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Speaking requires both sides of the brain. Each hemisphere takes over a part of the complex task of forming sounds, modulating the voice and monitoring what has been said. However, the distribution of tasks is different than has been thought up to now, as an interdisciplinary team of neuroscientists and phoneticians at Goethe University Frankfurt and the Leibniz-Centre General Linguistics Berlin has discovered: it is not just the right hemisphere that analyses how we speak - the left hemisphere also plays a role.

Until now, it has been assumed that the spoken word arises in left side of the brain and is analysed by the right side. According to accepted doctrine, this means that when we learn to speak English and for example practice the sound equivalent to "th", the left side of the brain controls the motor function of the articulators like the tongue, while the right side analyses whether the produced sound actually sounds as we intended.

The division of labour actually follows different principles, as Dr Christian Kell from the Department of Neurology at Goethe University explains: "While the left side of the brain controls temporal aspects such as the transition between speech sounds, the right hemisphere is responsible for the control of the sound spectrum. When you say 'mother', for example, the left hemisphere primarily controls the dynamic transitions between "th" and the vowels, while the right hemisphere primarily controls the sounds themselves." His team, together with the phonetician Dr Susanne Fuchs, was able to demonstrate this division of labour in temporal and spectral control of speech for the first time in studies in which speakers were required to talk while their brain activities were recorded using functional magnetic resonance imaging.

A possible explanation for this division of labour between the two sides of the brain is that the left hemisphere generally analyses fast processes such as the transition between speech sounds better than the right hemisphere. The right hemisphere could be better at controlling the slower processes required for analysing the sound spectrum. A previous study on hand motor function that was published in the scientific publication "elife" demonstrates that this is in fact the case. Kell and his team wanted to learn why the right hand was preferentially used for the control of fast actions and the left hand preferred for slow actions. For example, when cutting bread, the right hand is used to slice with the knife while the left hand holds the bread.

In the experiment, scientists had right-handed test persons tap with both hands to the rhythm of a metronome. In one version they were supposed to tap with each beat, and in another only with every fourth beat. As it turned out, the right hand was more precise during the quick tapping sequence and the left hemisphere, which controls the right side of the body, exhibited increased activity. Conversely, tapping with the left hand corresponded better with the slower rhythm and resulted in the right hemisphere exhibiting increased activity.

Taken together, the two studies create a convincing picture of how complex behaviour - hand motor functions and speech - are controlled by both cerebral hemispheres. The left side of the brain has a preference for the control of fast processes while the right side tends to control the slower processes in parallel.

The parasites responsible for malaria seem to march to their own beat.

The mystery behind the molecular basis of how these parasites synch their rhythm in replication to the host's clock-driven rhythms has been solved. A new genetic analysis led by KAUST scientists revealed Plasmodium parasites have internal timekeeping systems that help the organism maintain essential oscillations in gene expression levels and cell cycle activities.

Just as humans reset their own biological clocks in response to light-dark cues, malaria parasites time their own rhythms to host signals to maximize their growth success.

The finding of a genetic metronome within the malaria parasite, as well as one component of this timekeeping mechanism, could open new pathways for combatting one of the world's deadliest contagious diseases. Saudi Arabia is on the verge of malaria eradication, but the disease continues to affect its southwestern border, where infections have proven difficult to treat and parasites are increasingly resistant to existing drugs.

"The knowledge from our study has the potential to inform new therapies for malaria elimination," says Amit Subudhi, a postdoctoral research fellow in Arnab Pain's group and the first author of the new report. "This information might allow doctors to formulate drug regimens in which patients take anti-malarial therapies with known target genes at particular times of the day so as to eliminate the malaria parasite more effectively."

Subudhi and Pain teamed up with colleagues from the University of Edinburgh, U.K., and from Nagasaki University, Japan, to profile gene activity patterns in mouse-infecting malaria parasites. They found that more than half of all the parasite's genes exhibited 24-hour cycles of activity, ramping up and down at regular daily intervals. This pattern is consistent with the characteristic rhythms of fevers and chills seen in people infected with malaria.

Around half of the rhythmic genes lost their periodicity when the clocks of the parasite and mouse fell out of synchrony. Likewise ; in a lab dish, human malaria parasites cultured without timing cues also displayed some degree of daily rhythmicity in gene expression. One of these genes coded for a receptor protein called SR10, which the researchers showed acts as a cog in the parasite's intrinsic clock machinery.

Without this protein, the usual 24-hour cycle of the rodent Plasmodium parasite became shorter, leading to defects in DNA replication and other cellular processes as well as protein breakdown. According to Subudhi, SR10 likely serves as a link between host circadian rhythms and the endogenous time-keeping ability of the parasite.

The KAUST researchers plan to dissect the molecular components of the SR10-mediated signaling pathway in search of novel drug targets. "Our work does not stop here," notes Pain. "Our next aim is to understand the chemical nature of the host-derived cues that the parasite receives to adjust its life cycle and its biological clock," he says.

A new research paper co-authored by a Virginia Tech assistant professor of physics provides a new explanation for two recent strange events that occurred in Antarctica - high-energy neutrinos appearing to come up out of the Earth on their own accord and head skyward.

The anomalies occurred in 2016 and 2018 and were discovered by scientists searching for ultra-high-energy cosmic rays and neutrinos coming from space, all tracked by an array of radio antennas attached to a balloon floating roughly 23 miles above the South Pole. Neutrinos are exceedingly small particles, created in a number of ways, including exploding stars and gamma ray bursts. They are everywhere within the universe and are tiny enough to pass through just about any object, from people to lead to buildings and the Earth itself.

The events were discovered by scientists at the ANITA experiment -- that's short for Antarctic Impulsive Transient Antenna, started in 2006 -- in the South Pole. Twice, ANITA scientists discovered radio signals mimicking highly energetic neutrinos seemingly coming upward out of the ground on their own accord. Scientists remain perplexed by the activity, with some 40 papers so far giving wildly different answers -- the pulses are neutrinos that passed unencumbered through the entire core of Earth and came out of the ground; the pulses are the long sought-after "fourth" neutrino known as the sterile neutrino; the mysterious "dark matter" of space is to blame; or this is an entirely unknown frontier of particle and/or astrophysics physics begging for a Nobel.

