• DNA damage represents a persistent threat

  2019-07-08

  

  DNA damage represents a persistent threat to genomic stability. A critical link exists between DNA mutation, chromosomal rearrangement and cancer development. In myeloid malignancies, various chromosomal translocations and/or mutations increased cellular reactive oxygen species (ROS), followed by DS

• To examine the influence of aromatic motifs on

  2019-07-08

  

  To examine the influence of aromatic motifs on the bridging lysine esters we analysed DNA alkylating activity of the set of compounds 1–6. The lysine derivatives were chosen as it is relatively easy to prepare different esters and thereby study the impact of different groups on the reactivity toward

• Some pyrimidine analogs are substrate based

  2019-07-08

  

  Some pyrimidine analogs are substrate-based inhibitors that bind to the dihydroorotate binding site, but most reported inhibitors of DHODH bind to the site occupied by the ubiquinone co-factor., , , , , , , , , , , , , , , , , X-ray crystallographic studies of inhibitor complexes with DHODH and DHO

• br Materials and methods br Acknowledgements SD was

  2019-07-08

  

  Materials and methods Acknowledgements SD was supported by a pre-doctoral research fellowship from the Flanders Agency for Innovation and Entrepreneurship (VLAIO-Flanders, Belgium). YB is supported by a postdoctoral fellowship from Research Foundation Flanders (FWO, Belgium). We thank Isabelle

• br Clinical trials of CRM inhibitors

  2019-07-08

  

  Clinical trials of CRM1 inhibitors KPT-330 clinical trials have been initiated with promising very early results. One trial includes patients with advanced solid tumors whose disease has progressed after at least one prior therapy for metastatic disease (NCT01607905). Another trial includes patie

• Estrogen related receptors ERRs are orphan

  2019-07-08

  

  Estrogen-related receptors (ERRs) are orphan nuclear receptors and have three members including ERRα, ERRβ, and ERRγ (Yasumoto et al., 2007). Though they are termed as ERRs due to the sequence homology with estrogen receptors, they don’t need to bind estrogens to exert action. Generally, ERRs bind t

• Although several genomic technologies including the generati

  2019-07-08

  

  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

• Introduction Neuropathic pain occurs in approximately one th

  2019-07-08

  

  Introduction Neuropathic pain occurs in approximately one-third of patients with diabetes and is refractory to currently available analgesic drugs (Abbott et al., 2011). This painful diabetic neuropathy (PDN) is associated with elevated levels of methylglyoxal (MG; a reactive glucose metabolite) an

• Oleamide PKA signalling in the nucleus was thought

  2019-07-08

  

  PKA signalling in the nucleus was thought to be due to the translocation of the catalytic subunit upon activation from the Oleamide 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 func

• Previous studies in the Swiss Webster mouse

  2019-07-08

  

  Previous studies in the Swiss Webster mouse (Rosengren et al., 1995) and the Sprague–Dawley rat (El Sisi et al., 1993) have shown that retinol pretreatment potentiates the hepatotoxicity of paracetamol. The current study is designed to investigate further this interaction in mice. To accomplish this

• br Significance Our understanding of the ubiquitin

  2019-07-08

  

  Significance Our understanding of the ubiquitin biology has been rapidly expanding. The role of the ubiquitin system in the pathogenesis of numerous disease states has increased the interest in finding new strategies to pharmacologically interfere with the enzymes responsible of the ubiquitinatio

• Most enzymes involved in the addition and removal of ubiquit

  2019-07-08

  

  Most SKF 83566 hydrobromide weight involved in the addition and removal of ubiquitin bind weakly to an overlapping surface on ubiquitin. Previously, Sidhu and colleagues diversified this surface and then used phage display to screen these libraries of ubiquitin variants (UbVs) for binding to DUBs an

• More unusual modifications also regulate

  2019-07-08

  

  More unusual modifications also regulate DUBs. Recent reports have illustrated how reactive oxygen species (ROS) can regulate DUB activity 87, 88, 89, 90. ROS can serve as potent signaling molecules by reacting with active site cysteines of tyrosine phosphatases and some cysteine peptidases to form

• AZ191 In summary we hypothesize that targeting the A R D

  2019-07-08

  

  In summary, we hypothesize that targeting the A1R–D1R heterotetramer with heteromer-selective drugs might improve safety and efficacy of the pharmacological therapy for RLS and other motor diseases, resulting in fewer side effects than classical drugs developed for targeting monomeric A1R or D1R.

• br Structure of ketosteroid dehydrogenase

  2019-07-08

  

  Structure of 3-ketosteroid Δ1-dehydrogenase Overall fold — High-resolution crystal structures of Δ1-KSTD are currently available for the Δ1-KSTD1 isoenzyme from R. erythropolis SQ1 [30]. The Δ1-KSTD1 molecule has an elongated shape, and consists of two domains, an FAD-binding domain and a catalyt

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