A world first: Human liver was treated in a machine and then successfully transplanted
The Liver4Life research has developed a perfusion machine that makes it possible to implant a human organ into a patient after a storage period of three days outside a body. The machine mimics the human body as accurately as possible, in order to provide ideal conditions for human livers. A pump serves as a replacement heart, an oxygenator replaces the lungs and a dialysis unit performs the functions of the kidneys. In addition, numerous hormone and nutrient infusions perform the functions of the intestine and pancreas.
Like the diaphragm in the human body, the machine also moves the liver to the rhythm of human breathing. In January 2020, the multidisciplinary Zurich research team—involving the collaboration of University Hospital Zurich (USZ), ETH Zurich and the University of Zurich (UZH)—demonstrated for the first time that perfusion technology makes it possible to store a liver outside the body for several days.
The team prepared the liver in the machine with various drugs. In this way, it was possible to transform the liver into a good human organ, even though it was originally not approved for transplantation due to its poor quality. The multi-day perfusion—the mechanical circulation of the organ—enables antibiotic or hormonal therapies or the optimization of liver metabolism, for example. In addition, lengthy laboratory or tissue tests can be carried out without time pressure. Under normal circumstances, this is not possible because organs can only be stored for 12 hours if they are stored conventionally on ice and in commercially available perfusion machines.
As part of an approved individual treatment attempt, the doctors gave a cancer patient on the Swiss transplant waiting list the choice of using the treated human liver. Following his consent, the organ was transplanted in May 2021. The patient was able to leave hospital a few days after the transplantation and is now doing well.
Science academies publish statements on primary concerns for international action ahead of the G7 summit
The science academies of the G7 states are calling for urgent international action to protect the ocean and polar regions and to accelerate decarbonization. In the healthcare sector, scientists demand increased global pandemic preparedness and the implementation of a One Health approach, which considers the health of humans, animals, plants and the wider environment as closely linked and interdependent. Their recommendations are set out in four statements which were submitted to the German federal government today at the Science7 Dialogue Forum 2022 in Berlin/Germany.
Alzheimer's disease causes cells to overheat and 'fry like eggs'
Researchers have shown that aggregation of amyloid-beta, one of two key proteins implicated in Alzheimer's disease, causes cells to overheat and "fry like eggs."
The researchers used sensors small and sensitive enough to detect temperature changes inside individual cells , and found that as amyloid-beta misfolds and clumps together, it causes cellsto overheat.
In an experiment using human cell lines, the researchers found the heat released by amyloid-beta aggregationcould potentially cause other, healthy amyloid-beta to aggregate, causing more and more aggregates to form.
The researchers used tiny temperature sensors called fluorescent polymeric thermometers (FTPs) to study the link between aggregation and temperature. They added amyloid-beta to human cell lines to kickstart the aggregation process and used a chemical called FCCP as a control, since it is known to induce an increase in temperature.
They found that as amyloid-beta started to form thread-like aggregates called fibrils, the average temperature of the cells started to rise. The increase in cellular temperature was significant compared to cells that did not have any amyloid-beta added.
As the fibrils start elongating, they release energy in the form of heat. Amyloid-beta aggregation requires quite a lot of energy to get going, but once the aggregation process starts, it speeds up and releases more heat, allowing more aggregates to form.
Once the aggregates have formed, they can exit the cell and be taken up by neighboring cells, infecting healthy amyloid-beta in those cells.
In the same series of experiments, the researchers also showed that amyloid-beta aggregation can be stopped, and the cell temperature lowered, with the addition of a drug compound. The experiments also suggest that the compound has potential as a therapeutic for Alzheimer's disease, although extensive tests and clinical trials would first be required.
Using a drug that inhibits amyloid-beta aggregation, the researchers were able to pinpoint the fibrils as the cause of thermogenesis. It had previously been unknown whether protein aggregation or potential damage to mitochondria—the "batteries" that power cells—was responsible for this phenomenon.
The researchers say their assay could be used as a diagnostic toolfor Alzheimer's disease, or to screen potential drug candidates.
Chyi Wei Chung et al, Intracellular Aβ42 Aggregation Leads to Cellular Thermogenesis, Journal of the American Chemical Society (2022). DOI: 10.1021/jacs.2c03599
Animals possess circadian clocks, or 24-hour oscillators, to regulate daily behaviour. These typically take their cues from the periodic change of sunlight and darkness. However, many animals are also exposed to moonlight, which reoccurs with ~25h periodicity.
Researchers have now discovered that moonlight adjusts the daily clock of marine bristle worms, which helps them to fine-tune their reproductive cycle to certain hours during the night. The study, published in the Proceedings of the National Academy of Sciences, provides an explanation for the phenomenon that daily clocks from flies to humans can exhibit plastic run-times.
In order to produce the next generation, the marine bristle worm Platynereis dumerilii releases its eggs and sperm freely into the open seawater. The correct timing of their reproductive cycles is therefore essential for the survival of the species. It was already known that bristle worms schedule their reproduction to few days of the month. Now, the researchers uncovered that they also synchronize to very specific hours during each night.
Moonlight determines when, precisely, during the night the worms start their reproductive behavior, which is always during the darkest portion of the night.
Rather than acting as the direct stimulus for swarming, moonlight changes the circadian clock period length. In nature, the time of moonlight changes every day by about 50 minutes. The plasticity of the clock allows the worms to factor in these changes.
Humans show such circadian plasticity, too. For instance, patients with bipolar disorder exhibit enigmatic circalunidian (i.e. 24.8h) periods correlated with their mood switches. The scientists hope that their work will help to understand the origin and consequences of biological timer plasticity, as well as its interplay with natural timing cues.
Martin Zurl et al, Two light sensors decode moonlight versus sunlight to adjust a plastic circadian/circalunidian clock to moon phase, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2115725119
From frogs remaining airborne using their webbed feet to lizards and snakes gliding by expanding their ribcages, biologists might have thought they had seen every unusual aerial strategy — but now they report flying salamanders.
Single hybrid seagrass plant now stretches across 180 kilometers
Two closely related species hybridize and create a superorganism whose growth and expansion seems unstoppable. That’s what’s happened in Western Australia’s Shark Bay, researchers say, where a seagrass meadow (see above) stemming from a single hybrid plant has extended its reach across more than 180 kilometers—an area the size of Washington, D.C. Two years ago, scientists discovered some of the seagrass there was a clone of a Poseidon’s ribbon weed (Posidonia australis) that had 40 chromosomes instead of the typical 20. They think half those chromosomes may come from the ribbon weed and half from an unknown species. That second half appears to have provided a big survival advantage, as this hybrid has taken over all but one of the 10 seagrass meadows surveyed, the scientists report today in the Proceedings of the Royal Society B. The clone is about 1.5 orders of magnitude larger than the largest fungi and the longest sea animal. The team suspects the clone arose 4500 years ago and has been spreading ever since. That would make it among the oldest organisms on Earth, although not quite as old as the oldest tree. Shark Bay is at the northern edge of where this seagrass can survive, and global warming is making it harder for the plants to hang on there. Low rainfall and high evaporation rates have also caused the water to become much saltier. The clone’s extra genes may be providing a way for it to adapt to these stresses, the authors note.
When your brain needs you to pay attention to something important, one way it can do that is to send out a burst of noradrenaline, according to a new study.
This neuromodulator, produced by a structure deep in the brain called the locus coeruleus, can have widespread effects throughout the brain. In a study of mice, the MIT team found that one key role of noradrenaline, also known as norepinephrine, is to help the brain learn from surprising outcomes.
Noradrenaline is one of several neuromodulators that influence the brain, along with dopamine, serotonin, and acetylcholine. Unlike neurotransmitters, which enable cell-to-cell communication, neuromodulators are released over large swathes of the brain, allowing them to exert more general effects.
Neuromodulatory substances are thought to perfuse large areas of the brain and thereby alter the excitatory or inhibitory drive that neurons are receiving in a more point-to-point fashion. This suggests they must have very crucial brain-wide functions that are important for survival and for brain state regulation.
The researchers also found that the neurons that generate this noradrenaline signal appear to send most of their output to the motor cortex, which offers more evidence that this signal stimulates the animals to take action.
Noradrenaline has been linked to arousal and boosting alertness, but too much noradrenaline can lead to anxiety.
This work shows that the locus coeruleus encodes unexpected events, and paying attention to those surprising events is crucial for the brain to take stock of its environment.
In addition to its role in signaling surprise, the researchers also discovered that noradrenaline helps to stimulate behavior that leads to a reward, particularly in situations where there is uncertainty over whether a reward will be offered.
Molecular machines that kill infectious bacteria have been taught to see their mission in a new light.
The latest iteration of nanoscale drills developed by researchers are activated by visible light rather than ultraviolet (UV), as in earlier versions. These have also proven effective at killing bacteria through tests on real infections.
Six variants of molecular machines were successfully tested by chemists. All of them punched holes in the membranes of gram-negative and gram positive bacteria in as little as two minutes. Resistance was futile for bacteria that have no natural defenses against mechanical invaders. That means they are unlikely to develop resistance, potentially offering a strategy to defeat bacteria that have become immune to standard antibacterial treatments over time.
The new version gets its energy from still-blueish light at 405 nanometers, spinning the molecules' rotors at 2 to 3 million times per second.
It's been suggestedby other researchers that light at that wavelength has mild antibacterial properties of its own, but the addition of molecular machinessupercharges it. Bacterial infections like those suffered by burn victims and people with gangrene will be early targets.
The researchers also found the machines effectively break up biofilms and persister cells, which become dormant to avoid antibacterial drugs.
The new machines also promise to revive antibacterial drugs considered ineffective. Drilling through the microorganisms' membranes allows otherwise ineffective drugs to enter cells and overcome the bug's intrinsic or acquired resistance to antibiotics.
How electric fish were able to evolve electric organs
Electric organs help electric fish, such as the electric eel, do all sorts of amazing things: They send and receive signals that are akin to bird songs, helping them to recognize other electric fish by species, sex and even individual. A new study in Science Advances explains how small genetic changes enabled electric fish to evolve electric organs. The finding might also help scientists pinpoint the genetic mutations behind some human diseases.
Evolution took advantage of a quirk of fish genetics to develop electric organs. All fish have duplicate versions of the same gene that produces tiny muscle motors, called sodium channels. To evolve electric organs, electric fish turned off one duplicate of the sodium channel gene in muscles and turned it on in other cells. The tiny motors that typically make muscles contract were repurposed to generate electric signals, and voila! A new organ with some astonishing capabilities was born.
In the new paper, researchers describe discovering a short section of this sodium channel gene—about 20 letters long—that controls whether the gene is expressed in any given cell. They confirmed that in electric fish, this control region is either altered or entirely missing. And that's why one of the two sodium channel genes is turned off in the muscles of electric fish. But the implications go far beyond the evolution of electric fish.
