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In order to evaluate the in vivo pharmacology associated
2019-12-17

In order to evaluate the in vivo pharmacology associated with EP receptor antagonism, we wished to discover antagonists presenting a higher degree of selectivity over the other prostanoid receptors. We also wanted to increase the brain–blood ratio since it is probable that centrally mediated EP agon
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What are the molecular signals that guide Tfh
2019-12-17

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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The strand domain swap in the UbV XR dimer
2019-12-17

The β strand domain swap in the UbV.XR dimer appears to be a unique arrangement for a Ub-based dimer. In solution, free Ub has a KD of ∼5 mM for the monomer-dimer equilibrium, and the two subunits in the dimer adopt a range of relative orientations involving residues from Ub’s β sheet (Liu et al., 2
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INCB28060 synthesis Since the interaction between the
2019-12-17

Since the interaction between the E2 and E3 is weak and transient, it has been difficult to identify novel interactions between specific E2/E3 complexes [59], [64]. Here we used a modified bait consisting of the Mulan RING domain fused to one of the four E2s isolated in our screen and expressed in y
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emca The kinase activity of DNA PKcs is essential
2019-12-17

The kinase activity of DNA-PKcs is essential for NHEJ, but the exact role of the enzymatic activity of DNA-PKcs plays in NHEJ is not fully understood [57]. In vitro, DNA-PKcs can phosphorylate each of the canonical NHEJ factors including Ku70/80 [58], [59], XRCC4 [60], [61], emca IV [62], and XLF [6
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In this report we present
2019-12-17

In this report, we present spectroscopic evidence on the effect of different solvents having proton acceptor and proton donor ability and pH of the medium on the abstraction of amino proton of PI (Scheme 1) for controlling the nonradiative rates. Despite the general utility of PI as a DNA intercalat
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Upon assembly of HLA tetramers loaded with either
2019-12-16

Upon assembly of HLA tetramers loaded with either of the two peptide versions, we could query the T cell repertoires of RA subjects and healthy individuals for the presence of cognate T luciferin definition recognizing the respective peptide-HLA complexes. We found no significant difference in frequ
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br Experimental Procedures br Author Contributions
2019-12-16

Experimental Procedures Author Contributions Acknowledgments Introduction In addition to the HLA region numerous other loci have shown association with type 1 diabetes risk [1], and susceptibility Tanshinone IIA---sulfonic sodium have been identified in many of these regions [2]. How th
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Recently a non proteolytic role of COP
2019-12-16

Recently, a non-proteolytic role of COP1 in stabilizing PIF3 proteins in the dark has been revealed . Previous studies have shown that the endogenous levels of PIF3 protein in etiolated seedlings were nearly undetectable . Ling found that the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) p
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Our study provides proof of principle for dimerizing two dif
2019-12-16

Our study provides proof of principle for dimerizing two different E3 ligases as a novel approach to inducing one ligase to degrade the other one. The outcome of ‘ligase versus ligase’ PROTAC-mediated activity might be unpredictable a priori, but could reveal a new mechanism for proximity-mediated h
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One of the most fundamental distinctions between Ub
2019-12-16

One of the most fundamental distinctions between Ub signals is substrate monoubiquitination versus polyubiquitination. With the exception of the E2, UBE2W, which represents a special case because it FTY720 Phosphate only ubiquitinates the flexible N-termini of substrates [5], [6], [20], most exampl
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br Funding This work was supported by
2019-12-16

Funding This work was supported by the grants from MSD, Terumo Life Science Foundation, Takeda Science Foundation, and Japan Diabetes Foundation. Disclosures Acknowledgments The authors thank C. Morimoto (Juntendo University, Tokyo, Japan) and K. Takeda (Immunology Frontier Research Center
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The ability of minor groove binding agents to inhibit
2019-12-16

The ability of minor groove binding agents to inhibit the activity of DNA helicases is not without precedence. Similar effective inhibition of the unwinding of DNA by the BLM and Werner\'s DNA helicases by the minor groove binder distamycin A has been observed. Further, and similar to RecBCD, interc
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For the first time the V carinata transcriptome was
2019-12-16

For the first time, the V. carinata transcriptome was analyzed and its transcript coding sequences comprehensively characterized. The non-redundant contigs encoding putative CysPs were identified and their Epigenetics Compound Library mg patterns in different tissues were investigated. Our study sh
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Many processes can lead to changes in soil
2019-12-16

Many processes can lead to changes in soil P pools over time. Plant-available P (when measured as DGT P) decreased over time for the INORG-P treatment (Fig. 1a). Orthophosphate can be stabilised with cations such as calcium to produce insoluble phosphates, reducing plant-available P (Bünemann et al.
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