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RIVERSIDE, Calif. -- A top goal in cosmology is to precisely measure the total amount of matter in the universe, a daunting exercise for even the most mathematically proficient. A team led by scientists at the University of California, Riverside, has now done just that.

Reporting in the Astrophysical Journal, the team determined that matter makes up 31% of the total amount of matter and energy in the universe, with the remainder consisting of dark energy.

"To put that amount of matter in context, if all the matter in the universe were spread out evenly across space, it would correspond to an average mass density equal to only about six hydrogen atoms per cubic meter," said first author Mohamed Abdullah, a graduate student in the UCR Department of Physics and Astronomy. "However, since we know 80% of matter is actually dark matter, in reality, most of this matter consists not of hydrogen atoms but rather of a type of matter which cosmologists don't yet understand."

Abdullah explained that one well-proven technique for determining the total amount of matter in the universe is to compare the observed number and mass of galaxy clusters per unit volume with predictions from numerical simulations. Because present-day galaxy clusters have formed from matter that has collapsed over billions of years under its own gravity, the number of clusters observed at the present time is very sensitive to cosmological conditions and, in particular, the total amount of matter.

"A higher percentage of matter would result in more clusters," Abdullah said. "The 'Goldilocks' challenge for our team was to measure the number of clusters and then determine which answer was 'just right.' But it is difficult to measure the mass of any galaxy cluster accurately because most of the matter is dark so we can't see it with telescopes."

To overcome this difficulty, the UCR-led team of astronomers first developed "GalWeight", a cosmological tool to measure the mass of a galaxy cluster using the orbits of its member galaxies. The researchers then applied their tool to observations from the Sloan Digital Sky Survey (SDSS) to create "GalWCat19," a publicly available catalog of galaxy clusters.  Finally, they compared the number of clusters in their new catalog with simulations to determine the total amount of matter in the universe.

"We have succeeded in making one of the most precise measurements ever made using the galaxy cluster technique," said coauthor Gillian Wilson, a professor of physics and astronomy at UCR in whose lab Abdullah works. "Moreover, this is the first use of the galaxy orbit technique which has obtained a value in agreement with those obtained by teams who used noncluster techniques such as cosmic microwave background anisotropies, baryon acoustic oscillations, Type Ia supernovae, or gravitational lensing."

"A huge advantage of using our GalWeight galaxy orbit technique was that our team was able to determine a mass for each cluster individually rather than rely on more indirect, statistical methods," said the third coauthor Anatoly Klypin, an expert in numerical simulations and cosmology.

By combining their measurement with those from the other teams that used different techniques, the UCR-led team was able to determine a best combined value, concluding that matter makes up 31.5±1.3% of the total amount of matter and energy in the universe.

Unconventional T cells called mucosa-associated invariant T (MAIT) cells are recruited to the airways and strongly activated in some patients with severe COVID-19, a new study has found, suggesting the cells' possible involvement in the development of disease. These findings corroborate other recent studies that highlight potential associations between strong MAIT cell activation and severe COVID-19 outcomes. MAIT cells, representing 1% to 10% of T cells in the blood, can readily home into specific tissues and are particularly abundant in the liver and lungs. Emerging evidence has shown these primarily antibacterial cells can also act as quick-acting sensors of viral infection as well, leading Tiphaine Parrot and colleagues to investigate the MAIT cell population in the context of SARS-CoV-2. They analyzed blood samples taken from 24 hospitalized COVID-19 patients with moderate and severe disease, as well as 23 patients recovering from mild disease and 22 in recovery after severe disease. They discovered MAIT cells declined significantly in the blood and swarmed the airways of patients with COVID-19, compared with controls. By contrast, MAIT cell levels normalized in the blood of patients in recovery. Together, these patterns are consistent with the concept that MAIT cells home into tissues during disease and later return into the blood when disease is resolved. Furthermore, gene expression analyses revealed that MAIT cell expression of certain inflammatory proteins in the airways - including IL-17A, CD69, and CXCR3 - was associated with poor clinical outcome. Four out of 24 patients studied here who died at hospital had significantly higher CD69 expression by MAIT cells than patients who survived. The authors note several limitations of their study that must be resolved with further work, including that the cohorts studied here do not reflect the full complexity of COVID-19.

A new study conducted by SISSA and the University of Trieste shows the efficacy of carbon nanotube implants to restore motor functions and paves the way for a new therapeutic approach for spinal cord injuries.

Re-establishing motor skills and neuronal connectivity thanks to the implantation of carbon nanotubes in the injury site. This is the result of a new study conducted by SISSA - Scuola Internazionale Superiore di Studi Avanzati and the University of Trieste that rewards a ten years interdisciplinary collaboration. For the first time, the researchers have used nanomaterial implants in animals with spinal injury, observing the regrowth of nerve fibres and the restoration of motor functions. The research, published in PNAS - Proceedings of the National Academy of Sciences, shows the potential of therapeutic approaches that use the mechanical and electric properties of regenerative scaffolds to treat the injured area.

