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Comment by Dr. Krishna Kumari Challa on May 7, 2024 at 9:32am

Nanotech opens door to future of insulin medication

An international research team has developed a system using nanotechnology that could allow people with diabetes to take oral insulin in the future. The researchers say the new insulin could be eaten by taking a tablet or even embedded within a piece of chocolate.

The new nano carrier, tested in mice, rats and baboon animal models, could help people with diabetes avoid side-effects linked to insulin injections such as hypoglycemia (a low blood sugar event, when too much insulin has been injected).

These animal studies have shown that the greatest strength of the nano-scale material is that it can react to the body's blood sugar levels. The coating dissolves and releases the insulin when there is a high concentration of blood sugar and importantly does not release the insulin in low blood sugar environments.

The new oral insulin uses a type of nano-scale material that is 1/10,000th the width of a human hair. The material acts similarly to acid resistant coating on tablets, which protects it from being destroyed by stomach acid. But this new coating instead surrounds individual insulin molecules and becomes a "nano carrier"—acting like a courier to ferry insulin molecules in the body to the places it needs to act.

Nicholas J. Hunt et al, Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia, Nature Nanotechnology (2024). DOI: 10.1038/s41565-023-01565-2

Comment by Dr. Krishna Kumari Challa on May 7, 2024 at 9:26am

A new study managed to accurately date findings from 1st Temple period found in the City of David

A team of archaeologists, antiquities specialists, Bible scholars and mass spectrometry specialists, affiliated with several institutions in Israel working with one colleague from the U.K. and another from the U.S., has dated material uncovered in the First Temple in the city of David, in Jerusalem, to an unpreceded level of accuracy.

In their paper published in the Proceedings of the National Academy of Sciences, the group describes how they used radio-carbon dating, tree ring analysis and other techniques to accurately date artifacts collected from a dig site in one of the oldest parts of Jerusalem.

The ancient history of Israel, and most particularly the city of Jerusalem, has taken on increased significance over the past several decades as religious and political entities have used it to make claims about current rights to certain parts of the city. One such site is believed to be what has been described in ancient texts as the City of David.

The work by the team involved analysis of artifacts (such as seeds and a bat skull) found among strata dated to between 770 and 420 BC—which has been named the Hallstatt Plateau. The team performed 103 carbon-14 measurements, providing high-resolution results.

The researchers also dated material in the same strata using tree-ring measurements, which allowed for annual resolution. After dating the artifacts, the researchers looked for and found associations between the nature of the artifacts and reported historical events mentioned in several ancient texts, including the Bible.

The team found that they were able to date many of the artifacts to historical events, which allowed them to verify that the city was first settled sometime between the 12th and 10th century BC, and that it expanded westward thereafter. They also found evidence of an earthquake and the rebuilding that occurred thereafter during the 8th century BC—and the Babylonian destruction of the city of Jerusalem in 586 BC.

Johanna Regev et al, Radiocarbon chronology of Iron Age Jerusalem reveals calibration offsets and architectural developments, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2321024121

Israel Antiquities Authority announcement: www.facebook.com/AntiquitiesEN … Ymyxcnz6GBXxmejmabdl

Comment by Dr. Krishna Kumari Challa on May 6, 2024 at 10:36am

 Parrots prefer live calls over pre-recorded videos

Comment by Dr. Krishna Kumari Challa on May 6, 2024 at 10:32am

In translational patient-based studies, the team also analyzed human tissue, blood and stool samples from Weill Cornell Medicine's Jill Roberts Institute for Research in Inflammatory Bowel Disease Live Cell Bank. This analysis revealed that patients with inflammatory bowel disease, like the mice fed inulin, had higher levels of bile acids in their blood and stool and excessive levels of eosinophils in their intestine compared with people without the condition.

The results suggest that the inflammation cascade similar to that in the mice fed inulin is already primed in humans with inflammatory bowel disease, and dietary uptake of inulin may further exacerbate the disease.
These unexpected discoveries may help explain why high-fiber diets often exacerbate inflammatory bowel disease in patients. It may also help scientists develop therapeutic diets to reduce symptoms and gut damage in patients with inflammatory bowel disease or related conditions.

New therapies are urgently needed for these increasingly common gut conditions. Existing biologic therapies can increase the risk of developing infections or autoimmune diseases, which cause the immune system to attack the body. 
The present study shows that not all fibers are the same in how they influence the microbiota and the body's immune system.
These findings could have broader implications for the delivery of precision nutrition to individual patients to promote their overall health based on their unique symptoms, microbiota composition and dietary needs.

