β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.

(American Association for the Advancement of Science) A one-hour exercise designed to increase feelings of social belonging administered during the first year of college appears to significantly improve the lives and careers of black students up to 11 years later, psychologists report.

With the northeast monsoon over southern China being generally weaker than normal for most of the time in March, the month was much warmer than usual, the Hong Kong Observatory said today.

The monthly mean temperature was 21.3 degrees Celsius, 2.2 degrees above normal and the mean minimum temperature was 19.7 degrees Celsius, 2.5 degrees above average. Both were the joint second highest on record for March.

The monthly mean maximum temperature was 23.8 degrees Celsius, 2.4 degrees above normal and the fifth highest on record for the month.

The month was also drier than usual with a total rainfall of 41.3mm, about half of the normal figure.

The accumulated rainfall recorded in the first three months of the year was 135.9mm, about 16% below average.

(University of Helsinki) Mutations in white blood cells can contribute to abnormal immune profile after hematopoietic stem cell transplantation.

(University of Houston) A University of Houston biomedical researcher is developing a new device to treat babies with blood disorders, because current technology is designed for adults. The ability to perform lifesaving leukapheresis safely and effectively in these most vulnerable pediatric patients will significantly increase their access to highly effective cell-based therapies.

(St. Jude Children's Research Hospital) Funding will help expand collaboration across engineering and physical sciences to expand tools for studying pediatric diseases.

(George Mason University) The team's work supports evidence-based decision making, informed by models, to rethink and facilitate hospital operations during the pandemic.

(Northwestern University) Northwestern University researchers are using artificial intelligence (AI) to speed up the search for COVID-19 treatments and vaccines. The AI-powered tool makes it possible to prioritize resources for the most promising studies -- and ignore research that is unlikely to yield benefits.

(DOE/Pacific Northwest National Laboratory) Software vulnerabilities are more likely to be discussed on social media before they're revealed on a government reporting site, a practice that could pose a national security threat, according to computer scientists at Pacific Northwest National Laboratory.

(Carnegie Mellon University) A new study sought to determine how the impact of recommender systems (also called recommenders) is affected by factors such as product type, attributes, and other sources of information about products on retailers' websites. The study found that recommenders increased the number of consumer views of product pages as well as the number of products consumers consider, but that the increase was moderated by product attributes and review ratings.

(University of Massachusetts Lowell) A UMass Lowell researcher investigating how to identify damage in wind turbines before they fail has received $1.4 million to develop a solution.

(Brown University) Strange spots scattered across the moon's nearside where bedrock is conspicuously exposed are evidence of seismic activity set in motion 4.3 billion years ago that could be ongoing today, the researchers say.

(University of British Columbia) Mars had a global magnetic field much earlier -- and much later -- than previously known. Analysis of new satellite data found clear evidence of a magnetic field coming from a lava flow that formed less than 3.7 billion years ago, half a billion years after many people thought the Martian dynamo had ceased. The researchers also detected low-intensity magnetic fields over the Borealis Basin, believed to be one of the oldest features on Mars.

(Kudos Innovations Ltd) Kudos helps researchers maximize reach and visibility of research by opening up Kudos Pro. The platform helps showcase work to a range of target audiences, supporting researchers in fields where conferences have been cancelled -- and those with COVID-19-relevant work that needs rapid communication. Over 2,000 researchers have already signed up.

(University of California - Irvine) Cyanobacteria living in rocks in Chile's Atacama Desert extract water from the minerals they colonize and, in doing so, change the phase of the material from gypsum to anhydrite. Researchers at the University of California, Irvine and Johns Hopkins University gained verification of this process through experiments, and the work points to possible strategies for humans to stay hydrated in harsh environments.

(Arizona State University) An interdisciplinary team of researchers, led by Arizona State University, has provided a framework called a 'detectability index' to help prioritize exoplanets to study and provide scientists with a tool to select the best targets for observation and maximize the chances of detecting life.

(Florida Museum of Natural History) Florida and Georgia archaeologists have discovered the location of Fort San Antón de Carlos, home of one of the first Jesuit missions in North America. The Spanish fort was built in 1566 in the capital of the Calusa, the most powerful Native American tribe in the region, on present-day Mound Key in the center of Estero Bay on Florida's Gulf Coast.

