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Bernstein Bowers posted an update 25 days ago
from a national cohort of children. Understanding of the molecular basis of host cell-miRNA interactions is prerequisite to the successful application of miRNAs as potential therapeutic agents. FG-4592 We studied the morphological and molecular consequences of over expression of three sequence divergent miRNAs previously implicated in the mesenchymal-to-epithelial transition process (MET) in three distinct mesenchymal-like cancer cell lines. The ability of miRNAs to induce morphological changes characteristic of MET positively correlated with induced changes in the expression of genes previously implicated in the process. Variability in the responses of different mesenchymal-like cells to over expression of the same miRNAs was attributable to inherent differences in trans-regulatory profiles pre-disposing these cells to miRNA-induced MET. Collectively our results indicate that miRNA-mediated regulation of MET is a highly integrated process that is significantly modulated by the molecular background of individual cells. Dendritic cells are professional antigen-presenting cells that play a critical role in the development of immune responses. DCs express a variety of Siglecs on their surface, which play a regulatory role modulating their activation through interaction with sialylated structures expressed by cells or pathogens. Here, we characterized the phenotype of porcine conventional dendritic cells subsets from blood, spleen and lymph nodes, emphasizing the analysis of the expression of Siglecs. Siglec-1 was detected in type 1 cDC and, at lower levels, in type 2 cDC in the spleen, being low to negative in blood and lymph node cDC. Siglec-3 and Siglec-5 were expressed in cDC1 at lower levels than in cDC2. Porcine cDCs did not express Siglec-10. cDC2 showed a higher capacity to phagocytose microspheres and to process DQ™-OVA than cDC1, but none of these functions was affected by engagement of Siglec-3 and -5 with antibodies on blood cDC. Pseudomaintenance (PM) is a Transtheoretical Model (TTM) stage of change that refers to individuals who believe they eat enough fruit and vegetables (FV) despite their low FV intake. It is not known how they change behavior after usual TTM-based interventions. Thus, this randomized controlled community trial describes the effect of PM on progression through the stages of change for FV intake among adult and elderly health promotion service users after TTM-based intervention. The stage of change for FV intake was assessed; FV intake was estimated from brief validated questions at baseline (n = 3414) and follow-up (n = 1782). Individuals whose perception of adequacy matched the estimated intake were labeled as “concordant perception,” while those with low intake who believed that their intake was adequate were classified as being in PM. The intervention group received the intervention while the control group received usual care. The prevalence of “no stage progression” at follow-up was close to 50% for those in PM at baseline. After adjustment for demographics, randomization, self-efficacy, decisional balance, and baseline intake, users in PM at baseline had higher odds [OR = 1.53 (1.21-1.94)] of progressing to higher stages for fruit and no difference in progression for vegetables. We propose strategies to approach FV intake in future studies and reinforce the need for additional trials aimed at describing changes in FV intake among individuals in PM, in order to continue answering the scientific questions that we began to investigate. The biosynthesis of bacterial cell envelope polysaccharides such as peptidoglycan relies on the use of a dedicated carrier lipid both for the assembly of precursors at the cytoplasmic face of the plasma membrane and for the translocation of lipid linked oligosaccharides across the plasma membrane into the periplasmic space. This dedicated carrier lipid, undecaprenyl phosphate, results from the dephosphorylation of undecaprenyl pyrophosphate, which is generated de novo in the cytoplasm by undecaprenyl pyrophosphate synthase and released as a by-product when newly synthesized glycans are incorporated into the existing cell envelope. The de novo synthesis of undecaprenyl pyrophosphate has been thoroughly characterized from a structural and mechanistic standpoint; however, its dephosphorylation to the active carrier lipid form, both in the course of de novo synthesis and recycling, has only been begun to be studied in depth in recent years. This review provides an overview of bacterial carrier lipid synthesis and presents the current state of knowledge regarding bacterial carrier lipid recycling. Tafazzin is a mitochondrial enzyme that exchanges fatty acids between phospholipids by phospholipid-lysophospholipid transacylation. The reaction alters the molecular species composition and, as a result, the physical properties of lipids. In vivo, the most important substrate of tafazzin is the mitochondria-specific lipid cardiolipin. Tafazzin mutations cause the human disease Barth syndrome, which presents with cardiomyopathy, skeletal muscle weakness, fatigue, and other symptoms, probably all related to mitochondrial dysfunction. The reason why mitochondria require tafazzin is still not known, but recent evidence suggests that tafazzin may lower the energy cost associated with protein crowding in the inner mitochondrial membrane. While most of the articles in this issue review the workings of integral membrane enzymes, in this review, we describe the catalytic mechanism of an enzyme that contains a soluble catalytic domain but appears to catalyze its reaction on the membrane surface, anchored and assisted by a separate regulatory amphipathic helical domain and inter-domain linker. Membrane partitioning of CTP phosphocholine cytidylyltransferase (CCT), a key regulatory enzyme of phosphatidylcholine metabolism, is regulated chiefly by changes in membrane phospholipid composition, and boosts the enzyme’s catalytic efficiency >200-fold. Catalytic enhancement by membrane binding involves the displacement of an auto-inhibitory helix from the active site entrance-way and promotion of a new conformational ensemble for the inter-domain, allosteric linker that has an active role in the catalytic cycle. We describe the evidence for close contact between membrane lipid, a compact allosteric linker, and the CCT active site, and discuss potential ways that this interaction enhances catalysis.