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41.
Kleinau G Brehm M Wiedemann U Labudde D Leser U Krause G 《Molecular endocrinology (Baltimore, Md.)》2007,21(2):574-580
Comparison between wild-type and mutated glycoprotein hormone receptors (GPHRs), TSH receptor, FSH receptor, and LH-chorionic gonadotropin receptor is established to identify determinants involved in molecular activation mechanism. The basic aims of the current work are 1) the discrimination of receptor phenotypes according to the differences between activity states they represent, 2) the assignment of classified phenotypes to three-dimensional structural positions to reveal 3) functional-structural hot spots and 4) interrelations between determinants that are responsible for corresponding activity states. Because it is hard to survey the vast amount of pathogenic and site-directed mutations at GPHRs and to improve an almost isolated consideration of individual point mutations, we present a system for systematic and diversified sequence-structure-function analysis (http://www.fmp-berlin.de/ssfa). To combine all mutagenesis data into one set, we converted the functional data into unified scaled values. This at least enables their comparison in a rough classification manner. In this study we describe the compiled data set and a wide spectrum of functions for user-driven searches and classification of receptor functionalities such as cell surface expression, maximum of hormone binding capability, and basal as well as hormone-induced Galphas/Galphaq mediated cAMP/inositol phosphate accumulation. Complementary to known databases, our data set and bioinformatics tools allow functional and biochemical specificities to be linked with spatial features to reveal concealed structure-function relationships by a semiquantitative analysis. A comprehensive discrimination of specificities of pathogenic mutations and in vitro mutant phenotypes and their relation to signaling mechanisms of GPHRs demonstrates the utility of sequence-structure-function analysis. Moreover, new interrelations of determinants important for selective G protein-mediated activation of GPHRs are resumed. 相似文献
42.
Alexandra Rosa Carolina Ornelas Mark A Jobling António Brehm Richard Villems 《BMC evolutionary biology》2007,7(1):124
Background
The geographic and ethnolinguistic differentiation of many African Y-chromosomal lineages provides an opportunity to evaluate human migration episodes and admixture processes, in a pan-continental context. The analysis of the paternal genetic structure of Equatorial West Africans carried out to date leaves their origins and relationships unclear, and raises questions about the existence of major demographic phenomena analogous to the large-scale Bantu expansions. To address this, we have analysed the variation of 31 binary and 11 microsatellite markers on the non-recombining portion of the Y chromosome in Guinea-Bissau samples of diverse ethnic affiliations, some not studied before. 相似文献43.
Gunnar Brehm 《ZooKeys》2015,(537):131-156
Three new Hagnagora Druce species (Geometridae, Larentiinae) are described: Hagnagora
richardi Brehm, sp. n. from Ecuador, Hagnagora
hedwigae Brehm, sp. n. from Ecuador, and Hagnagora
mirandahenrichae Brehm, sp. n. from Costa Rica. A checklist of taxa assigned to Hagnagora is provided. Hagnagora is provisionally divided into six clades: the anicata clade (6 species), the buckleyi clade (3 species), the croceitincta clade (3 species), the ephestris clade (3 species), the mortipax clade (4 species) and Hagnagora
subrosea (1 species). Two taxa are revived from synonymy: Hagnagora
catagrammina Druce, stat. rev. and Hagnagora
luteoradiata Thierry-Mieg, stat. rev. Two taxa are reinstated from subspecies to species level: Hagnagora
acothysta Schaus, stat. rev. and Hagnagora
jamaicensis Schaus, stat. rev. Four taxa are provisionally removed from Hagnagora: “Hagnagora” ignipennis, “Hagnagora” mesenata, “Hagnagora” vittata, and “Hagnagora” ceraria. After these changes, the genus Hagnagora now comprises 20 valid species. 相似文献
44.
TRP channels have emerged as key biological sensors in vision, taste, olfaction, hearing, and touch. Despite their importance, virtually nothing is known about the folding and transport of TRP channels during biosynthesis. Here, we identify XPORT (exit protein of rhodopsin and TRP) as a critical chaperone for TRP and its G protein-coupled receptor (GPCR), rhodopsin (Rh1). XPORT is a resident ER and secretory pathway protein that interacts with TRP and Rh1, as well as with Hsp27 and Hsp90. XPORT promotes the targeting of TRP to the membrane in Drosophila S2 cells, a finding that provides a critical first step toward solving a longstanding problem in?the successful heterologous expression of TRP. Mutations in xport result in defective transport of TRP and Rh1, leading to retinal degeneration. Our results identify XPORT as a molecular chaperone and provide a mechanistic link between TRP channels and their GPCRs during biosynthesis and transport. 相似文献
45.
