To edit even larger sequences, the researchers used their twin prime editing system to install "landing sites" in the genome for enzymes called site-specific recombinases, which catalyze the integration of DNA at specific sites in the genome. The team then treated the cells with a recombinase enzyme and introduced the long pieces of DNA they wanted to insert into the genome. Combining twinPE and recombinase enzymes allowed the scientists to edit sequences thousands of base pairs long—the length of entire genes.

 Andrew V. Anzalone et al, Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing, Nature Biotechnology (2021). DOI: 10.1038/s41587-021-01133-w

https://phys.org/news/2021-12-prime-inserts-entire-genes-human.html...

Inching closer towards "living biotherapeutics"

The human gut is home to thousands of species of bacteria, and some of those bacteria have the potential to treat a variety of gastrointestinal diseases. Some species may help to combat colon cancer, while others could help treat or prevent infections such as C. difficile.

One of the obstacles to developing these "living biotherapeutics" is that many of the species that could be beneficial are harmed by oxygen, making it difficult to manufacture, store, and deliver them. Chemical engineers have now shown that they can protect those bacteria with a coating that helps them to survive the manufacturing process.

In a study appearing today in the Journal of the American Chemical Society, the researchers showed they could use the coating on a strain of E. coli as well as another species that may aid in digestion of plant starches. The coating could be applied to many other species as well, they say. They think this coating could be used to protect pretty much any microbe of interest.

Most of the microbes that live in the human gut are anaerobic, and they have varying degrees of sensitivity to oxygen. Some can tolerate a little bit of oxygen, while for others, oxygen is deadly.

This makes it difficult to test their potential as treatments for human disease, because bacteria need to be freeze-dried and formulated as capsules in order to be used therapeutically. In this study, researchers decided to try protecting anaerobic bacteria by coating them with a material made from metal ions and organic compounds called polyphenols.

When polyphenols and metal ions are put into a solution, they form a two-dimensional, grid-like sheet. For this study, the researchers used iron, which is safe for human consumption, and three polyphenols that are all classified as GRAS (generally regarded as safe) : gallic acid, tannic acid, and epigallocatechin (EGCG), all of which are found in tea and other plant products.

If bacteria are also added to the solution, the material self-assembles into a coating on individual bacterial cells. This coating protects bacteria during the freeze-drying and manufacturing process. The researchers showed that the coated cells were healthy and able to perform normal cellular activities, although their growth was temporarily inhibited.

When exposed to an acidic environment, such as that of the stomach, the coating breaks down and releases the bacteria. Coating the bacteria with a protective layer could eliminate the need for cold storage and make distribution easier. This would make a lot of therapeutics more widely available.

Gang Fan et al, Protection of Anaerobic Microbes from Processing Stressors Using Metal–Phenolic Networks, Journal of the American Chemical Society (2021). DOI: 10.1021/jacs.1c09018

https://phys.org/news/2021-12-biotherapeutics.html?utm_source=nwlet...

Science with Webb: the nearby cosmos

Scientists Smash Temperature Record on Keeping 'Freezing Cold' Water in Liquid Form

Scientists have just proven that the freezing temperature of water can be even lower than what we thought was possible.

Taking tiny droplets of water, up to just 150 nanometers in size, a team of engineers at the University of Houston has pushed the critical temperature threshold to -44 degrees Celsius (-47.2 degrees Fahrenheit) – and, more saliently, accurately measured it.

common H₂O is actually pretty weird; it doesn't behave like any other liquid. Even the way it freezes is weird: where other liquids increase in density as they cool, water actually becomes less dense as it freezes.

Water's behavior has been fairly well characterized and studied. We know, for example, that it tends to nucleate, or form ice crystals, at a variety of temperatures, sometimes resisting the process as far as -38 degrees Celsius. Any colder, and even the most stubborn water molecules will stick together as ice.

pushed that temperature downwards by placing nanodroplets of water on a soft surface, like a gel or a lipid. Then, they probed the droplets using electrical resistance metrology and Fourier transform infrared spectroscopy to take their temperature as they froze.

The soft interface between the surface and the tiny droplet seemed to play a role in the suppression of ice nucleation, possibly because of the way the interface generates a large pressure on the droplet.

This is because the freezing temperature of water drops as ambient pressure rises. The most pronounced effect was seen in a droplet of water just 2 nanometers across.

If a water droplet is in contact with a soft interface, freezing temperature could be significantly lower than hard surfaces. And a few-nanometer water droplet could avoid freezing down to -44 degrees Celsius if it is in contact with a soft interface.

The way tiny water droplets freeze is vitally important to cryopreservation, since the freezing of tiny droplets within cells can cause those cells to rupture and die. Learning how to slow or halt that process could help scientists find ways to mitigate that effect. It could also help us better understand how nucleation happens in the atmosphere, where microscopic droplets of water freeze. And it could also help us to better design technology that suffers from ice exposure, such as aircraft and wind turbines.

https://www.nature.com/articles/s41467-021-27346-w

https://www.sciencealert.com/scientists-break-a-temperature-record-...

Synthetic Food Dyes and health risk

Early-onset colorectal cancer incidence among the young, defined as those under age 50, has been rising globally since the early 1990s. Rates for colon and rectal cancers are expected to increase by 90 percent and 124 percent, respectively, by 2030.

One suspected reason behind this trend is increased global consumption of a Westernized diet that consists heavily of red and processed meats, added sugar, and refined grains. Modern day diet is made up of ultra-processed food such as industrial baked sweets, soft drinks, and processed meat. It is associated with an increased risk of colorectal cancer.

One aspect of ultra-processed foods I'm concerned about is how colorful they are. This characteristic is on full display in many delicious foods and treats present during the year-end holidays.

