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Comment by Dr. Krishna Kumari Challa on June 7, 2022 at 8:00am

New nanoparticles aid sepsis treatment in mice

Sepsis, the body's overreaction to an infection, affects more than 1.5 million people and kills at least 270,000 every year in the U.S. alone. The standard treatment of antibiotics and fluids is not effective for many patients, and those who survive face a higher risk of death.

In new research published in the journal Nature Nanotechnology recently,  reported a new nanoparticle-based treatment that delivers anti-inflammatory molecules and antibiotics.

The new system saved the lives of mice with an induced version of sepsis meant to serve as a model for human infections, and is a promising proof-of-concept for a potential new therapy, pending additional research.

The new nanoparticles delivered the chemical NAD⁺ or its reduced form NAD(H), a molecule that has an essential role in the biological processes that generate energy, preserve genetic material and help cells adapt to and overcome stress. While NAD(H) is well known for its anti-inflammatory function, clinical application has been hindered because NAD(H) cannot be taken up by cells directly.

These nanoparticles can directly transport and release NAD(H) into the cell, while preventing premature drug release and degradation in the bloodstream.

Sepsis can be deadly in two phases. First, an infection begins in the body. The immune system responds by creating drastic inflammation that impairs blood flow and forms blood clots, which can cause tissue death and trigger a chain reaction leading to organ failure. Afterward, the body overcorrects itself by suppressing the immune system, which in turn increases infection susceptibility. Controlling complications caused by inflammation is vital in sepsis therapy.

The lipid-coated calcium phosphate or metal-organic framework nanoparticles designed by the researchers can be used to co-deliver NAD(H) and antibiotics.

Shaoqin Gong, NAD(H)-loaded nanoparticles for efficient sepsis therapy via modulating immune and vascular homeostasis, Nature Nanotechnology (2022). DOI: 10.1038/s41565-022-01137-w. www.nature.com/articles/s41565-022-01137-w

Comment by Dr. Krishna Kumari Challa on June 4, 2022 at 9:24am

Scientists announce a breakthrough in determining life's origin on Earth

Scientists  announced recently that ribonucleic acid (RNA), an analog of DNA that was likely the first genetic material for life, spontaneously forms on basalt lava glass. Such glass was abundant on Earth 4.35 billion years ago. Similar basalts of this antiquity survive on Mars today.

The study shows that long RNA molecules, 100-200 nucleotides in length, form when nucleoside triphosphates do nothing more than percolate through basaltic glass.

Basaltic glass was everywhere on Earth at the time. For several hundred million years after the Moon formed, frequent impacts coupled with abundant volcanism on the young planet formed molten basaltic lava, the source of the basalt glass. Impacts also evaporated water to give dry land, providing aquifers where RNA could have formed.

The same impacts also delivered nickel, which the team showed gives nucleoside triphosphates from nucleosides and activated phosphate, also found in lava glass. Borate (as in borax), also from the basalt, controls the formation of those triphosphates.

The same impactors that formed the glass also transiently reduced the atmosphere with their metal iron-nickel cores. RNA bases, whose sequences store genetic information, are formed in such atmospheres. The research team had previously showed that nucleosides are formed by a simple reaction between ribose phosphate and RNA bases

The beauty of this model is its simplicity. It can be tested by anybody. Mix the ingredients, wait for a few days and detect the RNA. The same rocks resolve the other paradoxes in making RNA in a path that moves all of the way from simple organic molecules to the first RNA.

Craig A. Jerome et al, Catalytic Synthesis of Polyribonucleic Acid on Prebiotic Rock Glasses, Astrobiology (2022). DOI: 10.1089/ast.2022.0027

Hyo-Joong Kim et al, Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine nucleotide from nucleobases and phosphorylated carbohydrates, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1710778114

Hyo-Joong Kim et al, A Prebiotic Synthesis of Canonical Pyrimidine and Purine Ribonucleotides, Astrobiology (2019). DOI: 10.1089/ast.2018.1935

Comment by Dr. Krishna Kumari Challa on June 4, 2022 at 8:46am

A soft wearable stethoscope designed for automated remote disease diagnosis

Digital stethoscopes provide better results compared to conventional methods to record and visualize modern auscultation(the action of listening to sounds from the heart, lungs, or other organs, typically with a stethoscope, as a part of medical diagnosis). Current stethoscopes are bulky, non-conformal, and not suited for remote use, while motion artifacts can lead to inaccurate diagnosis. In a new report now published in Science Advances,  a research team in engineering, nanotechnology, and medicine described a class of methods to offer real-time, wireless, continuous auscultation. The devices are part of a soft wearable system for quantitative disease diagnosis across various pathologies. Using the soft device, researchers  detected continuous cardiopulmonary sounds with minimal noise to characterize signal abnormalities in real-time. The team conducted a clinical study with multiple patients and control subjects to understand the unique advantage of the wearable auscultation method, with integrated machine learning, to automate diagnoses of four types of disease in the lung, ranging from a crackle, to a wheeze, stridor and rhonchi, with 95% accuracy. The soft system is applicable for a sleep study to detect disordered breathing and to detect sleep apnea.

