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mitoxantrone Likewise the conserved cysteine in the E protei
2020-06-13
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 Authors contribution br Disclosure statement
2020-06-13
Authors contribution Disclosure statement Acknowledgements This study has received funding from the Italian Ministry of University and Research (PRIN 2015, grant number 2015373Z39_008) and from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115797 (INNODIA)
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In anticipation of an approach based
2020-06-13
In anticipation of an approach based on modification of the cyclohexylacetic Betulinic Acid subunit of 1 as a means of improving permeability, a set of analogs were prepared to map out the optimum display of the acidic functionality. Homologated acids 25 and 26 were found to be equipotent to 1, alt
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Consistent with previous simulations on the DFG Asp
2020-06-13
Consistent with previous simulations on the DFG-Asp-out/-in interconversion of Abl kinase, we only observe the DFG flip with protonated Asp747 (Shan et al., 2009). We showed previously that the pKa for the DFG-Asp in Abl is elevated at 6.5. Further “constant pH” simulations whereby protonation event
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Consistent with prior reports this study
2020-06-13
Consistent with prior reports, this study also found the level of 11 cytokines (MIF, IL-1Ra, CTACK, M-CSF, Basic FGF, VCAM-1, SDF-1α, IL-8, IL-16, PDGF-β, and GRO-α) significantly decreased in the sera of adult HFMD patients in comparison with controls. MIF is a pro-inflammaory cytokine that is asso
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momelotinib In rats exposed to day of nicotine
2020-06-13
In rats exposed to 1 day of nicotine withdrawal (24 h after the last nicotine administration) we expected a decrease of general locomotor activity and a decrease of global striatal dopamine release, which were assessed in a previous study following 14 days of nicotine exposure and 24 h of nicotine w
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Pridinol Methanesulfonate mg br COTSget based Architectures
2020-06-13
COTSget-based Architectures This section describes how our COTSget-based architectures are defined. We use a design inspired by MDE to build a Domain-Specific Language (DSL) of the architecture, as can be seen in the metamodel of Fig. 3. This metamodel defines the abstract syntax of our DSL and i
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Dopamine activity in the PFC and striatum
2020-06-13
Dopamine activity in the PFC and striatum may be antagonistic, meaning that lower levels of dopamine in the striatum tend to correspond to higher levels of dopamine in the PFC and vice versa (Cools and D\'Esposito, 2011; Tunbridge et al., 2006). Human PET studies have reported that dopaminergic PFC
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ApicomplexansApicomplexans are unicellular and spore forming
2020-06-12
ApicomplexansApicomplexans are unicellular and spore-forming obligate intracellular parasites that occupy diverse host niches (Mogi and Kita 2010). They have remodeled mitochondrial carbon and energy metabolism through reductive evolution. The development of novel drugs is now a very serious challen
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wnt signaling pathway br Most reported binding data are obta
2020-06-12
Most reported binding data are obtained by performing heterologous competition binding experiments and expressing the results as relative binding affinity (RBA). The constructed binding curves should theoretically be sigmoidal in shape with a Hill slope value of one, for a single ligand binding to
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Like all other cellular processes ubiquitination
2020-06-12
Like all other cellular processes, ubiquitination is also tightly regulated; more so, as myriads of pathways are controlled via this conjugation and dysregulation of ubiquitination has been implicated in various diseases including cancer [16], [17]. Quite a few of such regulatory mechanisms that con
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The following are the supplementary
2020-06-12
The following are the supplementary data related to this article. Acknowledgments Introduction Drug-resistant epilepsy (DRE) occurs in approximate 30% of patients who suffer from epilepsy [1]. Temporal lobe epilepsy (TLE) is one of the most common partial seizures and the common cause of DRE
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Unlike CRM exportins Cse and Xpot lack a C extension
2020-06-12
Unlike CRM1, exportins Cse1 and Xpot lack a C-extension and instead rely primarily on changes in HEAT-repeat conformation and direct Ran-cargo contacts to ensure low cargo-binding affinity in the cytosol and cooperative assembly of the exportin/Ran/cargo complex in the nucleus (Cook et al., 2005, Co
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Based on the above we hypothesized that
2020-06-12
Based on the above, we hypothesized that a PROTAC strategy would be effective to induce CK2 protein degradation. Herein reported is an approach for the preparation of novel PROTACs via “click reaction” for degradation of CK2 protein (Fig. 2). Importantly, “click reaction” is a very facile, selective
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LLY507 In addition to an action via P Y receptors
2020-06-11
In addition to an action via P2Y receptors, extracellular UDP activates GPCRs for cysteinyl leukotrienes (CysLT1, CysLT2; Mellor et al., 2001, 2003). GPR17 has been reported to function as a receptor for cysteinyl leukotrienes and uracil nucleotides (Boda et al., 2011; Fumagalli et al., 2011; but se
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