"We have been studying the interaction between neurons and carbon nanotubes for 15 years. Finally, we have been able to challenge their function in vivo", say Laura Ballerini, neurophysiologist at SISSA, and Maurizio Prato, chemist at the University of Trieste, who have been investigating nerve cell growth when interfaced to smart materials, such as carbon nanotubes in the last decade, using increasingly complex systems. "In recent years, we passed from single neurons to brain tissue explants and from single nanotubes to two-dimensional structures and, now, three dimensional ones."

"We studied the effect of the carbon nanotube implant in small mammals with a disease model of incomplete spinal cord injury," explains Sadaf Usmani, PhD in neurobiology and lead author of the study. "We observed their motor recovery during the next six months through standard protocols for locomotor evaluation which revealed a greater recovery of motor skills when compared to non-implanted animals".

This phenomenon is associated with nerve fibre regrowth through the injury site, as shown by the magnetic resonance experiments carried out in collaboration with the Center for Cooperative Research in Biomaterials (CIC biomaGUNE). A regrowth that is certainly favoured by nanotube implantation, explain Ballerini and Prato. "Nerve fibre regeneration is promoted by the physical characteristics of nanomaterials. These implants are able to guarantee mechanical support and, at the same time, interact electrically with neurons."

"The functionality of the regenerated tissue was not taken for granted, just as the biocompatibility of the implants" continue the researchers "And yet, not only there have been no cases of rejection, but electron microscope observations and the use of specific markers have confirmed that there is no real boundary between the tissue surrounding the injury, the regenerated tissue and the nanomaterials."

These results not only confirm the possible applications of the nanomaterials in the biomedical sector but also pave the way to new therapeutic approaches which use the physical, mechanical and electrical properties in particular, of the injured zone to favour functional recovery.

Organisms, ranging from bacteria to humans, run on an interconnected series of metabolic pathways--with glycolysis being the essential process that generates energy from sugars (glucose) in food. Pyruvate is the final product of glycolysis: it is an important molecule that acts as a node between different pathways (Figure 1). To better understand how these pathways work, a team of scientists, led by Dr Tomohiro Shimada from Meiji University and including Dr Akira Ishihama from Hosei University and Dr Sousuke Imamura from Tokyo Institute of Technology (Tokyo Tech), decided to investigate a protein called "PdhR," the master regulator of pyruvate catabolism (or breakdown) in Escherichia coli (a common model organism). They knew from previous research that PdhR regulates the expression of at least nine proteins involved in carbon metabolism pathways (breakdown of sugars into energy sources). But, given the many roles of pyruvate from scavenging free radicals to generating amino acids, it was logical to think PdhR had multiple targets.

Researchers used a process called gSELEX (Genomic SELEX) screening, in which PdhR is mixed with small pieces of E. coli genome. PdhR was tagged with a marker that allowed researchers to isolate the targets of PdhR. This led to the successful identification of multiple targets of PdhR. "We were able to find 16-27 possible targets of PdhR this way," Dr Shimada explained. "And from these, we decided to analyze the ones that had never been identified before. The goal was to find new pathways involving PdhR."

The team identified PdhR regulatory targets that were involved in bacterial movement, specifically acting as a repressor of genes affecting flagella (the appendage that many bacteria use to move). They also found that PdhR regulated breakdown of fatty acids (an important energy source in bacteria) by suppressing a protein that inhibits this process. In other words, active PdhR decreases bacterial mobility and increases fatty acid degradation--functions of PdhR that are completely novel. Moreover, the scientists also identified other carbon-metabolism genes regulated by PdhR, including enzymes that produces pyruvate during glycolysis, lactate metabolism, and TCA cycle.

The scientists are optimistic that these findings from E. coli can be applied to more complex, multicellular animals. They could also help us to better manipulate E. coli metabolism, which has important implications for bioengineering and molecular biology experiments." Dr Shimada concludes, "Our work allowed us to expand the role of PdhR beyond what was already known. Because pyruvate concentrations influence PdhR activity, these results really helps us better understand the critical central role of pyruvate in E. coli metabolism. E. coli is an extremely common bacteria, and understanding it can lead to significant insights into the medical field."

While debate over COVID-19 guidelines and vaccine development has raised skeptics' eyebrows and undermined confidence, a West Virginia University associate professor says that communication is essential for the science community to gain the American public's trust. According to Geah Pressgrove, scientists and communications professionals need to rethink how they communicate through four distinct dimensions of trust: competence, integrity, benevolence and openness.

Quotes

"In practice, communication objectives should be considered when assessing trust. In other words, 'What are you trying to accomplish with the communication to your audience?' Those objectives should influence the ways in which you assess perceptions. For instance, we see many science communicators simply assessing the outcome of knowledge gain; however, there is substantial evidence that knowledge doesn't change behaviors."

"We set out to increase conceptual clarity of trust and found that a four-factor measurement scale provides value when measuring perceptions of scientists, depending on the communication objectives and research goals. In this solution, items measure competence (ability/expertise), integrity (honesty), benevolence (warmth) and openness (willingness to listen)."

