Culture

Low levels of serotonin in the brain are seen as a possible cause of depression and many antidepressants act by blocking a protein that transports serotonin away from the nerve cells. A brain imaging study at Karolinska Institutet now shows that the average level of the serotonin transporter increased in a group of 17 individuals who recovered from depression after cognitive behavioural therapy. The results are published in the journal Translational Psychiatry.

"Our results suggest that changes to the serotonin system are part of the biology of depression and that this change is related to the episode rather than a static feature - a state rather than a trait," says the study's last author Johan Lundberg, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. "The finding raises many questions about the function of the serotonin system in depression and opens up for lines of research that could challenge the prevailing concept of serotonin and depression."

Serotonin is a neurotransmitter that affects, amongst other things, mood and emotion. Its transporter protein, 5-HTT, is considered to play a critical part in depression, as it pumps serotonin away from the cerebral neuron synapses, thus regulating the amount of active serotonin the brain.

Many modern antidepressant drugs inhibit this transporter, which increases the concentration of serotonin in the synapses. However, the effect of these drugs can be delayed by several weeks and in certain cases they have no effect at all, so the need for new or improved drug therapies is pressing. To achieve this, more knowledge is needed about the biological causes of the disease.

Earlier studies have shown that depressed individuals have lower levels of 5-HTT in the brain than healthy individuals. This finding is somewhat surprising given the dominant theory of serotonin function in depression, "the serotonin hypothesis." This theory dictates that low levels of synaptic serotonin causes depressive symptoms, and since the function of 5-HTT is to reduce the concentration of serotonin, high levels of the protein could be expected in depressed individuals. To better understand these findings a longitudinal or post-treatment study design can be used to answer the question of whether 5-HTT is temporarily or chronically low in people with depression.

In this study, the researchers sought to investigate how the serotonin transporter changes when a depressed person is successfully treated. To do this, they measured levels of 5-HTT in 17 individuals with depression before and after a course of internet-based cognitive behavioural therapy. The measurements were achieved with positron emission tomography (PET), a brain imaging technique in which scientists can gauge levels of different substances in the brain using radioactive tracers.

The researchers found that levels of 5-HTT were on average 10 percent higher after three months' treatment, when 13 of the 17 patients reported a significant improvement in their symptoms. Prior to treatment, the individuals with depression had roughly the same average level of 5-HTT as a control group of 17 healthy individuals.

"Instead of lower levels of serotonin transporter when depression had been treated, we found the opposite - more transporter after improved symptoms," says Jonas Svensson, postdoc researcher in Dr Lundberg's group. "One possible interpretation is that the serotonin system doesn't cause depression but is part of the brain's defence mechanism for protecting itself against depression. One might hypothesize, for example, that the level of 5-HTT drops when an individual is subjected to stress, such as during a depressive state, and that the level rises or normalises when this stress goes away. It's important to point out, however, that even if these ideas are raised by our study, its design doesn't allow us to draw any conclusions about why levels of 5-HTT change."

The study had some limitations, such as that it only included 17 individuals with depression, which is a heterogeneous state, and that the control group was examined only once.
The researchers are now designing new studies to test whether the dynamic function of the serotonin system can be part of a stress-defence system.

In 1884, Edwin Abbott wrote the novel Flatland: A Romance in Many Dimensions as a satire of Victorian hierarchy. He imagined a world that existed only in two dimensions, where the beings are 2D geometric figures. The physics of such a world is somewhat akin to that of modern 2D materials, such as graphene and transition metal dichalcogenides, which include tungsten disulfide (WS2), tungsten diselenide (WSe2), molybdenum disulfide (MoS2) and molybdenum diselenide (MoSe2).

Modern 2D materials consist of single-atom layers, where electrons can move in two dimensions but their motion in the third dimension is restricted. Due to this 'squeeze', 2D materials have enhanced optical and electronic properties that show great promise as next-generation, ultrathin devices in the fields of energy, communications, imaging and quantum computing, among others.

Typically, for all these applications, the 2D materials are envisioned in flat-lying arrangements. Unfortunately, however, the strength of these materials is also their greatest weakness - they are extremely thin. This means that when they are illuminated, light can interact with them only over a tiny thickness, which limits their usefulness. To overcome this shortcoming, researchers are starting to look for new ways to fold the 2D materials into complex 3D shapes.

In our 3D universe, 2D materials can be arranged on top of each other. To extend the Flatland metaphor, such an arrangement would quite literally represent parallel worlds inhabited by people who are destined to never meet.

Now, scientists from the Department of Physics at the University of Bath in the UK have found a way to arrange 2D sheets of WS2 (previously created in their lab) into a 3D configuration, resulting in an energy landscape that is strongly modified when compared to that of the flat-laying WS2 sheets. This particular 3D arrangement is known as a 'nanomesh': a webbed network of densely-packed, randomly distributed stacks, containing twisted and/or fused WS2 sheets.

Modifications of this kind in Flatland would allow people to step into each other's worlds. "We didn't set out to distress the inhabitants of Flatland," said Professor Ventsislav Valev who led the research, "But because of the many defects that we nanoengineered in the 2D materials, these hypothetical inhabitants would find their world quite strange indeed.

