbon dioxide we're putting into the atmosphere. It's not stopping climate change by any means, but it is helping us slow it down.

Trevor Keenan, A constraint on historic growth in global photosynthesis due to rising CO2 (N&V), Nature (2021). DOI: 10.1038/s41586-021-04096-9. www.nature.com/articles/s41586-021-04096-9

https://phys.org/news/2021-12-climate-changebut.html?utm_source=nwl...

Comment by Dr. Krishna Kumari Challa on December 9, 2021 at 10:55am

Removing a single protein, clusterin, from marathoner mice's plasma largely negated its anti-inflammatory effect on sedentary mice's brains. No other protein the scientists similarly tested had the same effect.

Clusterin, an inhibitor of the complement cascade, was significantly more abundant in the marathoners' blood than in the couch potatoes' blood.

Further experiments showed that clusterin binds to receptors that abound on brain endothelial cells, the cells that line the blood vessels of the brain. These cells are inflamed in the majority of Alzheimer's patients

Research has shown that blood endothelial cells are capable of transducing chemical signals from circulating blood, including inflammatory signals, into the brain.

Tony Wyss-Coray, Exercise plasma boosts memory and dampens brain inflammation via clusterin, Nature (2021). DOI: 10.1038/s41586-021-04183-x. www.nature.com/articles/s41586-021-04183-x

https://medicalxpress.com/news/2021-12-blood-marathoner-mice-boosts...

Part 2

Comment by Dr. Krishna Kumari Challa on December 9, 2021 at 10:54am

Blood from marathoner mice boosts brain function in their couch-potato counterparts

Physical exercise is great for a mouse's brain, and for yours. Numerous studies conducted in mice, humans and laboratory glassware have made this clear. Now, a new study shows it's possible to transfer the brain benefits enjoyed by marathon-running mice to their couch-potato peers.

Researchers have shown that blood from young adult mice that are getting lots of exercise benefits the brains of same-aged, sedentary mice. A single protein in the blood of exercising mice seems largely responsible for that benefit.

The discovery could open the door to treatments that—by taming brain inflammation in people who don't get much exercise—lower their risk of neurodegenerative disease or slow its progression.

Researchers compared blood samples from exercising and sedentary mice of the same age. They showed that transfusions of blood from running mice reduced neuroinflammation in the sedentary mice and improved their cognitive performance. In addition, the researchers isolated a blood-borne protein that appears to play an important role in the anti-neuroinflammatory exercise effect.

Neuroinflammation has been strongly tied to neurodegenerative diseases in humans.  Animal studies have indicated that neuroinflammation precipitates neurodegenerative disorders and that reversing or reducing neuroinflammation can prolong cognitive health

part1

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