Serendipitous Discovery Could Lead to Treatment For Strokes, Cardiac Arrest (Medicine)

Researchers identify a mechanism that could lead to new treatments for brain injuries caused by oxygen deprivation

In a surprising discovery, researchers at Massachusetts General Hospital (MGH) identified a mechanism that protects the brain from the effects of hypoxia, a potentially lethal deprivation of oxygen. This serendipitous finding, which they report in Nature Communications, could aid in the development of therapies for strokes, as well as brain injury that can result from cardiac arrest, among other conditions.

However, this study began with a very different objective, explains senior author Fumito Ichinose, MD, PhD, an attending physician in the Department of Anesthesia, Critical Care and Pain Medicine at MGH, and principal investigator in the Anesthesia Center for Critical Care Research. One area of focus for Ichinose and his team is developing techniques for inducing suspended animation, that is, putting a human’s vital functions on temporary hold, with the ability to “reawaken” them later. This state of being would be similar to what bears and other animals experience during hibernation. Ichinose believes that the ability to safely induce suspended animation could have valuable medical applications, such as pausing the life processes of a patient with an incurable disease until an effective therapy is found. It could also allow humans to travel long distances in space (which has frequently been depicted in science fiction).

A 2005 study found that inhaling a gas called hydrogen sulfide caused mice to enter a state of suspended animation. Hydrogen sulfide, which has the odor of rotten eggs, is sometimes called “sewer gas.” Oxygen deprivation in a mammal’s brain leads to increased production of hydrogen sulfide. As this gas accumulates in the tissue, hydrogen sulfide can halt energy metabolism in neurons and cause them to die. Oxygen deprivation is a hallmark of ischemic stroke, the most common type of stroke, and other injuries to the brain.

In the Nature Communications study, Ichinose and his team initially set out to learn what happens when mice are exposed to hydrogen sulfide repeatedly, over an extended period. At first, the mice entered a suspended-animation-like state–their body temperatures dropped and they were immobile. “But, to our surprise, the mice very quickly became tolerant to the effects of inhaling hydrogen sulfide,” says Ichinose. “By the fifth day, they acted normally and were no longer affected by hydrogen sulfide.”

Interestingly, the mice that became tolerant to hydrogen sulfide were also able to tolerate severe hypoxia. What protected these mice from hypoxia? Ichinose’s group suspected that enzymes in the brain that metabolize sulfide might be responsible. They found that levels of one enzyme, called sulfide:quinone oxidoreductase (SQOR), rose in the brains of mice when they breathed hydrogen sulfide several days in a row. They hypothesized that SQOR plays a part in resistance to hypoxia.

There was strong evidence for this hypothesis in nature. For example, female mammals are known to be more resistant than males to the effects of hypoxia–and the former have higher levels of SQOR. When SQOR levels are artificially reduced in females, they become more vulnerable to hypoxia. (Estrogen may be responsible for the observed increase in SQOR, since protection from the adverse effects of hypoxia is lost when a female mammal’s estrogen-producing ovaries are removed.) Moreover, some hibernating animals, such as the thirteen-lined ground squirrel, are highly tolerant of hypoxia, which allows them to survive as their bodies’ metabolism slows down during the winter. A typical ground squirrel’s brain has 100 times more SQOR than that of a similar-sized rat. However, when Ichinose and colleagues “turned off” expression of SQOR in the squirrels’ brains, their protection against the effects of hypoxia vanished.

Meanwhile, when Ichinose and colleagues artificially increased SQOR levels in the brains of mice, “they developed a robust defense against hypoxia,” explains Ichinose. His team increased the level of SQOR using gene therapy, an approach that is technically complex and not practical at this point. On the other hand, Ichinose and his colleagues demonstrated that “scavenging” sulfide, by using an experiment drug called SS-20, reduced levels of the gas, thereby sparing the brains of mice when they were deprived of oxygen.

Human brains have very low levels of SQOR, meaning that even a modest accumulation of hydrogen sulfide can be harmful, says Ichinose. “We hope that someday we’ll have drugs that could work like SQOR in the body,” he says, noting that his lab is studying SS-20 and several other candidates. Such medications could be used to treat ischemic strokes, as well as patients who have suffered cardiac arrest, which can lead to hypoxia. Ichinose’s lab is also investigating how hydrogen sulfide affects other parts of the body. For example, hydrogen sulfide is known to accumulate in other conditions, such as certain types of Leigh syndrome, a rare but severe neurological disorder that usually leads to early death. “For some patients,” says Ichinose, “treatment with a sulfide scavenger might be lifesaving.”

