Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies

Type 2 diabetes mellitus (T2DM) influences bone metabolism, but the relation of T2DM with bone mineral density (BMD) remains inconsistent across studies. The objective of this study was to perform a meta-analysis and meta-regression of the literature to estimate the difference in BMD (g/cm2) between diabetic and non-diabetic populations, and to investigate potential underlying mechanisms. A literature search was performed in PubMed and Ovid extracting data from articles prior to May 2010. Eligible studies were those where the association between T2DM and BMD measured by dual energy X-ray absorptiometry was evaluated using a cross-sectional, cohort or case–control design, including both healthy controls and subjects with T2DM. The analysis was done on 15 observational studies (3,437 diabetics and 19,139 controls). Meta-analysis showed that BMD in diabetics was significantly higher, with pooled mean differences of 0.04 (95% CI: 0.02, 0.05) at the femoral neck, 0.06 (95% CI: 0.04, 0.08) at the hip and 0.06 (95% CI: 0.04, 0.07) at the spine. The differences for forearm BMD were not significantly different between diabetics and non-diabetics. Sex-stratified analyses showed similar results in both genders. Substantial heterogeneity was found to originate from differences in study design and possibly diabetes definition. Also, by applying meta-regression we could establish that younger age, male gender, higher body mass index and higher HbA1C were positively associated with higher BMD levels in diabetic individuals. We conclude that individuals with T2DM from both genders have higher BMD levels, but that multiple factors influence BMD in individuals with T2DM

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Interaction of Streptococcus mutans YidC1 and YidC2 with Translating and Nontranslating Ribosomes

<p>The YidC/OxaI/Alb3 family of membrane proteins is involved in the biogenesis of integral membrane proteins in bacteria, mitochondria, and chloroplasts. Gram-positive bacteria often contain multiple YidC paralogs that can be subdivided into two major classes, namely, YidC1 and YidC2. The Streptococcus mutans YidC1 and YidC2 proteins possess C-terminal tails that differ in charges (+9 and +14) and lengths (33 and 61 amino acids). The longer YidC2 C terminus bears a resemblance to the C-terminal ribosome-binding domain of the mitochondrial OxaI protein and, in contrast to the shorter YidC1 C terminus, can mediate the interaction with mitochondrial ribosomes. These observations have led to the suggestion that YidC1 and YidC2 differ in their abilities to interact with ribosomes. However, the interaction with bacterial translating ribosomes has never been addressed. Here we demonstrate that Escherichia coli ribosomes are able to interact with both YidC1 and YidC2. The interaction is stimulated by the presence of a nascent membrane protein substrate and abolished upon deletion of the C-terminal tail, which also abrogates the YidC-dependent membrane insertion of subunit c of the F1F0-ATPase into the membrane. It is concluded that both YidC1 and YidC2 interact with ribosomes, suggesting that the modes of membrane insertion by these membrane insertases are similar.</p>