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br Mechanisms of acquired resistance to
2019-12-14

Mechanisms of acquired resistance to 1st and 2nd generation EGFR inhibitors After treatment with first or second generation EGFR TKIs, virtually all patients after approximately 12 months develop acquired resistance (AR). Different mechanisms of AR to EGFR TKIs have been reported to date and may
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The fact that the mean tumor size of the
2019-12-14

The fact that the mean tumor size of the E1202-654 + α-GalCer group was much smaller than that of the α-GalCer inoculated group in both protocols indicates that immunization with E1202-654 plus α-GalCer, which induces a strong CD8+ T cell E1 antigen-specific immune response, is involved in the elimi
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Substituents at the C position An oxygen containing substitu
2019-12-14

Substituents at the C11 position — An oxygen-containing substituent at the C11 position also affects the catalytic activity of Δ1-KSTDs. The Δ1-KSTDs from the Gram-positive bacteria R. equi [29], N. simplex ATCC 6946 and IFO 12069 [48,49,52], and R. rhodochrous IFO 3338 [27] were able to 1(2)-dehydr
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Our recent discovery M P H R A S
2019-12-14

Our recent discovery (M.P., H.R., A.S.) of a highly selective and in vivo active DDR1 small-molecule inhibitor provides evidence that DDR1 is a druggable pharmaceutical target, and some details of our efforts are provided below. To avoid the repurposing of known kinase inhibitor structural motifs, w
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In contrast to SQLE HMGCR could be efficiently degraded in
2019-12-13

In contrast to SQLE, HMGCR could be efficiently degraded in L-Cysteinesulfinic acid lacking UBE2J2. However, this was not the case in cells devoid of UBE2G2, as these cells were unable to support 25-hydroxycholesterol (25-HC)-stimulated degradation of HMGCR (Fig. 1C). This finding is consistent wit
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The first ones class A
2019-12-13

The first ones class A receptors found as heterodimers were reported by Gomes et al. (2000), who identified a heteromer constituted by two subtypes of opioid receptors (μ and δ) in heterologous cells. The same year, Ginés et al. (2000) showed the first heteromer composed of two different receptors,
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Finally unilateral microinjection of CP Astressin B
2019-12-13

Finally, unilateral microinjection of CP-376395, Astressin 2B, CP-376395 + CRF or ASTR 2B + CRF into the BLA (Fig. 3A) or CeA (Fig. 3B) did not significantly alter spontaneous motor activity in the open field test (F4,24 = 0.148, P > 0.05; F4,29 = 0.290, P > 0.05 in the BLA and CeA, respectively, AN
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Therefore HNE is an attractive therapeutic target and the
2019-12-13

Therefore, HNE is an attractive therapeutic target and the design of new HNE inhibitors is a demanding field that has been extensively investigated in order to provide inhibitors with new molecular architectures, including the potent oxo-β-lactam class [14]. In the present work, a coumarin-based oxo
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Mulan is one of three
2019-12-13

Mulan is one of three E3 ubiquitin ligases that are present in the mitochondria along with MARCH5/MITOL (membrane associated RING-CH5) and RNF185 [14], [15], [16], [17]. Mulan is a 352-residue polypeptide that crosses the mitochondrial outer membrane (OMM) twice, its amino-terminus, which includes t
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It is of interest to consider an explanation
2019-12-13

It is of interest to consider an explanation for the apparent phosphorylation of hSSB1 in undamaged cells. One such may be that in order to execute a rapid response to replication inhibition, basal S134 phosphorylation could function to keep hSSB1 in a ‘primed’ state prior to stress. Such an arrange
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Besides the regulation of the stress
2019-12-13

Besides the regulation of the stress responses, CRF and the urocortins have been implicated in drug addiction (Bruijnzeel and Gold, 2005, Sarnyai et al., 2001). For instance nicotine, the addictive substance of tobacco, can activate the HPA axis, just like any other stressor may do, although its imp
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Although the findings detailed above provide ample
2019-12-13

Although the findings detailed above provide ample evidence that the activity of the CRF1 receptor in the amygdala plays a role in the acute and chronic effects of alcohol exposure, several important areas of investigation remain understudied. The majority of the work on CRF1-alcohol interactions ha
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Taken together our results demonstrate
2019-12-13

Taken together, our results demonstrate that the changes of striatal dopamine release and locomotor activity observed following chronic nicotine treatment and consequent acute withdrawal are mediated by CRF1, but not CRF2. Previous studies have already indicated that blocking CRF1 would prevent some
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In the Cu bioassay notwithstanding the absence of significan
2019-12-13

In the Cu bioassay, notwithstanding the absence of significant Cu bioaccumulation in bulk tissues over the 96-h exposure period (less than 2-fold difference in tissue Cu between controls and the second-highest treatment), T-ChE activity increased with Cu concentration in gill and, to a lesser extent
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npy br Ubiquitylation of the TGF BMP pathway components
2019-12-12

Ubiquitylation of the TGFβ/BMP pathway components Ubiquitylation is a reversible post-translational modification that is essential in many cellular regulatory mechanisms [20], [21]. During the ubiquitylation cascade, ubiquitin is attached to target proteins through the concerted actions of an E1-
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