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Comment by Dr. Krishna Kumari Challa on October 7, 2022 at 7:45am

 How dormant bacteria calculate their return to life

While facing starvation and stress conditions, some bacteria enter a dormant state in which life processes stop. Shutting down into a deep dormancy allows these cells, called spores, to withstand punishing extremes of heat, pressure and even the harsh conditions of outer space.

Eventually, when conditions become favorable, spores that may have been dormant for years can wake up in minutes and spring back to life.

Spores wake up by re-hydrating and restarting their metabolism and physiology. But until now scientists did not know whether spores can monitor their environment "in their sleep" without waking up. In particular it was not known how spores deal with vague environmental signals that do not indicate clearly favorable conditions. Would spores just ignore such mixed conditions or take note?

Now biologists have solved this mystery in a new study published in the journal Science. Researchers  discovered that spores have an extraordinary ability to evaluate their surrounding environment while remaining in a physiologically dead state. They found that spores use stored electrochemical energy, acting like a capacitor, to determine whether conditions are suitable for a return to normal functioning life.

They show that cells in a deeply dormant state have the ability to process information. They discovered that spores can release their stored electrochemical potential energy to perform a computation about their environment without the need for metabolic activity.

A composite movie showing the phase contrast of a single spore (top left) to visualize the dormant state. A movie (top right) shows the color-coded electrochemical potential of the same spore. The plot (bottom left) shows the corresponding time trace of the electrochemical potential values changing over time. Finally, a corresponding bar plot (bottom right) visualizes the jumps toward the threshold for returning to life. Credit: Süel Lab

Kaito Kikuchi et al, Electrochemical potential enables dormant spores to integrate environmental signals, Science (2022). DOI: 10.1126/science.abl7484. www.science.org/doi/10.1126/science.abl7484

Comment by Dr. Krishna Kumari Challa on October 6, 2022 at 11:52am

Parental age could be key factor in helping thoroughbred horses be first past the post

In a sport where the finest of margins can determine the winner, a new study has shown that parental age can be a determining factor in who comes out on top in horse races.

Experts  have shown that the speed of thoroughbred horses declines as parental age at conception increases. The research team analyzed more than 900,000 race performances from more than 100,000 racehorses from races across Great Britain.

They found that the age of both the mothers and fathers of the horses played a significant role in the overall speed of the racehorses.

The researchers believe the study can play a pivotal part not only in optimizing racehorse breeding, but crucially offers further evidence that parental age can affect offspring characteristics.

Evidence of maternal and paternal age effects on speed in thoroughbred racehorses. Royal Society Open Science. doi.org/10.5061/dryad.qbzkh18m0

Comment by Dr. Krishna Kumari Challa on October 6, 2022 at 11:26am

A series of studies  over the last three years has demonstrated pTrMA's potential. A recent study published in ACS Applied Materials & Interfaces found that the polymer preserved insulin at temperatures of nearly 200 degrees Fahrenheit—close to water's boiling point—and through almost a year of refrigerated storage, with 87% of the medication remaining intact, compared with less than 8% of insulin alone. Laboratory experiments into pTrMA's safety showed that it did not trigger an immune response in mice.

A 2021 study showed that insulin plus pTrMA has a low enough viscosity to be safely injected, and 2020 research demonstrated that a version of pTrMA designed to degrade inside the body retained the ability to stabilize insulin.

An early finding, from 2014, that pTrMA actually works better than trehalose as a preserving agent hasn't been the only pleasant surprise along the way.

Madeline B. Gelb et al, Poly(trehalose methacrylate) as an Excipient for Insulin Stabilization: Mechanism and Safety, ACS Applied Materials & Interfaces (2022). DOI: 10.1021/acsami.2c09301

Madeline B. Gelb et al, Effect of Poly(trehalose methacrylate) Molecular Weight and Concentration on the Stability and Viscosity of Insulin, Macromolecular Materials and Engineering (2021). DOI: 10.1002/mame.202100197

Emma M. Pelegri-O'Day et al, Synthesis of Zwitterionic and Trehalose Polymers with Variable Degradation Rates and Stabilization of Insulin, Biomacromolecules (2020). DOI: 10.1021/acs.biomac.0c00133

Juneyoung Lee et al, Trehalose Glycopolymers as Excipients for Protein Stabilization, Biomacromolecules (2013). DOI: 10.1021/bm4003046

Part 2

Comment by Dr. Krishna Kumari Challa on October 6, 2022 at 11:18am

How the secrets of the tardigrade could improve lifesaving drugs like insulin

Tardigrade: This stocky microscopic animal, also known as a water bear, can survive in environments where survival seems impossible. Tardigrades have been shown to endure extremes of heat, cold and pressure—and even the vacuum of space—by entering a state of suspended animation and revitalizing, sometimes decades later, under more hospitable conditions.

