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1.
Urinary bladder function consists in the storage and controlled voiding of urine. Translational studies require animal models that match human characteristics, such as Octodon degus, a diurnal rodent. This study aims to characterize the contractility of the detrusor muscle and the morphology and code of the vesical plexus from O. degus. Body temperature was measured by an intra-abdominal sensor, the contractility of detrusor strips was evaluated by isometric tension recording, and the vesical plexus was studied by electrical field stimulation (EFS) and immunofluorescence. The animals showed a diurnal chronotype as judged from core temperature. The myogenic contractile response of the detrusor muscle to increasing doses of KCl reached its maximum (31.04 mN/mm2) at 60 mM. In the case of cumulative dose–response of bethanecol, the maximum response (37.42 mN/mm2) was reached at 3.2 × 10?4 M. The response to ATP was clearly smaller (3.8 mN/mm2). The pharmacological dissection of the EFS-induced contraction identified ACh and sensory fibers as the main contributors to this response. The neurons of the vesical plexus were located mainly in the trigone area, grouped in big and small ganglia. Out of them, 48.1 % of the neurons were nitrergic and 62.7 % cholinergic. Our results show functional and morphological similarities between the urinary bladder of O. degus and that of humans.  相似文献   
2.
Internalization of G protein-coupled receptors can be triggered by agonists or by other stimuli. The process begins within seconds of cell activation and contributes to receptor desensitization. The Rab GTPase family controls endocytosis, vesicular trafficking, and endosomal fusion. Among their remarkable properties is the differential distribution of its members on the surface of various organelles. In the endocytic pathway, Rab 5 controls traffic from the plasma membrane to early endosomes, whereas Rab 4 and Rab 11 regulate rapid and slow recycling from early endosomes to the plasma membrane, respectively. Moreover, Rab 7 and Rab 9 regulate the traffic from late endosomes to lysosomes and recycling to the trans-Golgi. We explore the possibility that α1B-adrenergic receptor internalization induced by agonists (homologous) and by unrelated stimuli (heterologous) could involve different Rab proteins. This possibility was explored by Fluorescence Resonance Energy Transfer (FRET) using cells coexpressing α1B-adrenergic receptors tagged with the red fluorescent protein, DsRed, and different Rab proteins tagged with the green fluorescent protein. It was observed that when α1B-adrenergic receptors were stimulated with noradrenaline, the receptors interacted with proteins present in early endosomes, such as the early endosomes antigen 1, Rab 5, Rab 4, and Rab 11 but not with late endosome markers, such as Rab 9 and Rab 7. In contrast, sphingosine 1-phosphate stimulation induced rapid and transient α1B-adrenergic receptor interaction of relatively small magnitude with Rab 5 and a more pronounced and sustained one with Rab 9; interaction was also observed with Rab 7. Moreover, the GTPase activity of the Rab proteins appears to be required because no FRET was observed when dominant-negative Rab mutants were employed. These data indicate that α1B-adrenergic receptors are directed to different endocytic vesicles depending on the desensitization type (homologous vs. heterologous).  相似文献   
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A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA.  相似文献   
5.
A tRNAVal (GAC) gene is located in opposite orientation 552 nucleotides (nt) down-stream of the cytochrome oxidase subunit III (coxIII) gene in sunflower mitochondria. The comparison with the homologous chloroplast DNA revealed that the tRNAVal gene is part of a 417 nucleotides DNA insertion of chloroplast origin in the mitochondrial genome. No tRNAVal is encoded in monocot mitochondrial DNA (mtDNA), whereas two tRNAVal species are coded for by potato mtDNA. The mitochondrial genomes of different plant species thus seem to encode unique sets of tRNAs and must thus be competent in importing the missing differing sets of tRNAs.  相似文献   
6.
