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The synthetic route chosen for
2019-12-10

The synthetic route chosen for the preparation of the substrates 18 is shown in Scheme 3. Commercially available 4-aminobenzyl alcohol 13 was found to be relatively unstable to storage and hence it was prepared immediately before use by reduction of the readily available and inexpensive 4-nitrobenzy
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Even more unambiguous was the relative contribution of Gq si
2019-12-10

Even more unambiguous was the relative contribution of Gq/11 signaling in AngII-mediated transactivation as measured by the ERK1/2 and the BRET-based readout. Although Gq/11 was absolutely required for ERK1/2 phosphorylation following AngII-stimulation, in contrast, we observed a sustained EGFR-Grb2
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br Results br Discussion The process by
2019-12-10

Results Discussion The process by which MBCs differentiate from GC B cell precursors remains mostly uncharacterized, in large part because of the uncertainty surrounding the nature of the precursor wnt signaling within the GC. The identification here of a distinct subset of GC B cells, CCR6+
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CXCR is not only critical in the
2019-12-10

CXCR5 is not only critical in the B cell lineage in FL. A high proportion of CXCR5-expressing follicular helper T cells (TFH) were observed in FL but not in closely related DLBCL [141] and further investigation revealed that FL regulatory T cells (Tregs) used a CXCL13-CXCR5 autocrine loop for positi
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EBI remains an orphan GPCR and the identity and
2019-12-10

EBI2 remains an orphan GPCR and the identity and source of its ligand are yet to be described. Molecular studies of EBI2 have suggested that this receptor has constitutive activity, similar to that observed for many herpesvirus-encoded 7TM receptors (Benned-Jensen and Rosenkilde, 2008, Rosenkilde et
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The potential off target activity
2019-12-10

The potential off-target activity of against other ATP-dependent enzymes, such as kinases, was also investigated. Encouragingly, there was no significant inhibition of ATP binding to 97 human kinases, when was evaluated at 10μM within a DiscoveRx scanEDGE® kinome screen (, ). All together, these d
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Except for S adenosylmethionine SAM Fig sources
2019-12-10

Except for S-adenosylmethionine (SAM, Fig. 1), sources of endogenous DNA alkylation are not well defined. Other possible sources include nitroso compounds related to the well known mutagen methylnitrosourea which are generated in vitro by nitrosation of cellular amines including amino acids, protei
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Our observation that FAK is downregulated in vascular smooth
2019-12-10

Our observation that FAK is downregulated in vascular smooth muscle Angiotensin 1/2 (1-5) on fibrillar collagen confirms observations reported for other cell types [14]. However, unlike the results reported previously [14], our work suggests that matrix rigidity per se does not determine FAK downre
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CYP A is involved in the metabolism of approximately
2019-12-10

CYP3A is involved in the metabolism of approximately 50% of all drugs that are currently prescribed to patients [1], [15], [16]. Marked interindividual variabilitity of the catalytic function for metabolizing CYP3A substrates has been demonstrated with variability exceeding 20-fold [1]. Levonorgestr
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Mitophagy is a selective autophagic process which
2019-12-10

Mitophagy is a selective autophagic process which leads to the degradation of damaged mitochondria in response to metabolic or environmental stress conditions. In this study, we found that LFS-01 treatment significantly enhances p62 in a time-dependent manner. We found that the upregulation of p62 i
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Among the various neurotransmitter systems pointed
2019-12-10

Among the various neurotransmitter systems pointed out to play a role in the mediation of defensive and antinociceptive responses elicited by environmentally aversive stimuli, the neuropeptide corticotropin-releasing factor or hormone (CRF or CRH) has attracted the interest of many researchers inves
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br Results br Discussion Cell responds
2019-12-10

Results Discussion Cell responds to fluctuating environmental factors by activating a set of compensatory mechanisms including changes in the lipid profile. Compensatory reactions occurring in membranes in response to phosphate deprivation include replacement of phospholipids by phosphorus-fre
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Interestingly selective ETA blockade increased cutaneous
2019-12-10

Interestingly, selective ETA blockade increased cutaneous blood flow as measured by laser Doppler fluxmetry. This is a measure of total blood flow in the different vessels in the skin including venules, ro bio 2 as well as arterioles. This finding is in accordance with the previous demonstration tha
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br Structure and function of EPAC isoforms
2019-12-10

Structure and function of EPAC isoforms EPACs are guanine nucleotide exchange factors (GEFs) for the Ras-like GTPases Rap1 and Rap2 [9]. There are two mammalian EPAC isoforms, EPAC1 and EPAC2 1, 2 (Figure 1). Whereas EPAC1 displays a wide tissue distribution, the expression of EPAC2 is more restr
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Although the mechanisms underlying the EP mediated increase
2019-12-10

Although the mechanisms underlying the EP4-mediated increase in the frequency of mEPSCs via PGE2 remain unclear, mechanisms similar to those driven by EP2 may be involved because activation of both these receptor subtypes increases the intracellular concentration of cAMP (Nishigaki et al., 1995, Sug
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