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Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 10:44am

Targeting 'undruggable' diseases: Researchers reveal new levels of detail in targeted protein degradation

Researchers  have revealed in the greatest detail yet the workings of molecules called protein degraders which can be deployed to combat what have previously been regarded as "undruggable" diseases, including cancers and neurodegenerative diseases.

Protein degrader molecules are heralding a revolution in drug discovery, with more than 50 drugs of this type currently being tested in clinical trials for patients with diseases for which no other options exist.

Now researchers have revealed previously invisible levels of detail and understanding of how the protein degraders work, which in turn is allowing for even more targeted use of them at the molecular level.

They used a technique called cryo-electron microscopy (cryo-EM), which enables scientists to see how biomolecules move and interact with each other.

This works by flash-freezing proteins and using a focused electron beam and a high-resolution camera to generate millions of 2D images of the protein. They then used sophisticated software and artificial intelligence (AI) models which allowed them to generate 3D snapshots of the degrader drugs working in action.

Their latest research is published in the journal Science Advances and is expected to constitute a landmark contribution to research in the field of TPD and ubiquitin mechanisms.

They  have reached a level of detail where they can see how these protein degraders work and can be deployed to recruit the disease-causing protein  and target the 'bull's eye,' in molecular terms.

Part 1

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 10:32am

Scientists discover how innate immunity envelops bacteria and destroy them

The protein GBP1 is a vital component of our body's natural defense against pathogens. This substance fights against bacteria and parasites by enveloping them in a protein coat, but how the substance manages to do this has remained unknown until now.

Researchers  have now unraveled how this protein operates. This new knowledge, published in Nature Structural & Molecular Biology, could aid in the development of medications and therapies for individuals with weakened immune systems.

Guanylate Binding Proteins (GBPs) play a crucial role in our innate immune system. GBPs form the first line of defense against various infectious diseases caused by bacteria and parasites. Examples of such diseases include dysentery, typhoid fever caused by Salmonella bacteria, and tuberculosis. The protein also plays a significant role in the sexually transmitted infection chlamydia as well as in toxoplasmosis, which is particularly dangerous during pregnancy and for unborn children. 

In their publication,  researchers describe for the first time how the innate immune system fights against bacteria using GBP1 proteins.

The protein surrounds bacteria by forming a sort of coat around them. By pulling this coat tighter, it breaks the membrane of the bacteria—the protective layer surrounding the intruder—after which immune cells can clear the infection.

To decode the defense strategy of GBPs, the researchers examined how GBP1 proteins bind to bacterial membranes using a cryogenic electron microscope. This allowed them to see the process in great detail down to the scale of molecules.

 Tanja Kuhm et al, Structural basis of antimicrobial membrane coat assembly by human GBP1, Nature Structural & Molecular Biology (2024). DOI: 10.1038/s41594-024-01400-9

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 9:45am

The level of contamination they studied is on par with a soil contaminated with microplastics. Contaminated soils have been found to have up to approximately 100,000 mg per kg of microplastics with most soils below 10,000 mg per kg.

In comparison to conventional glitter, there were no toxic effects on springtail reproduction at any concentration of the cellulose glitter.

So, although it's promising that neither type of glitter was directly harmful to the springtails, it's worrying that the conventional glitter affected their ability to reproduce.

Fewer springtails being born can weaken their population, which might lead to bigger problems for soil health like less organic matter breaking down and fewer nutrients being released for plants.

The researchers suggest you think twice before using conventional glitter in make-up, clothing or for arts and crafts, but are hopeful that peope will soon be able to buy a safer, more sustainable and just as sparkly alternative.

Po-Hao Chen et al, Assessing the ecotoxicological effects of novel cellulose nanocrystalline glitter compared to conventional polyethylene terephthalate glitter: Toxicity to springtails (Folsomia candida), Chemosphere (2024). DOI: 10.1016/j.chemosphere.2024.143315

Part 4

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Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 9:44am

They have created a novel nanocrystal made from cellulose that sparkles in light and is biodegradable. Cellulose is made from glucose and is the component that gives tree wood its strength.

They wanted to compare the potential toxicity of conventional glitter with the new cellulose glitter as part of testing how sustainable the new glitter is.