However, many of the colours that make up candy canes, sugar cookies, and even cranberry sauce and roast ham, are synthetic. And there's some evidence that these artificial food dyes may trigger cancer-causing processes in the body.

Part 1

The food industry uses synthetic dyes because they make food look better. The first food dyes were created from coal tar in the late 1800s. Today, they are often synthesized from a chemical derived from petroleum called naphthalene to make a final product called an azo dye.

Food manufacturers prefer synthetic dyes over natural dyes like beet extract because they are cheaper, brighter, and last longer. While manufacturers have developed hundreds of synthetic food dyes over the past century, the majority of them are toxic. Only nine are approved for use in food under U.S. Food and Drug Administration policy, and even fewer pass European Union regulations.

What drives colorectal cancer?

DNA damage is the primary driver of colorectal cancer. When DNA damage occurs on cancer driver genes, it can result in a mutation that tells the cell to divide uncontrollably and turn cancerous.

Another driver of colorectal cancer is inflammation. Inflammation occurs when the immune system sends out inflammatory cells to begin healing an injury or capture disease-causing pathogens.

When this inflammation persists over time, it can harm otherwise healthy cells by releasing molecules called free radicals that can damage DNA.

Another type of molecule called cytokines can prolong inflammation and drive increased cell division and cancer development in the gut when there isn't an injury to heal.

Long-term poor dietary habits can lead to a simmering low-grade inflammation that doesn't produce noticeable symptoms, even while inflammatory molecules continue to damage otherwise healthy cells.

Part 2

Synthetic food dyes and cancer

Although none of the FDA-approved synthetic food colors are classified as carcinogens, currently available research points to potential health risks and   researchers  find this concerning.

For instance, the bacteria in your gut can break down synthetic dyes into molecules that are known to cause cancer. More research is needed on how the microbiome interacts with synthetic food coloring and potential cancer risk.

Studies have shown that artificial food dyes can bind to the DNA and proteins inside cells. There is also some evidence that synthetic dyes can stimulate the body's inflammatory machinery. Both of these mechanisms may pose a problem for colon and rectal health.

Synthetic food dyes have been found to damage DNA in rodents. This is supported by unpublished data from my research team showing that Allura Red, or Red 40, and Tartrazine, or Yellow 5, can cause DNA damage in colon cancer cells with increased dosages and length of exposure in vitro in a controlled lab environment.

Our results will need to be replicated in animal and human models before we can say that these dyes directly caused DNA damage, however.

Finally, artificial food coloring may be of particular concern for children. It's known that children are more vulnerable to environmental toxins because their bodies are still developing. I and others believe that this concern may extend to synthetic food dyes, especially considering their prevalence in children's food.

A 2016 study found that over 40 percent of food products marketed toward children in one major supermarket in North Carolina contained artificial food coloring. More research needs to be done to examine how repeated exposure to artificial food dyes may affect children.

A few treats during the holidays won't cause colorectal cancer. But a long-term diet of processed foods might. While more research is needed on the link between synthetic food dyes and cancer, there are evidence-based steps you can take now to reduce your risk of colorectal cancer.

One way is to get screened for colon cancer. Another is to increase your physical activity. Finally, you can eat a healthy diet with more whole grains and produce and less alcohol and red and processed meat. Though this means eating fewer of the colorful, ultra-processed foods that may be plentiful during the holidays, your gut will thank you in the long run.

https://theconversation.com/colorful-sweets-may-look-tasty-but-some...

Researchers discover how cells from tumors remain dormant for years before metastasis occurs

Researchers have solved a major mystery in cancer research: How cancer cells remain dormant for years after they leave a tumor and travel to other parts of the body, before awakening to create metastatic cancer.

According to findings reported in Nature Cancer in December, the cells remain quiet by secreting a type of collagen, called type III collagen, in the environment around themselves, and only turn malignant once the level of collagen tapers off. The researchers found that by enriching the environment around the cells with this collagen, they could force the cells to remain in a dormant state and prevent tumour recurrence.

Most cancer deaths are due to metastases, which can occur several years after a tumor is removed. Previous research has studied how dispersed tumor cells come out of dormancy; this new work showed how the cells remain dormant.

In patient samples, the researchers showed that an abundance of the collagen could be used as a potential measurement to predict tumor recurrence and metastasis. In the mouse models, when scientists increased the amount of type III collagen around cancer cells that had left a tumor, cancer progression was interrupted and the disseminated cells were forced into a dormant state. Similar to wound treatment, in which collagen scaffolds have been proposed as a therapeutic alternative for complex skin wounds, this study suggest that by using strategies that aim to enrich the tumor microenvironment in type III collagen, metastasis may be prevented by activating tumor cell dormancy.

Jose Bravo-Cordero, A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy, Nature Cancer (2021). DOI: 10.1038/s43018-021-00291-9. www.nature.com/articles/s43018-021-00291-9

https://medicalxpress.com/news/2021-12-cells-tumors-dormant-years-m...

New resistance-busting antibiotic combination could extend the use of 'last-resort' antibiotics

Scientists have discovered a new potential treatment that has the ability to reverse antibiotic resistance in bacteria that cause conditions such as sepsis, pneumonia, and urinary tract infections.

Carbapenems, such as meropenem, are a group of vital often 'last-resort' antibiotics used to treat serious, multi-drug resistant infections when other antibiotics, such as penicillin, have failed. But some bacteria have found a way to survive treatment with carbapenems, by producing enzymes called metallo-beta-lactamases (MBLs) that break down the carbapenem antibiotics, stopping them from working.