Ian Shoemaker, an assistant professor in the Department of Physics and the Center for Neutrino Physics, both part of the Virginia Tech College of Science, has a different, simpler explanation. In a recent paper published in the journal Annals of Glaciology, Shoemaker and several colleagues posit that the anomalies are not from neutrinos, but are merely unflipped reflections of the ultra-high-energy cosmic rays that arrive from space -- miss the top layer ice -- then enter the ground, striking deep, compacted snow known as firn.

"We think sub-surface firn is the culprit," said Shoemaker, adding that "firn is something between snow and glacial ice. It's compacted snow that's not quite dense enough to be ice. So, you can have density inversions, with ranges where you go from high density back to low density, and those crucial sorts of interfaces where this reflection can happen and could explain these events."

Shoemaker was joined on the paper by his former Ph.D. advisor, Alexander Kusenko of the University of California Los Angeles' Department of Physics and Astronomy; Andrew Romero-Wolf, a member of the ANITA team and a researcher at the California Institute of Technology's Jet Propulsion Laboratory; and four other researchers, including two glaciologists: Dustin Shroeder from Stanford University and Martin Siegert from Imperial College London.

Call it a case of Occam's razor (that's the centuries-old theory that the simplest solution in most likely the correct one, for those who skipped philosophy in college), but Shoemaker isn't railing ANITA. "Whatever ANITA has found, it is very interesting, but it may not be a Nobel prize-winning particle physics discovery." But he's not discounting that the so-called anomalies have no scientific merit. "ANITA still could have discovered something interesting about glaciology instead of particle physics, it could be ANITA discovered some unusual small glacial lakes."

Sub-glacial lakes were another consideration by Shoemaker and his team for the reflections. These lakes, deep underground, though, are too far spread apart according to current research, and hence are not the most likely explanation. But if there are far more lakes than previously known, this discovery would be a big win for scientists who study the landscape and interior of Antarctica. Shoemaker and his team suggest scientists purposefully blast radio signals into the areas where the anomalies occurred.

"I didn't know anything about them, but they really do exist," Shoemaker said of sub-glacier lakes in Antarctica. "There are lakes under the ice in Antarctica, and those would have the right reflective properties, but they're not widespread enough. Our idea is that part of the radio pulse from a cosmic ray can get deep into the ice before reflecting, so you can have the reflection without the phase flip. Without flipping the wave, in that case, it really looks like a neutrino."

Shoemaker added that, "When cosmic rays, or neutrinos, go through ice at very high energies, they scatter on materials inside the ice, on protons and electrons, and they can make a burst of radio, a big nice radio signal that scientists can see. The problem is that these signals have the radio pulse characteristic of a neutrino, but are appear to be traversing vastly more than is possible given known physics. Ordinary neutrinos just don't so this. But cosmic rays at these energies are common occurrences and have been seen by many, many experiments."

WASHINGTON, June 9, 2020 -- Benchtop tools for studying the respiratory system misrepresent the interdependence between the diaphragm, abdomen and lungs. Meanwhile, computational models often hide the mechanisms in a black box computation, without a clear picture of what transpires in the process.

This means students form a poor understanding of respiratory mechanisms and makes it hard to train clinicians for real scenarios or prototype embeddable medical devices.

"If students can visualize pleural and abdominal pressure curves being generated in real time, while simultaneously observing diaphragm motion and lung inflation and deflation, it helps them establish an mental model, which can be called on and interrogated for different conditions, both physiological and pathological," author Ellen Roche said.

In a paper published in APL Bioengineering, by AIP Publishing, Roche and co-authors created a high-fidelity respiratory simulator that accurately represents the interplay between the abdomen, diaphragm, lungs and pleural space, the fluid-filled membrane surrounding the thorax and lungs.

"We are excited about using synthetic actuators to actuate organic material, because we can preserve tissue structures while achieving reliable, tunable and deterministic motion with a soft robotic structure," Roche said. "Our ultimate goal is to develop a model that combines the mechanics of the respiratory and cardiovascular systems to elucidate and characterize their interdependency and to test new therapeutic strategies."

The model they created, using swine lungs, soft robotic materials and artificial muscles, allows precise tuning of pressure in each part of the system, so specific disease conditions can be tested to show how even minor changes affect overall respiratory function.

For example, the model was successfully used to test three types of pneumothorax, when air enters the pleural space, and obstructive lung disease by increasing flow resistance in the airway. The authors also tested a patch for repairing lung punctures and showed the system of sensors measuring flow, volume and pressure in the model is able to precisely measure airway pressure and pleural pressure.

The model, which is completely modular with parts that can be removed or replaced, also proved extremely useful for testing ventilator-only respiration by removing the elastomeric diaphragm.

"We are currently using it as a realistic testbed to test different ventilator options that have been developed for the COVID-19 pandemic," Roche said.

The authors plan to add cardiovascular components to their model to further increase its usability to study complex problems involving respiratory and cardiovascular systems.

DALLAS - June 9, 2020 - Serotonin, a chemical known for its role in producing feelings of well-being and happiness in the brain, can reduce the ability of some intestinal pathogens to cause deadly infections, new research by UT Southwestern scientists suggests. The findings, publishing online today in Cell Host & Microbe, could offer a new way to fight infections for which few truly effective treatments currently exist.

Although the vast majority of research on serotonin has centered on its effects in the brain, about 90 percent of this neurotransmitter - a chemical that nerve cells use to communicate with each other - is produced in the gastrointestinal tract, explains study leader Vanessa Sperandio, Ph.D., a professor of microbiology and biochemistry at UT Southwestern Medical Center. In humans, trillions of bacteria live within this space. Most of these gut bacteria are beneficial, but pathogenic bacteria can also colonize the gastrointestinal tract, causing serious and potentially fatal infections.

