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External factors such as protein partners can
2020-10-20

External factors, such as protein partners, can also activate DUBs by either reinforcing the stimulatory effects of intramolecular factors or by other means. The intramolecular activation of the USP7 CD by its HUBL domain is allosterically potentiated by external factor GMP synthase (GMPS), which co
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Contrary to the profuse dopaminergic innervation
2020-10-20

Contrary to the profuse dopaminergic innervation of the thalamus found in human and non-human primates (Brown et al., 1979, Sanchez-Gonzalez et al., 2005), in rodents, the RTn is one the few thalamic nuclei that receives dopaminergic input (Anaya-Martinez et al., 2006, Garcia-Cabezas et al., 2007, G
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Acknowledgments We are grateful to Dr Jean Marie
2020-10-20

Acknowledgments We are grateful to Dr. Jean-Marie Bernassau for his leadership in establishing our virtual screening platform and Dr. Julie Bick for protein purification. X-ray data collection for compound 4 was performed by Shamrock Structures at Southeast Regional Collaborative Access Team (SER-C
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Previous studies showed that many steroidogenic enzymes act
2020-10-20

Previous studies showed that many steroidogenic enzymes act when the enzyme binds to the cofactor first [30]. In the present study, we showed that HPTE inhibited both AKR1C14 and RDH2 in a mixed mode when cofactor was used. This indicates that HPTE interferes with cofactor-binding residues although
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br Conclusions The PQQ dependent CcPDH is
2020-10-20

Conclusions The PQQ-dependent CcPDH is the first PQQ-dependent enzyme identified in eukaryotes. The PQQ cofactor binds the enzyme with high affinity, reflected in a Kd of 1.1 nM, and the enzyme oxidizes 2KG, l-fucose, and rare sugars such as d-arabinose and l-galactose. The AA8 cytochrome b domai
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Apart from neutrophil mediated inflammation the production o
2020-10-20

Apart from neutrophil-mediated inflammation, the production of pro-inflammatory cytokines and chemokines from PGD2/CRTH2 activated macrophages could further aggravate LPS-induced lung injury (Eguchi et al., 2011; Jandl et al., 2016). Interestingly, genetic ablation of CRTH2 diminishes the TNF-α prod
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T helper Th cells play a central role in
2020-10-20

T helper (Th) Ac-YVAD-CHO receptor play a central role in activation of immune system against infectious agents through secretion of lymphokines or cytokines. African trypanosomes target the Th cells and alter their activation, possibly for their own survival and perpetuity (Namangala, 2011). Trypa
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casein kinase 2 inhibitor The previously described endogenou
2020-10-20

The previously described endogenous patterns of IGF-1-induced kinase signaling, and resulting interaction between MAPK and PI3K, differ across neuronal sub-types. In R28 retinal neuron-like cells, IGF-1 treatment elicits prolonged activation (at least 80 min) of both PI3K and MAPK (Kong et al., 2016
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cAMP mediated signaling pathways are
2020-10-20

cAMP-mediated signaling pathways are important for maintaining metabolic homeostasis, and the effects of the glucagon/catecholamine–cAMP–PKA axis on energy balance have been well documented [20]. For example, vasopressin receptor antagonists of the PKA 2β regulatory subunit (RIIβ) in mice leads to
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br Funding This work was supported by
2020-10-20

Funding This work was supported by the grants from MSD, Terumo Life Science Foundation, Takeda Science Foundation, and Japan Diabetes Foundation. Disclosures Acknowledgments The authors thank C. Morimoto (Juntendo University, Tokyo, Japan) and K. Takeda (Immunology Frontier Research Center
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More recently Boskovic et al have visually corroborated
2020-10-20

More recently, Boskovic et al. (2003) have visually corroborated that purified DNA-PKcs can bind short DNA fragments by using single particle EM. DNA biotinylated at the 5′ end was labelled by coupling to commercial streptavidin–gold particles (Fig. 4D). When analysed in the microscope, DNA-PKcs mol
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Previous synthetic lethal screening efforts
2020-10-20

Previous synthetic lethal screening efforts (Cox et al., 2014) have mainly used RNAi as a means of identifying potential targets (Barbie et al., 2009, Kim et al., 2016, Luo et al., 2009, Scholl et al., 2009), although a few screens (Shaw et al., 2011, Steckel et al., 2012) have been performed with s
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Interestingly genome wide association studies have linked th
2020-10-20

Interestingly, genome-wide association studies have linked the chromosomal region harboring RDHE2 (SDR16C5) and seven other genes to stature and growth in cattle, humans, and pigs [30], [31], [32], [33], [34], [35], [36], [37], and beak deformity in chickens [38]. The most recent study specifically
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AMD is equally active against a broad range of
2020-10-19

AMD3100 is equally active against a broad range of HIV-1 and HIV-2 strains, but not against simian immunodeficiency virus (SIV) strains in human PBMC (De Clercq et al., 1994). At this moment it is not clear what coreceptor SIV is using in human PBMC, but it does not seem to be CXCR-4 (Feng et al., 1
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Although differences in several nociceptive
2020-10-19

Although, differences in several nociceptive tests have previously been described across strains (Mogil et al., 1999), it is the first time that pain sensitivity in response to chemical and thermal stimuli has been evaluated in B6,129CRHtklee mice. Our results showed no differences in pain sensitivi
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