"First, our WS2 sheets have finite dimensions with irregular edges, so their world would have a strangely shaped end. Also, some of the sulphur atoms have been replaced by oxygen, which would feel just wrong to any inhabitant. Most importantly, our sheets intersect and fuse together, and even twist on top of each other, which modifies the energy landscape of the materials. For the Flatlanders, such an effect would look like the laws of the universe had suddenly changed across their entire landscape."

Dr Adelina Ilie, who developed the new material together with her former PhD student and post-doc Zichen Liu, said: "The modified energy landscape is a key point for our study. It is proof that assembling 2D materials into a 3D arrangement does not just result in 'thicker' 2D materials - it produces entirely new materials. Our nanomesh is technologically simple to produce, and it offers tunable material properties to meet the demands of future applications."

Professor Valev added: "The nanomesh has very strong nonlinear optical properties - it efficiently converts one laser colour into another over a broad palette of colours. Our next goal is to use it on Si waveguides for developing quantum optical communications."

PhD student Alexander Murphy, also involved in the research, said: "In order to reveal the modified energy landscape, we devised new characterisation methods and I look forward to applying these to other materials. Who knows what else we could discover?"

SAN FRANCISCO, CA (May 10, 2021) -- The Gulf of Guinea islands harbor an abundance of species found nowhere else on Earth. But for over 100 years, scientists have wondered whether or not a population of limbless, burrowing amphibians--known as caecilians--found on one of the islands is a single or multiple species. Now, a team of researchers from the California Academy of Sciences and the Smithsonian National Museum of Natural History has contributed the strongest evidence to date that there is not one, but two different species of caecilians on São Tomé island. Their findings, published today in Molecular Ecology, also suggest that volcanic activity may have led to the divergence of the species.

"To judge whether one species is in fact composed of multiple lineages, scientists have to build a case," says senior author and Academy Curator of Herpetology Rayna Bell. "By conducting a population level genomic study of these amphibians across the entire island, we are adding a crucial line of evidence that the São Tomé caecilian is actually two unique species."

Initially described by Portuguese scientists during colonial times, the São Tomé caecilians were later split into two distinct species based on their variation in color and location on the island--solid lemon yellow in the north and yellow with brown splotches to the south. Since then, subsequent research has bounced back and forth, grouping the species together then separating them out again, based on the best available evidence.

Then, in 2014, a study by former Academy Curator of Herpetology Robert Drewes and graduate student Ricka Stoelting using mitochondrial DNA indicated that not only were there likely two unique species, but they might be interbreeding. Bell and her colleagues build upon those previous findings by sampling 85 caecilians from 21 locations across the island for genome-wide genetic markers that more accurately confirm the presence--and interbreeding--of the two species.

"That earlier study was the first clue towards unraveling the mystery of the São Tomé caecilians," Bell says. "Our study provides further proof of the presence of two separate, interbreeding species and quantifies how much overlap--or hybridization--is occurring between them."

Once the research team confirmed the existence of two different but interbreeding species, they started to work backward through time to try to determine how the species diverged.

"It's pretty remarkable that there are two unique species on such a small island," says Academy collections manager and study co-author Lauren Scheinberg. "It really makes you wonder how natural selection is acting to drive speciation."

Through their analysis, the researchers found that the two species diverged around 300,000 years ago, a time period that coincides with a burst of volcanic activity on the island. The researchers suggest that lava flows during this period may have led to the speciation of the caecilians by dividing the island into a patchwork of smaller habitats with unique environmental pressures. As the lava flows eroded, resulting in suitable habitat for caecilians, the two species came back into contact and started to hybridize, obscuring the evidence of their separation.

"These findings are an important reminder that islands are not static," Bell says. "Even though they can be small and isolated, they are dynamic systems that are actively accumulating new species. It's also an important consideration for the conservation of São Tomé caecilians to know that we have two, genetically and morphologically unique species."

Though the picture of their past is becoming clearer, there is still much to learn about these enigmatic amphibians. For example, while most caecilians spend a majority of their time underground, the São Tomé caecilians can be readily found on the forest floor, raising questions about how the bright yellow amphibians avoid predation.

While one century-long mystery is nearing a resolution, it seems more are taking its place. But Bell is looking forward to the challenge. "These are perhaps the most well-studied caecilians on Earth because of their accessibility and how long ago they were described to science. Yet there is still so much to learn about them, from their mating behavior to how they deter predators," Bell says. "For a biologist, what could be more exciting than that?"

Infertility affects females and males equally. In male infertility, azoospermia (a medical condition with no sperm in semen) is a major problem that prevents a couple from having a child. For the treatment of patients with azoospermia, testicular sperm extraction (TESE) is required to obtain mature sperms. When examined, histological specimens are typically given a score, called the Johnsen score, on a scale of 1 to 10, based on the histopathological features of the testis.

"The Johnsen score has been widely used in urology since it was first reported 50 years ago. However, histopathological evaluation of the testis is not an easy task and takes much time due to the complexity of testicular tissue arising from the multiple, highly specialized steps in spermatogenesis. Our goal was to simplify this time consuming step of diagnosis by taking advantage of AI technology. To do this, we chose Google's automated machine learning (AutoML) Vision, which requires no programming, to create an AI model for individual patient data sets. With AutoML Vision, clinicians with no programming skills can use deep learning in building their own models without help from data scientists," said Dr. Hideyuki Kobayashi, Associate Professor of Urology department at Toho University School of Medicine (Fig. 1).

