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This work describes a role for the lipid phosphatidylinositol 4-phosphate (PI4P) and lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ) in cell motility, cell shape, and focal adhesion (FA) formation. During fibroblast migration, PI4P vesicles move to the leading edge and fuse with FA there. Deletion of PI4KIIIB impairs fibroblast migration, increases the number of FA, and alters cell shape.

Previous studies suggest that regulatory microRNAs (miRs) may modulate neuro-inflammatory processes. The purpose of the present study was to examine the role of miR-17 following intervertebral disc herniation. In a cohort of 97 patients with leg pain and disc herniation verified on MRI, we investigated the association between circulating miR-17 and leg pain intensity. A rat model was used to examine possible changes in miR-17 expression in nucleus pulposus (NP) associated with leak of NP tissue out of the herniated disc. The functional role of miR-17 was addressed by transfection of miR-17 into THP-1 cells (human monocyte cell line). An association between the level of miR-17 in serum and the intensity of lumbar radicular pain was shown. Up-regulation of miR-17 in the rat NP tissue when applied onto spinal nerve roots and increased release of TNF following transfection of miR-17 into THP-1 cells were also observed. Hence, our data suggest that miR-17 may be involved in the pathophysiology underlying lumbar radicular pain after disc herniation. We conclude that miR-17 may be associated with the intensity of lumbar radicular pain after disc herniation, possibly through a TNF-driven pro-inflammatory mechanism.

The links among smoking, inflammation, and cardiovascular disease (CVD) are well established. Several studies have demonstrated that quitting smoking reverses the risk of coronary heart disease within 5 to 10 years. However, the immediate effects of quitting smoking on inflammatory biomarkers associated with CVD risk have not been well described.

Three new antibiotics, neopyrrolomycins B (1), C (2), and D (3), with potent activity against Gram-positive pathogens were discovered. They exhibited MIC values < 1 μg/mL versus a number of resistant strains. The compounds were obtained from the ethyl acetate extracts of a Streptomycessp.after purification by column chromatography and RP-HPLC. Their structures were elucidated using X-ray crystallography (1) and NMR spectroscopy (2and 3).

Two new xanthone antibiotics, citreamicin δ (1) and ε (2), with potent activity against Gram-positive pathogens including multidrug-resistant Staphylococcus aureus(MDRSA) were discovered. Compounds 1and 2exhibited MIC values < 1 μg/mL versus a number of resistant strains. The compounds were obtained from EtOAc extracts of Streptomyces vinaceusand were purified by countercurrent chromatography and reversed-phase HPLC. Their structures were elucidated using primarily NMR and mass spectroscopy.

Background: Plants can transmit somatic mutations and epimutations to offspring, which in turn can affect fitness. Knowledge of the rate at which these variations arise is necessary to understand how plant development contributes to local adaption in an ecoevolutionary context, particularly in long-lived perennials. Results: Here, we generate a new high-quality reference genome from the oldest branch of a wild Populus trichocarpatree with two dominant stems which have been evolving independently for 330 years. By sampling multiple, age-estimated branches of this tree, we use a multi-omics approach to quantify age-related somatic changes at the genetic, epigenetic, and transcriptional level. We show that the per-year somatic mutation and epimutation rates are lower than in annuals and that transcriptional variation is mainly independent of age divergence and cytosine methylation. Furthermore, a detailed analysis of the somatic epimutation spectrum indicates that transgenerationally heritable epimutations originate mainly from DNA methylation maintenance errors during mitotic rather than during meiotic cell divisions. Conclusion: Taken together, our study provides unprecedented insights into the origin of nucleotide and functional variation in a long-lived perennial plant.