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Comment by Dr. Krishna Kumari Challa on November 21, 2020 at 7:35am

How rotavirus causes severe gastrointestinal disease

Rotavirus is a major cause of diarrhea and vomiting, especially in children, that results in approximately 128,000 deaths annually. The virus triggers the disease by infecting enterocyte cells in the small intestine, but only a fraction of the susceptible cells has the virus. In the mid-90s, scientists proposed that the small portion of infected cells promotes severe disease by sending out signals that disrupt the normal function of neighbouring uninfected cells, but the nature of the signal has remained a mystery.

In the current study published in the journal Science, a team led by researchers at Baylor College of Medicine discovered that rotavirus-infected cells release signaling molecules, identified as adenosine diphosphate (ADP), which binds its cellular receptor P2Y1 on neighboring cells. Activating P2Y1 by ADP results in signals called intercellular calcium waves in these uninfected cells. Disrupting ADP binding to its receptor reduced the severity of diarrhea in a mouse model of the disease, suggesting that targeting the P2Y1 may be an effective strategy to control viral diarrhea in human populations.

Further studies revealed previously unknown roles of ADP on rotavirus infection and replication, shining a spotlight on ADP as an important trigger of the multiple factors involved in severe diarrhea and vomiting caused by rotavirus. For instance, the researchers found evidence that ADP signaling increases rotavirus infection, the expression of inflammatory cytokine IL1-alpha and the secretion of serotonin, an inducer of diarrhea. ADP signaling also increases the expression of enzymes that produce prostaglandin and nitric oxide, potentially causing the increases in those compounds observed in rotavirus infection. Preventing ADP signaling and intercellular calcium waves reduced the production of the compounds mentioned above.

 Alexandra L. Chang-Graham et al, Rotavirus induces intercellular calcium waves through ADP signaling, Science (2020). DOI: 10.1126/science.abc3621

https://medicalxpress.com/news/2020-11-rotavirus-severe-gastrointes...

Comment by Dr. Krishna Kumari Challa on November 20, 2020 at 10:13am

Your Tears Might Save Your Life Someday

They could ultimately be used to find diseases the way blood tests do now—but cheaper and more easily

At any given moment, about seven microliters of tears are present in each of our eyes—about a tenth of a drop of water. You might think of them as nothing more than salty water, but it’s more accurate to think if them filtered blood; they deliver oxygen and nutrients to our eyes, removing waste, serving as the first line of defense against pathogens and helping to heal injuries.

Tears also contain traces of the various chemicals originally present in blood, some of which serve as markers of illness—glucose, for example, which can signal diabetes, or enzymes that point to possible liver disease. That’s a primary reason doctors order blood tests. But it also that means that physicians—and maybe, in the near future, you—can look for indicators of illness by looking at your tears.

https://www.scientificamerican.com/article/your-tears-might-save-yo...

Comment by Dr. Krishna Kumari Challa on November 20, 2020 at 9:37am

Scientists identify brain cells that drive wakefulness and resist general anesthetics
Neuroscientists don’t know precisely what brain circuits control wakefulness and sleep, nor exactly how drugs for general anesthesia affect those circuits. But a new study from Penn Medicine researchers brings neuroscience a step closer to solving that important conundrum.

A team of researchers from the Perelman School of Medicine at the University of Pennsylvania, in a study published online Nov. 13 in Current Biology, identified a population of neurons in the hypothalamus region of the brain that keeps mice from sleeping when they normally would when they are activated. Activating these neurons also “wakes” them from ongoing exposure to inhaled anesthetics like isoflurane or sevoflurane, and even helps maintain the alert state when animals are dosed with anesthetics.

The study also supports a hypothesis long debated by neuroscientists: that the parts of the brain regulating sleep and waking are also capable of regulating the brain’s response to general anesthetics.

https://www.pennmedicine.org/news/news-releases/2020/november/scien...

https://researchnews.cc/news/3673/Scientists-identify-brain-cells-t...