This control region is in most vertebrates, including humans. So, the next step in terms of human health would be to examine this region in databases of human genes to see how much variation there is in normal people and whether some deletions or mutations in this region could lead to a lowered expression of sodium channels, which might result in disease.
An integrated approach to land management practices in the U.S. can reduce carbon dioxide in the atmosphere far more than earlier estimates based on separate approaches, Michigan State University researchers say. Their research was published May 31 in the journal Global Change Biology.
In the future, cameras could spot blackbirds feeding on grapes in a vineyard and launch drones to drive off the avian irritants, then return to watch for the next invading flock. All without a human nearby.
In collaboration with the group of Professor Mordechai Segev (Technion, Israel Institute of Technology), physicists from the group of Professor Alexander Szameit (University of Rostock) have demonstrated a novel type of mechanism that can prevent light waves from spreading freely. So far, the underlying physical effect had been considered far too weak to fully arrest wave expansion. In their recent experiments, the physicists observed that such light localization is nevertheless possible, demonstrating the uncanny sensitivity of wave propagation across a wide range of spatial length scales. Their discovery was recently published in the journal Science Advances.
Usually, increasing agricultural productivity depends on adding something, such as fertilizer or water. A new Stanford University-led study reveals that removing one thing in particular—a common air pollutant—could lead to dramatic gains in crop yields. The analysis, published June 1 in Science Advances, uses satellite images to reveal for the first time how nitrogen oxides—gases found in car exhaust and industrial emissions—affect crop productivity. Its findings have important implications for increasing agricultural output and analyzing climate change mitigation costs and benefits around the world.
Researchers once thought that the brain was walled off from the rest of the body’s immune system, butan 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.
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 crystalsinteracting as described by quantum physics.
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
Scientists May Have Found a Way to Inject Oxygen Into The Bloodstream Intravenously
There are many illnesses and injuries, includingCOVID-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 likerefractory 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.
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.
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 inDrosophilamutants 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.
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.
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
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
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 journalNature 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 thebiological processesthat 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 applicationhas 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.
X-rays make it possible to explore inside human bodies or peer inside objects. The technology used to illuminate the detail in microscopically small structures is the same as that used in familiar situations—such as medical imaging at a clinic or luggage control at the airport. X-ray microscopy enables scientists to study the three-dimensional structure of materials, organisms or tissues without cutting and damaging the sample. Unfortunately, the performance of X-ray microscopy is limited by the difficulties in producing the perfect lens. A team from the Institute for X-ray Physics at the University of Göttingen has now shown that, despite the manufacturing limitations of lenses, a much higher image quality and sharpness than ever before can be achieved using a special experimental arrangement and numerical image reconstruction downstream: an algorithm compensates for the deficits of the lenses. The results were published in the journal Physical Review Letters.
Live-cell imaging of the eye’s transparent cornea has revealed a surprising resident — specialized immune cells that circle the tissue, ready to attack pathogens. “We thought that the central cornea was devoid of any immune cells,” says clinician-scientist Esen Akpek. The cornea has a dampened response to infection, in part because aggressive immune cells could damage the clear layer of tissue and obstruct vision. Butmicroscopes reveal that long-lived immune cells, known as T cells, do reside there.
In a first, researchers use Bluetooth signals to identify and track smartphones
A team of engineers has demonstrated for the first time that the Bluetooth signals emitted constantly by our mobile phones have a unique fingerprint that can be used to track individuals' movements.
Mobile devices, including phones, smartwatches and fitness trackers, constantly transmit signals, known as Bluetooth beacons, at the rate of roughly 500 beacons per minute.These beacons enable features like Apple's "Find My" lost device tracking service; COVID-19 tracing apps; and connect smartphones to other devices such as wireless earphones.
Prior research has shown that wireless fingerprinting exists in WiFi and other wireless technologies. The critical insight of this new work was that this form of tracking can also be done with Bluetooth, in a highly accurate way.
All wireless devices have small manufacturing imperfections in the hardware that are unique to each device. These fingerprints are an accidental byproduct of the manufacturing process. These imperfections in Bluetooth hardware result in unique distortions, which can be used as a fingerprint to track a specific device. For Bluetooth, this would allow an attacker to circumvent anti-tracking techniques such as constantly changing the address a mobile device uses to connect to Internet networks.
Tracking individual devices via Bluetooth is not straightforward. Prior fingerprinting techniques built for WiFi rely on the fact that WiFi signals include a long known sequence, called the preamble. But preambles for Bluetooth beacon signals are extremely short.
The short durationgives an inaccurate fingerprint, making prior techniques not useful for Bluetooth tracking. Instead, the researchers designed a new method that doesn't rely on the preamble but looks at the whole Bluetooth signal. They developed an algorithm that estimates two different values found in Bluetooth signals. These values vary based on the defects in the Bluetooth hardware, giving researchers the device's unique fingerprint.
Although their finding is concerning, the researchers also discovered several challenges that an attacker will face in practice. Changes in ambient temperature for example, can alter the Bluetooth fingerprint. Certain devices also send Bluetooth signals with different degrees of power, and this affects the distance at which these devices can be tracked.
Researchers also note that their method requires an attacker to have a high degree of expertise, so it is unlikely to be a widespread threat to the public today.
Despite the challenges, the researchers found that Bluetooth tracking is likely feasible for a large number of devices. It also does not require sophisticated equipment: the attack can be performed with equipment that costs less than $200.
The largest ever series of phage therapy case studies shows a success rate of more than half
The number of reported cases using viruses to treat deadly Mycobacterium infections just went up by a factor of five.
In a new paper published recently in the journal Clinical Infectious Diseases, a team of researchers report 20 new case studies on the use of the experimental treatment, showing the therapy's success in more than half of the patients.
It's the largest ever set of published case studies for therapy using bacteria-killing viruses known as bacteriophages, providing unprecedented detail on their use to treat dire infections while laying the groundwork for a future clinical trial.
The phages are contributing to favorable outcomes—and in patients who have no other alternatives
Each patient treated in the study was infected with one or more strains of Mycobacterium, a group of bacteria that can cause deadly, treatment-resistant infections in those with compromised immune systems or with the lung disorder cystic fibrosis.
For clinicians, these are really a nightmare: They're not as common as some other types of infections, but they're amongst some of the most difficult to treat with antibiotics. And especially when you take these antibiotics over extended periods of time, they're toxic or not very well-tolerated.
Looking at measures of patient health and whether samples from the patient still showed signs of Mycobacterium infections, the team found that the therapy was successful in 11 out of 20 cases. No patients showed any adverse reactionsto the treatment.
In another five patients the results of the therapy were inconclusive, and four patients showed no improvement.
Several unexpected patterns emerged from the case studies. In 11 cases, researchers were unable to find more than one kind of phage that could kill the patient's infection, even though standard practice would be to inject a cocktail of different viruses so the bacteria would be less likely to evolve resistance.
In addition, the team saw that some patients' immune systems attacked the viruses, but only in a few cases did their immune systems render the virus ineffective. And in some instances, the treatment was still successful despite such an immune reaction. The study paints an encouraging picture for the therapy.
hage Therapy of Mycobacterium Infections: Compassionate-use of Phages in Twenty Patients with Drug-Resistant Mycobacterial Disease, Clinical Infectious Diseases (2022). DOI: 10.1093/cid/ciac453
Physicists Caught Sound Moving at Two Different Speeds in 3D Quantum Gas
After previously studying the phenomena oftwo sound wavesin quantum liquids, scientists have now observed sound moving at two different speeds in a quantum gas.
If you were somehow immersed in the three-dimensional gas used for this study, you would hear every sound twice: each individual sound carried by two different sound waves moving at two different speeds.
This is an important development in the field of superfluidity – fluids with no viscosity that can flow without any loss of energy.
Remarkably, the behavior observed in the gas in terms of densities and velocities matched the parameters set down byLandau's two-fluid model, a theory developed for superfluid helium in the 1940s. To a large extent, it seems that when it comes to quantum gas setups, the same rules apply.
"These observations demonstrate all the key features of the two-fluid theory for a highly compressible gas.
Neuroscientists find new factors behind better vision
The size of our primary visual cortex and the amount of brain tissue we have dedicated to processing visual information at certain locations of visual space can predict how well we can see, a team of neuroscientists has discovered. Its study, which appears in the journal Nature Communications, reveals a new link between brain structure and behavior.
Scientists can now predict how well someone can see based on the unique structure of their primary visual cortex. By showing that individual variation in the structure of the human visual brain is linked to variation in visual functioning, they can better understand what underlies differences in how people perceive and interact with their visual environment.
As with fingerprints, the bumps and grooves on each person's brain surface are unique. However, the significance of these differences is not fully understood, especially when it comes to their impact on behavior, such as distinctions in our ability to see.
Using functional magnetic resonance imaging (fMRI), the scientists mapped the primary visual cortex (or "V1") size of more than two dozen humans. The researchers also measured the quantity of V1 tissue these individuals have dedicated to processing visual information from different locations in their field of view—locations to the left, right, above, and below fixation.
The results showed that differences in V1 surface area could predict measurements of people's contrast sensitivity. First, people with a large V1 had better overall contrast sensitivity than did those with a small V1 (the largest surface area being 1,776 square millimeters [mm2] and the smallest being 832 mm2). Second, people whose V1 had more cortical tissue processing visual information from a specific region in their field of view had higher contrast sensitivity at that region relative to those with less cortical tissue dedicated to the same region. Third, across participants, higher contrast sensitivity at a specific location (e.g., left) than at another location equidistant from fixation (e.g., above) corresponded to regions with more or less cortical tissue, respectively.
In sum, the more local V1 surface area dedicated to encoding a specific location, the better the vision at that location.
Linking individual differences in human primary visual cortex to contrast sensitivity around the visual field, Nature Communications (2022). DOI: 10.1038/s41467-022-31041-9
Study describes new way of generating insulin-producing cells
Researchers show how a molecule that they have identified stimulates the formation of new insulin-producing cells in zebrafish and mammalian tissue, through a newly described mechanism for regulating protein synthesis. The results are published in Nature Chemical Biology.
These findings indicate a new potential target for treating diabetes, in that researchers demonstrate a possible way of stimulating the formation of new insulin-producingcells.
Insulin injections and glucose-lowering drugs can control the disease, but not cure it.
One alternative could be a treatment that regulates blood glucose by increasing the number of insulin-producing pancreatic β cells.
The researchers has previously identified a small molecule able to stimulate the regeneration of insulin-producing β cells. This they did by analyzing a large quantity of substances in a zebra fish model.
In this present study, they examined the molecular mechanism of this stimulation.
By analyzing a large number of molecular interactions in yeast cells, the researchers show that their molecule binds to a protein called MNK2. Subsequent studies of zebrafish and cell cultures indicate that the molecule operates by regulating the translation of mRNA and boosting the synthesis of proteins, without which the formation of new β cells cannot be increased. Zebrafish given the molecule also showed lower levels of blood glucose than controls.