Mohammad Arifuzzaman et al, Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation, Journal of Experimental Medicine (2024). DOI: 10.1084/jem.20232148

Part 2

Comment by Dr. Krishna Kumari Challa on May 6, 2024 at 10:31am

A common type of fiber may trigger bowel inflammation

Inulin, a type of fiber found in certain plant-based foods and fiber supplements, causes inflammation in the gut and exacerbates inflammatory bowel disease in a preclinical model, according to a new study by  investigators. The surprising findings could pave the way for therapeutic diets that may help ease symptoms and promote gut health. 

The study, published March 20 in the Journal of Experimental Medicine, shows that inulin, which is found in foods such as garlic, leeks and sunchoke, as well as commonly used fiber supplements and foods with added fiber, stimulates microbes in the gut to release bile acids that increase the production of molecules that promote intestinal inflammation.

One such protein, IL-33, causes immune cells called group 2 innate lymphoid cells (ILC2s) to become activated, triggering an excessive immune response similar to an allergic reaction. That excessive immune response then exacerbates intestinal damage and symptoms in an animal model of inflammatory bowel disease.
Dietary fiber, including inulin, is considered an essential part of a healthy diet for most people. Gut microbes turn inulin and other types of dietary fiber into short-chain fatty acids that turn on immune cells called regulatory T cells, which help reduce inflammation and have other beneficial effects throughout the body. This led to a remarkable rise in use of dietary fiber as an additive in both foods and supplements, and purified inulin or inulin-rich chicory root is often the main source of the fiber.
Inulin is now everywhere, from clinical trials to prebiotic sodas.
Feeding inulin to mice in the context of a model of inflammatory bowel disease increased the production of certain bile acids by specific groups of gut bacteria. The increased bile acids boosted the production of an inflammatory protein called IL-5 by ILC2s. The ILC2s also failed to produce a tissue-protecting protein called amphiregulin.

In response to these changes, the immune system promotes the production of immune cells called eosinophils, which further ramp up inflammation and tissue damage. Previously, a 2022 study by the same team of investigators showed that this flood of eosinophils may help protect against parasite infections. However, in the inflammatory bowel disease model, this chain reaction exacerbated intestinal inflammation, weight loss and other symptoms like diarrhea. 
Part 1

Comment by Dr. Krishna Kumari Challa on May 6, 2024 at 10:03am

A 'cosmic glitch' in gravity: New model may explain strange behaviour on a cosmic scale

A group of researchers  have discovered a potential "cosmic glitch" in the universe's gravity, explaining its strange behavior on a cosmic scale.

The paper is published in the Journal of Cosmology and Astroparticle Physics.
For the last 100 years, physicists have relied upon Albert Einstein's theory of "general relativity" to explain how gravity works throughout the universe. General relativity, proven accurate by countless tests and observations, suggests that gravity impacts not simply three physical dimensions but also a fourth dimension: time.

This model of gravity has been essential for everything from theorizing the Big Bang to photographing black holes.
But when we try to understand gravity on a cosmic scale, at the scale of galaxy clusters and beyond, we encounter apparent inconsistencies with the predictions of general relativity. It's almost as if gravity itself stops perfectly matching Einstein's theory. We are calling this inconsistency a 'cosmic glitch': gravity becomes around one percent weaker when dealing with distances in the billions of light years.
For more than twenty years, physicists and astronomers have been trying to create a mathematical model that explains the apparent inconsistencies of the theory of general relativity. Many of those efforts have taken place at Waterloo, which has a long history of cutting-edge gravitational research resulting from ongoing interdisciplinary collaboration between applied mathematicians and astrophysicists.

"Almost a century ago, astronomers discovered that our universe is expanding.
The farther away galaxies are, the faster they are moving, to the point that they seem to be moving at nearly the speed of light, the maximum allowed by Einstein's theory. Our finding suggests that, on those very scales, Einstein's theory may also be insufficient.
The research team's new model of a "cosmic glitch" modifies and extends Einstein's mathematical formulas in a way that resolves the inconsistency of some of the cosmological measurements without affecting existing successful uses of general relativity.

"Think of it as being like a footnote to Einstein's theory," the researchers say. "Once you reach a cosmic scale, terms and conditions apply."

"This new model might just be the first clue in a cosmic puzzle we are starting to solve across space and time".

Robin Y. Wen et al, A cosmic glitch in gravity, Journal of Cosmology and Astroparticle Physics (2024). DOI: 10.1088/1475-7516/2024/03/045

Comment by Dr. Krishna Kumari Challa on May 6, 2024 at 9:52am

New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumour

Glioblastoma is among the most devastating diagnoses, with median survival around 15 months. The current standard of care involves surgery, radiation and some combination of chemotherapy.

In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed by scientists quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumour.

The results mirror those in 10 pet dog patients suffering from naturally occurring brain tumors whose owners approved of their participation, as they had no other treatment options, as well as results from preclinical mouse models. The breakthrough now will be tested in a Phase I pediatric clinical trial for brain cancer.