Comment by Dr. Krishna Kumari Challa on November 20, 2020 at 9:30am

Gut microbiome manipulation could result from virus discovery

Scientists have discovered how a common virus in the human gut infects and takes over bacterial cells – a finding that could be used to control the composition of the gut microbiome, which is important for human health.

The Rutgers co-authored research, which could aid efforts to engineer beneficial bacteria that produce medicines and fuels and clean up pollutants.
CrAssphages are the most abundant viruses infecting bacteria in the human gut. As such, they likely control our intestinal community of microbes (the microbiome).Understanding how these tiny viruses infect bacteria may allow scientists to control and manipulate the makeup of the microbiome, either by increasing the proportion of beneficial bacteria in our intestines or decreasing the number of harmful bacteria, thus promoting health and fighting disease.
Scientists found that crAssphages use their own enzyme (an RNA polymerase) to make RNA copies of their genes. RNA has the genetic information to make proteins. All cells, ranging from bacterial to human, use such enzymes to make RNA copies of their genes. And these enzymes are very similar in all living matter, implying that they’re ancient and related by common ancestry.
The atomic structure of a crAssphage enzyme is distinct from other RNA polymerases but closely resembles an enzyme in humans and other higher organisms that is involved in RNA interference. Such interference silences the function of some genes and may lead to certain diseases.

This is a startling result. It suggests that enzymes of RNA interference, a process that was thought to occur only in cells of higher organisms, were ‘borrowed’ from an ancestral bacterial virus early in evolution. The result provides a glimpse of how cells of higher organisms evolved by mixing and matching components of simpler cells and even their viruses.

In addition to deep evolutionary insights, phage (viral) enzymes such as crAssphage RNA polymerase may be used in synthetic biology to generate genetic circuits that do not exist in nature.

https://www.rutgers.edu/news/gut-microbiome-manipulation-could-resu...

https://researchnews.cc/news/3670/Gut-microbiome-manipulation-could...

Comment by Dr. Krishna Kumari Challa on November 20, 2020 at 8:00am

The fundamental chemistry behind electrocatalytic water splitting

https://phys.org/news/2020-11-fundamental-chemistry-electrocatalyti...

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New system can sterilize medical tools using solar heat

Comment by Dr. Krishna Kumari Challa on November 20, 2020 at 7:27am

Undesirable rejection mechanism identified in stem cell transplantation

In the treatment of leukemia, stem cell transplantation subsequent to chemotherapy and radiation can often engender severe adverse inflammatory reactions—especially in the skin or in the gut, since these so-called barrier organs are more frequently affected. Up until now, the reason for this was unclear till now. Scientists now identified an immune mechanism that is partially responsible for this.

The term leukemia is used to describe a group of malignant diseases of the haematopoietic system, in which precursors of the white blood cells (leucocytes) proliferate uncontrollably. Chemotherapy and radiotherapy are used to destroy the abnormal blood cells, which are then replaced by means of a stem cell transplant. In leukemia, the transplantation of healthy bone marrow stem cells or haematopoietic stem cells is often the only hope of recovery for patients. The process involves "replacing" all the recipient's blood cells that were previously destroyed by the treatment with donor cells.

However, the MedUni Vienna dermatologists have now found that there are so-called skin-resident and inactive T cells in the endogenous immune system that survive chemotherapy and radiotherapy intact and go on to survive for a further ten years between and beneath the epithelial cells of the skin, while the circulating T cells are destroyed.

"We were able to demonstrate that T cells surviving in the skin tissue are responsible for the inflammatory reaction following a stem cell transplant. These phenomena often occur within the first 100 days and can cause anything from mild eczema through to extensive fibrosis, hardening of the tissue, or blistering on the surface of the skin. In other words, the endogenous T cells attack the recipient (host) following stem cell transplantation." In specialist jargon, the condition is also referred to as Graft versus Host Disease (GvHD), and, for the first time, this study identified an inverse "Host-versus-graft reaction."