The lead author of the study is Eizo Marutani, MD, an investigator in MGH’s Department of Anesthesia Critical Care and Pain Medicine and an instructor at Harvard Medical School (HMS). Ichinose is also the William Thomas Green Morton Professor of Anaesthesia at HMS.

This study was funded by grants from the Japanese Ministry of Education, Sciences, Sports, and Technology; the Japan Science and Technology Agency; the Japan Agency for Medical Research and Development; the National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; the National Institute of General Medical Science; and the National Science Foundation.


Reference: Marutani, E., Morita, M., Hirai, S. et al. Sulfide catabolism ameliorates hypoxic brain injury. Nat Commun 12, 3108 (2021). https://doi.org/10.1038/s41467-021-23363-x


Provided by Massachusetts General Hospital

New Study Shows How To Boost Muscle Regeneration and Rebuild Tissue (Biology)

Salk research reveals clues about molecular changes underlying muscle loss tied to aging

One of the many effects of aging is loss of muscle mass, which contributes to disability in older people. To counter this loss, scientists at the Salk Institute are studying ways to accelerate the regeneration of muscle tissue, using a combination of molecular compounds that are commonly used in stem-cell research.

In a study published on May 25, 2021, in Nature Communications, the investigators showed that using these compounds increased the regeneration of muscle cells in mice by activating the precursors of muscle cells, called myogenic progenitors. Although more work is needed before this approach can be applied in humans, the research provides insight into the underlying mechanisms related to muscle regeneration and growth and could one day help athletes as well as aging adults regenerate tissue more effectively.

“Loss of these progenitors has been connected to age-related muscle degeneration,” says Salk Professor Juan Carlos Izpisua Belmonte, the paper’s senior author. “Our study uncovers specific factors that are able to accelerate muscle regeneration, as well as revealing the mechanism by which this occurred.”Induction of Yamanaka factors (OKSM) in muscle fibers increases the number of myogenic progenitors. Top, control; bottom, treatment. Red-pink color is Pax7, a muscle stem-cell marker. Blue indicates muscle nuclei.
Click here for a high-resolution image.
Credit: Salk Institute

The compounds used in the study are often called Yamanaka factors after the Japanese scientist who discovered them. Yamanaka factors are a combination of proteins (called transcription factors) that control how DNA is copied for translation into other proteins. In lab research, they are used to convert specialized cells, like skin cells, into more stem-cell-like cells that are pluripotent, which means they have the ability to become many different types of cells.

“Our laboratory previously showed that these factors can rejuvenate cells and promote tissue regeneration in live animals,” says first author Chao Wang, a postdoctoral fellow in the Izpisua Belmonte lab. “But how this happens was not previously known.”

Muscle regeneration is mediated by muscle stem cells, also called satellite cells. Satellite cells are located in a niche between a layer of connective tissue (basal lamina) and muscle fibers (myofibers). In this study, the team used two different mouse models to pinpoint the muscle stem-cell-specific or niche-specific changes following addition of Yamanaka factors. They focused on younger mice to study the effects of the factors independent of age.

In the myofiber-specific model, they found that adding the Yamanaka factors accelerated muscle regeneration in mice by reducing the levels of a protein called Wnt4 in the niche, which in turn activated the satellite cells. By contrast, in the satellite-cell-specific model, Yamanaka factors did not activate satellite cells and did not improve muscle regeneration, suggesting that Wnt4 plays a vital role in muscle regeneration.

According to Izpisua Belmonte, who holds the Roger Guillemin Chair, the observations from this study could eventually lead to new treatments by targeting Wnt4.

“Our laboratory has recently developed novel gene-editing technologies that could be used to accelerate muscle recovery after injury and improve muscle function,” he says. “We could potentially use this technology to either directly reduce Wnt4 levels in skeletal muscle or to block the communication between Wnt4 and muscle stem cells.”

The investigators are also studying other ways to rejuvenate cells, including using mRNA and genetic engineering. These techniques could eventually lead to new approaches to boost tissue and organ regeneration.

Other authors included: Ruben Rabadan Ros, Paloma Martinez Redondo, Zaijun Ma, Lei Shi, Yuan Xue, Isabel Guillen-Guillen, Ling Huang, Tomoaki Hishida, Hsin-Kai Liao, Concepcion Rodriguez Esteban, and Pradeep Reddy of Salk; Estrella Nuñez Delicado of Universidad Católica San Antonio de Murcia in Spain; and Pedro Guillen Garcia of Clinica CEMTRO in Spain.

