Evidence for genetic association of TBX21 and IFNG with systemic lupus erythematosus in a Chinese Han population

TBX21 recode T-bet which is an important transcription factor that drives the Th1 immune response primarily by promoting expression of the interferon-gamma (IFNG) gene. Recent studies have shown that genetic variants in TBX21 and IFNG are connected with risk of systemic lupus erythematosus (SLE). The aim of the present study was to replicate these genetic associations with SLE in Anhui Chinese population. Genotyping of 3 variants (rs4794067 in TBX21, rs2069705 and rs2069718 in IFNG) was performed. A total of 3732 subjects were included in the final analysis. The study only identified the association of rs2069705 with SLE susceptibility (T vs. C: odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.00-1.26, P = 0.046). Combined analysis with Hong Kong GWAS showed that the OR for rs2069705 was 1.10 (95% CI: 1.01-1.21, P = 0.027). Further pooled analysis with Korean populations involving 10498 subjects showed a more significant association between rs2069705 and SLE (T vs. C: OR = 1.11, 95%CI = 1.04-1.19, P = 0.002; TT + TC vs. CC: OR = 1.11, 95%CI = 1.02-1.21, P = 0.012; TT vs. TC + CC: OR = 1.28, 95%CI = 1.07-1.54, P = 0.008; TT vs. CC: OR = 1.33, 95%CI = 1.10-1.60, P = 0.003). In addition, we also identified a significant genetic interaction between rs2069705 and rs4794067 in Anhui Chinese population. Our study suggests that IFNG and IFNG-TBX21 interaction are involved in SLE susceptibility.published_or_final_versio

Estrogen Receptor Alpha Is Expressed in Mesenteric Mesothelial Cells and Is Internalized in Caveolae upon Freund's Adjuvant Treatment

Transformation of epithelial cells into connective tissue cells (epithelial-mesenchymal transition, EMT) is a complex mechanism involved in tumor metastasis, and in normal embryogenesis, while type II EMT is mainly associated with inflammatory events and tissue regenaration. In this study we examined type II EMT at the ultrastructural and molecular level during the inflammatory process induced by Freund's adjuvant treatment in rat mesenteric mesothelial cells. We found that upon the inflammatory stimulus mesothelial cells lost contact with the basal lamina and with each other, and were transformed into spindle-shaped cells. These morphological changes were accompanied by release of interleukins IL-1alpha, -1beta and IL-6 and by secretion of transforming growth factor beta (TGF-beta) into the peritoneal cavity. Mesothelial cells also expressed estrogen receptor alpha (ER-alpha) as shown by immunolabeling at the light and electron microscopical levels, as well as by quantitative RT-PCR. The mRNA level of ER-alpha showed an inverse correlation with the secretion of TGF-beta. At the cellular and subcellular levels ER-alpha was colocalized with the coat protein caveolin-1 and was found in the plasma membrane of mesothelial cells, in caveolae close to multivesicular bodies (MVBs) or in the membrane of these organelles, suggesting that ER-alpha is internalized via caveola-mediated endocytosis during inflammation. We found asymmetric, thickened, electron dense areas on the limiting membrane of MVBs (MVB plaques) indicating that these sites may serve as platforms for collecting and organizing regulatory proteins. Our morphological observations and biochemical data can contribute to form a potential model whereby ER-alpha and its caveola-mediated endocytosis might play role in TGF-beta induced type II EMT in vivo

Monsoon versus Uplift in Southwestern China–Late Pliocene Climate in Yuanmou Basin, Yunnan

Yuanmou Basin of Yunnan, SW China, is a famous locality with hominids, hominoids, mammals and plant fossils. Based on the published megaflora and palynoflora data from Yuanmou Basin, the climate of Late Pliocene is reconstructed using the Coexistence Approach. The results indicate a warm and humid subtropical climate with a mean annual temperature of ca. 16–17°C and a mean annual precipitation of ca. 1500–1600 mm in the Late Pliocene rather than a dry, hot climate today, which may be due to the local tectonic change and gradual intensification of India monsoon. The comparison of Late Pliocene climate in Eryuan, Yangyi, Longling, and Yuanmou Basin of Yunnan Province suggests that the mean annual temperatures generally show a latitudinal gradient and fit well with their geographic position, while the mean annual precipitations seem to be related to the different geometries of the valleys under the same monsoon system

