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Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 10:19am

 Study reveals that immune cells cooperate to trap and kill bacteria

Like a spider trapping its prey, our immune system cells cooperate to capture and "eat" bacteria.

The newly identified antibacterial mechanism, reported Sept. 10 in Science Advances, could inspire novel strategies for combating Staphylococcus aureus (staph) and other extracellular bacterial pathogens.

It was known that neutrophils—first responder immune cells that migrate to sites of infection—can self-destruct and release their protein and DNA contents to generate neutrophil extracellular traps (NETs). Now, Vanderbilt researchers led by postdoctoral fellow Andrew Monteith, Ph.D., have discovered that NETs boost the bacterial killing power of another type of immune cell: macrophages.

Neutrophils produce the spider webs that immobilize the bacteria, and macrophages are the spiders that engulf and kill the bacteria. Neutrophils and macrophages are both phagocytic cells known for ingesting bacteria and producing antimicrobial peptides, reactive oxygen species and other enzymes to fight infection. NET generation (NETosis), thought to be a form of programmed cell death, is a more recently discovered neutrophil antibacterial strategy. The released neutrophil DNA creates a sticky trap that is also studded with antimicrobial peptides.

The macrophages end up with not only their own antibacterial arsenal, but also the neutrophils' antibacterial arsenal, all in the same compartment killing the bacteria.

 Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens, Science Advances (2021). DOI: 10.1126/sciadv.abj2101

https://phys.org/news/2021-09-caught-web-reveals-immune-cells.html?...

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 9:21am

A new gold standard for detecting cancer mutations

An international research collaboration has identified a new gold standard for detecting cancer mutations using genomic pathology.

This research set out to understand why there has been a history of low reproducibility of genomic testing results between different labs when detecting cancers.

Scientists found factors like sample and library preparation, differing sequencing technology and bioinformatic tools were affecting the reproducibility and performance of the genomic analytical techniques.

The research team have now developed a set recommendations and guidelines on how to improve the reproducibility and precision of the tumor mutation detection in clinical practice.

All stages of mutation detection are interdependent and this dependency is complex.

There is no 'one way' to detect cancerous tumor mutations. For example, the amount of DNA sequencing needed to detect a cancer mutation will vary based on the amount of tumor content.

Every person is different and should be treated differently. And our research provides a new tool to improve precision medicine.

Wenming Xiao et al, Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing, Nature Biotechnology (2021). DOI: 10.1038/s41587-021-00994-5

https://medicalxpress.com/news/2021-09-gold-standard-cancer-mutatio...

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 9:15am

First, the scientists investigated various cell lines to examine their gene expression levels of ACE2. They found that those cells originating in the oral cavity, lungs and liver had the highest ACE2 expression.

These high-ACE2-expression cells were then subjected to various doses of cigarette-smoke extract (CSE) for 24 hours. After this, the rate of expression of the CYP1A1 gene, which is known to be inducible by CSE, was evaluated. The CSE treatment had induced increased expression of CYP1A1 gene in liver and lung cells in a dose-dependent manner—the greater the dose, the greater the effect. However, this effect was not as pronounced in oral cavity cells. In other words, greater activity of the CYP1A1, less production of the ACE2 receptors—the route that the virus is able to enter cells.

In order to explain why this was happening in the presence of cigarette smoke, the researchers then used RNA sequencing analysis to investigate what was happening with gene expression more comprehensively. They found that CSE increased the expressions of genes related to a number of key signaling processes within the cell that are regulated by AHR.

To more directly observe this mechanism by which AHR acts on ACE2 expression, the effects of two drugs that can activate AHR were evaluated on the liver cells. The first, 6‑formylindolo(3,2‑b)carbazole (FICZ) is derivative of the amino acid tryptophan, and the second, omeprazole (OMP), is a medication already widely used in the treatment of acid reflux and peptic ulcers.

RNA sequencing data suggested that the CYP1A1 gene was strongly induced in liver cells by these AHR activators, and expression of the ACE2 gene was strongly inhibited, again in a dose-dependent manner.

In other words, the cigarette smoke extract and these two drugs—all of which act as activators of AHR—are able to suppress the expression of ACE2 in mammalian cells, and by doing so, reduce the ability of the SARS-CoV-2 virus to enter the cell.

Keiji Tanimoto et al, Inhibiting SARS-CoV-2 infection in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl-hydrocarbon receptor signal, Scientific Reports (2021). DOI: 10.1038/s41598-021-96109-w

https://medicalxpress.com/news/2021-09-drugs-mimic-effects-cigarett...

Part 2

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 9:14am

Drugs that mimic effects of cigarette smoke reduce SARS-CoV-2's ability to enter cells

Researchers have identified a potential reason why lower numbers of COVID cases have appeared amongst smokers compared to non-smokers, even as other reports suggest smoking increases severity of the disease.

Researchers have identified two drugs that mimic the effect of chemicals in cigarette smoke to bind to a receptor in mammalian cells that inhibits production of ACE2 proteins, a process that appears to reduce the ability of the SARS-CoV-2 virus to enter the cell.

The findings appear in the journal Scientific Reports on 17 August.

Something of a paradox exists with respect to smoking cigarettes and COVID-19. Active smoking is associated with increased severity of disease, but at the same time, many reports have suggested lower numbers of COVID cases amongst smokers than amongst non-smokers.

Something strange was going on here. We must stress the presence of strong evidence showing that smoking increases the severity of COVID-19. But the mechanism now discovered  is worth further investigation as a potential tool to fight SARS-CoV-2 infections.

--

It is known that cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs). These can bind to and activate aryl hydrocarbon receptors (AHRs). A receptor is any structure of the surface or inside of a cell that is shaped to receive and bind to a particular substance. AHRs are a type of receptor inside of mammalian cells that is in turn a transcription factor—something that can induce a wide range of cellular activities through its ability to increase or decrease the expression of certain genes.