"It is reasonable to assume the public is skeptical of science-related issues. In the past, there has been a tendency towards dumping volumes of information and expecting our audience to naturally understand and accept the claims. Instead, we need to refocus on the communication objectives that make the most sense for science-based communication. Recognizing when and why people trust scientists will help us communicate more effectively by putting the emphasis where needed." - Geah Pressgrove, associate professor, advertising and public relations program chair, WVU Reed College of Media

(Boston)--High blood pressure (hypertension) affects one in two U.S. adults and can cause hardening and thickening of the arteries (atherosclerosis), which can lead to heart attacks, strokes or other complications including chronic kidney disease. Dietary salt intake can evoke salt-sensitive hypertension, which exists in approximately half of hypertensive patients.

A new study from Boston University School of Medicine (BUSM) has found that an alpha adrenoceptor blocker (a class of drugs that relaxes smooth muscle or blood vessels) may represent a new treatment approach for patients with salt sensitive hypertension. This is the first study to demonstrate that α1-adrenoceptor antagonism reduces the activity of a mechanism in the kidney that reabsorbs salt to reduce blood pressure.

The researchers used an experimental model that was fed a high salt diet (to model the content of a western diet) which led to an increase in their blood pressure. A portion of these models were then treated with an alpha 1 adrenoceptor blocker that reduced their blood pressure by decreasing the activity of a pathway in the kidney that reabsorbs salt. "Our data suggest blocking renal α1-adrenoceptors may represent a new treatment approach for patients with salt sensitive hypertension," said corresponding author Richard Wainford, PhD, associate professor of Pharmacology & Experimental Therapeutics at BUSM.

According to the researcher this study highlights the critical role of looking at the disease of hypertension in an integrated way by examining the interaction between multiple organ systems, in this case the sympathetic nervous system and kidney versus working in isolation. "We hope that these studies, that highlight a new mechanism underlying the salt sensitivity of blood pressure, will drive new treatment approaches for hypertension."

SAN ANTONIO -- Sept. 28, 2020 -- A new study authored by Southwest Research In-stitute scientists Rodrigo Leiva and Marc Buie reveals the binary nature of a trans-Neptunian object (TNO). Leiva and Buie utilized data obtained by the Research and Education Collaborative Occultation Network (RECON), a citizen science research net-work dedicated to observing the outer solar system. The study was published this month in The Astrophysical Journal.

Trans-Neptunian objects (TNOs) are small icy bodies that orbit the Sun beyond Nep-tune. Binary TNOs occur when two of these objects orbit each other while together or-biting the Sun. Leiva and Buie discovered two objects in a particularly close gravita-tional configuration. The pair was detected using a stellar occultation, which occurs when an object passes between Earth and a distant star which hides, or "occults," the star from view. Observers located in the path of the object's shadow can record the star blinking out and reappearing. The length of time that the object blocks the starlight can be used to determine its size.

"In this instance, the occulted star also turned out to be a binary system. Binary stars are not unusual and binary objects are not unusual," Buie said. "But it is unusual that we had a binary TNO occulting a binary star."

"What's also interesting and unusual is this object's characteristics," Leiva said. "The two components are quite close, only 350 kilometers apart. Most binary TNOs are very separated, usually 1,000 kilometers or more. This closeness makes this type of binary TNO difficult to detect with other methods, which is what RECON was designed to ac-complish."

The discovery of the new TNO was made possible by RECON, a collection of 56 obser-vation stations stretching from Yuma, Arizona, to Orville, Washington. The NSF-funded project provides each station with an array of observation equipment, including 11-inch telescopes. High school teachers are trained by Leiva, Buie and Fiske Planetari-um Director Dr. John Keller to operate the stations and observe occultations so they can then teach students how to make the same observations. RECON has seen several stu-dents go on to do research related to their observations in college.

"To me this project is citizen science at its best," Buie said. "They're learning as well as making observations and helping to collect data. If they didn't do this, we wouldn't learn about these objects."

RECON stations are commonly placed in small communities along an ideal line, from the southern to the northern border of the United States, for observation of stellar occul-tations. Eight additional stations were established in Canada in 2018 by colleagues of Leiva and Buie.

Going forward, Leiva and Buie will continue to search for previously unobserved TNOs, with the aim of discovering whether close binaries are common or unusual in our Solar System.

"Most models of the Solar System indicate that binaries are very common, particularly close binaries like this one," Leiva said. "If you have an accurate measurement of how common they are, you can fine tune these models."

"Our overarching aim is to know how common close binary TNOs are," Buie said. "Is this object one in a million or just like 90% of them? This is fueling our knowledge for building better models of how the Solar System formed."

A new field of research in microbiology is transforming the way scientists see fungi, bacteria and other microorganisms. Microbiome research is so promising that it has drawn attention from funders and industry as well as scientists. In the United States alone, the market for microbiome-based agricultural products is expected to be worth more than $10 billion by 2025. Research on the human microbiome has surpassed $1.7 billion in the past decade.

Scientific study of microbiomes is growing exponentially, encompassing topics that range from the influence of gut microbiota on brain functioning in humans to the impact of marine bacteria on climate change. To address this extraordinary thematic diversity, agree on a definition of microbiome, and pursue guidelines for investment in research, the European Union-funded Microbiome Support project brought together a panel of experts from 28 institutions in various countries. The conclusions are published in the journal Microbiome.

