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Comment by Dr. Krishna Kumari Challa on December 21, 2021 at 11:38am

The new study by the University of Exeter, published in Cell Host Microbe, has cast new light on how to best combine antibiotics and phage therapy. Researchers conducted laboratory experiments on Pseudomonas aeruginosa a bacterium which causes disease in immunocompromised and cystic fibrosis patients. They exposed the bacterium to eight types of antibiotics—and found differences in the mechanisms by which the bacteria evolve resistance to phages, which affect how harmful they are.

Viruses penetrate molecules on the cell surface to infect bacteria. Like the human immune system, bacteria have their own CRISPR defense system, made up of proteins that fight off infection. As in human immune responses, this means that the virus infects the bacteria, and is then killed. In the process, the bacteria's CRISPR system learns to recognize and attack the virus in future.

However, the bacteria have a second defense option. They can also change their own cell surface to ward off infection, losing the receptor to which phages normally attach. This option comes with a cost to bacteria—the bacteria become less virulent, meaning they no longer cause disease, or the disease becomes less severe.

In the study, four of the eight antibiotics tested caused a dramatic increase in the levels of CRISPR-based immunity. These antibiotics are all bacteriostatic—they do not directly kill cells  but act by slowing down cell growth.

 Phage therapy could be an important part of the toolkit, in reducing antibiotic use, and in using them in combination to increase their efficiency. We found that by changing the type of antibiotics that are used in combination with phage, we can manipulate how bacteria evolve phage resistance, increasing the chances that treatment is effective. These effects should be considered during phage-antibiotic combination therapy, given their important consequences for pathogen virulence.

The researchers show that the effect of bacteriostatic antibiotics triggering CRISPR-Cas immunity results from slower phage replication inside the cell, which provides more time for the CRISPR-Cas system to acquire immunity and clear the phage infection. The research therefore identifies the speed of phage replication as a crucial factor controlling the possibility for CRISPR-Cas systems to defend against viruses.

Part 2

Comment by Dr. Krishna Kumari Challa on December 21, 2021 at 11:36am

Harnessing viruses to fight bacteria and reduce antibiotic use

New research has moved a step closer to harnessing viruses to fight bacterial infection, reducing the threat of antibiotic resistance.

A growing number of infections, including pneumonia, tuberculosis, gonorrhea, and salmonellosis, are developing antibiotic resistance, which means they becoming harder to treat, resulting in higher death rates, longer hospital stays and higher costs.

Phage therapy is the concept of using viruses (known as phage) that are harmless to humans to kill bacteria. Phage therapy can be used in combination with antibiotics to cure infections more effectively, and reduce the opportunity for bacteria to develop antibiotic resistance. However, bacteria can also evolve resistance to phages.

Part 1

Comment by Dr. Krishna Kumari Challa on December 21, 2021 at 10:59am

Chasing an Asteroid's Shadow

Comment by Dr. Krishna Kumari Challa on December 19, 2021 at 1:29pm

Fuel Cell Cars

Comment by Dr. Krishna Kumari Challa on December 19, 2021 at 1:06pm

How organs evolve

Comment by Dr. Krishna Kumari Challa on December 19, 2021 at 1:00pm

Scientists unveil drug discovery tool to screen more than 11 billion compounds

Scientists unveil drug discovery tool to screen more than 11 billion compounds

On the surface of our cells are docking stations called receptors. All kinds of compounds from caffeine and dopamine to heroin, THC and LSD bind to these receptors. In fact, G protein-coupled receptors are the intended targets of more than 30 percent of pharmaceutical products currently on the market. But these drugs often hit unintended targets—think carpet bombing the nervous system—leading to the laundry list of side effects commonly heard at the end of pharmaceutical commercials.

What we need are more precise and less harmful treatments that are just as effective.

But creating these better drugs isn't easy. Drug developers need to know the exact chemical structure of a drug and the intended receptor to produce the exact chemical reaction we want inside cells. The kicker is to make sure the drug doesn't affect other receptors or bind to the target receptors but bind in such a way to trigger unintended consequences inside cells.