Suppression of Estrogen Receptor Transcriptional Activity by Connective Tissue Growth Factor

Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER) that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF) physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs

Estrogen Induced Metastatic Modulators MMP-2 and MMP-9 Are Targets of 3,3′-Diindolylmethane in Thyroid Cancer

Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM), to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor.Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2) enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9.Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease

Peregrine and saker falcon genome sequences provide insights into evolution of a predatory lifestyle

As top predators, falcons possess unique morphological, physiological and behavioral adaptations that allow them to be successful hunters: for example, the peregrine is renowned as the world's fastest animal. To examine the evolutionary basis of predatory adaptations, we sequenced the genomes of both the peregrine (Falco peregrinus) and saker falcon (Falco cherrug), and we present parallel, genome-wide evidence for evolutionary innovation and selection for a predatory lifestyle. The genomes, assembled using Illumina deep sequencing with greater than 100-fold coverage, are both approximately 1.2 Gb in length, with transcriptome-assisted prediction of approximately 16,200 genes for both species. Analysis of 8,424 orthologs in both falcons, chicken, zebra finch and turkey identified consistent evidence for genome-wide rapid evolution in these raptors. SNP-based inference showed contrasting recent demographic trajectories for the two falcons, and gene-based analysis highlighted falcon-specific evolutionary novelties for beak development and olfaction and specifically for homeostasis-related genes in the arid environment–adapted saker

Development of Useful Recombinant Promoter and Its Expression Analysis in Different Plant Cells Using Confocal Laser Scanning Microscopy

BACKGROUND: Designing functionally efficient recombinant promoters having reduced sequence homology and enhanced promoter activity will be an important step toward successful stacking or pyramiding of genes in a plant cell for developing transgenic plants expressing desired traits(s). Also basic knowledge regarding plant cell specific expression of a transgene under control of a promoter is crucial to assess the promoter's efficacy. METHODOLOGY/PRINCIPAL FINDINGS: We have constructed a set of 10 recombinant promoters incorporating different up-stream activation sequences (UAS) of Mirabilis mosaic virus sub-genomic transcript (MS8, -306 to +27) and TATA containing core domains of Figwort mosaic virus sub-genomic transcript promoter (FS3, -271 to +31). Efficacies of recombinant promoters coupled to GUS and GFP reporter genes were tested in tobacco protoplasts. Among these, a 369-bp long hybrid sub-genomic transcript promoter (MSgt-FSgt) showed the highest activity in both transient and transgenic systems. In a transient system, MSgt-FSgt was 10.31, 2.86 and 2.18 times more active compared to the CaMV35S, MS8 and FS3 promoters, respectively. In transgenic tobacco (Nicotiana tabaccum, var. Samsun NN) and Arabidopsis plants, the MSgt-FSgt hybrid promoter showed 14.22 and 7.16 times stronger activity compared to CaMV35S promoter respectively. The correlation between GUS activity and uidA-mRNA levels in transgenic tobacco plants were identified by qRT-PCR. Both CaMV35S and MSgt-FSgt promoters caused gene silencing but the degree of silencing are less in the case of the MSgt-FSgt promoter compared to CaMV35S. Quantification of GUS activity in individual plant cells driven by the MSgt-FSgt and the CaMV35S promoter were estimated using confocal laser scanning microscopy and compared. CONCLUSION AND SIGNIFICANCE: We propose strong recombinant promoter MSgt-FSgt, developed in this study, could be very useful for high-level constitutive expression of transgenes in a wide variety of plant cells

Microfluidic preparation of polymer nanospheres

In this work, solid polymer nanospheres with their surface tailored for drug adhesion were prepared using a V-shaped microfluidic junction. The biocompatible polymer solutions were infused using two channels of the microfluidic junction which was also simultaneously fed with a volatile liquid, perfluorohexane using the other channel. The mechanism by which the nanospheres are generated is explained using high speed camera imaging. The polymer concentration (5-50 wt%) and flow rates of the feeds (50-300 µl min(-1)) were important parameters in controlling the nanosphere diameter. The diameter of the polymer nanospheres was found to be in the range of 80-920 nm with a polydispersity index of 11-19 %. The interior structure and surfaces of the nanospheres prepared were studied using advanced microscopy and showed the presence of fine pores and cracks on surface which can be used as drug entrapment locations

Ovarian cancer molecular pathology.

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