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br Discussion The biochemical separation of exonuclease acti
2019-09-24

Discussion The biochemical separation of exonuclease activity from DNA-PK dependent endonuclease activity reported in this manuscript is consistent with genetic separation of Artemis enzymatic activity. Mutations in the protein which result in disruption of endonuclease activity have no effect on
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DHODH activity has been traditionally measured with the
2019-09-24

DHODH activity has been traditionally measured with the standard colorimetric assay that monitors 2,6-dichloroindophenol (DCIP) reduction as absorbance decrease at 600 nm . This assay has permitted the identification of several families of DHODH inhibitors in a successful high-throughput screening (
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We then evaluated in vivo DHODH
2019-09-24

We then evaluated in vivo DHODH mRNA BGJ 398 using data from TCGA (Lee, Palm, Grimes, & Ji, 2015). To perform a pan-disease comparison of DHODH expression, log2 TPM expression values were converted to z-scores calculated per patient. Fig. 6 shows that across all 34 diseases (9726 unique patient sam
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For the SAR optimization of the
2019-09-24

For the SAR optimization of the right hand side, it was decided to explore the inclusion of the key carboxylic Ketorolac tromethamine salt clinical moiety present in the original DGAT-1 inhibitors from . Analogs were constructed by the synthetic routes outlined in , . In , the methylene-oxy linker
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Previous studies have demonstrated the role
2019-09-23

Previous studies have demonstrated the role of the COMT Val158Met in response to positive and negative emotional stimuli (Bouhuys et al., 1999, Cohn et al., 2009), a fundamental process involved in well-being (Diener et al., 2009a, Diener et al., 1999, Gross and John, 2003). A handful of studies rep
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The importance of AAE in enhancing
2019-09-23

The importance of AAE3 in enhancing the survival of plants and yeast when confronted with certain environmental stresses has been documented in recent reports. In response to biotic stress such as oxalate-secreting micro-organisms, AAE3 was found to reduce the inhibitory growth effects of the secret
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WNV a member of the genus Flavivirus within the
2019-09-23

WNV, a member of the genus Flavivirus within the family Flaviviridae, was first isolated in 1937 from a febrile woman in the West Nile region of Uganda (Brinton, 2002). Until 1999, WNV was mainly confined to Southern Europe, the Middle East, Africa, West and Central Asia, Indonesia and Australia. In
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br Results br Discussion Our UbV
2019-09-23

Results Discussion Our UbV library was originally designed to develop inhibitors of deubiquitinases (Ernst et al., 2013). Recently, we showed that UbVs could exhibit multiple binding modes and mechanisms to modulate HECT E3 activity (Zhang et al., 2016)—one set occupied the HECT domain E2-bind
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The synthesis of compounds a and b are
2019-09-23

The synthesis of compounds 7a and 7b are outlined in Scheme 2. Compound 5 was obtained by di-tert-butyl pyrocarbonate protection of BMX-IN-1 4a. Then, compounds 6a and 6b were obtained by amination of the fluoride with a morpholino and dimethylamine, respectively. Target compounds 7a and 7b were ob
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br Acknowledgements The authors are supported
2019-09-23

Acknowledgements The authors are supported by National Institutes of Health grants (CA162804, CA92584, and CA13499 to DJC and CA166677 to BPPC) and Cancer Prevention and Research Institute of Texas (RP110465 to DJC). The cellular response to DNA double-strand break (DSB) formation is an essent
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br Experimental methods br Results and discussion br
2019-09-23

Experimental methods Results and discussion Conclusion Rational design of highly selective fluorescent probes to detect G-quadruplexes is of profound importance for basic research. On this basis, we designed and synthesized a series of N-alkylated styrylquinolinium dyes Ls-1, Ls-2 and Ls-3.
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MTX and MTXPGs block the activity of the
2019-09-23

MTX and MTXPGs block the activity of the key enzyme DHFR (Fig. 1), which converts folates to their active forms – dihydrofolate (DHF) and tetrahydrofolate (THF). MTXPGs also potently inhibit thymidylate synthase (TS). Furthermore, during dTMP synthesis, TS utilizes the cofactor 5,10-methylene THF, w
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Unlike the CRF receptor the CRF
2019-09-23

Unlike the CRF1 receptor, the CRF2(a) receptor binds and is activated by agonists with a broad range of potencies. Therefore, we assessed the ability of strong and weak ligands to desensitize retinoblastoma CRF2(a) receptors. Although stresscopin\'s N-terminus is two Chrysin longer than the N-termi
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Kim et al reported for bioactive compounds originating
2019-09-23

Kim et al. reported for bioactive compounds originating from the endemic species in Korea, the hexane and EtOAc fractions of the MeOH extracts from the roots of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity b
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Stable carbon and nitrogen isotope ratios in
2019-09-23

Stable carbon and nitrogen isotope ratios in bone collagen and carbon isotope ratios in bone apatite data were obtained by the means of the techniques described in supplementary data (SD1). For collagen, standard indicators have been used to assess its preservation, such as collagen yield, carbon an
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