123,740 research outputs found
Erbb4 (Jm-B/Cyt-1)-Induced Expression and Phosphorylation of C-Jun Is Abrogated by Human Papillomavirus Type 16 E5 Protein
No full textHuman papillomavirus type 16 E5 (HPV-16 E5) is a highly hydrophobic membrane protein with weak-transforming activity , which is associated with ErbB4 receptor in HPV-16-infected cervical lesions. Presently, we investigated the transforming mechanisms of E5 involving ErbB4 signaling. Firstly, we report a role for ErbB4 (JM-b/CYT-1) receptor that activates c -jun gene expression and phosphorylating at Ser63 and Ser73 of the c-Jun protein in ligand-independent and Ras-c-jun NH2-terminal kinase-dependent pathway. Secondly, we show that HPV-16 E5 protein can form a complex with ErbB4 via binding to the extracellular and transmembrane domains of ErbB4 (JM-b/CYT-1). When co- expressing HPV-16 E5 and ErbB4 in cells, E5 can abrogate ErbB4-induced c-Jun protein expression and phosphorylation resulted in increasing cell proliferation compared to ErbB4- expressing cells. The interaction between of HPV-16 E5 and ErbB4 provides more insight into the mechanisms of HPV-16 E5 transformation induction
Expression and Androgen Regulation of C-Cam Cell Adhesion Molecule Isoforms in Rat Dorsal and Ventral Prostate
No full textC-CAM is an epithelial cell adhesion molecule with two major splice variants that differ in the length of the cytoplasmic domain. C-CAM1 (long (L)-form) strongly suppresses the tumorigenicity of human prostate carcinoma cells. In contrast, C-CAM2 (short (S)-form) does not exhibit tumor-suppressive activity. In the present study we have investigated the functional significance of L-form and S- form C-CAM in rat prostate by examining their expression and distribution in different prostate lobes and their response to androgen deprivation. RNase protection assays with a probe for both C-CAM isoforms detected high levels of C-CAM messages in the rat dorso-lateral prostate (DLP). L- and S- form proteins, localized by indirect immunofluorescence using isoform-specific antipeptide antibodies, were co- expressed on the apical surface of prostate epithelial cells in normal DLP. Androgen depletion did not significantly change the steady state levels of C-CAM message and protein expression in the DLP, although there was a change in the pattern of protein expression in these lobes. In contrast, C -CAM isoform messages and proteins were undetectable in normal ventral prostate (VP) but increased markedly in this lobe in response to castration, producing isoform ratios similar to those in DLP. These results demonstrate that coordinate expression of C- CAM isoforms is maintained in the VP following androgen depletion and suggest that androgen suppresses C-CAM expression in VP but not in DLP. These results suggest that balanced expression of L- and S-form C- CAM is important for normal prostate growth and differentiation
Electrochemical Detection of High-Sensitivity C-Reactive Protein Based on Biomimic Design of Electroactive Nanoassembly Multilayers
No full textIn this study, the gold electrode was modified with a ferrocene-terminated alkanethiol and phospholipid complex layer, which is designed and fabricated to serve as a C-reactive protein sensor using electrochemical determination. The scope of this research is to know whether a ferrocene-terminated self-assembled monolayer and hydrogenated phosphocholine hybrid bilayer could be used to perform C-reactive protein detection or not. After a series of experiments, the result shows that mixed electroactive SAM can facilitate electrons transferring from the solution to the electrode. And after coating phospholipids, this phenomenon seems to be hindered from the electrode. But this provoked small electrical signal of the recognition layer still allows for further usage. According to the result, it can be used to measure C-reactive protein and its electrochemical property and the changes of the electrode's electron transfer ability are characterized by cyclic voltammetry. This study demonstrates self-assembled ferrocene-terminated alkanethiol and phospholipid complex structure has potential as a C-reactive protein sensor and is stable to detect in the aqueous phase.補正完
Cystatin C and Long-Term Mortality among Subjects with Normal Creatinine- Based Estimated Glomerular Filtration Rates
No full textObjectives The objective was to test the association of cystatin C (Cys-C ) with long-term mortality risk in the subjects with normal creatinine- based estimated glomerular filtration rates (eGFR). Background Cys-C has been proposed as a sensitive indicator of renal dysfunction that is associated with cardiovascular events. The predictive value of Cys-C for mortality risk (both cardiovascular and noncardiovascular) and its utility among persons with normal kidney function remains unclear. Methods The analysis included 2,990 subjects over 40 years of age with normal eGFR who participated in NHANES III (Third National Health and Nutrition Examination Survey). Normal eGFR was defined by Modification of Diet in Renal Disease (MDRD) equation >= 60 ml/min/1.73 m(2). Serum Cys-C was categorized as high, medium, or low. In 1 analysis, the high and low groups were the top and bottom 10%, and in the second analysis, they were the upper and lower thirds. All-cause and cause- specific mortality were obtained from the NHANES III-linked follow-up file through December 31, 2006. Multivariate Cox