(C) 2014 Elsevier Inc. All rights reserved.”
“Solution NMR studies of alpha-helical membrane proteins

are often complicated by severe spectral crowding. In addition, hydrophobic environments like detergent micelles, isotropic bicelles or nanodiscs lead to considerably reduced molecular tumbling rates which translates into line-broadening and low sensitivity. Both difficulties can be addressed by selective isotope labeling methods. In this publication, we propose a combinatorial protocol that utilizes four different classes of labeled amino acids, in which the three backbone heteronuclei (amide nitrogen, alpha-carbon and carbonyl carbon) are enriched in N-15 or C-13 isotopes individually as well as simultaneously. This results in eight different combinations of dipeptides giving rise to cross peaks in H-1-N-15 correlated spectra. Their differentiation is achieved by recording a series of HN-detected 2D triplere-sonance spectra. PD173074 clinical trial Prexasertib mw The utility of this new scheme is demonstrated with a homodimeric 142-residue membrane protein in DHPC micelles. Restricting the number of selectively labeled samples to three allowed the identification of the amino-acid type for 77 % and provided sequential information for 47 % of its residues. This enabled us to complete the backbone resonance assignment of the uniformly labeled protein merely with the help of a 3D HNCA spectrum, which

can be collected with reasonable sensitivity even for relatively large, non-deuterated proteins.”
“Chronic idiopathic urticaria (CIU) impairs quality of life (QoL). Currently, no consensus exists regarding how second-generation H(1)-antihistamines TNF-alpha inhibitor (proven to control CIU symptoms) should be taken long-term: as daily treatment or only when symptoms return (PRN). We sought to determine which regimen improves or better maintains QoL in CIU: desloratadine (DL) daily or PRN.\n\nSubjects with CIU initially responding to DL 5 mg/day for 4 weeks were randomized for an additional 8 weeks, to DL 5 mg/day (arm 1: ‘continuous’, n = 46) or to DL only on days when urticarial

wheals were present (arm 2: “PRN”, n = 60). To ensure blinding, treatment was presented in both arms as a combination of daily treatment (arm 1: DL; arm 2: placebo), plus a “rescue” tablet (arm 1: placebo; arm 2: DL) to be taken only in case of symptoms. The main outcome measure was QoL assessed by the VQ-Dermato, a validated French QoL instrument, and the Dermatology Life Quality Index (DLQI).\n\nAt 4 and 8 weeks after randomization, subjects taking continuous DL showed statistically significant improvements in VQ-Dermato Global Index score (P = 0.001 and P = 0.016, respectively) and dimension scores for daily living activity, mood state, and social functioning vs subjects taking DL PRN. Improvement in DLQI score at Week 4 was also significantly greater with continuous DL (P = 0.001).