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Individual Domains (individual + domain)
Selected AbstractsComparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patientsALLERGY, Issue 1 2009C. Bachert Background:, Bilastine is a novel, nonsedating H1 -antihistamine developed for symptomatic treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria. The objective of this study was to compare the efficacy and safety of bilastine 20 mg vs placebo and desloratadine 5 mg in subjects with seasonal allergic rhinitis (SAR). Methods:, This randomized, double blind, placebo-controlled, parallel-group multicentre study evaluated the effect of 2 weeks' treatment with bilastine 20 mg, desloratadine 5 mg or matched placebo once daily, in 12,70 years old symptomatic SAR patients. All subjects assessed the severity of nasal (obstruction, rhinorrhoea, itching, and sneezing) and nonnasal (ocular itching, tearing, ocular redness, itching of ears and/or palate) symptoms on a predetermined scale to provide a total symptom score (TSS), composed of nasal and nonnasal symptom scores (NSS and NNSS, respectively). The primary efficacy measure was the area under the curve (AUC) for the TSS over the entire treatment period. Results:, Bilastine 20 mg significantly reduced the AUC of TSS to a greater degree from baseline compared to placebo (98.4 with bilastine vs 118.4 with placebo; P < 0.001), but not compared to desloratadine 5 mg (100.5). Bilastine 20 mg was not different from desloratadine 5 mg but significantly more effective than placebo in improving the NSS, NNSS, and rhinitis-associated discomfort scores (P < 0.05), and rhinoconjunctivitis quality of life questionnaire total (P < 0.005) and four out of seven individual domain (P < 0.05) scores. The incidence of treatment emergent adverse events was similar for bilastine (20.6%), desloratadine (19.8%), and placebo (18.8%). Conclusion:, Bilastine 20 mg once daily was efficacious, safe and not different from desloratadine 5 mg once daily in the treatment of SAR symptoms. [source] Primitive complement system of invertebratesIMMUNOLOGICAL REVIEWS, Issue 1 2004Masaru Nonaka Summary:, Most components of the human complement system have unmistakable domain architectures, making evolutionary tracing feasible. In contrast to the major genes of the adaptive immune system, which are present only in jawed vertebrates, complement component genes with unique domain structures are present not only in jawed vertebrates but also in jawless fish and non-vertebrate deuterostomes. Recent progress in genome analysis in several eukaryotes, occupying the phylogenetically critical positions, showed that most individual domains found in the complement components are metazoa specific, being found both in deuterostomes and in protostomes but not in yeast or plant. However, unique domain architecture of complement components is not present in protostomes, suggesting that the complement system has been established in the deuterostome lineage not by invention of new domains but by innovation of unique combination of the pre-existing domains. The recently assembled Ciona intestinalis draft genome contained the most modular complement genes, except for factor I. However, some possible C. intestinalis complement components show critical structural divergence from the mammalian counterparts, casting doubt on their mutual interaction. Thus, another integrative step seems to have been required to establish the modern complement system of higher vertebrates. [source] Different models for the polar nanodomain structure of PZN and other relaxor ferroelectricsJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3 2008T. R. Welberry Computer simulations have been carried out to test the recently proposed model for the nanodomain structure of relaxor ferroelectrics such as lead zinc niobate (PZN). In this recent model it was supposed that the polar nanodomains are three-dimensional, that the observed diffuse rods of scattering originate from the boundaries between domains and that the Pb displacements may be directed along , or . This is in marked contrast to a previously published model, which described the polar domains as thin plates with Pb displacements confined to the directions within the essentially two-dimensional domains. The present results confirm that and types of Pb displacement are viable possibilities, but the number of domain boundaries required to produce sufficiently strong diffuse rods of scattering means that individual domains cannot be described as three-dimensional and must still be relatively thin. The current work has been carried out with no direct involvement of the B -site cation ordering, which many workers assume is necessary to understand the formation of the polar nanodomains. While it may be true that the B -site cation distribution could provide an underlying perturbation field that might ultimately