Brazil was represented on the panel by the Genomics for Climate Change Research Center (GCCRC), one of the Engineering Research Centers (ERCs) funded by São Paulo Research Foundation - FAPESP. In this case, its partner is the Brazilian Agricultural Research Corporation (EMBRAPA). GCCRC is hosted by the University of Campinas (UNICAMP), and its principal investigator is Professor Paulo Arruda.

"The discussion reached conclusions that very clearly distinguish between the concepts of microbiota and microbiome. Microbiota is the community of microorganisms in a given environment, such as your office desk, plants, skin, or gut. Microbiota is everywhere. If you add the functions it performs in that environment, you're talking about microbiome," said Rafael Soares Correa de Souza, the leader of GCCRC's microbiome team. Souza is supported by FAPESP via a postdoctoral scholarship.

"When we speak of a plant's microbiome, for example, we're not referring only to the microorganism community present in the plant but also to all the functions performed by that community, such as absorption of nutrients, protection from pathogens and drought resistance, among many others," he said.

Advances in genetic sequencing and bioinformatics in recent decades have enabled scientists to discover not only that microorganisms such as bacteria, fungi, and protozoa are far more diverse than they thought but also that many of their functions have been poorly understood or simply unknown until recently.

These tools can now be used to identify the community of microorganisms and their "theater of activity", the term coined by the panel for the "whole spectrum" of molecules they produce, including their structural elements (nucleic acids, proteins, lipids, polysaccharides) and metabolites, and the "molecules produced by coexisting hosts and structured by the surrounding environmental conditions".

"The concept of microbiome is much more holistic than the concept of microbiota," Souza said.

Market and legislation

Many microbiome-based products have come to market, and defining concepts is important, among other reasons, to facilitate communication with society and offer a basis for lawmakers to legislate on the subject.

Meat from chickens whose diets have been supplemented with microbial agents that eliminate the need for antibiotics can be purchased in supermarkets even in Europe, a strictly regulated market. Fecal microbiota transplantation is an approved treatment for antibiotic-resistant infections in Brazil and the US.

Given the field's potential, Microbiome Support was set up to decide on research priorities for funding by Horizon Europe, the EU's scientific research and innovation initiative that will succeed Horizon 2020 and will invest €100 billion in all research fields between 2021 and 2027.

"Here at GCCRC we want to understand how to modulate the microbiome in order to improve the agricultural performance of plants, raise yields, and reduce fertilizer and agrochemical usage to enhance environmental safety and eliminate human health hazards. Brazil is one of the world's leading agricultural producers, so this is an opportunity for our science and industry," Souza said.

WASHINGTON -- Biometric authentication, which uses unique anatomical features such as fingerprints or facial features to verify a person's identity, is increasingly replacing traditional passwords for accessing everything from smartphones to law enforcement systems. A newly developed approach that uses 3D images of finger veins could greatly increase the security of this type of authentication.

"The 3D finger vein biometric authentication method we developed enables levels of specificity and anti-spoofing that were not possible before," said Jun Xia, from University at Buffalo, The State University of New York, research team leader. "Since no two people have exactly the same 3D vein pattern, faking a vein biometric authentication would require creating an exact 3D replica of a person's finger veins, which is basically not possible."

In the Optical Society (OSA) journal Applied Optics, the researchers describe their new approach, which represents the first time that photoacoustic tomography has been used for 3D finger vein biometric authentication. Tests of the method on people showed that it can correctly accept or reject an identity 99 percent of the time.

"Due to the COVID-19 pandemic, many jobs and services are now performed remotely," said research team member Giovanni Milione, from NEC Laboratories America, Inc. "Because our technique detects invisible features in 3D, it could be used to enable better authentication techniques to protect personnel data and sensitive documents."

Adding depth information

Although other biometric authentication approaches based on finger veins have been developed, they are all based on 2D images. The additional depth from a 3D image increases security by making it more difficult to fake an identity and less likely that the technique will accept the wrong person or reject the right one.

To accomplish 3D biometric authentication using the veins in a person's fingers, the researchers turned to photoacoustic tomography, an imaging technique that combines light and sound. First, light from a laser is used to illuminate the finger. If the light hits a vein, it creates a sound much in the same way that a grill creates a "poof" sound when it is first lit. The system then detects that sound with an ultrasound detector and uses it to reconstruct a 3D image of the veins.

"It has been challenging to use photoacoustic tomography for 3D finger vein biometric authentication because of the bulky imaging system, small field of view and inconvenient positioning of the hand," said Xia. "We addressed these issues in the new system design through a better combination of light and acoustic beams and custom-made transducers to improve the imaging field of view."

Designing a practical system

To better integrate light illumination and acoustic detection, the researcher fabricated a new light- and acoustic-beam combiner. They also designed an imaging window that allows the hand to be naturally placed on the platform, similar to a full-size fingerprint scanner. Another critical development was a new matching algorithm, developed by Wenyao Xu from the Computer science and Engineering department that allows biometric identification and matching of features in 3D space.

The researchers tested their new system with 36 people by imaging their four left and four right fingers. The tests showed that the approach was not only feasible but also accurate, especially when multiple fingers were used.