Neotropical seasonally dry forests (NSDFs) are widely distributed and possess high levels of species richness and endemism; however, their biogeography remains only partially understood. Using species distribution modelling and parsimony analysis of endemicity, we analysed the distributional patterns of the NSDF avifauna in order to identify their areas of endemism and provide a better understanding of the historical relationships among those areas. The strict consensus trees revealed 17 areas of endemism for NSDFs, which involve four large regions: Baja California, Caribbean–Antilles islands, Mesoamerica and South America. These well-resolved clades are circumscribed by geographical and ecological barriers associated with the Gulf of California, the leading edge of the Caribbean plate, the Tehuantepec Isthmus, the Polochic–Motagua fault, the Nicaragua Depression, the Chocó forest, the Amazon basin and the Andean Cordillera. Relationships among groups of NSDFs found here suggest that evolution of their avifauna involved a mixture of vicariance and dispersal events. Our results support the idea of independent diversification patterns and biogeographical processes in each region, including those previously associated with the Pleistocene Arc Hypothesis for NSDFs of south-eastern South America. This study provides a biogeographical framework to open new lines of research related to the biotic diversification of NSDFs.  相似文献   
7.
During seed development, phytic acid (PA) associated with mineral cations is stored as phytin and mobilized following germination in support of seedling growth. Two parallel biosynthetic pathways for PA have been proposed; yet the pathway is still poorly understood in terms of its regulation and the enzymes involved. Here, the castor bean (Ricinus communis L.) gene for inositol 1,3,4,5,6-pentakisphosphate 2-kinase (RcIPK1) has been identified. This encodes the enzyme implicated in catalyzing the final reaction in PA biosynthesis, and its expression is enhanced in isolated germinated embryos by application of phosphate and myo-inositol (Ins). Even though only one copy of the RcIPK1 gene is present in the genome, numerous RNA variants are present, most likely due to alternative splicing. These are translated into six closely related protein isoforms according to in silico analysis. Functional analyses using yeast ipk1Δ revealed that only three of the mRNA variants can rescue a temperature-sensitive growth phenotype of this strain. High-performance liquid chromatography (HPLC) analysis of the synthesized inositol phosphates demonstrated that the ability to complement the missing yeast IPK1 enzyme is associated with the production of enzyme activity. The three active isoforms possess unique conserved motifs important for IPK1 catalytic activity.  相似文献   
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Natural antibodies to interferon-gamma   总被引:3,自引:0,他引:3  
Natural antibodies to interferon (IFN)-γ were detected in the serum of virus-infected patients and also, at a low titre, in the serum of healthy subjects. The increased titre of antibodies to IFN-γ in the sera of virus-infected patients, and its decrease with clinical resolution, indicate that these antibodies are related to viral infection and probably reflect IFN-γ production as a result of antigenic stimulationin vivo. Natural antibodies to IFN-γ were affinity purified and studied for their capability to interferein vitro with the multiple activities of the lymphokine. Data obtained show that these human anti-IFN-γ antibodies have no inhibitory effect on the antiviral and antiproliferative activity of IFN-γ and do not interfere with the binding of the lymphokine to its specific cell receptor. Instead, they can inhibit the expression of HLA-DR antigens induced by IFN-γ on U937 cells and interfere, in mixed lymphocyte culture, with the proliferation of lymphocytes and the generation of cytotoxic lymphocytes. Experiments in animal models suggest that natural antibodies to IFN-γ may have a role in the immunoregulatory process limiting the intensity and/or duration of immune response. As they can interfere only with the immunomodulating activities of IFN-γ, these antibodies might open up new therapeutic approaches to diseases with evidence of activated cell-mediated immunity.  相似文献   
10.
Experimental conditions such as shaking (aeration) rate, concentration of reagents and extent of culture growth for the optimal synthesis of adenosine using Escherichia coli BL21 as biocatalyst were assessed, achieving 95% yield in 30 min of reaction using microorganisms harvested from late exponential phase. The ability of E. coli BL21 to synthesise purine nucleosides containing sugar residues such as 2'-deoxyribose, 2',3'-dideoxyribose and arabinose was also verified. 2'-Deoxyribo- and arabinonucleosides could be prepared in high yield, while the results obtained with 2',3'-dideoxyribonucleosides were not satisfactory. In the case of 2'-deoxyadenosine, using thymidine as a starting material, a yield of 94% was achieved at 45°C.  相似文献   
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