A large-scale transcontinental river system crossed West Antarctica during the Eocene

Extensive ice coverage largely prevents investigations of Antarctica’s unglaciated past. Knowledge about environmental and tectonic development before large-scale glaciation, however, is important for understanding the transition into the modern icehouse world. We report geochronological and sedimentological data from a drill core from the Amundsen Sea shelf, providing insights into tectonic and topographic conditions during the Eocene (~44 to 34 million years ago), shortly before major ice sheet buildup. Our findings reveal the Eocene as a transition period from &gt;40 million years of relative tectonic quiescence toward reactivation of the West Antarctic Rift System, coinciding with incipient volcanism, rise of the Transantarctic Mountains, and renewed sedimentation under temperate climate conditions. The recovered sediments were deposited in a coastal-estuarine swamp environment at the outlet of a &gt;1500-km-long transcontinental river system, draining from the rising Transantarctic Mountains into the Amundsen Sea. Much of West Antarctica hence lied above sea level, but low topographic relief combined with low elevation inhibited widespread ice sheet formation.</jats:p

Enhanced Fusion Pore Expansion Mediated by the Trans-Acting Endodomain of the Reovirus FAST Proteins

The reovirus fusion-associated small transmembrane (FAST) proteins are virus-encoded membrane fusion proteins that function as dedicated cell–cell fusogens. The topology of these small, single-pass membrane proteins orients the majority of the protein on the distal side of the membrane (i.e., inside the cell). We now show that ectopic expression of the endodomains of the p10, p14, and p15 FAST proteins enhances syncytiogenesis induced by the full-length FAST proteins, both homotypically and heterotypically. Results further indicate that the 68-residue cytoplasmic endodomain of the p14 FAST protein (1) is endogenously generated from full-length p14 protein expressed in virus-infected or transfected cells; (2) enhances syncytiogenesis subsequent to stable pore formation; (3) increases the syncytiogenic activity of heterologous fusion proteins, including the differentiation-dependent fusion of murine myoblasts; (4) exerts its enhancing activity from the cytosol, independent of direct interactions with either the fusogen or the membranes being fused; and (5) contains several regions with protein–protein interaction motifs that influence enhancing activity. We propose that the unique evolution of the FAST proteins as virus-encoded cellular fusogens has allowed them to generate a trans-acting, soluble endodomain peptide to harness a cellular pathway or process involved in the poorly understood process that facilitates the transition from microfusion pores to macrofusion and syncytiogenesis

Esophageal motor abnormalities in scleroderma and related diseases

Esophageal motor activity was measured by intra-esophageal pressure recordings in 53 patients with scleroderma and 29 patients with other collagen diseases. The purpose of the study was to determine the relationship of motor abnormalities to esophageal symptoms, to compare the abnormalities in scleroderma with those in other collagen diseases, and to try to increase understanding of the responsible mechanism. Methacholine was given to 36 of the 53 patients with scleroderma to confirm that the Mecholyl test is negative in scleroderma and to see whether intraluminal pressure changes accompany the resulting improvement in esophageal emptying.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44360/1/10620_2005_Article_BF02233564.pd

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The HtrA family of proteases: implications for protein composition and cell fate

Cells precisely monitor the concentration and functionality of each protein for optimal performance. Protein quality control involves molecular chaperones, folding catalysts, and proteases that are often heat shock proteins. One quality control factor is HtrA, one of a new class of oligomeric serine proteases. The defining feature of the HtrA family is the combination of a catalytic domain with at least one C-terminal PDZ domain. Here, we discuss the properties and roles of this ATP-independent protease chaperone system in protein metabolism and cell fate

Monetary policy and the banking sector in Turkey

We find that monetary policy influenced Turkish bank lending between 1991 and 2007 through the money and bank lending channels. While capital and GDP growth have positive and significant long-run effects on bank loan growth, inflation, bank size and efficiency are not significant determinants. The latter is despite our finding that all Turkish banks’ efficiency improved over the period. Domestic banks are unexpectedly found to be more efficient than foreign banks. With no evident dynamics or fixed-effects in loan growth we prefer the pooled-OLS estimator. We caution against assuming fixed-effects and dynamics are present as this may adversely affect inference

Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy in the Adult ICU Setting

International audienceBackground: High-flow nasal cannula (HFNC) oxygen therapy has been broadly used. However, no consensus has been achieved on the practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult patients.Methods: An online anonymous questionnaire survey endorsed by 4 academic societies from America, Europe, mainland China, and Taiwan was administered from May to December 2019. Clinicians who had worked in adult ICUs for > 1 year and had used HFNC to treat patients within 30 days were included.Results: A total of 2,279 participants clicked on the survey link, 1,358 respondents completed the HFNC section of the questionnaire, whereas 1,014 completed the whole survey. Postextubation hypoxemia and moderate hypoxemia were major indications for HFNC. The initial flow was mainly set at 40-50 L/min. Aerosol delivery via HFNC was used by 24% of the participants (248/1,014), 30% (74/248) of whom reported reducing flow during aerosol delivery. For the patients who required aerosol treatment during HFNC therapy, 40% of the participants (403/1,014) reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC whereas 33% (331/1,014) discontinued HFNC to use conventional aerosol devices. A vibrating mesh nebulizer was the most commonly used nebulizer (40%) and was mainly placed at the inlet of the humidifier.Conclusions: The clinical utilization of HFNC was variable, as were indications, flow settings, and criteria for adjustment. Many practices associated with concomitant aerosol therapy were not consistent with available evidence for optimal use. More efforts are warranted to close the knowledge gap

Insights into the tectonic and climatic evolution of West Antarctica from the Amundsen Sea sediment record

West Antarctica hosts one of the largest continental rift systems on earth. Due to the extensive ice cover and the lack of exposed sedimentary rocks, little is known about the detailed geological and climatic evolution of West Antarc- tica. Here we present initial geochronologic, petrographic, stratigraphic, palynologic and clay mineralogy data of the first drill cores from the Amundsen Sea, off West Antarctica. The drilled succession revealed fine-grained, plant- bearing sediments of late Cretaceous age (∼93 to 85 Ma), deposited during continental stretching and breakup between West Antarctica and New Zealand. The Cretaceous deposits are separated by a peat layer from coarse- grained sandstones, which contain zircon and apatite yielding U-Pb ages of ca. 46-39 Ma. This implies a hiatus of at least 40 Myr between the fine-grained Cretaceous deposits and the overlying sandstones, which is in agreement with the absence of in-situ or reworked Paleocene to early/mid-Eocene palynomorphs. We tentatively interpret this hiatus as reflecting tectonic quiescence and slow downwearing, or non-deposition. This interpretation supports our previous thermochronological data from the onshore realm, which show that extension-related exhumation ceased at the end of the Cretaceous. We interpret renewed deposition during the upper Eocene to Oligocene to reflect renewed rapid exhumation along the West Antarctic Rift System and the rise of the Transantarctic Mountains. As well as the Eocene dates, the Eocene to Oligocene sandstones contain Cambro-Silurian, Permo-Triassic, Early Jurassic and Cretaceous apatite U-Pb age groups, which we interpret as derived from the Transantarctic Moun- tains (igneous and metamorphic rocks of the Cambro-Ordovician Ross Orogeny, and volcanic rocks related to the Early Jurassic Ferrar volcanic event) and Marie Byrd Land / West Antarctica (Permo-Triassic magmatic arc and widespread Cretaceous batholiths). Unusual for this kind of lithology, the sandstones’ apatite yield is low, and lattice defects of apatite grains frequently show etching features. Cretaceous rhyolite clasts, abundant in the sandstones, are sometimes heavily kaolinized, and the clay fraction of the sandstones contains up to >70% kaoli- nite. All these features, along with the results of palynology, imply an acidic, swamp-like deposition environment characterised by moderate to strong chemical weathering, and a temperate climate with warm intervals, becoming cooler towards the Oligocene