"We envision this technique being used in critical facilities, such as banks and military bases, that require a high level of security," said Milione. "With further miniaturization 3D vein authentication could also be used in personal electronics or be combined with 2D fingerprints for two-factor authentication."

The researchers are now working to make the system even smaller and to reduce the imaging time to less than one second. They note that it should be possible to implement the photoacoustic system in smartphones since ultrasound systems have already been developed for use in smartphones. This could enable portable or wearable systems that perform biometric authentication in real time.

In an article published in Nature Genetics, researchers confirm that about 14% of all cases of cerebral palsy, a disabling brain disorder for which there are no cures, may be linked to a patient's genes and suggest that many of those genes control how brain circuits become wired during early development. This conclusion is based on the largest genetic study of cerebral palsy ever conducted. The results led to recommended changes in the treatment of at least three patients, highlighting the importance of understanding the role genes play in the disorder. The work was largely funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

"Our results provide the strongest evidence to date that a significant portion of cerebral palsy cases can be linked to rare genetic mutations, and in doing so identified several key genetic pathways involved," said Michael Kruer, M.D., a neurogeneticist at Phoenix Children's Hospital and the University of Arizona College of Medicine - Phoenix and a senior author of the article. "We hope this will give patients living with cerebral palsy and their loved ones a better understanding of the disorder and doctors a clearer roadmap for diagnosing and treating them."

Cerebral palsy affects approximately one in 323 children in the United States. Signs of the disorder appear early in childhood resulting in a wide range of permanently disabling problems with movement and posture, including spasticity, muscle weakness, and abnormal gait. Nearly 40% of patients need some assistance with walking. In addition, many patients may also suffer epileptic seizures, blindness, hearing and speech problems, scoliosis, and intellectual disabilities.

Since its first official description in 1862, scientists have hotly debated whether cerebral palsy is caused by problems at birth. For instance, it is known that babies born prematurely or who experience a lack of blood flow or oxygen during birth have a greater chance of suffering from the disorder. Later though, researchers concluded that a majority (85-90%) of all cases are congenital, or born with the disease, and some studies had suggested that cerebral palsy could be inherited. Despite this, the causes of many children's cases had remained elusive.

Then in 2004, scientists discovered the first genetic mutation known to cause cerebral palsy. Since then several more mutations have been identified and depending on how an experiment was performed, scientists have estimated that anywhere from 2 to 30% of all cases may be linked to a misspelling in a patient's DNA. In this study, the researchers provided support for a previous estimate and highlighted which genes may play a critical role in the disorder.

"Cerebral palsy is one of neurology's oldest unresolved mysteries. The results from this study show how advances in genomic research provide scientists with the hard evidence they need to unravel the causes behind this and other debilitating neurological disorders," said Jim Koenig, Ph.D., program director at NINDS.

The study was led by Sheng Chih (Peter) Jin, Ph.D., assistant professor of genetics at Washington University School of Medicine, St. Louis, and Sara A. Lewis, Ph.D., a post-doc in the lab Dr. Kruer leads.

The researchers searched for what are known as "de novo," or spontaneous, mutations in the genes of 250 families from the United States, China, and Australia through a collaboration made possible by the International Cerebral Palsy Genomics Consortium. These rare mutations are thought to happen when cells accidentally make mistakes copying their DNA as they multiply and divide. An advanced technique, called whole exome sequencing, was used to read out and compare the exact codes of each gene inscribed in the chromosomes of the patients with that of their parents. Any new differences represented de novo mutations that either happened while a parent's sperm or egg cell multiplied or after conception.

Initially the researchers found that the cerebral palsy patients had higher levels of potentially harmful de novo mutations than their parents. Many of these mutations appeared to be concentrated in genes that are highly sensitive to the slightest changes in the DNA letter code. In fact, they estimated that about 11.9% of the cases could be explained by damaging de novo mutations. This was especially true for the idiopathic cases which had no known cause and represented the majority (62.8%) of cases in the study.

Approximately another 2% of the cases appeared to be linked to recessive, or weaker, versions of genes. This raised the estimate of cases that could be linked to genetic problems from 11.9% to 14%, as has been previously reported.

Moreover, the results led to recommendations for more tailored treatments of three patients.

"The hope of human genome research is that it will help doctors find the best, most personalized, matches between treatments and diseases. These results suggest that this may be possible for some patients with cerebral palsy," said Chris Wellington, program director in the Division of Genome Sciences at the NIH's National Institute of Human Genome Research, which also provided support for the study.

When the researchers looked more closely at the results, they found that eight genes had two or more damaging de novo mutations. Four of these genes, labeled RHOB, FBXO31, DHX32, and ALK, were newly implicated in CP while the other four had been identified in previous studies.

The researchers were especially surprised by the RHOB and FBXO31 results. Two cases in the study had the same spontaneous mutation in RHOB. Likewise, two other cases had the same de novo mutation in FBXO31.

"The odds of this randomly happening are incredibly low. This suggests that these genes are highly linked to cerebral palsy," said Dr. Jin.

