Dobsonhawley8336

Pine Island Glacier and Thwaites Glacier in the Amundsen Sea Embayment are among the fastest changing outlet glaciers in West Antarctica with large consequences for global sea level. Yet, assessing how much and how fast both glaciers will weaken if these changes continue remains a major uncertainty as many of the processes that control their ice shelf weakening and grounding line retreat are not well understood. Here, we combine multisource satellite imagery with modeling to uncover the rapid development of damage areas in the shear zones of Pine Island and Thwaites ice shelves. These damage areas consist of highly crevassed areas and open fractures and are first signs that the shear zones of both ice shelves have structurally weakened over the past decade. Idealized model results reveal moreover that the damage initiates a feedback process where initial ice shelf weakening triggers the development of damage in their shear zones, which results in further speedup, shearing, and weakening, hence promoting additional damage development. This damage feedback potentially preconditions these ice shelves for disintegration and enhances grounding line retreat. The results of this study suggest that damage feedback processes are key to future ice shelf stability, grounding line retreat, and sea level contributions from Antarctica. Moreover, they underline the need for incorporating these feedback processes, which are currently not accounted for in most ice sheet models, to improve sea level rise projections.At the beginning of life, inexperienced babies and human fetuses, domestic chicks, and monkeys exhibit a preference for faces and face-like configurations (three blobs arranged like an upside-down triangle). Because all of these species have parental care, it is not clear whether the early preference for faces is a mechanism for orienting toward the conspecifics and sustaining parental care, or a more general mechanism to attend to living beings. We contrasted these hypotheses by testing inexperienced hatchlings of five species of tortoises, solitary animals with no parental care. If early face-like preference evolved in the context of parental care, solitary species should not exhibit it. We observed that visually naïve tortoises prefer to approach face-like patterns over alternative configurations. The predisposition to approach face-like stimuli observed in hatchlings of these solitary species suggests the presence of an ancient mechanism, ancestral to the evolution of reptiles and mammals, that sustains the exploratory responses, and potentially learning, in both solitary and social species.Calcium signals are initiated in immune cells by the process of store-operated calcium entry (SOCE), where receptor activation triggers transient calcium release from the endoplasmic reticulum, followed by opening of plasma-membrane calcium-release activated calcium (CRAC) channels. ORAI1, ORAI2, and ORAI3 are known to comprise the CRAC channel; however, the contributions of individual isoforms to neutrophil function are not well understood. Here, we show that loss of ORAI1 partially decreases calcium influx, while loss of both ORAI1 and ORAI2 completely abolishes SOCE. In other immune-cell types, loss of ORAI2 enhances SOCE. CK-666 In contrast, we find that ORAI2-deficient neutrophils display decreased calcium influx, which is correlated with measurable differences in the regulation of neutrophil membrane potential via KCa3.1. Decreased SOCE in ORAI1-, ORAI2-, and ORAI1/2-deficient neutrophils impairs multiple neutrophil functions, including phagocytosis, degranulation, leukotriene, and reactive oxygen species (ROS) production, rendering ORAI1/2-deficient mice highly susceptible to staphylococcal infection. This study demonstrates that ORAI1 and ORAI2 are the primary components of the neutrophil CRAC channel and identifies subpopulations of neutrophils where cell-membrane potential functions as a rheostat to modulate the SOCE response. These findings have implications for mechanisms that modulate neutrophil function during infection, acute and chronic inflammatory conditions, and cancer.Like most RNA viruses, influenza viruses generate defective viral genomes (DVGs) with large internal deletions during replication. There is accumulating evidence supporting a biological relevance of such DVGs. However, further understanding of the molecular mechanisms that underlie the production and biological activity of DVGs is conditioned upon the sensitivity and accuracy of detection methods, that is, next-generation sequencing (NGS) technologies and related bioinformatics algorithms. Although many algorithms were developed, their sensitivity and reproducibility were mostly assessed on simulated data. Here, we introduce DG-seq, a time-efficient pipeline for DVG detection and quantification, and a set of biological controls to assess the performance of not only our bioinformatics algorithm but also the upstream NGS steps. Using these tools, we provide the first rigorous comparison of the two commonly used sample processing methods for RNA-seq, with or without a PCR preamplification step. Our data show that preamplification confers a limited advantage in terms of sensitivity and introduces size- but also sequence-dependent biases in DVG quantification, thereby providing a strong rationale to favor preamplification-free methods. We further examine the features of DVGs produced by wild-type and transcription-defective (PA-K635A or PA-R638A) influenza viruses, and show an increased diversity and frequency of DVGs produced by the PA mutants compared to the wild-type virus. Finally, we demonstrate a significant enrichment in DVGs showing direct, A/T-rich sequence repeats at the deletion breakpoint sites. Our findings provide novel insights into the mechanisms of influenza virus DVG production.RNA-based therapies, including RNA molecules as drugs and RNA-targeted small molecules, offer unique opportunities to expand the range of therapeutic targets. Various forms of RNAs may be used to selectively act on proteins, transcripts, and genes that cannot be targeted by conventional small molecules or proteins. Although development of RNA drugs faces unparalleled challenges, many strategies have been developed to improve RNA metabolic stability and intracellular delivery. A number of RNA drugs have been approved for medical use, including aptamers (e.g., pegaptanib) that mechanistically act on protein target and small interfering RNAs (e.g., patisiran and givosiran) and antisense oligonucleotides (e.g., inotersen and golodirsen) that directly interfere with RNA targets. Furthermore, guide RNAs are essential components of novel gene editing modalities, and mRNA therapeutics are under development for protein replacement therapy or vaccination, including those against unprecedented severe acute respiratory syndrome coronavirus pandemic.