They used a little soil critter called a springtail (Folsomia candida). Springtails are small, white, eyeless invertebrates that are closely related to insects. They are widespread in soils around the world where they feed on leaf litter and compost.

These critters are used as an indicator of soil quality and, because they are sensitive to toxic compounds, are often used to test for potential pollutants.

Using soil from the University of Melbourne's Dookie campus, the researchers exposed the springtails to different concentrations of conventional and cellulose glitter and studied the impact on their reproduction, survival and growth.

They found that neither glitter impacted springtail survival or size. However, once the concentrations of conventional glitter in the soil reached 1,000 mg of glitter per kg of soil, the reproduction of the springtails was reduced by 61%.
Part 3

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 9:43am

In 2023, the European Union officially banned the sale of loose plastic glitter and some other products that contain microbeads, in a bid to cut environmentally harmful microplastic pollution in member nations by 30% by 2030.
One study in New South Wales, Australia, found that 24% of the microplastics in sewage sludge were glitter.
Once glitter gets into the environment, it is difficult to remove because of its tiny size and because it can become transparent over time on losing the metal components.

While biodegradable glitter is already commercially available, previous research indicates these products could be just as harmful or even more toxic to aquatic organisms than conventional PET glitter because most biodegradable varieties on the market need to be coated in a colored aluminum layer and topped with a thin plastic layer.

Part of a research team, based at the University of Cambridge, has been working on making more sustainable glitter. The study is published in the journal Chemosphere.

Part 2

Comment by Dr. Krishna Kumari Challa on October 12, 2024 at 9:41am

New plant-based glitter shows no harm to soil organisms

Plastic pollution is everywhere. Each year, over 368 million metric tons of plastics are produced with over 13 million metric tons of it ending up in the soil where it can be toxic to wildlife.

Researchers are particularly worried about the environmental impacts of 'microplastics' which are small plastic particles less than 5 mm in size.

Microplastics can be produced from products like glitter or when larger objects, including water bottles, break down into smaller and smaller pieces once they're in the environment.

Due to their small size, animals can eat microplastics, mistaking them for food, which can cause starvation and malnutrition as well as abrasions to the gastrointestinal tract.
A lot of research has shown microplastics are toxic to ocean species but far fewer studies have investigated the impacts of microplastics on land-dwelling species. This is despite annual plastic release onto the land being estimated at over four times the level that enters the oceans.

Glitter is a type of microplastic used in cosmetics, clothing or for decorative purposes.

Most glitter is made of a plastic called polyethylene terephthalate which you probably know as PET. It's the same plastic that is used for bottled water and soft drink containers.

Conventional glitter also often contains aluminum or other metals, which is where the sparkle comes from.

It is not known how much glitter is getting into the environment, but anyone who has ever worn glitter make-up or used glitter in art and craft knows it seems to end up everywhere.

Part 1

Comment by Dr. Krishna Kumari Challa on October 11, 2024 at 11:09am

The new fashion: Clothes that help combat rising temperatures

A team of international researchers has developed a natural fabric that urban residents could wear to counter rising temperatures in cities worldwide, caused by buildings, asphalt, and concrete.

As heat waves become more prominent, cooling textiles that can be incorporated into clothes, hats, shoes and even building surfaces provide a glimpse into a future where greenhouse gas-emitting air conditioners may no longer be needed in our cities.

Engineers  say the wearable fabric is designed to reflect sunlight and allow heat to escape, while blocking the sun's rays and lowering the temperature. They have described the textiles in Science Bulletin.

The fabric promises to bring relief to millions of city dwellers experiencing warmer and more uncomfortable temperatures caused by global climate change and fewer green spaces.

 The fabric leverages the principle of radiative cooling, a natural process where materials emit heat into the atmosphere, and ultimately into space.

Unlike conventional fabrics that retain heat, these textiles are made of three layers that are engineered to optimize cooling. 

The upper layer, made of polymethyl pentene fibers, allows heat to radiate effectively. The middle layer, composed of silver nanowires, enhances the fabric's reflectivity, preventing additional heat from reaching the body. The bottom layer, made of wool, directs heat away from the skin, ensuring that wearers remain cool, even in the hottest urban environments.

