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Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 11:09am

Scientists discover a new set of cells that control the blood-brain barrier

Researchers have discovered a new set of cells that can protect blood vessel structure in the central nervous system (CNS) known as the blood-brain barrier. Their findings have been published in the journal Science Advances.

They identified a new set of astrocytes (type of brain cells) that can control the integrity of the blood-brain barrier.

The blood-brain barrier (BBB) is a selective semi-permeable membrane between the blood and the interstitium of the brain, allowing cerebral blood vessels to regulate molecule and ion movement between the blood and the brain.

With age, or in brain disorders, the function of the blood-brain barrier is reduced.

This newly discovered subset of astrocytes expressed a protein found in bone tissue called dentin matrix protein 1 (DMP-1). These cells generate 'endfeet' and transfer mitochondria (energy generating cells) to endothelial cells which line the blood vessels of the CNS.

Reduction in the function of these astrocytes inhibited mitochondrial transfer and caused leakage of the blood-brain barrier. Mitochondrial transfer from astrocytes to blood vessel cells was identified as crucial to the maintenance of the blood-brain barrier.

Delin Liu et al, Regulation of blood-brain barrier integrity by Dmp1 -expressing astrocytes through mitochondrial transfer, Science Advances (2024). DOI: 10.1126/sciadv.adk2913

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 8:59am

Researchers decided to investigate how the protein functioned in mice, which retain brown fat throughout their lives. They found that KLF-15 was much less abundant in white fat cells than in brown or beige fat cells.

When they then bred mice with white fat cells that lacked KLF-15, the mice converted them from white to beige. Not only could the fat cells switch from one form into another, but without the protein, the default setting appeared to be beige.

The researchers then looked at how KLF-15 exerts this influence. They cultured human fat cells and found that the protein controls the abundance of a receptor called Adrb1, which helps maintain energy balance.

Scientists knew that stimulating a related receptor, Adrb3, caused mice to lose weight. But human trials of drugs that act on this receptor have had disappointing results.
A different drug targeting the Adrb1 receptor in humans is more likely to work, according to Feldman, and it could have significant advantages over the new, injectable weight-loss drugs that are aimed at suppressing appetite and blood sugar.

This approach might avoid side effects like nausea because its activity would be limited to fat deposits, rather than affecting the brain. And the effects would be long lasting, because fat cells are relatively long-lived.
These discoveries could have a big impact on treating obesity.

Source: Journal of Clinical Investigation (2024)

https://www.jci.org/articles/view/172360

Part 2 

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 8:55am

Scientists turn white fat cells into calorie-burning beige fat

A new study shows that suppressing a protein turns ordinary fat into a calorie burner and may explain why drug trials attempting the feat haven't been successful.

Researchers  have figured out how to turn ordinary white fat cells, which store calories, into beige fat cells that burn calories to maintain body temperature.

The discovery could open the door to developing a new class of weight-loss drugs and may explain why clinical trials of related therapies have not been successful.

Until now, researchers thought creating beige fat might require starting from stem cells. The new study published July 1 in the Journal of Clinical Investigation, showed that ordinary white fat cells can be converted into beige fat simply by limiting production of a protein.

Many mammals have three "shades" of fat cells: white, brown and beige. White fat serves as energy reserves for the body, while brown fat cells burn energy to release heat, which helps maintain body temperature.

Beige fat cells combine these characteristics. They burn energy, and unlike brown fat cells, which grow in clusters, beige fat cells are embedded throughout white  fat deposits.

Humans and many other mammals are born with brown fat deposits that help them maintain body temperature after birth. But, while a human baby's brown fat disappears in the first year of life, beige fat persists.

Humans can naturally turn white fat cells into beige ones in response to diet or a cold environment. Scientists tried to mimic this by coaxing stem cells into becoming mature beige fat cells.

But stem cells are rare, and the researchers wanted to find a switch he could flip to turn white fat cells directly into beige ones. They knew a protein called KLF-15 plays a role in metabolism and the function of fat cells.

Part 1

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 8:46am

Among the targets unique to bacteria are various protein functions and also the bacterial cell wall is considered a suitable target, as it is very different from the human cell wall.

The uncharacterized PA3040-3042 operon is part of the cell envelope stress response and a tobramycin resistance determinant in a clinical isolate of Pseudomonas aeruginosa", Microbiology Spectrum (2024). DOI: 10.1128/spectrum.03875-23. journals.asm.org/doi/10.1128/spectrum.03875-23

Part 2

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 8:46am

Researchers thwart resistant bacteria's strategy

Antibiotic resistant bacteria are experts in evolving new strategies to avoid being killed by antibiotics. One such bacterium is Pseudomonas aeruginosa, which is naturally found in soil and water, but also hospitals, nursing homes and similar institutions for persons with weakened immune systems are home for strains of this bacterium.