The study also shows that the molecule can induce the formation of new pancreatic β cells from pigs and stimulate the expression of insulin in human organoids (organ-like cell formations).
Scientists now will be studying the effect of this and similar molecules in human tissue and analyzing the molecule's target protein, MNK2, in tissue from healthy donors and donors with diabetes.
Many different types of bacteria and viruses can cause pneumonia, but there is no easy way to determine which microbe is causing a particular patient's illness. This uncertainty makes it harder for doctors to choose effective treatments because the antibiotics commonly used to treat bacterial pneumonia won't help patients with viral pneumonia. In addition, limiting the use of antibiotics is an important step toward curbing antibiotic resistance.
One of the primary ways harmful bacteria acquire resistance to antibiotics is by receiving DNA from other bacteria that are already resistant. This DNA exchange is made via a process called conjugation, akin to bacterial sex, whereby two bacteria form an intimate attachment, and one transfers a packet of DNA to the other.
Oregon State University scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group.
Scientists discover and characterize a novel membraneless organelle that could play a role in Alzheimer's treatment
Researchers have discovered a novel organelle—a previously unknown cell structure whose function it is to help clean up faulty proteins in times of stress and keep cells functioning in top condition. Optimizing this membraneless organelle, which they call a BAG2 condensate, could lead to treatments for conditions that are the result of misfolded proteins, including Alzheimer's disease, Parkinson's disease and other neurodegenerative conditions. Their results are reported in a paper and published in the journal Nature Communications.
People have known for quite a while that are a few objects floating around in cells that don't have membranes. And it's never been clear how they're held together, what they are and what they're doing until relatively recently.
Thanks to advanced imaging techniques, scientists have uncovered structures that were once invisible, revealing cells for the truly complex and sophisticated systems that they are.
Of particular interest are biomolecular condensates, which don't have the recognizable cell membrane enclosure, but instead, are separated from the surrounding cytoplasm by a difference in density that can be loosely compared to a drop of oil in water. Thisliquid-liquid phase separationcreates a specialized, relatively concentrated environment for certain functions and reactions. For example, a stress granule is a membraneless organelle that appears when the cell is under stress—maybe there's too much glucose, maybe it's too hot or cold, maybe the cell is experiencing dehydration—and its job is to sweep up RNA floating around in the cytoplasm, storing those genetic instructions and pausing their translation into proteins. If your cell is under stress, you want to shut down making proteins so you can really conserve your energy and get past the stress.
But that's only part of the picture, according to the researchers.
When there's stress, what happens to the proteins that are already in the cell?. If they're under those stress conditions, some of those proteins could get damaged and they could misfold." Misfolds of the tauprotein, for example, can become pathological and turn into theneurofibrillary tanglesthat characterize Alzheimer's disease.
This is where the researchers' newly discovered BAG2 condensate comes in. Named for the BAG2 protein that it contains, the organelle, they found, is capable of sweeping up these faulty proteins in the cytoplasm and stuffing them into a proteasome—the cell's version of a trash can—located in the organelle.
A few proteins form a little barrel, and as the protein is threaded through that little cylinder, it gets degraded. This inactivates and breaks down the protein. Many proteasomes are present in cells at any given time, he added, but what makes this particular proteasome (labeled 20S) special is that it can accept proteins that are already somewhat misfolded and would not fit in the other cellular trash cans.
The limiting cap present on many proteasomes is not there in the BAG2 condensates. These promising results could point to a way to interrupt the development of Alzheimer's disease, which is marked by an accumulation of misfolded tau.
Daniel C. Carrettiero et al, Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate, Nature Communications (2022). DOI: 10.1038/s41467-022-30751-4
Shedding light on how bacteria communicate their way to causing infection
Scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group. The research is important because understanding this type of signaling, known as quorum sensing and integral to bacterial pathogens, opens the door to potential new drugs that can disrupt it and thwart infection. Findings were published in the Proceedings of the National Academy of Sciences.
Sometimes single-celled organisms need to work together with other cells. Bacteria and other single-celled microbes can coordinate behaviors and act as a group via quorum sensing, in which cells produce and sense a small chemical signal that is shared within the population. As the signal is released from cells and reaches a high enough concentration in their environment, a quorum is achieved—certain genes are simultaneously activated and specific group behaviors are set in motion.
It's a strength-in-numbers approach that allows bacteria to join forces to do things they could not do by themselves, like causing infection in animals and plants, acquiring certain nutrients and competing against other microbes.
Bacterial infection often involves toxins that only harm the host at high levels, when produced by all bacterial cells at once.
A major unresolved question about quorum sensing, the researchers said, has been why the signal that's produced inside an individual cell is not sensed by that same cell before it is released, spurring the cell into premature, solo action. What prevents signal 'short-circuiting' from happening? A set of proteins called antiactivators are crucial for short-circuit prevention. The proteins work as a quorum sensing "tuner" by causing cells to be less sensitive to the quorum signal.
This research shows how bacteria put the brakes on quorum sensing to achieve true communication in a group.
In addition to helping the quest for new antibiotics that can inhibit quorum sensing in bacterial pathogens, the findings also provide background knowledge useful for the engineering of cells with new properties in a field called synthetic biology.
Antiactivators prevent self-sensing in quorum sensing, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2201242119.
New work upends understanding of how blood is formed
The origins of our blood may not be quite what we thought. Using cellular "barcoding" in mice, a groundbreaking study finds that blood cells originate not from one type of mother cell, but two, with potential implications for blood cancers, bone marrow transplant, and immunology.
Till now people thought that most of our blood comes from a very small number of cells that eventually become blood stem cells, also known as hematopoietic stem cells. Scientists are now surprised to find another group of progenitor cells that do not come from stem cells. They make most of the blood in fetal life until young adulthood, and then gradually start decreasing.
The researchers are now following up to see if the findings also apply to humans. If so, these cells, known as embryonic multipotent progenitor cells (eMPPs), could potentially inform new treatments for boosting aging people's immune systems. They could also shed new light on blood cancers, especially those in children, and help make bone marrow transplants more effective.
Researchers applied a barcoding technique they developed several years ago and documented in Cell. Using either an enzyme known as transposase or CRISPR gene editing, they inserted unique genetic sequences into embryonic mouse cells in such a way that all the cells descended from them also carried those sequences. This enabled the team to track the emergence of all the different types of blood cells and where they came from, all the way to adulthood.
Through barcoding, the researchers found that eMPPs, as compared with blood stem cells, are a more abundant source of most lymphoid cells important to the immune responses, such as B cells and T cells. They think the decrease in eMPPs that they observed with age may explain why people's immunity weakens as they get older.They are now trying to understand why these cells peter out in middle age, which could potentially allow us to manipulate them with the goal of rejuvenating the immune system.
In theory, there could be two approaches: extending the life of eMPP cells, perhaps through growth factors or immune signaling molecules, or treating blood stem cells with gene therapyor other approaches to make them more like eMPPs.
Finally, the recognition that there are two types of mother cells in the blood could revolutionize bone marrow transplant.
Sarah Bowling et al, An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells,Cell(2020).DOI: 10.1016/j.cell.2020.04.048
A Common Epilepsy Drug Causes Birth Defects, And We May Finally Know Why
Valproic acid – a drug commonly used to treat epilepsy and bipolar disorder – can cause birth defects and developmental disorders if taken during pregnancy, but the reason why has long been a mystery.
Now, in a study using mice and human tissue, scientists discovered that the medication locks some embryonic cells into a suspended state where they can't properly grow or divide.
By forcing key stem cellss into this state, called senescence, valproic acid may disrupt brain development in the womb and therefore cause cognitive and developmental disorders down the line, according to the study, published Tuesday (June 14) in the journal PLOS Biology.
An estimated 30 to 40 percent of infants exposed to the drug in the womb develop cognitive impairments orautism spectrum disorder, the study authors noted in their report, and these laboratory studies hint at why that happens.
In a subset of affected children, valproic acid exposure can also cause birth defects beyond the brain, including heart malformations and spina bifida, where part of the spinal column doesn't form properly and thus leaves the spinal cord exposed.
However, the new study suggests that these physical birth defects, though also linked to valproic acid, are triggered by a different mechanism than the cognitive impairment.
Which cells are involved in heart repair and how they communicate with each other
Thousands of people suffer heart attacks every year. In this case, the heart muscle is no longer supplied with sufficient blood and oxygen, and part of the heart muscle tissue dies and becomes scarred. The consequences can range from massive cardiac insufficiency to heart failure. Unlike the liver, the heart of an adult human being cannot regenerate. However, it is able to initiate repair processes. Exactly how these repair processes take place has not been known until now. Therefore, there are still no drugs that can specifically promote healing.
Now a research team has found out which cells are involved in heart repair and how they communicate with each other. The researchers have discovered a new messenger substance that controls wound healing, thus revealing an approach for a new therapy. The research has been published in Science.
The focus of the study is the receptor KIT. The protein is produced by various cells, including the hematopoietic stem cells in the bone marrow. Here, KIT plays an important role as a binding site for the so-called stem cell factor. This messenger substance activates the KIT-positive stem cells and causes them to develop into the various cells of the blood. KIT-positive cells are also found in the heart.
"However, these are not stem cells, as long suspected, but vascular cells. The KIT-positive vascular cells ensure that new heart vessels form after a heart attack. However, the stem cell factor necessary for KIT activation can barely be detected in the heart. The researchers have now resolved this contradiction. They discovered a new messenger substance in the heart that can also bind precisely to the KIT receptor and set the repair process in motion: the protein meteorin-like (METRNL).
After a heart attack, the immune systemreacts with an inflammatory response . The inflammatory cells produce METRNL, which stimulates the KIT-positive vascular cells to form new blood vessels.
Studies in the mouse modelshowed that without METRNL, heart repair no longer worked. In contrast, when mice were treated with METRNL, new vessels formed in the infarct area. This alleviates scarring and prevents severe heart failure.
The newly discovered messenger substance could now be the decisive building block to a drug that specifically supports heart repair.
Marc R. Reboll et al, Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase, Science (2022). DOI: 10.1126/science.abn3027
Electrons take the fast and slow lanes at the same time
Imagine a road with two lanes in each direction. One lane is for slow cars, and the other is for fast ones. For electrons moving along a quantum wire, researchers have discovered that there are also two "lanes," but electrons can take both at the same time!
Current in a wire is carried by the flow of electrons. When the wire is very narrow (one-dimensional, 1D) then electrons cannot overtake each other, as they strongly repel each other. Current, or energy, is carried instead by waves of compression as one particle pushes on the next.
