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Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 11:45am

Researchers identify 'first responder' cells in pancreas crucial for blood sugar control

How does our body control blood sugar so precisely?

Researchers found a special group of "first responder" cells in the pancreas that are crucial for triggering blood sugar response.

Their findings were published in the journal Science Advances.

Our bodies need to keep blood sugar levels just right. Too high or too low can be dangerous. This balance is disturbed in diabetes, leading to serious health issues. Beta cells in the pancreas manage this balance by releasing insulin when blood sugar levels rise.

Understanding how beta cells work and coordinate the response to rising blood sugar can ultimately help develop better treatments for diabetes.

To understand the work of the pancreas, the research team turned to zebrafish. This small tropical fish has a pancreas that works similarly to a human one. At the same time, it offers a huge advantage. Researchers can use transparent fish that have no pigment whatsoever and observe the pancreas at work in real-time in the living fish.

The group discovered that a small group of beta cells are more sensitive to sugar levels than the others. These cells respond to glucose quicker than the rest of the cells, so the research  team referred to them as "first responder" cells. They initiate the glucose response, which is followed by the remaining "follower cells."

The team wanted to test if first responders are necessary for the follower cells to respond to glucose.

Using transparent fish, the  group took advantage of optogenetics, a modern light-based technology that allows to turn single cells on or off with a beam of light.

Turning off the first responder cells lowered the response to the blood sugar of the follower cells. At the same time, when the first responders were selectively activated, the response of the follower cells was enhanced.

The first responders lie at the top of the beta cell hierarchy when it comes to control of the sugar response. Interestingly, only about 10% of the beta-cells act as first responders. It suggests that this small population of cells serves as a control centre for regulating the activity of the rest of the beta cells.

To find out what makes the first responder cells unique, the researchers compared the gene expression of highly glucose-sensitive beta cells to those that are less sensitive. They found that first responders are involved in vitamin B6 production. The first responder cells express a key enzyme involved in transforming the inactive form of dietary vitamin B6 into the form that is active in the cells.

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Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 11:27am

Caterpillars pass down food preferences to offspring through blood

Many caterpillars are known for their specific food preferences, which they bring with them when they morph into butterflies. For instance, the monarch butterfly only feeds on milkweed plants, while the Lime butterfly feeds on lime leaves. Despite deriving from a common ancestral species, these unique diet preferences are a point of interest for researchers.

In an earlier study by researchers, they demonstrated that when caterpillars fed on leaves outside of their usual diet, they would prefer the smell of that type of plant after a few days. Remarkably, these caterpillars also passed on the acquired smell preference to their offspring.

Such a phenomenon is also seen in nature when caterpillars find themselves on a new food plant when the female butterfly lays eggs on the wrong plant by mistake. The new plant is edible but has a new smell, the caterpillars will learn to prefer this new smell and pass this preference on to their offspring.

This type of inheritance may facilitate host switching and ultimately the formation of new species, each with their own food preferences.

 V. Gowri et al, Haemolymph transfusions transfer heritable learned novel odour preferences to naive larvae of Bicyclus anynana butterflies, Biology Letters (2024). DOI: 10.1098/rsbl.2023.0595

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 11:15am

These oldest inhabited termite mounds have been active for 34,000 years

Scientists in South Africa have been stunned to discover that termite mounds that are still inhabited in an arid region of the country are more than 30,000 years old, meaning they are the oldest known active termite hills.

Some of the mounds near the Buffels River in Namaqualand were estimated by radiocarbon dating to be 34,000 years old, according to the researchers from Stellenbosch University.

Some fossilized termite mounds have been discovered dating back millions of years. The oldest inhabited mounds before this study were found in Brazil and are around 4,000 years old. They are visible from space.

