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br Acknowledgments Studies in the Tomkinson laboratory on DN
2019-07-18
Acknowledgments Studies in the Tomkinson laboratory on DNA ligase III are supported by research grants from the National Institutes of Health (P01 CA92584 and ES12512 to AET), a grant from the V Foundation and the University of New Mexico Cancer Center. Introduction Ionizing radiation (IR) as
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br Results br Discussion Repair by NHEJ implicitly requires
2019-07-18
Results Discussion Repair by NHEJ implicitly requires the pairing together of broken chromosome ends. A complex of Ku, XRCC4, DNA ligase IV, and XLF (PEC) is necessary and sufficient for this purpose (Reid et al., 2015). Here, we describe dynamic changes in this complex that are triggered by d
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AAG has a broad substrate specificity
2019-07-18
AAG has a broad substrate specificity and besides 3-methyladenine can excise other altered purine residues, such as the minor lesions hypoxanthine and 1, N6-ethenoadenine from DNA. AAG initially activates these neutral base lesions by protonation of the base to allow for general positive people cat
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Classical DHFR inhibitors such as methotrexate MTX bind
2019-07-18
Classical DHFR inhibitors such as methotrexate (MTX) bind tightly to the enzyme and possess adequate clinical pharmacokinetics. MTX bind to the DHFR binding site through the formation of hydrogen bonds with Asn64, Lys68, Arg28, Arg70, Val115 and Ile7 amino phospholipase a2 inhibitor residues as wel
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The aim of this study
2019-07-18
The aim of this study was to evaluate the role of aberrant methylation of promoter regions of tumor suppressor genes in the clonal evolution from MGUS to MM. Thus, we analyzed in MGUS, SMM, and symptomatic MM patients, the methylation status of 4 genes—p15, p16, p53, and DAPK—whose promoter hypermet
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br Acknowledgement AM and SK thank
2019-07-18
Acknowledgement AM and SK thank ICMR, New Delhi, India for the financial assistance BIC/12(32)/2012. SK is the recipient of JRF from the project. RK and GJ thank Bristol-Myer Squibb (Grant # 34003085), USA for financial support. Introduction Proliferating Cell Nuclear Antigen (PCNA) is a high
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br Materials and methods br Results
2019-07-18
Materials and methods Results Discussion In this study, we investigated two novel candidate therapeutics, the related CRM1-inhibiting SINEs KPT-185 and KPT-276, in treatment of NHL. The results showed that KPT-185 induced growth inhibition, cell-cycle arrest, and apoptosis in tumor faah inh
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Our results indicate that C
2019-07-18
Our results indicate that C75-CoA is formed in the hypothalamus following stereotaxic injection of C75. Inhibition of hypothalamic CPT1 by C75-CoA in vivo, as seen in our experiments, is independent of the putative inhibition by malonyl-CoA, which may be formed after the action of C75 either on FAS
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A topological property P is said to be cut
2019-07-18
A topological property P is said to be cut point hereditary [3] if whenever a space X has property P, then, for every there exists some separation of such that each of and has property P. A space X is called connected ordered topological space (COTS) [5] if it is connected and has the property
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During ischemia the impact of CK on mitochondria varies in
2019-07-18
During ischemia, the impact of CK2 on mitochondria varies in different organs/tissues. For example, CK2α upregulation during ischemia leads to disrupted mitochondrial homeostasis and mediates cardiomyocyte ischemic injury [31]. Specifically, ischemia/reperfusion (I/R) progressively increases CK2α to
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br RING type E s
2019-07-18
RING-type E3s and their substrates There is enormous diversity in substrate ubiquitination and its regulation, as the targets of RING-type E3s are incredibly varied. RING-type E3s are implicated as tumor suppressors, oncogenes, and mediators of endocytosis, and play critical roles in complex mult
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In the context of E ligase drug
2019-07-18
In the context of E3 ligase drug discovery, it is critical to identify the appropriate E2/E3 substrate pairing to ensure the development and use of the most physiologically relevant screening assay. There have been many reports of limited E2/E3 activity profiling with a small number of E2 and E3 bet
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br Introduction The ubiquitination status of a
2019-07-18
Introduction The ubiquitination status of a target protein is achieved via a delicate balance between two opposing forces: ubiquitin E3 ligases and DUBs. It has been postulated that the majority of proteins in a cell are regulated and modified by ubiquitin at some point (Hershko and Ciechanover,
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The first hint that GLP might
2019-07-18
The first hint that GLP-1 might not be completely stable came from a meeting abstract in 1992, reporting that GLP-1 could be degraded in plasma incubations [16], although the enzyme(s) involved was not identified. A year later, Mentlein and colleagues [17], in a search for peptide substrates of the
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During mouse embryogenesis RLIM protein is detectable throug
2019-07-18
During mouse embryogenesis, RLIM protein is detectable throughout preimplantation development, consistent with its functions in iXCI maintenance. However, in contrast to differentiating ESCs in culture (Figure 2A), RLIM protein levels are downregulated in nuclei of epiblast cells of implanting embry
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