MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF

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Essential Role for miR-196a in Brown Adipogenesis of White Fat Progenitor Cells

Brown adipocytes can differentiate from white fat progenitor cells in mice exposed to cold or β3-adrenergic stimulation, and this process is regulated by a microRNA that regulates the expression of Hoxc8, a master regulator of brown adipogenesis

Role of Histone Tails in Structural Stability of the Nucleosome

Histone tails play an important role in nucleosome structure and dynamics. Here we investigate the effect of truncation of histone tails H3, H4, H2A and H2B on nucleosome structure with 100 ns all-atom molecular dynamics simulations. Tail domains of H3 and H2B show propensity of -helics formation during the intact nucleosome simulation. On truncation of H4 or H2B tails no structural change occurs in histones. However, H3 or H2A tail truncation results in structural alterations in the histone core domain, and in both the cases the structural change occurs in the H2A3 domain. We also find that the contacts between the histone H2A C terminal docking domain and surrounding residues are destabilized upon H3 tail truncation. The relation between the present observations and corresponding experiments is discussed

Computational analysis of expression of human embryonic stem cell-associated signatures in tumors

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach.</p> <p>Results</p> <p>We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells.</p> <p>Conclusions</p> <p>The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further.</p

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway

miR-27b inhibits fibroblast activation via targeting TGFB signaling pathway

Background: MicroRNAs are a group of small RNAs that regulate gene expression at the posttranscriptional level. They regulate almost every aspect of cellular processes. In this study, we investigated whether miR-27b regulates pulmonary fibroblast activation.Results: We found that miR-27b was down-regulated in fibrotic lungs and fibroblasts from an experimental mouse model of pulmonary fibrosis. The overexpression of miR-27b with a lentiviral vector inhibited TGFB1-stimulated mRNA expression of collagens (COL1A1, COL3A1, and COL4A1) and alpha-smooth muscle actin, and protein expression of Col3A1 and alpha-smooth muscle actin in LL29 human pulmonary fibroblasts. miR-27b also reduced contractile activity of LL29. TGFB receptor 1 and SMAD2 were identified as the targets of miR-27b by 3'-untranslated region luciferase reporter and western blotting assays.Conclusions: Our results suggest that miR-27b is an anti-fibrotic microRNA that inhibits fibroblast activation by targeting TGFB receptor 1 and SMAD2. This discovery may provide new targets for therapeutic interventions of idiopathic pulmonary fibrosis.Peer reviewedPhysiological SciencesOklahoma Center for Respiratory and Infectious Disease

Regulation of MicroRNA Biogenesis: A miRiad of mechanisms

microRNAs are small, non-coding RNAs that influence diverse biological functions through the repression of target genes during normal development and pathological responses. Widespread use of microRNA arrays to profile microRNA expression has indicated that the levels of many microRNAs are altered during development and disease. These findings have prompted a great deal of investigation into the mechanism and function of microRNA-mediated repression. However, the mechanisms which govern the regulation of microRNA biogenesis and activity are just beginning to be uncovered. Following transcription, mature microRNA are generated through a series of coordinated processing events mediated by large protein complexes. It is increasingly clear that microRNA biogenesis does not proceed in a 'one-size-fits-all' manner. Rather, individual classes of microRNAs are differentially regulated through the association of regulatory factors with the core microRNA biogenesis machinery. Here, we review the regulation of microRNA biogenesis and activity, with particular focus on mechanisms of post-transcriptional control. Further understanding of the regulation of microRNA biogenesis and activity will undoubtedly provide important insights into normal development as well as pathological conditions such as cardiovascular disease and cancer

Embryonic and induced pluripotent stem cells: understanding, creating, and exploiting the nano-niche for regenerative medicine.

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any specialized cell type of the human body, and therefore, ESC/iPSC-derived cell types offer great potential for regenerative medicine. However, key to realizing this potential requires a strong understanding of stem cell biology, techniques to maintain stem cells, and strategies to manipulate cells to efficiently direct cell differentiation toward a desired cell type. As nanoscale science and engineering continues to produce novel nanotechnology platforms, which inform, infiltrate, and impinge on many aspects of everyday life, it is no surprise that stem cell research is turning toward developments in nanotechnology to answer research questions and to overcome obstacles in regenerative medicine. Here we discuss recent advances in ESC and iPSC manipulation using nanomaterials and highlight future challenges within this area of research

Farming systems in sheep rearing: Impact on growth and reproductive performance, nutrient digestibility, disease incidence and heat stress indices.

The experiment was conducted with an intent to know the effect of different farming systems on the growth performance, nutrient digestibility coefficients, reproductive traits, disease incidence, heat stress indices, and cost economics of Nellore sheep. The study includes two parallel trials to prevent the influence of age on heat stress indices (panting score and erythrocyte osmotic fragility (EOF)). One hundred and twenty lambs (60 ram-lambs and 60 ewe-lambs) were allotted in a randomized block design under extensive, semi-intensive, and intensive systems for trial I, whereas trial II include eighteen rams assigned to the three respective farming systems in a completely randomised design. Both, season (summer) and grazing practice increased the panting score and EOF. The heat stress indices were positively correlated (P<0.01) with dry-bulb temperature and temperature-humidity index (THI) and inversely correlated (P<0.01) to relative humidity. Allotting the sheep to intensive system increased (P<0.001) weight gain and average daily gain with higher effect in males compared to females. The parameters of asymptotic weight (A), integration constant (B), and maturation rate were higher for intensive males. The male Nellore lambs had higher asymptotic weight and lower maturity rate than females, irrespective of the rearing system. Intensive sheep revealed a higher dry matter intake, digestibility coefficients, feed conversion ratio. The instantaneous bite mass (IBM) was higher for Commelina benghalensis, while instantaneous bite frequency (IBF), instantaneous intake rate (IIR) were higher for Cyanodon dactylon and amaranthus viridis, respectively. The proportion of intakes were highest for Stylo hemata followed by Cynodon dactylon and Tridax procumbens species. No differences were observed for the weight at puberty, oestrus cycle length, oestrus duration, conception percent, gestation period, and lambing percent in three rearing systems; however, the age at puberty was lower (P<0.001) and the birth weight was higher (P<0.001) for sheep reared under intensive farming system. Highest disease incidence was observed in rainy and winter seasons, particularly in sheep reared under extensive system. The capital expenditure was same for the three rearing systems, while the recurring expenditure was higher for Intensive farming system. The gross income and net income were higher for intensive system on account of higher weight gains. However, the higher returns per rupee of expenditure project the extensive farming as an ideal rearing system for small farmers and entrepreneurs with a low initial capital