Highly collaborative research, conducted by scientists from the Ineos Oxford Institute (IOI) for Antimicrobial Research at the University of Oxford and several institutions across Europe, found that the new class of enzyme blockers, called indole carboxylates, can stop MBL resistance enzymes working leaving the antibiotic free to attack and kill bacteria such as E. coli in the lab and in infections in mice.

The researchers first screened hundreds of thousands of chemicals to see which would attach tightly to MBLs to stop them working, and which didn't react with any human proteins, leading to the discovery of the indole carboxylates as promising new candidates. Using a process called crystallography to zoom in to take a closer look at how they work, the researchers found these potential drugs attach to MBLs in a completely different way to any other drugs—they imitate the interaction of the antibiotic with the MBLs. This clever Trojan Horse trick allows these potential drugs to be highly effective against a very wide range of MBL-producing superbugs.

Jürgen Brem, Imitation of β-lactam binding enables -spectrum metallo-β-lactamase inhibitors, Nature Chemistry (2021). DOI: 10.1038/s41557-021-00831-x. www.nature.com/articles/s41557-021-00831-x

https://phys.org/news/2021-12-resistance-busting-antibiotic-combina...

Testing Mars Sample Return

Teams across multiple NASA centers and the European Space Agency are working together to prepare a set of missions that would return the samples being collected by the Mars Perseverance rover safely back to Earth. This video features some of that prototype testing underway for the proposed Sample Retrieval Lander, Mars Ascent Vehicle launch systems, and the Earth Entry System. Credit: NASA/JPL-Caltech

A longer-lasting COVID vaccine

Researchers have identified rare, naturally occurring T cells that are capable of targeting a protein found in SARS-CoV-2 and a range of other coronaviruses.

The findings suggest that a component of this protein, called viral polymerase, could potentially be added to COVID-19 vaccines to create a longer-lasting immune response and increase protection against new variants of the virus.

Most COVID-19 vaccines use part of the spike protein found on the surface of the virus to prompt the immune system to produce antibodies. However, newer variants — such as delta and omicron — carry mutations to the spike protein, which can make them less recognizable to the immune cells and antibodies stimulated by vaccination. Researchers say that a new generation of vaccines will likely be needed to create a more robust and wide-ranging immune response capable of beating back current variants and those that may arise in the future.

One way to accomplish this is by adding a fragment of a different viral protein to vaccines — one that is less prone to mutations than the spike protein and that will activate the immune system’s T cells. T cells are equipped with molecular receptors on their surfaces that recognize foreign protein fragments called antigens. When a T cell encounters an antigen its receptor recognizes, it self-replicates and produces additional immune cells, some of which target and kill infected cells immediately and others which remain in the body for decades to fight that same infection should it ever return.

The researchers focused on the viral polymerase protein, which is found not only in SARS-CoV-2 but in other coronaviruses, including those that cause SARS, MERS and the common cold. Viral polymerases serve as engines that coronaviruses use to make copies of themselves, enabling infection to spread. Unlike the spike protein, viral polymerases are unlikely to change or mutate, even as viruses evolve.

To determine whether or not the human immune system has T cell receptors capable of recognizing viral polymerase, the researchers exposed blood samples from healthy human donors (collected prior to the COVID-19 pandemic) to the viral polymerase antigen. They found that certain T cell receptors did, in fact, recognize the polymerase. They then used a method they developed called CLInt-Seq to genetically sequence these receptors. Next, the researchers engineered T cells to carry these polymerase-targeting receptors, which enabled them to study the receptors’ ability to recognize and kill SARS-CoV-2 and other coronaviruses.

The study was published online in the journal Cell Reports.

https://researchnews.cc/news/10477/A-longer-lasting-COVID-vaccine--...

**

Using AI to Navigate Flow

Sodium-based material yields stable alternative to lithium-ion batteries

Researchers have created a new sodium-based battery material that is highly stable, capable of recharging as quickly as a traditional lithium-ion battery and able to pave the way toward delivering more energy than current battery technologies.

For about a decade, scientists and engineers have been developing sodium batteries, which replace both lithium and cobalt used in current lithium-ion batteries with cheaper, more environmentally friendly sodium. Unfortunately, in earlier sodium batteries, a component called the anode would tend to grow needle-like filaments called dendrites that can cause the battery to electrically short and even catch fire or explode.

Typically, the faster you charge, the more of these dendrites you grow. So if you suppress dendrite growth, you can charge and discharge faster, because all of a sudden it's safe.

 Yixian Wang et al, A Sodium–Antimony–Telluride Intermetallic Allows Sodium‐Metal Cycling at 100% Depth of Discharge and as an Anode‐Free Metal Battery, Advanced Materials (2021). DOI: 10.1002/adma.202106005

In one of two recent sodium battery advances from UT Austin, the new material solves the dendrite problem and recharges as quickly as a lithium-ion battery. The team published their results in the journal Advanced Materials.

https://techxplore.com/news/2021-12-sodium-based-material-yields-st...

**

How NASA’s Webb Telescope Will Transform Our Place in the Universe

World's first optical oscilloscope

 A team from UCF has developed the world's first optical oscilloscope, an instrument that is able to measure the electric field of light. The device converts light oscillations into electrical signals, much like hospital monitors convert a patient's heartbeat into electrical oscillation.

Until now, reading the electric field of light has been a challenge because of the high speeds at which light waves oscillates. The most advanced techniques, which power our phone and internet communications, can currently clock electric fields at up to gigahertz frequencies—covering the radio frequency and microwave regions of the electromagnetic spectrum. Light waves oscillate at much higher rates, allowing a higher density of information to be transmitted. However, the current tools for measuring light fields could resolve only an average signal associated with a 'pulse' of light, and not the peaks and valleys within the pulse. Measuring those peaks and valleys within a single pulse is important because it is in that space that information can be packed and delivered.

