miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival.

Coordinate control of T cell proliferation, survival, and differentiation are essential for host protection from pathogens and cancer. Long-lived memory cells, whose precursors are formed during the initial immunological insult, provide protection from future encounters, and their generation is the goal of many vaccination strategies. microRNAs (miRNAs) are key nodes in regulatory networks that shape effective T cell responses through the fine-tuning of thousands of genes. Here, using compound conditional mutant mice to eliminate miR-15/16 family miRNAs in T cells, we show that miR-15/16 restrict T cell cycle, survival, and memory T cell differentiation. High throughput sequencing of RNA isolated by cross-linking immunoprecipitation of AGO2 combined with gene expression analysis in miR-15/16-deficient T cells indicates that these effects are mediated through the direct inhibition of an extensive network of target genes within pathways critical to cell cycle, survival, and memory.

Benign cardiac tumours associated with sudden death.

AIMS: Sudden cardiac death (SCD) accounts for 50% of cardiovascular mortality with an estimated annual toll of 300 000 deaths in the USA and 60 000 deaths in the UK. Benign primary cardiac tumours are extremely rare, and although many of these entities are clinically silent, a few can cause significant morbidity or even sudden death. The objective of the study is to raise awareness of benign primary cardiac tumours as a possible cause of SCD so that more cases are identified by pathologists during life. METHODS AND RESULTS: Between 1994 and 2012, the hearts of more than 1600 people who had SCD were referred for pathological assessment to ascertain the precise aetiology of SCD. Eleven cases of SCD associated with benign cardiac tumours were identified; four were cystic tumours of the atrioventricular (AV) node, three lipomas, two rhabdomyomas, one haemangioma, and one myxoma. CONCLUSION: This study highlights that benign cardiac tumours are exceptionally uncommon yet potentially lethal. Careful examination of the heart will identify most of these lesions. A major exception, however, is cystic tumour of the AV node, the most common primary cardiac tumour causing sudden death. Since the gross findings of this lesion may be minimal, we recommend taking a routine section of the conducting system, including the AV node, in all cases of sudden death.