Non-contact confocal calcium imaging of murine corneal nerves.

Abnormal corneal nerve function and associated disease is a significant public health concern. It is associated with prevalent ocular surface diseases, including dry eye disease. Corneal nerve dysfunction is also a common side effect of refractive surgeries, as well as a symptom of diseases that cause peripheral neuropathies.

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.

Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.

Peri-operative identification and management of patients with unhealthy alcohol intake.

Introduction: This consensus statement gives practical advice for the safe management of patients with harmful alcohol intake undergoing elective and emergency surgery. The wide spectrum of alcohol-related organ dysfunction observed in this cohort of patients may have a profound impact on care, and the additional effects of alcohol withdrawal may further exacerbate postoperative morbidity and mortality.

Methods: A working party was assembled based on clinical and/or academic expertise in the area.

Biochemical and structural characterization of Rab3GAP reveals insights into Rab18 nucleotide exchange activity.

The heterodimeric Rab3GAP complex is a guanine nucleotide exchange factor (GEF) for the Rab18 GTPase that regulates lipid droplet metabolism, ER-to-Golgi trafficking, secretion, and autophagy. Why both subunits of Rab3GAP are required for Rab18 GEF activity and the molecular basis of how Rab3GAP engages and activates its cognate substrate are unknown. Here we show that human Rab3GAP is conformationally flexible and potentially autoinhibited by the C-terminal domain of its Rab3GAP2 subunit.