Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline.

Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes. Here, we combine deep-sequencing and genetic approaches to explore the biogenesis and function of endo-siRNAs in C. elegans. We describe conditional alleles of the Dicer-related helicase, drh-3, that abrogate both RNA interference and the biogenesis of endo-siRNAs, called 22G-RNAs. DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems. We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germline nuage structures called P granules. WAGO-1 silences certain genes, transposons, pseudogenes, and cryptic loci. Finally, we demonstrate that components of the nonsense-mediated decay pathway function in at least one WAGO-mediated surveillance pathway. These findings broaden our understanding of the biogenesis and diversity of 22G-RNAs and suggest additional regulatory functions for small RNAs.

Non-resident orthopaedic admissions to Dunedin Hospital 1997 to 2017 and Southland Hospital 2011 to 2017.

AIMS: The purpose of this study is to audit the numbers of non-residents requiring orthopaedic admission to Dunedin and Southland Hospitals and determine the effects of increasing tourist numbers on healthcare resources. METHOD: All non-resident orthopaedic admissions to Dunedin Hospital from January 2005 to December 2017 and Invercargill Hospital from January 2011 to December 2017 were analysed with respect to country of residence, mechanism of injury, primary diagnosis and case weights consumed. The results were combined with figures from 1997-2004 to give a 21-year series for Dunedin Hospital. RESULTS: There has been a significant increase in the number of admissions and case weights (CW) over the past 21 years at Dunedin Hospital (p<0.001). The most common mechanisms of injury were snow sports at Dunedin Hospital and falls for Southland Hospital. Between 2011 and 2017 there were on average 50 non-resident admissions per year (92.9 CW/year) to Dunedin Hospital and 74 admissions (120.7 CW/year) in Southland. CONCLUSION: Increasing tourist numbers have resulted in an increase number of orthopaedic admissions to Dunedin Hospital over the last two decades although it remains a small proportion of the total workload. Southland Hospital is relatively more affected. These patients represent an annual cost in excess of $1,000,000 to Southern DHB.

The use of CT in the management of minor head injuries in Queenstown.

AIM This study retrospectively reviewed the management of head injury at Lakes District Hospital in Queenstown, New Zealand. The aim is to describe the management of minor head injury with particular reference to the current Traumatic Brain Injury guidelines of the New Zealand Guidelines Group. METHODS We identified all patients with head injury as a primary diagnosis who were seen in the Emergency Department at Lakes District Hospital during 2013-2015. We recorded clinical criteria indicating need for computed tomography (CT) scanning according to current guidelines for management of minor head injury. RESULTS A total of 883 patients were seen with head injury as their primary diagnosis: 280 patients aged >15 years had a minor head injury that met current criteria for immediate CT scanning. Of these, 66 (23.6%) actually had a CT head scan. CONCLUSION The rate of CT head scanning for minor head injury in Queenstown does not comply with current New Zealand guidelines.

The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues.

Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an eight-residue ovalbumin epitope from precursors extended on the NH2 terminus that were generated either in the ER or cytosol. Purified ERAP1 also trimmed nearly half the nine-residue peptides tested. By destroying such nine-residue peptides in normal human cells, ERAP1 reduced the overall supply of antigenic peptides. However, after interferon-gamma treatment, which causes proteasomes to produce more NH2-extended antigenic precursors, ERAP1 increased the supply of peptides for MHC class I antigen presentation.