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Our previous high throughput screening HTS campaign using au
2020-11-12

Our previous high-throughput screening (HTS) campaign using automated, robust, and sensitive fluorescence based 5-Methoxy-CTP mg assay [10], [11] led to the identification of several EPAC specific inhibitors (ESIs), and was subsequently followed by extensive hit-to-lead optimizations [20], [21], [2
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Our results demonstrate that pt PGE
2020-11-12

Our results demonstrate that 17-pt-PGE2 - in addition to its described effects on EP1 and EP3 receptors - also acts as an EP4 agonist and thereby enhances vascular barrier function. Materials and methods Results Discussion In this study we demonstrate that the purported EP1/EP3 receptor ag
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What are the molecular signals that guide Tfh cells as
2020-11-12

What are the molecular signals that guide Tfh cells as they navigate around the lymph node in the course of the immune response? It was recently reported that Tfh cells inside GCs have high expression of SIPR2, which acts to repel them from the S1P-rich lymph in the SCS and promote their retention i
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These studies established IAP proteins as dimeric RING
2020-11-12

These studies established IAP proteins as dimeric RING E3 ligases, but did not account for the essential role of dimerization. In IAPs and related E3s, such as RNF4 and MDM2, dimerization not only depends on contacts from the core RING domain but also residues N- and C-terminal to the RING domain (B
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The interface between the E ligase
2020-11-12

The interface between the E3 ligase and the E2 enzyme can vary, and ZNF451 and SP-RING ligases stabilize this interaction via noncovalent binding to a scaffold SUMO (SUMOB) on the backside of the E2 (Cappadocia et al., 2015; Eisenhardt et al., 2015; Streich & Lima, 2016). By contrast, RanBP2 does no
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Consistent with a clear separation
2020-11-12

Consistent with a clear separation of biological function between ARISC and BRISC in cells, mutations in BRCC36 and Abraxas are prevalent in cancer genomes whereas mutations in KIAA0157 are rare. A survey of the Catalogue of Somatic Mutations in Cancer (COSMIC) consortium, revealed that to date, 37
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Thymine glycol severely inhibits DNA synthesis
2020-11-11

Thymine glycol severely inhibits DNA synthesis by replicative DNA polymerases and requires the action of specialized DNA polymerases for translesion synthesis (e.g. Ref. [26]). Eukaryotic and archaeal RNAPs were shown to pause after nucleotide insertion opposite TG [27,28]. Surprisingly, we found th
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DGK is also involved in cell
2020-11-11

DGKδ is also involved in cell differentiation. Previously, to investigate the physiological roles of DGKδ, DGKδ-deficient mice have been generated. On the basis of the analysis of DGKδ-deficient mice, Crotty et al. reported that DGKδ regulates the epidermal growth factor receptor (EGFR) pathway by a
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Analysis of Table shows that compound b in
2020-11-11

Analysis of Table 1 shows that compound 7b, in which the biphenyl scaffold does not bear any substituent, displays its inhibitory potency in the micromolar range (IC50 = 11 μM). If the amide bridge is moved from position 1 to 3 of the biphenyl system, product 7c is yielded, whose potency is about 4
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br Materials and methods br
2020-11-11

Materials and methods Results Discussion Our study assessed the cytokine and chemokine changes associated with first onset PP as compared to HP and HNP groups. In the monocytes/ macrophages/ dendritic BI 6015 panel, IL-6 levels were found to be significantly elevated in both HP and PP grou
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The sequence identity of CYP A with CYP A
2020-11-11

The sequence identity of CYP3A163 with CYP3A sequences from other species is maximum in reptiles ranging (75-91)%, gradually decreasing from L-161,982 synthesis (63-71)% to mammals 62% to downwards based on evolutionary distances. The high level of homology with CYP3A77 in Alligator mississippiensi
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R co localizes Golgi marker GM
2020-11-11

R co-localizes Golgi marker GM130 (Fig. 5). Our metabolic pulse-chase studies carried out in the presence of CSF-1 exposed the newly synthesized CSF-1R to its ligand, which promoted its rapid degradation. While this was clearly seen in control BMDMs, the mature band of CSF-1R remained intact for the
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Several extragenic cot ts suppressors have been identified A
2020-11-11

Several extragenic cot-1 (ts) suppressors have been identified. Among them, cytoplasmic dynein, dynactin, and nuclear distribution mutants of N. crassa, as well as an additional gene gul-1 (NCU01197), have been shown to have genetic interactions with cot-1 (Bruno et al., 1996, Seiler et al., 2006, T
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Materials and methods br Results br Discussion Hydroxylation
2020-11-11

Materials and methods Results Discussion Hydroxylation of proline in bacterial Difopein is one of the oxygen-requiring metabolic reactions, which needs efficient oxygen. Oxygen supply is always a rate-limiting step for tyrosinase production even though pure oxygen is purged in a bioreactor (
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br Materials and methods br Results br Discussion One novel
2020-11-11

Materials and methods Results Discussion One novel finding in our study is that CK2 inhibition preserved axon function and structure in WM against ischemia. Consistent with these findings, oligodendrocytes, astrocytes, myelin, and Folinic acid australia were found to express CK2α. The robus
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