The researchers also looked at the genes behind other brain development disorders and found that about 28% of the cerebral palsy genes identified in this study have been linked to intellectual disability, 11% to epilepsy and 6.3% to autism spectrum disorders. In contrast, the researchers found no significant overlap between cerebral palsy genes and those involved with the neurodegenerative disorder Alzheimer's disease which attacks the brain later in life.

"Our results support the idea that cerebral palsy is not one narrow disease but a spectrum of overlapping neurodevelopmental problems," said Dr. Lewis.

Further analysis of the results suggested that many of the genes they found in this study, including six of the eight genes that had two or more de novo mutations, control the wiring of neural circuits during early development. Specifically, these genes are known to be involved in either the construction of protein scaffolds that line the perimeters of neural circuits or in the growth and extension of neurons as they wire up.

Experiments on fruit flies, formally known as Drosophila melanogaster, supported this idea. To do this, the researchers mutated fly versions of the wiring genes they identified in the cerebral palsy patients. They found that mutations in 71% of these genes caused flies to have problems with movement, including walking, turning, and balancing. The results suggested that these genes play a critical role in movement. They estimated that there was only a 3% chance these problems would happen if they had blindly mutated any gene in the fly genome.

"Treatments for cerebral palsy patients have not changed for decades," said Dr. Kruer. "In the future, we plan to explore how these results can be used to change that."

Because gastrointestinal stromal tumors (GIST) are sensitive to the targeted small molecule therapy imatinib, oncologists tend to treat all patients with metastatic GIST with this drug. However, because this rare type of cancer is caused by different genetic mutations, imatinib does not help all patients equally.

To determine whose cancer may be most responsive, the National Comprehensive Cancer Network suggests that patients undergo genetic testing to identify each individuals' tumor mutations. And yet, only 30 percent of patients have genetic testing at the time of diagnosis, likely due to concerns over cost and utility of testing, said Jason Sicklick, MD, professor of surgery in the Division of Surgical Oncology at University of California San Diego School of Medicine.

"We recommend that all patients with a new diagnosis of metastatic GIST undergo genetic testing prior to the initiation of first-line chemotherapy," said Sicklick, surgical oncologist and co-leader of the Sarcoma Disease Team at Moores Cancer Center at UC San Diego Health. "In doing so, those who are unlikely to benefit from imatinib can be given a treatment better suited for their individual tumor."

In a paper published online on September 29, 2020 in the journal JAMA Network Open, Sicklick and colleagues reported that genetic testing is cost-effective and beneficial for newly diagnosed patients with metastatic GIST, a type of soft tissue sarcoma that develops in specialized nerve cells in the wall of the digestive system, most often occurring in the stomach or small intestine.

The team developed a model to compare the cost effectiveness of targeted gene testing and personalized therapy to patients with metastatic GIST who were prescribed imatinib (marketed as Gleevec). Data analyses were conducted October 2019 to January 2020.

"Genetic testing is cost-effective as it allows clinicians to prescribe chemotherapy in a tumor-specific manner. Patients who would not benefit from imatinib, because of primary tumor resistance, are given alternative therapy," said first author Sudeep Banerjee, MD, who did the research while in the Sicklick lab at Moores Cancer Center and who is now chief resident at David Geffen Medical School at UCLA. "Avoiding ineffective treatment and reduced rates of disease progression are the reasons why genetic testing is cost-effective."

Although the most common sarcoma, GIST is rare with an estimated annual incidence of 6.8 cases per million people in the United States. Eventually this cancer becomes highly resistant to existing drug therapies.

Clinicians fight the growth with progressively aggressive drugs, the downside being that each line of therapy has diminishing effectiveness and higher toxicity for patients. More than 95 percent of patients eventually succumb to drug-resistant GIST, underscoring the importance of starting patients on the most effective available drug not only because it is most cost-effective, but crucial for maintaining and improving quality of life in these patients, said Sicklick, co-corresponding author on the paper.

"The treatment of cancer is becoming an increasingly personalized process," said Banerjee. "There is a rapidly expanding body of research around gene-specific and even mutation-specific therapies that can be effective independent of the site of origin of a given tumor. Genetic testing provides the necessary information for patients to potentially benefit from those novel therapies."

Simultaneous heatwaves and droughts are becoming increasingly common in western parts of the Unites States, according to a new study led by researchers from McGill University. Periods of dry and hot weather, which can make wildfires more likely, are becoming larger, more intense, and more frequent because of climate change.

In a study published by Science Advances, the researchers analyzed heat and drought events across the contiguous United States over the past 122 years. They found that combined dry and hot events have not only increased in frequency, but also in size geographically. Where such events were once confined to small parts of the United States, now they cover whole regions, such as the entire west coast and parts of the Northeast and Southeast.

"Dry-hot events can cause large fires. Add wind and a source of ignition, and this results in 'megafires' like the 2020 fires across the west coast of the United States. Drought and record-breaking heatwaves, coupled with a storm that brought strong winds and 12,000 lightning events in a span of 72 hours, caused more than 500 wildfires," says lead author Mohammad Reza Alizadeh, a PhD student under the supervision of Professor Jan Adamowski in the Department of Bioresource Engineering at McGill University.