In the past, scientists would test molecules in a one-by-one fashion against a therapeutic target in a lengthy and expensive operation. So scientists created virtual libraries of molecules and fancy computer programs to test hundreds of thousands of molecules at a time. By "test" we mean that the computer program scoured a database of molecules that theoretically could be created and theoretically could bind with the proper affinity to a given cell receptor. And then scientists could tinker with chemical bonds in a computer program to optimize a molecule's structure. Then scientists could physically make a tiny sliver of these molecules and test them in cell cultures.

The creation of virtual libraries was a giant leap in the field. Testing hundreds of thousands of possible molecules, some of which might be candidates with properties worth investigating, sounds like a lot. But there are billions upon billions of possible chemical combinations that could theoretically lead to the creation of a near infinite number of molecules or potential drugs. As a result, scientists wound up creating vast libraries of theoretical compounds, billions of mostly "undiscovered" and unexplored molecules that may or may not bind to a given cellular target; they may or may not have therapeutic value at all.

Unfortunately, chemical space is vast. It has been estimated that there exists, theoretically, more chemicals than there are actual molecules in the universe. And only a small sliver of the potential chemicals can be physically tested.

Researchers to validate V-SYNTHES, a new type of computational method that allows scientists to first identify the best combinations of chemical building blocks called synthons – hypothetical units within molecules – to serve as seeds that can grow into a hierarchy of molecules with the best predicted ability to bind to the receptor targets. This approach allows researchers to computationally test billions of compounds against a therapeutic target.

As described in their Nature paper, scientists tested 11 billion theoretical compounds against a cannabinoid receptor (CB2) that marijuana's active ingredient THC targets.

https://www.nature.com/articles/s41586-021-04220-9

https://www.med.unc.edu/pharm/scientists-unveil-drug-discovery-tool...

https://researchnews.cc/news/10594/Scientists-unveil-drug-discovery...

Comment by Dr. Krishna Kumari Challa on December 19, 2021 at 10:48am

In last 15 years, deforestation made outdoor work unsafe for millions

The tropics is becoming hotter due to a combination of warming associated with deforestation and climate change—and that can reduce the ability of outdoor workers to perform their jobs safely. Researchers reporting in the journal One Earth on December 17 estimate how many safe working hours people living in the tropics have lost due to local temperature change associated with loss of trees during the past 15 years.

There is a huge disproportionate decrease in safe work hours associated with heat exposure for people in deforested locations versus people in forestated locations just over the past 15 or 20 years.

There is a small amount of climate change that has happened over the same 15-year period, but the increase in humid heat exposure for people living in deforested relative to forested locations was much larger than that from recent climate change.

Previous research has revealed deforestation is associated with an increase in local temperature. Trees block out the sun's radiation and provide shade. They also cool down the air via evapotranspiration, a process when plants transport water from the soil then evaporate water from the leaf surface, similar to how sweating cools the skin.

"The trees in the tropics seem to limit the maximum temperatures that the air can reach. Once we cut those trees down, we lose that cooling service from the trees, and it can get really, really hot. In the Brazilian Amazon, for example, where huge swaths of the rainforest have been cleared in the last 15 or 20 years, the afternoons can be up to 10 degrees Celsius warmer than forested regions.

The One Earth study went a step further and estimated the number of people who live in locations affected by warming associated with deforestation. Using satellite data and meteorological observations, Parsons and his team tracked the local temperature and humidity in 94 low-latitude countries with tropical forests, including countries in the Americas, Africa, and Asia, from 2003 to 2018.

They estimated that in recently deforested locations, almost 5 million people lost at least half an hour of safe work time per day—when the weather outside is too hot and humid to safely conduct heavy labor. Among them, at least 2.8 million people are outdoor workers that perform heavy physical work in the agriculture and construction sectors. Heavy physical work increases heat generated within the human body, which when combined with hot and humid environments, increases the risk of heat strain and heat-related illnesses, including heat stroke, which can be fatal.

Luke AParsons, Tropical deforestation accelerates local warming and loss of safe outdoor working hours, One Earth (2021). DOI: 10.1016/j.oneear.2021.11.016. www.cell.com/one-earth/fulltex … 2590-3322(21)00664-3

https://phys.org/news/2021-12-years-deforestation-outdoor-unsafe-mi...