It has long been known that there are two types of excitation for electrons, as in addition to their charge they have a property calledspin. Spin and charge excitations travel at fixed, but different speeds, as predicted by the Tomonaga-Luttinger model many decades ago. However, theorists are unable to calculate what precisely happens beyond only small perturbations, as the interactions are too complex. The Cambridge team has measured these speeds as their energies are varied, and find that a very simple picture emerges (now published in the journalScience Advances). Each type of excitation can have low or high kinetic energy, like cars on a road, with the well-known formulaE=1/2 mv2, which is a parabola. But for spin and charge the massesmare different, and, since charges repel and so cannot occupy the same state as another charge, there is twice as wide a range of momentum for charge as for spin. The results measure energy as a function of magnetic field, which is equivalent to momentum or speedv, showing these two energy parabolas, which can be seen in places all the way up to five times the highest energy occupied by electrons in the system.
It's as if the cars (like charges) are traveling in the slow lane but their passengers (like spins) are going more quickly, in the fast lane! Even when the cars and passengers slow down or speed up, they still remain separate!
These results now open the question of whether this spin-charge separation of the whole electron sea remains robust beyond 1D, e.g., in high-temperature superconducting materials. It may also now be applied to logic devices that harness spin (spintronics), which offer a drastic reduction (by three orders of magnitude!) of the energy consumption of a transistor, simultaneously improving our understanding of quantum matter as well as offering a new tool for engineering quantum materials
Pedro M. T. Vianez et al, Observing separate spin and charge Fermi seas in a strongly correlated one-dimensional conductor, Science Advances (2022). DOI: 10.1126/sciadv.abm2781
Transplanting kidneys without need for immune-suppressing drugs
Physicians have developed a way to provide pediatric kidney transplants without immune-suppressing drugs. Their key innovation is a safe method to transplant the donor's immune system to the patient before surgeons implant the kidney.
The medical team has named the two-transplant combination a "dual immune/solid organ transplant," or DISOT. A scientific paper describing the first three DISOT cases, all performed at Lucile Packard Children's Hospital Stanford, published online June 15 in the New England Journal of Medicine.
This innovation removes the possibility that the recipient will experience immune rejection of their transplanted organ. (Organ rejection is the most common reason for a second organ transplant.) The new procedure also rids recipients of the substantial side effects of a lifetime of immune-suppressing medications, including increased risks for cancer, diabetes, infections and high blood pressure.
The first three DISOT patients were children with a rare immune disease, but the team is expanding the types of patients who could benefit.
The doctors anticipate that the protocol will eventually be available to many people needing kidney transplants, starting with children and young adults, and later expanding to older adults. The researchers also plan to investigate DISOT's utility for other types of solid-organ transplants.
The scientific innovation from the team has another important benefit: It enables safe transplantation between a donor and recipient whose immune systems are genetically half-matched, meaning children can receive stem cell and kidney donations from a parent.
The idea of transplanting a patient with their organ donor's immune system has been around for decades, but it has been difficult to implement. Transplants of stem cells from bone marrow provide the patient with a genetically new immune system, as some of the bone marrow stem cells mature into immune cells in the blood. First developed for people with blood cancers, stem cell transplants carry the risk of the new immune cells attacking the recipient's body, a complication called graft-versus-host disease. Severe GVHD can be fatal.
Researchers working with adult patients have performed sequential stem cell and kidney transplants from living donors. When the donor was half-matched they had partial success, but patients were either unable to completely discontinue immune-suppressing drugs after transplant, or—in other trials not conducted at Stanford—they had unacceptably high risks of severe GVHD.
This new work introduced refinements that greatly improve the success of the two-transplant combination with much lower risk. This key innovation is a change in how the donor's stem cells are processed.
After stem cells are removed from the donor's body, technicians perform alpha-beta T cell depletion, which removes the type of immune cells that cause GVHD. Bertaina's team had showed that alpha-beta T cell depletion—which she developed while working in Italy prior to coming to Stanford—makes stem cell transplants safer and enables genetically half-matched transplants. The protocol is relatively gentle, making it safe for children with immune disorders who are too medically fragile for a traditional stem cell transplant. The alpha-beta T cells recover in the patient after 60 to 90 days, meaning they regain full immune function.
A study finds that injuries to certain areas of the brain were associated with quitting smoking more quickly, easily, and with no cravings.
Astudy of people who effortlessly quit smoking after a stroke or other brain injury—and of those who suffered an injury but then kept smoking—has pinpointed a brain network involved in addiction, researchers reported June 13 in Nature Medicine. Experts say the findings may help identify targets for therapies that could treat addictions.
Keeping objects levitated by sound airborne despite interference
A team of researchers has developed a way to keep objects levitated by sound waves airborne when other objects interfere with the levitation path. In their paper published in the journal Science Advances, the group describes their self-correcting levitation system.
Prior research has shown that it is possible to levitate objects by firing sound waves at them. Because sound waves are nothing more than air particles moving together in a certain way, the object being levitated will fall if an object interferes with the sound waves. In this new effort, the researchers developed new features to address this problem.
To protect the sound waves from interference, the researchers increased the number of speakersused—in their work, they used 256. They also added software to control each of the speakers. The speakers were arranged in a grid and objects were levitated by specifically shaped sound waves. By programming the speakers in specific ways, the team was able to get the system to work together to keep an object above the gridin the air despite interruptions. If some of the soundwaves were blocked, other sound waveswere redirected to take their place.
The researchers proved their system was viable by testing it using a 3D-printed white rabbit as an interference object. Objects were levitated around the rabbit regardless of its location. In one experiment, the researchers levitated beads around the rabbit that formed into a flying butterfly. They also levitated a piece of clear fabric that they used as a screen for projection of the rabbit they had printed. And they levitated a single drop of water over a glass of water, showing that their system would work even when the interfering object was a jiggling glass of liquid.
Ryuji Hirayama et al, High-speed acoustic holography with arbitrary scattering objects, Science Advances (2022). DOI: 10.1126/sciadv.abn7614
Lack of diversity of microorganisms in the gut or elevated gut metabolites implicated in heart failure severity
Some people who experience heart failure have less biodiversity in their gut or have elevated gut metabolites, both of which are associated with more hospital visits and greater risk of death, according to a systematic review of research findings.
The gut microbiome is a delicately balanced ecosystem comprised primarily of bacteria as well as viruses, fungi and protozoa. The microbiome can affect cardiovascular disease, which is a leading cause of death in many parts of the world.
For their overview, the investigators looked at seven years of genetic, pharmacologic and other types of research findings from around the world to generate a wide perspective on how the microbiome can influence heart failure. The investigators zeroed in on one harmful metabolite, trimethylamine-N-oxide (TMAO), that can be produced by churning gut microbiota when full-fat dairy products, egg yolks and red meat are consumed.
The Heart and Gut Relationship: A Systematic Review of the Evaluation of the Microbiome and Trimethylamine-N-Oxide (TMAO) in Heart Failure, Heart Failure Reviews (2022). DOI: 10.1007/s10741-022-10254-6
Scientists develop antimicrobial, plant-based food wrap designed to replace plastic
Aiming to produce environmentally friendly alternatives to plastic food wrap and containers, a scientist has developed a biodegradable, plant-based coating that can be sprayed on foods, guarding against pathogenic and spoilage microorganisms and transportation damage.
The scalable process could potentially reduce the adverse environmental impact of plastic food packaging as well as protect human health.
Their article, published in the science journalNature Food, describes the new kind of packaging technology using the polysaccharide/biopolymer-based fibers. Like the webs cast by the Marvel comic book character Spider-Man, the stringy material can be spun from a heating device that resembles a hair dryer and "shrink-wrapped" over foods of various shapes and sizes, such as an avocado or a sirloin steak. The resulting material that encases food productsis sturdy enough to protect bruising and contains antimicrobial agents to fight spoilage and pathogenic microorganismssuch as E. coli and listeria.
The research paper includes a description of the technology called focused rotary jet spinning, a process by which the biopolymer is produced, and quantitative assessments showing the coating extended the shelf lifeof avocados by 50 percent. The coating can be rinsed off with water and degrades in soil within three days, according to the study.
The new packaging is targeted at addressing a serious environmental issue: the proliferation of petroleum-based plastic products in the waste stream.
High-throughput coating with biodegradable antimicrobial pullulan fibres extends shelf life and reduces weight loss in an avocado model, Nature Food (2022). DOI: 10.1038/s43016-022-00519-6
Dr. Krishna Kumari Challa
Driver mutations vs passenger mutations
Jun 1, 2022
Dr. Krishna Kumari Challa
A world first: Human liver was treated in a machine and then successfully transplanted
The Liver4Life research has developed a perfusion machine that makes it possible to implant a human organ into a patient after a storage period of three days outside a body. The machine mimics the human body as accurately as possible, in order to provide ideal conditions for human livers. A pump serves as a replacement heart, an oxygenator replaces the lungs and a dialysis unit performs the functions of the kidneys. In addition, numerous hormone and nutrient infusions perform the functions of the intestine and pancreas.
Like the diaphragm in the human body, the machine also moves the liver to the rhythm of human breathing. In January 2020, the multidisciplinary Zurich research team—involving the collaboration of University Hospital Zurich (USZ), ETH Zurich and the University of Zurich (UZH)—demonstrated for the first time that perfusion technology makes it possible to store a liver outside the body for several days.
The team prepared the liver in the machine with various drugs. In this way, it was possible to transform the liver into a good human organ, even though it was originally not approved for transplantation due to its poor quality. The multi-day perfusion—the mechanical circulation of the organ—enables antibiotic or hormonal therapies or the optimization of liver metabolism, for example. In addition, lengthy laboratory or tissue tests can be carried out without time pressure. Under normal circumstances, this is not possible because organs can only be stored for 12 hours if they are stored conventionally on ice and in commercially available perfusion machines.
As part of an approved individual treatment attempt, the doctors gave a cancer patient on the Swiss transplant waiting list the choice of using the treated human liver. Following his consent, the organ was transplanted in May 2021. The patient was able to leave hospital a few days after the transplantation and is now doing well.
Pierre-Alain Clavien, Transplantation of a human liver following 3 days of ex situ normothermic preservation, Nature Biotechnology (2022). DOI: 10.1038/s41587-022-01354-7. www.nature.com/articles/s41587-022-01354-7
Jun 1, 2022
Dr. Krishna Kumari Challa
Science academies publish statements on primary concerns for international action ahead of the G7 summit
The science academies of the G7 states are calling for urgent international action to protect the ocean and polar regions and to accelerate decarbonization. In the healthcare sector, scientists demand increased global pandemic preparedness and the implementation of a One Health approach, which considers the health of humans, animals, plants and the wider environment as closely linked and interdependent. Their recommendations are set out in four statements which were submitted to the German federal government today at the Science7 Dialogue Forum 2022 in Berlin/Germany.
https://www.leopoldina.org/en/events/event/event/2962/
Jun 1, 2022
Dr. Krishna Kumari Challa
Alzheimer's disease causes cells to overheat and 'fry like eggs'
Researchers have shown that aggregation of amyloid-beta, one of two key proteins implicated in Alzheimer's disease, causes cells to overheat and "fry like eggs."
The researchers used sensors small and sensitive enough to detect temperature changes inside individual cells , and found that as amyloid-beta misfolds and clumps together, it causes cells to overheat.
