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Comment by Dr. Krishna Kumari Challa on June 2, 2022 at 6:15am

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

Comment by Dr. Krishna Kumari Challa on June 2, 2022 at 6:09am

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

Comment by Dr. Krishna Kumari Challa on June 2, 2022 at 5:55am

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

Comment by Dr. Krishna Kumari Challa on June 1, 2022 at 8:56am

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...

Comment by Dr. Krishna Kumari Challa on June 1, 2022 at 8:52am

How wingless salamanders fly

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.

https://www.nature.com/articles/d41586-022-01375-x

Comment by Dr. Krishna Kumari Challa on June 1, 2022 at 8:45am

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

Comment by Dr. Krishna Kumari Challa on June 1, 2022 at 8:37am

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

Comment by Dr. Krishna Kumari Challa on June 1, 2022 at 8:28am

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/

Comment by Dr. Krishna Kumari Challa on June 1, 2022 at 8:04am

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

Comment by Dr. Krishna Kumari Challa on June 1, 2022 at 7:18am

Driver mutations vs passenger mutations

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