Poetry at the End of the World

Agli inizi della poesia apocalittica durante la Guerra Fredda, gli scrittori americani si sono concentrati specialmente sulla bomba. Dagli anni Ottanta, invece, i poeti hanno scelto altri approcci – politici, religiosi, ambientali – con cui esplorare il tema apocalittico, considerato non necessariamente come un avvenimento alla fine dei tempi, ma come un’attuale esperienza di crisi, o addirittura evento già passato (o “post”). Mark Strand, Jorie Graham e John Ashbery vengono presi in esame per la spiccata originalità della loro poesia apocalittica postmoderna

Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome

Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations — a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient‐parent trios, from the NIDDK‐supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a pre‐specified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious bi‐allelic variants in polycystin 1‐like 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other non‐cholestatic diseases. Conclusion WES identified bi‐allelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome

COVID-19 outcomes in UK centre within highest health and wealth band: a prospective cohort study.

OBJECTIVES: To describe the characteristics and outcomes of hospitalised patients with COVID-19 from UK in the highest decile of health and gross regional products per capita. DESIGN: Prospective cohort study. SETTING: Recruited all adult inpatients with laboratory-confirmed COVID-19 symptoms admitted to a single Surrey centre between March and April 2020. Extensive demographic details were documented. OUTCOME MEASURE: COVID-19 status of alive/dead and intensive care unit (ICU) status of yes/no. PARTICIPANTS: Patients with COVID-19 from Surrey centre UK (n=429). RESULTS: 429 adult inpatients (mean age 70±18 years; men 56.4%) were included in this study, of whom, 19.1% required admission to ICU and 31.9% died. Adverse outcomes were associated with age (OR with each decade of years: 1.78, 95% CI 1.53 to 2.11, p<0.001 for mortality); male gender (OR=1.08, 95% CI 0.72 to 1.63, p=0.72, present in 70.7%, of admissions to ICU versus 53% of other cases, p=0.004); cardiac disease (OR=3.43, 95% CI 2.10 to 5.63, p<0.001), diabetes mellitus (OR=2.37, 95% CI 1.09 to 5.17, p=0.028) and dementia (OR=5.06, 95% CI 2.79 to 9.44, p<0.001). There was no significant impact of ethnicity or body mass index on disease outcome. CONCLUSIONS: Despite reports of worse outcomes in deprived regions, we show similar complication and mortality rates due to COVID-19 in an affluent and high life expectancy region

Characterization of Antibodies against Receptor Activity-Modifying Protein 1 (RAMP1): A Cautionary Tale

Calcitonin gene-related peptide (CGRP) is a key component of migraine pathophysiology, yielding effective migraine therapeutics. CGRP receptors contain a core accessory protein subunit: receptor activity-modifying protein 1 (RAMP1). Understanding of RAMP1 expression is incomplete, partly due to the challenges in identifying specific and validated antibody tools. We profiled antibodies for immunodetection of RAMP1 using Western blotting, immunocytochemistry and immunohistochemistry, including using RAMP1 knockout mouse tissue. Most antibodies could detect RAMP1 in Western blotting and immunocytochemistry using transfected cells. Two antibodies (844, ab256575) could detect a RAMP1-like band in Western blots of rodent brain but not RAMP1 knockout mice. However, cross-reactivity with other proteins was evident for all antibodies. This cross-reactivity prevented clear conclusions about RAMP1 anatomical localization, as each antibody detected a distinct pattern of immunoreactivity in rodent brain. We cannot confidently attribute immunoreactivity produced by RAMP1 antibodies (including 844) to the presence of RAMP1 protein in immunohistochemical applications in brain tissue. RAMP1 expression in brain and other tissues therefore needs to be revisited using RAMP1 antibodies that have been comprehensively validated using multiple strategies to establish multiple lines of convincing evidence. As RAMP1 is important for other GPCR/ligand pairings, our results have broader significance beyond the CGRP field