In an experiment using human cell lines, the researchers found the heat released by amyloid-beta aggregation could potentially cause other, healthy amyloid-beta to aggregate, causing more and more aggregates to form.
The researchers used tiny temperature sensors called fluorescent polymeric thermometers (FTPs) to study the link between aggregation and temperature. They added amyloid-beta to human cell lines to kickstart the aggregation process and used a chemical called FCCP as a control, since it is known to induce an increase in temperature.
They found that as amyloid-beta started to form thread-like aggregates called fibrils, the average temperature of the cells started to rise. The increase in cellular temperature was significant compared to cells that did not have any amyloid-beta added.
As the fibrils start elongating, they release energy in the form of heat. Amyloid-beta aggregation requires quite a lot of energy to get going, but once the aggregation process starts, it speeds up and releases more heat, allowing more aggregates to form.
Once the aggregates have formed, they can exit the cell and be taken up by neighboring cells, infecting healthy amyloid-beta in those cells.
In the same series of experiments, the researchers also showed that amyloid-beta aggregation can be stopped, and the cell temperature lowered, with the addition of a drug compound. The experiments also suggest that the compound has potential as a therapeutic for Alzheimer's disease, although extensive tests and clinical trials would first be required.
Using a drug that inhibits amyloid-beta aggregation, the researchers were able to pinpoint the fibrils as the cause of thermogenesis. It had previously been unknown whether protein aggregation or potential damage to mitochondria—the "batteries" that power cells—was responsible for this phenomenon.
The researchers say their assay could be used as a diagnostic tool for Alzheimer's disease, or to screen potential drug candidates.
Chyi Wei Chung et al, Intracellular Aβ42 Aggregation Leads to Cellular Thermogenesis, Journal of the American Chemical Society (2022). DOI: 10.1021/jacs.2c03599
Jun 1, 2022
Dr. Krishna Kumari Challa
How moonlight fine-tunes animal reproduction
Animals possess circadian clocks, or 24-hour oscillators, to regulate daily behaviour. These typically take their cues from the periodic change of sunlight and darkness. However, many animals are also exposed to moonlight, which reoccurs with ~25h periodicity.
Researchers have now discovered that moonlight adjusts the daily clock of marine bristle worms, which helps them to fine-tune their reproductive cycle to certain hours during the night. The study, published in the Proceedings of the National Academy of Sciences, provides an explanation for the phenomenon that daily clocks from flies to humans can exhibit plastic run-times.
In order to produce the next generation, the marine bristle worm Platynereis dumerilii releases its eggs and sperm freely into the open seawater. The correct timing of their reproductive cycles is therefore essential for the survival of the species. It was already known that bristle worms schedule their reproduction to few days of the month. Now, the researchers uncovered that they also synchronize to very specific hours during each night.
Moonlight determines when, precisely, during the night the worms start their reproductive behavior, which is always during the darkest portion of the night.
Rather than acting as the direct stimulus for swarming, moonlight changes the circadian clock period length. In nature, the time of moonlight changes every day by about 50 minutes. The plasticity of the clock allows the worms to factor in these changes.
Humans show such circadian plasticity, too. For instance, patients with bipolar disorder exhibit enigmatic circalunidian (i.e. 24.8h) periods correlated with their mood switches. The scientists hope that their work will help to understand the origin and consequences of biological timer plasticity, as well as its interplay with natural timing cues.
Martin Zurl et al, Two light sensors decode moonlight versus sunlight to adjust a plastic circadian/circalunidian clock to moon phase, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2115725119
Jun 1, 2022
Dr. Krishna Kumari Challa
How wingless salamanders fly
Jun 1, 2022
Dr. Krishna Kumari Challa
World’s largest organism found in Australia
Single hybrid seagrass plant now stretches across 180 kilometers
Two closely related species hybridize and create a superorganism whose growth and expansion seems unstoppable. That’s what’s happened in Western Australia’s Shark Bay, researchers say, where a seagrass meadow (see above) stemming from a single hybrid plant has extended its reach across more than 180 kilometers—an area the size of Washington, D.C. Two years ago, scientists discovered some of the seagrass there was a clone of a Poseidon’s ribbon weed (Posidonia australis) that had 40 chromosomes instead of the typical 20. They think half those chromosomes may come from the ribbon weed and half from an unknown species. That second half appears to have provided a big survival advantage, as this hybrid has taken over all but one of the 10 seagrass meadows surveyed, the scientists report today in the Proceedings of the Royal Society B. The clone is about 1.5 orders of magnitude larger than the largest fungi and the longest sea animal. The team suspects the clone arose 4500 years ago and has been spreading ever since. That would make it among the oldest organisms on Earth, although not quite as old as the oldest tree. Shark Bay is at the northern edge of where this seagrass can survive, and global warming is making it harder for the plants to hang on there. Low rainfall and high evaporation rates have also caused the water to become much saltier. The clone’s extra genes may be providing a way for it to adapt to these stresses, the authors note.
https://www.science.org/content/article/world-s-largest-organism-fo...
Jun 1, 2022
Dr. Krishna Kumari Challa
How the brain responds to surprising events
When your brain needs you to pay attention to something important, one way it can do that is to send out a burst of noradrenaline, according to a new study.
This neuromodulator, produced by a structure deep in the brain called the locus coeruleus, can have widespread effects throughout the brain. In a study of mice, the MIT team found that one key role of noradrenaline, also known as norepinephrine, is to help the brain learn from surprising outcomes.
Noradrenaline is one of several neuromodulators that influence the brain, along with dopamine, serotonin, and acetylcholine. Unlike neurotransmitters, which enable cell-to-cell communication, neuromodulators are released over large swathes of the brain, allowing them to exert more general effects.
Neuromodulatory substances are thought to perfuse large areas of the brain and thereby alter the excitatory or inhibitory drive that neurons are receiving in a more point-to-point fashion. This suggests they must have very crucial brain-wide functions that are important for survival and for brain state regulation.
The researchers also found that the neurons that generate this noradrenaline signal appear to send most of their output to the motor cortex, which offers more evidence that this signal stimulates the animals to take action.
Noradrenaline has been linked to arousal and boosting alertness, but too much noradrenaline can lead to anxiety.
This work shows that the locus coeruleus encodes unexpected events, and paying attention to those surprising events is crucial for the brain to take stock of its environment.
In addition to its role in signaling surprise, the researchers also discovered that noradrenaline helps to stimulate behavior that leads to a reward, particularly in situations where there is uncertainty over whether a reward will be offered.
Mriganka Sur, Spatiotemporal dynamics of noradrenaline during learned behaviour, Nature (2022). DOI: 10.1038/s41586-022-04782-2. www.nature.com/articles/s41586-022-04782-2
Jun 2, 2022
Dr. Krishna Kumari Challa
Bacteria-killing nano-drills : Visible light triggers molecular machines to treat infections
Molecular machines that kill infectious bacteria have been taught to see their mission in a new light.
The latest iteration of nanoscale drills developed by researchers are activated by visible light rather than ultraviolet (UV), as in earlier versions. These have also proven effective at killing bacteria through tests on real infections.
Six variants of molecular machines were successfully tested by chemists. All of them punched holes in the membranes of gram-negative and gram positive bacteria in as little as two minutes. Resistance was futile for bacteria that have no natural defenses against mechanical invaders. That means they are unlikely to develop resistance, potentially offering a strategy to defeat bacteria that have become immune to standard antibacterial treatments over time.
The new version gets its energy from still-blueish light at 405 nanometers, spinning the molecules' rotors at 2 to 3 million times per second.
It's been suggested by other researchers that light at that wavelength has mild antibacterial properties of its own, but the addition of molecular machines supercharges it. Bacterial infections like those suffered by burn victims and people with gangrene will be early targets.
The researchers also found the machines effectively break up biofilms and persister cells, which become dormant to avoid antibacterial drugs.
The new machines also promise to revive antibacterial drugs considered ineffective. Drilling through the microorganisms' membranes allows otherwise ineffective drugs to enter cells and overcome the bug's intrinsic or acquired resistance to antibiotics.
Ana L. Santos et al, Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane, Science Advances (2022). DOI: 10.1126/sciadv.abm2055. www.science.org/doi/10.1126/sciadv.abm2055
Jun 2, 2022
Dr. Krishna Kumari Challa
How electric fish were able to evolve electric organs
Electric organs help electric fish, such as the electric eel, do all sorts of amazing things: They send and receive signals that are akin to bird songs, helping them to recognize other electric fish by species, sex and even individual. A new study in Science Advances explains how small genetic changes enabled electric fish to evolve electric organs. The finding might also help scientists pinpoint the genetic mutations behind some human diseases.
Evolution took advantage of a quirk of fish genetics to develop electric organs. All fish have duplicate versions of the same gene that produces tiny muscle motors, called sodium channels. To evolve electric organs, electric fish turned off one duplicate of the sodium channel gene in muscles and turned it on in other cells. The tiny motors that typically make muscles contract were repurposed to generate electric signals, and voila! A new organ with some astonishing capabilities was born.
In the new paper, researchers describe discovering a short section of this sodium channel gene—about 20 letters long—that controls whether the gene is expressed in any given cell. They confirmed that in electric fish, this control region is either altered or entirely missing. And that's why one of the two sodium channel genes is turned off in the muscles of electric fish. But the implications go far beyond the evolution of electric fish.
This control region is in most vertebrates, including humans. So, the next step in terms of human health would be to examine this region in databases of human genes to see how much variation there is in normal people and whether some deletions or mutations in this region could lead to a lowered expression of sodium channels, which might result in disease.
Sarah LaPotin et al, Divergent cis-regulatory evolution underlies the convergent loss of sodium channel expression in electric fish, Science Advances (2022). DOI: 10.1126/sciadv.abm2970. www.science.org/doi/10.1126/sciadv.abm2970
Jun 2, 2022
Dr. Krishna Kumari Challa
Jun 2, 2022
Dr. Krishna Kumari Challa
Capturing carbon with crops, trees and bioenergy
An integrated approach to land management practices in the U.S. can reduce carbon dioxide in the atmosphere far more than earlier estimates based on separate approaches, Michigan State University researchers say. Their research was published May 31 in the journal Global Change Biology.
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Automated drones could scare birds off agricultural fields
In the future, cameras could spot blackbirds feeding on grapes in a vineyard and launch drones to drive off the avian irritants, then return to watch for the next invading flock. All without a human nearby.
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Physicists demonstrate novel mechanism that can prevent light waves...
In collaboration with the group of Professor Mordechai Segev (Technion, Israel Institute of Technology), physicists from the group of Professor Alexander Szameit (University of Rostock) have demonstrated a novel type of mechanism that can prevent light waves from spreading freely. So far, the underlying physical effect had been considered far too weak to fully arrest wave expansion. In their recent experiments, the physicists observed that such light localization is nevertheless possible, demonstrating the uncanny sensitivity of wave propagation across a wide range of spatial length scales. Their discovery was recently published in the journal Science Advances.