The work was funded by NIH-NCI CCSG: P30 014195, the Helmsley Trust, Fundacion Ramon Areces, Asociación de Futbolistas Españoles (AFE), Fundacion Pedro Guillen, Universidad Católica San Antonio de Murcia (UCAM), the Moxie Foundation and CIRM (GC1R-06673-B).

DOI: 10.1038/s41467-021-23353-z

Featured image: Induction of Yamanaka factors (OKSM) in muscle fibers increases the number of myogenic progenitors. Top, control; bottom, treatment. Red-pink color is Pax7, a muscle stem-cell marker. Blue indicates muscle nuclei. © Salk Institute


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Provided by Salk Institute

Study Explores Role of Fungi and Bacteria in Activation of Genes Associated with Head and Neck Cancer (Biology)

An in vitro study conducted by a group of researchers at São Paulo State University (UNESP) in Araraquara, Brazil, shows how fungi and bacteria can activate genes associated with head and neck tumors, as the metabolism of biofilms (communities in which these microorganisms self-organize in a structured and coordinated manner) stimulate tumor cells by favoring the cell signaling pathways required for tumor development and resistance to treatment. The findings include entirely novel information on the links between microbial biofilms and cell behavior in head and neck cancer.

The researchers discovered that metabolites secreted by biofilms, termed the secretome, can modulate the expression of proto-oncogenes and cell cycle genes associated with tumor cell growth and survival. Their analysis of gene expression focused on two signaling pathways (EGFR/RAS/RAF/MEK/ERK and EGFR/PI3K/AKT/mTOR) that play a key role in tumor cell proliferation, differentiation, and survival. Alterations to gene expression in these pathways are highly prevalent in various types of tumor.

The researchers analyzed head and neck and oral cavity squamous carcinoma cells. Squamous cell carcinoma is the most common type of mouth cancer, which produces functional and aesthetic changes that degrade the patient’s quality of life. 

The cells were challenged via stimulation by metabolites from biofilms of Candida albicans fungi and Staphylococcus aureus bacteria. These microorganisms are very frequent in users of dentures: prior research found both in 30%-40% of subjects examined. 

Oral microbiota is known to play an important role in the development of cancer. Genetic markers associated with the presence of microorganisms have been identified for some types, such as stomach cancer, but there is no consensus regarding the most prevalent genes linked to head and neck cancer, and no molecular markers had hitherto been found for this disease, especially HPV-negative cancer, which has a worse prognosis. 

According to a report on the study published in Frontiers in Cellular and Infection Microbiology, metabolites from C. albicans and S. aureus biofilms can endanger the homeostasis of normal and neoplastic oral epithelial cells, altering the expression of important genes such as CDKN1A, Bcl-2, PI3K, BRAF, hRAS and mTOR, impairing cell viability and survival, and disrupting the cell cycle profile.

The study was supported by FAPESP and the National Council for Scientific and Technological Development (CNPq). The project was also awarded funding by Colombia’s COLCIENCIAS and SAPIENCIA agencies (2015 call for doctorates abroad), and involved partnerships with UNESP’s Araraquara Dental School (FOAr) and Araraquara School of Pharmaceutical Sciences (FCFAr).

Understanding the cell cycle is important because cancer entails unchecked cell division and growth, with tumor cells potentially invading tissues and organs throughout the body. Failure of the inhibitors of this cycle and excessive signaling by cell division regulators can lead to tumor progression.

The oral microbiome is a diversified community of microorganisms with as many as 700 species of viruses, protozoans, bacteria and fungi. When biofilms develop, they produce metabolites that alter the immune response and can lead to chronic inflammation and even production of cancerous substances. 

According to Paula Aboud Barbugli, a professor at FOAr-UNESP and co-leader of the study, the findings show that “molecules secreted by these microorganisms in biofilms may modulate host cell activities even far away from the primary infection site”.

For Carlos Eduardo Vergani, also a professor at FOAr-UNESP and principal investigator for the project, the results serve as a warning on the treatment of cancer patients who have dentures. “Control of biofilms, including denture and oral cavity hygiene, is extremely important to minimize inflammatory processes, as shown by our prior research and the study just published, which points to interference with the expression of genes associated with tumor progression,” Vergani told Agência FAPESP.

Another study led by Vergani and published in 2017 showed that soluble factors in methicillin-sensitive C. albicans and S. aureus biofilm promoted cell death and inflammatory responses. 

According to a report issued in March by Brazil’s National Cancer Institute (INCA), some 22,800 new cases of laryngeal and oral cavity cancer are reported each year, most of them in male patients. 