In the experiments conducted, when placed vertically, the fabric was found to be 2.3°C cooler than traditional textiles, and up to 6.2°C cooler than the surrounding environment when used as a horizontal surface covering.

The fabric's ability to passively reduce temperatures offers a sustainable alternative to conventional air conditioning, providing energy savings and reducing the strain on power grids during heat waves.

It is hoped the technology could be adapted for even broader applications, including construction materials, outdoor furniture and urban planning.

While the fabric holds significant promise, researchers say the current production process is costly, and the long-term durability of the textiles needs further investigation and government support before it can be commercialized.

Xianhu Liu et al, Radiation cooling textiles countering urban heat islands, Science Bulletin (2024). DOI: 10.1016/j.scib.2024.09.008

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Comment by Dr. Krishna Kumari Challa on October 11, 2024 at 10:56am

Comment by Dr. Krishna Kumari Challa on October 11, 2024 at 10:33am

Personal care products affect indoor air quality

The personal care products we use on a daily basis significantly affect indoor air quality, according to new research.

When used indoors, these products release a cocktail of more than 200 volatile organic compounds (VOCs) into the air, and when those VOCs come into contact with ozone, the chemical reactions that follow can produce new compounds and particles that may penetrate deep into our lungs. Scientists are now wondering how inhaling these particles on a daily basis affects our respiratory health.

These products are roll-on deodorant, spray deodorant, hand lotion, perfume and dry shampoo hair spray—all produced by leading brands and available in major stores across the world. 

During their experiments, in one test, the researchers applied the products under typical conditions, while the air quality was carefully monitored. In another test, they did the same thing but also injected ozone, a reactive outdoor gas that occurs in some latitudes during the summer months.

Ozone can infiltrate homes through open windows, but can also come from indoors, for example, when using laser printers and 3D printers. Around five sophisticated measuring instruments were deployed to quantify and identify the gases and particles present in the chamber.

It took the scientists two years to process all the collected data. In the first case without ozone, over 200 VOCs were emitted from the personal care products, which gradually dissipated with ventilation. The most abundant molecules they found were ethanol and monoterpenes, typically used in these products. However, when ozone was introduced into the chamber, not only new VOCs but also new particles were generated, particularly from perfume and sprays, exceeding concentrations found in heavily polluted urban areas.

Some molecules 'nucleate'—in other words, they form new particles that can coagulate into larger ultrafine particles that can effectively deposit into our lungs.

We still don't fully understand the health effects of these pollutants, but they may be more harmful than we think, especially because they are applied close to our breathing zone. This is an area where new toxicological studies are needed, say the researchers.

To limit the effect of personal care products on indoor air air quality, we could consider several alternatives for how buildings are engineered: introducing more ventilation—especially during the products' use—incorporating air-cleaning devices (e.g., activated carbon-based filters combined with media filters), and limiting the concentration of indoor ozone.

The researchers stress that we're going to have to reduce our reliance on these products, or if possible, replace them with more natural alternatives that contain fragrant compounds with low chemical reactivity. Another helpful measure would be to raise awareness of these issues among medical professionals and staff working with vulnerable groups, such as children and the elderly.

Tianren Wu et al, Indoor Emission, Oxidation, and New Particle Formation of Personal Care Product Related Volatile Organic Compounds, Environmental Science & Technology Letters (2024). DOI: 10.1021/acs.estlett.4c00353

Comment by Dr. Krishna Kumari Challa on October 11, 2024 at 10:07am

Microscopic marine organisms can create parachute-like mucus structures that stall CO₂ absorption from atmosphere

New research unveils a hidden factor that could change our understanding of how oceans mitigate climate change. The study, published Oct. 11 in Science, reveals never-before seen mucus "parachutes" produced by microscopic marine organisms that significantly slow their sinking, putting the brakes on a process crucial for removing carbon dioxide from the atmosphere.

The surprising discovery implies that previous estimates of the ocean's carbon sequestration potential may have been overestimated, but also paves the way toward improving climate models and informing policymakers in their efforts to slow climate change.

Rahul Chajwa et al, Hidden comet tails of marine snow impede ocean-based carbon sequestration, Science (2024). DOI: 10.1126/science.adl5767. www.science.org/doi/10.1126/science.adl5767

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