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排序方式: 共有222条查询结果,搜索用时 15 毫秒
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Abdullah Jaffer Brian Harvey Vivienne Ann Russell Machteld Elizabeth Carstens Anna Susanna de Villiers Joshua Joachim Fransua Taljaard 《Neurochemical research》1993,18(10):1057-1061
Chronic treatment of rats with lithium chloride was examined in order to determine its effect on hypothalamic monoamine and metabolite content, basal thyrotropin (TSH) secretion and thyroid function. The hypothalamic concentrations of noradrenaline (NA), dopamine (DA) and its metabolites, dihydroxyphenylacetic acid. (DOPAC) and homovanillic acid (HVA) in the lithium treated rats remained unaltered when compared to control levels. NA turnover and the NA metabolite, 3-methoxy-4-hydroxyphenylglycol (total MHPG), were significantly lower (p<0.01), whereas both serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), were significantly higher (p<0.01 and p<0.02, respectively) in the lithium treated rat hypothalami than in controls. Chronic lithium treatment significantly elevated basal TSH levels (p<0.05). This effect was antagonized by methylp-hydroxybenzoate (methylparaben, p<0.01), which did not itself affect basal TSH levels. Free serum T3 and T4 levels were not significantly affected by chronic lithium treatment, although T4 tended to be slightly lower than control levels. The monoamine changes observed in the hypothalamus of lithium treated rats did not appear to account for the elevated TSH levels observed in these rats since NA activity which is generally regarded as stimulatory was decreased and 5-HT which has an inhibitory effect on TSH secretion, was increased. The elevated TSH levels may have been due to a reduced negative feedback inhibition of TSH release by the mildly reduced circulating T4 levels caused by chronic lithium treatment. A further possibility is that the pituitary cGMP (and hence TSH) response to TRH may have been enhanced by chronic lithium treatment and methylparaben may have antagonized this effect. 相似文献
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Vivienne C.M. Neeve Angela Pyle Veronika Boczonadi Aurora Gomez-Duran Helen Griffin Mauro Santibanez-Koref Ulrike Gaiser Peter Bauer Andreas Tzschach Patrick F. Chinnery Rita Horvath 《Mitochondrion》2013,13(6):743-748
Exome sequencing identified compound heterozygous mutations in the recently discovered mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene in two sisters with mild Leigh syndrome and combined respiratory chain deficiency. The mutations lead to undetectable levels of the MTFMT protein. Blue native polyacrylamide gel electrophoresis showed decreased complexes I and IV, and additional products stained with complex V antibodies, however the overall steady state level of mt-tRNAMet was normal. Our data illustrate that exome sequencing is an excellent diagnostic tool, and its value in clinical medicine is enormous, however it can only be optimally exploited if combined with detailed phenotyping and functional studies. 相似文献
5.
Khairunadwa Jemon Vivienne Young Michelle Wilson Sara McKee Vernon Ward Margaret Baird Sarah Young Merilyn Hibma 《PloS one》2013,8(6)
Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV) and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV) virus-like particle (VLP)-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48–57) from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25) or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages. 相似文献
6.
David G. McLaren Sheng-Ping Wang Steven J. Stout Dan Xie Paul L. Miller Vivienne Mendoza Raymond Rosa Jose Castro-Perez Stephen F. Previs Douglas G. Johns Thomas P. Roddy 《Journal of lipid research》2013,54(1):276-281
Isotopic tracers have been used to examine lipid trafficking for many years, and data from those studies have typically yielded novel insight regarding the pathophysiology of dyslipidemia. Previous experimental designs were suitable for studies in humans because relatively large volumes of plasma could be regularly sampled. We have expanded on the earlier logic by applying high-throughput analytical methods that require reduced sample volumes. Specifically, we have examined the possibility of coupling gel-based separations of lipoproteins (e.g., lipoprint) with LC-MS/MS analyses of complex lipid mixtures as a way to routinely measure the labeling profiles of distinct lipids in discrete lipoprotein subfractions. We demonstrate the ability to measure the incorporation of [U-13C]oleate into triglycerides (TG), PLs (PL), and cholesterol esters (CE) in VLDL, LDL, and HDL particles in mice. Although rodent models of dyslipidemia are inherently different from humans because of alterations in enzyme activities and underlying metabolism, rodent models can be used to screen novel compounds for efficacy in altering a given biochemical pathway and therein enable studies of target engagement in vivo. We expect that it is possible to translate our approach for application in other systems, including studies in humans. 相似文献
7.
