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Apart from its high affinity the selection of
2020-09-09
Apart from its high affinity, the selection of GW2580 as MLCK inhibitor peptide 18 lead in our radiotracer development program was motivated by its exceptional selectivity. The observed profound impact of small structural modifications on the selected panel of four kinases tested prompted us to cond
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Previous studies reported that NE and MHPG
2020-09-09
Previous studies reported that NE and MHPG are deeply involved in depression and that NE reuptake inhibitors are approved for use in patients with depression (for review, see [2]). We found increased hippocampal content of NE and MHPG in the CORT-treated CRTH2−/− mice (Fig. 3). In the hippocampus, a
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According to these results the power
2020-09-09
According to these results, the power GaN seems more robust than existing technologies (VDMOS, Superjunction, IGBT,) [5,10] and [11]. Comparing with the SiC technology, the previous works show a low SEE tolerance [[12], [13], [14]] and [15]. The SOA of power GaN devices can be equivalent to the IGBT
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The first mammalian mutation linked to CR was identified
2020-09-08
The first mammalian mutation linked to CR was identified in golden hamsters (Mesocricetus auratus). The mutation was an autosomal allele first described in the late 1980s [8] and was identified using positional cloning [9]. These animals displayed a shortened period length (20h in homozygous animals
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br Introduction In addition to the canonical double stranded
2020-09-08
Introduction In addition to the canonical double stranded structure, DNA can form various higher order structures such as bulges, and various kinds of mismatches, triplexes, to the G-quadruplex (G4). Over the past decades, accumulating evidence has begun to emerge that these non-canonical structu
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DGK is a key enzyme
2020-09-08
DGKδ is a key enzyme in glucose uptake in skeletal muscle. Chibalin et al. demonstrated that a decrease in DGKδ expression increases the severity of type 2 diabetes [20]. Additionally, DGKδ expression was increased in people who exhibited enhanced insulin sensitivity after exercise training [56]. Fr
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br Acknowledgement br Introduction Human dihydroorotate dehy
2020-09-08
Acknowledgement Introduction Human dihydroorotate dehydrogenase (hDHODH), a flavin-dependent mitochondrial enzyme involved in de novo CP 154526 biosynthesis, is a validated therapeutic target for the treatment of autoimmune diseases such as rheumatoid arthritis and cancer [1], [2], [3]. Leflu
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The current study provides evidence for a previously unknown
2020-09-08
The current study provides evidence for a previously unknown role for DHODH as a growth/survival factor in KRAS mutant tumors. While many aspects of the link between DHODH inhibition and survival of KRAS mutant cells remain to be established, de novo pyrimidine biosynthesis appears to be a crucial
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The aim of this paper is to study the long
2020-09-08
The aim of this paper is to study the long-term socioeconomic impacts of local heat entrepreneurship from 2000 to 2016. The analysis focuses on impacts of the biomass-based district heat production on employment and income in a small peripheral community, called Eno, located in North Karelia, Finlan
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The cytoplasmic domain of classical cadherins is highly
2020-09-08
The cytoplasmic domain of classical cadherins is highly conserved and can interact with different cytosolic proteins. Typically this domain is associated with catenin family members, including p120 catenin, β-catenin, and α-catenin, which form a cadherin-catenin complex (Fig. 1). The catenin family
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Among the other mediators which have been
2020-09-07
Among the other mediators which have been reported to play a role in erection are prostaglandins (PGs). Several studies have reported that alprostadil- synthetic PGE1- showed high efficacy in management of erectile dysfunction as it induces corpus cavernosal relaxation. Alprostadil has been first d
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Partial suppression of the cot ts phenotype by deletion
2020-09-07
Partial suppression of the cot-1 (ts) phenotype by deletion of gul-1 has been well documented (Seiler et al., 2006). This is now also very clearly evident in the transcriptional profile of the various strains (Fig. 2). Furthermore, the comparative analysis of the single and double mutants revealed,
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To investigate the mechanism of action of
2020-09-07
To investigate the mechanism of action of 2,4,5-trisubstituted azoles, we profiled selected 2,4,5-trisubstituted azoles against a panel of 97 kinases to identify potential targets that could be involved in cardiogenesis. We narrowed down the identified targets to the casein kinase 1 (CK1) family due
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Two additional hydrogen bonds are formed by
2020-09-07
Two additional hydrogen-bonds are formed by the -substituted methoxy-group with Ser and Asp. Ser exerts the role of a gate keeper in CK1: Entry of the ATP in the binding-site causes a conformational change into the closed form by Ser, which locks the binding-site and prevents ATP-diffusion out of th
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The causes of POD are complex and not
2020-09-07
The causes of POD are complex, and not entirely clear. Androsova et al, believed that the main molecular mechanism of POD is a central cholinergic deficiency caused by deregulation of cholinergic anti-inflammatory pathways leading to increased inflammation. The cholinergic anti-inflammatory pathway,
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