 M.L. Francis et al, Calcareous termite mounds in South Africa are ancient carbon reservoirs, Science of The Total Environment (2024). DOI: 10.1016/j.scitotenv.2024.171760

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 11:10am

Health study illustrates the interconnectedness of humans and wildlife

According to a growing body of evidence, including a recent study, the seemingly separate fields of health sciences and conservation are inextricably linked.

The study, published in the journal Environmental Science & Technology, measured lead levels in the blood of house sparrows (Passer domesticus) in Australian mining towns to accurately predict lead levels in the blood of children living in the same areas.

It shows that wildlife and human health are so intimately linked that when something like lead, which we know is a toxin, gets out into the environment and affects wildlife, it's also affecting people.

The study illustrates the growing relevance of the One Health concept, coalescing aspects of public health, veterinary health and conservation.

Max M. Gillings et al, House Sparrows as Sentinels of Childhood Lead Exposure, Environmental Science & Technology (2024). DOI: 10.1021/acs.est.4c00946

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 10:57am

Air pollution drives 7% of deaths in big Indian cities: Study

More than seven percent of all deaths in 10 of India's biggest cities are linked to air pollution, a large study said recently, leading researchers to call for action to save tens of thousands of lives a year.

Smog-filled Indian cities including the capital Delhi suffer from some of the world's worst air pollution, choking the lungs of residents and posing a rising threat to health still being revealed by researchers.

For the new study, an Indian-led team looked at the levels of cancer-causing microparticles known as PM2.5 pollutants in the cities of Ahmedabad, Bengaluru, Chennai, Delhi, Hyderabad, Kolkata, Mumbai, Pune, Shimla and Varanasi.

From 2008 to 2019, more than 33,000 deaths a year could be attributed to PM2.5 exposure above the World Health Organization's recommendation of 15 micrograms per cubic meter, the study said.

That represents 7.2 percent of the recorded deaths in those cities during that period, according to the study in The Lancet Planetary Health journal.

India's capital Delhi was the worst offender, with 12,000 annual deaths linked to air pollution -- or 11.5 percent of the total.

But even cities where air pollution is not thought to be as bad -- such as Mumbai, Kolkata and Chennai -- had high death rates, the researchers emphasized.

They called for India's air quality standards to be toughened.

The country's current recommendation is 60 micrograms of PM2.5 per cubic meter, which is four times higher than the WHO's guidelines.

Lowering and enforcing the limit "will save tens of thousands of lives per year", say the researchers. 

"Methods for controlling pollution exist and are used elsewhere. They urgently need to be applied in India," they said in a statement.

The WHO says that almost everyone on Earth breathes in more than the recommended amount of air pollution, which can trigger strokes, heart disease, lung cancer and other respiratory diseases.

Jeroen de Bont et al, Ambient air pollution and daily mortality in ten cities of India: a causal modelling study, The Lancet Planetary Health (2024). DOI: 10.1016/S2542-5196(24)00114-1

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 10:49am

Cool roofs outperform green roofs in urban climate modeling study

Painting roofs white or covering them with a reflective coating would be more effective at cooling cities than vegetation-covered "green roofs," street-level vegetation or solar panels, finds a new study  by  researchers.

Conversely, extensive use of air conditioning would warm the outside environment by as much as 1 degree C in a dense city center, the researchers found.

The research, published in Geophysical Research Letters, used a three-dimensional urban climate model of Greater London to test the thermal effects of different passive and active urban heat management systems, including painted "cool roofs," rooftop solar panels, green roofs, ground level tree vegetation and air conditioning during the two hottest days of the summer of 2018.

It found that if adopted widely throughout London, cool roofs could reduce outdoor temperatures across the city, on average, about 1.2 degrees C, and up to 2 degrees C in some locations. Other systems, such as extensive street-level vegetation or solar panels would provide a smaller net cooling effect, only about 0.3 degrees C on average across London, though they offer other environmental benefits. Similarly, while green roofs offer benefits like water drainage and wildlife habitats, their net cooling effect on the city was found to be negligible on average.

