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Introduction Protein ubiquitination is a posttranslational m
2019-11-19

Introduction Protein ubiquitination is a posttranslational modification that plays a major role in almost all cellular processes in eukaryotes (Hochstrasser, 2009; Komander & Rape, 2012). It involves the covalent attachment of ubiquitin (Ub) via its C-terminal glycine carboxylate to a primary amine
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br Conclusion br Conflict of
2019-11-19

Conclusion Conflict of interest Introduction The sexual exploitation and internal trafficking of British children within the UK has received growing public and policy attention in recent years. This has largely been in response to a number of high profile police investigations into cases in
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For the SAR optimization of the
2019-11-19

For the SAR optimization of the right hand side, it was decided to explore the inclusion of the key carboxylic norepinephrine bitartrate moiety present in the original DGAT-1 inhibitors from . Analogs were constructed by the synthetic routes outlined in , . In , the methylene-oxy linker was introdu
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On the basis of the findings
2019-11-19

On the basis of the findings described above, a series of heterotricyclic analogs were designed and synthesized. The human CRF1 receptor binding and antagonist activity data for newly designed heterotricyclic core antagonists 28–33 are described in Table 3. Most of the tricyclic core analogs listed
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Next we elucidated that the Mtb enolase binds to host
2019-11-19

Next, we elucidated that the Mtb enolase binds to host plasminogen with a high affinity. The KD value of 360nM for this interaction suggested an avid binding between the two proteins in vivo. This observation is also in conciliation with the observed KD values for enolase-plasminogen interactions in
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Given that CE plays an essential role in schistosome
2019-11-19

Given that CE plays an essential role in schistosome invasion, its immunoreactivity and protective potential is of significant interest. The native form of SmCE was found to be poorly immunogenic in immunized mice. An earlier study found that sera from S. mansoni patients have shown the presence of
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br Acknowledgements The present study was supported by the M
2019-11-19

Acknowledgements The present study was supported by the Medical Science and Technology Program of Zhejiang Province2014KYA228 (Zhijun Zhou), 2016KYA195 (Jie Li) and 2017KY714 (Qingqing Xia); Zhejiang Provincial Natural Science Foundation of ChinaQ17H120001 (Jie Li); and Scientific Research Projec
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Among the Ub interactions observed in the HOIP
2019-11-19

Among the ~Ub interactions observed in the HOIP structure is one that involves a RING2 domain (from the non-cognate HOIP) [47]. A similar binding interaction was defined between HHARI RING2 and the hydrophobic patch on Ub by NMR [54]. HHARI RING2 mutations that ablate the interaction inhibit formati
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br Substoichiometric substrate modification E ligases
2019-11-19

Substoichiometric substrate modification E3 ligases catalyze the rapid transfer of the SUMOD from the E2 enzyme to the substrate. By definition, enzymes are recycled in the reaction, allowing multiple rounds of substrate modification by a single enzyme. Thus, enzymes function at substoichiometric
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Compounds were synthesized using a facile step convergent sy
2019-11-19

Compounds were synthesized using a facile 8-step convergent synthesis ( and ). Briefly, (Boc)cyclen (compound ) was coupled using TBTU to Fmoc- or Cbz-protected amino alkyl acids (–), followed by deprotection using 20% piperidine in DMF, or H on Pd/C, respectively (–) (). Deprotected linkers were co
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bibn br Materials and methods br Results br Discussion Drug
2019-11-19

Materials and methods Results Discussion Drug of abuse induces widespread bibn changes in the molecular and cellular functions in circuits between VTA and its neighbored regions such as NAC, and amygdala. It is belived that these changes result behavioral phenotype that characterize addicti
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Epigenetic silencing of genes that determine tumor
2019-11-18

Epigenetic silencing of genes that determine tumor invasiveness, growth patterns of tumors, and tumor-cell apoptosis12, 29 may also affect the expression of drug-metabolizing enzymes, thereby providing an additional genetic mechanism in pharmacogenomics. Trisomy 8 that contains wild-type GGH could b
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While a growing body of knowledge demonstrates the importanc
2019-11-18

While a growing body of knowledge demonstrates the importance of COX-1 and COX-2 accompanied with neuroinflammation in altitude related conditions. In fact, PGE2 has been widely thought to promote the neuronal inflammation and degeneration in many neurological maladies (Griffin et al., 2013, Jiang a
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In conclusion we propose that UBE T FANCT mutations
2019-11-18

In conclusion, we propose that UBE2T (FANCT) mutations define a FA subtype. This is also a rare example of a mutated E2 enzyme causing an inherited human disorder, like UBE2A. The p.Gln2Glu substitution is probably hypomorphic, as indicated by the fact that a siUBE2T knockdown made AP65P-hTERT Fidax
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Our recent discovery M P H R
2019-11-18

Our recent discovery (M.P., H.R., A.S.) of a highly selective and in vivo active DDR1 small-molecule inhibitor provides evidence that DDR1 is a druggable pharmaceutical target, and some details of our efforts are provided below. To avoid the repurposing of known kinase inhibitor structural motifs, w
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