Local chromatin dynamics of transcription factors imply cell-lineage specific functions during cellular differentiation

Chromatin dynamics across cellular differentiation states is an emerging perspective from which the mechanism of global gene expression regulation may be better understood. While the roles of some histone marks have been partially interpreted in terms of their association with gene transcription, the dynamics of histone marks from a loci-specific perspective during cellular differentiation is not well studied. We established a method to systematically assess the histone modification variations of genes across various cellular differentiation states. We calculated the histone modification variation scores of H3K4me3, H3K27me3 and H3K36me3 for over 1300 curated transcription factors (TFs) during human blood cell differentiation. Hematopoietic-specific TFs (identified by literature mining) were significantly overrepresented by TFs with higher histone modification variation scores. Hierarchical clustering of all TFs based on the histone modification variation scores defined a group of TFs where known or potential hematopoietic-specific TFs were remarkably enriched. Our results suggest that local chromatin state dynamics of transcription factors across cellular differentiation states could imply cell lineage-specific functions. More importantly, our method can be applied to broader systems, holding the promise to discover de novo, lineage-specific TFs by interrogating their histone modification dynamics across cell lineages

Quantitative Polymerase Chain Reaction Coupled With Sodium Dodecyl Sulfate and Propidium Monoazide for Detection of Viable Streptococcus agalactiae in Milk

Streptococcus agalactiae is an important pathogen causing bovine mastitis. The aim of this study was to develop a simple and specific method for direct detection of S. agalactiae from milk products. Propidium monoazide (PMA) and sodium dodecyl sulfate (SDS) were utilized to eliminate the interference of dead and injured cells in qPCR. Lysozyme (LYZ) was adopted to increase the extraction efficiency of target bacteria DNA in milk matrix. The specific primers were designed based on cfb gene of S. agalactiae for qPCR. The inclusivity and exclusivity of the assay were evaluated using 30 strains. The method was further determined by the detection of S. agalactiae in spiked milk. Results showed significant differences between the SDS–PMA–qPCR, PMA–qPCR and qPCR when a final concentration of 10 mg/ml (R2 = 0.9996, E = 95%) of LYZ was added in DNA extraction. Viable S. agalactiae was effectively detected when SDS and PMA concentrations were 20 μg/ml and 10 μM, respectively, and it was specific and more sensitive than qPCR and PMA–qPCR. Moreover, the SDS–PMA–qPCR assay coupled with LYZ was used to detect viable S. agalactiae in spiked milk, with a limit of detection of 3 × 103 cfu/ml. Therefore, the SDS–PMA–qPCR assay had excellent sensitivity and specificity for detection of viable S. agalactiae in milk

MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells

microRNAs play an important roles in cell growth, differentiation, proliferation and apoptosis. They can function either as tumor suppressors or oncogenes. We found that the overexpression of miR-192 inhibited cell proliferation in A549, H460 and 95D cells, and inhibited tumorigenesis in a nude mouse model. Both caspase-7 and the PARP protein were activated by the overexpression of miR-192, thus suggesting that miR-192 induces cell apoptosis through the caspase pathway. Further studies showed that retinoblastoma 1 (RB1) is a direct target of miR-192. Over-expression of miR-192 decreased RB1 mRNA and protein levels and repressed RB1-3′-UTR reporter activity. Knockdown of RB1 using siRNA resulted in a similar cell morphology as that observed for overexpression of miR-192. Additionally, RB1-siRNA treatment inhibited cell proliferation and induced cell apoptosis in lung cancer cells. Analysis of miRNA expression in clinical samples showed that miR-192 is significantly downregulated in lung cancer tissues compared to adjacent non-cancerous lung tissues. In conclusion, our results demonstrate that miR-192 is a tumor suppressor that can target the RB1 gene to inhibit cell proliferation and induce cell apoptosis in lung cancer cells. Furthermore, miR-192 was expressed at low levels in lung cancer samples, indicating that it might be a promising therapeutic target for lung cancer treatment

A comparative study on the innovativeness held by the entrepreneurs from flanders, Belgium and Hebei, China

Entrepreneurial orientation (EO) has been the focus of entrepreneurship research for a considerable time. Researchers believe the concept of entrepreneurial orientation can significantly assist in explaining the growth potential of an enterprise and the success of a business (e.g., Covin & Slevin, 1988; Wiklund. 1998, Wiklund and Shepherd, 2005). Researchers have made studies on entrepreneurial orientation using multiple dimensions, which mainly include innovativeness, risk-taking, and proactiveness, with innovativeness being taken as the most essential dimension (e.g., Lumpkin & Dess, 1996; 2005; Covin & Slevin, 1996; Miller & Friesen, 1986). Based on an extensive review of the studies about entrepreneurial orientation, especially in terms of innovativeness, the authors took case study as the research method, and accomplished a firm level empirical research, with the intention of making a comparative study on the innovativeness held by the entrepreneurs from Flanders, Belgium and Hebei, China Furthermore, taking as the contextual framework the major dimensions of entrepreneurship (GEM Executive Report, 2004), the authors intended to interpret the contextual determinants underpinning the differences and similarities in innovativeness between the entrepreneurs in the two countries. This pioneering empirical research contributes to understanding questions such as "How and why do the Chinese enterprises in manufacturing industry accomplish innovation, if compared with the international counterparts

IGFBP1 inhibits the invasion, migration, and apoptosis of HTR-8/SVneo trophoblast cells in preeclampsia

Objective To investigate the effects and underlying mechanisms of IGFBP1 on the biological functions of trophoblasts in simulated preeclampsia. Methods IGFBP1 expression in placenta was determined by immunohistochemistry. HTR-8/SVneo cells were stimulated with/without IGFBP1-overexpression and hypoxia-reoxygenation, and the proliferation, invasion, migration, and apoptosis were detected by CCK8, transwell, and flow cytometry, respectively. Results IGFBP1 expression was increased in placenta of preeclampsia. IGFBP1 overexpression inhibited proliferation, invasion, migration, and apoptosis of HTR-8/SVneo cells and induced MMP-26 expression with/without hypoxia-reoxygenation challenge. Conclusion IGFBP1 affects biological functions of trophoblasts, and it may play a role in pathophysiology of preeclampsia by inducing MMP-26