The researchers also found that dry and hot weather events are intensifying, with longer periods of drought and higher temperatures. These dual "dry-hot extremes" are not only self-intensifying - more heat causes more drought and vice versa - but are also self-propagating, meaning they are able to move from region to region. "As increased temperatures are driving and expanding aridity, droughts and heatwaves move from one region to downwind regions," says Alizadeh. These extremes can be particularly damaging for agricultural production and ecosystems, they warn.

According to the researchers, the trigger for these hot-dry events is shifting. Looking back at the catastrophic Dust Bowl of the 1930s, they explain that the dust storms were driven by a lack of rainfall coupled with poor land management practices. In recent decades, however, dry-hot disasters are driven more often by excess heat than a lack of rainfall.

The future will bring us more of these disasters, if the current warming trends continue, the researchers caution. They suggest their findings could be used to inform climate mitigation and adaptation efforts. "We need to understand how things are changing in order to adapt," says Professor Jan Adamowski.

Results of recent studies involving valproic acid, used for decades as an anti-convulsant drug, show that it can interact with the conformation of DNA and regulate gene expression.

These are some of the key findings from a project led by biologist Maria Luiza S. Mello at the University of Campinas (UNICAMP) in the state São Paulo, Brazil, with the collaboration of Benedicto de Campos Vidal, Emeritus Professor in the Biology Institute’s Department of Structural and Functional Biology.

The group has been studying the functions of valproic acid, or sodium valproate (VPA), for over a decade and have demonstrated the compound’s action on the expression of genes associated with diabetes in cellular models (read more at: agencia.fapesp.br/23819).

Its interaction with DNA is reported in an article published in the International Journal of Biological Macromolecules. The study was part of a Thematic Project supported by FAPESP to study the action of VPA. “Elucidating the drug’s action mechanisms is important because it paves the way for novel pharmaceutical research,” Mello said.

Changes in histones and DNA

The epigenetic action of VPA – its capacity to influence gene expression without changing the subject’s DNA – was already well-known. “In 2017, Iranian researchers mooted the possibility of an action mechanism that was not only epigenetic but also involved direct interaction with the structure of histone H1,” Mello said. “So we decided to study how histones and DNA itself respond to VPA.” Histones are cell nucleus proteins and key components of chromatin, the substance of chromosomes. These are made up of DNA tightly wound around histones.

The group tested samples containing VPA-DNA and VPA-histone mixtures. They analyzed the interactions between H1, H3, and VPA by means of high-performance polarization microscopy and Fourier-transform infrared microspectroscopy, using equipment previously acquired by FAPESP for Campos Vidal.

“The samples with DNA, histones, and VPA were analyzed first under the polarization microscope and then under the infrared microspectroscope” Mello said. This type of measurement, performed with a spectroscope coupled to a special microscope, produces a spectral signature of molecular structure – a graphical record of how the molecules are organized.

The graph of the signature displays curves with peaks and troughs. “The frequency of the peaks points to a specific chemical group,” Mello said.

The group then compared histone and DNA organization with and without VPA. “We found that VPA can cause changes in the conformation, or spatial arrangement, of the two histones of interest, H1 and H3. In addition, we observed changes in DNA superstructure and molecular order,” he said. The next step will be to confirm whether the effect also occurs in cells treated with VPA in vitro.

Tumor gene expression

Besides this discovery, as part of the master’s research of Marina Amorim Rocha, in December 2019 the group published in Scientific Reports another important finding about the epigenetic action of VPA in laboratory-grown HeLa cells, which are derived from human cervical cancer cells. The focus for the investigation was a specific kind of epigenetic alteration known as DNA methylation.

Methylation occurs when a methyl group (CH3) is added to the carbon 5 position in the DNA nitrogenous base cytosine. “When this happens in the promoter of a gene, the functioning of the gene itself is altered,” Mello explained. If large-scale methylation occurs in the promoter of a tumor suppressor gene, for example, the gene can become inactive and cease performing its function.

The process can be manipulated, passively by inhibiting an enzyme involved in methylation or actively via a recently discovered pathway. “In this case a group of enzymes from the TET family lets these methylated cytosines transform themselves into other derived molecules until demethylation is complete,” Mello said.

In their study, the UNICAMP researchers found that the mechanism induced by VPA in HeLa cells was predominantly but not exclusively active. “It also acts via the passive pathway, and this finding can enhance the expertise of scientists dedicated to drug development,” Mello said. In other words, the fact that the compound reduces methylation in cultured cells during the stationary phase of the life cycle suggests that in future it can be tested as a candidate to reverse this process in cells that have stopped dividing.

Researcher Steven Emslie encountered a puzzle at Cape Irizar, a rocky cape located just south of the Drygalski Ice Tongue on the Scott Coast, Ross Sea. He found both ancient and what appeared to be fresh remains of Adelie penguins, mostly of chicks, which frequently die and accumulate at these colonies. However, the "fresh" remains were puzzling, he says, because there are no records of an active penguin colony at this site since the first explorers (Robert Falcon Scott) in 1901-1903 came to the Ross Sea.

