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Diacylglycerol kinases DGK and are lipid kinases
2021-03-02
Diacylglycerol kinases (DGK) α and ζ are lipid kinases that limit diacylglycerol (DAG)-dependent activation pathways downstream of the TCR (Merida et al., 2015). Their upregulation in tumor infiltrating lymphocytes (TIL) has been linked to generation of hyporesponsive states that contribute to immun
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Thus DGK active sites remain ill defined
2021-03-02
Thus, DGK-active sites remain ill-defined and, combined with the lack of crystal structures for mammalian DGKs, have limited our understanding of substrate and inhibitor binding. As a result, current DGK inhibitors consist of compounds with poor specificity within the DGK superfamily (de Chaffoy de
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The all NTP pyrophosphatase and NUDIX families maintain
2021-03-02
The all-α NTP pyrophosphatase and NUDIX families maintain the deoxynucleotide triphosphate (dNTP) pool balance, limit the incorporation of harmful nucleotides, and represent a promising therapeutic approach to develop anticancer and immunosuppressive agents., , , , Among these housekeeping enzymes
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Studies also provide evidence that cytokines such as
2021-03-02
Studies also provide evidence that cytokines such as TGF-β, a TH3-type cytokine, may also play a role in airway remodeling. Data obtained by Cohen et al suggest that TGF-β1 can induce human BSMC proliferation by increasing the expression of IGFBP-3. Hence, the mitogenic action of TGF-β1 could be rel
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Pattern separation is a process that takes place in the
2021-03-02
Pattern separation is a process that takes place in the hippocampus and more specifically in the dentate gyrus (DG) and Cornu Ammonis region 3 (CA3) (Morris, Churchwell, Kesner, & Gilbert, 2012). The main source of input in the hippocampus is derived from the enthorinal cortex (EC) that mainly proje
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The present study sought to determine if chlorodifluoroaceto
2021-03-02
The present study sought to determine if chlorodifluoroacetophenones, such as 3 and 4, were amenable to a radiolabelling methodology to generate potential 18F imaging agents with high cholinesterase affinity. A number of procedures have been reported for the synthesis of trifluoromethyl ketones, inc
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In the present study promoting bile acid synthesis by
2021-03-02
In the present study, promoting bile Neurotensin synthesis synthesis by activating EP4 receptors was shown to exert protection against hepatic steatosis. This finding may be relevant for treatment of non-alcoholic fatty liver disease, a major cause of liver disease and prominent indication for live
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Obviously there are some limitations in our study
2021-03-02
Obviously, there are some limitations in our study; due to sample constraints, we had to focus our efforts on one specific T cell epitope from one candidate autoantigen. Optimally, we could have studied several different peptides in parallel. Additionally, all RA patients included in the study have
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Imatinib STI is a first line tyrosine kinase
2021-03-02
Imatinib (STI-571) is a first-line tyrosine kinase inhibitor (TKI) targeted at breakpoint cluster region-Abelson kinase (ABL) for the treatment of chronic myeloid leukemia (CML) [26]. As a type II inhibitor, imatinib achieves significant selectivity by binding to an inactive DFG-out conformation (D
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The best characterized APC C substrates are recruited via
2021-03-01
The best-characterized APC/C substrates are recruited via various linear motifs (e.g., D boxes, KEN boxes, and ABBA motifs) that serve as degrons, binding to distinct regions of the β-propeller domain of a coactivator (Figure 1, Figure 3B) (reviewed in [44]). In addition, D boxes also simultaneously
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Inflammatory action of certain cytokines can influence cell
2021-03-01
Inflammatory action of certain cytokines can influence cell proliferative routes (Deshmane et al., 2009). When mTOR is inhibited, for instance by the action of Rapa, TGF-β1, which has an anti-inflammatory action, is increased. The relationship between high levels of TGF-β1 and anatoxin a synthesis
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br Patients and Methods Patients who had been initiated
2021-03-01
Patients and Methods Patients who had been initiated on a DPP-4 inhibitor (see in the online version at doi:10.1016/j.clinthera.2018.06.002) between April 2012 and June 2017, when the common threshold for dose adjustment for all non-linagliptin DPP-4 inhibitors was a creatinine clearance (CrCl) l
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The inhibition of NPY cleavage may also contribute
2021-03-01
The inhibition of NPY cleavage may also contribute to the effect of gliptins on blood pressure [123]: NPY is an agonist of Y1 receptor mediating peripheral vasoconstriction. Interestingly, blood pressure in adult SHRs was not affected by single dose administration of a specific DPP-4i whereas blood
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In addition to G coupling it is
2021-03-01
In addition to Gα coupling, it is important to consider that the transition from goal-directed to habitual drug taking also relies on striatal D2R-A2AR heterodimers. Following cocaine self-administration, D2R-A2AR density is increased in the NAc, leading to greater antagonism of the inhibitory (anti
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While apparent that His Artemis fractionated
2021-03-01
While apparent that [His]6-Artemis fractionated over a HAP column is devoid of 5′–3′ exonuclease activity but still retains DNA-PK dependent hairpin-opening activity, we sought to further assess DNA-PK dependent Artemis overhang cleavage activity to ensure all the in vivo, intrinsic enzymatic activ
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