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Herein we report the discovery
2022-07-29
Herein, we report the discovery of AM-3189 (). AM-3189 maintains the in vivo efficacy of AMG 837 while displaying a superior pharmacokinetic profile and minimal CNS exposure. As we reported previously, activity on the GPR40 receptor varies significantly with substitution at the β-carbon relative to
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The improved glucose tolerance of Ffar R W R W
2022-07-29
The improved glucose tolerance of Ffar1R258W/R258W mice on HFD was unexpected. In combination with similar fasting blood glucose levels, the significant lower fasting plasma insulin of mutant mice compared to wild-type mice is indicative of improved insulin sensitivity. However, peripheral insulin r
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Following these discoveries the term
2022-07-29
Following these discoveries, the term ferroptosis was coined in 2012 [25], to describe this iron-dependent, non-apoptotic form cell death induced by erastin and RSL3. This discovery was accompanied by the development of the first small molecule ferroptosis inhibitor, termed ferrostatin-1, and the de
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Consideration must be given to both the tissues themselves a
2022-07-28
Consideration must be given to both the tissues themselves and to infiltrating immune cells. As highlighted by Maxwell and Eckardt [88], clinical trials of compounds targeting these pathways will require large numbers of participants and prolonged follow-up to identify rare and late complications or
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Since its development the HCV replicon system Lohmann et
2022-07-28
Since its development, the HCV replicon system (Lohmann et al., 1999) has been a critical tool in the HCV antiviral discovery process (Gottwein et al., 2009, Imhof and Simmonds, 2010, Lohmann et al., 1999, Pietschmann et al., 2001, Imhof and Simmonds, 2010, Gottwein et al., 2009). The replicon assay
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Subcellular domains where Rac is
2022-07-27
Subcellular domains where Rac is active show limited Rho activity and vice versa (Fig. 4). This distinctive patterning in Rho activity is achieved via the downstream Rac effector Par6, an important part of the so-called Par polarity complex. In primary epithelium, the cytoskeleton and associated Rho
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The GSTP promoter region in PCA cells without or with
2022-07-27
The GSTP1 promoter region in PCA cells without or with reduced GSTP1 mRNA expression had a different histone modification pattern than BPH-1 cells with GSTP1 mRNA expression: the repressive histone modifications H3K9me3/H3K27me2 were distinctly increased and H3K27me3/H3K9me2 were slightly decreased
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Using RT PCR we demonstrated the expression
2022-07-27
Using RT-PCR we demonstrated the expression of GPR55 receptor mRNA in the ileum and colon of mice, which is in good agreement with previous reports (Lin et al., 2011). The quantitative analysis showed the abundance of GPR55 mRNA in the mucosa of the ileum and colon. In contrast, in LMMP preparations
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br Action of GPR in metabolically active tissues In addition
2022-07-27
Action of GPR55 in metabolically active tissues In addition to being highly expressed by discrete brain regions, as described in Section 2, GPR55 is also expressed in a wide range of peripheral tissues, including spleen, adrenals and bone (Sawzdargo et al., 1999, Ryberg et al., 2007, Whyte et al.
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The discovery that the physiological functions
2022-07-27
The discovery that the physiological functions of LPI are associated with the activation of specific GPR55 membrane receptor [4] has launched a new era of research on this lysophospholipid. However, the activation of membrane receptors by lysophospholipids is extremely complex due to the multitude o
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Notably we observed that GPR activation induced by
2022-07-27
Notably, we observed that GPR35 activation induced by PA, an in vivo GPR35 agonist [6], significantly decreased DAI, colon weight, and histological score, while increasing colon length in mice with DSS-induced colitis. Furthermore, fibronectin and integrin α5 were co-localized with GPR35 on the colo
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For some agonists these stable GPR
2022-07-27
For some agonists, these stable GPR119 responses were resistant to washing. Thus, sustained activation could continue, for at least a number of hours, even after removal of free agonist. These data are consistent with reports for other GPCR systems that do not desensitize (Calebiro et al., 2009, Fer
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br Concluding Remarks br Outstanding Questions br
2022-07-27
Concluding Remarks Outstanding Questions Acknowledgments Research on DNA glycosylases in our laboratory is supported by the National Science Foundation (MCB-1517695). A.A.R. and N.P.B. are supported by the National Science Foundation Graduate Research Fellowship Program (DGE-1445197). In
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br Materials and methods br Results br Discussion Neurotrans
2022-07-27
Materials and methods Results Discussion Neurotransmitter uptake is one of the most important aspects of synaptic transmission, it fact, the existence of a specific uptake system is one of the requisites that any neuroactive substance has to cover to be considered a neurotransmitter. It has
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Which is the preferred dimer configuration the one correspon
2022-07-27
Which is the preferred dimer configuration, the one corresponding to the active state or the one corresponding to the desensitized state? Umbrella sampling simulations of a pair of GluA2 LBDs, using distances at the top (proximal to the ATD) and the bottom (proximal to the TMD), indicate that the de
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