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br Results br Discussion Taking advantage of the highly spec
2021-07-15
Results Discussion Taking advantage of the highly specific protein–protein interactions among cognate prostaglandin synthase that mediate SUMO conjugation to substrates, we have developed a novel strategy for achieving inhibition of SUMO conjugation in vivo based on disruption of SUMO E1–E2 i
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Based on the SUMO SIM interaction involved
2021-07-15
Based on the SUMO–SIM interaction involved in SUMOD positioning, a SUMO2ΔSBD (SIM-binding domain; Q30A, F31A, I33A) mutant can be investigated that disrupts this important binding interface (Eisenhardt et al., 2015; Meulmeester, Kunze, Hsiao, Urlaub, & Melchior, 2008). In Fig. 4A, multiturnover assa
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Although PD is traditionally viewed as
2021-07-15
Although PD is traditionally viewed as a motor disorder, evidence from numerous epidemiologic (Shiba et al., 2000) as well as case–control studies (Richard, 2005) suggest the occurrence of non-motor symptoms including hyposmia/anosmia, gastrointestinal disturbances, sleep abnormalities, autonomic dy
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DGAT is specifically responsible for endogenous synthesis
2021-07-15
DGAT2 is specifically responsible for endogenous synthesis of TAGs which are then packed into cytosolic LDs in the cytosol for storage and luminal apolipoprotein B (apoB)-containing LDs in the ER lumen destined for VLDL secretion [122,127]. DGAT2 can also synthesize TAG using exogenous FAs and supp
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Apart from neutrophil mediated inflammation
2021-07-14
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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The CPA EoS was presented by Kontogeorgis
2021-07-14
The CPA EoS was presented by Kontogeorgis et al., in 1996 [23]. The proposed equation is composed of two parts (SRK EOS + association term) such that it can well predict the thermodynamic behavior of hydrogen bonding materials as a result of considering the association term. Yakoumis et al. (1997) e
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Daun02 sale Alzheimer s disease AD is a chronic progressive
2021-07-14
Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative disorder of the Daun02 sale which is considered a leading cause of dementia and affects 20–30 million people worldwide. Presently, a suitable treatment and prevention strategy against AD is hardly available. Various studies have be
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ClC is not only a chloride ion
2021-07-14
ClC-3 is not only a chloride ion channel but also a regulatory protein involved in the regulation of multiple signaling pathways. The PI3K/AKT/mTOR signaling pathway plays a crucial role in regulating cell growth, migration, invasion, and distant metastasis [13,14]. Although abnormal PI3K/AKT/mTOR a
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irak1 br Allosteric inhibitors In general candidate drugs th
2021-07-14
Allosteric inhibitors In general, candidate drugs that bind to a GPCR at a site that is distinct (allosteric site) from the binding site of the endogenous agonist (orthosteric site) are attracting increasing attention 39, 42, 58. Allosteric modulators display saturability of their effect, probe d
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Molecular docking study of compound was performed using
2021-07-14
Molecular docking study of PDK1 inhibitor was performed using the Schrödinger Small-Molecule Drug Discovery Suite taking advantage of known X-ray crystal structures of activated EPAC2 protein. The model shows that compound occupies the CBD of EPAC2 and forms hydrogen bonds with Arg448 and the cya
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While we previously demonstrated that TraG is inhibited by s
2021-07-14
While we previously demonstrated that TraG is inhibited by specific transglycosylase inhibitors and that enzymatic activity is strongly reduced upon mutation of the potential catalytic core (Arends et al., 2013), the enzymatic mechanism of both domains was not assigned. Here, by mass spectrometry an
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alk pathway Studies using SERPINB deficient mice established
2021-07-14
Studies using SERPINB1-deficient mice established the significant role for SERPINB1 in protecting lung antimicrobial proteins from proteolysis during microbe infection and its regulatory role in sustaining the balance of neutrophil reserve [15]. Neutrophil serine proteases (NSPs) (elastase, cathepsi
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Haj Yahya et al applied native chemical ligation
2021-07-14
Haj-Yahya et al. [52] applied native chemical ligation for the construction of diubiquitin probes. They attached a cysteine residue to the lysine side chain of the proximal ubiquitin and ligated the distal module using the C-terminal thioester of ubiquitin. Elimination of the sulfur bapta resulted i
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Elevated production of cysLTs in asthma and rhinitis
2021-07-13
Elevated production of cysLTs in gp120 and rhinitis in general and aspirin-sensitive disease in particular10, 11, 26, 27 has been implicated in causing epithelial cell activation and excessive mucus secretion, which characterize these diseases.2, 28 It is of particular interest, therefore, that we
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CRF binds to CRF and CRF receptor subtypes triggering downst
2021-07-13
CRF binds to CRF1 and CRF2 receptor subtypes, triggering downstream cascades and leading to stimulatory G protein (GsP) activation. Once activated, GsP undergoes a structural change provoking the separation of the subunits Gα and Gβγ. The Gα subunit induces the production of the second messenger cAM
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