Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease's complex pathophysiology, yet ...these cells have been little studied.
To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared with healthy volunteer cells, and to define their sensitivity to phosphoinositide 3-kinase inhibition.
Twenty-three ventilated patients underwent bronchoalveolar lavage. Alveolar and blood neutrophil apoptosis, phagocytosis, and adhesion molecules were quantified by flow cytometry, and oxidase responses were quantified by chemiluminescence. Cytokine and transcriptional profiling were used in multiplex and GeneChip arrays.
Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed constitutive apoptosis, and primed oxidase responses. Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype, and this could be reversed by phosphoinositide 3-kinase inhibitors. In contrast, the prosurvival phenotype of patient cells was resistant to phosphoinositide 3-kinase inhibition. RNA transcriptomic analysis revealed modified immune, cytoskeletal, and cell death pathways in patient cells, aligning closely to sepsis and burns datasets but not to phosphoinositide 3-kinase signatures.
Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed prosurvival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase-dependent but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells.
Diel vertical migration is a widespread behavioral phenomenon where organisms migrate through the water column and may modify behavior relative to changing environmental conditions based on ...physiological tolerances. Here, we combined a novel suite of biologging technologies to examine the thermal physiology (intramuscular temperature), fine-scale swimming behavior and activity (overall dynamic body acceleration as a proxy for energy expenditure) of bluntnose sixgill sharks (Hexanchus griseus) in response to environmental changes (depth, water temperature, dissolved oxygen) experienced during diel vertical migrations. In the subtropical waters off Hawai'i, sixgill sharks undertook pronounced diel vertical migrations and spent considerable amounts of time in cold (5-7°C), low oxygen conditions (10-25% saturation) during their deeper daytime distribution. Further, sixgill sharks spent the majority of their deeper daytime distribution with intramuscular temperatures warmer than ambient water temperatures, thereby providing them with a significant thermal advantage over non-vertically migrating and smaller-sized prey. Sixgill sharks exhibited relatively high rates of activity during both shallow (night) and deep (day) phases and contrary to our predictions, did not reduce activity levels during their deeper daytime distribution while experiencing low temperature and dissolved oxygen levels. This demonstrates an ability to tolerate the low oxygen conditions occurring within the local oxygen minimum zone. The novel combination of biologging technologies used here enabled innovative in situ deep-sea natural experiments and provided significant insight into the behavioral and physiological ecology of an ecologically important deepwater species.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The El Niño–Southern Oscillation (ENSO) represents the largest source of year‐to‐year global climate variability. While Earth system models suggest a range of possible shifts in ENSO properties under ...continued greenhouse gas forcing, many centuries of preindustrial climate data are required to detect a potential shift in the properties of recent ENSO extremes. Here we reconstruct the strength of ENSO variations over the last 7,000 years with a new ensemble of fossil coral oxygen isotope records from the Line Islands, located in the central equatorial Pacific. The corals document a significant decrease in ENSO variance of ~20% from 3,000 to 5,000 years ago, coinciding with changes in spring/fall precessional insolation. We find that ENSO variability over the last five decades is ~25% stronger than during the preindustrial. Our results provide empirical support for recent climate model projections showing an intensification of ENSO extremes under greenhouse forcing.
Plain Language Summary
Recent modeling studies suggest that El Niño will intensify due to greenhouse warming. Here new coral reconstructions of the El Niño–Southern Oscillation (ENSO) record sustained, significant changes in ENSO variability over the last 7,000 years and imply that ENSO extremes of the last 50 years are significantly stronger than those of the preindustrial era in the central tropical Pacific. These records suggest that El Niño events already may be intensifying due to anthropogenic climate change.
Key Points
Line Island corals provide 1,751 years of monthly resolved ENSO variability from the mid‐Holocene to present
ENSO strength is significantly weaker between 3,000 and 5,000 years ago compared to the 2,000‐year periods both before and after
ENSO extremes of the last 50 years are significantly stronger than those of the preindustrial era in the central tropical Pacific
We developed a single step, cation-exchange reaction that produces air-stable PbSe quantum dots (QDs) from ZnSe QDs and PbX2 (X = Cl, Br, or I) precursors. The resulting PbSe QDs are terminated with ...halide anions and contain residual Zn cations. We characterized the PbSe QDs using UV–vis–NIR absorption, photoluminescence quantum yield spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy. Solar cells fabricated from these PbSe QDs obtained an overall best power conversion efficiency of 6.47% at one sun illumination. The solar cell performance without encapsulation remains unchanged for over 50 days in ambient conditions; and after 50 days, the National Renewable Energy Laboratory certification team certified the device at 5.9%.
