Molecular alignment in molecular fluids induced by coupling between density and thermal gradients

We investigate, using non-equilibrium molecular dynamics simulations and theory, the response of molecular fluids confined in slit pores under the influence of a thermal gradient and/or an applied force. The applied force which has the same functional form as a gravitational force induces an inhomogeneous density in the confined fluid, which results in a net orientation of the molecules with respect to the direction of the force. The orientation is qualitatively similar to that induced by a thermal gradient. We find that the average degree of orientation is proportional to the density gradient of the fluid in the confined region and that the orientation increases with the magnitude of the force. The concurrent application of the external force and the thermal gradient allows us to disentangle the different mechanisms leading to the thermal orientation of molecular fluids. One mechanism is connected to the density variation of the fluid, while the second mechanism can be readily observed in molecular fluids consisting of molecules with mass or size asymmetry, even in the absence of a density gradient, hence it is connected to the application of the thermal gradient only

MiR-107 and MiR-185 Can Induce Cell Cycle Arrest in Human Non Small Cell Lung Cancer Cell Lines

BACKGROUND: MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. CONCLUSIONS/SIGNIFICANCE: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

<div><p>Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.</p></div

Treatment of myofascial trigger points in common shoulder disorders by physical therapy: A randomized controlled trial [ISRCTN75722066]

Contains fulltext : 52454.pdf (publisher's version ) (Open Access

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Polarisation of polar dumbbell fluids in thermal gradients: the importance of the treatment of electrostatic interactions

We use non-equilibrium molecular dynamics simulations to study dipolar dumbbell fluids in a thermal gradient. We study the relative orientation of size asymmetric molecules with respect to the thermal gradient, and the sensitivity of the orientation to whether the Wolf method or Ewald summation is employed to compute the electrostatic interactions. For these systems, we find that the Wolf method overestimates the degree of molecular orientation. We also present new data on fluids with very small dipole moments which give novel insight into how the molecular asymmetry influences the polarisation response in the thermal gradient