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Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 11:02am

Treatment with a mixture of antimicrobial peptides found to impede antibiotic resistance

A common infection-causing bacteria was much less likely to evolve antibiotic resistance when treated with a mixture of antimicrobial peptides rather than a single peptide, making these mixtures a viable strategy for developing new antibiotic treatments. Researchers report these findings in a study published July 2 in PLOS Biology.

Antibiotic-resistant bacteria have become a major threat to public health. The World Health Organization estimates that 1.27 million people died directly from drug-resistant strains in 2019 and these strains contributed to 4.95 million deaths.
While bacteria naturally evolve resistance to antibiotics, misuse and overuse of these drugs has accelerated the problem, rendering many antibiotics ineffective. One emerging strategy to combat antibiotic resistance is the use of antimicrobial peptides, which are chains of amino acids that function as broad-spectrum antimicrobial compounds and are key components of the innate immune system in animals, fungi and plants.

In the new study, researchers investigated whether antimicrobial peptide mixtures synthesized in the lab could reduce the risk of the pathogen Pseudomonas aeruginosa from evolving antimicrobial resistance, compared to exposure to a single antimicrobial peptide.

They found that using antimicrobial peptide mixtures carried a much lower risk of the bacteria developing resistance. The mixtures also helped prevent the bacteria from developing cross-resistance to other antimicrobial drugs, while maintaining—or even improving—drug sensitivity.

Overall, the findings suggest that the use of antimicrobial peptide mixtures is a strategy worth pursuing in the search for new, longer-lasting treatments for bacteria.

The researchers suspect that using a cocktail of multiple antimicrobial peptides creates a larger set of challenges for bacteria to overcome, which can potentially delay the evolution of resistance, compared to traditional antibiotics. Furthermore, these cocktails can be synthesized affordably, and previous studies have shown them to be non-toxic in mice.

Bernardo Antunes et al, The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures, PLoS Biology (2024). DOI: 10.1371/journal.pbio.3002692

Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 10:50am

Due to this connection, the team set out to test if exercise could influence thermal age. They asked 23 participants to jump rope for at least 800 times daily for two weeks. To the team's surprise, these participants reduced their thermal age by five years after just two weeks of exercise.

Next, the team wants to explore if they can use thermal facial imaging to predict other diseases, such as sleeping disorders or cardiovascular problems.
Applying thermal facial imaging in clinical settings holds significant potential for early disease diagnosis and intervention.

Yu et al. Thermal Face Image Analyses Reveal Quantitative Hallmarks of Aging and Metabolic Diseases, Cell Metabolism (2024). DOI: 10.1016/j.cmet.2024.05.012. www.cell.com/cell-metabolism/f … 1550-4131(24)00188-8

Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 10:48am

Doctors could soon use facial temperature for early diagnosis of metabolic diseases

A colder nose and warmer cheeks may be a telltale sign of rising blood pressure. Researchers discovered that temperatures in different face regions are associated with various chronic illnesses, such as diabetes and high blood pressure. These temperature differences are not easily perceptible by one's own touch but can instead be identified using specific AI-derived spatial temperature patterns that require a thermal camera and a data-trained model.

The results appeared July 2 in the journal Cell Metabolism. With further research, doctors could one day use this simple and non-invasive approach for early detection of diseases.

The researchers had previously used 3Dfacial structure to predict people's biological age, which indicates how well the body is aging. Biological age is closely related to the risk of diseases, including cancer and diabetes. They were curious if other features of the face, such as temperature, could also predict aging rate and health status.

They 

 analyzed facial temperatures of more than 2,800 Chinese participants between the ages of 21 and 88. Then, the researchers used the information to train AI models that could predict a person's thermal age. They identified several key facial regions where the temperatures were significantly related to age and health, including the nose, eyes and cheeks.

The research team found the temperature of the nose decreases with age at a rate faster than other parts of the face, meaning people with warmer noses have a younger thermal age. At the same time, temperatures around the eyes tend to increase with age.

The team also found that people with metabolic disorders such as diabetes and fatty liver disease had faster thermal aging. They tended to have higher eye area temperatures than their healthy counterparts of the same age. People with elevated blood pressure also had higher cheek temperatures.
By analyzing participants' blood samples, the team revealed that the increase in temperatures around the eyes and cheeks was mainly because of an increase in cellular activities related to inflammation, such as repairing damaged DNAs and fighting infections. The increase in these activities led to a rise in temperatures in certain facial regions.