Because gut bacteria are significantly affected by their environment, Sperandio, along with UTSW doctoral student Aman Kumar, laboratory manager Regan Russell, and their colleagues, wondered whether the serotonin produced in the gut can affect the virulence of pathogenic bacteria that infect the gastrointestinal tract.

The researchers worked with Escherichia coli O157, a species of bacteria that causes periodic outbreaks of often deadly foodborne infection. The team grew these pathogenic bacteria in petri dishes in the lab, then exposed them to serotonin. Gene expression tests showed that serotonin significantly reduced the expression of a group of genes that these bacteria use to cause infections. Additional experiments using human cells showed that the bacteria could no longer cause infection-associated lesions on the cells if these bacteria were exposed to serotonin.

Next, the researchers examined how serotonin affected virulence in living hosts. Using mice, the researchers studied how serotonin might change the ability for Citrobacter rodentium - a mouse gut bacterium often used as an analog for E. coli in humans - to infect and sicken their hosts. These mice were genetically modified to either over- or underproduce serotonin in their gastrointestinal tracts. Those that overproduced this neurotransmitter were less likely to become colonized by C. rodentium after being exposed to this bacterium or had relatively minor courses of illness. Treating mice with fluoxetine (sold under the brand name Prozac) to increase serotonin levels prevented them from getting sick from C. rodentium exposure. However, the mice that underproduced serotonin became much sicker after bacterial exposure, often dying from their illness.

Further experiments identified the receptor for serotonin on the surfaces of both E. coli and C. rodentium, a protein known as CpxA. Because many species of gut bacteria also have CpxA, it's possible that serotonin could have wide-ranging effects on gut bacterial health, Sperandio says.

In the future, she adds, she and her colleagues plan to study the feasibility of manipulating serotonin levels as a way of fighting bacterial infections in the gastrointestinal tract. Currently, few available antibiotics can effectively fight E. coli O157 - some antibiotics actually worsen the consequences of infection, causing the bacteria to release more damaging toxins.

"Treating bacterial infections, especially in the gut, can be very difficult," Sperandio says. "If we could repurpose Prozac or other drugs in the same class, it could give us a new weapon to fight these challenging infections."

A study led by the Institut de Neurociències (INc-UAB) describes a new strategy to tackle cancer, based on inducing a potent stress in tumor causing cell destruction by autophagy. The mechanism has been revealed using the new antitumor drug ABTL0812, currently in clinical trial. Results has been validated using samples from oncologic patients and published in Autophagy.

A study led by researchers from the Institut de Neurociències (INc-UAB), in collaboration with the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), describes a new mechanism by which the antitumor drug ABTL0812 induces stress in tumors, causing cell destruction by cytotoxic autophagy. This molecule is currently being tested in patients with advanced endometrial and squamous lung carcinoma, in combination with standard chemotherapy.

The findings were published in the Autophagy journal and show a new strategy to tackle cancer based on the manipulation of dihydroceramides, a group of cellular lipids. The authors also describe for the first time the detection of mRNAs of two stress-related proteins - CHOP and TRIB3- in blood samples from patients undergoing clinical trial, supporting their use as pharmacodynamic biomarkers.

The research team was coordinated by Jose Miguel Lizcano from the INC and the UAB Biochemistry and Molecular Biology Department. For the past years, this team has investigated how ABTL0812 exerts its antitumor action. This molecule was developed by the biopharmaceutical company AbilityPharma located at the UAB Research Park. AbilityPharma contacted Dr. Lizcano to uncover the antitumor mechanism of action of ABTL0812. Since then, clinical trials have advanced in parallel with research in the laboratory.

In 2016, when clinical studies began, Dr. Lizcano's laboratory discovered that this was the first anticancer drug in trials to induce toxic autophagy in tumor cells. Now, with this drug being tested in clinical phase II, the new study shows how toxic autophagy is produced.

"Cancer cell death comes from alterations in the levels of cellular dihydroceramides, a family of cellular lipids. Elevated levels of dihydroceramides provoke a severe stress of the endoplasmic reticulum, a cellular organelle in charge of protein synthesis, resulting in the accumulation of defective proteins. As a consequence, cells activate a compensatory response, called Unfolded Protein Response (UPR). This response, when sustained in time, can induce autophagy that results in cancer cell death", says Jose Miguel Lizcano.

The study also explains why ABTL0812 does not affect non-cancer cells: "The main advantage of this molecule lies in its specificity for tumor cells. To survive the hostile environment, cancer cells overtake it by having elevated levels of ER stress and UPR activity. Our drug provokes cancer cells to overpass the stress level in which this response has protective effects, causing their death, while healthy cells still have a wider margin", says Pau Muñoz, researcher at the INC and first author of the article.

Researchers consider that this new mechanism of action could be used safely in the treatment of different types of cancers. In fact, the study also served to present the preliminary results on pancreatic and other biliary tract cancer models.

This work will be presented by AbilityPharma at the American Association for Cancer Research (AACR) 2020 Congress. "The description of this mechanism of action is a very important step for AbilityPharma, and shows the excellent collaboration engaged by our company and the INc-UAB. Also, it supports a broader use of ABTL0812 in other cancer paradigms, apart from endometrial and squamous lung carcinoma" explains Carles Domènech, AbilityPharma's executive chairman.

When a lake is covered with green scums during a warm summer, cyanobacteria - often called blue-green algae - are usually involved. Mass development of such cyanobacteria is bad for water quality because they can deprive the water of oxygen and produce toxins. But cyanobacteria can become sick, when for instance infected by fungal parasites. Researchers from the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB) found out that these infections do not only kill cyanobacteria, they also make them easier to consume for their natural predators. Fungal parasites thus help to slow down the growth of blue-green algae.