Ali C Akyildiz Lambert Speelman Harald van Brummelen Miguel A Gutiérrez Renu Virmani Aad van der Lugt Anton FW van der Steen Jolanda J Wentzel Frank JH Gijsen 《Biomedical engineering online》2011,10(1):25
Background
Rupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress. 相似文献46.
Biomanipulation measures in lakes, taken to diminish algal blooms, have mainly been restricted to the reduction of zooplanktivorous
fish with the aim to stimulate the grazing pressure by native filter feeders such as Daphnia. However, larger filter feeders like the exotic zebra mussel, Dreissena polymorpha, have been suggested as an optional tool because of their high filtering capacity. We compared grazing by two filter feeders,
D. polymorpha and Daphnia galeata, offered seston from Lake IJsselmeer, the Netherlands in two consecutive years: 2002 and 2003. The seston in both years was
dominated by the colony-forming cyanobacterium Microcystis aeruginosa. The grazing studies were performed under controlled conditions in the laboratory and samples were analyzed on a flow cytometer,
making it possible to quantify grazing on different seston components and size fractions, including cyanobacteria, other phytoplankton
(green algae, diatoms, etc.), and detritus. No differences in clearance rates, on a per weight basis, were found between the
two grazer species. The clearance rate on cyanobacteria (especially <20 μm) was lower in 2003 than in 2002. In 2003, the microcystin
concentration of cyanobacteria was higher than in 2002, suggesting that the observed lower clearance rate in 2003 was due
to the enhanced toxin content of the cyanobacteria. Zebra mussels, although indiscriminately filtering all seston groups out
of the water, positively selected for phytoplankton in their mantle cavity, irrespective of its toxicity, and rejected detritus.
Since no differences in clearance rates were found between the two grazer species, we conclude that for biomanipulation purposes
of shallow lakes, native species like the daphnids should be preferred over exotic species like zebra mussels. When the seston
is dominated by phytoplankton that cannot be filtered out of the water column by Daphnia, however, the use of zebra mussels may be considered. Care should be taken, however, in the choice of the lakes since the
mussels may have severe ecological and economic impacts. 相似文献
47.
Nielsen BB Pickering DS Greenwood JR Brehm L Gajhede M Schousboe A Kastrup JS 《The FEBS journal》2005,272(7):1639-1648
The X-ray structure of the ionotropic GluR2 ligand-binding core (GluR2-S1S2J) in complex with the bicyclical AMPA analogue (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]-4-isoxazolyl)propionic acid [(S)-4-AHCP] has been determined, as well as the binding pharmacology of this construct and of the full-length GluR2 receptor. (S)-4-AHCP binds with a glutamate-like binding mode and the ligand adopts two different conformations. The K(i) of (S)-4-AHCP at GluR2-S1S2J was determined to be 185 +/- 29 nM and at full-length GluR2(R)o it was 175 +/- 8 nM. (S)-4-AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17 degrees). Also, functionally (S)-4-AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)-glutamate. The proximity of bound (S)-4-AHCP to domain D2 prevents full D1-D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand. 相似文献
48.
David?E?Comings Thomas?JH?Chen Kenneth?BlumEmail author Julie?F?Mengucci Seth?H?Blum Brian?Meshkin 《Theoretical biology & medical modelling》2005,2(1):50
Background
Attention Deficit Hyperactivity Disorder, commonly referred to as ADHD, is a common, complex, predominately genetic but highly treatable disorder, which in its more severe form has such a profound effect on brain function that every aspect of the life of an affected individual may be permanently compromised. Despite the broad base of scientific investigation over the past 50 years supporting this statement, there are still many misconceptions about ADHD. These include believing the disorder does not exist, that all children have symptoms of ADHD, that if it does exist it is grossly over-diagnosed and over-treated, and that the treatment is dangerous and leads to a propensity to drug addiction. Since most misconceptions contain elements of truth, where does the reality lie?Results
We have reviewed the literature to evaluate some of the claims and counter-claims. The evidence suggests that ADHD is primarily a polygenic disorder involving at least 50 genes, including those encoding enzymes of neurotransmitter metabolism, neurotransmitter transporters and receptors. Because of its polygenic nature, ADHD is often accompanied by other behavioral abnormalities. It is present in adults as well as children, but in itself it does not necessarily impair function in adult life; associated disorders, however, may do so. A range of treatment options is reviewed and the mechanisms responsible for the efficacy of standard drug treatments are considered.Conclusion
The genes so far implicated in ADHD account for only part of the total picture. Identification of the remaining genes and characterization of their interactions is likely to establish ADHD firmly as a biological disorder and to lead to better methods of diagnosis and treatment.49.
50.