As many P. aeruginosa strains found in hospitals are resistant to most antibiotics in use, science is forced to constantly search for new ways to kill them.

Now, a team of researchers has discovered a weakness in P. aeruginosa with the potential to become the target for a new way to attack it.

The team discovered a mechanism, that reduces the formation of biofilm on the surface of P. aeruginosa. The formation of sticky, slimy biofilm is a powerful tool used by bacteria to protect themselves against antibiotics—a trick also used by P. aeruginosa.

This biofilm can be so thick and gooey that antibiotic cannot penetrate the cell surface and reach its target inside the cell. 

The researchers now worked with three newly discovered genes in a lab-grown strain of P. aeruginosa. When they overexpressed these genes, they saw a strong reduction of biofilm. Of significance is that the system affected by the genes is part of the P. aeruginosa core genome, meaning that it is universally found in all the P. aeruginosa strains sequenced so far.

Being part of P. aeruginosa's core genome, this system has been found in all investigated strains of P. aeruginosa, including a large variety of strains isolated from patients. So, there is reason to think that reduction of biofilm via this system should be effective in all known strains of P. aeruginosa.

Bacteria strains can evolve individually and mutate quickly and constantly when they are under pressure. It is not uncommon for patients infected with a P. aeruginosa strain to initially respond well to antibiotic treatment but then become resistant as the strain evolves resistance during treatment. Strains mutate, but their common core genome does not change.

In their experiments, the researchers activated the biofilm reducing system by overexpressing genes. But they also discovered that the system is naturally stimulated by cell wall stress.

So, if we stress the cell wall, it may naturally lead to a reduction in biofilm, making it easier for antibiotic to penetrate the cell wall, Currently, cell wall-targeted drugs are not widely used against P. aeruginosa, but perhaps, they could start to be used as additives to help reduce biofilm production and improve access of the existing antibiotics to the cells.

When combating infectious bacteria, there are only a limited number of targets to attack. Targets found in both bacterial and human cells cannot be attacked, as the antibiotics would also affect human cells.

Bacterial cells and human cells have some targets in common, such as the process that replicates DNA and the processes controlling basic glucose metabolism or respiration in cells.

Part 1

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 8:37am

AI model finds the cancer clues at lightning speed

have developed an AI model that increases the potential for detecting cancer through sugar analyses. The AI model is faster and better at finding abnormalities than the current semi-manual method.

Glycans, or structures of sugar molecules in our cells, can be measured by mass spectrometry. One important use is that the structures can indicate different forms of cancer in the cells.

However, the data from the mass spectrometer measurement must be carefully analyzed by humans to work out the structure from the glycan fragmentation. This process can take anywhere from hours to days for each sample and can only be carried out with high confidence by a small number of experts in the world, as it is essentially detective work learned over many years.

The process is thus a bottleneck in the use of glycan analyses, for example for cancer detection, when there are many samples to be analyzed.

Researchers  have developed an AI model to automate this detective work. The AI model, named Candycrunch, solves the task in just a few seconds per test. The results are reported in a scientific article in the journal Nature Methods.

The AI model was trained using a database of over 500,000 examples of different fragmentations and associated structures of sugar molecules. The training has enabled Candycrunch to calculate the exact sugar structure in a sample in 90% of cases.

Predicting glycan structure from tandem mass spectrometry via deep learning, Nature Methods (2024). DOI: 10.1038/s41592-024-02314-6

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 8:27am

Nanorobot kills cancer cells in mice with hidden weapon

Researchers have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is exposed only in the tumor microenvironment, sparing healthy cells. The study is published in the journal Nature Nanotechnology.

The research group has previously developed structures that can organize so-called death receptors on the surface of cells, leading to cell death. The structures exhibit six peptides (amino acid chains) assembled in a hexagonal pattern. "This hexagonal nanopattern of peptides becomes a lethal weapon".

If you were to administer it as a drug, it would indiscriminately start killing cells in the body, which would not be good. To get around this problem, the researchers have hidden the weapon inside a nanostructure built from DNA.

The art of building nanoscale structures using DNA as a building material is called DNA origami and is something the research team has been working on for many years. Now they have used the technique to create a 'kill switch' that is activated under the right conditions.

They have managed to hide the weapon in such a way that it can only be exposed in the environment found in and around a solid tumor. This means that they have created a type of nanorobot that can specifically target and kill cancer cells.

The key is the low pH, or acidic microenvironment that usually surrounds cancer cells, which activates the nanorobot's weapon. In cell analyses in test tubes, the researchers were able to show that the peptide weapon is hidden inside the nanostructure at a normal pH of 7.4, but that it has a drastic cell-killing effect when the pH drops to 6.5.