Sung Hoon Lee et al, Fully portable continuous real-time auscultation with a soft wearable stethoscope designed for automated disease diagnosis, Science Advances (2022). DOI: 10.1126/sciadv.abo5867

Pranav Gupta et al, Precision wearable accelerometer contact microphones for longitudinal monitoring of mechano-acoustic cardiopulmonary signals, npj Digital Medicine (2020). DOI: 10.1038/s41746-020-0225-7

Comment by Dr. Krishna Kumari Challa on June 3, 2022 at 12:44pm

The researchers suppose, existing indefinitely in a new, low-metabolic state. Also, exactly how erebotic cells begin to lose organelles or break down cytoplasmic proteins is still unknown. “It’s really hard to prove that a cell is dying” . It’s almost . . . a philosophical question. But without organelles or a nucleus, say teh scientists, it only makes sense that death is on the horizon for these cells. 

It’s still unclear how [erebosis] fits into homeostasis . . . and they want to know more about where else erebosis is happening. If erebosis is a death pathway, it could help explain confusing results from other studies.

The findings could also have clinical implications. Defective cell turnover, Yoo says, is related to several gastrointestinal diseases, including ulcerative colitis and gastroenteritis. If erebosis occurs in the human gut, it could go wrong and play a role in certain diseases.

And in a strange twist, the researchers have already found that Ance isn’t actually required. The process of molecule- and organelle-dumping and nuclei flattening continued unabated when Ance was knocked out using miRNAs. So, although gut cells tend to take up Ance during erebosis, the researchers don’t yet know why. 

The story continues as researchers try to learn what really is happening. 

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pb...

https://www.the-scientist.com/news-opinion/move-over-apoptosis-anot...

**

Part 3

Comment by Dr. Krishna Kumari Challa on June 3, 2022 at 12:41pm

l cells have a limited lifespan, and their death can come about in several ways. As they age and accumulate mutations, internal or external signals trigger apoptosis, which can be thought of as an organized auto-destruct. The cell shrinks and dissolves into discrete packages called apoptotic bodies, which are later consumed by cell-eating immune cells called phagocytes. Less commonly, damaged, oxygen-starved, or cancerous cells can undergo necrosis, swelling and eventually bursting open to spill their contents into the body. Cells can also die via autophagy, a process akin to consuming themselves, which is thought to be brought about by a lack of food. In autophagy, cells dissolve their internal contents through autophagosomes, large vesicles that break down the cell’s contents. 

At that point, these researchers were still trying to explain Ance cell activity within the context other forms of cell death, especially apoptosis, as it is thought to be the most common driver of the gut’s quick (once every four-day to three-week) tissue turnover. They began searching for evidence that Ance cells were producing markers of necrosis and autophagy, the other, less-common forms of cell death. But they failed to find evidence that any of the three were taking place. Furthermore, inactivating caspases (which are molecules typically found in cells undergoing apoptosis that signal cells to start breaking down) with microRNAs failed to stop the cells from losing organelles, proteins, or ATP. 

To figure out what was going on, the researchers used a general cell death marker called TUNEL, which labels fragmented DNA. TUNEL labeled some Ance cells but not others. The cells that were labeled had lower GFP signals and squatter nuclei, which strongly indicated that these cells were indeed approaching the end of their lives. 

The researchers also looked at whether this newly-described, Ance-related pathway to death still occurred in Drosophila mutants that lacked important apoptosis, necrosis, and autophagy-related proteins. In all cases, erebosis persisted. In all, their findings pointed to one conclusion: Ance was a marker for a cell’s eventual fate—a kind of cell death no one had described before, which they decided to call erebosis.

 Technically, the team didn’t prove that cells are dying through erebosis, nor have they worked out a lot of the details. Though they’ve documented that these cells are undergoing a process that seems difficult to bounce back from, they haven’t shown them disappearing in real-time. They could still be alive.

Part 2

Comment by Dr. Krishna Kumari Challa on June 3, 2022 at 12:38pm

Move Over Apoptosis: Another Form of Cell Death May Occur in the Gut

Though scientists don’t yet know much about it, a newly described process called erebosis might have profound implications for how the gut maintains itself.

Every day, billions of our cells die and new, healthy ones take their place. In a healthy gut lining, as in most tissues, a type of cell death called apoptosis is thought to mediate this process almost entirely on its own. But researchers from RIKEN in Kobe, Japan, suspect they have discovered a new kind of cell death in the gut of a fruit fly. The new process, which they call erebosis or “deep darkness,” may be present in other tissues, the team reports April 25 in PLOS Biology —and if found in humans, it could affect how we understand diseases of the gastrointestinal tract. 

https://www.the-scientist.com/news-opinion/move-over-apoptosis-anot...

Part 1

Comment by Dr. Krishna Kumari Challa on June 3, 2022 at 12:26pm

Scientists May Have Found a Way to Inject Oxygen Into The Bloodstream Intravenously

There are many illnesses and injuries, including COVID-19, where the body struggles to get the amount of oxygen into the lungs necessary for survival.

