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281.
Sousa AM Liu T Guevara O Stevens J Fanburg BL Gaestel M Toksoz D Kayyali US 《Journal of cellular biochemistry》2007,100(6):1581-1592
Fibroblasts play a major role in processes such as wound repair, scarring, and fibrosis. Differentiation into myofibroblasts, characterized by upregulation of smooth muscle alpha-actin (smalpha) in response to profibrotic agents such as TGFbeta is believed to be an important step in fibrosis. Therefore, elucidating mechanisms of myofibroblast differentiation might reveal novel targets in treating diseases such as idiopathic pulmonary fibrosis (IPF). MK2 is a kinase substrate of p38 MAP kinase that mediates some effects of p38 activation on the actin cytoskeleton. Using mouse embryonic fibroblasts (MEF) from MK2 knockout (MK2(-/-)) mice, we demonstrate that disrupting expression of MK2 expression reduces filamentous actin and stress fibers. It also causes MK2(-/-) MEF to express less smalpha than their corresponding wild-type (WT) MEF at baseline and in response to TGFbeta. Furthermore, TGFbeta causes downregulation of smalpha in MK2(-/-) MEF, instead of upregulation observed in WT MEF. Expression of other fibroblast markers, such as collagen, is not altered in MK2(-/-) MEF. Our results further suggest that downregulation of smalpha in MK2(-/-) MEF is not due to lack of activation of serum responsive promoter elements, but probably due to reduced smalpha message stability in these cells. These results indicate that MK2 plays a key role in regulation of smalpha expression, and that targeting MK2 might present a therapeutic approach in managing conditions such as pulmonary fibrosis. 相似文献
282.
Aziz Inan Celik Mehmet Kanadasi Mesut Demir Ali Deniz Rabia Eker Akilli Onur Sinan Deveci Caglar Emre Cagliyan Caglar Ozmen Firat Ikikardes Muhammet Bugra Karaaslan 《Indian pacing and electrophysiology journal》2019,19(1):9-14
Background
Cryoballoon-based pulmonary vein isolation (PVI) is a treatment option for atrial fibrillation (AF). Left atrial volume (LAV) and left atrial volume index (LAVi) are important parameters for long term success of PVI. Galectin-3 (Gal-3) and neutrophil to lymphocyte ratio (N/L ratio) are biomarkers to demonstrate the cardiac fibrosis and remodelling.Methods
50 patients with symptomatic PAF despite ≥1 antiarrhythmic drug(s), who underwent PVI were enrolled. LAV, LAVi, Gal-3 and N/L ratio were calculated before ablation and after ablation at 6 and 12 months. According to AF recurrence patients were divided into two groups, recurrent AF (n?=?14) and non-recurrent AF (n?=?36).Results
In both groups (recurrent and non-recurrent), initial and 12 months follow-up LAV values were 41.39?±?18.13?ml and 53.24?±?22.11?ml vs 48.85?±?12.89?ml and 42.08?±?13.85 (p?=?0.037). LAVi were 20.9?±?8.91 ml/m2 and 26.85?±?11.28 ml/m2 vs 25.36?±?6.21 and 21.87?±?6.66 (p?=?0.05) for recurrent and non-recurrent AF groups, respectively. In both groups PVI had no significant effect on serum Gal-3 levels and N/L ratio during 12 months follow-up. The comparison between two groups at the end of 12th month showed Gal-3 values of 6.66?±?4.09?ng/ml and 6.02?±?2.95?ng/ml (p?=?0.516), N/L ratio values of 2.28?±?1.07 103/μl and 1.98?±?0.66?103/μl (p?=?0.674).Conclusion
LAV and LAVi are useful to predict the remodelling of the left atrium and AF recurrence after cryoballoon-based PVI. However, biomarkers such as Gal-3 and N/L ratio are not associated with AF recurrence. 相似文献283.