"The model we created can classify histological images of the testis without help from pathologists. I hope that our approach will enable clinicians in any field of medicine to build AI-based models which can be used in their daily clinical practice", he said.

To simplify the use of Johnsen scores in clinical practice, Dr. Kobayashi defined four labels: Johnsen score 1-3, 4-5, 6-7, and 8-10 (Fig. 2). He and his co-researchers obtained a dataset of 7155 images at magnification X400. All images were uploaded to the Google Cloud AutoML Vision platform. For the X400 magnification image dataset, the average precision (positive predictive value) of the algorithm was 82.6%, precision was 80.31%, and recall was 60.96% (Fig. 3).

AI has become popular and is being applied in all fields of medicine. However, the use of AI by clinicians in hospitals is still hampered by the need of help from data scientists in the proper use of AI. "The cloud-based machine learning framework we used is for everyone. It can become such a powerful tool in medicine that, in the near future, doctors in hospitals will be using AI-based medical image classifiers with ease, in the same way they use Microsoft PowerPoint or Excel now", Dr. Kobayashi said. He added, "The most difficult part was taking images of testis pathology and it was very time consuming. Two colleagues worked very hard to obtain all the images used in the study. I really appreciate their dedicated efforts."

Dr. Kobayashi's group has described the development of an AI-based algorithm for evaluating Johnsen scores combining original images (X400), which achieved high accuracy. This is the first report of an algorithm that can be used for predicting Johnsen scores without having to rely on pathologists and data science experts.

As humans, the weather where we live influences our energy consumption. In climates where weather shifts from hot summers to very cold winters, humans consume more energy since the body has to work harder to maintain temperature.

In much the same way, weather influences microbes such as bacteria and fungi in the soil. Seasonal fluctuations in soil temperature and moisture impact microbial activities that in turn impact soil carbon emissions and nutrient cycles.

Microbes consume carbon as the source of energy. As microbes increase in quantity and activities, they consume more carbon which results in more carbon emissions and vice versa.

In a modeling study published in Global Change Biology on May 10, San Diego State University ecologists found that this microbial seasonality has a significant impact on global carbon emissions and acts as a fundamental mechanism that regulates terrestrial-climate interactions and below ground soil biogeochemistry.

"When microbial colonies in the soil are in a productive phase, increasing in numbers and size, they will need more carbon to fuel their growth," said Xiaofeng Xu, global change ecologist and lead author. "When we manipulated the quantities and activities of soil microbes in simulations and observed the reciprocal changes in soil carbon, we found that when seasonal variation was removed, microbial respiratory rates went down."

By keeping the microbial population at a constant average level, carbon emissions can be reduced.

Stewards of the land could look at reducing fluctuation in soil microbial population by reducing tillage and other management practices in order to reduce soil carbon emissions, the researchers said. It can also help agricultural scientists and growers to sustain soil fertility

Using a microbial modeling framework -- CLM-Microbe (Community Land Model) -- developed in the Ecological Modeling and Integration Lab at SDSU where he studies how climate change impacts the terrestrial carbon cycle -- Xu and colleagues deployed the model on an SDSU supercomputer to reach this conclusion.

"We know soil microbes drive carbon flux -- the amount of carbon exchanged between land, ocean and atmosphere -- by producing enzymes that impact carbon flux," Xu said. "Soil carbon completes its cycle with the help of these microbes which have a hand in ultimate control of the carbon."

Different soil microbial groups play distinct roles in the carbon cycle.

"The model's ability to simulate bacterial and fungal dynamics improves our understanding of the soil microbial community's impact on the carbon cycle," said Liyuan He, first author and doctoral student at SDSU.

The finding advances soil microbial ecology and shows the ecological significance of microbial seasonality and our understanding of soil carbon storage under changing climate conditions.

The authors modeled and validated carbon fluxes observed at an individual plot scale in nine natural biomes including tropical/subtropical forest, temperate coniferous forest, temperate broadleaf forest, boreal forest, shrubland, grassland, desert, tundra, and wetland.

"This study demonstrates the need to incorporate microbial seasonality in earth system models so we can better predict climate-carbon interactions," said Chun-Ta Lai, co-author and an ecosystem ecologist at SDSU.

Next, the researchers will explore microbial seasonality and its impact on global carbon balance, given the dynamics of land use change around the world.

BEER-SHEVA, Israel May 10, 2021 - Researchers from Ben-Gurion University (BGU), together with American and German colleagues, have developed new "molecular tweezers" to combat antibiotic-resistant bacteria. Their recently announced findings were published in Cell Chemical Biology.

For years, medical professionals have struggled with bacterial infections becoming increasingly resistant to antibiotics. These molecular tweezers may be the key to battling one of greatest public health issues of the 21st century.

"Our discovery prevents infection without building up antibiotic resistance, and it might even be preferable to develop treatments based on molecular tweezers rather than antibiotics," said BGU Department of Chemistry Prof. Raz Jelinek.

The research team, led by Prof. Jelinek and his Ph.D. student Ravit Malishev, tested their molecular tweezers on the Staphylococcus aureus (Staph) bacteria. In the U.S. staph infections have an estimated mortality rate of over 25%, and 40% for drug-resistant strains.

The tweezers target biofilm, a thin layer of fibers that protects the bacteria. By gripping the fibers and destroying the protective layer, the tweezers impair the bacteria without directly attacking it, which prevents resistance from occurring.