Abstract
Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in ...the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of interfaces to genomic data across the tree of life, including reference genome sequence, gene models, transcriptional data, genetic variation and comparative analysis. Data may be accessed via our website, online tools platform and programmatic interfaces, with updates made four times per year (in synchrony with Ensembl). Here, we provide an overview of Ensembl Genomes, with a focus on recent developments. These include the continued growth, more robust and reproducible sets of orthologues and paralogues, and enriched views of gene expression and gene function in plants. Finally, we report on our continued deeper integration with the Ensembl project, which forms a key part of our future strategy for dealing with the increasing quantity of available genome-scale data across the tree of life.
Blood vessels in the body are lined with endothelial cells which have vital roles in numerous physiological and pathological processes. Collagens are major constituents of the extracellular matrix, ...and many adherent cells express several collagen-binding adhesion receptors. Here, we study the endothelium-collagen interactions mediated by the collagen-binding integrins, α1β1, α2β1, α10β1 and α11β1 expressed in human umbilical vein endothelial cells (HUVECs). Using qPCR, we found expression of the α10 transcript of the chondrocyte integrin, α10β1, along with the more abundant α2, and low-level expression of α1. The α11 transcript was not detected. Inhibition or siRNA knockdown of the α2-subunit resulted in impaired HUVEC adhesion, spreading and migration on collagen-coated surfaces, whereas inhibition or siRNA knockdown of α1 had no effect on these processes. In tube formation assays, inhibition of either α1 or α2 subunits impaired the network complexity, whereas siRNA knockdown of these integrins had no such effect. Knockdown of α10 had no effect on cell spreading, migration or tube formation in these conditions. Overall, our results indicate that the collagen-binding integrins, α1β1 and α2β1 play a central role in endothelial cell motility and self-organisation.
The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the ...phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2519 out of 5385) of the GWAS loci examined.
During the COVID-19 pandemic, there were alarming reports of children missing out on online special educational activities due to a lack of access to those resources. We evaluated a simple online ...intervention using a concurrent multiple baseline design for three second-grade students with disabilities who unreliably accessed the remote curriculum. The dependent variable was the number of daily assignments completed. During baseline, the teacher provided students and parents with educational activities via Google Classroom, and the teacher contacted parents when a student missed educational activities. For intervention, the teacher implemented a task analysis that listed five daily assignments. Students earned preferred rewards contingent on completing all activities. Results showed that the intervention was effective in increasing engagement in online learning.
Abstract
The evolutionary fitness payoffs of moral condemnation are greatest within an individual’s immediate social milieu. Accordingly, insofar as human moral intuitions have been shaped by ...adaptive design, we can expect transgressive harms to be perceived as more wrong when transpiring in the here and now than when occurring at a distance, or with the approval of local authority figures. This
moral parochialism
hypothesis has been supported by research conducted in diverse societies, but has yet to be tested in an East Asian society, despite prior research indicating that East Asians appraise transgressive acts as being caused by situational and contextual factors to a greater extent than do Westerners, who tend to emphasize dispositional factors (i.e., the transgressor’s personal nature). Here, in a quasi-experiment using field samples recruited in Seoul and Los Angeles, we tested (i) the moral parochialism hypothesis regarding the perceived wrongness of transgressions, as well as (ii) the extent to which these wrongness judgments might be influenced by cross-cultural differences in causal appraisals. Despite notably large differences across the two societies in situational versus dispositional appraisals of the causes of the transgressions, replicating previous findings elsewhere, in both societies we found that transgressions were deemed less wrong when occurring at spatial or temporal remove or with the consent of authorities. These findings add to the understanding of morality as universally focused on local affairs, notwithstanding cultural variation in perceptions of the situational versus dispositional causes of (im)moral acts.
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