regression models were applied to assess the association of interest. Results Within an average of 13.7 years follow-up , 488 cardiovascular and 719 noncardiovascular deaths occurred. When the first and last deciles were compared, the relative risks were all increased statistically as follows: allcause, 4.36 (95% confidence interval [CI]: 2.52 to 7.82) ; cardiovascular, 7.44 (95% CI: 3.06 to 18.1) ; cancer, 2.45 (95% CI: 0.85 to 7.04); and noncardiovascular 3.15 (95% CI: 1.53 to 6.49) mortalities. Relative risks all moderated to lower values when the comparisons were expanded to include the upper and lower thirds. Similar associations were still present when Cys-C was modeled on a continuous scale, suggesting a linear relationship between Cys-C and mortality outcomes. Conclusions Serum Cys-C is prognostic of long- term mortality in the subjects with relatively normal renal function, independent of MDRD eGFR and albuminuria
Hyllus C. L. Koch 1846
No full textGenus Hyllus C. L. Koch, 1846 Type species. Hyllus giganteus C. L. Koch, 1846 from Indonesia.Published as part of Lin, Yejie, Zhao, Huifeng, Koh, Joseph K H & Li, Shuqiang, 2022, Taxonomy notes on twenty-eight spider species (Arachnida: Araneae) from Asia, pp. 198-270 in Zoological Systematics 47 (3) on page 230, DOI: 10.11865/zs.2022303, http://zenodo.org/record/717585
A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation
No full text. Chang S-N, Tsai C-T, Wu C-K, Lee J-K, Lai L-P, Huang S-W, Huang L-Y, Tseng C-D, Lin J-L, Chiang F-T, Hwang J-J (National Taiwan University Hospital Yun-Lin Branch, Yun-Lin; National Taiwan University Hospital, Taipei; National Taiwan University Hospital, Taipei; Institute of Pharmacology, Taipei; and Graduate Institute of Biomedical Engineering, Taipei, Taiwan). A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med 2012; 272: 305315. Objectives. In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. Methods.similar to A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. Results.similar to Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. Conclusion.similar to A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis
Differential roles of the microRNA let-7 in C. elegans tissue development
No full textThe organs and tissues of the human body comprise of an astonishing variety of cells as different in morphology and function as muscle cells and neurons. Amazingly, despite their different protein contents, they largely contain the identical genomic information. In order to understand the processes that enable this differentiation, we need to determine the underlying regulatory mechanisms. A very recent discovery in this context was the posttranscriptional regulation of gene expression by microRNAs (miRNAs). miRNAs are small RNA molecules that mediate translational repression and degradation of mRNA transcripts through partial complementarity to their 3’ untranslated region (UTR) . Among the first miRNAs to be identified, let-7 stands out for its high conservation in sequence and developmental functions in development throughout the animal kingdom. During my PhD, I studied the role of let-7 in Caenorhabditis elegans in the context of two distinct processes of tissue development, namely differentiation of the epidermis (called hypodermis), and morphogenesis of the vulva. The functions of the let-7 miRNA in formation of the adult cuticle have been extensively studied and are well understood. let-7 controls differentiation of specific, mitotically active epidermal cells by inducing cell cycle exit, fusion, and switch to an adult specific transcriptional program upon repression of targets such as lin-41, daf-12, hbl-1 and let-60/ras. I set out to identify novel interactors of let-7 in a genome-wide RNAi screen for suppression of the lethal let-7 bursting phenotype. Candidates were then verified using fluorescence-based reporter systems for onset of hypodermis differentiation and intensity of repression of a known target. Thereby, I was able to validate a whole set of novel members of the let-7 network, comprising genes downstream in the pathway as well as potential regulators of let-7 activity. Notably, both groups of repressors contain factors required for cell cycle progression and mitosis, which indicates an active crosstalk between let-7 and the cell-cycle machinery. In a second project, I explored the molecular basis for the prominent let-7 vulval bursting phenotype. Despite the absence of overproliferation or any other obvious phenotype in vulval morphogenesis, I was able to show that let-7 activity is required in the vulva, and that its major function in this context is repression of a single target, namely lin-41. Disruption of let-7 binding to lin-41 through modification of the let-7 complementary sites by CRISPR/Cas9 mediated genome editing suffices to trigger the bursting phenotype, proving that repression of a single target is the key function of the miRNA in this context. In summary, my work shows that while both differentiation of hypodermis as well as vulval integrity are mediated through repression of lin-41, the downstream effect of this regulation seem to differ, suggesting that let-7 can be wired to control distinct processes depending on the cellular context. With respect to the latest findings both in C. elegans as well as in mammals, it will be interesting to determine if this depends on differential molecular functions of LIN-41 in the two tissues
- …
