Eukaryotic translation initiation factor eIF4E-5 is required for spermiogenesis in Drosophila melanogaster.

Drosophila sperm development is characterized by extensive post-transcriptional regulation whereby thousands of transcripts are preserved for translation during later stages. A key step in translation initiation is the binding of eukaryotic initiation factor 4E (eIF4E) to the 5' mRNA cap. In addition to canonical eIF4E-1, Drosophila has multiple eIF4E paralogs, including four (eIF4E-3, -4, -5, and -7) that are highly expressed in the testis. Among these, only eIF4E-3 has been characterized genetically. Here, using CRISPR/Cas9 mutagenesis, we determined that eIF4E-5 is essential for male fertility. eIF4E-5 protein localizes to the distal ends of elongated spermatid cysts, and eIF4E-5 mutants exhibit defects during post-meiotic stages, including a mild defect in spermatid cyst polarization. eIF4E-5 mutants also have a fully penetrant defect in individualization, resulting in failure to produce mature sperm. Indeed, our data indicate that eIF4E-5 regulates non-apoptotic caspase activity during individualization by promoting local accumulation of the E3 ubiquitin ligase inhibitor Soti. Our results further extend the diversity of non-canonical eIF4Es that carry out distinct spatiotemporal roles during spermatogenesis.

Prognostic value of visually detected coronary artery calcification on unenhanced non-gated thoracic computed tomography for prediction of non-fatal myocardial infarction and all-cause mortality.

PURPOSE: To determine the prognostic value of visually detected coronary artery calcification (CAC) on unenhanced non-gated thoracic computed tomography (CT) for non-fatal myocardial infarction (MI) and all-cause mortality. METHODS: This retrospective single-centre cohort study comprised of 410 consecutive patients aged 40-80 years without any known cardiovascular disease at baseline. CT images without electrocardiogram-gating were acquired for a variety of respiratory medicine indications. CAC was examined by a single reader blinded to clinical data and outcome, using 1) the Agatston coronary calcium score (CCS), 2) visual CAC and 3) number of visually calcified coronary arteries. RESULTS: Visible CAC was identified in 201 (49.0%) of the 410 patients (60.5 ± 10.0 years old, 42.4% males). After a median follow up of 7.0 years, 39 patients (9.5%) experienced an event (death or non-fatal MI). After adjustment for cardiovascular risk factors, those with 1) higher CCS, 2) presence of visual CAC or 3) greater number of calcified coronary arteries by visual assessment, had an increased risk of adverse outcome (all p-value <0.05). There was no significant difference in c-statistics of the three methods of assessment (0.81, 0.80, 0.81 respectively), indicating that simple visual assessment of CAC may have a prognostic value similar to CCS. CONCLUSION: Among patients with no known cardiovascular disease who underwent unenhanced non-gated CT for a pulmonary-related indication, visually detected CAC was a strong independent predictor of non-fatal MI and all-cause mortality.