362,883 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
Molecular structure of highly excited resonant states in Mg-24 and the corresponding Be-8+O-16 and C-12+C-12 decays
No full textExotic Be-8 and C-12 decays from high-lying resonances in Mg-24 are analyzed in terms of a cluster model. The calculated quantities agree well with the corresponding experimental data. It is found that the calculated decay widths are very sensitive to the angular momentum carried by the outgoing cluster. It is shown that this property makes cluster decay a powerful tool to determine the spin as well as the molecular structures of the resonances.Physics, NuclearSCI(E)7ARTICLE5null8
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Quantitative Insights into Developmental Signals and Phenotypes in C. elegans
Full text linkDesign of biomaterials and cellular scaffolds for tissue-engineering applications and regenerative medicine requires a precise understanding of the principles underlying multicellular patterning. Adhesion, migration, division, differentiation, and apoptosis are characteristic cellular behaviors, the engineering of which has the potential to allow creation of custom, multicellular structures. These cellular events occur naturally during embryonic and postembryonic development of multicellular organisms. Development thus offers the opportunity to learn about the design principles and molecular mechanisms that guide cellular patterning.
A key finding in developmental biology is that a limited set of conserved molecular signaling pathways act at multiple times and locations throughout the embryo to introduce cell-fate asymmetries in homogenous populations of cells. In turn, these asymmetries serve as starting points for the patterning of new organs. These signaling pathways interact quantitatively at multiple levels, including signaling cues, post-translational regulation, and gene-regulatory networks, to guide multicellular patterning.
How does the quantitative performance of these signaling networks ensure the intended phenotype pattern? How do changes in the quantitative performance of these networks, possibly over the course of evolution, give rise to new phenotypes? These are the central questions pursued in this thesis.
In order to answer such questions, we used vulva formation in the nematode Caenorhabditis elegans as a model system of cellular patterning. We formulated a mathematical model of the molecular network underlying cellular-fate specification in this system. Computational analysis of this molecular network reveals that cell–cell coupling through lateral LIN-12/Notch signaling amplifies the perception of the gradient in the epidermal-growth-factor-like soluble cue, LIN-3. Thus, the gradient in LIN-3 concentration produces an even steeper difference in LIN-3-mediated intracellular signals between adjoining cells. Such gradient amplification may be particularly important in converting a shallow, graded-specification signal into a spatial pattern of distinct fate choices.
Through quantitative perturbations of interaction strengths between components of the vulval patterning network, we further show that our modeling approach can correctly predict phenotype patterns observed in C. elegans mutation studies. This study generated a framework for quantitative analysis of molecular networks that links quantitative molecular perturbations to patterning outcomes. This framework will prove useful in the analysis of other systems involving cellular fate decisions and in tissue engineering applications where the generation of precise cell patterns is needed. We demonstrate the generality of our approach through an application to evolutionary developmental biology. Since molecular connectivity of the vulva patterning network of several closely related Caenorhabditis species is preserved, we correctly predict the quantitative diversification that must have occurred in this network during species evolution.</p
Social Capital and Cross-Selling within Financial Holding Companies in an Emerging Economy
No full textCystatin 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
On the sheaf-theoretic SL(2, C) Casson–Lin invariant
No full textWe prove that the (τ-weighted, sheaf-theoretic) SL(2, C) Casson–Lin invariant introduced by Manolescu and the first author is generically independent of the parameter τ and additive under connected sums of knots in integral homology 3-spheres. This addresses two questions asked by Manolescu and the first author. Our arguments involve a mix of topology and algebraic geometry, and rely crucially on the fact that the SL(2, C) Casson–Lin invariant admits an alternative interpretation via the theory of Behrend functions.</p
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