Prof. Jelinek, who is also BGUs vice president of Research & Development and a member of the Ilse Katz Institute for Nanoscale Science and Technology explained, "The tweezers are just like your home tweezers but a million times smaller, and instead of plucking hairs they attack fibers of the bacteria's biofilm." By doing that they break the biofilm, making it more vulnerable to human immune defenses and external substances that are used against bacteria like antibiotics."

“The success of the study indicates an innovative direction of antibiotic treatments against pathogenic bacteria. We found that binding the tweezers to the biofilm disrupts its protective capabilities. Consequently, the bacterial pathogens become, less virulent to the human body, and, more vulnerable to elimination by the immune system. This breakthrough may open up new ways to fight antibiotic-resistant bacteria.” Prof. Jelinek hopes that following further testing, a pill containing millions of “swallowable tweezers” could identify biofilms in the body and break them apart.

Whether wastewater is full of "waste" is a matter of perspective.

"Why is it waste?" asked Zhen (Jason) He, professor in the Department of Energy, Environmental & Chemical Engineering in the McKelvey School of Engineering at Washington University in St. Louis.

"It's organic materials," He said, and those can provide energy in a number of ways. Then there's the other valuable resource in wastewater.

Water.

He's lab has developed one system that recovers both, filtering wastewater while creating electricity. Results from bench-scale trials were published May 6 and featured as a front cover article in the journal Environmental Science: Water Research & Technology.

The waste materials in wastewater are full of organic materials which, to bacteria, are food.

"Bacteria love them and can convert them into things we can use," He said. "Biogas is the primary source of energy we can recover from wastewater; the other is bioelectricity."

There already exist ways to capitalize on bacteria to produce energy from wastewater, but such methods often do so at the expense of the water, which could be filtered and otherwise be used -- if not for drinking -- for "grey water" purposes such as irrigation and toilet flushing.

He's lab took the two processes -- filtration and energy production -- and combined them, integrating the filtration system into the anode electrode of a microbial electrochemical system.

The system is set up like a typical microbial fuel cell, a bacterial battery that uses electrochemically active bacteria as a catalyst where a traditional fuel cell would use platinum. In this type of system, the bacteria are attached to the electrode. When wastewater is pumped into the anode, the bacteria "eat" the organic materials and release electrons, creating electricity.

To filter that same water, however, requires a different system.

He's lab combined the systems, developing a permeable anode that acts as a filter.

The anode is a dynamic membrane, made of conductive, carbon cloth. Together, the bacteria and membrane filter out 80% to 90% of organic materials -- that leaves water clean enough to be released into nature or further treated for non-potable water uses.

He used a mixed culture of bacteria, but they had to share one feature -- the bacteria had to be able to survive in a zero-oxygen environment.

"If there was oxygen, bacteria would just dump electrons to the oxygen not the electrode," He said. "If you cannot respire with the electrode, you'll perish."

To find the correct bacteria, He mostly defers to nature.

"It's not 100 percent natural, but we select those that can survive in this condition," He said. "It's more like 'engineered selection,'" the bacteria that did survive and respire with the electrode were selected for the system.

The amount of electricity created is not enough to, say, power a city, but it is in theory enough to help to offset the substantial amount of energy used in a typical U.S. water treatment plant.

"In the U.S., about 3% to 5% of electricity is used for water and wastewater activity," He said. Considering the usage by a local municipal plant, He believes his system can reduce energy consumption significantly.

"Typically, the process consumes about 0.5 KWH of electricity per cubic meter," He said. Based on bench scale experiments, "We can reduce it by half, or more of that."

But the primary goal of He's system isn't electricity production, it's wastewater treatment and nutrient recovery.

"Bacteria can convert those organic materials into things we can use," He said. "We can also recover nutrients like nitrogen or phosphorus for fertilizer. We can use it to feed plants. It's only when we don't use it, then it becomes waste.

"Wastewater is a resource in the wrong location."

Chinese researchers achieved 51.5dB nonreciprocal isolation in the atomic ensemble, which is the highest isolation ratio in the non-magnetic nonreciprocal field. They discussed the quantum noise problem in nonreciprocal devices for the first time.

The result was published on Nature Communications on April 22, 2021.

Nonreciprocity is an important basic concept in the optical field. The isolators and circulators derived from it are all indispensable components in the optical path. Faraday isolator based on circular birefringence of magneto-optical effect is widely used because of its easy construction, high isolation and low loss.

However, in the integrated optical path, the traditional faraday isolator is subject to various limitations. On one hand, it is difficult to prepare high-performance magneto-optical media on chip. On the other hand, the required strong magnetic field will interfere with the surrounding devices. Realizing the integrated non-magnetic nonreciprocal has attracted much attention in recent years. The research team led by Academician GUO Guangcan from University of Science and Technology of China (USTC) of CAS has investigated on nonreciprocal photonic devices for several years.

In this work, Prof. ZOU Changling from the research team, cooperating with researchers from Shanxi University, has achieved an isolation ratio of 30dB first. They took use of circularly polarized pump light to polarize the atoms in the gas chamber to a specific magnetic spin state, achieving different absorptions and dispersions for different polarized lights. Based on this, they further added a traveling wave cavity which greatly enhanced the interaction between light and atoms. The isolation ratio was finally increased to 51.5dB and the nonreciprocal medium was prepared based on atomic ensemble.