If scientists  could understand the mechanism behind this extraordinary preservation they might be able to use the knowledge to improve medicines so that they remain potent longer and are less vulnerable to typical environmental challenges, ultimately broadening access and benefiting human health.

It turns out that one of the processes protecting tardigrades is spurred by a sugar molecule called trehalose, commonly found in living things from plants to microbes to insects, some of which use it as blood sugar. For a few select organisms, such as the water bear and the spiky resurrection plant, that can revive after years of near-zero metabolism and complete dehydration, trehalose's stabilizing power is the secret to their unearthly fortitude.

Armed with this insight, researchers invented a polymer based on the sugar. This polymer, called poly(trehalose methacrylate), or pTrMA, actually seems to improve upon nature in its ability to render drugs more robust to the ravages of time and temperature. They opted to investigate pTrMA's effects on insulin, a World Health Organization "essential medicine" that many people with diabetes inject daily to manage the disease.

Part 1

Comment by Dr. Krishna Kumari Challa on October 6, 2022 at 10:40am

For some materials like glass, this involves carefully heating the material so its molecules are unstuck and can arrange themselves in a more organized way. But for some materials, like mayonnaise, heating has destructive or unappetizing side effects. So for materials where heating is not an option, we use a process called mechanical annealing to physically deform the material and bring it to a lower energy state.

Researchers previously investigated how mechanical annealing of disordered solids can allow a material to a form a memory of that deformation, impacting how it responds to future deformation. In a new paper appearing Oct. 5 in the journal Science Advances, the researchers provide a more refined understanding of how memories form in disordered solids and how existing memories can be "read" and even erased.

Nathan C. Keim et al, Mechanical annealing and memories in a disordered solid, Science Advances (2022). DOI: 10.1126/sciadv.abo1614

part2 

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Comment by Dr. Krishna Kumari Challa on October 6, 2022 at 10:37am

Some everyday materials have memories, and now they can be erased

Some solid materials have a memory of how they have previously been stretched out, which impacts how they respond to these kinds of deformations in the future. A new study lends insight into memory formation in the foams and emulsions common in food products and pharmaceuticals and provides a new method to erase this memory, which could guide how materials are prepared for future use.

A crease in a piece of paper serves as a memory of being folded or crumpled. A lot of other materials form memories when they are deformed, heated up, or cooled down, and you might not know it unless you ask the right questions. Improving our understanding of how to write, read, and erase memories provides new opportunities for diagnostics and programming of materials. We can find out the history of a material by doing some tests or erase a material's memory and program a new one to prepare it for consumer or industrial use.

The researchers studied memory in a type of material called disordered solids, which have particles that are often erratically arranged. For example, ice cream is a disordered solid made up of a combination of ice crystals, fat droplets, and air pockets mixed together in a random way. This is in stark contrast to materials with "crystalline structures," with particles arranged in highly ordered rows and columns. Disordered solids are common in food sciences, consumer products, and pharmaceuticals and include foams like ice cream and emulsions like mayonnaise.

"Preparation of materials often includes manipulating them in ways that change the arrangement of their molecules, bubbles, or drops, taking them from a higher energy state to a lower energy, more stable state.

part1

Comment by Dr. Krishna Kumari Challa on October 6, 2022 at 8:39am

Nobel prize for three chemists who made molecules 'click'

Three scientists were jointly awarded this year's Nobel Prize in chemistry  this year for developing a way of "snapping molecules together" that can be used to explore cells, map DNA and design drugs that can target diseases such as cancer more precisely.

Americans Carolyn R. Bertozzi and K. Barry Sharpless, and Danish scientist Morten Meldal were cited for their work on click chemistry and bioorthogonal reactions. It's all about snapping molecules together.

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 11:57am

Aftermath of DART Impact

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 11:40am

The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication. After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.

By further optimizing the identified molecules, for which extremely high-resolution cryo-electron microscopic imaging was used, the researchers were able to synthesize agonists that produced high concentrations in the brain and reduced the sensation of pain effectively in investigations with animal models.

The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication , especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients.

Elissa A. Fink et al, Structure-based discovery of nonopioid analgesics acting through the α 2A -adrenergic receptor, Science (2022). DOI: 10.1126/science.abn7065

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Part 2

Comment by Dr. Krishna Kumari Challa on October 5, 2022 at 11:39am

Pain relief without side effects and addiction

New substances that activate adrenalin receptors instead of opioid receptors have a similar pain relieving effect to opiates, but without the negative aspects such as respiratory depression and addiction.

This is the result of research carried out by an international team of researchers. 

Opiates cause addiction, new substances do not

They are a blessing for patients suffering from severe pain, but they also have serious side effects: Opioids, and above all morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure. In addition, opiates are addictive—a high percentage of the drug problem  is caused by pain medication, for example.

In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics.

They are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances. It is only when researchers understand these on the atomic level that they can develop effective and safe active substances. They have now turned their attention to a new receptor that is responsible for binding adrenaline—the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine.

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