Air conditioning, which transfers heat from within buildings to the outside, would warm the outdoor urban environment by about 0.15 degrees C for the city overall, but by as much as 1 degree C in dense central London. The researchers also found that the increase in the distribution of air conditioning units in their model could be entirely powered by photovoltaic solar panels if they were similarly installed to their fullest extent.

To gauge the potential full effect of each method, the team modeled each one as though they had been as widely adopted as theoretically feasible across housing, commercial and industrial buildings throughout Greater London.

The researchers  comprehensively tested multiple methods that cities like London could use to adapt to and mitigate warming temperatures, and found that cool roofs were the best way to keep temperatures down during extremely hot summer days. Other methods had various important side benefits, but none were able to reduce outdoor urban heat to nearly the same level.

 Cool roofs could be most effective at reducing outdoor urban temperatures in London compared with other roof top and vegetation interventions: a mesoscale urban climate modelling study, Geophysical Research Letters (2024). DOI: 10.1029/2024GL109634

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 9:48am

Phage viruses, used to treat antibiotic resistance, gain advantage by cutting off competitors' reproduction ability

Curious bits of DNA tucked inside genomes across all kingdoms of life historically have been disregarded since they don't seem to have a role to play in the competition for survival, or so researchers thought.

These DNA pieces came to be known as "selfish genetic elements" because they exist, as far as scientists could tell, to simply reproduce and propagate themselves, without any benefit to their host organisms. They were seen as genetic hitchhikers that have been inconsequentially passed from one generation to the next.

Research conducted by scientists at the University of California San Diego has provided fresh evidence that such DNA elements might not be so selfish after all. Instead, they now appear to factor considerably into the dynamics between competing organisms.

Publishing in the journal Science, researchers in the School of Biological Sciences studied selfish genetic elements in bacteriophages (phages), viruses that are considered the most abundant organisms on Earth. To their surprise, researchers found that selfish genetic elements known as "mobile introns" provide their virus hosts with a clear advantage when competing with other viruses: Phages have weaponized mobile introns to disrupt the ability of competing phage viruses to reproduce.

This is the first time a selfish genetic element has been demonstrated to confer a competitive advantage to the host organism it has invaded.

Understanding that selfish genetic elements are not always purely 'selfish' has wide implications for better understanding the evolution of genomes in all kingdoms of life.

Erica A. Birkholz et al, An intron endonuclease facilitates interference competition between coinfecting viruses, Science (2024). DOI: 10.1126/science.adl1356. www.science.org/doi/10.1126/science.adl1356

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 9:38am

Researchers identify unknown signaling pathway in the brain responsible for migraine with aura

A previously unknown mechanism by which proteins from the brain are carried to a particular group of sensory nerves causes migraine attacks, a new study shows. This may pave the way for new treatments for migraine and other types of headaches.

In around a fourth of all migraine patients, headache attacks are preceded by aura—symptoms from the brain such as temporary visual or sensory disturbances preceding the migraine attack by 5–60 minutes.

While we know with some certainty why patients experience aura, it has been a bit of a mystery why they get headaches, and why migraines are one-sided, until now.

A new study in mice conducted by researchers  is the first to demonstrate that proteins released from the brain during migraine with aura are carried with cerebrospinal fluid to the pain-signaling nerves responsible for headaches.

The researchers have discovered that these proteins activate a group of sensory nerve cell bodies at the base of the skull, the so-called trigeminal ganglion, which can be described as a gateway to the peripheral sensory nervous system of the skull.

At the root of the trigeminal ganglion, the barrier that usually prevents substances from entering the peripheral nerves is missing, and this enables substances in the cerebrospinal fluid to enter and activate pain-signaling sensory nerves, resulting in headaches.

The research results  results suggest that they have identified the primary channel of communication between the brain and the peripheral sensory nervous system. It is a previously unknown signaling pathway important for the development of migraine headache, and it might be associated with other headache diseases too.