Fiber optic communications have taken advantage of light to make things faster, but we are still functionally limited by the speed of the oscilloscope. This new  optical oscilloscope may be able to increase that speed by a factor of about 10,000.

The research team developed the device and demonstrated its capability for real-time measurement of the electric fields of individual laser pulses. The next step for the team is to see how far they can push the speed limits of the technique.

https://www.ucf.edu/news/ucf-develops-the-worlds-first-optical-osci...

https://researchnews.cc/news/10569/Team-develops-the-world-s-first-...

New Maze-Like Surface Kills Bacteria in 2 Minutes: 120x Faster Than Normal Copper

If dangerous 99.99 percent of bacteria can be killed within 2 minutes? That is exactly this porous copper maze can do!

A newly developed copper surface does the job in just a couple of minutes, though, some 120 times faster than normal copper. The less time the bacteria hang around, of course, the safer that surfaces like door handles and worktops are going to be.

Crucial to the bacteria-killing abilities of the new material is its porous nature, which significantly increases the surface area compared with smooth copper. That means more of the bacteria cells can be attacked at once when they land.

To make this copper as porous as possible, researchers produced an alloy of copper and manganese  atoms, before applying a cheap and scalable "dealloying" technique to remove the manganese atoms.

That left behind a maze-like copper surface full of very small holes for the bacteria to get trapped inside – and it actually makes it harder for bacteria cells to form in the first place.

No special drugs or other treatments are required for the copper material to work, and when water hits the surface, it forms a thin film rather than droplets. That again improves the effectiveness of the copper ions in wiping out bacteria.

These combined effects not only cause structural degradation of bacterial cells, making them more vulnerable to the poisonous copper ions, but also facilitates uptake of copper ions into the bacterial cells.

https://www.sciencedirect.com/science/article/abs/pii/S014296122100...

https://www.sciencealert.com/new-copper-surface-kills-bacteria-in-2...

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-...

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...

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...

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...

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...

How organs evolve

Fuel Cell Cars

Chasing an Asteroid's Shadow

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

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

Bacteriostatic antibiotics promote CRISPR-Cas adaptive immunity by enabling increased spacer acquisition, Cell Host Microbe, 2021.

https://phys.org/news/2021-12-closer-harnessing-viruses-bacteria-an...

Part 3

Your seat on public transportation determines level of exposure to exhaled droplets

The COVID-19 pandemic has revealed the urgency of understanding how public transportation ventilation systems transmit viruses and how exhaled droplets evolve in ventilated spaces. Researchers have wondered if those ventilation systems can be improved to mitigate virus transmission.

In Physics of Fluids, researchers at IBM Research Europe developed a model with an unprecedented level of detail and focused on conditions that are more characteristic of asymptomatic transmission. The multiphysics model involved air and droplet dynamics, heat transfer, evaporation, humidity, and effects of ventilation systems.

"By visualizing the droplets and the flow, you realize the number of physical phenomena taking place around us that go unnoticed, such as the complex interactions between natural body plumes, exhalation, and ventilation.

Part 1

**

When it comes to preventing risk of infection, this is precisely what makes it difficult to contain."

The researchers analyzed what happens when speech droplets are exhaled from a row of sitting passengers in a ventilated space, like those in public transportation vehicles. In some of these systems, air is injected at the top and extracted at the bottom through the vents near the window seats.

This generates an internal recirculation to enhance thermal comfort and remove contaminants, but the researchers were interested in whether certain seat positions affect the circulation adversely.

The team found droplets from the window seat rose more and invaded the space of other passengers to a lesser extent shortly after exhalation. Moreover, droplets released from the middle seat contaminated the aisle passengers more, indicating the downward flow of personal ventilation in aisle seats could move droplets down and increase the risk of infection.

Droplets released from the aisle were dragged down by the ventilation system immediately.

Part 2

The researchers modeled various scenarios in close detail, such as a situation where passengers in different seats were pronouncing a vowel for a few seconds. By creating detailed representation of the flow field and tracking every single droplet, they were able to reconstruct their ventilation paths.

In the future, the team will reproduce conditions that more closely represent the diverse human activity on public transport vehicles to help inform actions, design, and operation of future ventilation systems for safer environments.

"These high-resolution simulations were focused on public transportation vehicles, but they could be extended to commercial or residential buildings, health care facilities, offices, or schools.

"Numerical investigation of droplets in a cross-ventilated space with sitting passengers under asymptomatic virus transmission conditions" Physics of Fluids, DOI: 10.1063/5.0070625

https://phys.org/news/2021-12-seat-exposure-exhaled-droplets.html?u...

Part 3

**

No mountain is high enough for microplastics

From Mount Everest to the Mariana Trench, microplastics are everywhere—even high in the Earth's troposphere where wind speeds allow them to travel vast distances, a study showed recently. 

Microplastics are tiny fragments—measuring less than 5 millimeters—that come from packaging, clothing, vehicles and other sources and have been detected on land, in water and in the air.

Scientists sampled air 2,877 meters above sea level at the Pic du Midi Observatory in the French Pyrenees, a so-called "clean station" because of the limited influence exerted on it by the local climate and environment.

There they tested 10,000 cubic meters of air per week between June and October of 2017 and found all samples contained microplastics.

Using weather data they calculated the trajectories of different air masses preceding each sample and discovered sources as far away as North Africa and North America.

The study's main author Steve Allen of Dalhousie University in Canada told AFP that the particles were able to travel such distances because they were able to reach great altitudes.

The research also points to microplastic sources in the Mediterranean Sea and the Atlantic Ocean.