Blue-green algal blooms are an increasing problem in waterbodies worldwide: Higher temperatures and growing nutrient loads lead to excessive growth of cyanobacteria. These mass developments affect water quality because many cyanobacteria produce toxins and reduce the oxygen concentration in the water, sometimes leading to death of fish and other aquatic organisms.

The international team led by IGB found that algal growth can be controlled by parasitic fungi. "Many of these algae have long filamentous shapes or grow in colonies, which makes them difficult to be eaten by their natural predators", explains Dr. Thijs Frenken, first author of the study and researcher at IGB and the University of Windsor in Canada. Chytrids, a very common group of fungi, often infect cyanobacteria. The researchers have now shown that, in addition to infecting and killing algae, the fungi "chop" the algae into shorter pieces, making them easier to be eaten by small aquatic organisms. "We knew that fungal infections reduce the growth of cyanobacteria, but now we know that they also make them easier prey", says IGB researcher Dr. Ramsy Agha, head of the study.

Fungi as food supplements for zooplankton

The researchers showed that in addition to "chopping" infected cyanobacteria filaments and making them more vulnerable to predation by small organisms in the water, zooplankton, parasitic fungi themselves serve as a valuable food supplement. Chytrid fungi contain various fats and oils that are an important part of the diet of small freshwater organisms and are not present in blue-green algae. Parasitic fungi therefore serve as an important dietary connection between different levels of aquatic food webs.

"These results show how parasites, although usually perceived as something bad, also have important positive effects on the functioning of aquatic ecosystems", says Professor Justyna Wolinska, head of the IGB research group Disease Evolutionary Ecology.

Scientists have described a potential new therapeutic strategy for slowing down early-stage Huntington's disease in a new study published today in eLife.

The research in mice indicates that targeting the histamine H3 receptor (H3R) - a well-established drug target for other conditions such as hay fever - could help to prevent imbalances in dopamine signalling that lead to brain-cell death and deficits in movement and memory.

"It was already well known that dopamine signalling goes away in Huntington's disease, but we and other research teams have shown more recently that dopamine receptors and histamine receptors are found together and control signalling in the brain," explains lead author David Moreno-Delgado, who was a Postdoctoral Research Scientist at the University of Barcelona, Spain, at the time the research was carried out, and is now Biology Team Leader at NovAliX, Belgium. "Because dopamine receptors are found in many normal cells throughout the central nervous system, we proposed that targeting dopamine signalling through the histamine receptor might be a more effective strategy to slow the progression of Huntington's disease."

The team looked at whether these protein partners are found together in mice with Huntington's disease and could potentially be targets for treatment. They found that at two- and four-months-old, both healthy mice and those with asymptomatic Huntington's disease have the dopamine D1 receptor (D1R)-H3R complex. But when the team looked at older mice aged six- and eight-months-old, the mice with Huntington's disease (now symptomatic) had completely lost the D1R-H3R complexes. The individual receptors were still present, but at the most advanced stage of the disease, these proteins were no longer acting together as partners.

To confirm the role of the D1R-H3R complex, the team tested the effects of an antihistamine drug called thioperamide on movement, learning and memory in mice with Huntington's disease. Mice treated with thioperamide were only as likely to fall as healthy mice of the same age, while those treated with saline were unable to maintain their balance. Moreover, in a test of memory, the mice treated with saline showed no preference for familiar objects, whereas those treated with thioperamide had no such memory deficits.

The team next explored whether these results were due to the treatment preserving the D1R-H3R complexes. Studies of tissues from treated and untreated mice showed that only the treated animals still had H3R/D1R complexes at six and eight months of age. Moreover, when they treated mice with Huntington's disease that had already reached seven months of age (when these protein partners are no longer found together), thioperamide had no effect on movement, learning or memory deficits. This confirms that the protective effects of thioperamide occurs through the D1R-H3R complexes and that these need to be present for the drug to work.

Finally, the team looked at human brain tissue samples for the presence of D1R-H3R complexes. They found that, in healthy individuals and people with early-stage Huntington's disease, the D1R-H3R complexes were present. By contrast, in people with more advanced disease, the D1R-H3R complexes were almost absent.

"The imbalance of dopamine signalling in disease progression represents a potential 'point of no return' for Huntington's disease patients as it can eventually lead to nerve-cell dysfunction and death," explains senior author Peter McCormick, Senior Lecturer at Queen Mary University of London, UK. "In this study we show that D1R/H3R complexes are found within the brain at early- but not late-disease stages and that targeting these complexes could potentially slow the progression of early-stage disease.

"In addition, our data help explain previous studies attempting to target H3R by showing the dependency on D1R/H3R complexes for these drugs to work. This is important as there are multiple H3R compounds either in the clinic or that have been through phase two and three trials that could be opportunities for drug repurposing."

A key set of proteins that help regulate hormones necessary for many essential functions in humans and other vertebrates have ancient origins in much simpler creatures such as sea cucumbers, says a new study published today in eLife.

The kisspeptin system consists of a group of proteins that help control hormones released by trio of organs: the hypothalamus, the pituitary gland and the testicles in men or the ovaries in women. This trio regulates reproduction, metabolism, the immune system and other important body functions. Tracing the evolutionary origins of the kisspeptin proteins may help scientists learn more about why they developed and how they work.

"The origins of these proteins have previously been traced to very simple creatures with spinal cords, but it hadn't been traced back any further," says lead author Tianming Wang, Professor at the Marine Science and Technology College, Zhejiang Ocean University, China. "This raises an important question: does the kisspeptin system have an ancient evolutionary origin, or did it first emerge in animals with spinal cords?"

To answer this question, Wang and his colleagues searched for kisspeptin system genes in the sea cucumber, a very simple sea creature with no spinal cord. They identified equivalents of the kisspeptin genes in the sea cucumber.

Next, they found that administering kisspeptin-like cucumber proteins to mammal cells causes them to release calcium, similar to how human versions of the protein would behave. The sea cucumber proteins were also able to interact with receptors in the human cells, suggesting that little has changed in these proteins over the course of evolution.

