Near-axis seamounts as probes of mantle melting at the East Pacific Rise

Understanding how melts are generated and focused from the upper mantle to mid-ocean ridges is imperative to understanding how the majority of Earths lithosphere is formed. The classic paradigm is that, as melts are produced due to decompression at mid-ocean spreading centers, they migrate 100s of kilometers to the ridge axis where they are erupted on the sea floor to form new oceanic crust. However, it is very difficult to test the hypothesis of three-dimensional melt migration because the majority of mid-ocean ridge basalt samples come from the ridge axis. Near-axis seamounts provide excellent opportunities to test hypotheses of melt distribution and variation in melt sources because they act as geochemical probes that tap into the melt of the upper mantle as it rises to the ridge axis. The region of interest in this study is the East Pacific Rise and the seamount chains located between 14'N and 4'N. Here, a total of eight near-axis chains have been sampled and analyzed for basalt lava composition. Major element data derived from glass and whole rock analyses are used to produce chemical variation diagrams and liquid lines of decent plots for the seamount rock suites. Geodynamic models that combine mantle convection, melt generation, and melt migration are used to predict the composition variation that is expected at the East Pacific Rise. Real world data are combined with the model predictions to investigate near-axis melt migration processes. We compare the data and the models to test the hypotheses for melt migration and creation of near-axis seamounts. The results provide a view of the complexities of melt migration and the formation of new crust at mid-ocean ridgesOpe

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

A new chemical probe for phosphatidylinositol kinase activity

Phosphatidylinositol kinases (PIKs) are key enzymatic regulators of membrane phospholipids and membrane environments that control many aspects of cellular function, from signal transduction to secretion, through the Golgi apparatus. Here, we have developed a photoreactive "clickable" probe, PIK-BPyne, to report the activity of PIKs. We investigated the selectivity and efficiency of the probe to both inhibit and label PIKs, and we compared PIK-BPyne to a wortmannin activity-based probe also known to target PIKs. We found that PIK-BPyne can act as an effective in situ activity-based probe, and for the first time, report changes in PI4K-III\u3b2 activity induced by the hepatitis C virus. These results establish the utility of PIK-BPyne for activity-based protein profiling studies of PIK function in native biological systems. Active PIKs: Phosphatidylinositol kinases (PIKs) are key enzymatic regulators of membrane phospholipids and environments that control many aspects of cellular function, from signal transduction to secretion. We developed a photoreactive "clickable" probe, PIK-BPyne, to assess activity of PIKs in native biological systems and demonstrated its ability to monitor hepatitis C virus-induced changes in PIK-III\u3b2 activity.Peer reviewed: YesNRC publication: Ye