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br Genomic actions in the breast br
2019-10-14
Genomic actions in the breast Conclusion Clinical studies suggest that progesterone and/or progestins may play a decisive role in the development of breast cancer in women using hormone therapy or oral contraceptives [3], [4]. However, this data are controversial to most experimental investiga
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Thus the understanding of the various mechanisms of action o
2019-10-14
Thus, the understanding of the various mechanisms of action of estrogen and SERMs is an important medical challenge and could help to develop an “ideal” SERM, preserving the beneficial effects of estrogen in the bone and urogenital system, and reducing the unwanted side effects, mainly increased ris
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One possibility to differentiate between the
2019-10-14
One possibility to differentiate between the two failure modes, and also to identify the corresponding characteristics of the resulting fracture surface, is a series of FNCT measurements with varying nominal (initial) stress. The dependence of the observed time to failure tf on the actual stress cha
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Another milestone in the field is the de
2019-10-14
Another milestone in the field is the de novo discovery of EPAC2 and EPAC1 specific inhibitors through fluorescence-based HTS assays. Due to the excellent EPAC/PKA selectivity of Pertussis Toxin , it has been widely applied as a useful chemical probe to discriminate EPAC related signaling pathways a
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br Structure of USP Schematic representation of the USP doma
2019-10-14
Structure of USP7 Schematic representation of the USP7 domain architecture is shown in Fig. 3B. USP7 is a 135 kDa protein that consists of seven domains, including the N-terminal TRAF-like (Tumor necrosis factor Receptor–Associated Factor) domain, followed by the catalytic core domain and the fiv
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br Ubiquitin Capture by the
2019-10-14
Ubiquitin Capture by the Mobile APC11 RING Domain Contributes to Processive Substrate Ubiquitylation Although the rules of Ub-mediated proteolysis are only beginning to emerge, the rate and order in which different APC/C substrates are degraded during the JQ1 correlates with processivity of their
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Another pathway that requires proper DUB
2019-10-14
Another pathway that requires proper DUB recruitment is the DNA damage response (DDR). After ultraviolet (UV)-induced DNA damage, monoubiquitylated proliferating cell nuclear antigen (PCNA) mediates signaling that leads to repair. The DUB complex USP1/USP1-associated factor 1 (UAF1) deubiquitylates
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br Molecular modeling study Molecular modeling study was
2019-10-14
Molecular modeling study Molecular modeling study was essentially needed to understand and interpret the DHFR inhibitory pattern of this new class of compounds. Computational docking is an algorithm designed to estimate two main terms. The first is to determine the suitable position and the orien
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As a basis for the DDR substrate identification approach det
2019-10-14
As a basis for the DDR1 substrate identification approach detailed below, we first set out to perform 2D-gel electrophoresis with lysates isolated from collagen-stimulated human breast cancer MDA-MB-231 Obeticholic Acid overexpressing DDR1 (b-isoform). This allowed us to determine whether DDR1 is no
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In the pleural exudates which
2019-10-14
In the pleural exudates, which reflect the in vivo conditions, the concentrations of CysLTs and PGE2 were quite similar. However, when cancer NECA were cultured for 24 h, both analyses of cell culture medium and cell incubations with Ca2+ ionophore showed low levels of CysLTs. In contrast, the pred
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br Introduction br Conclusion br Acknowledgments and
2019-10-14
Introduction Conclusion Acknowledgments and Funding Introduction Reversible protein phosphorylation is an important post-translational modification of proteins regulating many processes in the cell. Approximately one third of the cellular proteome is phosphorylated, and several sites are
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Although CK phosphorylated Msn as well as
2019-10-14
Although CK2 phosphorylated Msn4 as well as Msn2 (Fig. 1A), the two CK2-dependent phosphorylation sites in Msn2 are not conserved in Msn4. Thus, Msn2 and Msn4 might be differently regulated by CK2-dependent phosphorylation. Msn2 and Msn4, which have 41% identity and similarity in size and amino sali
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Although several genomic technologies including the generati
2019-10-14
Although several genomic technologies, including the generation of ERRγ-specific knockout mice, have revealed that ERRγ plays a pivotal role in cellular bioenergetics [1], its involvement in other metabolic pathways has been appreciated only recently. Therefore, we highlight recent findings on the r
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Recently roflumilast has been approved as the first selectiv
2019-10-14
Recently, roflumilast has been approved as the first selective PDE4 inhibitor for the treatment of chronic obstructive pulmonary disease (COPD) [2]. Roflumilast has been suggested to target several different pathogenetic mechanisms, including inflammation, fibrotic, emphysematous and vascular remode
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The synthetic routes to the substrates
2019-10-14
The synthetic routes to the substrates based on the 2,3-dihydroxynaphthalene and 6,7-dibromo-2,3-dihydroxynaphthalene cores are depicted in Scheme 3. A Michael-type glycosylation of 2,3-dihydroxynaphthalene 16a gave the acetylated sugar 17a which was deprotected giving the required β-glucosidase sub