There were also cases in which the donor T cells further "supported," and thus intensified, this reaction. Affected patients are treated with cortisone, which causes an additional burden for patients who are already immunosuppressed following the transplantation. The study found that in patients who do not develop graft-versus-host disease, tissue-resident T cells remaining after treatment even proved to be beneficial to the recipient, in that they assumed their role in immune defense and protecting against infection.

In the future, the exemplary study results could lead to new treatment strategies that help to avoid, or at least to minimize, undesirable and violent inflammatory reactions following stem cell transplants by manipulating the recipient's inactive T cells in advance. In addition, the manipulation of tissue-resident T cells might lead to new therapeutic approaches for other chronic inflammatory skin diseases, such as psoriasis or neurodermatitis.

Johanna Strobl et al. Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease, Science Translational Medicine (2020). DOI: 10.1126/scitranslmed.abb7028

https://medicalxpress.com/news/2020-11-undesirable-mechanism-stem-c...

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Comment by Dr. Krishna Kumari Challa on November 20, 2020 at 7:18am

Researchers show water has multiple liquid states

An international team of researchers has shown that water can exist in two different liquid states—a finding that can explain many of water's anomalous properties.

The possibility that water could exist in two different liquid states was proposed approximately 30 years ago, based on results obtained from computer simulations. This hypothesis has been one of the most important questions in the chemistry and physics of water, and a controversial scenario since its beginnings. This is because experiments that can access the two liquid states in water have been very challenging due to the apparently unavoidable ice formation at the conditions where the two liquids should exist.

The usual "liquid" state of water that we are all familiar with corresponds to liquid water at normal temperatures (approximately 25 degrees C). However, a new research paper shows that water at low temperatures (approximately -63 degrees C) exists in two different liquid states, a low-density liquid at low pressures and a high-density liquid at high pressures. These two liquids have noticeably different properties and differ by 20% in density. The results imply that at appropriate conditions, water should exist as two immiscible liquids separated by a thin interface similar to the coexistence of oil and water.

Because water is one of the most important substances on Earth—the solvent of life as we know it—its phase behaviour plays a fundamental role in different fields, including biochemistry, climate, cryopreservation, cryobiology, material science, and in many industrial processes where water acts as a solvent, product, reactant, or impurity. It follows that unusual characteristics in the phase behaviour of water, such as the presence of two liquid states, can affect numerous scientific and engineering applications.

Experimental observation of the liquid-liquid transition in bulk supercooled water under pressure. Science (2020). science.sciencemag.org/lookup/ … 1126/science.abb9385

https://phys.org/news/2020-11-multiple-liquid-states.html?utm_sourc...

Comment by Dr. Krishna Kumari Challa on November 20, 2020 at 6:55am

New effective and safe antifungal isolated from sea squirt microbiome

By combing the ocean for antimicrobials, scientists have discovered a new antifungal compound that efficiently targets multi-drug-resistant strains of deadly fungi without toxic side effects in mice.

The new molecule was discovered in the microbiome of a sea squirt from the Florida Keys as part of an effort to identify novel antimicrobials from understudied ecosystems. Scientists named the antifungal turbinmicin, after the sea squirt from which it was isolated, Ecteinascidia turbinate.

The researchers tested purified turbinmicin against a slate of 39 fungi isolated from patients. These strains both represented diverse species and encompassed all the known ways that fungi have evolved resistance to existing drugs. In lab experiments, turbinmicin halted or killed nearly all fungal strains at low concentrations, indicating a potent effect.

Similar experiments in mice infected with drug-resistant strains of Candida auris and Aspergillus fumigatus also demonstrated turbinmicin's ability to attack resistant fungi. Because fungi and animals are closely related, and thus share similar cellular machinery, antifungals can prove toxic to animals as well. Yet, turbinmicin did not show toxic side effects in mice, even at concentrations 1000 times higher than the minimum dose. The effective dose would work out to tens of milligrams for an average-weight adult, less than for many other antibiotics.

