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981.
Phylogenomic analyses support the monophyly of Taphrinomycotina, including Schizosaccharomyces fission yeasts 总被引:1,自引:0,他引:1
Liu Y Leigh JW Brinkmann H Cushion MT Rodriguez-Ezpeleta N Philippe H Lang BF 《Molecular biology and evolution》2009,26(1):27-34
Several morphologically dissimilar ascomycete fungi includingSchizosaccharomyces, Taphrina, Saitoella, Pneumocystis, andNeolecta have been grouped into the taxon Taphrinomycotina (Archiascomycotaor Archiascomycotina), originally based on rRNA phylogeny. Theseanalyses lack statistically significant support for the monophylyof this grouping, and although confirmed by more recent multigeneanalyses, this topology is contradicted by mitochondrial phylogenies.To resolve this inconsistency, we have assembled phylogenomicmitochondrial and nuclear data sets from four distantly relatedtaphrinomycotina taxa: Schizosaccharomyces pombe, Pneumocystiscarinii, Saitoella complicata, and Taphrina deformans. Our phylogenomicanalyses based on nuclear data (113 proteins) conclusively supportthe monophyly of Taphrinomycotina, diverging as a sister groupto Saccharomycotina + Pezizomycotina. However, despite the improvedtaxon sampling, Taphrinomycotina continue to be paraphyleticwith the mitochondrial data set (13 proteins): Schizosaccharomycesspecies associate with budding yeasts (Saccharomycotina) andthe other Taphrinomycotina group as a sister group to Saccharomycotina+ Pezizomycotina. Yet, as Schizosaccharomyces and Saccharomycotinaspecies are fast evolving, the mitochondrial phylogeny may beinfluenced by a long-branch attraction (LBA) artifact. Afterremoval of fast-evolving sequence positions from the mitochondrialdata set, we recover the monophyly of Taphrinomycotina. Ourcombined results suggest that Taphrinomycotina is a legitimatetaxon, that this group of species diverges as a sister groupto Saccharomycotina + Pezizomycotina, and that phylogeneticpositioning of yeasts and fission yeasts with mitochondrialdata is plagued by a strong LBA artifact. 相似文献
982.
Analysis of structure and function of the giant protein Pf332 in Plasmodium falciparum 总被引:1,自引:0,他引:1
Anthony N. Hodder Alexander G. Maier Melanie Rug Monica Brown Mirja Hommel Ivan Pantic Marina Puig-de-Morales-Marinkovic Brian Smith Tony Triglia James Beeson Alan F. Cowman 《Molecular microbiology》2009,71(1):48-65
Virulence of Plasmodium falciparum , the most lethal parasitic disease in humans, results in part from adhesiveness and increased rigidity of infected erythrocytes. Pf332 is trafficked to the parasite-infected erythrocyte via Maurer's clefts, structures for protein sorting and export in the host erythrocyte. This protein has a domain similar to the Duffy-binding-like (DBL) domain, which functions by binding to receptors for adherence and invasion. To address structure of the Pf332 DBL domain, we expressed this region, and validated its fold on the basis of the disulphide bond pattern, which conformed to the generic pattern for DBL domains. The modelled structure for Pf332 DBL had differences compared with the erythrocyte-binding region of the αDBL domain of Plasmodium knowlesi Duffy-binding protein (Pkα-DBL). We addressed the function of Pf332 by constructing parasites that either lack expression of the protein or express an altered form. We found no evidence that Pf332 is involved in cytoadhesion or merozoite invasion. Truncation of Pf332 had a significant effect on deformability of the P. falciparum -infected erythrocyte, while loss of the full protein deletion did not. Our data suggest that Pf332 may contribute to the overall deformability of the P. falciparum -infected erythrocyte by anchoring and scaffolding. 相似文献
983.
Nicolas Grillet Martin Schwander Michael S. Hildebrand Anand Kolatkar Jennifer A. Webster Hossein Najmabadi Dietrich Stephan Melanie Bahlo Lisa M. Tarantino Richard J.H. Smith 《American journal of human genetics》2009,85(3):328-337
Hearing loss is the most common form of sensory impairment in humans and is frequently progressive in nature. Here we link a previously uncharacterized gene to hearing impairment in mice and humans. We show that hearing loss in the ethylnitrosourea (ENU)-induced samba mouse line is caused by a mutation in Loxhd1. LOXHD1 consists entirely of PLAT (polycystin/lipoxygenase/α-toxin) domains and is expressed along the membrane of mature hair cell stereocilia. Stereociliary development is unaffected in samba mice, but hair cell function is perturbed and hair cells eventually degenerate. Based on the studies in mice, we screened DNA from human families segregating deafness and identified a mutation in LOXHD1, which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). LOXHD1, MYO3a, and PJVK are the only human genes to date linked to progressive ARNSHL. These three genes are required for hair cell function, suggesting that age-dependent hair cell failure is a common mechanism for progressive ARNSHL. 相似文献
984.
