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br Conclusions When the authors joined the field
2019-10-22

Conclusions When the authors joined the field of oxysterol analysis around the turn of the century, oxysterols and cholestenoic acids were mostly considered as uninteresting intermediates of cholesterol metabolism. Some oxysterols had been shown to have biological activity, but the most studied o
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Here we discuss implications of several major
2019-10-22

Here, we discuss implications of several major families of RING-type E3 ubiquitin ligases (MDM, Cullin, GRAIL, TRAF, TRIM) as targets in inflammation and immunity, and provide insights into potential small molecule interventions to mediate the cellular responses (summarized in Table 1). We briefly c
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br Materials and methods br Results br Discussion UPP compon
2019-10-22

Materials and methods Results Discussion UPP components including the proteasome, E1s, E2s, E3s and DUBs may become one the most important PS-1145 mg of therapeutic targets for the pharmaceutical industry in the near future and supersede those which are involved in the phosphorylation syst
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The aniline R group was extensively explored
2019-10-21

The aniline R2 group was extensively explored and a large variety of substitution was tolerated at several positions on the aryl ring (). Notably, substitution at the 3-position often gave increased potency. Increasing lipophilic bulk at this position gave increasing potency within an ether series (
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Peptides undergoing only a single hydroxylation
2019-10-21

Peptides undergoing only a single hydroxylation, i.e. PA-Hyp-KPAPK and PAPK-Hyp-APK, were then used to investigate the kinetics of vCPH co-factor and co-substrate dependences. The values for KMapp for Fe(II) and KM for 2OG for the two peptide substrates were within error (KMapp, Fe(II): 0.9 μM ± 0.1
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Bromoenol lactone Previously published data showed an intera
2019-10-21

Previously published data showed an interaction of α-tubulin and CK1δ [15] that was validated in the present study using SPR (Fig. 1A). The dominant motifs involved in the CK1δ/α-tubulin interface were defined using a peptide library of peptides covering the CK1δ amino Bromoenol lactone sequence (S
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br Loss of Chk sensitizes cells to hypoxia reoxygenation In
2019-10-21

Loss of Chk 1 sensitizes Fmoc-Cys(Trt)-ol to hypoxia/reoxygenation In contrast to Chk 2, studies have identified Chk 1 as being phosphorylated in an ATR-dependent manner at residue serine 345 during hypoxia [18]. More recently, siRNA mediated inhibition of Chk 1 signaling was found to sensitize
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br Introduction Hematopoietic stem cells and
2019-10-21

Introduction Hematopoietic stem Oxytocin and leukemic stem cells (HSCs and LSCs, respectively) both have a capacity of self-renewal. Whereas HSCs give rise to all blood lineages during lifetime hematopoiesis, LSCs are responsible for the initiation and propagation of leukemia, as well as drug re
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Although MMP might be a downstream target of
2019-10-21

Although MMP-9 might be a downstream target of Src kinase signaling (Liu and Sharp, 2011), a direct connection has not been established. We showed for the first time that, in the collagenase-induced ICH model, Src kinase signaling regulates MMP-9 activity and mediates EP1R toxicity. Consistent with
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Omar Farha and coworkers have recently successfully
2019-10-21

Omar Farha and coworkers have recently successfully employed metal-organic frameworks (MOFs) to tackle these limitations while retaining the essential characteristics of an immobilization material. MOFs consist of metal ions, or small clusters thereof, coordinated with organic ligands. MOFs are high
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Likewise the conserved cysteine in the
2019-10-21

Likewise, the conserved cysteine in the E2 protein is the only residue shown to be essential for the transfer of Ub/Ubl from E2 to the HECT ligases (Dye and Schulman, 2007, Wu et al., 2003). However, all other terminal Ub/Ubl transfer reactions involving E2 enzymes suggest a critical role for the ta
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br Material and methods br Results
2019-10-19

Material and methods Results Discussion Monomeric CDK5 shows no enzymatic activity and requires the association with a regulatory partner for activation (Dhavan and Tsai, 2001). Here, we found that CDK7 might be one of the partners required for activation of CDK5 in the skin tissue, based o
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LPS is the major toxic component of
2019-10-19

LPS is the major toxic component of the outer membrane of gram-negative bacteria and high dose of LPS challenge in animal can induce a rapid systemic inflammatory response which resembles septic shock in clinical [15]. We demonstrated that administration of KPT330 significantly attenuated lung injur
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br Conclusion and future perspectives LDL cholesterol loweri
2019-10-19

Conclusion and future perspectives LDL cholesterol-lowering therapy is essential for cardiovascular risk reduction. On the background of a high inter-personal variation of cholesterol synthesis and cholesterol trpv4 the efficacy of cholesterol lowering, both, with statins and with ezetimibe exhib
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An Ubl modification requires several steps that are catalyze
2019-10-19

An Ubl modification requires several steps that are catalyzed by three enzymes, referred to as E1 (activating enzyme), E2 (conjugation enzyme), and E3 (ligase). The SUMO E1 is a heterodimer of SAE1 and Uba2 (also known as SAE2). In brief, an Ubl is first activated by E1 through ATP hydrolysis and fo
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