Once in the air or ocean, it is moving around and around in an indefinite cycle.

Steve Allen, Evidence of free tropospheric and long-range transport of microplastic at Pic du Midi Observatory, Nature Communications (2021). DOI: 10.1038/s41467-021-27454-7. www.nature.com/articles/s41467-021-27454-7

https://phys.org/news/2021-12-microplastic-pristine-pyrenees-mounta...

What is the UV index? 

You've probably seen the UV index in the day's weather forecast, and you know it tells you when you need to cover up and wear sunscreen.

The Sun showers Earth with light at a huge spectrum of different wavelengths, and each wavelength can have a slightly different effect on human skin.

An important part of the spectrum is ultraviolet or UV radiation: light with wavelengths too short for our eyes to see, from around 400 nanometres to 10 nanometres.

There are two important kinds of UV radiation: UV-A, with wavelengths from 400–315 nanometres, and UV-B with wavelengths from 315–280 nanometres. (Shorter wavelengths are called UV-C, but are mainly blocked by the atmosphere so we don't need to worry about it.)

UV-A and UV-B both contribute to skin damage, aging and skin cancer. But UV-B is the more dangerous: it is the major cause of sunburn, cataracts and skin cancer.

The UV index tells you how much ultraviolet radiation is around at ground level on a given day, and its potential to harm your skin.

UV radiation is a component of sunlight that can cause tanning and sunburn in the short term. In the longer term, too much exposure to UV can cause cataracts and skin cancer.

In 2002, the World Health Organization devised the UV index in an effort to make people around the world more aware of the risks.

The index boils down several factors into a single number that gives you an idea of how careful you need to be in the sun. A score of 1 or 2 is low, 3–5 is moderate, 6 or 7 is high, 8–10 is very high, and 11 and above is extreme.

Part 1

The UV index takes into account how much UV radiation of different wavelengths is around and how each of those wavelengths affects our skin.

ARPANSA has a network of sensors around Australia measuring sunlight at different wavelengths to determine the UV index, with the information available online in real time.

This data is combined with other information about location, cloud cover and atmospheric conditions to produce maps and forecasts of the UV index for the whole country.

The UV index you see reported is usually the daily maximum—that's the highest it will be all day.

How high it gets depends on lots of factors, including your location, the time of year, the amount of cloud cover, and ozone and pollution in the atmosphere.

The index tends to be higher closer to the Equator and at high altitudes, as the sunlight has to pass through less air before it reaches the ground.

https://theconversation.com/what-is-the-uv-index-an-expert-explains...

Part 2

**

Hubble and Webb: A New Golden Age of Astronomy

Fire and Ice: The Puzzling Link Between Western Wildfires & Arctic Sea Ice

Researchers identify mechanism that explains how tissues form complex shapes that enable organ function

Our bodies are made of tissues arranged in complex shapes that aid in performing specific functions.

But how do cells fold themselves so precisely into such complicated configurations during development? What are the fundamental forces driving this process?

Now, researchers at Harvard Medical School have discovered a mechanical process by which sheets of cells morph into the delicate, looping semicircular canals of the inner ear.

The research reveals that the process involves a combination of hyaluronic acid, produced by cells, that swells with water, and thin connectors between cells that direct the force of this swelling to shape the tissue.

The conventional thinking is that the proteins actin and myosin act as tiny motors inside cells, pushing and pulling them in different directions to fold a tissue into a specific shape. However, the researchers discovered that zebrafish semicircular canals form through a markedly different process. During development, the cells produce hyaluronic acid, which is perhaps most well known as an antiwrinkle agent in beauty products. Once in the extracellular matrix the acid swells up, not unlike a diaper in a swimming pool. This swelling creates enough force to physically move nearby cells, but since the pressure is the same in all directions, the researchers wondered how the tissue ends up stretching in one direction and not another to form an elongated shape. The team found that this is accomplished by thin connectors between cells—dubbed cytocinches—that constrain the force.

It's like if you were to put a corset on a water balloon and deform it into an oblong structure. This combination of swelling and cinching progressively shapes an initially flat sheet of cells into tubes.

Although conducted in zebrafish, the work reveals a basic mechanism for how tissues take on shapes—one that is likely to be conserved across vertebrates, the researchers say, and may also have implications for bioengineering.

The genes that control hyaluronic acid production in zebrafish semicircular canals are also present in the semicircular canals  of mammals, suggesting that a similar process may be occurring. Moreover, hyaluronic acid is found in multiple parts of the human body, including skin and joints, indicating that it may play a role in shaping many tissues and organs—an avenue for future research.

If that does turn out to be the case, then studying the genes involved in hyaluronic acid production could help researchers understand congenital defects in organs where hyaluronic acid drives development.

Sean G. Megason, Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis, Cell (2021). DOI: 10.1016/j.cell.2021.11.025. www.cell.com/cell/fulltext/S0092-8674(21)01373-8

https://phys.org/news/2021-12-mechanism-tissues-complex-enable-func...

Scientists Just Identified a Brand New Muscle Layer in The Human Jaw

Undoubtedly there are still exciting new discoveries to be made in a field as well-studied as human anatomy: researchers have confirmed the existence of a layer of muscle in the human jaw that has until now eluded anatomists.

This new muscle is a deeper, third section of the masseter muscle. It's the most prominent jaw muscle: press your hand against the back of your jaw while you chew and you'll feel it moving.

Typically represented as having just two layers, there has been suspicions based on animal studies that there is more to its structure. However until now, attempts to describe it have been contradictory and confusing.

Through an analysis of more than two dozen human heads – including one living subject and 12 heads preserved in formaldehyde – it's been established through a new study that the masseter muscle does indeed have three distinct sections, not two.

