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br The GLI code The GLI code model considers the
2022-03-22
The GLI code The GLI code model [21], [22] considers the total GLI function as a balance of positive activator (GLIA) and negative repressive (GLIR) activities with GLI1 being mostly a positive transcription factor and GLI3 mostly a transcriptional repressor. The GLIA:GLIR ratio is thus critical,
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CSL is endowed with an intrinsic transcription
2022-03-22
CSL is endowed with an intrinsic transcription-repressive function, and CAF-effector genes are induced as a consequence of CSL downmodulation (Hu et al., 2012, Procopio et al., 2015), as it can occur upon exposure to pro-carcinogenic stimuli such as UVA or smoke-derived compounds (Menietti et al., 2
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The significance of A and
2022-03-22
The significance of Aβ and tau as therapeutic targets is not only derived from pathological evidence of postmortem brain but also from biochemical analysis of cultured human neurons. This is largely based on the induced pluripotent stem cell (iPSC) technology that has been established to study Aβ, t
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MPEP Hydrochloride The diverse biochemistry of zinc
2022-03-22
The diverse biochemistry of zinc means that, in many cases, more than one factor (or pathway) is at play. Whilst catalytic Zn2+ sites are now typically well-understood, the recognition that Zn2+ levels regulate the function of many cell types has led to vigorous interest in the fate and role of mobi
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The co crystal structure of GPR complexed with TAK provided
2022-03-22
The co-crystal structure of GPR40 complexed with TAK-875 provided precise structural information for the rational design of novel GPR40 agonists. The key interactions between the carboxylate with the residues Arg183, Arg258, Tyr91 and Tyr240 of GPR40 were observed. And Trp174ECL2 was oriented nearly
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In the FARM motifs of GGPPSs hydrophobic
2022-03-22
In the FARM motifs of GGPPSs, hydrophobic s3i 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) acti
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In conclusion we have demonstrated that the ejection
2022-03-22
In conclusion, we have demonstrated that the ejection of structural zinc ions from G9a and GLP in the presence of selenium-, and sulfur-containing electrophilic small Orlistat leads to inhibition of these two biomedically important epigenetic enzymes. Our work demonstrates that clinically used ebse
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Despite these data implicating Kdm b as a positive regulator
2022-03-22
Despite these data implicating Kdm6b as a positive regulator of neuronal differentiation, and surprisingly, given the evidence that germline knockouts die perinatally due to an inability to breathe, the brains of Kdm6b knockout mice are remarkably normal in gross morphology [26,]. Interestingly, Kdm
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Under most circumstances NO is a potent endogenous
2022-03-21
Under most circumstances, NO is a potent endogenous vasodilator. Therefore, its involvement in an endothelium-dependent contraction seems paradoxical, to say the least. Soluble guanylyl cyclase (sGC) is the major downstream target of NO; its inhibition results in the lack of vasoconstrictor response
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Although it has been observed in numerous studies
2022-03-21
Although it has been observed in numerous studies and by many investigators that intraplatelet cGMP elevation results in platelet inhibition, there are a few papers which proposed a platelet stimulatory role for cGMP when elevated in response to NO donors or PDE5 inhibitors in mouse and human platel
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br GPR GPR has been
2022-03-21
GPR55 GPR55 has been described as a type 3 cannabinoid receptor due to its ability to detect endocannabinoids and may play a role in the endocannabinoid lipid sensing system [28]. GPR55 is activated by both cannabinoid endogenous agoinsts (endocannabinoids) and non-cannabinoids fatty acids namely
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br Niacin has long been used for
2022-03-21
Niacin () () has long been used for the treatment of lipid disorders and for the prevention of cardiovascular disease, the leading cause of death in the U.S., as a result of its ability to raise high-density lipoprotein (HDL) levels. Recent mechanistic investigations have shown that niacin may exe
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Taken together specific antibodies and
2022-03-21
Taken together, specific AM095 and SR-SIM used in the study helped uniquely visualize the distribution of lymphocytes and macrophages with their molecular expression in human cochleae. Using SR-SIM, we verified that resident IBA1-positive macrophages are widely distributed in human cochlea (Liu et a
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It is important to clarify
2022-03-21
It is important to clarify whether the decrease in USV after administration was secondary to the central depressant actions of the test compounds. Several reports have addressed the possibility that central depressant actions such as motor incoordination or changes in body temperature might affect U
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The calculations for the R substrate showed
2022-03-21
The calculations for the R substrate showed that, like the S substrate, the coordination shell of the Zn calmodulin dependent protein kinase is more symmetric than in the HIC-SG crystal structure. This symmetry indicates that the enzyme could use the same reaction mechanisms as for the S substrate,
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