The Functional Microdomain in Transmembrane Helices 2 and 7 Regulates Expression, Activation, and Coupling Pathways of the Gonadotropin-releasing Hormone Receptor

Structural microdomains of G protein-coupled receptors (GPCRs) consist of spatially related side chains that mediate discrete functions. The conserved helix 2/helix 7 microdomain was identified because the gonadotropin-releasing hormone (GnRH) receptor appears to have interchanged the Asp(2.50) and Asn(7.49) residues which are conserved in transmembrane helices 2 and 7 of rhodopsin-like GPCRs. We now demonstrate that different side chains of this microdomain contribute specifically to receptor expression, heterotrimeric G protein-, and small G protein-mediated signaling. An Asn residue is required in position 2.50(87) for expression of the GnRH receptor at the cell surface, most likely through an interaction with the conserved Asn(1.50(53)) residue, which we also find is required for receptor expression. Most GPCRs require an Asp side chain at either the helix 2 or helix 7 locus of the microdomain for coupling to heterotrimeric G proteins, but the GnRH receptor has transferred the requirement for an acidic residue from helix 2 to 7. However, the presence of Asp at the helix 7 locus precludes small G protein-dependent coupling to phospholipase D. These results implicate specific components of the helix 2/helix 7 microdomain in receptor expression and in determining the ability of the receptor to adopt distinct activated conformations that are optimal for interaction with heterotrimeric and small G proteins

The gas-phase structure of the decasilsesquioxane Si₁₀O₁₅H₁₀

International audienc

Molecular structure of 1,2-bis(trifluoromethyl)-1,1,2,2-tetramethyldisilane in the gas, liquid, and solid phases : Unusual conformational changes between phases

The molecular structure of 1,2-bis(trifluoromethyl)-1,1,2,2-tetramethyldisilane has been determined in three different phases (solid, liquid, and gas) using various spectroscopic and diffraction techniques. Both the solid-state and gas-phase investigations revealed only one conformer to be present in the sample analyzed, whereas the liquid phase revealed the presence of three conformers. The data have been reproduced using computational methods and a rationale is presented for the observation of three conformers in the liquid state

A conformational and vibrational study of CF₃COSCH₂CH₃

The molecular structure and conformational properties of S -ethyl trifluorothioacetate, CF3 COSCH2 CH3, were determined in the gas phase by electron diffraction and vibrational spectroscopy (IR and Raman). The experimental investigations were supplemented by ab initio (Møller Plesset of second order) and density functional theory quantum chemical calculations at different levels of theory. Both experimental and theoretical methods reveal two structures with Cs (anti, anti) and C1 (anti, gauche) symmetries, although there are disagreements about which is more stable. The electron diffraction intensities are best interpreted with a mixture of 51(3)% anti, anti and 49(3)% anti, gauche conformers. This conformational preference was studied using the total energy scheme and the natural bond orbital scheme. In addition, the infrared spectra of CF3 COSCH2 CH3 are reported for the gas, liquid and solid phases as well as the Raman spectrum of the liquid. Using calculated frequencies as a guide, evidence for both Cs and C1 structures is obtained in the IR spectra. Harmonic vibrational frequencies and scaled force fields have been calculated for both conformers.Fil: Defonsi Lestard, Maria Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Física; ArgentinaFil: Tuttolomondo, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Física; ArgentinaFil: Wann, Derek A.. University of Edinburgh; Reino UnidoFil: Robertson, Heather E.. University of Edinburgh; Reino UnidoFil: Rankin, David W. H.. University of Edinburgh; Reino UnidoFil: Ben Altabef, Aída. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Física; Argentin

DBD––taxonomically broad transcription factor predictions: new content and functionality