Yi Liu Vivienne Gianinazzi-Pearson Christine Arnould Daniel Wipf Bin Zhao Diederik van Tuinen 《Fungal biology》2013,117(1):22-31
Fluctuations in intracellular calcium levels generate signalling events and regulate different cellular processes. Whilst the implication of Ca2+ in plant responses during arbuscular mycorrhiza (AM) interactions is well documented, nothing is known about the regulation or role of this secondary messenger in the fungal symbiont. The spatio-temporal expression pattern of putatively Ca2+-related genes of Glomus intraradices BEG141 encoding five proteins involved in membrane transport and one nuclear protein kinase, was investigated during the AM symbiosis. Expression profiles related to successful colonization of host roots were observed in interactions of G. intraradices with roots of wild-type Medicago truncatula (line J5) compared to the mycorrhiza-defective mutant dmi3/Mtsym13. Symbiotic fungal activity was monitored using stearoyl-CoA desaturase and phosphate transporter genes. Laser microdissection based-mapping of fungal gene expression in mycorrhizal root tissues indicated that the Ca2+-related genes were differentially upregulated in arbuscules and/or in intercellular hyphae. The spatio-temporal variations in gene expression suggest that the encoded proteins may have different functions in fungal development or function during symbiosis development. Full-length cDNA obtained for two genes with interesting expression profiles confirmed a close similarity with an endoplasmic reticulum P-type ATPase and a Vcx1-like vacuolar Ca2+ ion transporter functionally characterized in other fungi and involved in the regulation of cell calcium pools. Possible mechanisms are discussed in which Ca2+-related proteins G. intraradices BEG141 may play a role in mobilization and perception of the intracellular messenger by the AM fungus during symbiotic interactions with host roots. 相似文献
8.
Vivienne Foroughirad Alexis L. Levengood Janet Mann Cline H. Frre 《Molecular ecology resources》2019,19(5):1181-1194
Kinship plays a fundamental role in the evolution of social systems and is considered a key driver of group living. To understand the role of kinship in the formation and maintenance of social bonds, accurate measures of genetic relatedness are critical. Genotype‐by‐sequencing technologies are rapidly advancing the accuracy and precision of genetic relatedness estimates for wild populations. The ability to assign kinship from genetic data varies depending on a species’ or population's mating system and pattern of dispersal, and empirical data from longitudinal studies are crucial to validate these methods. We use data from a long‐term behavioural study of a polygynandrous, bisexually philopatric marine mammal to measure accuracy and precision of parentage and genetic relatedness estimation against a known partial pedigree. We show that with moderate but obtainable sample sizes of approximately 4,235 SNPs and 272 individuals, highly accurate parentage assignments and genetic relatedness coefficients can be obtained. Additionally, we subsample our data to quantify how data availability affects relatedness estimation and kinship assignment. Lastly, we conduct a social network analysis to investigate the extent to which accuracy and precision of relatedness estimation improve statistical power to detect an effect of relatedness on social structure. Our results provide practical guidance for minimum sample sizes and sequencing depth for future studies, as well as thresholds for post hoc interpretation of previous analyses. 相似文献
9.
Vivienne Litzke Meinolf Ottensmann Jaume Forcada Louise Heitzmann Joseph Ivan Hoffman 《Ecology and evolution》2019,9(14):7985-7996
Numerous studies have reported correlations between the heterozygosity of genetic markers and fitness. These heterozygosity–fitness correlations (HFCs) play a central role in evolutionary and conservation biology, yet their mechanistic basis remains open to debate. For example, fitness associations have been widely reported at both neutral and functional loci, yet few studies have directly compared the two, making it difficult to gauge the relative contributions of genome‐wide inbreeding and specific functional genes to fitness. Here, we compared the effects of neutral and immune gene heterozygosity on death from bacterial infection in Antarctic fur seal (Arctocephalus gazella) pups. We specifically developed a panel of 13 microsatellites from expressed immune genes and genotyped these together with 48 neutral loci in 234 individuals, comprising 39 pups that were classified at necropsy as having most likely died of bacterial infection together with a five times larger matched sample of healthy surviving pups. Identity disequilibrium quantified from the neutral markers was positive and significant, indicative of variance in inbreeding within the study population. However, multilocus heterozygosity did not differ significantly between healthy and infected pups at either class of marker, and little evidence was found for fitness associations at individual loci. These results support a previous study of Antarctic fur seals that found no effects of heterozygosity at nine neutral microsatellites on neonatal survival and thereby help to refine our understanding of how HFCs vary across the life cycle. Given that nonsignificant HFCs are underreported in the literature, we also hope that our study will contribute toward a more balanced understanding of the wider importance of this phenomenon. 相似文献
10.
Hughes AE Orr N Patterson C Esfandiary H Hogg R McConnell V Silvestri G Chakravarthy U 《PLoS medicine》2007,4(12):e355