Finally, the team carried out a series of experiments where they activated or blocked this signalling system in sea cucumbers. This showed that these proteins are crucial for reproduction and metabolism in the creatures.

These experiments suggest that the kisspeptin system predates the evolution of the spinal cord in animals and that it will also be present in other creatures closely related to the sea cucumber, according to senior author Naiming Zhou, Professor at the Institute of Biochemistry, Zhejiang University, China.

"Our findings indicate the existence of a kisspeptin signaling system in a very simple organism lacking a spinal cord," Zhou concludes. "They provide new evidence to support the ancient evolutionary origin of the physiological functions in vertebrates that are controlled by the kisspeptin system."

AUGUSTA, Ga. (June 9, 2020) - Particularly in females with untreated hypertension, reducing salt intake to what's considered a healthier level appears to be good for both their gut microbiome and their blood pressure, scientists report.

In the blood of 145 adults with untreated hypertension, the scientists found that, particularly for the females, just six weeks of a daily sodium intake close to the 2,300 milligrams recommended by groups like the American Heart Association, resulted in increased levels of short-chain fatty acids, an indicator of a healthy microbiome, circulating in the blood. The hypertensive adults also experienced decreased blood pressure and more compliant blood vessels.

"There is a connection," Dr. Haidong Zhu, molecular geneticist at the Georgia Prevention Institute at the Medical College of Georgia at Augusta University, says of increasing evidence that the microbiome has a direct role in regulating blood pressure and how the average American high-salt diet can interfere with a healthy direction.

To the scientists' knowledge their study in the journal Hypertension is the first to look at how decreasing salt intake in humans affects circulating short-chain fatty acids, or SCFAs, says Zhu, the study's corresponding author.

Emerging evidence suggests that a high-salt diet alters the gut microbiome, particularly in animal models of salt-sensitive hypertension, but there is little human data. "We are trying to understand underlying mechanisms," says Zhu, whose research focus incudes increasing understanding of the ways a high-salt diet induces high blood pressure.

The gut microbiota are all the bacteria, viruses, protozoa and fungi populating your gastrointestinal tract, which have a wide range of functions from helping digest your food to your immune response to influencing a propensity to gain weight. Problems with the microbiome are associated with a wide range of diseases from cancer to gastrointestinal problems to allergies.

Short-chain fatty acids, or SCFAs, are known to play a role in blood pressure regulation. These small metabolites originating from the gut, get absorbed into the entire circulation, binding to receptors on the lining of blood vessels and in the kidneys, regulating things like the release of renin, an enzyme that works to keep the kidneys well perfused and a major player in blood pressure control. Blood levels of SCFAs can be considered an indicator of the health of the gut microbiome.

Their hypothesis was even a modest reduction in salt intake would alter concentrations of circulating SCFAs and lower blood pressure.

The scientists looked at a mix of blacks, whites, Asians, males and females, ages 30 to 75 who had in common untreated high blood pressure and were enrolled in a previous study at the Queen Mary University of London. Because stool samples were not taken on the study participants, they could not look more directly at the gut microbiota, so instead measured circulating SCFAs, the main metabolite produced by gut microbiota.

All the individuals were given two weeks of detailed instruction by nurses on how to lower their sodium intake to about 2,000 milligrams daily, information that was reinforced over the course of the study. Then in what is called a randomized, placebo-controlled study, half the participants got either a sodium tablet or placebo tablet nine times daily for six weeks, then switched groups.

They found sodium reduction increased all eight of the SCFAs, the end product of the fermentation of fibers we consume by our microbiota. We don't naturally contain enzymes to digest many of these fibers. The increased SCFA levels they found were consistently associated with lower blood pressure and increased blood vessel flexibility.

While periods of higher salt intake drove up blood pressures in both males and females and improvements were noted in both sexes with a move to lower salt, the shifts were most dramatic in females, Zhu says. While we all have slightly distinctive microbiota -- influenced by things like diet and environment -- there tend to be consistent differences between males and females generally.

"Sodium is a factor in both sexes but the impact in relationship to the gut microbiome seems more in females," Zhu says. "We need to study it further to see if that is true and why it's true if it holds." It may be that high-salt affects blood pressure through different pathways in males and females, she adds.

As examples, the 24-hour systolic pressure, the top number which indicates pressure when the heart is contracting, was almost five points lower when females were on a low-salt versus high-salt diet and a little more than three points lower in the males. Nighttime pressures, an important time for the heart and body to rest, also dropped, with systolic numbers decreasing nearly five points in females and just under three points in the males as they decreased salt intake.

In the future, the MCG scientists want to do a larger study that also examines fecal samples to more directly assess microbiome content and health and to see if the sex differences they found hold.

A 2017 study in the journal Nature showed a high-salt diet impacted the gut microbiome of mice, depleting in particular Lactobacillus murinus, a normally predominant microbe known to curb inflammation, and driving blood pressure up; giving the microbe back prevented this blood pressure increase. The gut microbiome changes also held true in a small pilot study of humans, and the study by German investigators appeared to be the first, or among the first, highlighting the gut microbiome health as a factor in high blood pressure.

The American Heart Association recommends Americans consume less than 2,300 milligrams of sodium daily but most adults consume more like 3,400 milligrams. More traditionally, high salt's impact on factors like the renin-angiotensin-aldosterone system, known to regulate blood pressure, and the sympathetic nervous system, which drives the so called 'fight or flight' response, have been a study focus. "We are trying to identify maybe some new pathways," Zhu says, in the complex area of blood pressure regulation.

The gut microbiome can have 200 times more genes than the 20,000 gene human genome and weighs up to five pounds. SCFAs are a major energy source for the epithelial cells lining the colon, which keep contents from leaking out of the gastrointestinal tract into the body. SCFAs are thought to play a role in protecting us from common problems like inflammation, obesity and diabetes.

Patients recovering from COVID-19 could suffer significant long-term effects, according to research into the experiences of people hospitalised by previous coronavirus outbreaks.