Future

The COVID-19 pandemic forced the group to interrupt the clinical trial they had planned to conduct on the basis of their research. Barbugli said a PhD project supervised by another member of the group and approved by the Ministry of Health’s Research Ethics Committee (CONEP) will investigate the prevalence of C. albicans and S. aureus biofilms in the dentures and oral cavities of head and neck cancer patients treated at Araraquara’s Santa Casa de Misericórdia Hospital to understand how they influence prognosis in these cases. 

For Vergani, the results obtained so far pave the way for future metabolomics and proteomics research into oral biofilms.

The article “Proto-oncogenes and cell cycle gene expression in normal and neoplastic oral epithelial cells stimulated with soluble factors from single and dual biofilms of Candida albicans and Staphylococcus aureus” is at: www.frontiersin.org/articles/10.3389/fcimb.2021.627043/full#h4.

Featured image: A research group at São Paulo State University (UNESP) analyzed how Candida albicans fungi and Staphylococcus aureus bacteria influence gene expression and tumor cell survival (image: SCC25 cell stimulated with metabolites of C. albicans biofilm seen under confocal microscope/FOAr-UNESP)


Provided by FAPESP

Candid Cosmos: eROSITA Cameras Set A Benchmark For Astronomical Imaging (Cosmology)

An overview and performance assessment of the seven cameras of eROSITA, a space x-ray telescope launched in 2019

Recently, the eROSITA (extended Roentgen Survey with an Imaging Telescope Array) x-ray telescope, an instrument developed by a team of scientists at Max-Planck-Institut für Extraterrestrische Physik (MPE), has gained attention among astronomers. The instrument performs an all-sky survey in the x-ray energy band of 0.2-8 kilo electron volts aboard the Spectrum-Roentgen-Gamma (SRG) satellite that was launched in 2019 from the Baikonur cosmodrome in Kazakhstan.

“The eROSITA has been designed to study the large-scale structure of the universe and test cosmological models, including dark energy, by detecting galaxy clusters with redshifts greater than 1, corresponding to a cosmological expansion faster than the speed of light,” said Dr. Norbert Meidinger from MPE, a part of the team that developed the instrument. “We expect eROSITA to revolutionize our understanding of the evolution of supermassive black holes.” The details of the developmental work have been published in SPIE’s Journal of Astronomical Telescopes, Instruments, and Systems (JATIS).

eROSITA is not one telescope, but an array of seven identical, co-aligned telescopes, with each one composed of a mirror system and a focal-plane camera. The camera assembly, in turn, consists of the camera head, camera electronics, and filter wheel. The camera head is made up of the detector and its housing, a proton shield, and a heat pipe for detector cooling. The camera electronics include supply, control, and data acquisition electronics for detector operation. The filter wheel is mounted above the camera head and has four positions including an optical and UV blocking filter to reduce signal noise, a radioactive x-ray source for calibration, and a closed position that allows instrumental background measurements.

“It’s exciting to read about these x-ray cameras that are in orbit and enabling a broad set of scientific investigations on a major astrophysics mission,” says Megan Eckart of Lawrence Livermore National Laboratory, USA, who is the deputy editor of JATIS. “Dr. Meidinger and his team provide a clear description of the hardware development and ground testing, and wrap up the paper with a treat: first-light images from eROSITA and an assessment of onboard performance. Astrophysicists around the world will analyze data from these cameras for years to come.”

The eROSITA telescope is well on its way to becoming a game changer for x-ray astronomy.

First light of the eROSITA X-ray telescope in space
First light of the eROSITA X-ray telescope in space.

Read the open-access article by Norbert Meidinger et al., “eROSITA camera array on the SRG satellite,” J. Astron. Telesc. Instrum. Syst7(2), 025004 (2021). doi 10.1117/1.JATIS.7.2.025004

Featured image: A team of scientists from the Max-Planck-Institut für Extraterrestrische Physik, Germany, built an x-ray telescope called eROSITA consisting of an array of co-aligned focal plane cameras with one in the center and six surrounding it. Image credit: P. Friedrich, doi 10.1117/1.JATIS.7.2.025004


Provided by SPIE

Scientists Discover A Protein That Naturally Enhances Wheat Resistance to Head Scab (Agriculture)

Fusarium Head Blight (FHB), also known as scab, is a significant disease of small grain cereals, such as wheat and barley, that impacts farmers around the world. The disease has been reducing acreage and increasing the price of wheat production in the United States since the early 1990s, which in turn increases costs for downstream producers, such as millers and brewers.

