Structural Studies of Wnts and Identification of an LRP6 Binding Site

SummaryWnts are secreted growth factors that have critical roles in cell fate determination and stem cell renewal. The Wnt/β-catenin pathway is initiated by binding of a Wnt protein to a Frizzled (Fzd) receptor and a coreceptor, LDL receptor-related protein 5 or 6 (LRP5/6). We report the 2.1 Å resolution crystal structure of a Drosophila WntD fragment encompassing the N-terminal domain and the linker that connects it to the C-terminal domain. Differences in the structures of WntD and Xenopus Wnt8, including the positions of a receptor-binding β hairpin and a large solvent-filled cavity in the helical core, indicate conformational plasticity in the N-terminal domain that may be important for Wnt-Frizzled specificity. Structure-based mutational analysis of mouse Wnt3a shows that the linker between the N- and C-terminal domains is required for LRP6 binding. These findings provide important insights into Wnt function and evolution

A multicenter study of acute testicular torsion in the time of COVID-19

Background: Testicular torsion is a surgical emergency, and time to detorsion is imperative for testicular salvage. During the COVID-19 pandemic, patients may delay emergency care due to stay-at-home orders and concern of COVID-19 exposure. Objective: To assess whether emergency presentation for testicular torsion was delayed during the COVID-19 pandemic, and whether the rate of orchiectomy increased compared to a retrospective period. Study design: Patients were prospectively enrolled in a multicenter study from seven institutions in the United States and Canada. Inclusion criteria were patients two months to 18 years of age with acute testicular torsion from March through July 2020. The retrospective group included patients from January 2019 through February 2020. Statistical analysis was performed using Kruskal–Wallis tests, Chi-square tests, and logistic regression. Results: A total of 221 patients were included: 84 patients in the COVID-19 cohort and 137 in the retrospective cohort. Median times from symptom onset to emergency department presentation during COVID-19 compared to the retrospective period were 17.9 h (IQR 5.5–48.0) and 7.5 h (IQR 4.0–28.0) respectively (p = 0.04). In the COVID-19 cohort, 42% of patients underwent orchiectomy compared to 29% of pre-pandemic controls (p = 0.06). During COVID-19, 46% of patients endorsed delay in presentation compared to 33% in the retrospective group (p = 0.04). Discussion: We found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a higher proportion of patients reported delaying care. Strengths of the study include the number of included patients and the multicenter prospective design during the pandemic. Limitations include a retrospective pre-pandemic comparison group. Conclusions: In a large multicenter study we found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a significantly higher proportion of patients reported delaying care. Based on the findings of this study, more patient education is needed on the management of testicular torsion during a pandemic

A multicenter study of acute testicular torsion in the time of COVID-19

Background: Testicular torsion is a surgical emergency, and time to detorsion is imperative for testicular salvage. During the COVID-19 pandemic, patients may delay emergency care due to stay-at-home orders and concern of COVID-19 exposure. Objective: To assess whether emergency presentation for testicular torsion was delayed during the COVID-19 pandemic, and whether the rate of orchiectomy increased compared to a retrospective period. Study design: Patients were prospectively enrolled in a multicenter study from seven institutions in the United States and Canada. Inclusion criteria were patients two months to 18 years of age with acute testicular torsion from March through July 2020. The retrospective group included patients from January 2019 through February 2020. Statistical analysis was performed using Kruskal–Wallis tests, Chi-square tests, and logistic regression. Results: A total of 221 patients were included: 84 patients in the COVID-19 cohort and 137 in the retrospective cohort. Median times from symptom onset to emergency department presentation during COVID-19 compared to the retrospective period were 17.9 h (IQR 5.5–48.0) and 7.5 h (IQR 4.0–28.0) respectively (p = 0.04). In the COVID-19 cohort, 42% of patients underwent orchiectomy compared to 29% of pre-pandemic controls (p = 0.06). During COVID-19, 46% of patients endorsed delay in presentation compared to 33% in the retrospective group (p = 0.04). Discussion: We found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a higher proportion of patients reported delaying care. Strengths of the study include the number of included patients and the multicenter prospective design during the pandemic. Limitations include a retrospective pre-pandemic comparison group. Conclusions: In a large multicenter study we found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a significantly higher proportion of patients reported delaying care. Based on the findings of this study, more patient education is needed on the management of testicular torsion during a pandemic

Ocean Acidification at High Latitudes: Potential Effects on Functioning of the Antarctic Bivalve Laternula elliptica

Ocean acidification is a well recognised threat to marine ecosystems. High latitude regions are predicted to be particularly affected due to cold waters and naturally low carbonate saturation levels. This is of concern for organisms utilising calcium carbonate (CaCO3) to generate shells or skeletons. Studies of potential effects of future levels of pCO2 on high latitude calcifiers are at present limited, and there is little understanding of their potential to acclimate to these changes. We describe a laboratory experiment to compare physiological and metabolic responses of a key benthic bivalve, Laternula elliptica, at pCO2 levels of their natural environment (430 µatm, pH 7.99; based on field measurements) with those predicted for 2100 (735 µatm, pH 7.78) and glacial levels (187 µatm, pH 8.32). Adult L. elliptica basal metabolism (oxygen consumption rates) and heat shock protein HSP70 gene expression levels increased in response both to lowering and elevation of pH. Expression of chitin synthase (CHS), a key enzyme involved in synthesis of bivalve shells, was significantly up-regulated in individuals at pH 7.78, indicating L. elliptica were working harder to calcify in seawater undersaturated in aragonite (ΩAr = 0.71), the CaCO3 polymorph of which their shells are comprised. The different response variables were influenced by pH in differing ways, highlighting the importance of assessing a variety of factors to determine the likely impact of pH change. In combination, the results indicate a negative effect of ocean acidification on whole-organism functioning of L. elliptica over relatively short terms (weeks-months) that may be energetically difficult to maintain over longer time periods. Importantly, however, the observed changes in L. elliptica CHS gene expression provides evidence for biological control over the shell formation process, which may enable some degree of adaptation or acclimation to future ocean acidification scenarios

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data