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Less air pollution leads to higher crop yields, study shows
Usually, increasing agricultural productivity depends on adding something, such as fertilizer or water. A new Stanford University-led study reveals that removing one thing in particular—a common air pollutant—could lead to dramatic gains in crop yields. The analysis, published June 1 in Science Advances, uses satellite images to reveal for the first time how nitrogen oxides—gases found in car exhaust and industrial emissions—affect crop productivity. Its findings have important implications for increasing agricultural output and analyzing climate change mitigation costs and benefits around the world.
Jun 2, 2022
Dr. Krishna Kumari Challa
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.
Jun 2, 2022
Dr. Krishna Kumari Challa
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
Jun 3, 2022
Dr. Krishna Kumari Challa
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
Jun 3, 2022
Dr. Krishna Kumari Challa
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
Jun 3, 2022
Dr. Krishna Kumari Challa
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
Jun 3, 2022
Dr. Krishna Kumari Challa
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
Jun 3, 2022
Dr. Krishna Kumari Challa
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...
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Part 3
Jun 3, 2022
Dr. Krishna Kumari Challa
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
Jun 4, 2022
Dr. Krishna Kumari Challa
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
Jun 4, 2022
Dr. Krishna Kumari Challa
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
Jun 7, 2022
Dr. Krishna Kumari Challa
Sharp X-ray images despite imperfect lenses
X-rays make it possible to explore inside human bodies or peer inside objects. The technology used to illuminate the detail in microscopically small structures is the same as that used in familiar situations—such as medical imaging at a clinic or luggage control at the airport. X-ray microscopy enables scientists to study the three-dimensional structure of materials, organisms or tissues without cutting and damaging the sample. Unfortunately, the performance of X-ray microscopy is limited by the difficulties in producing the perfect lens. A team from the Institute for X-ray Physics at the University of Göttingen has now shown that, despite the manufacturing limitations of lenses, a much higher image quality and sharpness than ever before can be achieved using a special experimental arrangement and numerical image reconstruction downstream: an algorithm compensates for the deficits of the lenses. The results were published in the journal Physical Review Letters.
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How species form: What the tangled history of polar bear and brown ...
A new study is providing an enhanced look at the intertwined evolutionary histories of polar bears and brown bears.
Jun 7, 2022
Dr. Krishna Kumari Challa
Your Gas Stove is Polluting Your Home
Jun 7, 2022
Dr. Krishna Kumari Challa
Long-lived T cells patrol the cornea
Live-cell imaging of the eye’s transparent cornea has revealed a surprising resident — specialized immune cells that circle the tissue, ready to attack pathogens. “We thought that the central cornea was devoid of any immune cells,” says clinician-scientist Esen Akpek. The cornea has a dampened response to infection, in part because aggressive immune cells could damage the clear layer of tissue and obstruct vision. But microscopes reveal that long-lived immune cells, known as T cells, do reside there.
Reference: Cell Reports paper
Jun 7, 2022
Dr. Krishna Kumari Challa
In a first, researchers use Bluetooth signals to identify and track smartphones
A team of engineers has demonstrated for the first time that the Bluetooth signals emitted constantly by our mobile phones have a unique fingerprint that can be used to track individuals' movements.
Mobile devices, including phones, smartwatches and fitness trackers, constantly transmit signals, known as Bluetooth beacons, at the rate of roughly 500 beacons per minute.These beacons enable features like Apple's "Find My" lost device tracking service; COVID-19 tracing apps; and connect smartphones to other devices such as wireless earphones.
Prior research has shown that wireless fingerprinting exists in WiFi and other wireless technologies. The critical insight of this new work was that this form of tracking can also be done with Bluetooth, in a highly accurate way.
All wireless devices have small manufacturing imperfections in the hardware that are unique to each device. These fingerprints are an accidental byproduct of the manufacturing process. These imperfections in Bluetooth hardware result in unique distortions, which can be used as a fingerprint to track a specific device. For Bluetooth, this would allow an attacker to circumvent anti-tracking techniques such as constantly changing the address a mobile device uses to connect to Internet networks.
Tracking individual devices via Bluetooth is not straightforward. Prior fingerprinting techniques built for WiFi rely on the fact that WiFi signals include a long known sequence, called the preamble. But preambles for Bluetooth beacon signals are extremely short.
The short duration gives an inaccurate fingerprint, making prior techniques not useful for Bluetooth tracking. Instead, the researchers designed a new method that doesn't rely on the preamble but looks at the whole Bluetooth signal. They developed an algorithm that estimates two different values found in Bluetooth signals. These values vary based on the defects in the Bluetooth hardware, giving researchers the device's unique fingerprint.
Although their finding is concerning, the researchers also discovered several challenges that an attacker will face in practice. Changes in ambient temperature for example, can alter the Bluetooth fingerprint. Certain devices also send Bluetooth signals with different degrees of power, and this affects the distance at which these devices can be tracked.
Part 1
Jun 9, 2022
Dr. Krishna Kumari Challa
Researchers also note that their method requires an attacker to have a high degree of expertise, so it is unlikely to be a widespread threat to the public today.
Despite the challenges, the researchers found that Bluetooth tracking is likely feasible for a large number of devices. It also does not require sophisticated equipment: the attack can be performed with equipment that costs less than $200.
Evaluating physical-layer BLE location tracking attacks on mobile devices, IEEE Security & Privacy conference in Oakland, Calif., May 24, 2022. PDF: cseweb.ucsd.edu/~schulman/docs … nd22-bletracking.pdf
Part 2
Jun 9, 2022
Dr. Krishna Kumari Challa
The largest ever series of phage therapy case studies shows a success rate of more than half
The number of reported cases using viruses to treat deadly Mycobacterium infections just went up by a factor of five.
In a new paper published recently in the journal Clinical Infectious Diseases, a team of researchers report 20 new case studies on the use of the experimental treatment, showing the therapy's success in more than half of the patients.
It's the largest ever set of published case studies for therapy using bacteria-killing viruses known as bacteriophages, providing unprecedented detail on their use to treat dire infections while laying the groundwork for a future clinical trial.
The phages are contributing to favorable outcomes—and in patients who have no other alternatives
Part 1
Jun 10, 2022
Dr. Krishna Kumari Challa
Each patient treated in the study was infected with one or more strains of Mycobacterium, a group of bacteria that can cause deadly, treatment-resistant infections in those with compromised immune systems or with the lung disorder cystic fibrosis.
For clinicians, these are really a nightmare: They're not as common as some other types of infections, but they're amongst some of the most difficult to treat with antibiotics. And especially when you take these antibiotics over extended periods of time, they're toxic or not very well-tolerated.
Looking at measures of patient health and whether samples from the patient still showed signs of Mycobacterium infections, the team found that the therapy was successful in 11 out of 20 cases. No patients showed any adverse reactions to the treatment.
In another five patients the results of the therapy were inconclusive, and four patients showed no improvement.
Several unexpected patterns emerged from the case studies. In 11 cases, researchers were unable to find more than one kind of phage that could kill the patient's infection, even though standard practice would be to inject a cocktail of different viruses so the bacteria would be less likely to evolve resistance.
In addition, the team saw that some patients' immune systems attacked the viruses, but only in a few cases did their immune systems render the virus ineffective. And in some instances, the treatment was still successful despite such an immune reaction. The study paints an encouraging picture for the therapy.
hage Therapy of Mycobacterium Infections: Compassionate-use of Phages in Twenty Patients with Drug-Resistant Mycobacterial Disease, Clinical Infectious Diseases (2022). DOI: 10.1093/cid/ciac453
Jun 10, 2022
Dr. Krishna Kumari Challa
Physicists Caught Sound Moving at Two Different Speeds in 3D Quantum Gas
After previously studying the phenomena of two sound waves in quantum liquids, scientists have now observed sound moving at two different speeds in a quantum gas.
If you were somehow immersed in the three-dimensional gas used for this study, you would hear every sound twice: each individual sound carried by two different sound waves moving at two different speeds.
This is an important development in the field of superfluidity – fluids with no viscosity that can flow without any loss of energy.
Remarkably, the behavior observed in the gas in terms of densities and velocities matched the parameters set down by Landau's two-fluid model, a theory developed for superfluid helium in the 1940s. To a large extent, it seems that when it comes to quantum gas setups, the same rules apply.
"These observations demonstrate all the key features of the two-fluid theory for a highly compressible gas.
https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.128.223601
Jun 14, 2022
Dr. Krishna Kumari Challa
Neuroscientists find new factors behind better vision
The size of our primary visual cortex and the amount of brain tissue we have dedicated to processing visual information at certain locations of visual space can predict how well we can see, a team of neuroscientists has discovered. Its study, which appears in the journal Nature Communications, reveals a new link between brain structure and behavior.
Scientists can now predict how well someone can see based on the unique structure of their primary visual cortex. By showing that individual variation in the structure of the human visual brain is linked to variation in visual functioning, they can better understand what underlies differences in how people perceive and interact with their visual environment.
As with fingerprints, the bumps and grooves on each person's brain surface are unique. However, the significance of these differences is not fully understood, especially when it comes to their impact on behavior, such as distinctions in our ability to see.
Using functional magnetic resonance imaging (fMRI), the scientists mapped the primary visual cortex (or "V1") size of more than two dozen humans. The researchers also measured the quantity of V1 tissue these individuals have dedicated to processing visual information from different locations in their field of view—locations to the left, right, above, and below fixation.
Part 1
Jun 14, 2022
Dr. Krishna Kumari Challa
The results showed that differences in V1 surface area could predict measurements of people's contrast sensitivity. First, people with a large V1 had better overall contrast sensitivity than did those with a small V1 (the largest surface area being 1,776 square millimeters [mm2] and the smallest being 832 mm2). Second, people whose V1 had more cortical tissue processing visual information from a specific region in their field of view had higher contrast sensitivity at that region relative to those with less cortical tissue dedicated to the same region. Third, across participants, higher contrast sensitivity at a specific location (e.g., left) than at another location equidistant from fixation (e.g., above) corresponded to regions with more or less cortical tissue, respectively.
In sum, the more local V1 surface area dedicated to encoding a specific location, the better the vision at that location.
Linking individual differences in human primary visual cortex to contrast sensitivity around the visual field, Nature Communications (2022). DOI: 10.1038/s41467-022-31041-9
Part 2
Jun 14, 2022
Dr. Krishna Kumari Challa
Study describes new way of generating insulin-producing cells
Researchers show how a molecule that they have identified stimulates the formation of new insulin-producing cells in zebrafish and mammalian tissue, through a newly described mechanism for regulating protein synthesis. The results are published in Nature Chemical Biology.
These findings indicate a new potential target for treating diabetes, in that researchers demonstrate a possible way of stimulating the formation of new insulin-producingcells.
Insulin injections and glucose-lowering drugs can control the disease, but not cure it.
One alternative could be a treatment that regulates blood glucose by increasing the number of insulin-producing pancreatic β cells.