The disease is caused by a fungus that produces heat-stable trichothecene mycotoxins, which help the disease spread. To stop the spread, plant breeders are working to develop cultivars with improved resistance to FHB. A team of plant pathologists primarily based at Rutgers University recently generated wheat overexpressing two non-specific lipid transfer proteins and found that this enhanced protection against the fungus and led to a reduction of one of the major mycotoxins.

“We found that the AtLTp4.4 protein, from the large gene family of nsLTPs, had both antifungal and antioxidant properties,” said John McLaughlin. “This is the first study to show that nsLTPs have dual functions and the first study to explore how these functions contribute to FHB-resistance in wheat.”

The discovery that genes like nsLTPs can improve FHB-resistance in wheat adds to the catalog of genes that plant breeders can use in their breeding programs. This discovery also opens new research avenues for McLaughlin and his colleagues.

“We are exploring if nsLTP overexpression in barley can impact FHB resistance and if the increase of nsLTPs in the grain improves the antioxidant properties of malt,” said McLaughlin. “Additionally, nsLTPs are predicted to improve beer shelf life and flavor stability, and we will be testing that.”

Their research also highlights the need to better understand the connection between the induction of reactive oxygen species and mycotoxin production/accumulation in small grain cereals as the scientists found that application of trichothecenes to wheat leaf tissue and the accumulation of reactive oxygen species, independent of the fungus, can be significantly impacted by the overexpression of nsLTPs.

“Our research shows that gain-of-function mutants can be used to enhance plant disease resistance, and our article shows some of the techniques involved to explore the mechanisms of disease resistance,” McLaughlin added.

For more information, read “A Lipid Transfer Protein has Antifungal and Antioxidant Activity and Suppresses Fusarium Head Blight Disease and DON Accumulation in Transgenic Wheat” published in the April issue of Phytopathology.

Featured image: John McLaughlin in the Rutgers greenhouse with hard red spring wheat. © John McLaughlin


Provided by American Phytopathological Society

Probing Deeper Into Origins of Cosmic Rays (Planetary Science)

Simulation model provides first step in developing algorithms to enhance detection methods

Cosmic rays are high-energy atomic particles continually bombarding Earth’s surface at nearly the speed of light. Our planet’s magnetic field shields the surface from most of the radiation generated by these particles. Still, cosmic rays can cause electronic malfunctions and are the leading concern in planning for space missions.

Researchers know cosmic rays originate from the multitude of stars in the Milky Way, including our sun, and other galaxies. The difficulty is tracing the particles to specific sources, because the turbulence of interstellar gas, plasma, and dust causes them to scatter and rescatter in different directions.

In AIP Advances, by AIP Publishing, University of Notre Dame researchers developed a simulation model to better understand these and other cosmic ray transport characteristics, with the goal of developing algorithms to enhance existing detection techniques.

Brownian motion theory is generally employed to study cosmic ray trajectories. Much like the random motion of pollen particles in a pond, collisions between cosmic rays within fluctuating magnetic fields cause the particles to propel in different directions.

But this classic diffusion approach does not adequately address the different propagation rates affected by diverse interstellar environments and long spells of cosmic voids. Particles can become trapped for a time in magnetic fields, which slow them down, while others are thrust into higher speeds through star explosions.

To address the complex nature of cosmic ray travel, the researchers use a stochastic scattering model, a collection of random variables that evolve over time. The model is based on geometric Brownian motion, a classic diffusion theory combined with a slight trajectory drift in one direction.

In their first experiment, they simulated cosmic rays moving through interstellar space and interacting with localized magnetized clouds, represented as tubes. The rays travel undisturbed over a long period of time. They are interrupted by chaotic interaction with the magnetized clouds, resulting in some rays reemitting in random directions and others remaining trapped.

Monte Carlo numerical analysis, based on repeated random sampling, revealed ranges of density and reemission strengths of the interstellar magnetic clouds, leading to skewed, or heavy-tailed, distributions of the propagating cosmic rays.

The analysis denotes marked superdiffusive behavior. The model’s predictions agree well with known transport properties in complex interstellar media.

“Our model provides valuable insights on the nature of complex environments crossed by cosmic rays and could help advance current detection techniques,” author Salvatore Buonocore said.

The article “Anomalous diffusion of cosmic rays: A geometric approach” is authored by Salvatore Buonocore and Mihir Sen. The article will appear in AIP Advances on May 25, 2021 (DOI: 10.1063/5.0049401). After that date, it can be accessed at https://aip.scitation.org/doi/10.1063/5.0049401.