Melanie J. Morris 《生物化学与生物物理学报:生物膜》2009,1788(3):676-5289
Glutathione transferases are a family of enzymes that are traditionally known to contribute to the phase II class of detoxification reactions. However, a novel property of the Schistosoma japonicum glutathione transferase (Sj.GST26) involves its translocation from the external medium into a variety of different cell types. Here we explore the efficiency and mechanism of cell entry for this class of protein. Using flow cytometry and confocal microscopy, we have examined the internalisation of Sj.GST26 into live cells under a variety of conditions designed to shed light on the mode of cellular uptake. Our results show that Sj.GST26 can effectively enter cells through an energy-dependent event involving endocytosis. More specifically, Sj.GST26 was found to colocalise with transferrin within the cell indicating that the endocytosis process involves clathrin-coated pits. A comprehensive study into the cellular internalisation of proteins from other classes within the GST structural superfamily has also been conducted. These experiments suggest that the ‘GST-fold’ structural motif influences cellular uptake, which presents a novel glimpse into an unknown aspect of GST function. 相似文献
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Halina Machelska Matthias Schroff Detlef Oswald Waltraud Binder Nicolle Sitte Shaaban A Mousa Heike L Rittner Alexander Brack Dominika Labuz Melanie Busch Burghardt Wittig Michael Schäfer Christoph Stein 《Molecular pain》2009,5(1):1-13
Background
TRPA1 has been implicated in both chemo- and mechanosensation. Recent work demonstrates that inhibiting TRPA1 function reduces mechanical hypersensitivity produced by inflammation. Furthermore, a broad range of chemical irritants require functional TRPA1 to exert their effects. In this study we use the ex-vivo skin-nerve preparation to directly determine the contribution of TRPA1 to mechanical- and chemical-evoked responses at the level of the primary afferent terminal.Results
Acute application of HC-030031, a selective TRPA1 antagonist, inhibited all formalin responses in rat C fibers but had no effect on TRPV1 function, assessed by capsaicin responsiveness. Genetic ablation experiments corroborated the pharmacological findings as C fibers from wild type mice responded to both formalin and capsaicin, but fibers from their TRPA1-deficient littermates responded only to capsaicin. HC-030031 markedly reduced the mechanically-evoked action potential firing in rat and wild type mouse C fibers, particularly at high-intensity forces, but had no effect on the mechanical responsiveness of Aδ fiber nociceptors. Furthermore, HC-030031 had no effect on mechanically-evoked firing in C fibers from TRPA1-deficient mice, indicating that HC-030031 inhibits mechanically-evoked firing via a TRPA1-dependent mechanism.Conclusion
Our data show that acute pharmacological blockade of TRPA1 at the cutaneous receptive field inhibits formalin-evoked activation and markedly reduces mechanically-evoked action potential firing in C fibers. Thus, functional TRPA1 at sensory afferent terminals in skin is required for their responsiveness to both noxious chemical and mechanical stimuli. 相似文献990.
Jans T Weyers P Schneider M Hohage A Werner M Pauli P Warnke A 《Attention deficit and hyperactivity disorders》2009,1(2):215-222
Objective of the study was the investigation of the psychometric properties of a scale derived from the Kiddie-SADS used for a dimensional assessment of externalizing symptoms in children and adolescents. The scale consists of 26 DSM-IV Kiddie-SADS items for attention deficit hyperactivity disorder (ADHD, 18 items) and oppositional defiant disorder (ODD, 8 items). Patients and their mothers were interviewed separately on the patients' symptoms during the last 2 weeks prior to interview. An ADHD-ODD sum score ranging between 0 and 26 was computed reflecting the number of fulfilled diagnostic criteria within the 2-week period under investigation. Interviews were videotaped and re-rated by an independent second rater. Additionally, mothers filled out two questionnaires on their children's symptoms (FBB-HKS, a German ADHD scale based on ICD-10 and DSM-IV criteria; strength and difficulties questionnaire, SDQ). We investigated 59 patients affected by AD(H)D according to DSM-IV recruited from our Department for Child and Adolescent Psychiatry (39 males, 20 females; mean age: M=9.66, SD=2.30). Inter-rater correlation regarding the ADHD-ODD scores was r=0.98 with no significant differences in mean sum scores between rater 1 and rater 2. Internal consistency of the ADHD-ODD scale was 0.85 (Cronbach's alpha). Item difficulties and discriminative power of the items also proved to be adequate. Convergent and discriminant validity were indicated by middle to high correlations with mother-ratings of the children's externalizing symptoms and a low correlation with ratings of internalizing symptoms. Factor analysis revealed a three-factor solution mainly covering inattentive, hyperactive and oppositional symptoms. In summary, ADHD and ODD sections of the Kiddie-SADS allow a reliable and valid dimensional assessment of externalizing symptoms in AD(H)D children and adolescents. 相似文献