Comment by Dr. Krishna Kumari Challa on December 19, 2021 at 10:43am

Pain and anxiety impact breathing on a cellular level

You're startled by a threatening sound, and your breath quickens; you smash your elbow and pant in pain. Why a person's breathing rate increases dramatically when they're hurting or anxious was not previously understood. Now, a team of Salk scientists has uncovered a neural network in the brain that coordinates breathing rhythm with feelings of pain and fear. Along with contributions to the fields of pain management, psychological theories of anxiety, and philosophical investigations into the nature of pain, their findings could lead to development of an analgesic that would prevent opioid-induced respiratory depression (OIRD), the disrupted breathing that causes overdose deaths.

Scientists  focused on a group of neurons in the brainstem called the lateral parabrachial nucleus, which is arranged in a core-shell configuration. They found that neurons in the core project to the amygdala, an area of the brain that processes fear and the emotional experience of pain. Neurons in the shell project to the pre-Bötzinger complex, a region that generates breathing rhythm. The core and shell neurons influence each other according to inputs from these areas, making us breathe faster when we experience pain or anxiety.

SungHan, Divergent brainstem opioidergic pathways that coordinate breathing with pain and emotions, Neuron (2021). DOI: 10.1016/j.neuron.2021.11.029. www.cell.com/neuron/fulltext/S0896-6273(21)00990-9

https://medicalxpress.com/news/2021-12-pain-anxiety-impact-cellular...

Comment by Dr. Krishna Kumari Challa on December 19, 2021 at 10:23am

Visuals increase attention: science explains why

"Look at me!" we might say while attempting to engage  children. It turns out there is a neurochemical explanation for why looking at mom or dad or teacher actually helps kids pay better attention.

in a paper published recently scientists report that norepinephrine, a fundamental chemical for brain performance, is locally regulated in a brain region called the visual cortex.

Norepinephrine is known to be involved in paying attention. A certain amount of this chemical needs to be released for optimum brain performance and ability to pay attention. So, if there is either too much of it or too little of it, it may affect how we process information.

Disease states in which norepinephrine is known to be altered include substance use disorders, Alzheimer's disease, post-traumatic stress disorder (PTSD) and attention-deficit/hyperactivity disorder (ADHD). In some substance use, Alzheimer's and ADHD, the release of norepinephrine is reduced, resulting in lower attention. In other substance use and PTSD, the level is too high.

The team's findings also extend to cells called astrocytes that function as helper cells in the brain and central nervous system.

"When a person makes a movement, such as turning the head to listen to a parent, and that is combined with visual stimulation, then more norepinephrine is released where visual information is processed.

Astrocytes can reliably detect the rate of norepinephrine release. 

They are sensitive to it, in other words. Astrocytes alter their response accordingly, which is expected to change brain performance.

Understanding norepinephrine release, its local regulation and the astrocyte response may represent a mechanism by which one could enhance sensory-specific attention.

Shawn R. Gray et al, Noradrenergic terminal short-term potentiation enables modality-selective integration of sensory input and vigilance state, Science Advances (2021). DOI: 10.1126/sciadv.abk1378. www.science.org/doi/10.1126/sciadv.abk1378

https://medicalxpress.com/news/2021-12-visuals-attention-science.ht...

Comment by Dr. Krishna Kumari Challa on December 17, 2021 at 11:11am

Chemical Air Pollution Morphs Into Something Even More Toxic, Study Shows

Remnants of industrial chemicals in the air can potentially transform into new substances more toxic and persistent than the original pollution, according to a global study published recently.

Using samples gathered around the world, the study published in Nature found that these previously unidentified products are present in the atmospheres of 18 big cities around the world. The research proposes a new framework using laboratory tests and computer simulation to predict what chemicals will arise as products interact with the air and how toxic they will be.

They are chemicals that are added to a large variety of materials to delay the onset of fire. 

In a laboratory, scientists observed how these chemicals changed over time when in contact with oxidants in the air and found that they gave rise to 186 different substances.

Comparing these new substances with field samples, researchers  found 19 derived from the five most common flame retardants. None of the 19 had ever been identified in the ambient atmosphere before.

The researchers then used computer simulations to gauge the persistence, toxicity, and bio-accumulation of the derived chemicals.

They discovered that the new chemicals could have longer-lasting impacts on the environment and could be more toxic than their parent chemicals – in some cases 10 times as much.

https://www.nature.com/articles/s41586-021-04134-6

https://www.sciencealert.com/study-suggests-chemical-air-pollution-...

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