This deep section of the masseter muscle is clearly distinguishable from the two other layers in terms of its course and function.

The name Musculus masseter pars coronidea, or the coronoid section of the masseter, has been proposed for the new muscle layer by the researchers, because it attaches to the muscular (coronoid) process of the lower jaw – the mandible bone.

https://www.sciencedirect.com/science/article/pii/S0940960221002053

https://www.sciencealert.com/scientists-just-identified-a-new-muscl...

Alarming Levels of Microplastics in The Feces of People With Irritable Bowel Diseases or IDB

A recent investigation by a team of researchers in Nanjing, China, has uncovered worrying signs that elevated levels of microplastics could be inflaming our digestive systems.

Feces collected from 52 individuals diagnosed with inflammatory bowel disease (IBD) were found to contain around 1.5 times the number of plastic particles smaller than 5 millimeters (about 0.2 inches) than similar samples from volunteers without any chronic illnesses.

The vast majority of plastic particles were smaller than 300 micrometers, with a few detectable pieces coming in below a minuscule 5 micrometers across. The researchers noticed those with IBD also tended to have a greater proportion of smaller flakes of microplastic.

What's more, the greater the plastic load, the more severe the individual's IBD symptoms. 

A survey revealed nothing unusual about the origins of the plastic, suggesting it was the kinds of particles we all might ingest by drinking from PET bottles or eating out of single-use disposable containers.

As an observational study, the research doesn't establish cause and effect. Nobody can claim the difference in microplastic load is solely, or even partially responsible for the symptoms of diarrhea, rectal bleeding, and abdominal cramping associated with the illness.

It's even possible having IBD might make it harder to clear the build-up of plastic detritus that accumulates in our diets.

But the mere possibility of a connection is concerning enough to warrant further investigation, especially given the shocking rate at which plastic waste is spreading virtually unabated.

Part 1

Seven million people globally were diagnosed with IBD in 2017, a condition distinguished by regular bouts of discomfort and changes in bowel motion produced by a hair-trigger system overreacting to otherwise benign materials in the gut. 

The illness usually falls into one of two main diagnoses: Crohn's disease, which is typically characterized by an inflamed lining throughout the deeper layers of the digestive tract, and ulcerative colitis, which is marked by ulcers in the large intestine's lining.

In either case, the ultimate source of the errant immune response isn't yet fully understood, though suspicions lie with the complex way our guts negotiate diplomatic relations with our microflora, particularly during an infection.

Whether plastic particles might somehow involve themselves with a link in this chain has never been fully made clear, though animal studies have previously pointed to gut inflammation as a possible side effect of microplastic exposure.

Part 2

Circumstantially, microplastics have also been shown to stir up trouble by generating reactive oxygen species that are known to play a role in inflammation.

With that in mind, it's not at all surprising to imagine an increase in gut exposure to microplastic particles might play a similar role to certain microbes in sensitizing the lining to an exaggerated immune reaction.

Further studies will be needed before we can claim with any confidence that our dietary supplement of plastic dust is putting us at increased risk of any health problems. There are still too many unknowns.

But that doesn't mean we shouldn't be taking action. Evidence that the rising tide of plastic waste is affecting everything from the climate to the distribution of species to the health of marine life is mounting.

That our health might be just one more consequence is just more reason to wean ourselves off our dependence on this pervasive pollutant.

https://pubs.acs.org/doi/10.1021/acs.est.1c03924

https://www.sciencealert.com/inflammatory-bowel-disease-feces-found...

Part 3

**

Comets' heads can be green, but never their tails. We finally know now why.

 Every so often, the Kuiper Belt and Oort Cloud throw galactic snowballs made up of ice, dust and rocks our way: 4.6-billion-year-old leftovers from the formation of the solar system.

These snowballs – or as we know them, comets – go through a colourful metamorphosis as they cross the sky, with many comets’ heads turning a radiant green colour that gets brighter as they approach the Sun.

But strangely, this green shade disappears before it reaches the one or two tails trailing behind the comet.

Astronomers, scientists and chemists have been puzzled by this mystery for almost a century. In the 1930s, physicist Gerhard Herzberg theorised the phenomenon was due to sunlight destroying diatomic carbon (also known as dicarbon or C2), a chemical created from the interaction between sunlight and organic matter on the comet’s head – but as dicarbon isn’t stable, this theory has been hard to test.

A new UNSW Sydney-led study, published in Proceedings of the National Academy of Sciences (PNAS), has finally found a way to test this chemical reaction in a laboratory – and in doing so, has proven this 90-year-old theory correct.

This explains why the green coma – the fuzzy layer of gas and dust surrounding the nucleus – shrinks as a comet gets closer to the Sun, and also why the tail of the comet isn’t green.

The key player at the centre of the mystery, dicarbon, is both highly reactive and responsible for giving many comets their green colour. It’s made up of two carbon atoms stuck together and can only be found in extremely energetic or low oxygen environments like stars, comets and the interstellar medium.

Dicarbon doesn’t exist on comets until they get close to the Sun. As the Sun starts to warm the comet up, the organic matter living on the icy nucleus evaporates and moves to the coma. Sunlight then breaks up these larger organic molecules, creating dicarbon.

The UNSW-led team have now shown that as the comet gets even closer to the Sun, the extreme UV radiation breaks apart the dicarbon molecules it recently created in a process called ‘photodissociation’. This process destroys the dicarbon before it can move far from the nucleus, causing the green coma to get brighter and shrink – and making sure the green tinge never makes it into the tail.

This is the first time this chemical interaction has been studied here on Earth.