Deniz Yildirim Sevgi Ates Birgul Yazici S. Seyhan Tukel 《Biocatalysis and Biotransformation》2019,37(3):210-223
In this study, Rhizomucor miehei lipase (RML) was immobilized on the hexagonally-ordered nanoporous aluminium oxide membranes (RML-Al2O3-NP) by adsorption and as protein-coated microcrystals (RML-PCMCs) by simultaneously precipitating RML on micron-sized potassium sulfate crystals (K2SO4) in pre-chilled acetone. The hydrolytic activities of immobilized lipase preparations were investigated in terms of p-nitrophenyl palmitate hydrolysis and their esterification activities were examined for the synthesis of some aroma esters such as butyl acetate, isoamyl acetate, hexyl acetate, heptyl acetate, and geranyl acetate. The immobilization yields were 33.8 and 25.1%, respectively for RML immobilized on Al2O3-NP membranes and potassium sulfate crystals. The catalytic efficiency ratios of RML-Al2O3-NP and RML-PCMCs were 2.3- and 3.9-fold higher than that of the free lipase, respectively in terms of hydrolytic activity. The free lipase was stabilized as 4.1- and 10.5-fold, respectively at 40 and 50?°C when immobilized on Al2O3-NP. The corresponding stabilization factors were 4.6- and 12.8-fold higher for RML-PCMCs. RML-Al2O3-NP and RML-PCMCs maintained 84 and 86% of their initial hydrolytic activities, respectively after 10 reuses. Of the synthesized aroma esters, the highest yield was obtained for the geranyl acetate. After 4?h reaction time, no geraniol was detected in the preparative-scale (196?g/L) synthesis of geranyl acetate for both the immobilized lipases when the initial geraniol amount, vinyl acetate amount, RML-PCMCs amount, and reaction temperature values were 1?mmol, 3?mmol, 100?mg (or 300?mg RML-Al2O3-NP), and 50?°C, respectively. These results show that the immobilization of R. miehei lipase by adsorption on nanoporous aluminium oxide and as protein-coated microcrystals leads to the obtention of highly stable, catalytically more active, and reusable lipase preparations. 相似文献
284.
285.
Photochemical Transformations in Fullerene and Molybdenum Oxide Affect the Stability of Bilayer Organic Solar Cells
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Hui Zhang Andreas Borgschulte Fernando A. Castro Rowena Crockett Andreas C. Gerecke Okan Deniz Jakob Heier Sandra Jenatsch Frank Nüesch Carlos Sanchez‐Sanchez Alina Zoladek‐Lemanczyk Roland Hany 《Liver Transplantation》2015,5(2)
Thin films of fullerene C60 and molybdenum oxide (MoO3) are ubiquitously used as the electron acceptor material and hole extraction interfacial layer for the fabrication of organic photovoltaic (OPV) cells. It is well known that light exposure induces color changes in MoO3 (photochromism) and the formation of intermolecular bonds between C60 molecules (photopolymerization). The influence of these photoinduced reactions on the long‐term stability of OPV cells, however, has not previously been studied in detail. Here, a study and discussion of the early (<5 days) aging mechanisms occurring in illuminated ITO/MoO3/organic cyanine dye/C60/Alq3/Ag bilayer solar cells under nitrogen atmosphere is presented. A degradation process at the organic heterojunction is identified and the formation of Mo5+ species during illumination is found to adversely affect cell behavior. For these widely used materials, the results suggest that light processing is a first necessary step before OPV characteristics can be meaningfully rated. 相似文献
286.
Nausicaa V Licata Riccardo Cristofani Sally Salomonsson Katherine M Wilson Liam Kempthorne Deniz Vaizoglu Vito G DAgostino Daniele Pollini Rosa Loffredo Michael Pancher Valentina Adami Paola Bellosta Antonia Ratti Gabriella Viero Alessandro Quattrone Adrian M Isaacs Angelo Poletti Alessandro Provenzani 《The EMBO journal》2022,41(1)
Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat‐associated non‐AUG (RAN) translation of repeat‐containing C9orf72 RNA results in the production of neurotoxic dipeptide‐repeat proteins (DPRs). Here, we developed a high‐throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP‐elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA‐catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient‐derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD. 相似文献
287.
Elaine P. S. Gee Deniz Yüksel Collin M. Stultz Donald E. Ingber 《The Journal of biological chemistry》2013,288(29):21329-21340
Fibronectin (FN) assembly into extracellular matrix is tightly regulated and essential to embryogenesis and wound healing. FN fibrillogenesis is initiated by cytoskeleton-derived tensional forces transmitted across transmembrane integrins onto RGD binding sequences within the tenth FN type III (10FNIII) domains. These forces unfold 10FNIII to expose cryptic FN assembly sites; however, a specific sequence has not been identified in 10FNIII. Our past steered molecular dynamics simulations modeling 10FNIII unfolding by force at its RGD loop predicted a mechanical intermediate with a solvent-exposed N terminus spanning the A and B β-strands. Here, we experimentally confirm that the predicted 23-residue cryptic peptide 1 (CP1) initiates FN multimerization, which is mediated by interactions with 10FNIII that expose hydrophobic surfaces that support 8-anilino-1-napthalenesulfonic acid binding. Localization of multimerization activity to the C terminus led to the discovery of a minimal 7-amino acid “multimerization sequence” (SLLISWD), which induces polymerization of FN and the clotting protein fibrinogen in addition to enhancing FN fibrillogenesis in fibroblasts. A point mutation at Trp-6 that reduces exposure of hydrophobic sites for 8-anilino-1-napthalenesulfonic acid binding and β-structure formation inhibits FN multimerization and prevents physiological cell-based FN assembly in culture. We propose a model for cell-mediated fibrillogenesis whereby cell traction force initiates a cascade of intermolecular exchange starting with the unfolding of 10FNIII to expose the multimerization sequence, which interacts with strand B of another 10FNIII domain via a Trp-mediated β-strand exchange to stabilize a partially unfolded intermediate that propagates FN self-assembly. 相似文献
288.