The system has good robustness and is insensitive to the interference of external weak magnetic field. The fluctuation of pump frequency and power and considered has practical application value.

In addition, the team has proved that non-reciprocal devices don't produce noisy photons in the non-reciprocal field with a confidence level of 99.7%.

This achievement has opened up a new direction in the field of non-reciprocity and is of great significance in practical application. The reviewers praised highly on this work as "The results are very impressive and seem encouraging toward realizing non reciprocal devices".

COLUMBUS, Ohio - Watching meaningful films - those that we find moving and poignant - can make us feel more prepared to deal with life's challenges and want to be a better person, a new study found.

The findings point to one reason why people may choose to see movies that make them sad as well as happy and that may explore difficult subjects that aren't always uplifting.

Researchers found that when people recalled watching meaningful films like The Shawshank Redemption and Up, they reported a variety of positive reactions, such as being better able to accept the human condition and make sense of problems in life.

Those positive experiences were less likely to be reported when people thought about watching Hollywood fare like The Big Lebowski or Catch Me if You Can.

"Meaningful movies actually help people cope with difficulties in their own lives, and help them want to pursue more significant goals," said Jared Ott, lead author of the study and a graduate student in communication at The Ohio State University.

While many studies have looked at how people react to watching meaningful films or clips from films in a lab setting, this research was designed to see how these films affect people in the real world, said co-author Michael Slater, professor of communication at Ohio State.

"We wanted to find out how people experience these movies in their everyday lives," Slater said. "There hasn't been much research on that."

Ott and Slater conducted the study with Naomi Q.P. Tan, a former graduate student at Ohio State. The research was published online recently in the journal Mass Communication and Society.

The researchers created two lists of 20 Hollywood films, one a list of meaningful films and one a list of less meaningful films, all made after 1985 and with high viewer ratings.

Meaningful films, which included Hotel Rwanda, Schindler's List and Slumdog Millionaire, were ones that user-generated lists on the movie site IMDB described using terms like poignant, inspiring and meaningful.

These films were matched with films produced about the same time and with similar MPAA ratings (G, PG, R) that were not described by users with the same terms as meaningful films. Some of these movies included Ratatouille, Fight Club and Pulp Fiction.

The study involved 1,098 adults recruited online.

Participants were randomly selected to receive either the list of meaningful films or the list of less meaningful films and asked to indicate which ones they had seen. One of the films they had seen before was then randomly selected for each participant, who responded to the rest of the survey in relation to that movie.

The survey asked a variety of questions about how each participant reacted to the movie chosen for him or her.

Results showed that people who recalled a meaningful movie were more likely than the others to say the film helped them make sense of difficulties in life. For example, the film helped them "feel like struggles in life are for a reason" and "more easily handle difficult situations with grace and courage."

Meaningful films were also more likely than the other movies to help viewers accept the human condition, results showed. Participants recalling these movies said that the film left them with the feeling that "both happy and sad experiences give meaning to our life" and "gains and losses are part of life," among other similar statements.

Participants recalling the meaningful films were also more likely to say the movie motivated them to be a better person, do good things for other people and seek what really matters in life.

How did meaningful movies have these positive effects? The study found that the key elements of these films were their poignancy, the mixture of happiness and sadness; their emotional range; and their ability to make people feel elevated and inspired by watching them.

Overall, the meaningful films did have more of these positive effects than the other movies. But that doesn't mean people can't find meaning in films that are meant to be more entertaining than meaningful, the research showed.

The researchers asked participants to select up to three values from a list of 16 that they had seen represented in the film they were asked to recall. Some of those values included "achievement and personal success," "love and intimacy" and "courage and bravery." Participants then rated the personal importance of each value.

"We found that people felt better able to make sense of difficulties in their own life when they recalled a movie that focused on values that were important to them," Slater said.

"That happened even when the movie was classified as one of the less meaningful films."

The findings suggest why many people see movies as more than just entertainment, Ott said.

"Some films may help people cope and grow through difficult periods in their life," he said. "And people may recognize this effect years after they have seen a particular movie."

TAMPA, Fla. (May 10, 2021) -- Blocking the fat-busting enzyme lipoxygenase with a synthetic inhibitor throws the immune system's innate inflammatory response out of whack, compromising cardiac repair during acute heart failure, USF Health researchers found.

Their new preclinical study was published April 13 in Biomedicine & Pharmacotherapy.

Acute heart failure - triggered by a heart attack, severely irregular heartbeats, or other causes -- occurs suddenly when the heart cannot pump enough blood to meet the body's demands.

Following a heart attack or any cardiac injury, signals to immune cells called leukocytes carefully control physiological inflammation. Normally, there are two distinct but overlapping processes: an acute inflammatory response ("get in" signal), where leukocytes travel from the spleen to the injured heart to start removing dead or diseased cardiac tissue, and a resolving phase ("get out" signal), where inflammation is cleared with the help of macrophages that arrive to further repair the damage and form a stable scar.

A delay in either the initiation of inflammation or its timely clearance (resolution) can lead to impaired cardiac healing and progression to heart failure, said study principal investigator Ganesh Halade, PhD, an associate professor of cardiovascular sciences at the USF Health Morsani College of Medicine and a member of the USF Health Heart Institute.