The peripheral nervous system consists of all the nerve fibers responsible for communication between the central nervous system—the brain and spinal cord—and the skin, organs and muscles. The sensory nervous system, which is part of the peripheral nervous system, is responsible for communicating information about e.g. touch, itching and pain to the brain.

The study results offer insight into why migraine is usually one-sided. 

Most patients experience one-sided headaches, and this signaling pathway can help explain why. This study of how proteins from the brain are transported shows that the substances are not carried to the entire intracranial space, but primarily to the sensory system in the same side, which is what causes one-sided headaches.

The study was conducted on mice, but also included MR scans of the human trigeminal ganglion, and according to the scientists, there is every indication that the function of the signaling pathway is the same in mice and humans, and that in humans too, the proteins are carried by cerebrospinal fluid.

Martin Kaag Rasmussen et al, Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model, Science (2024). DOI: 10.1126/science.adl0544

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 9:26am

Using their new system, the researchers selectively activated certain types of receptors in the cancerous cells and adjusted the chemical and physical properties of their designer matrix. They found that pancreatic cancer needed two things to become resistant to chemotherapy: a physically stiff extracellular matrix and high amounts of hyaluronic acid—a polymer that helps stiffen the extracellular matrix and interacts with cells through a receptor called CD44.
Initially, the pancreatic cancer cells in a stiff matrix full of hyaluronic acid responded to chemotherapy. But after some time in these conditions, the cancerous cells became resistant to chemotherapy—they made proteins in the cell membrane that could quickly pump out chemotherapy drugs before they could take effect. The researchers found that they could reverse this development by moving the cells to a softer matrix (even if it was still high in hyaluronic acid) or blocking the CD44 receptor (even if the matrix was still stiff).

They could revert the cells back to a state where they are sensitive to chemotherapy. This suggests that if they can disrupt the stiffness signaling that's happening through the CD44 receptor, we could make patients' pancreatic cancer treatable by normal chemotherapy.

Other cancers can be affected by mechanical properties of the extracellular matrix, but these interactions typically work through a different class of receptors called integrins.

The researchers showed that pancreatic cancer cells weren't really using integrin receptors at all in our materials. That's important, because if you want to design a drug to resensitize patient cells to chemotherapy, you need to know which biological pathway to interfere with.

Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids, Nature Materials (2024). DOI: 10.1038/s41563-024-01908-x

Comment by Dr. Krishna Kumari Challa on July 5, 2024 at 9:21am

Reversing chemotherapy resistance in pancreatic cancer

Pancreatic cancer is a particularly aggressive and difficult-to-treat cancer, in part because it is often resistant to chemotherapy. Now, researchers  have revealed that this resistance is related to both the physical stiffness of the tissue around the cancerous cells and the chemical makeup of that tissue. Their work, published on July 4 in Nature Materials, shows that this resistance can be reversed and reveals potential targets for new pancreatic cancer treatments.

They found that stiffer tissue can cause pancreatic cancer cells to become resistant to chemotherapy, while softer tissue made the cancer cells more responsive to chemotherapy.

The researchers focused their efforts on pancreatic ductal adenocarcinoma, a cancer that starts in the cells lining the ducts of the pancreas and accounts for 90% of pancreatic cancer cases. In these cancers, the network of materials between the cells, known as the extracellular matrix, becomes notably stiffer. Scientists have theorized that this stiff material acts as a physical block, stopping chemotherapy drugs from reaching cancerous cells, but treatments based on this idea have not been effective in humans.

The researchers worked to develop a new system to study these changes to the extracellular matrix and better understand their impact on pancreatic cancer cells. They designed three-dimensional materials that mimicked the biochemical and mechanical properties of both pancreatic tumors and healthy pancreas tissues, and used them to culture cells from pancreatic cancer patients.

They  created a designer matrix that would allow us to test the idea that these cancerous cells might be responding to the chemical signals and mechanical properties in the matrix around them.

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