The researchers has previously identified a small molecule able to stimulate the regeneration of insulin-producing β cells. This they did by analyzing a large quantity of substances in a zebra fish model.
In this present study, they examined the molecular mechanism of this stimulation.
By analyzing a large number of molecular interactions in yeast cells, the researchers show that their molecule binds to a protein called MNK2. Subsequent studies of zebrafish and cell cultures indicate that the molecule operates by regulating the translation of mRNA and boosting the synthesis of proteins, without which the formation of new β cells cannot be increased. Zebrafish given the molecule also showed lower levels of blood glucose than controls.
The study also shows that the molecule can induce the formation of new pancreatic β cells from pigs and stimulate the expression of insulin in human organoids (organ-like cell formations).
Scientists now will be studying the effect of this and similar molecules in human tissue and analyzing the molecule's target protein, MNK2, in tissue from healthy donors and donors with diabetes.
Olov Andersson, MNK2 deficiency potentiates β-cell regeneration via translational regulation, Nature Chemical Biology (2022). DOI: 10.1038/s41589-022-01047-x. www.nature.com/articles/s41589-022-01047-x
Jun 14, 2022
Dr. Krishna Kumari Challa
Nanoparticle sensor can distinguish between viral and bacterial pne...
Many different types of bacteria and viruses can cause pneumonia, but there is no easy way to determine which microbe is causing a particular patient's illness. This uncertainty makes it harder for doctors to choose effective treatments because the antibiotics commonly used to treat bacterial pneumonia won't help patients with viral pneumonia. In addition, limiting the use of antibiotics is an important step toward curbing antibiotic resistance.
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Bacterial intimacy insights could help tackle antimicrobial resistance
One of the primary ways harmful bacteria acquire resistance to antibiotics is by receiving DNA from other bacteria that are already resistant. This DNA exchange is made via a process called conjugation, akin to bacterial sex, whereby two bacteria form an intimate attachment, and one transfers a packet of DNA to the other.
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Shedding light on how bacteria communicate their way to causing inf...
Oregon State University scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group.
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Polluted air cuts global life expectancy by two years
Microscopic air pollution caused mostly by burning fossil fuels shortens lives worldwide by more than two years, researchers reported Tuesday.
Jun 14, 2022
Dr. Krishna Kumari Challa
Scientists discover and characterize a novel membraneless organelle that could play a role in Alzheimer's treatment
Researchers have discovered a novel organelle—a previously unknown cell structure whose function it is to help clean up faulty proteins in times of stress and keep cells functioning in top condition. Optimizing this membraneless organelle, which they call a BAG2 condensate, could lead to treatments for conditions that are the result of misfolded proteins, including Alzheimer's disease, Parkinson's disease and other neurodegenerative conditions. Their results are reported in a paper and published in the journal Nature Communications.
People have known for quite a while that are a few objects floating around in cells that don't have membranes. And it's never been clear how they're held together, what they are and what they're doing until relatively recently.
Thanks to advanced imaging techniques, scientists have uncovered structures that were once invisible, revealing cells for the truly complex and sophisticated systems that they are.
Of particular interest are biomolecular condensates, which don't have the recognizable cell membrane enclosure, but instead, are separated from the surrounding cytoplasm by a difference in density that can be loosely compared to a drop of oil in water. This liquid-liquid phase separation creates a specialized, relatively concentrated environment for certain functions and reactions. For example, a stress granule is a membraneless organelle that appears when the cell is under stress—maybe there's too much glucose, maybe it's too hot or cold, maybe the cell is experiencing dehydration—and its job is to sweep up RNA floating around in the cytoplasm, storing those genetic instructions and pausing their translation into proteins. If your cell is under stress, you want to shut down making proteins so you can really conserve your energy and get past the stress.
But that's only part of the picture, according to the researchers.
When there's stress, what happens to the proteins that are already in the cell?. If they're under those stress conditions, some of those proteins could get damaged and they could misfold." Misfolds of the tau protein, for example, can become pathological and turn into the neurofibrillary tangles that characterize Alzheimer's disease.
This is where the researchers' newly discovered BAG2 condensate comes in. Named for the BAG2 protein that it contains, the organelle, they found, is capable of sweeping up these faulty proteins in the cytoplasm and stuffing them into a proteasome—the cell's version of a trash can—located in the organelle.
Part 1
Jun 15, 2022
Dr. Krishna Kumari Challa
A few proteins form a little barrel, and as the protein is threaded through that little cylinder, it gets degraded. This inactivates and breaks down the protein. Many proteasomes are present in cells at any given time, he added, but what makes this particular proteasome (labeled 20S) special is that it can accept proteins that are already somewhat misfolded and would not fit in the other cellular trash cans.
The limiting cap present on many proteasomes is not there in the BAG2 condensates. These promising results could point to a way to interrupt the development of Alzheimer's disease, which is marked by an accumulation of misfolded tau.
Daniel C. Carrettiero et al, Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate, Nature Communications (2022). DOI: 10.1038/s41467-022-30751-4
Jun 15, 2022
Dr. Krishna Kumari Challa
Shedding light on how bacteria communicate their way to causing infection
Scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group. The research is important because understanding this type of signaling, known as quorum sensing and integral to bacterial pathogens, opens the door to potential new drugs that can disrupt it and thwart infection. Findings were published in the Proceedings of the National Academy of Sciences.
Sometimes single-celled organisms need to work together with other cells. Bacteria and other single-celled microbes can coordinate behaviors and act as a group via quorum sensing, in which cells produce and sense a small chemical signal that is shared within the population. As the signal is released from cells and reaches a high enough concentration in their environment, a quorum is achieved—certain genes are simultaneously activated and specific group behaviors are set in motion.
It's a strength-in-numbers approach that allows bacteria to join forces to do things they could not do by themselves, like causing infection in animals and plants, acquiring certain nutrients and competing against other microbes.
Bacterial infection often involves toxins that only harm the host at high levels, when produced by all bacterial cells at once.
A major unresolved question about quorum sensing, the researchers said, has been why the signal that's produced inside an individual cell is not sensed by that same cell before it is released, spurring the cell into premature, solo action.
What prevents signal 'short-circuiting' from happening? A set of proteins called antiactivators are crucial for short-circuit prevention. The proteins work as a quorum sensing "tuner" by causing cells to be less sensitive to the quorum signal.
This research shows how bacteria put the brakes on quorum sensing to achieve true communication in a group.
In addition to helping the quest for new antibiotics that can inhibit quorum sensing in bacterial pathogens, the findings also provide background knowledge useful for the engineering of cells with new properties in a field called synthetic biology.
Antiactivators prevent self-sensing in quorum sensing, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2201242119.
Jun 15, 2022
Dr. Krishna Kumari Challa
New work upends understanding of how blood is formed
The origins of our blood may not be quite what we thought. Using cellular "barcoding" in mice, a groundbreaking study finds that blood cells originate not from one type of mother cell, but two, with potential implications for blood cancers, bone marrow transplant, and immunology.
Till now people thought that most of our blood comes from a very small number of cells that eventually become blood stem cells, also known as hematopoietic stem cells. Scientists are now surprised to find another group of progenitor cells that do not come from stem cells. They make most of the blood in fetal life until young adulthood, and then gradually start decreasing.
The researchers are now following up to see if the findings also apply to humans. If so, these cells, known as embryonic multipotent progenitor cells (eMPPs), could potentially inform new treatments for boosting aging people's immune systems. They could also shed new light on blood cancers, especially those in children, and help make bone marrow transplants more effective.
Researchers applied a barcoding technique they developed several years ago and documented in Cell. Using either an enzyme known as transposase or CRISPR gene editing, they inserted unique genetic sequences into embryonic mouse cells in such a way that all the cells descended from them also carried those sequences. This enabled the team to track the emergence of all the different types of blood cells and where they came from, all the way to adulthood.
Through barcoding, the researchers found that eMPPs, as compared with blood stem cells, are a more abundant source of most lymphoid cells important to the immune responses, such as B cells and T cells. They think the decrease in eMPPs that they observed with age may explain why people's immunity weakens as they get older.They are now trying to understand why these cells peter out in middle age, which could potentially allow us to manipulate them with the goal of rejuvenating the immune system.
In theory, there could be two approaches: extending the life of eMPP cells, perhaps through growth factors or immune signaling molecules, or treating blood stem cells with gene therapy or other approaches to make them more like eMPPs.
Finally, the recognition that there are two types of mother cells in the blood could revolutionize bone marrow transplant.
Fernando Camargo, Lifelong multilineage contribution by embryonic-born blood progenitors, Nature (2022). DOI: 10.1038/s41586-022-04804-z. www.nature.com/articles/s41586-022-04804-z
Sarah Bowling et al, An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells, Cell (2020). DOI: 10.1016/j.cell.2020.04.048
Jun 16, 2022
Dr. Krishna Kumari Challa
Gender Inclusive Science Communication-Opportunities & Challenges
Jun 16, 2022
Dr. Krishna Kumari Challa
A Common Epilepsy Drug Causes Birth Defects, And We May Finally Know Why
Valproic acid – a drug commonly used to treat epilepsy and bipolar disorder – can cause birth defects and developmental disorders if taken during pregnancy, but the reason why has long been a mystery.
Now, in a study using mice and human tissue, scientists discovered that the medication locks some embryonic cells into a suspended state where they can't properly grow or divide.
By forcing key stem cellss into this state, called senescence, valproic acid may disrupt brain development in the womb and therefore cause cognitive and developmental disorders down the line, according to the study, published Tuesday (June 14) in the journal PLOS Biology.
An estimated 30 to 40 percent of infants exposed to the drug in the womb develop cognitive impairments or autism spectrum disorder, the study authors noted in their report, and these laboratory studies hint at why that happens.
In a subset of affected children, valproic acid exposure can also cause birth defects beyond the brain, including heart malformations and spina bifida, where part of the spinal column doesn't form properly and thus leaves the spinal cord exposed.
However, the new study suggests that these physical birth defects, though also linked to valproic acid, are triggered by a different mechanism than the cognitive impairment.
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pb...
Jun 16, 2022
Dr. Krishna Kumari Challa
Climate change catastrophe: Phytoplankton Productivity Down 65%
Jun 17, 2022
Dr. Krishna Kumari Challa
Which cells are involved in heart repair and how they communicate with each other
Thousands of people suffer heart attacks every year. In this case, the heart muscle is no longer supplied with sufficient blood and oxygen, and part of the heart muscle tissue dies and becomes scarred. The consequences can range from massive cardiac insufficiency to heart failure. Unlike the liver, the heart of an adult human being cannot regenerate. However, it is able to initiate repair processes. Exactly how these repair processes take place has not been known until now. Therefore, there are still no drugs that can specifically promote healing.
Now a research team has found out which cells are involved in heart repair and how they communicate with each other. The researchers have discovered a new messenger substance that controls wound healing, thus revealing an approach for a new therapy. The research has been published in Science.