The USF Health researchers applied three investigational approaches (in vitro, ex vivo, and in vivo) to assess whether a potent lipoxygenase (12/15 LOX) inhibitor ML351 could selectively alter inflammatory responses in adult mice following cardiac injury similar to a heart attack. Previous studies by Dr. Halade's laboratory reported that lipoxygenase-deficient mice showed improved cardiac repair and heart failure survival after cardiac injury.

"We wondered if blocking a lipoxygenase with an external pharmacological compound (drug) would have the same beneficial effect -- but the answer was no," Dr. Halade said. "Instead, the collective results of our study indicate that ML351 dysregulated control of the normal physiological pathway of inflammation in cardiac repair, causing collateral damage."

In the mice treated mice with ML351, leukocyte recruitment to the site of cardiac injury was delayed, which subsequently amplified inflammation at the site. At the same time, instead of leaving once the repair job was done, the immune cells remained at the site beyond the typical acute (and beneficial) inflammatory response phase. Basically, the late arrival (get-in signal) and delayed clearance (get-out signal) of immune cells impaired cardiac repair, Dr. Halade said.

The latest study helps explain one more piece of the puzzle about the important role of immune-mediated acute inflammation and its clearance - both in promoting cardiac health and stopping the progression of heart failure, Dr. Halade said. Lipoxygenases, fatty-acid modifying enzymes that control metabolic and immune signaling, can promote either resolving (beneficial) or nonresolving (harmful) inflammation, he added.

"The take-home message is do not mess with (block) the lipoxygenase. Preserve it, because it's a key enzyme for our defensive, innate immune response," he said. "Knowing how drugs interact with the body's precisely-balanced immune responses will be critical for understanding mechanisms to prevent, delay or treat the unresolved inflammation influencing heart failure."

WASHINGTON - A neurologic pathway by which non-damaging but high frequency brain impact blunts normal brain function and causes long-term problems with learning and memory has been identified. The finding suggests that tailored drug therapy can be designed and developed to reactivate and normalize cognitive function, say neuroscientists at Georgetown University Medical Center.

The investigators, working with collaborators at the National Institutes of Health, had previously found that infrequent mild head impacts did not have an effect on learning and memory, but in their new study, reported May 10 in Nature Communications (DOI: 10.1038/s41467-021-22744-6), the investigators found that when the frequency of these non-damaging head impacts are increased, the brain adapts and changes how it functions. The investigators have found the molecular pathway responsible for this down-tuning of the brain that can prevent this adaptation from occurring.

This study is the first to offer a detailed molecular analysis of what happens in the brain after highly repetitive and very mild blows to the head, using mice as an animal model, says the study's senior investigator, Mark Burns, PhD, an associate professor in Georgetown's Department of Neuroscience and head of the Laboratory for Brain Injury and Dementia.

"Most research in this area has been in mouse models with more severe brain injury, or in human brains with chronic traumatic encephalopathy (CTE)," he says. CTE is a degenerative brain disease found in people with a history of repetitive head impact. "This means that we have been focusing only on how CTE pathology develops. Our goal was to understand how the brain changes in response to the low-level head impacts that many young football players, for example, are regularly experiencing."

Researchers have found that the average high school and college football player receives 21 head impacts per week, while some specialized players, such as defensive ends, experience twice as many. Behavioral issues believed to come from head impact have been reported in athletes with exposure to repeated head impacts. Issues range from mild learning and memory deficits to behavioral changes that include aggression, impulsivity and sleep disorders.

"These findings represent a message of hope to athletes and their families who worry that a change in behavior and memory means that CTE is in their future," says Burns.

In this study with mice, researchers mimicked the mild head impacts experienced by football players. The mice showed slower learning and impaired memory recall at timepoints long after the head impacts had stopped. After the experiment, a detailed analysis of their brains showed that there was no inflammation or tau pathology, as is usually seen in the brains of brain trauma or people with CTE.

To understand the physiology underlying these memory changes, the study's co-first author, Bevan Main, PhD, assistant professor of neuroscience at Georgetown, conducted RNA sequencing of the brain. "There are many things that this type of analysis can point you to, such as issues with energy usage or CTE-like pathways being activated in nerve cells, and so on," Main says. "All of our sequencing studies kept pointing to the same thing - the synapses that provide communication between neurons."

The next step was to figure out how synaptic function was altered. Stephanie Sloley, PhD, a graduate of Georgetown's Interdisciplinary Program for Neuroscience and the study's other first co-author, conducted electrophysiology studies of different neurons charged with releasing varied neurotransmitters - chemicals passed between neurons, via synapses, that carry functional instructions. "The brain is wired via synaptic communication pathways, and while we found that these wires were intact, the way that they communicated using glutamate was blunted, repressed," says Sloley.

Glutamate is the most abundant neurotransmitter in the brain, and is found in more than 60% of brain synapses. It plays a role in synaptic plasticity, which is the way the brain strengthens or weaken signals between neurons over time to shape learning and memory.

"Glutamate is usually very tightly regulated in the brain, but we know that head impacts cause a burst of glutamate to be released. We believe that brain is adapting to the repeated bursts of glutamate caused by high frequency head impact, and dampens its normal response to glutamate, perhaps as a way to protect the neurons," explains Sloley. She found that there was a shift in the way that neurons detected and responded to glutamate release, which reduced the neurons ability to learn new information.