Researchers at the universities of Leeds, Manchester and Hull have for the first time collated evidence on physical, psychological and social impacts among patients who fell victim to Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) - two previous viral infection outbreaks similar to the current COVID-19 pandemic.

These previous outbreaks resulted in respiratory and exercise capacity problems in the first six months after hospitalisation, mental health problems including post-traumatic stress disorder, anxiety and depression in up to a third of survivors at six months and beyond. Quality of life for one third of survivors was impaired even 12 months after discharge from hospital.

Publishing their findings in the Journal of Rehabilitation Medicine, the researchers warn that rehabilitation clinicians and services should anticipate similar health problems in survivors of COVID-19.

Dr Manoj Sivan, an Associate Clinical Professor and Consultant in Rehabilitation Medicine at the University of Leeds' Institute of Rheumatic and Musculoskeletal Medicine, was lead clinician on this research.

He said: "COVID-19 is a new illness and the acute phase has already been devastating for people in many countries across the globe.

"While we have all rightly been busy creating capacity in acute service and saving lives, we must not forget those being discharged from the hospitals. We don't really know the long-term health problems these survivors face in the recovery phase of this pandemic.

"We do though have the two previous coronavirus outbreaks to learn from. This research gives us a rough idea of the rehabilitation needs in the first year after discharge. This allows us to prepare and plan services to meet their needs and work towards the best possible care for these patients in the community."

Co-author Dr Stephen Halpin, Senior Research Fellow and Consultant in Rehabilitation Medicine at Leeds is, like Dr Sivan, also a member of the University of Manchester's Division of Neuroscience and Experimental Psychology.

He said: "This highlights the importance of developing strong follow-up multidisciplinary rehabilitation services and has directly informed our management of COVID-19 patients in Leeds."

Co-author Dr Abayomi Salawu is Honorary Senior Lecturer at Hull York Medical School and Consultant in Rehabilitation Medicine at Hull University Teaching Hospitals NHS Trust.

He said: "Considering the novel nature of COVID-19,?we can only guess what the impact in the medium to long term on the survivors will be. However, we do know that patients who required ICU input for more than two weeks are likely to have ongoing rehabilitation needs irrespective of the diagnosis.

"This work has enabled us to develop a unique comprehensive follow-up and rehabilitation pathway. This has been designed despite current prevailing circumstances that have had significant impact on what services can be provided by the rehabilitation therapy teams in the community.

"It is anticipated that when we subsequently do a service evaluation of this follow-up pathway that we have created across Yorkshire for patients with COVID-19, we will be able to add more evidence to the expanding knowledge base in managing it."

The authors identified almost 1,200 previous international studies into the harmful long-term clinical outcomes for survivors of SARS and MERS coronavirus infections after hospitalisation or intensive care unit admission. They carried out a systematic review of 28 of those studies - the majority of which related to SARS cases; 23 were included in their meta-analysis.

The researchers cautioned: "At this stage it is not possible to conclude whether the long-term outcomes identified in SARS and MERS patients will also occur in COVID-19 survivors.

"However, as SARS and MERS belong to the same family of virus as COVID-19, and the clinical features are looking identical, including severe respiratory distress and intensive care admission in severe cases, the long-term picture is likely to be similar with COVID-19.

"Rehabilitation clinicians and services should plan ahead for timely follow-up, screening and interventions to enable best possible recovery and quality of life for these individuals."

Acute multidisciplinary rehabilitation while in hospital, post-acute rehabilitation in rehabilitation or respiratory units once discharged from hospital, and long-term rehabilitation interventions in the community are all recommended to optimise physical, psychological and functional recovery for those recovering from coronavirus.

Ideal multidisciplinary rehabilitation teams must include physiotherapists, occupational therapists, psychologists, speech and language therapists, dietitians, and physicians in rehabilitation medicine - with links to acute respiratory and intensive care teams and relevant community rehabilitation teams.

The authors also recommend that further research should be carried out into COVID-19 survivors, focusing on capturing lung function abnormalities, exercise capacity, psychological and cognitive impairments and, ultimately, quality of life.

Amsterdam, June 9, 2020 - Solar energy is considered by some to be the ultimate solution to address the current energy crisis and global warming and the environmental crises brought about by excessive consumption of fossil fuels. However, this clean and inexhaustible energy source is difficult to capture and store. In a novel study, scientists propose using solar energy to produce hydrogen by splitting water, reports Biomedical Spectroscopy and Imaging.

Hydrogen is a clean, flexible energy carrier primarily produced from fossil fuels. Taking another approach, scientists looked at how plants and other organisms use photosynthesis to convert light energy into chemical energy that can be stored and later released as needed to fuel the organisms' activities. They designed a gold nanoparticle conjugate that could be used as a platform to develop a semi-artificial photosynthesis system using a light-driven, water-splitting nanodevice for generating hydrogen.

"Photosynthesis in plants and algae is an efficient means of converting light and energy to produce storable chemical energy," explained lead investigator Takumi Noguchi, PhD, Division of Material Science, Graduate School of Science, Nagoya University, Nagoya, Japan. "Artificial photosynthesis, which mimics natural photosynthesis but directly generates fuels such as alcohols and hydrogen rather than sugars, may be the key to solving our energy problem."

In this study, scientists assembled cyanobacterial photosystem I (PSI) and photosystem II (PSII) complexes on a gold nanoparticle (GNP) to generate a PSI-GNP-PSII conjugate through genetically modified histidine tags attached to the PSI and PSII proteins, aiming at the development of a water-splitting nanosystem. They were assembled by modifying the method of preparation of a PSII-GNP conjugate. Single-particle fluorescence measurement using a cryogenic microscope as well as conventional optical absorption and fluorescence measurements provided definitive evidence that both PSI and PSII complexes are bound together to a single GNP in the generated PSI-GNP-PSII conjugate.

