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PKA signalling in the nucleus was thought to be
2020-09-16
PKA signalling in the nucleus was thought to be due to the translocation of the catalytic subunit upon activation from the NAD+ to the nucleus via diffusion [72]. However, a new understanding has emerged, as both the regulatory and catalytic subunits have been identified in the nucleus and function
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The contribution of local ETA and ETB receptors towards heat
2020-09-16
The contribution of local ETA and ETB receptors towards heat hyperalgesia induced by inoculation of XC tumor Naringin in the paw of mice has been demonstrated by Baamonde and colleagues (Baamonde et al., 2004). Furthermore, using neuropathic and inflammatory nociception models, several studies have
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CSN was initially identified based on the constitutitvely ph
2020-09-16
CSN was initially identified based on the constitutitvely photormophogenic (cop) mutants from Arabidopsis thaliana [48]. csn mutants are Cullin deneddylation-deficient, consequently accumulate neddylated Cullins, and arrest growth shortly after germination [49, 50, 51]. Weak csn mutants have defects
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How does an increase in E
2020-09-16
How does an increase in E2 affinity for the RING domain favor higher activity and polyubiquitination by the E2? Binding of the RING domain to the E2 positions the donor Ub in the E2~Ub conjugate in a closed complex [16], [17], [18] that increases the reactivity of the thioester [60]. A higher affini
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Intriguingly one E residue may serve as a
2020-09-16
Intriguingly, one E2 residue may serve as a molecular ‘gate’ to allow the C-terminus of ubiquitin to access the closed E2~Ub conformations favorable for ubiquitin transfer. This residue, Asp87 in UbcH5 family members, resides on one side of the opening that leads to the active site Cys (Fig. 4D). In
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h89 aminoisobutyric acid BAIBA is a natural catabolite of th
2020-09-16
β-aminoisobutyric h89 (BAIBA) is a natural catabolite of the branched-chain amino acid thymine. BAIBA was recently found to reduce inflammation in skeletal muscle via the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor (PPAR)δ signaling pathway. BAIBA reportedly enhan
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Another example of negative regulation is the inhibition
2020-09-16
Another example of negative regulation is the inhibition of the yeast endosome-associated DUB Doa4 by Rfu1 (free ubiquitin chains 1). In a yeast genetics screen, deletion of Rfu1 was serendipitously found to alter global ubiquitin levels [69]. DUBs can regulate these levels by liberating conjugated
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The possibility of harm with DPP
2020-09-16
The possibility of harm with DPP-4 inhibitors in patients with clinically overt heart failure has been recently highlighted by the results of the VIVIDD (Vildagliptin in Ventricular Dysfunction Diabetes) trial (68), the only trial to date that has been designed to evaluate the effects of a DPP-4 in
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Everolimus treatment showed an increase in the number of pla
2020-09-16
Everolimus treatment showed an increase in the number of plaques and a reduction in plaque size, depending on concentration and treatment time (Fig. 1, Fig. 2). Everolimus-pretreated MMP-2 Inhibitor II synthesis adsorbed less virus with more plaque formation in the initial phase of infection (Fig.
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br Conclusions There is significant interest in understandin
2020-09-16
Conclusions There is significant interest in understanding the contribution of biological mechanisms to the non-linear/bilinear dose–response curves for DNA-reactive agents. Model monofunctional alkylating agents have datasets amenable to PoD determination for genotoxic effects in both in vitro a
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PF-5274857 mg In this review we present compelling
2020-09-16
In this review, we present compelling evidence in support of DHODH as an essential enzyme for the survival of cancer cells. DHODH, and its relationship to de novo pyrimidine metabolism, will be discussed along with factors that influence its regulation and expression. We will show evidence of DHODH\
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With the narrow SAR of the tail favouring
2020-09-16
With the narrow SAR of the tail favouring the ortho sulfone group, we examined the remaining position open to substitution at the pyrazole 3-position, in an attempt to at least moderate the excessive human PPB (). Lipophilic groups in this position maintained huge shifts in potency in the absence or
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Beside the previously reported Topo I inhibition time
2020-09-16
Beside the previously reported Topo I inhibition, time and concentration dependent CRM1 inhibitory properties of klavuzon derivatives have been shown as a second mechanism of action in this work. Especially, compounds 3 and 20 are the most effective derivatives and they completely inhibit CRM1 activ
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CRF binds to CRF and CRF receptor subtypes triggering downst
2020-09-15
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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Pahlavanzadeh and Fakouri Baygi employed PC SAFT
2020-09-15
Pahlavanzadeh and Fakouri-Baygi [6] employed PC-SAFT EoS to predict the nisoldipine australia of carbon dioxide by aqueous MEA solutions. They used the ideal form of Smith–Missen algorithm to calculate liquid phase concentrations. The results illustrate acceptable accuracies so that the AAD was ach
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