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Not only has the cortical actin network
2022-09-08

Not only has the cortical pd98059 network been found to influence plasma membrane properties but also to interact with exo- and endocytic vesicles (Gormal et al., 2015, Tomatis et al., 2013). The interplay between actin and membranes is integrally regulated by the phosphoinositide composition of the
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br Main Text Post translational modifications including acet
2022-09-08

Main Text Post-translational modifications including acetylation, methylation, phosphorylation, and ubiquitination, of core histones directly alter DNA-histone and histone-histone interactions and thus influence nucleosome dynamics. Tight regulation of these marks is required by cells for proper
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In addition to acting as the gatekeeper for the
2022-09-08

In addition to acting as the gatekeeper for the metabolic and antioxidant roles of glucose, HKs have also been found to regulate mPTP opening directly. First described in the cancer field, the high-affinity HK isoforms HK1 and HK2 are strongly anti-apoptotic when bound to the outer mitochondrial mem
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br Heme oxygenase inhibitors Historically the first class of
2022-09-08

Heme oxygenase-1 inhibitors Historically, the first class of competitive HO-1 inhibitors was represented by MPs, heme analogs in which the central iron Apamin of heme is exchanged by another element, such as zinc, cobalt, tin, or chromium. These molecules compete with heme for binding to the enzy
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Three additional Type I CDK
2022-09-08

Three additional Type I CDK8 and CDK19 kinase inhibitors have also been recently reported. Orally available 3-benzylindazole 12 was discovered by optimization of compounds with HSP90 affinity to yield potent and selective CDK8 inhibitors. Compound 12 showed strong binding activity for CDK8 with an I
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br GSK The GSK family is highly
2022-09-08

GSK-3 The GSK-3 family is highly conserved throughout evolution and is encoded by two genes, GSK-3α and GSK-3β, which are located in chromosomes 19q13.2 and 3q13.3 in human, respectively. Both GSK-3α and GSK-3β proteins exist in a variety of tissues with the highest levels found in ARRY334543 aus
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br Experimental section br Introduction Fasting hyperglycaem
2022-09-07

Experimental section Introduction Fasting hyperglycaemia in all forms of diabetes mellitus occurs primarily as a result of upsurge in hepatic glucose synthesis (HGS) [1], [2]. Two specific enzymes, glucokinase (GK) and glucose-6 phosphatase (Glu-6-Pase) play crucial role in hepatic glucose pro
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The mechanism by which Piezo acts in the regulation of
2022-09-07

The mechanism by which Piezo1 acts in the regulation of RBC volume is not firmly established. Its curved structure implies that it is activated by an increase in membrane tension (11), a mechanism indicated by electrophysiological measurements (16). However, the RBC membrane mechanics at its physiol
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trametinib Although domain organization had been
2022-09-07

Although domain organization had been clearly delineated by the 4.3-Å structure of T4-γ-secretase [], atomic modeling of the side chains had to wait for the 3.4-Å structure []. In total, 598 residues in the transmembrane region and 632 residues in the ECD were modeled for the four components of huma
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In the present studies we found that
2022-09-07

In the present studies, we found that genistein did not antagonize fMLF-induced Ca2+ mobilization in FPR1-HL60 keap1-nrf2 pathway and human neutrophils. Thus, the previously reported inhibitory effect of genistein on fMLF-stimulated degranulation, aggregation, and reactive oxygen species (ROS) prod
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In order to understand the determinants of high affinity of
2022-09-07

In order to understand the determinants of high affinity of with amide side chain, an X-ray crystal structure of human liver FBPase in complex with was determined (). The position of phosphonate group and tricyclic scaffold of is similar to those of with no side chain, which suggests the formati
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In the FARM motifs of GGPPSs hydrophobic amino acids
2022-09-07

In the FARM motifs of GGPPSs, hydrophobic AZD-4547 are replaced by aliphatic amino acids, which are more flexible residues and allow the entrance of longer substrates into the pocket (Wang and Ohnuma, 2000). It has been reported that the lepidopteran Manduca sexta CA possesses GGPP synthase (GGPPS)
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The Rho family of GTPases is composed of many small
2022-09-07

The Rho family of GTPases is composed of many small ubiquitous signaling G proteins that bind to guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). They act as switches: when binding to GTP, they are active and associate with a variety of target proteins that regulate intr
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br Acknowledgments I thank Takeshi Sakaba for
2022-09-07

Acknowledgments I thank Takeshi Sakaba for critical reading of the manuscript and helpful comments. This work was supported by JSPS/MEXT KAKENHI Grant Numbers 17K19466, 17H03548. Introduction The oral route of drug application is the main route in pharmacology since it is easy to handle and o
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Over the last decade intense efforts have
2022-09-07

Over the last decade, intense efforts have been devoted toward identifying IN inhibitors as potential drugs against HIV. Raltegravir and elvitegravir are integrase strand transfer inhibitors (INSTIs) that have been approved for therapy and dolutegravir is another INSTI that is currently in advanced
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