This research group had previously shown that PSII core complexes retained the oxygen evolving activity in PSII-GNP conjugates, in which the PSII complexes are bound to GNPs on the electron-acceptor side. It has also been reported that PSI complexes can evolve hydrogen upon irradiation using electrons from sacrificial electron donors when they are coupled to platinum nanoparticles.

"Thus, the PSI-GNP-PSII conjugate that we generated in the present study can be a useful platform for further development of a light-driven, water-splitting nanodevice for production of hydrogen from water using solar energy," concluded Dr. Noguchi.

CHAMPAIGN, Ill. -- For 25 years, Carol Augspurger visited a patch of ancient woods near Urbana, Illinois to look at the same 25 one-square-meter plots of earth she first demarcated for study in 1993. She surveyed the plots once a week in spring and summer, tracking the major life events of each of the herbaceous plants that grew there. In fall, she visited every other week. In winter, once a month.

Over the course of her study, Augspurger made nearly 600,000 observations of 43 plant species in Trelease Woods, a 60.5-acre remnant of old-growth forest in central Illinois. She noted 10 distinct developmental stages in the plants' lives, including when they emerged in spring, how long it took them to mature, when the flowers opened and died, when the leaves began to lose their greenness and when the plants went dormant. Augspurger is a professor emerita of plant biology at the University of Illinois at Urbana-Champaign.

By tracking these events and their relationship to average daily temperature and precipitation records, Augspurger and her colleague, Illinois Natural History Survey statistician and plant ecologist David Zaya, found that some shifts in the timing of plant seasonal life cycle events correlated with temperature trends.

The findings appear in the journal Ecological Monographs.

"We marked every major life cycle event in our plants from emergence until they went dormant," Augspurger said. "And we did it for an intact community, a natural forest community."

The analysis revealed that by the end of the study in 2017, the first spring plants were emerging almost four days later in March than they had in the early 1990s. But their growing seasons were getting shorter: Dormancy was occurring six days earlier. March average temperatures got slightly cooler over the same time period, but April temperatures were rising.

Plants that emerged in late spring - typically after April 1 - were undergoing even more dramatic shifts. Their growing seasons were lengthening: The period from emergence to dormancy lasted more than 40 days longer for these plants at the end of the study than at the beginning.

"For the early species, the growing season was a little bit shorter," Zaya said. "But for the late species, the growing season was 20 days longer per decade."

The duration of leaf expansion and flowering was shorter for the late-spring plants, while senescence, their period of aging, got longer. During senescence, plants gradually decline in making sugar and transfer their energy stores underground, but they do not produce new leaves, flowers or fruit. The increasing duration of senescence corresponded with higher average temperatures in the fall.

"It may be that the late-spring species are benefiting from changing temperature trends by being able to grow and get carbon for a longer period of time in the fall," Zaya said. "This suggests that there may be winners and losers in the plant community as a result of climate change, where some plants can respond more, some can respond less."

Many of the changes seen in the plants paralleled the temperature trends, but the researchers caution that the study does not prove that changing temperatures are driving the seasonal life cycle shifts in plants. Tying any specific trend in plants to climate change is tricky, Augspurger said.

"If you look at these 25 years of Illinois weather, climate change is not happening uniformly every month of the year," she said. "The minimum temperatures are changing more than the maximums, for example, and March is not changing as much as May. It's not only that the different plant species may respond in different ways to the changes, but the weather itself is changing differently."

Regardless of the cause, the shifting patterns among plant species likely influence their interactions with herbivores, pollinators and each other, Augspurger said.

"What they do developmentally ultimately affects their ability to survive, grow and reproduce," she said. "If they're changing their period of activity, they're either going to have a shorter or longer time to gain carbon, to absorb nutrients and to put it together into making flowers, seeds and offspring. This can affect species' abundance and survival, and the health of the overall ecosystem."

Inflammatory-rheumatic disorders are a widespread ailment, affecting at least 1.5 million people in Germany alone. Because there is a shortage of rheumatologists, however, only half of the patients in this country are adequately treated (1,2). The use of other health care professionals, as is the case in Denmark and the UK, could help to improve the situation. A study in Germany has shown for the first time that the care of patients with inflammatory-rheumatic diseases by 'rheumatological assistants' (RFA*) is just as effective as treatment by specialist rheumatologists. To reduce waiting times and prevent damage to health, the European League Against Rheumatism (EULAR) strongly recommends the use of RFAs in Germany, which will be announced at a press conference on 3 June 2020 held for its annual congress.

Around two percent of the adult population in Germany is affected by chronic inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) (1). "These patients have a considerable medical condition," explains Dr. Kirsten Hoeper from the Clinic for Rheumatology and Immunology at the Hanover Medical School in Germany.

Missed opportunities for treating patients due to long waiting times

Severe pain, extreme fatigue, lack of strength, stiffness and physical deformity can have a significant impact on activities, education and career, partnership and family and can lead to occupational disability. Early diagnosis and therapy are essential to prevent as far as possible such serious consequences of damage to the joints. "But the existing medical resources do not suffice to provide early, patient-centred and guideline-based care. The waiting times are far too long," states Hoeper. "This is despite the fact that new drugs could almost completely force the disease back into so-called remission for the majority of patients - provided that treatment is administered in good time."

The deployment of RFAs could improve the situation, as is already well-established in some Northern European countries. RFAs are members of related medical professions such as paramedic, nurse, student nurse or road traffic/motor traffic accidents, who have acquired additional theoretical and practical knowledge about the care of patients suffering from rheumatic and musculoskeletal diseases (RMDs) (3). Such a delegation of medical care in rheumatology is recommended worldwide (4-8, 9). "The legal framework for this also exists in Germany," says Hoeper (10). "In addition, the curriculum for the RFA degree exists since 2006, which is currently available to the German Medical Association for certification in an extended form (3).

In order to examine whether and how RFAs can also be used in the German health care system, a prospective, randomised, controlled and multi-centre study was conducted, which was completed in December 2019. "A total of 236 patients from eight German centres participated in the study, where a blood test had confirmed the diagnosis of rheumatoid arthritis," explains the author of the study Hoeper.