With a single head hit or infrequent hits, the synapses do not go through this readjustment, Burns says. But after only a week of frequent mild hits, glutamate detection remained blunted for at least a month after the impacts ended. The affected mice showed deficits in learning and memory, compared to a placebo group of animals.

The authors confirmed that the changes in cognition were due to glutamate by giving a group of mice a drug to block glutamate transmission before they experienced the series of head knocks. This drug is FDA-approved for the treatment of Alzheimer's disease. Despite being exposed to the hits, these mice did not develop adaptations in their synapses or neurotransmission, and did not develop cognitive problems.

"This tells us that the cognitive issues we see in our head impact mice are occurring due to a change in the way the brain is working, and not because we have irreparable brain damage or CTE," Main says. "It would be very unlikely that we would use a drug like this in young players as a neuroprotectant before they play sports, because not all players will develop cognitive disorders," he says. "More much likely is that we can use our findings to develop treatments that target the synapses and reverse this condition. That work is already underway"

Burns believes that CTE and this newly discovered mechanism is different. "I believe that CTE is a real concern for athletes exposed to head impact, but I also believe that our newly discovered communication issue is independent of CTE. While it is concerning that head impacts can change the way the brain works, this study reveals that learning and memory deficits after repeated head impacts do not automatically mean a future with an untreatable neurodegenerative disease."

A team of researchers at the Institute of Laser Engineering, Osaka University, in collaboration with Bielefeld University and Technical University Braunschweig in Germany, came closer to unraveling the complicated optical response of wide-bandgap semiconductor multiple quantum wells and how atomic-scale lattice vibration can generate free space terahertz emission. Their work provides a significant push towards the application of laser terahertz emission microscopes to nano-seismology of wide-bandgap quantum devices.

Terahertz (THz) waves can be generated by ultrafast processes occurring in a material. By looking at THz emission, researchers have been able to study different processes at the quantum level—from simple bulk semiconductors to advanced quantum materials such as multiple quantum wells (Fig.1).

The THz research group led by Prof. Masayoshi Tonouchi at the Institute of Laser Engineering, Osaka University and his PhD student Abdul Mannan, together with international collaborators Prof. Dmitry Turchinovich at Bielefeld University and Prof. Andreas Hangleiter at Technical University of Braunschweig, has measured multifunction response in buried GaInN/GaN multiple quantum wells (MQWs) which includes dynamic screening effect of the built-in field inside the GaInN quantum wells, capacitive charge oscillation between GaN and GaInN quantum wells, and acoustic wave beams launched by the stress release between GaN and GaInN. All these functions can be monitored by observing THz emission into free space. In addition, it was proven that the propagating acoustic waves provide a new technique to evaluate the thickness of buried structure in devices at the resolution of 10 nm on the wafer scale, making nano-seismology a unique LTEM application for wide-bandgap quantum devices.

Probing buried structures in opto-acoustic devices at ultra-high resolution is still an unexplored area of research. In the present work, acoustically driven electromagnetic THz emission into free space is utilized for probing GaInN/GaN MQWs sandwiched in GaN material (Fig.2(a)). Laser-induced polarization dynamics of charge carriers results in a partial release of coherent acoustic phonons (CAPs) in GaInN/GaN MQW. This CAP pulse propagating within a material creates the associated electric polarization wave-packet. Once the propagating CAP pulse encounters the discontinuity of acoustic impedance or piezoelectric constant within the structure, this will lead to the transient change in the associated electric polarization, which serves as the source of the acoustically driven electromagnetic THz emission into free space. The temporal separation between ultrafast polarization dynamics in GaInN/GaN MQW and acoustically driven THz emission gives the thickness of the CAP-propagating medium (nano seismology) (Fig.2(b)).

The specialist team organized for THz emission spectroscopy, opto-THz science, and wide-bandgap/quantum-well semiconductor material science has made a significant step towards 3D dynamic characterization, including buried active layers in various materials and devices. "A 3D active tool to characterize ultrafast carrier dynamics, strain physics, phonon dynamics, and ultrafast dielectric responses locally in a non-contact and non-destructive manner has become an essential area of research for new materials and devices. We hope the present work contributes to such an evolution," says Prof. Masayoshi Tonouchi.

Point-of-Care UltraSonography (POCUS) deployed during the emergency treatment of patients with acute dyspnea has enormous advantages over standard diagnostic pathways. This is the finding of a joint review conducted by Danube University Krems and MedUni Vienna and recently published in the prestigious Annals of Internal Medicine. It allows serious conditions to be identified more quickly so that appropriate treatment can be initiated.

Working on behalf of the American College of Physicians, a joint study group from MedUni Vienna and Danube University Krems conducted a review of the value of Point-of-Care UltraSonography (POCUS) in patients with acute dyspnea (shortness of breath), with a view to drawing up a practical clinical treatment guideline.

Point-of-care ultrasonography involves the use of a mobile ultrasound device by the treating clinician to carry out an ultrasound scan at bedside. This allows several organs (scanning of lung and usually also heart, inferior vena cava and leg veins) to be scanned very quickly.

"In this systematic review, we were able to show that, when added to a standard diagnostic pathway, multi-organ point-of-care ultrasonography can significantly improve the correctness of diagnosis compared to the standard diagnostic pathway alone," explains principal investigator Gerald Gartlehner from Cochrane Austria at Danube University Krems.

