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Based on the ability of CRF to
2021-01-07
Based on the ability of CRF to modulate nociception, we hypothesized that stress leads to hyperalgesia by the activation of CRF1 and/or CRF2 receptors in the spinal cord. We tested this hypothesis using an acute forced swim as a widely used and easily reproducible stressor and grip force as a measur
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In the particular case of metals several
2021-01-06
In the particular case of metals, several authors showed that AChE inhibition is somewhat contradictory and even questionable (Frasco et al., 2005, Nunes et al., 2005, Sáenz et al., 2010). Uranium is a particular metal, and one that has been shown to complex with several biologically important prote
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NPC L expression is both tissue and species specific Consist
2021-01-06
NPC1L1 expression is both tissue- and species-specific. Consistent with its function, NPC1L1 is mainly localized to the brush border membrane of enterocytes and the canalicular membrane of hepatocytes. NPC1L1, which is expressed in the liver of humans and rats but not mice, mediates cholesterol PU-W
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The genetic basis of resistance
2021-01-06
The genetic basis of resistance to dieldrin has been described for several insect species as a mutation in the transmembrane domain II of the GABA-Cl or rdl (resistance to dieldrin) gene (ffrench-Constant et al., 2004; Bass et al., 2004; Du et al., 2005). A mutation in the GABA-Cl gene was found at
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Identification of the drug to be used as first step
2021-01-06
Identification of the drug to be used as first-step antihypertensive treatment has always been, and remains, a matter of debate. The decision wihich drug (or drug combination) to choose as first-line therapy depend on many variables such as coexisting metabolic disorders, obesity, presence of subcli
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Current therapeutic protocols in OS and ES consist of neoadj
2021-01-06
Current therapeutic protocols in OS and ES consist of neoadjuvant chemotherapy and local surgical resection, followed by adjuvant chemotherapy. These treatments lead to a 70% overall survival for localized disease but can decrease to 15% in case of metastasis. With CS being resistant to conventional
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We continued to investigate the contribution of
2021-01-06
We continued to investigate the contribution of the EP1 SB 204070 to nociceptive sensitization by utilizing its natural ligand PGE and tested the effect of local subcutaneous injection of PGE (5nmol in 5μl) into one hindpaw on mechanical and heat pain thresholds. Wild-type mice displayed maximum sen
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The ADME profile of AAT was very promising
2021-01-06
The ADME profile of AAT-008 () was very promising, with high stability in HLM. The pre-clinical pharmacokinetic properties of AAT-008 were also assessed in rats (Sprague-Dawley, male), dogs (beagle, male), and monkeys (cynomolgus, male). The experimentally determined parameters are summarized in .
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In conclusion we have identified Ednra
2021-01-06
In conclusion, we have identified Ednra as a downstream direct target of Hoxa9 and Meis1. Upregulation of Ednra has a role in the progression of Hoxa9+Meis1-induced leukemia and targeting Ednra together with other chemotherapies may have therapeutic benefits for leukemia [30]. Ednra inhibitors in th
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In conclusion using human liver
2021-01-06
In conclusion, using human liver microsomes, supersomes from baculovirus-transformed insect cells expressing different human CYP450 isoforms, and V79MZh3A4 cells, MB2 and MB4 were formed from TRB and MC from TRC. The amounts of MB2, MB4, and MC formed were related to the 6β-testosterone hydroxylase
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MI has been detected in wastewater
2021-01-06
3MI has been detected in wastewater at concentrations of 640–700 μg L−1 (Hwang et al., 1995) and up to 20 mg L−1 in decaying algal water environments (Peller et al., 2014). It is likely that 3MI accumulation in fish might be due to the degradation of endogenous amino acids. The presence of this che
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ELUXA HM EMSI is an ongoing pivotal Phase
2021-01-06
ELUXA 1 (HM-EMSI-202) is an ongoing pivotal Phase II global clinical trial, designed to further investigate the efficacy and safety of Olmutinib in patients T790M-positive NSCLC with acquired resistance after first-line EGFR TKIs. Primary endpoint is ORR according to RECIST 1.1, while secondary endp
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The concept of GPCRs and EGFRs existing as heteromers is
2021-01-06
The concept of GPCRs and EGFRs existing as heteromers is consistent with previous studies. Co-immunoprecipitation studies have shown that agonist stimulation (both AngII and EGF) promotes a multi-protein complex containing the AT1R and EGFR, however these endpoint assays were not in live cells or in
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EDTA sale br Results br Discussion Our UbV library
2021-01-06
Results Discussion Our UbV library was originally designed to develop inhibitors of deubiquitinases (Ernst et al., 2013). Recently, we showed that UbVs could exhibit multiple binding modes and mechanisms to modulate HECT E3 activity (Zhang et al., 2016)—one set occupied the HECT domain E2-bind
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br Acknowledgments We thank Jon Clardy Juan Manuel Dom
2021-01-06
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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