Cytoplasmic processing bodies, termed P bodies, are involved in diverse post-transcriptional processes including mRNA decay, nonsense-mediated RNA decay (NMD), RNAi, miRNA-mediated translational repression and storage of translationally silenced mRNAs. Regulation of the formation of P bodies in the context of multicellular organisms is poorly understood. Here we describe a systematic RNAi screen in C. elegans that identified 224 genes with diverse cellular functions whose inactivations result in a dramatic increase in the number of P bodies. 83 of these genes form a complex functional interaction network regulating NMD. We demonstrate that NMD interfaces with many cellular processes including translation, ubiquitin-mediated protein degradation, intracellular trafficking and cytoskeleton structure.We also uncover an extensive link between translation and RNAi, with different steps in protein synthesis appearing to have distinct effects on RNAi efficiency. Moreover, the intracellular vesicular trafficking network plays an important role in the regulation of RNAi. A subset of genes enhancing P body formation also regulate the formation of stress granules in C. elegans. Our study offers insights into the cellular mechanisms that regulate the formation of P bodies and also provides a framework for system-level understanding of NMD and RNAi in the context of the development of multicellular organisms.
Animals ; Animals, Genetically Modified ; Caenorhabditis elegans ; genetics ; Cytoplasmic Structures ; Gene Expression Regulation ; Genes, Helminth ; Genome, Helminth ; genetics ; MicroRNAs ; genetics ; Nonsense Mediated mRNA Decay ; physiology ; RNA Interference ; RNA, Helminth ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

Objective To explore the plasma levels of soluble CD40 (sCD40) and soluble CD40 ligand (sCD40L) in the patients with Alzheimer’s disease (AD) and those with amnestic mild cognitive impairment (aMCI). Methods The levels of plasma sCD40 and sCD40L were measured in 20 patients with AD, 35 patients with aMCI, and 32 cognitively normal controls (NC) using commercially available ELISAs. The cognitive function of AD and aMCI patients was mea?sured by mini-mental state examination (MMSE). Results There were significant differences in plasma sCD40 among AD, aMCI and NC groups (P<0.05) as the medians (the upper and lower quartiles) of plasma levels were 123.3 (97.4, 149.5) pg/mL, 102.9 (63.6, 124.0) pg/mL and 70.66 (51.0, 90.8) pg/mL, respectively. There were significant differences in plasma sCD40L among AD, aMCI and NC groups (P<0.05) as plasma levels were 537.0 (316.0, 1134.0) pg/mL, 316.0 (190.0,546.0) pg/mL and 167.0 (107.5,478.0) pg/mL. A negative correlation between the plasma concentrations of sCD40L and the MMSE scores was found in aMCI patients (r=-0.736, P<0.001). Conclusions There are relevant chang?es of plasma sCD40 and sCD40L levels in patients with AD and aMCI. The present results suggest that plasma levels of sCD40 and sCD40L may be appropriate biomarkers for AD patients and indicate that CD40-CD40L signaling may be in?volved in AD pathophysiology.

BACKGROUNDT8590C polymorphism of CYP4A11 has been associated with hypertension, though with conflicting results. The aim of this study was to quantitatively summarize the evidence for CYP4A11 T8590C polymorphism and hypertension risk.

METHODSElectronic search of PubMed and the Chinese Biomedicine database was conducted to select studies. Case-control studies containing available genotype frequencies of T8590C were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.

RESULTSSeven case-control studies, including 3 295 cases and 3 192 controls, were identified. The meta-analysis, stratified by ethnicity, showed that individuals with the C allele carriers (CC+CT) had increased risk of hypertension in over all (OR = 1.184, 95% CI: 1.063-1.319, P = 0.002) and in others (OR = 1.217, 95% CI: 1.045-1.419, P = 0.012). The results among Asians did not suggest an association (OR = 1.152, 95% CI: 0.990-1.342, P = 0.068). A symmetric funnel plot, the Egger's test (P = 0.863), and the Begg test (P = 0.393) were all suggestive of the lack of publication bias.

CONCLUSIONSThis meta-analysis suggests the CYP4A11 T8590C polymorphism may be a risk factor for hypertension. Future well-designed large studies might be necessary to validate this association in different populations incorporated with environmental factors in the susceptibility of hypertension.

Case-Control Studies ; Cytochrome P-450 CYP4A ; Cytochrome P-450 Enzyme System ; genetics ; Humans ; Hypertension ; genetics ; Polymorphism, Genetic ; genetics ; Risk Factors