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Comment by Dr. Krishna Kumari Challa on February 2, 2022 at 10:30am

Key growth factor protects gut from inflammatory bowel disease

IBD, a disease category including ulcerative colitis and Crohn's disease, features chronic gut inflammation and many potential follow-on effects including arthritis and colorectal cancer.

 A growth factor protein produced by rare immune cells in the intestine can protect against the effects of inflammatory bowel disease (IBD), according to a new discovery. 

In their study, published in Nature Immunology, the researchers found that the growth factor, HB-EGF, is produced in response to gut inflammation by a set of immune-regulating cells called ILC3s. These immune cells reside in many organs including the intestines, though their numbers are known to be depleted in the inflamed intestines of IBD patients.

The researchers showed in experiments in mice that this growth factor can powerfully counter the harmful effects of a key driver of intestinal inflammation called TNF. In doing so, ILC3s protect gut-lining cells when they would otherwise die and cause a breach in the intestinal barrier. 

Lei Zhou, Wenqing Zhou, Ann M. Joseph, Coco Chu, Gregory G. Putzel, Beibei Fang, Fei Teng, Mengze Lyu, Hiroshi Yano, Katrin I. Andreasson, Eisuke Mekada, Gerard Eberl, Gregory F. Sonnenberg. Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation. Nature Immunology, 2022; DOI: 10.1038/s41590-021-01110-0

https://researchnews.cc/news/11380/Key-growth-factor-protects-gut-f...

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 1:07pm

Missing ear bone helps bats to echolocate

Some bats have an anatomical quirk in their ears that could explain how they evolved to hunt in specialized ways, from sensing small fish to catching insects midflight. In 2015, researchers took 3D images of the inner ear of a bat skull but couldn’t find a feature shared by almost all mammals: a bony tube that connects the ear to the brain and encases nerve cells. A more thorough search revealed many more bat species in which this bony nerve channel was missing or poked with large holes. Researchers suspect the loss of this bony channel gave the bats new hearing capabilities because the nerves are less confined.

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 12:41pm

How  Climate Change is Affecting Hibernation?

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 12:36pm

To test the particles, the researchers first injected them into the stomachs of mice, without using the delivery capsule. The RNA that they delivered codes for a reporter protein that can be detected in tissue if cells successfully take up the RNA. The researchers found the reporter protein in the stomachs of the mice and also in the liver, suggesting that RNA had been taken up in other organs of the body and then carried to the liver, which filters the blood.

Next, the researchers freeze-dried the RNA-nanoparticle complexes and packaged them into their drug delivery capsules. Working with scientists at Novo Nordisk, they were able to load about 50 micrograms of mRNA per capsule, and delivered three capsules into the stomachs of pigs, for a total of 150 micrograms of mRNA. This is the more than the amount of mRNA in the COVID vaccines now in use, which have 30 to 100 micrograms of mRNA.

In the pig studies, the researchers found that the reporter protein was successfully produced by cells of the stomach, but they did not see it elsewhere in the body. In future work, they hope to increase RNA uptake in other organs by changing the composition of the nanoparticles or giving larger doses. However, it may also be possible to generate a strong immune response with delivery only to the stomach.

"There are many immune cells in the gastrointestinal tract, and stimulating the immune system of the gastrointestinal tract is a known way of creating an immune response.

 Giovanni Traverso, Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections, Matter (2022). DOI: 10.1016/j.matt.2021.12.022. www.cell.com/matter/fulltext/S2590-2385(21)00680-9

https://medicalxpress.com/news/2022-01-pill-rna-stomach-vaccines.ht...

Part 3

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Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 12:35pm

For several years, scientists have been developing novel ways to deliver drugs to the gastrointestinal tract. In 2019, the researchers designed a capsule that, after being swallowed, can place solid drugs, such as insulin, into the lining of the stomach.

The pill, about the size of a blueberry, has a high, steep dome inspired by the leopard tortoise. Just as the tortoise is able to right itself if it rolls onto its back, the capsule is able to orient itself so that its contents can be injected into the lining of the stomach.

In 2021, the researchers showed that they could use the capsule to deliver large molecules such as monoclonal antibodies in liquid form. Next, the researchers decided to try to use the capsule to deliver nucleic acids, which are also large molecules.

Nucleic acids are susceptible to degradation when they enter the body, so they need to be carried by protective particles. For this study, the  team used a new type of polymeric nanoparticle  they had recently developed.

These particles, which can deliver RNA with high efficiency, are made from a type of polymer called poly(beta-amino esters). The MIT team's previous work showed that branched versions of these polymers are more effective than linear polymers at protecting nucleic acids and getting them into cells. They also showed that using two of these polymers together is more effective than just one.

Part 2

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 12:33pm

A pill that releases RNA in the stomach could offer a new way to administer vaccines

Like most vaccines, RNA vaccines have to be injected, which can be an obstacle for people who fear needles. Now, a team of  researchers has developed a way to deliver RNA in a capsule that can be swallowed, which they hope could help make people more receptive to them.

In addition to making vaccines easier to tolerate, this approach could also be used to deliver other kinds of therapeutic RNA or DNA directly to the digestive tract, which could make it easier to treat gastrointestinal disorders such as ulcers.

Nucleic acids, in particular RNA, can be extremely sensitive to degradation particularly in the digestive tract. Overcoming this challenge opens up multiple approaches to therapy, including potential vaccination through the oral route.

