Mejiabowers9024

BACKGROUND In contrast with the technical progress of the stethoscope, lung sound terminology has remained confused, weakening the usefulness of auscultation. We examined how observer preferences regarding terminology and auscultatory skill influenced the choice of terms used to describe lung sounds. METHODS Thirty-one staff physicians (SP), 65 residents (R) and 47 medical students (MS) spontaneously described the audio recordings of 5 lung sounds classified acoustically as (1) normal breath sound; (2) wheezes; (3) crackles; (4) stridor and (5) pleural friction rub. A rating was considered correct if a correct term or synonym was used to describe it (term use ascribed to preference). The use of any incorrect terms was ascribed to deficient auscultatory skill. RESULTS Rates of correct sound identification were (i) normal breath sound SP=21.4%; R=11.6%; MS=17.1%; (ii) wheezes SP=82.8%; R=85.2%; MS=86.4%; (iii) crackles SP=63%; R=68.5%; MS=70.7%; (iv) stridor SP=92.8%; R=90%; MS=72.1% and (v) pleural friction rus)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Metabolic rate underpins our understanding of how species survive, reproduce and interact with their environment, but can be difficult to measure in wild fish. Stable carbon isotopes (δ13C) in ear stones (otoliths) of fish may reflect lifetime metabolic signatures but experimental validation is required to advance our understanding of the relationship. To this end, we reared juvenile Australasian snapper (Chrysophrys auratus), an iconic fishery species, at different temperatures and used intermittent-flow respirometry to calculate standard metabolic rate (SMR), maximum metabolic rate (MMR) and absolute aerobic scope (AAS). Subsequently, we analysed δ13C and oxygen isotopes (δ18O) in otoliths using isotope-ratio mass spectrometry. We found that under increasing temperatures, δ13C and δ18O significantly decreased, while SMR and MMR significantly increased. Negative logarithmic relationships were found between δ13C in otoliths and both SMR and MMR, while exponential decay curves were observed between proportions of metabolically sourced carbon in otoliths (M oto) and both measured and theoretical SMR. We show that basal energy for subsistence living and activity metabolism, both core components of field metabolic rates, contribute towards incorporation of δ13C into otoliths and support the use of δ13C as a metabolic proxy in field settings. The functional shapes of the logarithmic and exponential decay curves indicated that physiological thresholds regulate relationships between δ13C and metabolic rates due to upper thresholds of M oto Here, we present quantitative experimental evidence to support the development of an otolith-based metabolic proxy, which could be a powerful tool in reconstructing lifetime biological trends in wild fish. © 2020. Published by The Company of Biologists Ltd.U2 and U6 small nuclear (sn)RNAs are the only snRNAs directly implicated in catalyzing the splicing of pre-mRNA, but assembly and rearrangement steps prior to catalysis require numerous proteins. Previous studies have shown that the protein-free U2-U6 snRNA complex adopts two conformations in equilibrium, characterized by four and three helices surrounding a central junction. The four-helix conformer is strongly favored in the in vitro protein-free state, but the three-helix conformer predominates in spliceosomes. To analyze the role of the central junction in positioning elements forming the active site, we derived three-dimensional models of the two conformations from distances measured between fluorophores at selected locations in constructs representing the protein-free human U2-U6 snRNA complex by time-resolved fluorescence resonance energy transfer. Data describing four angles in the four-helix conformer suggest tetrahedral geometry; addition of Mg2+ results in shortening of the distances between neighboring helices, indicating compaction of the complex around the junction. In contrast, the three-helix conformer shows a closer approach between helices bearing critical elements, but addition of Mg2+ widens the distance between them; thus in neither conformer are the critical helices positioned to favor the proposed triplex interaction. Presence of Mg2+ also enhances the fraction of the three-helix conformer, as does incubation with the Prp19-related protein RBM22, which has been implicated in the remodeling of the U2-U6 snRNA complex to render it catalytically active. These data suggest that although the central junction assumes a significant role in orienting helices, spliceosomal proteins and Mg2+ facilitate formation of the catalytically active conformer.  . Published by Cold Spring Harbor Laboratory Press for the RNA Society.Subcellular localization is essential to RNA biogenesis, processing, and function across the gene expression life cycle. However, the specific nucleotide sequence motifs that direct RNA localization are incompletely understood. Fortunately, new sequencing technologies have provided transcriptome-wide atlases of RNA localization, creating an opportunity to leverage computational modeling. Here we present RNA-GPS, a new machine learning model that uses nucleotide-level features to predict RNA localization across 8 different subcellular locations - the first to provide such a wide range of predictions. Selleck Repertaxin RNA-GPS's design enables high throughput sequence ablation and feature importance analyses to probe the sequence motifs that drive localization prediction. We find localization informative motifs to be concentrated on 3' UTRs and scattered along the coding sequence, and motifs related to splicing to be important drivers of predicted localization, even for cytotopic distinctions for membraneless bodies within the nucleus or for organelles within the cytoplasm. Overall, our results suggest transcript splicing is one of many elements influencing RNA subcellular localization. Published by Cold Spring Harbor Laboratory Press for the RNA Society.PURPOSE We assessed plasma circulating tumor DNA (ctDNA) level as a prognostic marker for progression-free survival (PFS) following first-line metastatic colorectal cancer (mCRC) therapy. EXPERIMENTAL DESIGN STEAM was a randomized, phase II trial investigating efficacy of bevacizumab (BEV) plus 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) and 5-fluorouracil/leucovorin/irinotecan (FOLFIRI), administered concurrently or sequentially, versus FOLFOX-BEV in first-line mCRC. Evaluation of biomarkers associated with treatment outcomes was an exploratory endpoint. Patients in the biomarker evaluable population (BEP) had 1 tissue sample, 1 pre-induction plasma sample, and 1 post-induction plasma sample collected ≤60 days of induction from last drug date. RESULTS Among the 280 patients enrolled in STEAM, 183 had sequenced and evaluable tumor tissue, 118 had matched pre-induction plasma, and 54 (BEP) had ctDNA-evaluable sequencing data for pre- and post-induction plasma. The most common somatic variants in tumor tissue and pre-induction plasma were TP53, APC, and KRAS Patients with lower-than-median versus higher-than-median post-induction mean allele fraction (mAF) levels had longer median PFS (17.