In severe cases, patients are put on a ventilator, but these machines are often scarce and can cause problems of their own, including infection and injury to the lungs.

Scientists may have now found a breakthrough, and it's one that that could significantly impact how ventilators are used. 

In addition to traditional mechanical ventilation, there's another technique called Extracorporeal Membrane Oxygenation (ECMO), where blood is carried outside the body so that oxygen can be added and carbon dioxide can be removed.

Thanks to a new discovery, oxygen may now be able to be added directly, and the patient's blood can stay where it is. With a condition like refractory hypoxemia, which can be brought on by being on a ventilator, having this approach available could save lives.

If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

The new technique works by channeling an oxygen-laden liquid through a series of nozzles that get smaller and smaller. By the time the process is finished, the bubbles are smaller than red blood cells – and that means they can be directly injected into the bloodstream without blocking blood vessels.

A lipid membrane is used to coat the bubbles before they're added to the blood, which prevents toxicity and stops the bubbles from clumping together. After the solution is injected, the membrane dissolves and the oxygen is released.

In experiments on donated human blood, blood oxygen saturation levels could be lifted from 15 percent to over 95 percent within just a few minutes. In live rats, the process was shown to increase saturation from 20 percent to 50 percent.

"Importantly, these devices allow us to control the dosage of oxygen delivered and the volume of fluid administered, both of which are critical parameters in the management of critically ill patients.

https://www.pnas.org/doi/full/10.1073/pnas.2115276119

Comment by Dr. Krishna Kumari Challa on June 3, 2022 at 12:09pm

Researchers develop nanoparticles that cross the blood-brain barrier

There are currently few good treatment options for glioblastoma, an aggressive type of brain cancer with a high fatality rate. One reason that the disease is so difficult to treat is that most chemotherapy drugs can't penetrate the blood vessels that surround the brain.

A team of  researchers is now developing drug-carrying nanoparticles that appear to get into the brain more efficiently than drugs given on their own. Using a human tissue model they designed, which accurately replicates the blood-brain barrier, the researchers showed that the particles could get into tumors and kill glioblastoma cells.

The researchers grew patient-derived glioblastoma cells in a microfluidic device. Then, they used human endothelial cells to grow blood vessels in tiny tubes surrounding the sphere of tumor cells. The model also includes pericytes and astrocytes, two cell types that are involved in transporting molecules across the blood-brain barrier.

Joelle P. Straehla et al, A predictive microfluidic model of human glioblastoma to assess trafficking of blood–brain barrier-penetrant nanoparticles, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2118697119

Cynthia Hajal et al, Engineered human blood–brain barrier microfluidic model for vascular permeability analyses, Nature Protocols (2022). DOI: 10.1038/s41596-021-00635-w

Comment by Dr. Krishna Kumari Challa on June 3, 2022 at 11:15am

Time crystals 'impossible' but obey quantum physics

Time crystals: First theorized in 2012 by Nobel Laureate Frank Wilczek and identified in 2016, time crystals exhibit the bizarre property of being in constant, repeating motion in time despite no external input. Their atoms are constantly oscillating, spinning, or moving first in one direction, and then the other.

Time crystals are different from a standard crystal—like metals or rocks—which is composed of atoms arranged in a regularly repeating pattern in space.

Scientists have created the first "time-crystal" two-body system in an experiment that seems to bend the laws of physics. It comes after the same team recently witnessed the first interaction of the new phase of matter.

Time crystals were long believed to be impossible because they are made from atoms  in never-ending motion. The discovery, published in Nature Communications, shows that not only can time crystals be created, but they have potential to be turned into useful devices.

Everybody knows that perpetual motion  machines are impossible. However, in quantum physics perpetual motion is okay as long as we keep our eyes closed. By sneaking through this crack we can make time crystals. It turns out putting two of them together works beautifully, even if time crystals should not exist in the first place. And we already know they also exist at room temperature.

A "two-level system" is a basic building block of a quantum computer. Time crystals could be used to build quantum devices that work at room temperature. 

An international team of researchers observed time crystals by using Helium-3 which is a rare isotope of helium with one missing neutron. The experiment was carried out in Aalto University.

They cooled superfluid helium-3 to about one ten thousandth of a degree from absolute zero (0.0001 K or -273.15 C). The researchers created two time crystals inside the superfluid, and brought them to touch. The scientists then watched the two time crystals interacting as described by quantum physics.

Nonlinear two-level dynamics of quantum time crystals, Nature Communications (2022). DOI: 10.1038/s41467-022-30783-w

Comment by Dr. Krishna Kumari Challa on June 2, 2022 at 6:48am

The brain’s immunological wonderland

Researchers once thought that the brain was walled off from the rest of the body’s immune system, but an exciting picture is emerging of the brain as a unique immunologi.... The brain’s border control actually does allow immune cells from the body into the fluid-filled membranes that surround the organ, which are an “immunological wonderland”, says neuroimmunologist Kiavash Movahedi. Special immune cells produced in the skull’s bone marrow could be gentler than normal immune cells. Researchers are exploring how these and other kinds of immune cells in the brain play a role in fighting diseases and could be harnessed in treatments.

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