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Therapeutic options targeting intrahepatic resistance
2020-11-03

Therapeutic options targeting intrahepatic resistance are very limited. Theoretically, the NO-cGMP pathway may be influenced at several sites. Yet, most strategies did not reach clinical practice or yielded disappointing results, such as activators of soluble guanylate cyclase [14], NO releasing der
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Although the mechanisms underlying the EP
2020-11-03

Although the mechanisms underlying the EP4-mediated increase in the frequency of mEPSCs via PGE2 remain unclear, mechanisms similar to those driven by EP2 may be involved because activation of both these receptor subtypes increases the intracellular concentration of cAMP (Nishigaki et al., 1995, Sug
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br Results br Discussion In this
2020-11-03

Results Discussion In this paper we present insights into the observed specificities of inhibitors targeting the ubiquitin-activating and related E1 LDE225 Diphosphate via crystal structures of the specific NEDD8-E1 inhibitor MLN4924, the dual NEDD8/Ub E1 inhibitor ABPA3, and the selective Ub
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It has previously been established
2020-11-03

It has previously been established that DDRs play an important role in collagen regulation in at least two distinct ways: (1) activation of DDRs by collagen results in up-regulation of the matrix metalloproteinases, which results in cleavage and degradation of the ECM20., 21., [22] and (2) gdc-0980
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br Concluding Remarks Recent studies have
2020-11-03

Concluding Remarks Recent studies have provided unprecedented details of APC/C structure and enzymology, which explain how the activity of this massive E3 ligase is controlled, and how ubiquitylation is achieved to temporally regulate cell division. Although one pervasive question has been why th
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br E E backside interaction The E possesses an
2020-11-03

E3–E2 backside interaction The E2 possesses an important regulatory interface which is termed its backside as it is opposite to the catalytic cleft that bears the active-site cysteine forming the thioester with SUMOD. This backside site interacts noncovalently with a scaffold SUMOB and was origin
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br Transparency document br Main
2020-11-03

Transparency document Main Text The centrosome is a non-membrane-bound organelle found in most animal cells. It has several important functions, including control of cilia formation, microtubule organization and nucleation, spindle assembly and transport of organelles and vesicles. Centrosomes
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br The central role of DNA PK in the
2020-11-03

The central role of DNA-PK in the NHEJ NHEJ can be divided in several steps (Fig. 1A): 1) recognition and binding of Ku at each ends of the DSB following by the assembly of the DNA-PK at the break points and bridging; 2) phosphorylation of the DNA ends by DNA-PKcs; 3) ligation of the ends by DNA
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To overcome problems with the biochemical reconstitution of
2020-11-03

To overcome problems with the biochemical reconstitution of these heterodimeric cytokines fusion strategies linking both subunits together have been proposed inspired by the “hyper-IL-6” [28]. Much like fusing a protein to a solubility enhancing protein such as MBP or SUMO, fusing two subunits of a
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br Genomic actions in the breast
2020-11-02

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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Additionally although the membrane localized ER
2020-11-02

Additionally, although the membrane-localized ER signaling described in this review has generally been studied in isolation from nuclear signaling, it is becoming clearer and clearer that integration of these mechanisms must be considered (Frick, 2015). Perhaps the distinct estradiol signaling mecha
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br Materials and methods br Results br
2020-11-02

Materials and methods Results Discussion PKA and Epac are two principal effector proteins involved in cAMP signaling; they are expressed in a wide range of tissues and control diverse biological functions [10]. The existence of two cAMP effectors provides more precise regulation of cAMP sig
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Because of the lack of sequence current
2020-11-02

Because of the lack of sequence, current knowledge on the cellular regulation of CoA-IT is scarce. However, recent work has suggested an interesting new role for CoA-IT in regulating the extent of the AA mobilization response in primed macrophages. Bacterial lipopolysaccharide (LPS) is a poor trigge
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PKA signalling in the nucleus was thought to
2020-11-02

PKA signalling in the nucleus was thought to be due to the translocation of the catalytic subunit upon activation from the CCT241533 to the nucleus via diffusion [72]. However, a new understanding has emerged, as both the regulatory and catalytic subunits have been identified in the nucleus and fun
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The glycolytic pathway is a catabolic route that ends
2020-11-02

The glycolytic pathway is a catabolic route that ends with the synthesis of pyruvate (Pyr). In Arabidopsis embryos, the conversion of phosphoenolpyruvate (PEP) to Pyr, catalyzed by pyruvate kinase (PK), is mainly located in the plastids [10], [11]. The preceding reaction is catalyzed by enolase (ENO
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