F. Zhang el al., "A marine microbiome antifungal targets urgent-threat drug-resistant fungi," Science (2020). science.sciencemag.org/cgi/doi … 1126/science.abd6919

"Drugs from bugs in creatures of the sea," Science (2020). science.sciencemag.org/cgi/doi … 1126/science.abf1675

https://phys.org/news/2020-11-effective-safe-antifungal-isolated-se...

Disease-causing fungi continue to evolve resistance to the small number of drugs available to thwart them. As a result, more people are dying from previously treatable diseases, such as candidiasis or aspergillosis, which are caused by common fungi that sometimes turn virulent. Identifying compounds like turbinmicin is key to developing new and effective drugs. However, while turbinmicin is a promising drug candidate, additional study of the molecule and extensive preclinical research must be performed before a new drug can become available.

Comment by Dr. Krishna Kumari Challa on November 19, 2020 at 12:12pm

Strange Case : Kids Develop Coronavirus Antibodies Without Ever Testing Positive

From the early days of the coronavirus pandemic, scientists observed that children seemed to be less susceptible to developing COVID-19, although the exact reasons why remain unclear.
Now, an unusual case in Australia may provide unique insight into the mystery. In this family of five, the two parents became sick with COVID-19 after attending an interstate wedding without their children. However, the symptoms didn't show until days after they had returned from the trip.

Nonetheless, completely unbeknownst to them, they had brought SARS-CoV-2 into their home, and exposed their children to it. Once both the parents developed symptoms – including cough, congested nose, fever and headache – the entire family was tested for the virus. The parents' tests came back positive. The children's tests came back negative.
Healthcare workers asked the family to repeat the tests, but again the children's tests came back negative for SARS-CoV-2, even though two of the boys in the family (aged 9 and 7) had mild symptoms.
The youngest child, a 5-year-old daughter, remained asymptomatic throughout the entire episode, even though she was frequently sleeping in the same bed as the parents during their sickness (physical distancing precautions not feasible in the household during their quarantine).

Intrigued by the children's negative results while living in such close proximity to their infected parents, researchers asked the family to take part in a study, analysing samples of their blood, saliva, stools, and urine, and taking nose and throat swabs every two to three days.

Strangely enough, despite repeated polymerase chain reaction (PCR) tests showing the children were consistently SARS-CoV-2 PCR negative, the researchers found SARS-CoV-2 specific antibodies in saliva of all the family members, and in detailed serology testing.

In other words, the children never tested positive for the virus, but some level of exposure to the virus had nonetheless triggered an immune response inside them, and one seemingly capable of countering the infection.
The youngest child, who showed no symptoms at all, had the strongest antibody response. Despite the active immune cell response in all children, levels of cytokines, molecular messengers in the blood that can trigger an inflammatory reaction, remained low. This was consistent with their mild or no symptoms.
The fact these children were able to shut down the virus and without even showing a positive test result suggests they have some level of their immune system which is able to respond and deal effectively with the virus, without them ever becoming very unwell.
In effect, the researchers think that the children did actually become infected by the virus, but their immune systems were somehow able to mount an anti-virus response that was highly effective in restricting virus replication, unlike their parents.

That immune response was so effective, it could have brought the viral load so low, that it went under the sensitivity of the PCR testing, which is another issue that bears further examination, the team thinks.

"The discordance between the virological PCR results and clinical serological testing, despite an evident immune response, highlights limitations to the sensitivity of nasopharyngeal PCR and current diagnostic serology in children," the researchers write.
https://www.nature.com/articles/s41467-020-19545-8
https://www.sciencealert.com/everyone-in-this-family-has-coronaviru...

Comment by Dr. Krishna Kumari Challa on November 19, 2020 at 10:06am

SCI-COM: Time for scientists to speak up and be heard

https://www.scidev.net/asia-pacific/governance/columns/time-for-sci...

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