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The regulation of the stem cell compartment in CML
2021-09-24
The regulation of the stem cell compartment in CML is dynamic, in particular, during disease progression to a blast crisis and might involve a complex cross-regulation of Hh, Wnt, Notch, and hox signaling pathways (). Significant upregulation of Ptch1 and cyclin D1, upon other proteins, marks the bl
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Whether or not SMO and
2021-09-24
Whether or not SMO and SMO-dependent HH signaling play a role in hematopoiesis is a subject of strong controversy. Obviously, the effects of SMO deletion are highly contextual and dependent on the timing of deletion. transplanted murine Smo−/− fetal liver Silvestrol into sublethally irradiated mic
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br Discussion According to the generally accepted notion whi
2021-09-24
Discussion According to the generally accepted notion which originated from the study of ATP-depleted Tubastatin A the changes in Ca2+ homeostasis induced by ATP depletion and leading to the activation of the Gárdos effect are due to the inhibition of Ca2+ pumping, and the subsequent entry of Ca
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Because AM had limited efficacy on
2021-09-24
Because (AM-3189) had limited efficacy on rodent GPR40, we used two rodent models expressing human GPR40 to demonstrate efficacy of (AM-3189). First, we used human islet transplanted nude mice. In this model, endogenous pancreatic β-cells were ablated using streptozotocin, and mice were rescued to e
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br Significance Metabolites present in the extracellular
2021-09-24
Significance Metabolites present in the extracellular environment can potently modulate cellular phenotypes and potentially serve as therapeutics for various diseases. Ferroptosis is a non-apoptotic cell death process characterized by the generation of toxic lipid reactive oxygen species (ROS). I
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Introduction Ventilator induced lung injury VILI is the most
2021-09-24
Introduction Ventilator-induced lung injury(VILI) is the most common complication in the mechanical ventilation in clinic. Repetitive opening and closing of SCH-900776 at high pressures during artificial ventilation would generate shear stress and then lead to the damage of cell junction and dysre
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The first phase of insulin secretion is due to
2021-09-24
The first phase of insulin secretion is due to calcium signaling because of glucose sensing, increased cytoplasmic ATP levels, cellular depolarization, calcium influx and activation of calcium sensing molecules that eventually causes the fusion of the insulin granules to plasma membrane (exocytosis)
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Drosophila is a well established model to investigate
2021-09-24
Drosophila is a well-established model to investigate the molecular and cellular defects underlying human neurodevelopmental disorders (Oortveld et al., 2013, van der Voet et al., 2014). Here, we establish Drosophila as a model for understanding the mechanisms linking mutations in KDM5 family protei
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NGS substitution linkage analysis and
2021-09-23
NGS substitution linkage analysis and haplotype reconstruction was previously only used for short genome segments and not in the context of antiviral resistance. We optimized this approach to cover a complete viral protein and major DAA target, enabling us to investigate resistance associated NS3P h
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50014 br Materials and methods br Results br Discussion
2021-09-23
Materials and methods Results Discussion Early studies in the mid 1980s tentatively identified cCMP in tissues using fast atom bombardment MS [3], [4], but specificity and sensitivity of the method are insufficient for unequivocal identification as compared to modern MS analytical methods.
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br Materials and methods br Results br
2021-09-23
Materials and methods Results Discussion Main results obtained in this work are presented in Table 1 and can be summarized as follows: 1) AEA inhibits FcεRI receptor-induced degranulation with the participation of CB2 and GPR55 receptors by a PTX-insensitive mechanism; 2) AEA does not block
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In summary we have designed and optimized a new
2021-09-23
In summary, we have designed and optimized a new series of 1,4-dioxycyclohexane GPR119 agonists. SAR studies led to the discovery of the preferred molecule that has potent and efficacious GPR119 activity across species. This lead compound exhibited an excellent ADME and safety profile, and demonstr
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GPR agonistic activity was evaluated for the human GPR recep
2021-09-23
GPR119 agonistic activity was evaluated for the human GPR119 receptor in a cell-based cAMP assay. The results expressed the potency as EC values and the inherent activity (IA) as percentages which were compared to the test compound with oleoylethanolamide (OEA), an endogenous ligand of GPR119 (defin
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A linker length of and atoms was found to be
2021-09-23
A linker length of 4 and 5 atoms was found to be optimal ( and ) compared to the only weakly active compounds with longer linkers ( and ) or the inactive compounds with shorter linker chains (–). In a next step incorporation of hetero-atoms in the linker was explored (). An amide linker as in and d
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dna ligase The activation of the ERK pathway participates
2021-09-23
The activation of the ERK pathway participates in the transmission of pain signaling by sensitizing primary afferents (Ji et al., 2009, Lai et al., 2011). Thus, the blockade of ERK activation in the primary sensory dna ligase can reduce the mechanical hypersensitivity and the thermal hypersensitivi
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