1. Jasmin Borsovszky, Klaas Nauta, Jun Jiang, Christopher S. Hansen, Laura K. McKemmish, Robert W. Field, John F. Stanton, Scott H. Kable, Timothy W. Schmidt. Photodissociation of dicarbon: How nature breaks an unusual multiple bond. Proceedings of the National Academy of Sciences, 2021; 118 (52): e2113315118 DOI: 10.1073/pnas.2113315118

Mind-controlled robots now one step closer

A special microbe turns oil into gases all by itself

Microorganisms can convert oil into natural gas, i.e. methane. Until recently, it was thought that this conversion was only possible through the cooperation of different organisms. In 2019, Rafael Laso-Pérez and Gunter Wegener from the Max Planck Institute for Marine Microbiology suggested that a special archaeon can do this all by itself, as indicated by their genome analyses. Now, in collaboration with a team from China, the researchers have succeeded in cultivating this “miracle microbe” in the laboratory. This enabled them to describe exactly how the microbe achieves the transformation. They also discovered that it prefers to eat rather bulky chunks of food.

Underground oil deposits on land and in the sea are home to microorganisms that use the oil as a source of energy and food, converting it into methane. Until recently, it was thought that this conversion was only possible in a complicated teamwork between different organisms: certain bacteria and usually two archaeal partners. Now the researchers have managed to cultivate an archaeon called Methanoliparia from a settling tank of an oil production facility that handles this complex reaction all by itself.

This “miracle microbe” breaks down oil into methane and carbon dioxide. Now that the researchers have succeeded in cultivating these microorganisms in the laboratory, they were able to investigate the underlying processes in detail. They discovered that its genetic make-up gives Methanoliparia unique capabilities. “In its genes it carries the blueprints for enzymes that can activate and decompose various hydrocarbons. In addition, it also has the complete gear kit of a methane producer.

n their laboratory cultures, the researchers offered the microbes various kinds of food and used a variety of different methods to keep a close eye on how Methanoliparia deal with it. What was particularly surprising to see was that this archaeon activated all the different hydrocarbons with one and the same enzyme.

Zhuo Zhou, Cui-jing Zhang, Peng-fei Liu, Lin Fu, Ra­fael Laso-Pérez, Lu Yang, Li-ping Bai, Ji­ang Li, Min Yang, Jun-zhang Lin, Wei-dong Wang, Gunter We­gener, Meng Li, Lei Cheng (2021): Non-syn­trophic meth­ano­genic hy­dro­car­bon de­grad­a­tion by an ar­chaeal spe­cies. Nature (2021)

DOI: 10.1038/s41586-021-04235-2 

https://researchnews.cc/news/10687/A-special-microbe-turns-oil-into...

Frog cells transform into tiny living robots

A Scent of Space

Study shows robotic-assisted bladder removal reduces blood loss and enhances post-operative recovery

 Robotic-assisted radical cystectomy (RARC), the complete removal of the bladder with the use of surgical robots, has gained increasing acceptance worldwide. After the removal of the bladder, patients need to undergo a urinary diversion, such as the reconstruction of a “new bladder”. In the past, a urinary diversion had to be performed through an open approach, i.e. extracorporeal urinary diversion (ECUD). Recently, an intracorporeal urinary diversion (ICUD) approach has been introduced, and the whole procedure can be performed in a minimally invasive manner.

The Chinese University of Hong Kong’s Faculty of Medicine has led a...

https://www.med.cuhk.edu.hk/press-releases/study-led-by-cuhk-shows-...

https://researchnews.cc/news/10723/Study-shows-robotic-assisted-bla...

What makes an mRNA vaccine so effective against severe COVID-19?

The first two vaccines created with mRNA vaccine technology—the Pfizer/BioNTech and Moderna COVID-19 vaccines—are arguably two of the most effective COVID vaccines developed to date. In clinical trials, both were more than 90% effective at preventing symptomatic infection, easily surpassing the 50% threshold the Food and Drug Administration had set for COVID-19 vaccines to be considered for emergency use authorization.

While breakthrough infections have increased with the emergence of the delta and omicron variants, the vaccines remain quite effective at preventing hospitalizations and deaths. The success of the new technology has led scientists to try to figure out why mRNA vaccines are so effective and whether the protection they provide is likely to endure as new variants arise.

A new study from researchers at Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital shines light on the quality of the immune response triggered by mRNA vaccines. The study shows that the Pfizer vaccine strongly and persistently activates a kind of helper immune cell that assists antibody-producing cells in creating large amounts of increasingly powerful antibodies, and also drives the development of some kinds of immune memory. Known as T follicular helper cells, these cells last for up to six months after vaccination, helping the body crank out better and better antibodies. Once the helper cells decline, long-lived antibody-producing cells and memory B cells help to provide protection against severe disease and death, the researchers said.

Further, many of the T follicular helper cells are activated by a part of the virus that doesn't seem to pick up mutations, even in the highly mutated omicron variant. The findings, published online in the journal Cell, help explain why the Pfizer vaccine elicits such high levels of neutralizing antibodies and suggests that vaccination may help many people continue producing potent antibodies even as the virus changes.

The longer the T follicular helper cells provide help, the better the antibodies are and the more likely you are to have a good memory response. In this study, researchers found that these T follicular helper cell responses just keep going and going. And what's more, some of them are responding to one part of the virus's spike protein that has very little variation in it. With the variants, especially delta and now omicron, we've been seeing some breakthrough infections, but the vaccines have held up very nicely in terms of preventing severe disease and death. This strong T follicular helper response is part of the reason why the mRNA vaccines continue to be so protective.