"It allows conditions such as heart failure, pneumonia, pulmonary embolism, pleural effusion or pneumothorax to be diagnosed more quickly, so that appropriate treatment can be initiated," adds Alexander Spiel, MedUni Vienna emergency doctor (on leave, head of the emergency department of the Clinic Ottakring, Vienna HealthCare Group), "the results of the review demonstrate the relevance of point-of-care ultrasonography as part of the acute diagnostic work-up."

PHILADELPHIA-- Alcohol-impaired driving kills 29 people a day and costs $121 billion a year in the U.S. After years of progress in reducing alcohol-impaired driving fatalities, efforts began to stall in 2009, and fatalities started increasing again in 2015. With several studies demonstrating that drinkers cannot accurately estimate their own blood alcohol concentration (BAC), handheld alcohol breath testing devices, also known as breathalyzers, allow people to measure their own breath alcohol concentration (BrAC) to determine if they are below the legal limit of .08% before attempting to drive.

The latest generation of personal alcohol breath testing devices pair with smartphones. While some of these devices were found to be relatively accurate, others may mislead users into thinking that they are fit to drive, according to a new study from the Perelman School of Medicine at the University of Pennsylvania.

The findings, published today in Alcoholism: Clinical & Experimental Research, compares the accuracy of six such devices with that of two validated alcohol-consumption tests - BAC taken from venipuncture, and a police-grade handheld breath testing device.

"All alcohol-impaired driving crashes are preventable tragedies," says lead investigator M. Kit Delgado, MD, MS, an assistant professor of Emergency Medicine and Epidemiology at Penn. "It is common knowledge that you should not drive if intoxicated, but people often don't have or plan alternative travel arrangements and have difficulty judging their fitness to drive after drinking. Some may use smartphone breathalyzers to see if they are over the legal driving limit. If these devices lead people to incorrectly believe their blood alcohol content is low enough to drive safely, they endanger not only themselves, but everyone else on the road or in the car."

To assess these devices, researchers engaged 20 moderate drinkers between the ages of 21 and 39. The participants were given three doses of vodka over 70 minutes with the goal of reaching a peak BAC over the legal driving limit of around 0.10%. After each dose, participants' BrAC was measured using smartphone-paired devices and a police-grade handheld device. After the third dose, their blood was drawn and tested for BAC, the most accurate way of measuring alcohol consumption. Researchers also explored the devices' ability to detect breath alcohol concentration above common legal driving limits (0.05% and 0.08%). They used statistical analysis to explore differences between the measurements.

All seven devices underestimated BAC by more than 0.01%, though the some were consistently more accurate than others. Two devices failed to detect BrAC levels of 0.08% as measured by a police-grade device more than half the time. Since the completion of the study, one of the devices was discontinued and is no longer sold, and other models have been replaced by newer technologies. However, two of the other devices had similar accuracy as a police-grade device. These devices have been used to remotely collect accurate measurements of alcohol consumption for research . They could also be used to scale up contingency management addiction treatment programs that have been shown to help promote abstinence among patients with alcohol use disorders. These programs, which have proven to be highly effective, have traditionally provided prizes for negative in person breathalyzer measurements. Smartphone breathalyzer apps allow these programs to be administered remotely as breath alcohol readings can be verified with automatically captured pictures of the person's face providing the reading and prize redemption could be automated.

"While it's always best to plan not to drive after drinking, if the public or addiction treatment providers are going to use these devices, some are more accurate than others. Given how beneficial these breathalyzer devices could be to public health, our findings suggest that oversight or regulation would be valuable," Delgado concludes. "Currently, the Food and Drug Administration doesn't require approval for these devices - which would involve clearance based on review of data accuracy - but it should reconsider this position in light of our findings."

A complicated interaction between different proteins is needed for information to pass from one nerve cell to the next. Researchers at the Martin Luther University Halle-Wittenberg (MLU) have now managed to study this process in the synaptic vesicles, which play an important role in this process. The study appeared in the journal Nature Communications.

Several billion nerve cells communicate with each other in the body so that humans and other living beings can perceive and react to their environment. A host of complex chemical and electrical processes occur within a few milliseconds. "Special messenger substances - known as neurotransmitters - are released at the synapses of the nerve cells. They transmit information between the individual nerve cells," explains Dr Carla Schmidt, an assistant professor at the Centre for Innovation Competence HALOmem at MLU. The messenger substances are packed into small vesicles called synaptic vesicles, which fuse with the cell membrane in response to an electrical impulse and release the messenger substances. The messenger substances are then recognised by special receptor proteins in the next nerve cell. For this to succeed, numerous proteins have to work together, meshing like cogs in a clockwork mechanism. However, too little is currently known about how this process precisely works, says Schmidt.

The researchers have used a special form of mass spectrometry to investigate the process. Cross-linking mass spectrometry helps identify the interaction sites of the proteins. These are mixed with a substance that binds together nearby proteins. This substance reacts at different places depending on how the proteins interact with one another. The mass spectrometer analyses the binding patterns, which can be used to draw conclusions about the arrangement of the proteins. This enables researchers to examine different stages of the vesicles and to detect which protein networks have formed.

The study from Halle enables a more thorough understanding of the process of signal transmission in nerve cells. Knowledge about normal processes helps scientists recognize and understand malfunctions that could trigger diseases such as Alzheimer's.