Reported May 1 in the journal Cell, the discovery represents a potential new way to recruit the immune system to fight notoriously treatment-resistant cancers using an iteration of mRNA technology and lipid nanoparticles, similar to COVID-19 vaccines, but with two key differences: use of a patient's own tumor cells to create a personalized vaccine, and a newly engineered complex delivery mechanism within the vaccine.

In less than 48 hours, the researchers could see these tumours shifting from what they refer to as 'cold'—immune cold, very few immune cells, very silenced immune response—to 'hot,' very active immune response.

The 10 pet dogs on which trials were done lived a median of 139 days, compared with a median survival of 30 to 60 days typical for dogs with the condition.

 RNA aggregates harness the danger response for potent cancer immunotherapy, Cell (2024). DOI: 10.1016/j.cell.2024.04.003. www.cell.com/cell/fulltext/S0092-8674(24)00398-2

Comment by Dr. Krishna Kumari Challa on May 4, 2024 at 11:38am

Most amniotic fluid cells are epithelial, but scientists knew very little about these cell populations. Everything changed when researchers started to look at the single cell level at what happened in the amniotic fluid.
used single-cell RNA sequencing to characterize the amniotic fluid of 12 patients and discovered subpopulations of epithelial cells that expressed markers typical of progenitors for the lung, kidney, and small intestine. The researchers cultured the tissue-specific progenitor cells, fed them a chemical cocktail to support growth, and watched as they proliferated, differentiated, and self-organized into 3D epithelial organoids. The mini-organs shared some transcriptomic and protein features found in their tissues of origin. For example, lung epithelial cells that developed and differentiated in culture had elevated expression of airway markers compared to their nondifferentiated counterparts. Similarly, kidney epithelial organoids expressed markers associated with renal tubules, which are integral components of the kidneys’ filtration system.

Although the amniotic fluid contained cells from other tissues, the researchers could not grow them into organoids, suggesting that they lack progenitor capabilities. Other research groups have successfully grown fetal organoids from somatic cells floating around the amniotic fluid, and the mini-organs generated using this approach are more complex.
reprogramming methods take up to 20 weeks to generate organoids. If the goal is to use organoids to inform prenatal interventions, timing is critical.
Part 3

Researchers re using these to study various diseases and find solutions to them.

More here: https://www.the-scientist.com/fetal-organoids-generated-from-human-...

Comment by Dr. Krishna Kumari Challa on May 4, 2024 at 11:35am

Scientists use patient cells to generate organoids that possess certain features and functions of the modeled organ while retaining the individual's genetic fingerprint. However, many of these platforms require lengthy dedifferentiation protocols to revert somatic cells into a state of pluripotency and then reprogram them to develop as another cell type. In contrast to organoids generated from pluripotent stem cells, primary organoids use tissue-specific stem cells or progenitor cells and therefore require minimal manipulation.3 While the organoid field is relatively advanced in terms of using adult tissues, researchers can only generate primary fetal organoids using tissue from terminated pregnancies. “This made it basically impossible to [generate organoids] compatible with the continuation of pregnancy, and therefore in a personalized medicine fashion”.
During gestation, the fetus floats in a protective pool of amniotic fluid.6 The yellowish liquid contains a concoction of nutrients and antibodies produced by the parent as well as less glamorous contributions from the fetus, including urine. It also includes fetal cells sloughed off during development, which doctors can extract and analyze for signs of disease.

“Those cells historically have been thought to be dead cells or cells that were shed from the lining of the amniotic fluid cavity.
Part 2

Comment by Dr. Krishna Kumari Challa on May 4, 2024 at 11:32am

Fetal Organoids Generated From Human Amniotic Fluid

A minimally invasive strategy for creating fetal organoids could facilitate precision medicine in the womb.

Moments after birth, a baby takes a first breath as the placenta, which has served as the fetus’ lungs during gestation, transfers responsibility to the baby's own organs. However, for patients born with congenital diaphragmatic hernia (CDH), a rare condition where the diaphragm fails to close, causing impaired lung development, entry into the world is more precarious. More severe cases of the disease lead to multiorgan damage, and approximately thirty percent of infants diagnosed with CDH never leave the hospital.

Diagnostic imaging and genetic screens help clinicians catch congenital fetal diseases in utero, but models for studying organ development and disease progression are limited. Over the last decade, organoids have become an increasingly popular platform for modeling organ function and disease. However, the generation of fetal organoids is complicated by ethical and legal restrictions on the harvesting of the human tissues needed to generate the mini-organs.

Now, reporting in Nature Medicine, researchers generated fetal organoids using cells derived from human amniotic and tracheal fluids. These mini-organs offer a minimally invasive approach for disease modeling during an active pregnancy and may eventually inform the development of personalized prenatal interventions.

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