limit the extent of any polar domain, it is certainly not necessary to produce the observed scattering effects. [source] Cone arrestin binding to JNK3 and Mdm2: conformational preference and localization of interaction sitesJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Xiufeng Song Abstract Arrestins are multi-functional regulators of G protein-coupled receptors. Receptor-bound arrestins interact with >30 remarkably diverse proteins and redirect the signaling to G protein-independent pathways. The functions of free arrestins are poorly understood, and the interaction sites of the non-receptor arrestin partners are largely unknown. In this study, we show that cone arrestin, the least studied member of the family, binds c-Jun N-terminal kinase (JNK3) and Mdm2 and regulates their subcellular distribution. Using arrestin mutants with increased or reduced structural flexibility, we demonstrate that arrestin in all conformations binds JNK3 comparably, whereas Mdm2 preferentially binds cone arrestin ,frozen' in the basal state. To localize the interaction sites, we expressed separate N- and C-domains of cone and rod arrestins and found that individual domains bind JNK3 and remove it from the nucleus as efficiently as full-length proteins. Thus, the arrestin binding site for JNK3 includes elements in both domains with the affinity of partial sites on individual domains sufficient for JNK3 relocalization. N-domain of rod arrestin binds Mdm2, which localizes its main interaction site to this region. Comparable binding of JNK3 and Mdm2 to four arrestin subtypes allowed us to identify conserved residues likely involved in these interactions. [source] Parabolic mirror-assisted tip-enhanced spectroscopic imaging for non-transparent materialsJOURNAL OF RAMAN SPECTROSCOPY, Issue 10 2009Dr. Dai Zhang Abstract A versatile and efficient tip-enhanced spectroscopic imaging technique based on a parabolic mirror (PM) assisted near-field optical microscope is demonstrated. The replacement of the conventional objective lens with a parabolic mirror allows the non-restricted investigation of sample materials regarding their opacity. In addition, an improved signal collection efficiency and effective excitation of the longitudinal plasmonic oscillation in the tip apex are obtained. The capabilities of PM-assisted tip-enhanced Raman (TER) and photoluminescence (PL) imaging in distinguishing the individual domains made of different chemical components in poly (3-hexythiophene)/[6, 6]-penyl-C61 butyric acid methyl ester (P3HT/PCBM) solar cell blend film and in the investigation of the plasmonic properties of geometrically well-defined Au cones are demonstrated. Copyright © 2009 John Wiley & Sons, Ltd. [source] Development and validation of an electronic version of the Rhinoconjunctivitis Quality of Life QuestionnaireALLERGY, Issue 9 2007E. F. Juniper Background:, As clinicians and pharmaceutical companies move from paper versions of health status questionnaires to electronic versions, it cannot be assumed that adaptations to other media will produce valid data. Aims:, The aims of this study were to (1) adapt the Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ(S); standardized version], for the Palm Treo 650, (2) test the device for ease and accuracy of understanding and (3) examine the validity of the electronic version by comparing it with the original paper version of the RQLQ(S). Methods:, Seventy adults with current rhinoconjunctivitis symptoms completed the electronic and paper versions of the RQLQ(S). They were randomized to complete either the paper or the electronic version first. After a 2-h break, they completed the other version. Results:, Concordance between paper and electronic versions for the overall RQLQ(S) score was acceptable with an intraclass correlation coefficient of 0.95 and there was no evidence of bias (P = 0.13). Concordance for the seven individual domains ranged from 0.86 to 0.94. A small but significant bias was observed in the activity and sleep domains (P = 0.02). Completion times were quicker with paper (4.1 vs 4.9 min, P < 0.0001). About 51% of patients preferred electronic, 17% preferred paper and 31% had no preference. Conclusions:, This electronic version of the RQLQ(S) was easy for patients to use and the concordance between paper and this version on the Palm Treo 650 provides evidence of the validity of this electronic version. [source] The RNA degradosome in Bacillus subtilis: identification of CshA as the major RNA helicase in the multiprotein complexMOLECULAR MICROBIOLOGY, Issue 4 2010Martin Lehnik-Habrink Summary In most organisms, dedicated multiprotein complexes, called exosome or RNA degradosome, carry out RNA degradation and processing. In addition to varying exoribonucleases or endoribonucleases, most of these complexes contain a RNA helicase. In the Gram-positive bacterium Bacillus subtilis, a RNA degradosome