Study Involvement of RFAs produces the same treatment results

On average, the patients were 58 years of age, over 70 percent were female and suffered from rheumatic complaints for a period of 130 (ranging from 12 to 144) months on average. While one study group was exclusively treated by rheumatologists during the twelve-month study period, the other study group RFAs temporarily took over the care at three fixed intervals with only brief contact to the physicians. The patients' condition was measured using the standard assessment form DAS28 (Disease Activity Score at 28 joints), which assesses the activity of the disease on an ascending scale from 2.0 to 10.0. Values between 3.2 and 5.1 are considered moderate.

Result of the study: The structured delegation of medical tasks to an RFA does not undermine the current standard of care. While the disease activity for the group co-treated by RFAs was on average DAS28 2.43, the value for the group with continuous rheumatologist consultation was on average DAS28 2.29. "This difference is not clinically or statistically significant", concludes EULAR President Professor Dr. Iain B. McInnes from Glasgow, Scotland, UK. "For the first time it can be shown for Germany that an RFA consultation is a safe way to complement the care of patients suffering from rheumatoid arthritis", says Professor Dr. med. John Isaacs from Newcastle, Great Britain, EULAR Scientific Programme Committee Chair.

Better care in a cost-efficient way

"Integrating a team approach comprising rheumatologists with other health professionals into the treatment of patients with inflammatory rheumatic diseases presents great opportunities," emphasises McInnes. "RFAs can complement a physician's workload, who in turn can use freed-up resources for more complex or new patients," Hoeper adds. The long waiting times for an appointment with a rheumatologist could thus be cut shorter. Hoeper concludes, "by following the international EULAR Recommendations regarding RFAs, Germany will lead to better patient care in a cost-efficient way".

Neurons that are responsible for new experiences interfere with the signals of neurons that contain memories and thereby disturb the recall of memories - at least in mice. The research group of Martin Fuhrmann of the German Center for Neurodegenerative Diseases (DZNE) reports this phenomenon in the scientific journal "Nature Neuroscience". The results of this study potentially shed new light on memory impairment in Alzheimer's disease.

The hippocampus is a brain region responsible for memories and is early affected during Alzheimer's disease. Neurons in the hippocampus respond to our experiences and build networks to store these memories. Thereby, experiences and learned content can be recalled: we can for example remember our way home or to work. Individuals suffering from dementia have problems retrieving this kind of memories - as a specific region in the hippocampus, the so-called CA1 area, responsible for spatial memory, is strongly affected by Alzheimer pathology. So far it was thought that neurons that "contain" a memory are impaired by the disease in a way that they fail to be reactivated and eventually lose the memory. Apparently, the process of forgetting during Alzheimer's disease - at least in a mouse model - works in a different way: a research group at the DZNE investigated mice with similar protein deposits in their brains (so-called amyloid-beta plaques) as people with Alzheimer's disease. The deposits resulted in symptoms in these mice similar to those seen in Alzheimer's disease. The researchers found that the neurons responsible for the memory were still active in the diseased mice. However, recall of the memory failed.

Signals of other neurons interfere with the memory

"The reason is novel experience encoding neurons disturbing the signals of memory-containing neurons and superimposing them with their signal", says Dr. Martin Fuhrmann, group leader at the DZNE. "It is like a noisy TV signal: the picture becomes diffuse and distorted; you might even see pixels or stripes. Something similar happened inside the mice's brain: Interfering signals suppressed their memories. This disturbance is obviously a result of the pathological changes in the brain."

When healthy mice remember a situation, like learning a new path or exploring a novel environment, the neuronal network will be reactivated that was active during encoding the initial experience. To find out what actually happens to this neuronal network, the researchers performed an experiment: They let healthy, as well as mice with Alzheimer-like pathology explore a novel environment. With the help of a special microscopy method - two-photon in vivo microscopy - the researchers were able to follow the activity of individual neurons in the hippocampus. When the mice were exposed to the very same environment a few days later both groups behaved differently: the healthy mice remembered the environment; mice with Alzheimer-like pathology did not. They explored the environment as if it was their first experience. This was accompanied by differences in brain activity. Dr. Stefanie Poll, postdoc in the lab of Martin Fuhrmann and first author of this study explained: "In the diseased mice we not only found active neurons encoding the memory, but also a group of active neurons that contained novel environmental information. The signal of these novelty-containing neurons caused a superimposition disturbing signal of the memory encoding neurons."

To verify this, the researchers employed a technique based on the combination of chemical molecules and genetics: "chemogenetics". Thereby, neurons encoding novelty were made responsive to a specific chemical molecule. "Applying this molecule, we were able to modulate the activity of these neurons. It works like a switch, the molecule presses the switch", says Stefanie Poll.

On and off switching of novelty-containing neurons

"Like that we were able to specifically target neurons encoding novel information and switch these neurons on and off - controlling their activity", explains Martin Fuhrmann. "In the diseased mice we switched these neurons off, in the healthy group we did the opposite." Thereby, it was possible to on the one hand to reduce and on the other hand to induce the disturbing noise artificially." This was evident in the mice's behavior: "Mice with Alzheimer-like pathology now recognized the environment again, their memory was restored. The memory of healthy mice, however, was impaired by the artificial noise", says Stefanie Poll.

"The results of this study indicate a previously unknown mechanism that may contribute to the memory impairment in Alzheimer's disease", explains Martin Fuhrmann. "Imagining future therapies, we might be able to rescue memories of individuals suffering from Alzheimer's disease or other diseases impacting memory recall. We might achieve this by lowering the activity of these noise-inducing neurons with future methods. Furthermore, it could be possibly helpful for individuals suffering from post-traumatic stress disorders. Here, noise-inducing neurons could be artificially activated to interfere with the traumatic memory aiming to overwrite it. The remaining question, whether our results can be translated to humans, has to be answered by future studies."