Featured image: Schematic representation of cosmic rays propagating through magnetic clouds. © Salvatore Buonocore


Provided by American Institute of Physics

‘Rejuvenating’ the Alzheimer’s Brain (Neuroscience)

Alzheimer’s disease is the main cause of dementia and current therapeutic strategies cannot prevent, slow down or cure the pathology. The disease is characterized by memory loss, caused by the degeneration and death of neuronal cells in several regions of the brain, including the hippocampus, which is where memories are initially formed. Researchers from the Netherlands Institute for Neuroscience (NIN) have identified a small molecule that can be used to rejuvenate the brain and counteract the memory loss.

NEW CELLS IN OLD BRAINS

The presence of adult-born cells in the hippocampus of old people was recently demonstrated in scientific studies. It suggests that, generally speaking, the so-called process of adult neurogenesis is sustained throughout adulthood. Adult neurogenesis is linked to several aspects of cognition and memory in both animal models and humans, and it was reported to sharply decrease in the brains of patients with Alzheimer’s disease. Researchers also found that higher levels of adult neurogenesis in these patients seem to correlate with better cognitive performance before death. “This could suggest that the adult-born neurons in our brain may contribute to a sort of cognitive reserve that could later on provide higher resilience to memory loss”, says Evgenia Salta, group leader at the NIN. Therefore, researchers from the NIN investigated if giving a boost to adult neurogenesis could help prevent or improve dementia in Alzheimer’s disease.

A SMALL MOLECULE WITH BIG POTENTIAL

Salta: “Seven years ago, while studying a small RNA molecule that is expressed in our brain, called microRNA-132, we came across a rather unexpected observation. This molecule, which we had previously found to be decreased in the brain of Alzheimer’s patients, seemed to regulate homeostasis of neural stem cells in the central nervous system”. Back then, Alzheimer’s was thought to be a disease affecting only mature neuronal cells, so at first glance this finding did not seem to explain a possible role of microRNA-132 in the progression of Alzheimer’s.

In this study, the researchers set out to address whether microRNA-132 can regulate adult hippocampal neurogenesis in healthy and Alzheimer’s brains. Using distinct Alzheimer’s mouse models, cultured human neural stem cells and post-mortem human brain tissue, they discovered that this RNA molecule is required for the neurogenic process in the adult hippocampus. “Decreasing the levels of microRNA-132 in the adult mouse brain or in human neural stem cells in a dish impairs the generation of new neurons. However, restoring the levels of microRNA-132 in Alzheimer’s mice rescues neurogenic deficits and counteracts memory impairment related to adult neurogenesis”, Sarah Snoeck, technician in the group of Salta, explains.

These results provide a proof-of-concept regarding the putative therapeutic potential of bringing about adult neurogenesis in Alzheimer’s. Salta: “Our next goal is to systematically assess the efficacy and safety of targeting microRNA-132 as a therapeutic strategy in Alzheimer’s disease”.


Reference: Hannah Walgrave, Sriram Balusu, Sarah Snoeck, Elke Vanden Eynden, Katleen Craessaerts, Nicky Thrupp, Leen Wolfs, Katrien Horré, Yannick Fourne, Alicja Ronisz, Edina Silajdžić, Amber Penning, Giorgia Tosoni, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, Dietmar Rudolf Thal, Henrik Zetterberg, Sandrine Thuret, Mark Fiers, Carlo Sala Frigerio, Bart De Strooper, Evgenia Salta, Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease, Cell Stem Cell, 2021, , ISSN 1934-5909, https://doi.org/10.1016/j.stem.2021.05.001. (https://www.sciencedirect.com/science/article/pii/S1934590921002198)


Provided by Netherlands Institute for Neuroscience

Technique to Evaluate Wind Turbines May Boost Wind Power Production (Engineering)

With a global impetus toward utilizing more renewable energy sources, wind presents a promising, increasingly tapped resource. Despite the many technological advancements made in upgrading wind-powered systems, a systematic and reliable way to assess competing technologies has been a challenge.

In a new case study, researchers at Texas A&M University, in collaboration with international energy industry partners, have used advanced data science methods and ideas from the social sciences to compare the performance of different wind turbine designs.

“Currently, there is no method to validate if a newly created technology will increase wind energy production and efficiency by a certain amount,” said Dr. Yu Ding, Mike and Sugar Barnes Professor in the Wm Michael Barnes ’64 Department of Industrial and Systems Engineering. “In this study, we  provided a practical solution to a problem that has existed in the wind industry for quite some time.”

The results of their study are published in the journal Renewable Energy.