Knowing this about the relationship between PAHs and AHRs, the researchers wanted to investigate the effect of drugs that activate AHR on expression of the genes that control production of the ACE2 protein—the infamous receptor protein on the surface of many cells types that works like a lock that the SARS-CoV-2 virus is able to pick. After binding the virus to the ACE2 protein, it can then enter and infect the cell.

Part 1

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 9:07am

Study: AI can make better clinical decisions than humans

There's no harm in getting a second opinion. But what if that second opinion could be generated by a computer, using artificial intelligence? Would it come up with better treatment recommendations than your professional proposes?

Medical and educational professionals frequently disagree on the effectiveness of behavioral interventions, which may cause people to receive inadequate treatment.

To find a better way, researchers compiled simulated data from 1,024 individuals receiving treatment for behavioral issues. The researchers then compared the treatment conclusions drawn in each case by five doctoral-level behavior analysts with those produced by a computer model the two academics developed using machine learning.

The five professionals only came to the same conclusions approximately 75 percent of the time. More importantly, machine learning produced fewer decision-making errors than did all the professionals.

Given these very positive results, the next step would be to "integrate these models in an app that could automatically make decisions or provide feedback about how treatment is progressing". 

The goal, the researchers think, should be to use machine learning to facilitate the work of professionals, not actually replace them, while also making treatment decisions more consistent and predictable.

 Marc J. Lanovaz et al, Machine learning to analyze single‐case graphs: A comparison to visual inspection, Journal of Applied Behavior Analysis (2021). DOI: 10.1002/jaba.863

https://techxplore.com/news/2021-09-ai-clinical-decisions-humans.ht...

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 9:01am

New technology designed to genetically control disease-spreading mosquitoes

Leveraging advancements in CRISPR-based genetic engineering, researchers have created a new system that restrains populations of mosquitoes that infect millions each year with debilitating diseases.

The new precision-guided sterile insect technique, or pgSIT, alters genes linked to male fertility—creating sterile offspring—and female flight in Aedes aegypti, the mosquito species responsible for spreading wide-ranging diseases including dengue fever, chikungunya and Zika.

pgSIT is a new scalable genetic control system that uses a CRISPR-based approach to engineer deployable mosquitoes that can suppress populations. Males don't transmit diseases so the idea is that as you release more and more sterile males, you can suppress the population without relying on harmful chemicals and insecticides.

pgSIT differs from "gene drive" systems that could suppress disease vectors by passing desired genetic alterations indefinitely from one generation to the next. Instead, pgSIT uses CRISPR to sterilize male mosquitoes and render female mosquitoes, which spread disease, as flightless. The system is self-limiting and is not predicted to persist or spread in the environment, two important safety features that should enable acceptance for this technology.

Suppressing mosquito populations with precision guided sterile males, Nature Communications (2021). DOI: 10.1038/s41467-021-25421-w

https://phys.org/news/2021-09-technology-genetically-disease-spread...

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 8:57am

New programmable gene editing proteins found outside of CRISPR systems

Within the last decade, scientists have adapted CRISPR systems from microbes into gene editing technology, a precise and programmable system for modifying DNA. Now, scientists at MIT's McGovern Institute and the Broad Institute of MIT and Harvard have discovered a new class of programmable DNA modifying systems called OMEGAs (Obligate Mobile Element Guided Activity), which may naturally be involved in shuffling small bits of DNA throughout bacterial genomes.

These ancient DNA-cutting enzymes are guided to their targets by small pieces of RNA. While they originated in bacteria, they have now been engineered to work in human cells, suggesting they could be useful in the development of gene editing therapies, particularly as they are small (~30% the size of Cas9), making them easier to deliver to cells than bulkier enzymes. The discovery, reported in the journal Science, provides evidence that natural RNA-guided enzymes are among the most abundant proteins on earth, pointing toward a vast new area of biology that is poised to drive the next revolution in genome editing technology.

Han Altae-Tran et al, The widespread IS200/605 transposon family encodes diverse programmable RNA-guided endonucleases, Science (2021). DOI: 10.1126/science.abj6856

https://phys.org/news/2021-09-programmable-gene-proteins-crispr.htm...

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 8:54am

Research on beards, wads of gum wins 2021 Ig Nobel prizes

Beards aren't just cool and trendy—they might also be an evolutionary development to help protect a man's delicate facial bones from a punch to the face.

That's the conclusion of a trio of scientists from the University of Utah who are among the winners of this year's Ig Nobel prizes, the Nobel Prize spoofs that honor—or maybe dishonor, depending on your point of view—strange scientific discoveries.

The winners of the 31st annual Ig Nobels being announced Thursday included researchers who figured out how to better control cockroaches on U.S. Navy submarines; animal scientists who looked at whether it's safer to transport an airborne rhinoceros upside-down; and a team that figured out just how disgusting that discarded gum stuck to your shoe is.

These sound like  silly studies, but as usual, there was some method to the madness. These findings have implications for a wide range of disciplines, including forensics, contagious disease control, or bioremediation of wasted chewing gum residues.

https://www.improbable.com/2021-ceremony/winners/

https://phys.org/news/2021-09-beards-wads-gum-ig-nobel.html?utm_sou...

Comment by Dr. Krishna Kumari Challa on September 11, 2021 at 6:45am

How Volcanic Eruptions Can Cool Earth? -- Explained!

Climate change includes both global warming driven by human-induced emissions of greenhouse gases and the resulting large-scale shifts in weather patterns.

Comment by Dr. Krishna Kumari Challa on September 10, 2021 at 12:03pm

Sim shows how COVID virus infects cells

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