The focus of the study is the receptor KIT. The protein is produced by various cells, including the hematopoietic stem cells in the bone marrow. Here, KIT plays an important role as a binding site for the so-called stem cell factor. This messenger substance activates the KIT-positive stem cells and causes them to develop into the various cells of the blood. KIT-positive cells are also found in the heart.
"However, these are not stem cells, as long suspected, but vascular cells. The KIT-positive vascular cells ensure that new heart vessels form after a heart attack. However, the stem cell factor necessary for KIT activation can barely be detected in the heart. The researchers have now resolved this contradiction. They discovered a new messenger substance in the heart that can also bind precisely to the KIT receptor and set the repair process in motion: the protein meteorin-like (METRNL).
After a heart attack, the immune system reacts with an inflammatory response . The inflammatory cells produce METRNL, which stimulates the KIT-positive vascular cells to form new blood vessels.
Studies in the mouse model showed that without METRNL, heart repair no longer worked. In contrast, when mice were treated with METRNL, new vessels formed in the infarct area. This alleviates scarring and prevents severe heart failure.
The newly discovered messenger substance could now be the decisive building block to a drug that specifically supports heart repair.
Marc R. Reboll et al, Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase, Science (2022). DOI: 10.1126/science.abn3027
Jun 18, 2022
Dr. Krishna Kumari Challa
Electrons take the fast and slow lanes at the same time
Imagine a road with two lanes in each direction. One lane is for slow cars, and the other is for fast ones. For electrons moving along a quantum wire, researchers have discovered that there are also two "lanes," but electrons can take both at the same time!
Current in a wire is carried by the flow of electrons. When the wire is very narrow (one-dimensional, 1D) then electrons cannot overtake each other, as they strongly repel each other. Current, or energy, is carried instead by waves of compression as one particle pushes on the next.
It has long been known that there are two types of excitation for electrons, as in addition to their charge they have a property called spin. Spin and charge excitations travel at fixed, but different speeds, as predicted by the Tomonaga-Luttinger model many decades ago. However, theorists are unable to calculate what precisely happens beyond only small perturbations, as the interactions are too complex. The Cambridge team has measured these speeds as their energies are varied, and find that a very simple picture emerges (now published in the journal Science Advances). Each type of excitation can have low or high kinetic energy, like cars on a road, with the well-known formula E=1/2 mv2, which is a parabola. But for spin and charge the masses m are different, and, since charges repel and so cannot occupy the same state as another charge, there is twice as wide a range of momentum for charge as for spin. The results measure energy as a function of magnetic field, which is equivalent to momentum or speed v, showing these two energy parabolas, which can be seen in places all the way up to five times the highest energy occupied by electrons in the system.
It's as if the cars (like charges) are traveling in the slow lane but their passengers (like spins) are going more quickly, in the fast lane! Even when the cars and passengers slow down or speed up, they still remain separate!
These results now open the question of whether this spin-charge separation of the whole electron sea remains robust beyond 1D, e.g., in high-temperature superconducting materials. It may also now be applied to logic devices that harness spin (spintronics), which offer a drastic reduction (by three orders of magnitude!) of the energy consumption of a transistor, simultaneously improving our understanding of quantum matter as well as offering a new tool for engineering quantum materials
Pedro M. T. Vianez et al, Observing separate spin and charge Fermi seas in a strongly correlated one-dimensional conductor, Science Advances (2022). DOI: 10.1126/sciadv.abm2781
Jun 18, 2022
Dr. Krishna Kumari Challa
Transplanting kidneys without need for immune-suppressing drugs
Physicians have developed a way to provide pediatric kidney transplants without immune-suppressing drugs. Their key innovation is a safe method to transplant the donor's immune system to the patient before surgeons implant the kidney.
The medical team has named the two-transplant combination a "dual immune/solid organ transplant," or DISOT. A scientific paper describing the first three DISOT cases, all performed at Lucile Packard Children's Hospital Stanford, published online June 15 in the New England Journal of Medicine.
This innovation removes the possibility that the recipient will experience immune rejection of their transplanted organ. (Organ rejection is the most common reason for a second organ transplant.) The new procedure also rids recipients of the substantial side effects of a lifetime of immune-suppressing medications, including increased risks for cancer, diabetes, infections and high blood pressure.
The first three DISOT patients were children with a rare immune disease, but the team is expanding the types of patients who could benefit.
The doctors anticipate that the protocol will eventually be available to many people needing kidney transplants, starting with children and young adults, and later expanding to older adults. The researchers also plan to investigate DISOT's utility for other types of solid-organ transplants.
The scientific innovation from the team has another important benefit: It enables safe transplantation between a donor and recipient whose immune systems are genetically half-matched, meaning children can receive stem cell and kidney donations from a parent.
Part 1
Jun 18, 2022
Dr. Krishna Kumari Challa
The idea of transplanting a patient with their organ donor's immune system has been around for decades, but it has been difficult to implement. Transplants of stem cells from bone marrow provide the patient with a genetically new immune system, as some of the bone marrow stem cells mature into immune cells in the blood. First developed for people with blood cancers, stem cell transplants carry the risk of the new immune cells attacking the recipient's body, a complication called graft-versus-host disease. Severe GVHD can be fatal.
Researchers working with adult patients have performed sequential stem cell and kidney transplants from living donors. When the donor was half-matched they had partial success, but patients were either unable to completely discontinue immune-suppressing drugs after transplant, or—in other trials not conducted at Stanford—they had unacceptably high risks of severe GVHD.
This new work introduced refinements that greatly improve the success of the two-transplant combination with much lower risk. This key innovation is a change in how the donor's stem cells are processed.
https://www.nejm.org/doi/full/10.1056/NEJMoa2117028
After stem cells are removed from the donor's body, technicians perform alpha-beta T cell depletion, which removes the type of immune cells that cause GVHD. Bertaina's team had showed that alpha-beta T cell depletion—which she developed while working in Italy prior to coming to Stanford—makes stem cell transplants safer and enables genetically half-matched transplants. The protocol is relatively gentle, making it safe for children with immune disorders who are too medically fragile for a traditional stem cell transplant. The alpha-beta T cells recover in the patient after 60 to 90 days, meaning they regain full immune function.
Part 2
Jun 18, 2022
Dr. Krishna Kumari Challa
Bluetooth signals can be used to identify and track smartphones
Jun 18, 2022
Dr. Krishna Kumari Challa
Damage to Brain Network Curbs Urge to Smoke
A study finds that injuries to certain areas of the brain were associated with quitting smoking more quickly, easily, and with no cravings.
Astudy of people who effortlessly quit smoking after a stroke or other brain injury—and of those who suffered an injury but then kept smoking—has pinpointed a brain network involved in addiction, researchers reported June 13 in Nature Medicine. Experts say the findings may help identify targets for therapies that could treat addictions.
https://www.the-scientist.com/news-opinion/damage-to-brain-network-...
Jun 18, 2022
Dr. Krishna Kumari Challa
Keeping objects levitated by sound airborne despite interference
A team of researchers has developed a way to keep objects levitated by sound waves airborne when other objects interfere with the levitation path. In their paper published in the journal Science Advances, the group describes their self-correcting levitation system.
Prior research has shown that it is possible to levitate objects by firing sound waves at them. Because sound waves are nothing more than air particles moving together in a certain way, the object being levitated will fall if an object interferes with the sound waves. In this new effort, the researchers developed new features to address this problem.
To protect the sound waves from interference, the researchers increased the number of speakers used—in their work, they used 256. They also added software to control each of the speakers. The speakers were arranged in a grid and objects were levitated by specifically shaped sound waves. By programming the speakers in specific ways, the team was able to get the system to work together to keep an object above the grid in the air despite interruptions. If some of the sound waves were blocked, other sound waves were redirected to take their place.
The researchers proved their system was viable by testing it using a 3D-printed white rabbit as an interference object. Objects were levitated around the rabbit regardless of its location. In one experiment, the researchers levitated beads around the rabbit that formed into a flying butterfly. They also levitated a piece of clear fabric that they used as a screen for projection of the rabbit they had printed. And they levitated a single drop of water over a glass of water, showing that their system would work even when the interfering object was a jiggling glass of liquid.
Ryuji Hirayama et al, High-speed acoustic holography with arbitrary scattering objects, Science Advances (2022). DOI: 10.1126/sciadv.abn7614
Jun 21, 2022
Dr. Krishna Kumari Challa
Lack of diversity of microorganisms in the gut or elevated gut metabolites implicated in heart failure severity
Some people who experience heart failure have less biodiversity in their gut or have elevated gut metabolites, both of which are associated with more hospital visits and greater risk of death, according to a systematic review of research findings.
The gut microbiome is a delicately balanced ecosystem comprised primarily of bacteria as well as viruses, fungi and protozoa. The microbiome can affect cardiovascular disease, which is a leading cause of death in many parts of the world.
For their overview, the investigators looked at seven years of genetic, pharmacologic and other types of research findings from around the world to generate a wide perspective on how the microbiome can influence heart failure. The investigators zeroed in on one harmful metabolite, trimethylamine-N-oxide (TMAO), that can be produced by churning gut microbiota when full-fat dairy products, egg yolks and red meat are consumed.
The Heart and Gut Relationship: A Systematic Review of the Evaluation of the Microbiome and Trimethylamine-N-Oxide (TMAO) in Heart Failure, Heart Failure Reviews (2022). DOI: 10.1007/s10741-022-10254-6
Jun 21, 2022
Dr. Krishna Kumari Challa
Scientists develop antimicrobial, plant-based food wrap designed to replace plastic
Aiming to produce environmentally friendly alternatives to plastic food wrap and containers, a scientist has developed a biodegradable, plant-based coating that can be sprayed on foods, guarding against pathogenic and spoilage microorganisms and transportation damage.
The scalable process could potentially reduce the adverse environmental impact of plastic food packaging as well as protect human health.
Their article, published in the science journal Nature Food, describes the new kind of packaging technology using the polysaccharide/biopolymer-based fibers. Like the webs cast by the Marvel comic book character Spider-Man, the stringy material can be spun from a heating device that resembles a hair dryer and "shrink-wrapped" over foods of various shapes and sizes, such as an avocado or a sirloin steak. The resulting material that encases food products is sturdy enough to protect bruising and contains antimicrobial agents to fight spoilage and pathogenic microorganisms such as E. coli and listeria.
The research paper includes a description of the technology called focused rotary jet spinning, a process by which the biopolymer is produced, and quantitative assessments showing the coating extended the shelf life of avocados by 50 percent. The coating can be rinsed off with water and degrades in soil within three days, according to the study.
The new packaging is targeted at addressing a serious environmental issue: the proliferation of petroleum-based plastic products in the waste stream.
High-throughput coating with biodegradable antimicrobial pullulan fibres extends shelf life and reduces weight loss in an avocado model, Nature Food (2022). DOI: 10.1038/s43016-022-00519-6
Jun 21, 2022