They then tested injecting the nanorobot into mice with breast cancer tumors. This resulted in a 70 percent reduction in tumor growth compared to mice given an inactive version of the nanorobot.

They now need to investigate whether this works in more advanced cancer models that more closely resemble the real human disease.

The researchers also plan to investigate whether it is possible to make the nanorobot more targeted by placing proteins or peptides on its surface that specifically bind to certain types of cancer.

A DNA Robotic Switch with Regulated Autonomous Display of Cytotoxic Ligand Nanopatterns, Nature Nanotechnology (2024). DOI: 10.1038/s41565-024-01676-4 , www.nature.com/articles/s41565-024-01676-4

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 8:14am

Scientists developing a monoclonal antibody to neutralize Nipah virus one of the deadliest zoonotic pathogens

Nipah virus is a highly pathogenic zoonotic paramyxovirus causing regular outbreaks in humans and animals in South and Southeast Asia.

Just like Ebolavirus, SARS, SARS-CoV-2, and Marburg virus, the Nipah pathogen originated in bats. The name Nipah is derived from the name of the Malaysian village where pig farmers were infected in the late 1990s. Measles virus, although not of bat origin, is another member of the paramyxovirus family and stands out as one of the most contagious viruses known to science. While Nipah is less contagious than measles, it is capable of much higher mortality.

No licensed vaccines or therapies exist for patients infected with Nipah virus.

People infected with Nipah virus can be afflicted with dangerous respiratory impairment and brain swelling, symptoms that fuel the extraordinary fatality rates. Mortality ranges from a low of 40% to a high of 90%. The virus has been responsible for several relatively recent outbreaks in Bangladesh and India.

An experimental monoclonal antibody has now been engineered to target the deadly Nipah virus, an emerging zoonotic pathogen with a human mortality rate ranging as high as a staggering 90%.

Urgency underlies the development of therapeutics against a wide range of zoonotic viruses. The emerging pathogens have the potential to spur pandemics—or fall into the hands of malevolent forces that may use them for purposes of bioterrorism.

 Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, modify or mimic the immune system's attack on cells that aren't wanted.

 Researchers hypothesized that a mAb (monoclonal antibody) against the prefusion conformation of the F glycoprotein may confer better protection than m102.4. To test this, two potent neutralizing mAbs against the Nipah virus F protein, hu1F5 and hu12B2, were compared in a hamster model. Hu1F5 provided superior protection to hu12B2 and was selected for comparison with m102.

In hamsters, the team found that administering hu1F5 one day after infection in hamsters led to 100% survival. It's important to note that hu1F5 also protected African green monkeys from Nipah virus even when given as late as five days after infection. In that arm of the research, all six infected animals survived. Hu1F5 also outperformed the earlier monoclonal antibody, m102.4, which protected only one out of six treated animals from death.

The team also introduced several mutations into the antibody to extend its half-life and reported that the monoclonal antibody that had superior performance in animal testing is progressing toward a phase 1 human clinical trial.

Larry Zeitlin et al, Therapeutic administration of a cross-reactive mAb targeting the fusion glycoprotein of Nipah virus protects nonhuman primates, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adl2055

Comment by Dr. Krishna Kumari Challa on July 1, 2024 at 9:25am

Without science is old really gold?

People argue that old is gold. "Oh, those old golden days!" They become nostalgic very often. 

But what type of gold is it? Without science?  

A new discovery of 33 ancient tombs in Egypt's southern city of Aswan  revealed "new information on diseases" prevalent at the time and how much people suffered in ancient times.

The tombs date back to the Ancient Egyptian Late Period and the Greco-Roman Periods, which collectively lasted from the seventh century BC until around the fourth century AD.

The burials were found by a joint Egyptian-Italian archaeological mission.

The studies of the mummies "indicate that 30 to 40 percent of those buried died in their youth, as newborns or as adolescents".

Preliminary studies on the remains showed that "some suffered from infectious diseases, while others had bone disorders".

The remains of several adult women showed signs of pelvic bone trauma.

Other mummies indicated "anemia, malnutrition, chest diseases, tuberculosis and signs of osteoporosis".

And there was no 'right treatment' as there was no 'science', the   pursuit and application of knowledge and understanding of the natural and social world following a systematic methodology based on evidence. 

People tried a few things based on their imagination and primitive understanding of things and people still suffered and died young.  

"Golden days"?

Source: News agencies and Science Art Lab.

Comment by Dr. Krishna Kumari Challa on June 29, 2024 at 11:52am

Pillars of Creation Star in New Visualization from NASA’s Hubble and Webb Telescopes

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