DNA-binding domain (DBD) is a database of predicted sequence-specific DNA-binding transcription factors (TFs) for all publicly available proteomes. The proteomes have increased from 150 in the initial version of DBD to over 700 in the current version. All predicted TFs must contain a significant match to a hidden Markov model representing a sequence-specific DNA-binding domain family. Access to TF predictions is provided through http://transcriptionfactor.org, where new search options are now provided such as searching by gene names in model organisms, searching for all proteins in a particular DBD family and specific organism. We illustrate the application of this type of search facility by contrasting trends of DBD family occurrence throughout the tree of life, highlighting the clear partition between eukaryotic and prokaryotic DBD expansions. The website content has been expanded to include dedicated pages for each TF containing domain assignment details, gene names, links to external databases and links to TFs with similar domain arrangements. We compare the increase in number of predicted TFs with proteome size in eukaryotes and prokaryotes. Eukaryotes follow a slower rate of increase in TFs than prokaryotes, which could be due to the presence of splice variants or an increase in combinatorial control

Dye-sensitized solar cells: Investigation of D-A-π-A organic sensitizers based on [1,2,5]selenadiazolo[3,4-c]pyridine

The authors gratefully acknowledge financial support from the Russian Science Foundation (grant no. 15-13-10022). Wenjun Wu thanks the Scientific Committee of Shanghai (14ZR1409700) for financial support. The authors thank the Leverhulme Trust for an International Network grant.We report two series of D-A-π-A metal-free organic sensitizers for dye-sensitized solar cells (DSSCs) based on triphenylamine and N-hexyl-carbazole as electronic donors, respectively. Through varying auxiliary acceptors and π-spacers, several significant consequences on cell efficiency were identified: (i) a broadened UV-Vis absorption spectrum and low-lying LUMO level with [1,2,5]selenadiazolo [3,4-c] pyridine as auxiliary acceptor; (ii) compensation for the absorption valley around 400 nm in the UV-vis spectra by the introduction of a thiophene unit into the π-bridge; (iii) effective improvement of the power conversion efficiency (PCE) by means of cosensitization, leading to dye OKT-1 , 3.10% PCE, increased to 4.19% with squaraine dye SQ2 as co-sensitizer. The design criteria identified have opened the door for further optimization of this new dye family.PostprintPeer reviewe

The Registry and Follow-Up of Complex Pediatric Therapies Program of Western Canada: A Mechanism for Service, Audit, and Research after Life-Saving Therapies for Young Children

Newly emerging health technologies are being developed to care for children with complex cardiac defects. Neurodevelopmental and childhood school-related outcomes are of great interest to parents of children receiving this care, care providers, and healthcare administrators. Since the 1970s, neonatal follow-up clinics have provided service, audit, and research for preterm infants as care for these at-risk children evolved. We have chosen to present for this issue the mechanism for longitudinal follow-up of survivors that we have developed for western Canada patterned after neonatal follow-up. Our program provides registration for young children receiving complex cardiac surgery, heart transplantation, ventricular assist device support, and extracorporeal life support among others. The program includes multidisciplinary assessments with appropriate neurodevelopmental intervention, active quality improvement evaluations, and outcomes research. Through this mechanism, consistently high (96%) follow-up over two years is maintained

The impact of dietary supplementation with astaxanthin on egg quality in Atlantic cod broodstock (Gadus morhua, L.)

This study investigated the effect on egg quality of dietary supplementation of Atlantic cod broodstock with the carotenoid astaxanthin (ASTA). Duplicate groups of farm-reared Atlantic cod broodstock were fed either a control diet with no added ASTA, or an ASTA supplemented diet (73.7 mg/kg dry weight; Carophyll Pink®) for 2 months prior to peak spawning. The results indicated that ASTA uptake into eggs from the broodstock diet was highly efficient. Fish fed the diet supplemented with ASTA produced fewer batches of eggs, but the mean number per batch of eggs spawned/kg female was higher, and numbers of floating eggs and numbers of fertilised eggs per kg female in each batch were also significantly improved. A correlation between the egg ASTA content and fertilisation success of individual batches was identified. This improvement in egg quality demonstrated the potential value of ASTA supplementation of broodstock diets for cod. ASTA supplementation produced a 20% increase in the number of eggs per batch spawned, a 37% increase in the number per batch of floating eggs per kg female and a 47% increase in the number per batch of fertilised eggs per kg female. These results clearly demonstrate significant benefits of ASTA supplementation of cod broodstock feeds in terms of improved egg quality and larval production