has recently been described; however, no RNA helicase was identified. In this work, we tested the interaction of the four DEAD box RNA helicases encoded in the B. subtilis genome with the RNA degradosome components. One of these helicases, CshA, is able to interact with several of the degradosome proteins, i.e. RNase Y, the polynucleotide phosphorylase, and the glycolytic enzymes enolase and phosphofructokinase. The determination of in vivo protein,protein interactions revealed that CshA is indeed present in a complex with polynucleotide phosphorylase. CshA is composed of two RecA-like domains that are found in all DEAD box RNA helicases and a C-terminal domain that is present in some members of this protein family. An analysis of the contribution of the individual domains of CshA revealed that the C-terminal domain is crucial both for dimerization of CshA and for all interactions with components of the RNA degradosome, including RNase Y. A transfer of this domain to CshB allowed the resulting chimeric protein to interact with RNase Y suggesting that this domain confers interaction specificity. As a degradosome component, CshA is present in the cell in similar amounts under all conditions. Taken together, our results suggest that CshA is the functional equivalent of the RhlB helicase of the Escherichia coli RNA degradosome. [source] The structure of receptor-associated protein (RAP)PROTEIN SCIENCE, Issue 8 2007Donghan Lee Abstract The receptor-associated protein (RAP) is a molecular chaperone that binds tightly to certain newly synthesized LDL receptor family members in the endoplasmic reticulum (ER) and facilitates their delivery to the Golgi. We have adopted a divide-and-conquer strategy to solve the structures of the individual domains of RAP using NMR spectroscopy. We present here the newly determined structure of domain 2. Based on this structure and the structures of domains 1 and 3, which were solved previously, we utilized experimental small-angle neutron scattering (SANS) data and a novel simulated annealing protocol to characterize the overall structure of RAP. The results reveal that RAP adopts a unique structural architecture consisting of three independent three-helix bundles that are connected by long and flexible linkers. The flexible linkers and the quasi-repetitive structural architecture may allow RAP to adopt various possible conformations when interacting with the LDL receptors, which are also made of repetitive substructure units. [source] Prediction of structures of multidomain proteins from structures of the individual domainsPROTEIN SCIENCE, Issue 2 2007Andrew M. Wollacott Abstract We describe the development of a method for assembling structures of multidomain proteins from structures of isolated domains. The method consists of an initial low-resolution search in which the conformational space of the domain linker is explored using the Rosetta de novo structure prediction method, followed by a high-resolution search in which all atoms are treated explicitly and backbone and side chain degrees of freedom are simultaneously optimized. The method recapitulates, often with very high accuracy, the structures of existing multidomain proteins. [source] Slicing a protease: Structural features of the ATP-dependent Lon proteases gleaned from investigations of isolated domainsPROTEIN SCIENCE, Issue 8 2006Tatyana V. Rotanova Abstract ATP-dependent Lon proteases are multi-domain enzymes found in all living organisms. All Lon proteases contain an ATPase domain belonging to the AAA+ superfamily of molecular machines and a proteolytic domain with a serine-lysine catalytic dyad. Lon proteases can be divided into two subfamilies, LonA and LonB, exemplified by the Escherichia coli and Archaeoglobus fulgidus paralogs, respectively. The LonA subfamily is defined by the presence of a large N-terminal domain, whereas the LonB subfamily has no such domain, but has a membrane-spanning domain that anchors the protein to the cytoplasmic side of the membrane. The two subfamilies also differ in their consensus sequences. Recent crystal structures for several individual domains and sub-fragments of Lon proteases have begun to illuminate similarities and differences in structure,function relationships between the two subfamilies. Differences in orientation of the active site residues in several isolated Lon protease domains point to possible roles for the AAA+ domains and/or substrates in positioning the catalytic residues within the active site. Structures of the proteolytic domains have also indicated a possible hexameric arrangement of subunits in the native state of bacterial Lon proteases. The structure of a large segment of the N-terminal domain has revealed a folding motif present in other protein families of unknown function and should lead to new insights regarding ways in which Lon interacts with substrates or other cellular