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An ideal CHK inhibitor would
2019-09-23
An ideal CHK-1 inhibitor would be minimally cytotoxic, while enhancing the anti-tumor effect of a real cytotoxic agent that would be used in combination with the inhibitor. Our CHK-1 inhibitors have shown excellent selectivity over a panel of kinases including those regulating the cell cycle, but th
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Prostaglandins PGs in particular PGE and PGF play pivotal ro
2019-09-23
Prostaglandins (PGs), in particular PGE2 and PGF2α, play pivotal roles in human parturition by stimulating cervical ripening, myometrial contraction and fetal membrane rupture (Challis et al., 1997). In human pregnancy, the amnion is the principle source of PGE2 (Duchesne et al., 1978). In the amnio
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Downregulation of tumor suppressors is a major
2019-09-23
Downregulation of tumor suppressors is a major factor that leads to tumorigenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a common tumor suppressor, the Sorbitol pathway of which is often downregulated or even absent in the majority of human cancers, functions as a phosphata
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In the present study we investigated
2019-09-21
In the present study, we investigated the role played by CRF1 and CRF2 receptors located within the mouse PAG on the anxiogenic and antinociceptive effects produced by local infusion of CRF. To block CRF receptors, we used the selective CRF1 and CRF2 2-Deoxycytidine antagonists, respectively, NBI 2
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Altogether the results of this study demonstrate that periph
2019-09-21
Altogether, the results of this study demonstrate that peripheral blockade of both ETA and ETB receptors reduces tumor-induced facial heat hyperalgesia and increased spontaneous grooming, without modifying ongoing nociception. It is possible to suggest that bosentan is acting upon both receptors pre
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This pre GC B cell differentiation
2019-09-21
This pre-GC B cell differentiation deficiency caused by RD2 loss of function was explained at least in part by the finding that the BCL6 RD2 domain is required to repress expression of the key migration factors GRP183 and S1PR1. Downregulation of GRP183 is critically important for B cell migration i
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Why are Tfh cell dynamics so fundamentally different in
2019-09-21
Why are Tfh cell dynamics so fundamentally different in naive and immune animals? Initially, GC Pentostatin must pass stringent affinity and specificity checkpoints to ensure only high-affinity non-self-reactive cells are selected. Therefore, restricting primary Tfh cells with the greatest helper ca
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To understand more clearly how
2019-09-21
To understand more clearly how these activities are combined in the heterotrimeric enzyme and to understand more clearly how DNA alkylation might effect DNA helicase activity, we summarize the relevant features of the structure of RecBCD determined in the presence of DNA. The RecB and RecC subunits
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Then what is the solution to tackle DNA damage
2019-09-20
Then what is the solution to tackle DNA damage-induced metabolic decline? The culprit here may be not DNA damage signaling per se, but rather the persistent activation of the DNA damage signaling pathways due to age-related accumulation of DNA damage. DNA repair, including repair by NHEJ, is an esse
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CFSs are recognized as a driver of
2019-09-20
CFSs are recognized as a driver of genome instability in human cells and are hotspots for deletions or translocations in cancers (Richards, 2001). The generally accepted model for their expression is that the CFS locus shows a delay in chromatin condensation in early mitosis caused by the persistenc
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br Conclusion The present work describes the synthesis of na
2019-09-20
Conclusion The present work describes the synthesis of 18 naphthoquinonolyl-1,2,3-triazole compounds based on natural product modification with antiplasmodial activity. Lapachol derivatives disclosed higher activity than the natural product. Six of these final modified lapachol 1,2,3-triazole com
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flt3 In conclusion the magnitude of the association between
2019-09-20
In conclusion, the magnitude of the association between prenatal exposure to MeHg and child neuropsychological development appears to be modified by polymorphisms in CYP3A7 and CYP3A5 genes in some of the populations studied. These results provide some support for the hypothesis that CYP3A genes may
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Since cognitive disturbances are core features of PTSD and
2019-09-20
Since cognitive disturbances are core features of PTSD [3,4], and in some studies COMT Val158/108Met was associated with cognition [10] and hippocampal volume [12], the hypothesis was that carriers of the Met allele will show better cognitive performance compared to Val/Val carriers in PTSD. The aim
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br Estrogen receptors activate mGluR signaling pathways In o
2019-09-20
Estrogen receptors activate mGluR signaling pathways In order to distinguish the opposing effects of estradiol on CREB phosphorylation, we turned to a “bottom-up” approach, working backwards from CREB phosphorylation to pharmacologically isolate the two signaling pathways (Boulware et al., 2005).
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The most common pathology associated with FGR
2019-09-20
The most common pathology associated with FGR is poor placental perfusion as a result of abnormal placentation [4]. Placental developmental disorders and insufficient hormone synthesis may lead to FGR [5,6]. However, the exact mechanism responsible for abnormal placental development remains unclear.
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