1. Philip A. Mudd, Anastasia A. Minervina, Mikhail V. Pogorelyy, Jackson S. Turner, Wooseob Kim, Elizaveta Kalaidina, Jan Petersen, Aaron J. Schmitz, Tingting Lei, Alem Haile, Allison M. Kirk, Robert C. Mettelman, Jeremy Chase Crawford, Thi H.O. Nguyen, Louise C. Rowntree, Elisa Rosati, Katherine A. Richards, Andrea J. Sant, Michael K. Klebert, Teresa Suessen, William D. Middleton, Joshua Wolf, Sharlene A. Teefey, Jane A. O’Halloran, Rachel M. Presti, Katherine Kedzierska, Jamie Rossjohn, Paul G. Thomas, Ali H. Ellebedy. SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans. Cell, 2021; DOI: 10.1016/j.cell.2021.12.026

https://researchnews.cc/news/10732/What-makes-an-mRNA-vaccine-so-ef...

Real-space subfemtosecond imaging of quantum electronic coherences in molecules

" It has been a long-time dream of scientists to capture image of electron moving inside the atoms. For this scientist have been using two techniques to track the movement of an electron inside a molecule. One of the techniques of attosecond science enables to generate and trace the consequences of this motion in real time, but not in real space. On the other hand, another technique Scanning tunneling microscopy, can locally probe the valence electron density in molecules, but cannot alone provide dynamical information at this ultrafast timescale.

These results are a major boon for the scientific research world because it will facilitate understanding of chemical reactions. With the help of these understandings, scientists can gain new insights into the most elementary processes such as photosynthesis in plants and the biochemical processes on our retina which are also triggered by light. These experimental achievements can enable the manipulation of electron movements which will allow unprecedented control over chemical reactions and biological processes. The scientists have now come a huge step closer to achieving this goal."

Tracking electron motion in molecules is the key to understanding and controlling chemical transformations. Contemporary techniques in attosecond science are able to generate and trace the consequences of this motion in real time, but not in real space. Scanning tunnelling microscopy, on the other hand, can locally probe the valence electron density in molecules, but cannot alone provide dynamical information at this ultrafast timescale. Here researchers show that, by combining scanning tunnelling microscopy and attosecond technologies, quantum electronic coherences induced in molecules by <6-fs-long carrier-envelope-phase-stable near-infrared laser pulses can be directly visualized at ångström-scale spatial and subfemtosecond temporal resolutions. They demonstrate concurrent real-space and -time imaging of coherences involving the valence orbitals of perylenetetracarboxylic dianhydride molecules, and full control over the population of the involved orbitals. This approach opens the way to the unambiguous observation and manipulation of electron dynamics in complex molecular systems.

https://www.nature.com/articles/s41566-021-00929-1

Parasitic worms in dogs, cats may jump into people

Parasitic worms that infect companion animals such as dogs and cats are more likely to make the leap into humans than other worm species, according to new research.

The study also identified three species of worms that don't currently infect people but have a more than 70% chance of crossing into humans in the future.

The close relationships that we have with pets is the predominant reason why people might become infected with new species of parasitic worms.

Parasitic worms, or helminths, are estimated to infect 1.5 billion people globally, according to the World Health Organization. Many of these parasites infect humans, causing a number of serious illnesses, including schistosomiasis and filariasis.

Published in The Royal Society journal Philosophical Transactions B, the study focused on 737 parasitic worm species that predominantly infect wild and domesticated mammals. Of these, 137 are known to be able to infect people.

The researchers categorized the worm species' traits and built a machine learning model to determine which characteristics were most commonly associated with transmission into humans.

They found that worms that can infect companion animals or fish are more likely to cause human infection than worms that infect other animal species. Geographically widespread parasites were also more likely to make the jump from animals into people.

The analyses showed that three worm species not currently known to infect people have traits that make them very likely to be able to do so: Paramphistomum cervi, a flatworm mostly found in livestock and some wild animals; Schistocephalus solidus, a fish-based tapeworm that also infects birds and rodents; and Strongyloides papillosus, a pinworm found largely in livestock.

The study marks the first time these species have been identified as likely to infect humans, suggesting they are candidates for surveillance and further study.

It's relatively easy for dogs and cats to become infected with parasitic worms, particularly if they're allowed to wander during the day.

Dogs and cats aren't the only transmission route, though.

Fish also host a variety of parasitic worms. People can easily become infected by eating raw, undercooked or improperly prepared fish. The roundworm that causes herring worm disease, for example, infects thousands of people each year, largely in areas where eating raw fish is common, like Japan and parts of Europe.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450625/

https://researchnews.cc/news/10746/Parasitic-worms-in-dogs--cats-ma...

Oral and gut microbes can inactivate an antidiabetic drug

Acarbose is a commonly prescribed antidiabetic drug that helps control blood sugar levels by inhibiting human enzymes that break down complex carbohydrates. Now, new research  demonstrates that some bacteria in the mouth and gut can inactivate acarbose and potentially affect the clinical performance of the drug and its impact on bacterial members of the human microbiome. The paper appeared online and in the December 2, 2021 issue of the journal Nature.

Acarbose was originally isolated from bacteria that live in soil. These bacteria secrete acarbose to hinder the growth of other types of bacteria in their environment, giving themselves a competitive advantage. Both the natural bacterial version and the drug acarbose inhibit a-glucosidases, enzymes expressed by humans and bacteria to break down complex sugars into a form that can be metabolized for energy.

But acarbose-producing bacteria also express an antidote to it—an enzyme called acarbose kinase that modifies acarbose, rendering it inactive. 

This mechanism may accidentally affect the response of diabetic patients to this drug as well as shape its impact on the microbiome.

https://www.nature.com/articles/s41586-021-04091-0?proof=t+target%3D

https://researchnews.cc/news/10757/Oral-and-gut-microbes-can-inacti...