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Blebbistatin Compounds and administered orally to
2020-05-21
Compounds , , and administered orally to fasted Harlan Sprague-Dawley rats 1h prior to trigeminal stimulation, decreased extravasation in this model in a dose-related manner, with an estimated ID of 1, 10 and 100μg/kg, respectively (determined 15min after stimulation, ). For comparison, the clinica
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Ligand binding RTK activation induces the endocytic internal
2020-05-21
Ligand binding (RTK activation) induces the endocytic internalization of RTKs, and this has been demonstrated for CSF-1R [15], [16], [17]. Endocytosed RTKs are targeted to the lysosome, which we and others have established to be dependent on ubiquitination via CBL-family and recognition by ESCRT com
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br Clinical trials of CRM inhibitors KPT clinical trials hav
2020-05-21
Clinical trials of CRM1 inhibitors KPT-330 clinical trials have been initiated with promising very early results. One trial includes patients with advanced solid tumors whose disease has progressed after at least one prior therapy for metastatic disease (NCT01607905). Another trial includes patie
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br Methods Adult male B CRHtklee mice g at
2020-05-21
Methods Adult male B6, 129 CRHtklee mice (25–30g at the beginning of the experiments) that were wild-type (CRF1R+/+) and recessive homozygous or knockout (CRF1R−/−) were housed six per cage. Mice were 3–5months old and derived from mating CRF1R+/− breeders (Jackson Laboratory, California). Wild-t
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Alternatively procedural factors may have contributed to the
2020-05-21
Alternatively, procedural factors may have contributed to the conflicting results. For instance, in order to have a more circumscribed area of drug diffusion, a volume of 0.05μl was injected in experiment 1b, which is four times lower than the one used in the mentioned plus-maze investigation. Besid
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The use of inhibitors clearly has its caveats
2020-05-21
The use of inhibitors clearly has its caveats and the field should come to a consensus on etomoxir concentration to maximally block LC-FAO while minimalizing off-target effects. The current papers convincingly show that 200 μM is too high, but it should be noted that 3 μM does not fully suppress LC-
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A further quandary concerning rediscoveries arises in
2020-05-21
A further quandary concerning rediscoveries arises in habitats modified and frequented by humans, where rediscovered species may occur through accidental or deliberate introductions (Metcalf et al., 2007) rather than having persisted despite adverse conditions. Confusion regarding origin could evoke
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br Materials and methods br Result and
2020-05-21
Materials and methods Result and discussion qRT-PCR was utilized to explore the effect of acetamizuril on the mRNA level of enolase. The results were analyzed according to the Livak 2−ΔΔCT method (Schmittgen and Livak, 2008): the mean CT of the enolase in treated and untreated samples was 29.8
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Even more unambiguous was the relative contribution of Gq si
2020-05-21
Even more unambiguous was the relative contribution of Gq/11 signaling in AngII-mediated transactivation as measured by the ERK1/2 and the BRET-based readout. Although Gq/11 was absolutely required for ERK1/2 phosphorylation following AngII-stimulation, in contrast, we observed a sustained EGFR-Grb2
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These data from developing brain are in contrast
2020-05-21
These data from developing fccp are in contrast to noradrenergic receptor regulation in the adult brain. In adult animals, a persistent increase in the α2-AR high affinity state is elicited as a result of DSP-4 lesion or reserpinization, as measured by [3H]clonidine binding to membrane preparations
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br Acknowledgments We thank Jon
2020-05-21
Acknowledgments We thank Jon Clardy, Juan Manuel Domínguez, José Francisco García Bustos, and the GlaxoSmithKline (GSK) Plasmodium falciparum dihydroorotate dehydrogenase project team for their contributions, helpful advice, and discussions. Introduction Dihydroorotate dehydrogenase (DHODH) i
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One possible explanation for differences in the binding abil
2020-05-21
One possible explanation for differences in the binding ability of monomeric versus dimeric forms of DDR2 ECD to collagen could be that the monomeric form only binds to the primary GVMGFO site, whereas dimeric (and oligomeric) DDR2 ECD binds to additional sites on the collagen triple-helical molecul
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Expression of DDR in endothelial cells has been
2020-05-21
Expression of DDR1 in endothelial cells has been previously described in human corneal blood vessels, and more recently, in murine atherosclerotic plaques (Franco et al., 2008, Mohan et al., 2001). So far, there is a lack of evidence for DDR1 expression in endothelial cells in the mouse Alda 1 (Fra
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In summary in the present study we
2020-05-21
In summary, in the present study we found that CysLT1 receptor attenuates while CysLT2 receptor facilitates OGD-induced PC12 cell death as confirmed by receptor over-expression and antagonism. However, we cannot explain why their roles are distinct and why the cell size is increased in the CysLT2 re
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A related cell based approach was used to
2020-05-21
A related, cell-based approach was used to test the functionality of the various HIV Rev fusions, but in a trans-complementation assay using 293T producers transfected with both VSV G and a Rev-deficient HIV reporter vector encoding both FFLUC and bsd (Fig. 2C). As expected, the non-fused, full-leng
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