The thermal clock is so strongly associated with metabolic diseases that previous facial imaging models were not able to predict these conditions.
Part 1

Comment by Dr. Krishna Kumari Challa on July 3, 2024 at 10:02am

How insulin-triggering nutrients vary from person to person, with implications for personalized nutrition

When it comes to managing blood sugar levels, most people think about counting carbs. But new research  shows that, for some, it may be just as important to consider the proteins and fats in their diet.

The study, published in Cell Metabolism, is the first large-scale comparison of how different people produce insulin in response to each of the three macronutrients: carbohydrates (glucose), proteins (amino acids) and fats (fatty acids).

The findings reveal that production of the blood sugar-regulating hormone insulin is much more dynamic and individualized than previously thought, while showing for the first time a subset of the population who are hyper-responsive to fatty foods.

Glucose is the well-known driver of insulin, but it is surprising to see such high variability, with some individuals showing a strong response to proteins, and others to fats, which had never been characterized before.

Insulin plays a major role in human health, in everything from diabetes, where it is too low, to obesity, weight gain and even some forms of cancer, where it is too high. These findings lay the groundwork for personalized nutrition that could transform how we treat and manage a range of conditions.

For the study, the researchers conducted tests on pancreatic islets from 140 deceased male and female donors across a wide age range. The islets were exposed to each of the three macronutrients, while the researchers measured the insulin response alongside 8,000 other proteins.

Although most donors' islet cells had the strongest insulin response to carbohydrates, approximately 9% responded strongly to proteins, while another 8% of the donor cells were more responsive to fats than any other nutrient—even glucose.

This research challenges the long-held belief that fats have negligible effects on insulin release in everyone. With a better understanding of a person's individual drivers of insulin production, we could potentially provide tailored dietary guidance that would help people better manage their blood sugar and insulin levels.

The research team also examined a subset of islet cells from donors who had type 2 diabetes. As expected, these donor cells had a low insulin response to glucose. However, the researchers were surprised to see that their insulin response to proteins remained largely intact.

"This really bolsters the case that protein-rich diets could have therapeutic benefits for patients with type 2 diabetes and highlights the need for further research into protein-stimulated insulin secretion.

In the future, the researchers say it could be possible use genetic testing to determine which macronutrients are likely to trigger a person's insulin response.

 Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease, Cell Metabolism (2024). DOI: 10.1016/j.cmet.2024.06.001. www.cell.com/cell-metabolism/f … 1550-4131(24)00226-2

Comment by Dr. Krishna Kumari Challa on July 2, 2024 at 11:28am

Incredible Hydrothermal Environment Discovered Deep Beneath The Ocean

A stunning new wonderland has been discovered, hidden deep beneath the ocean waves of the Arctic Circle. Off the coast of Svalbard, in Norway, more than 3,000 meters (9,842 feet) down, a field of hydrothermal vents unfolds along the Knipovich Ridge, an underwater mountain range previously thought to be fairly unremarkable. Instead, like underfloor heating, volcanic activity below the seafloor causes heat to seep through, creating havens of warmth and chemical reactions where life can gather and thrive. The field, measuring at least a kilometer in length and 200 meters in width, has been named Jøtul, for the giants of Norse mythology that live beneath mountains. In this case, the giant is Earth's internal processes, released through cracks in the seafloor. Water penetrates into the ocean floor where it is heated by magma. The overheated water then rises back to the sea floor through cracks and fissures. On its way up the fluid becomes enriched in minerals and materials dissolved out of the oceanic crustal rocks. These fluids often seep out again at the sea floor through tube-like chimneys called black smokers, where metal-rich minerals are then precipitated. Hydrothermal vent fields are some of the most interesting undersea environments. They're usually very deep beneath the ocean surface, so far down that light from the Sun can't penetrate the vast volume of water above them. At these depths, conditions are permanently dark, freezing cold, and surrounded by crushing pressures. This environment isn't exactly conducive to life, but hydrothermal vents act as strange oases. The minerals seeping out and dissolving in the water provide the basis for a food web reliant, not on photosynthesis as most life closer to the surface is, but chemosynthesis – harnessing chemical reactions for energy, rather than sunlight. These environs make for a much more dynamic and thriving deep seafloor than might be expected, giving us a clue about how life might emerge on worlds very different from our own.

https://www.nature.com/articles/s41598-024-60802-3

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.

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