Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.MethodsRECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes.DiscussionRECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC

Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes

Summary: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase with important roles in many cellular processes as well as in cancer and other diseases. EGF binding promotes EGFR dimerization and autophosphorylation through interactions that are well understood structurally. How these dimers relate to higher-order EGFR oligomers seen in cell membranes, however, remains unclear. Here, we used single-particle tracking (SPT) and Förster resonance energy transfer imaging to examine how each domain of EGFR contributes to receptor oligomerization and the rate of receptor diffusion in the cell membrane. Although the extracellular region of EGFR is sufficient to drive receptor dimerization, we find that the EGF-induced EGFR slowdown seen by SPT requires higher-order oligomerization—mediated in part by the intracellular tyrosine kinase domain when it adopts an active conformation. Our data thus provide important insight into the interactions required for higher-order EGFR assemblies involved in EGF signaling

Tropical Atlantic Observing System (TAOS) : review report

The tropical Atlantic observing system was last reviewed in 2006 by CLIVAR (Climate and Ocean: Variability, Predictability and Change) and GCOS-GOOS-WCRP through the OOPC (Ocean Observations Panel for Climate), with a primary focus on PIRATA (Prediction and Research Moored Array in the Tropical Atlantic). Since then, the CLIVAR Tropical Atlantic Climate Experiment (TACE) and the EU program Enhancing Prediction of Tropical Atlantic Climate and its Impacts (PREFACE) have been completed. Scientific priorities and observational technologies have evolved since 2006 and in parallel the observing system has evolved. For example, Argo is now fully developed and has been operating successfully for more than ten years. PIRATA has also expanded to new sites and has enhanced its measurement suite with higher vertical resolution in the mixed layer, and new CO2 and O2 measurements. It is therefore timely to systematically review the requirements for sustained observations in the tropical Atlantic, to critically review the design of the sustained observing system in order to take advantage of what has been learned to date, to collectively identify new opportunities to build on past accomplishments, and to explore the possibility for expanded interdisciplinary initiatives with other communities, e.g. in biogeochemistry.To that end, a Tropical Atlantic Observing System (TAOS) review was proposed by the CLIVAR Atlantic Region Panel (ARP) and has been organized by the CLIVAR ARP in close cooperation with the PIRATA consortium. The review is intended to evaluate scientific progress since the last review and recommend actions to advance sustained observing efforts in the tropical Atlantic