Wind turbines convert the energy transferred from air hitting their blades to electrical energy. As of 2020, about 8.4% of the total electricity produced in the United States comes from wind energy. Further, over the next decade, the Department of Energy plans to increase the footprint of wind energy in the electricity sector to 20% to meet the nation’s ambitious climate goals. 

In keeping with this target, there has been a surge of novel technologies, particularly to the blades that rotate in the wind. These upgrades promise an improvement in the performance of wind turbines and, consequently, power production. However, testing whether or how much these quantities will go up is arduous.

One of the many reasons that make performance evaluation difficult is simply because of the sheer size of wind turbines that are often several hundred feet tall. Testing the efficiency of these gigantic machines in a controlled environment, like a laboratory, is not practical. On the other hand, using scaled-down versions of wind turbines that fit into laboratory-housed wind tunnels yield inaccurate values that do not capture the performance of the actual-size wind turbines. Also, the researchers noted that replicating the multitude of air and weather conditions that occur in the open field is hard in the laboratory.

Hence, Ding and his team chose to collect data from inland wind farms for their study by collaborating with an industry that owned wind farms. For their analysis, they included 66 wind turbines on a single farm. These machines were fitted with sensors to continuously track different items, like the power produced by the turbines, wind speeds, wind directions and temperature. In totality, the researchers collected data over four-and-a-half years, during which time the turbines received three technological upgrades.

To measure the change in power production and performance before and after the upgrade, Ding and his team could not use standard pre-post intervention analyses, such as those used in clinical trials. Briefly, in clinical trials, the efficacy of a certain medicine is tested using randomized experiments with test groups that get the medication and controls that did not. The test and the control groups are carefully chosen to be otherwise comparable so that the effect of the medicine is the only distinguishing factor between the groups. However, in their study, the wind turbines could not be neatly divided into the test and control-like groups as needed for randomized experiments.

“The challenge we have here is that even if we choose ‘test’ and ‘control’ turbines similar to what is done in clinical trials, we still cannot guarantee that the input conditions, like the winds that hit the blades during the recording period, were the same for all the turbines,” said Ding. “In other words, we have a set of factors other than the intended upgrades that are also different pre- and post-upgrade.”

Hence, Ding and his team turned to an analytical procedure used by social scientists for natural experiments, called causal inference. Here, despite the confounding factors, the analysis still allows one to infer how much of the observed outcome is caused by the intended action, which in the case of the turbines, was the upgrade.

For their causal inference-inspired analysis, the researchers included turbines only after their input conditions were matched. That is, these machines were subject to similar wind velocities, air densities, or turbulence conditions during the recording period. Next, using an advanced data comparison methodology that Ding jointly developed with Dr. Rui Tuo, assistant professor in the industrial and systems engineering department, the research team reduced the uncertainty in quantifying if there was an improvement in wind turbine performance.

Although the method used in the study requires many months of data collection, Ding said that it provides a robust and accurate way of determining the merit of competing technologies. He said this information will be beneficial to wind operators who need to decide if a particular turbine technology is worthy of investment.

“Wind energy is still subsidized by the federal government, but this will not last forever and we need to improve turbine efficiency and boost their cost-effectiveness,” said Ding. “So, our tool is important because it will help wind operators identify best practices for choosing technologies that do work and weed out those that don’t.”

Ding received a Texas A&M Engineering Experiment Station Impact Award in 2018 for innovations in data and quality science impacting the wind energy industry.

Other contributors to the research include Nitesh Kumar, Abhinav Prakash and Adaiyibo Kio from the industrial and systems engineering department and technical staff of the collaborating wind company.

This research is funded by the National Science Foundation and industry.

Featured image: The improvement in wind power generation after a technological upgrade can now be evaluated using a technique that includes machine learning and social science analysis. | Image: Getty Images


Reference: Yu Ding, Nitesh Kumar, Abhinav Prakash, Adaiyibo E. Kio, Xin Liu, Lei Liu, Qingchang Li, A case study of space-time performance comparison of wind turbines on a wind farm, Renewable Energy, Volume 171, 2021, Pages 735-746, ISSN 0960-1481, https://doi.org/10.1016/j.renene.2021.02.136. (https://www.sciencedirect.com/science/article/pii/S0960148121003153)


Provided by TAMU

For Men, Low Testosterone Means High Risk of Severe COVID-19 (Medicine)

New clues on why more men than women develop severe disease

Throughout the pandemic, doctors have seen evidence that men with COVID-19 fare worse, on average, than women with the infection. One theory is that hormonal differences between men and women may make men more susceptible to severe disease. And since men have much more testosterone than women, some scientists have speculated that high levels of testosterone may be to blame.