factors. These first glimpses of the structure of Lon are heralding an exciting new era of research on this ancient family of proteases. [source] Improvement in health-related quality of life with fluticasone propionate compared with budesonide or beclomethasone dipropionate in adults with severe asthmaRESPIROLOGY, Issue 3 2003Carolyn RUTHERFORD Objective: Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD. Methodology: HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000,2000 µg/day (n = 67) compared with remaining on BDP/BUD ,1750 µg/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of ,0.5 was considered to be clinically meaningful. Results: There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful. Conclusion: Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL. [source] Impact of Adenotonsillectomy on Behavior in Children With Sleep-Disordered Breathing,THE LARYNGOSCOPE, Issue 7 2006Hsueh-Yu Li MD Abstract Objectives/Hypothesis: Children with sleep-disordered breathing may experience behavioral and learning problems such as inattentiveness and hyperactivity. The aim of this study was to measure the impact of adenotonsillectomy on sleep-related adverse events and behavioral problems in children with sleep-disordered breathing. Method: This prospective and interventional study enrolled 40 sleep-disordered breathing children (mean age, 8.4 ± 1.6 years) with hypertrophic tonsils and adenoids. All patients completed two polysomnographies, tests of variables of attention (TOVAs), and Child Behavior Checklists, one at baseline and the other 6 months after adenotonsillectomy. Results: The apnea,hypopnea index (P < .001), TOVA scores (P < .001), and 8 of 9 individual domains of the Child Behavior Checklist scores (P < .05) significantly improved after surgery. However, the change in the apnea,hypopnea index was not negatively correlated with TOVA score (r = ,0.17, P = .38). Conclusion: Adenotonsillectomy could significantly improve behavior (TOVA) scores, but the improvement may not simply be attributable to changes in sleep apnea events. [source] Ultralow-resolution ab initio phasing of filamentous proteins: crystals from a six-Ig fragment of titin as a case studyACTA CRYSTALLOGRAPHICA SECTION D, Issue 5 2008Alexandre Urzhumtsev Low-resolution diffraction data (resolution below 12,Å) from crystals of a filamentous six-Ig fragment of titin, I65,I70, were used in ab initio phasing with the aim of calculating its lattice packing and molecular envelope. Filamentous molecules, characterized by marked anisometry and idiosyncratic crystal lattices, have not been addressed before using this methodology. In this study, low-resolution phasing (19,122,Å) successfully identified the region of the unit cell occupied by the molecule. Phase extension to a higher resolution (12,Å) yielded regions of high density that corresponded either to the positions of individual Ig domains or to zones of dense intermolecular contacts, hindering the identification of individual domains and the interpretation of electron-density maps in terms of a molecular model. This problem resulted from the acutely uneven packing of the molecules in the crystal and it was further accentuated by the presence of partially disordered regions in the molecule. Addition of low-resolution reflections with phases computed ab initio to those obtained experimentally using MIRAS improved the initial electron-density maps of the atomic model, demonstrating the generic utility of low-resolution phases for the structure-elucidation process, even when individual molecules cannot be resolved in the lattice. [source] Biosynthesis of the Myxobacterial Antibiotic Corallopyronin ACHEMBIOCHEM, Issue 9 2010Özlem Erol Abstract Corallopyronin A is a myxobacterial compound with potent antibacterial activity. Feeding experiments with labelled precursors resulted in the deduction of all biosynthetic building blocks for corallopyronin A and revealed an unusual feature of this metabolite: its biosynthesis from two chains, one solely PKS-derived and the other NRPS/PKS-derived. The starter molecule is believed to be carbonic acid or its monomethyl ester. The putative corallopyronin A biosynthetic gene cluster is a trans-AT-type mixed PKS/NRPS gene cluster, containing a ,-branching cassette. Striking features of this gene cluster are a NRPS-like adenylation domain that is part of a PKS-type module and is believed to be responsible for glycine incorporation, as well as split modules with individual domains occurring on different genes. It is suggested that CorB is a trans-acting ketosynthase and it is proposed that it catalyses the Claisen condensation responsible for the interconnection of the two chains. Additionally, the stereochemistry of corallopyronin A was deduced by a combination of a modified Mosher's method and ozonolysis with subsequent chiral GC analyses. [source] | ||||||||||||||||