In a new study, researchers showed that they could use the capsule they developed to deliver up to 150 micrograms of RNA—more than the amount used in mRNA COVID vaccines—in the stomach of pigs.

part 1

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:55am

Melting causes gradients in the temperature of the water near the ice, which causes the liquid at different places to have different densities. This generates flows due to gravity—with heavier liquid sinking and lighter fluid rising—and such flows along the surface lead to different rates of melting at different locations and thus changes in shape.

The strange bit of physics is that liquid water has a highly unusual dependence of density on temperature, in particular a maximum of density at about 4 degrees C. "This 'density anomaly' makes water unique in comparison to other fluids."

The research shows that this property is responsible for producing very different flows, depending on the precise value of the water temperature. The downward pinnacles at low temperatures are associated with upward flows, while the upward pinnacles have downward flows. The scalloped patterns form because upward flows very near the surface interact with downward flows further away, destabilizing into vortices that carve pits into the ice.

Scott Weady et al, Anomalous Convective Flows Carve Pinnacles and Scallops in Melting Ice, Physical Review Letters (2022). DOI: 10.1103/PhysRevLett.128.044502

https://phys.org/news/2022-01-scientists-uncover-ice-temperature.ht...

Part 2

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:53am

Scientists uncover how the shape of melting ice depends on water temperature

A team of mathematicians and physicists has discovered how ice formations are shaped by external forces, such as water temperature. Its newly published research may offer another means for gauging factors that cause ice to melt.

The shapes and patterning of ice are sensitive indicators of the environmental conditions at which it melted, allowing researchers to 'read' the shape to infer factors such as the ambient water temperature. This  helps to understand how melting induces unusual flow patterns that in turn affect melting, which is one of the many complexities affecting the ice on our planet.

The researchers studied, through a series of experiments, the melting of ice in water and, in particular, how the water temperature affects the eventual shapes and patterning of ice. To do so, they created ultra-pure ice, which is free of bubbles and other impurities. The team recorded the melting of ice submerged into water tanks in a "cold room," which is similar to a walk-in refrigerator whose temperature is controlled and varied.

They focused on the cold temperatures—0 to 10 degrees Celsius—at which ice in natural waters typically melts, and  found a surprising variety of shapes that formed. 

Specifically, at very cold temperatures—those under about 5 degrees C—the pieces take on the shape of a spike or "pinnacle" pointing downward—similar to an icicle, but perfectly smooth (with no ripples). For temperatures above approximately 7 degrees C, the same basic shape forms, but upside down—a spike pointing upward. For in between temperatures, the ice has wavy and rippled patterns melted into its surface. Similar patterns, called "scallops," are found on icebergs and other ice surfaces in nature.

These shape differences are due to changes in water flows, which are determined by their temperatures.

Part 1

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:49am

Reference substances play an essential role in the interpretation of a screen, so they should be carefully evaluated and tested. The compounds identified by the cell painting show a wide variety of chemical scaffolds and even small chemical modifications can have a dramatic impact on the tubulin-binding properties of a compound. This risk is ubiquitous, especially during the compound optimization phase, where existing atoms are exchanged or removed and new atoms are added in order to improve the pharmacological properties. Additional morphological profiling during the search for hits and their optimization could not only help unmask side effects such as tubulin modulation early on, but also identify desired and new bioactivities. Moreover, this approach could save time and money as it helps to early assess whether a promising substance has what it takes to become a useful compound or not.

Mohammad Akbarzadeh, Ilka Deipenwisch, Beate Schoelermann, Axel Pahl, Sonja Sievers, Slava Ziegler, Herbert Waldmann. Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds. Cell Chemical Biology, 2021; DOI: 10.1016/j.chembiol.2021.12.009

https://researchnews.cc/news/11353/Morphological-fingerprinting-cou...

Part 2

Comment by Dr. Krishna Kumari Challa on February 1, 2022 at 11:48am

Morphological fingerprinting could help identify side effects and new bioactive compounds in drug discovery

Pharmaceutical researchers speak of a hit when they come across a promising substance with a desired effect in early drug discovery. Unfortunately, hits are rarely bull's-eyes, often showing undesirable side effects that not only complicate the search for new hits, but also the subsequent development into a drug. A new study  could now help to better identify one of the most frequently observed side effects already in early drug discovery, but also to find new bioactivities.

The most commonly used cancer drugs contain active substances that manipulate the cell's cytoskeleton by binding to microtubules. This can disrupt cell division as well as impair other essential processes, and leads to cell death. Such an effect is of course not desirable for other therapies. However, microtubules' surface has many deep binding pockets that makes them particularly susceptible to modulation by a wide variety of chemical substances with diverse chemical scaffolds.

In the search for and development of new active substances, the study of known side effects plays a crucial role, especially when one considers that about 13 years and more than one billion US dollars are needed to develop a new drug. Although there are already standardized test procedures (screens) for identifying undesirable side effects, they certainly do not cover all targets in cells, often do not correctly reflect the cellular context, or they allow targets to be overlooked, e.g. binding to tubulin. Thus, drug discovery is always biased to a certain extent.

Researchers now  used a new strategy to reliably detect side effects, such as the disruption of microtubules, at an early stage of the search for bioactive compounds. To do this, the researchers employed the so-called "cell painting" approach. Here, several functional areas of the cell are stained and then examined microscopically for changes after the addition of chemical substances. This enables recording hundreds of cellular parameters in a single morphological fingerprint. If one detects similarity of this fingerprint to those of known reference substances, conclusions about the effect of the unknown substance can be drawn. The value of this approach lies in the possibility of creating fingerprints for thousands of substances in a high-throughput process. This way, the researchers revealed that more than 1% of about 15,000 studied substances had a tubulin-modulating effect. Among them was also a large number of known reference substances for which an influence on tubulin was previously unknown.

Part 1

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