(Bentham Science Publishers) Two authors representing environmental geomorphology and historical archaeology collaborated in an investigation that aimed to examine the material culture still evident in urban burial sites with dated, upstanding headstone memorials.

(Universitat Pompeu Fabra - Barcelona) Expansions by groups of humans were common during prehistoric times, after the adoption of agriculture. Among other factors, this is due to population growth of farmers which was greater than of that hunter-gatherers. We can find one example of this during the Neolithic period, when farming was introduced to Europe by migrations from the Middle East.

(Perot Museum of Nature and Science) Published in PLOS ONE today, a study by an international team from the Perot Museum of Nature and Science in Dallas and Hokkaido University in Japan further explores the proliferation of the most commonly occurring duck-billed dinosaur of the ancient Arctic as the genus Edmontosaurus. The findings reinforce that the hadrosaurs -- dubbed 'caribou of the Cretaceous' -- had a geographical distribution of approximately 60 degrees of latitude, spanning the North American West from Alaska to Colorado.

(Queensland University of Technology) Robots that fly, swim and drive are being designed and built by internationally renowned Australian scientists from QUT.

(Brown University) A new study shows that coastal sea ice used by Arctic residents for hunting and fishing will be reduced as the planet warms.

(University of Hawaii at Manoa) In a study published in Scientific Reports, researchers at the University of Hawai'i at Mānoa, found in the next few decades, sea level rise will likely cause large and increasing percentages of land area to be impacted simultaneously by the three flood mechanisms. Further, they found direct marine inundation represents the least extensive--only three percent of the predicted flooding, while groundwater inundation represents the most extensive flood source.

(Florida State University) Florida State University and partner universities investigated current baseline conditions in the southern Gulf to create a series of maps and guides that detail the distribution of carbon, nitrogen and the carbon-14 isotope.

Gregory McMichael and his son, Travis, were charged with murder and aggravated assault in relation to the shooting death of Ahmaud Arbery in February.

(Damon Runyon Cancer Research Foundation) The first class of Damon Runyon Quantitative Biology Fellowship Awardees launched their research in novel directions that may lead to the next breakthroughs in cancer research. Nine brilliant young scientists will apply their quantitative skills to design innovative experiments and interpret massive data sets that may help solve important biological and clinical problems.

Current regulations do not effectively prevent potentially misleading claims, says Imperial scientists

(University of Stirling) Understanding the health impacts of the COVID-19 pandemic on people who use drugs in Scotland is the focus of a new University of Stirling study.

(American Geriatrics Society) The American Geriatrics Society (AGS) and the AGS Health in Aging Foundation today announced that two expert researchers--Kavita Dharmarajan, MD, MSc, an assistant professor in the Department of Radiation Oncology and the Brookdale Department of Geriatrics and Palliative Medicine at the Icahn School of Medicine at Mount Sinai in N.Y.; and Nazema Siddiqui, MD, MHSc, an associate professor of obstetrics and gynecology at Duke University Medical Center in Durham, N.C.--will receive the 2020 Jeffrey H. Silverstein Memorial Award.

(American Geriatrics Society) The American Geriatrics Society (AGS) today announced that John B. Murphy, MD, a clinician, educator, and administrator working to embed geriatrics education in the fabric of medical curricula and clinical operations will be honored with the 2020 Dennis W. Jahnigen Award celebrating work to train health professionals in the care we all need as we age.

(American Geriatrics Society) The American Geriatrics Society (AGS) and AGS Health in Aging Foundation today announced that Alexander K. Smith, MD, MPH, an associate professor of medicine at UCSF and one of geriatrics' most influential rising researchers and advocates, will be honored with the 2020/2021 Thomas and Catherine Yoshikawa Award for Outstanding Scientific Achievement in Clinical Investigation.

(The Korea Advanced Institute of Science and Technology (KAIST)) A research team led by Distinguished Professor Sang-Yup Lee reported the production of a microbial strain capable of the massive production of succinic acid with the highest production efficiency to date. This strategy of integrating systems metabolic engineering with enzyme engineering will be useful for the production of industrially competitive bio-based chemicals.