But a new study from Washington University School of Medicine in St. Louis suggests that, among men, the opposite may be true: that low testosterone levels in the blood are linked to more severe disease. The study could not prove that low testosterone is a cause of severe COVID-19; low levels could simply serve as a marker of some other causal factors. Still, the researchers urge caution with ongoing clinical trials investigating hormonal therapies that block or lower testosterone or increase estrogen as a treatment for men with COVID-19.

The study appears online May 25 in JAMA Network Open.

“During the pandemic, there has been a prevailing notion that testosterone is bad,” said senior author Abhinav Diwan, MD, a professor of medicine. “But we found the opposite in men. If a man had low testosterone when he first came to the hospital, his risk of having severe COVID-19 — meaning his risk of requiring intensive care or dying — was much higher compared with men who had more circulating testosterone. And if testosterone levels dropped further during hospitalization, the risk increased.”

The researchers measured several hormones in blood samples from 90 men and 62 women who came to Barnes-Jewish Hospital with symptoms of COVID-19 and who had confirmed cases of the illness. For the 143 patients who were admitted to the hospital, the researchers measured hormone levels again at days 3, 7, 14 and 28, as long as the patients remained hospitalized over these time frames. In addition to testosterone, the investigators measured levels of estradiol, a form of estrogen produced by the body, and IGF-1, an important growth hormone that is similar to insulin and plays a role in maintaining muscle mass.

Among women, the researchers found no correlation between levels of any hormone and disease severity. Among men, only testosterone levels were linked to COVID-19 severity. A blood testosterone level of 250 nanograms per deciliter or less is considered low testosterone in adult men. At hospital admission, men with severe COVID-19 had average testosterone levels of 53 nanograms per deciliter; men with less severe disease had average levels of 151 nanograms per deciliter. By day three, the average testosterone level of the most severely ill men was only 19 nanograms per deciliter.

The lower the levels of testosterone, the more severe the disease. For example, those with the lowest levels of testosterone in the blood were at highest risk of going on a ventilator, needing intensive care or dying. Thirty-seven patients — 25 of whom were men — died over the course of the study.

The researchers noted that other factors known to increase the risk of severe COVID-19, including advanced age, obesity and diabetes, also are associated with lower testosterone. “The groups of men who were getting sicker were known to have lower testosterone across the board,” said first author Sandeep Dhindsa, MD, an endocrinologist at Saint Louis University. “We also found that those men with COVID-19 who were not severely ill initially, but had low testosterone levels, were likely to need intensive care or intubation over the next two or three days. Lower testosterone levels seemed to predict which patients were likely to become very ill over the next few days.”

In addition, the researchers found that lower testosterone levels in men also correlated with higher levels of inflammation and an increase in the activation of genes that allow the body to carry out the functions of circulating sex hormones inside the cells. In other words, the body may be adapting to less testosterone circulating in the bloodstream by dialing up its ability to detect and use the hormone. The researchers don’t yet know the implications of this adaptation and are calling for more research.

“We are now investigating whether there is an association between sex hormones and cardiovascular outcomes in long COVID-19, when the symptoms linger over many months,” said Diwan, who is a cardiologist. “We also are interested in whether men recovering from COVID-19, including those with long COVID-19, may benefit from testosterone therapy. This therapy has been used in men with low levels of sex hormones, so it may be worth investigating whether a similar approach can help male COVID-19 survivors with their rehabilitation.”

This study used Washington University’s COVID-19 biorepository and was conducted as a collaboration of the university’s Institute of Clinical and Translational Sciences (ICTS), which includes Saint Louis University School of Medicine.

This work was supported by the National Institutes of Health (NIH), grant numbers R37 AI049653, P30 DK020579, HL107594 and HL143431; and a grant from The Foundation for Barnes-Jewish Hospital to facilitate data collection from the WU350 cohort, which supported these studies. These studies also were supported by the Washington University Institute of Clinical and Translational Sciences, grant number UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the NIH.

Featured image: A new study from Washington University School of Medicine in St. Louis suggests that, among men, low testosterone levels in the blood are linked to more severe COVID-19. The study contradicts widespread assumptions that higher testosterone may explain why men, on average, develop more severe COVID-19 than women do. © Sara Moser


Reference: Dhindsa S, Zhang N, McPhaul MJ, Wu Z, Ghoshal AK, Erlich EC, Mani K, Randolph GJ, Edwards JR, Mudd PA, Diwan A. Relationship of circulating sex hormones with inflammation and disease severity in COVID-19. JAMA Network Open. May 25, 2021.


Provided by Washington University School of Medicine at St. Louis