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The aldehyde reductase AKR A
2023-07-15

The aldehyde reductase (AKR1A1) and aldose reductase (AKR1B1) belong to aldo-ketoreductase (AKR) superfamily catalyzing the reduction of corresponding aldehydes and ketones involved. Both the closely related enzymes AKR1A1 and AKR1B1 have 65% structural similarity and differ only at the active site.
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Adiponectin is an adipokine whose circulating level is deple
2023-07-15

Adiponectin is an adipokine whose circulating level is depleted in a number of metabolic diseases including insulin resistance, diabetes and cancer (Khan et al., 2015, Singh et al., 2014a, Singh et al., 2014b, Yamauchi et al., 2014). Despite its importance in health and pathophysiology, adiponectin
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The activation of the A BR subtype
2023-07-15

The activation of the A2BR subtype triggers different intracellular metabolic pathways, often linked to the activation of adenylyl cyclase and increased levels of intracellular cAMP (Lynge et al., 2003, Bernareggi et al., 2015). The nAChR-channel Auranofin mediated by the cAMP/PKA pathway was repor
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br Actin cytoskeleton in protrusion Pushing force driving me
2023-07-15

Actin cytoskeleton in protrusion Pushing force driving membrane protrusion is generated by polymerizing 1215 filaments organized either into branched networks or parallel bundles. Branched networks are assembled through Arp2/3 complex-dependent actin nucleation and drive protrusion of lamellipod
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Since pyrrolopyrimidine dithiolanes and both
2023-07-15

Since pyrrolopyrimidine dithiolanes and both displayed particularly excellent levels of ACK1 inhibition, these analogs were viewed as potential candidates for further investigation in tumor xenograft experiments. While in vitro metabolic studies indicated that pyrrolidine was predicted to be sign
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Our initial approach to identify hits
2023-07-15

Our initial approach to identify hits was two-pronged and included a high-throughput screening (HTS) campaign of the OSI dabigatran etexilate library as well as a virtual screening (VS) campaign, utilizing a publically available crystal structure of ACK1 (PDB code: ). A tolerance for protein flexib
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To reconstruct the amino acid sequence of an ancestral subun
2023-07-15

To reconstruct the amino Ponesimod sequence of an ancestral β subunit a molecular phylogeny is required, which is inferred from a β subunit sequence alignment. To build this alignment we searched the NCBI database for proteins similar in sequence to the human muscle-type β subunit precursor protein
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However although in vitro studies in heterologous systems ha
2023-07-15

However, although in vitro studies in heterologous systems have provided very important indications of potential novel pharmacology, the studies with endogenous receptors in native tissues are essential to provide evidence for GPCR heteromerization in vivo and to confirm its physiological relevance.
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In conclusion AXL overexpression preexisted in a subgroup of
2023-07-15

In conclusion, AXL overexpression preexisted in a subgroup of treatment-naive lung adenocarcinoma specimens harboring an activating EGFR mutation or in those with wild-type EGFR. Anti-AXL therapeutics delivered up front in combination with the EGFR inhibitor might overcome intrinsic or acquired resi
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The earliest appearance of tumors
2023-07-15

The earliest appearance of tumors occurred at 12 months and the latest at 24 months, with an average onset at 18 months (Fig. 1B). This would be roughly equivalent to cancer presenting in a patient between 60 and 70 years of age. In transgenic animals, autotaxin Cy7 carboxylic acid (non-sulfonated)
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Although CP has been an important research
2023-07-15

Although CP has been an important research subject in the field of antigen processing and presentation, the mechanisms of presentation of intracellular Rapalink-1 by MHC II received considerably less attention. Interestingly, pioneering work by the Münz laboratory has pointed to an involvement of a
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While the yeasts and see Glossary each contain
2023-07-15

While the yeasts and (see Glossary) each contain only one Aurora homolog, Ipl1p (increase in ploidy 1) and Ark1 (Aurora-related kinase 1), respectively 5, 6, , and Xenopus laevis contain two Aurora kinases: Aurora A and Aurora B [4]. Mammals have three Aurora kinases, A, B, and C (Figure 1). In anim
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There are profound differences between acute and chronic
2023-07-15

There are profound differences between acute and chronic pain when dramatic changes occur in peripheral nociceptors and central nociceptive pathways and the pain system is sensitised thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allo
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On the other hand there were only a few
2023-07-15

On the other hand, there were only a few cases that expressed DA2R in our study. Additionally, in the cases whose ACTH-secreting pituitary adenomas expressed DA2R, the ratio of positive staining StemRegenin 1 synthesis was very low. This suggests that dopamine agonists may be less effective in cani
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TMC647055 Choline salt Recent progress has been made in tran
2023-07-15

Recent progress has been made in translating animal findings on memory performance and amnestic effects – that are largely determined by tonically active receptors in which α5 contributes to the benzodiazepine binding site. Based on the observation that deletion of this subunit led to improved spati
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