We report postmortem cardio-pulmonary findings including detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in formalin-fixed paraffin embedded tissue in 12 patients with COVID-19. The 5 women and 7 men (median age: 73 years; range 35-96) died 6-38 days after onset of symptoms (median: 14.5 days). Eight patients received mechanical ventilation. Ten patients showed diffuse alveolar damage (DAD), 7 as exudative and 3 as proliferative/organizing DAD. One case presented as acute fibrinous and organizing pneumonia. Seven patients (58%) had acute bronchopneumonia, 1/7 without associated DAD and 1/7 with aspergillosis and necrotic bronchitis. Microthrombi were present in 5 patients, only in exudative DAD. Reverse transcriptase quantitative PCR detected high virus amounts in 6 patients (50%) with exudative DAD and symptom-duration ≤14 days, supported by immunohistochemistry and in-situ RNA hybridization (RNAscope). The 6 patients with low viral copy levels were symptomatic for ≥15 days, comprising all cases with organizing DAD, the patient without DAD and one exudative DAD. We show the high prevalence of DAD as a reaction pattern in COVID-19, the high number of overlying acute bronchopneumonia, and high-level pulmonary virus detection limited to patients who died ≤2 weeks after onset of symptoms, correlating with exudative phase of DAD.

Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine.

Spinal muscular atrophy is a severe motor neuron disease caused by reduced levels of the ubiquitous Survival of MotoNeurons (SMN) protein. SMN is part of a complex that is essential for spliceosomal UsnRNP biogenesis. Signal recognition particle (SRP) is a ribonucleoprotein particle crucial for co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum. SRP biogenesis is a nucleo-cytoplasmic multistep process in which the protein components, except SRP54, assemble with 7S RNA in the nucleolus. Then, SRP54 is incorporated after export of the pre-particle into the cytoplasm. The assembly factors necessary for SRP biogenesis remain to be identified. Here, we show that 7S RNA binds to purified SMN complexes in vitro and that SMN complexes associate with SRP in cellular extracts. We identified the RNA determinants required. Moreover, we report a specific reduction of 7S RNA levels in the spinal cord of SMN-deficient mice, and in a Schizosaccharomyces pombe strain carrying a temperature-degron allele of SMN. Additionally, microinjected antibodies directed against SMN or Gemin2 interfere with the association of SRP54 with 7S RNA in Xenopus laevis oocytes. Our data show that reduced levels of the SMN protein lead to defect in SRP steady-state level and describe the SMN complex as the first identified cellular factor required for SRP biogenesis.