One of the central puzzles in the study of sociocultural evolution is how and why transitions from small-scale human groups to large-scale, hierarchically more complex ones occurred. Here we develop a spatially explicit agent-based model as a first step towards understanding the ecological dynamics of small and large-scale human groups. By analogy with the interactions between single-celled and multicellular organisms, we build a theory of group lifecycles as an emergent property of single cell demographic and expansion behaviours. We find that once the transition from small-scale to large-scale groups occurs, a few large-scale groups continue expanding while small-scale groups gradually become scarcer, and large-scale groups become larger in size and fewer in number over time. Demographic and expansion behaviours of groups are largely influenced by the distribution and availability of resources. Our results conform to a pattern of human political change in which religions and nation states come to be represented by a few large units and many smaller ones. Future enhancements of the model should include decision-making rules and probabilities of fragmentation for large-scale societies. We suggest that the synthesis of population ecology and social evolution will generate increasingly plausible models of human group dynamics. 相似文献
289.
Christian Erbel Deniz Okuyucu Mohammadreza Akhavanpoor Li Zhao Susanne Wangler Maani Hakimi Andreas Doesch Thomas J. Dengler Hugo A. Katus Christian A. Gleissner 《Journal of visualized experiments : JoVE》2014,(87)
Atherosclerosis is a chronic inflammatory disease of the vasculature. There are various methods to study the inflammatory compound in atherosclerotic lesions. Mouse models are an important tool to investigate inflammatory processes in atherogenesis, but these models suffer from the phenotypic and functional differences between the murine and human immune system. In vitro cell experiments are used to specifically evaluate cell type-dependent changes caused by a substance of interest, but culture-dependent variations and the inability to analyze the influence of specific molecules in the context of the inflammatory compound in atherosclerotic lesions limit the impact of the results. In addition, measuring levels of a molecule of interest in human blood helps to further investigate its clinical relevance, but this represents systemic and not local inflammation. Therefore, we here describe a plaque culture model to study human atherosclerotic lesion biology ex vivo. In short, fresh plaques are obtained from patients undergoing endarterectomy or coronary artery bypass grafting and stored in RPMI medium on ice until usage. The specimens are cut into small pieces followed by random distribution into a 48-well plate, containing RPMI medium in addition to a substance of interest such as cytokines or chemokines alone or in combination for defined periods of time. After incubation, the plaque pieces can be shock frozen for mRNA isolation, embedded in Paraffin or OCT for immunohistochemistry staining or smashed and lysed for western blotting. Furthermore, cells may be isolated from the plaque for flow cytometry analysis. In addition, supernatants can be collected for protein measurement by ELISA. In conclusion, the presented ex vivo model opens the possibility to further study inflammatory lesional biology, which may result in identification of novel disease mechanisms and therapeutic targets. 相似文献
290.
Marquitta J. White Fatih Eren Deniz Agirbasli Scott M. Williams Mehmet Agirbasli 《PloS one》2015,10(2)
BackgroundMetabolic syndrome (MetS) is a complex disorder characterized by coexistence
of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high
blood pressure and insulin resistance. The presence of MetS is strongly
associated with increased risk of cardiovascular disease (CVD). The syndrome
was originally defined as an adult disorder, but MetS has become
increasingly recognized in children and adolescents.MethodsGenetic variants influence biological components common to the CM factors
that comprise MetS. We investigated single locus associations between six
single nucleotide polymorphisms (SNPs), previously shown to modulate lipid
or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish
pediatric cohort (37 cases, 323 controls).ResultsLogistic regression analysis revealed a significant association between
rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006). The
association with MetS remained after sequential adjustment for each CM
factor included in the syndrome definition, indicating that the identified
association is not being driven by any single trait. A relationship between
rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS
status. In control subjects, the A allele of rs1799941 associated with a
significant increase in SHBG levels (p = 0.012), while in cases there was no
association between rs1799941 and SHBG levels (p = 0.963).ConclusionsThe significant association between rs1799941 and MetS in children is not
contingent on any single CM trait. Additionally, the presence of MetS may
abrogate effect of rs1799941 polymorphism on SHBG levels in children. 相似文献