Emslie found abundant penguin chick bones scattered on the surface, along with guano stains, implying recent use of the site, but that wasn't possible, says Emslie. Some of the bones were complete chick carcasses with feathers, now falling apart from decay as at a modern colony, as well as intact mummies. Emslie and his colleagues collected some of these surface remains for further analysis and radiocarbon dating to try and figure out what was going on there.

The team found old pebble mounds scattered about the cape. These mounds are former nesting sites of Adélie penguins because they use pebbles to build their nests. When they abandon a site, the pebbles become scattered and stand out on the landscape, since they are all about the same size.

"We excavated into three of these mounds, using methods similar to archaeologists, to recover preserved tissues of penguin bone, feather, and eggshell, as well as hard parts of prey from the guano (fish bones, otoliths). The soil was very dry and dusty, just as I've found at other very old sites I've worked on in the Ross Sea, and also had abundant penguin remains in them. Overall, our sampling recovered a mixture of old and what appeared to be recent penguin remains implying multiple periods of occupation and abandonment of this cape over thousands of years. In all the years I have been doing this research in Antarctica, I've never seen a site quite like this."

The analyses reported in Emslie's recent paper published in Geology indicate at least three occupation periods of the cape by breeding penguins, with the last one ending at about 800 years ago. When that occupation ended, either due to increasing snow cover over the cape or other factors (the Little Ice Age was beginning about then too), the "fresh" remains on the surface were covered in snow and ice and preserved intact until recent exposure from snowmelt.

Global warming has increased the annual temperature in the Ross Sea by 1.5-2.0 °C since the 1980s, and satellite imagery over the past decade shows the cape gradually emerging from under the snow. Thus, says Emslie, "This recent snowmelt revealing long-preserved remains that were frozen and buried until now is the best explanation for the jumble of penguin remains of different ages that we found there."

Acta Pharmaceutica Sinica B publishes special issue on 'Research on Emerging COVID-19 (Target, Mechanism, and Therapeutics)' edited by Hai-Bin Luo, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Shilin Chen, Institute of Chinese Materia Medica, Beijing, China and Peiqing Liu, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. In recent months, due to its high infectivity and pathogenicity, SARS-CoV-2 has gradually spread to more than 200 countries and regions, resulting in more than 500,000 deaths globally. There is an urgent need for effective prevention and treatment (drugs and vaccines) against this highly pathogenic coronavirus. This special issue includes original five research articles, three review articles, and two letters to the editor covering topics around the identification of readily available drugs or natural products as a rapid way to provide clinical treatment in COVID-19 therapy.

Featured papers in this issue are:

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19 by authors Xiaoyan Liu, Zhe Li, Shuai Liu, Jing Sun and Hai-Bin Luo (https://doi.org/10.1016/j.apsb.2020.04.008). Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, the authors found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, the authors identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro.

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites by authors Sisi Kang, Mei Yang, Zhongsi Hong, Liping Zhang and Shoudeng Chen (https://doi.org/10.1016/j.apsb.2020.04.009). The structural information of SARS-CoV-2 nucleocapsid protein remains unclear. The authors have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein and revealed potential unique drug targeting sites, which can help guide the design of novel antiviral agents targeting SARS-CoV-2.

D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19 by authors Yulong Shi, Xinben Zhang, Kaijie Mu, Cheng Peng and Weiliang Zhu (https://doi.org/10.1016/j.apsb.2020.04.006). The authors have developed a molecular docking-based web server D3Targets-2019-nCoV to accelerate drug discovery against COVID-19. The server has two functions; one, to predict targets for active compounds, and two, to identify potent compounds via virtual screening. The webserver is useful to medical chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against SARS-CoV-2.

Other articles published in the issue include:

Review articles

Combating COVID-19 with integrated traditional Chinese and Western medicine in China
Liqiang Ni, Lili Chen, Xia Huang, Chouping Han, Hongzhuan Chen
https://doi.org/10.1016/j.apsb.2020.06.009

Bioactive natural compounds against human coronaviruses: a review and perspective
Yanfang Xian, Juan Zhang, Zhaoxiang Bian, Hua Zhou, Hongxi Xu
https://doi.org/10.1016/j.apsb.2020.06.002

Highly pathogenic coronaviruses: thrusting vaccine development in the spotlight
Chunting He, Ming Qin, Xun Sun
https://doi.org/10.1016/j.apsb.2020.05.009

Original articles

Analysis on herbal medicines utilized for treatment of COVID-19
Lu Luo, Jingwen Jiang, Cheng Wang, Martin Fitzgerald, Shilin Chen
https://doi.org/10.1016/j.apsb.2020.05.007

Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model
Cheng Cui, Miao Zhang, Xueting Yao, Siqi Tu, Dongyang Liu
https://doi.org/10.1016/j.apsb.2020.04.007

Letters to the Editor
Comment on GLP-1-based drugs and COVID-19 treatment
Tianru Jin, Mingyao Liu
https://doi.org/10.1016/j.apsb.2020.05.006

Anti-RAS drugs and SARS-CoV-2 infection
Jingwei Bian, Rongsheng Zhao, Suodi Zhai, Zijian Li
https://doi.org/10.1016/j.apsb.2020.04.013

Keywords: SARS-CoV-2; COVID-19; Prevention; Treatment