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41.
West Nile virus-induced neuroinflammation: glial infection and capsid protein-mediated neurovirulence
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van Marle G Antony J Ostermann H Dunham C Hunt T Halliday W Maingat F Urbanowski MD Hobman T Peeling J Power C 《Journal of virology》2007,81(20):10933-10949
West Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia. Upregulation of proinflammatory genes, CXCL10, interleukin-1beta, and indolamine-2',3'-deoxygenase with concurrent suppression of the protective astrocyte-specific endoplasmic reticulum stress sensor gene, OASIS (for old astrocyte specifically induced substance), was evident in WNVE patients compared to non-WNVE controls. These findings were supported by increased ex vivo expression of these proinflammatory genes in glia infected by WNV-NY99. WNV infection caused endoplasmic reticulum stress gene induction and apoptosis in neurons but did not affect glial viability. WNV-infected astrocytic cells secreted cytotoxic factors, which caused neuronal apoptosis. The expression of the WNV-NY99 capsid protein in neurons and glia by a Sindbis virus-derived vector (SINrep5-WNVc) caused neuronal death and the release of neurotoxic factors by infected astrocytes, coupled with proinflammatory gene induction and suppression of OASIS. Striatal implantation of SINrep5-WNV(C) induced neuroinflammation in rats, together with the induction of CXCL10 and diminished OASIS expression, compared to controls. Moreover, magnetic resonance neuroimaging showed edema and tissue injury in the vicinity of the SINrep5-WNVc implantation site compared to controls, which was complemented by neurobehavioral abnormalities in the SINrep5-WNVc-implanted animals. These studies underscore the important interactions between the WNV capsid protein and neuroinflammation in the pathogenesis of WNV-induced neurological disorders. 相似文献
42.
Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study
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Faivre L Collod-Beroud G Loeys BL Child A Binquet C Gautier E Callewaert B Arbustini E Mayer K Arslan-Kirchner M Kiotsekoglou A Comeglio P Marziliano N Dietz HC Halliday D Beroud C Bonithon-Kopp C Claustres M Muti C Plauchu H Robinson PN Adès LC Biggin A Benetts B Brett M Holman KJ De Backer J Coucke P Francke U De Paepe A Jondeau G Boileau C 《American journal of human genetics》2007,81(3):454-466
Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes. Clinical care is complicated by variable age at onset and the wide range of severity of aortic features. The factors that modulate phenotypical severity, both among and within families, remain to be determined. The availability of international FBN1 mutation Universal Mutation Database (UMD-FBN1) has allowed us to perform the largest collaborative study ever reported, to investigate the correlation between the FBN1 genotype and the nature and severity of the clinical phenotype. A range of qualitative and quantitative clinical parameters (skeletal, cardiovascular, ophthalmologic, skin, pulmonary, and dural) was compared for different classes of mutation (types and locations) in 1,013 probands with a pathogenic FBN1 mutation. A higher probability of ectopia lentis was found for patients with a missense mutation substituting or producing a cysteine, when compared with other missense mutations. Patients with an FBN1 premature termination codon had a more severe skeletal and skin phenotype than did patients with an inframe mutation. Mutations in exons 24-32 were associated with a more severe and complete phenotype, including younger age at diagnosis of type I fibrillinopathy and higher probability of developing ectopia lentis, ascending aortic dilatation, aortic surgery, mitral valve abnormalities, scoliosis, and shorter survival; the majority of these results were replicated even when cases of neonatal MFS were excluded. These correlations, found between different mutation types and clinical manifestations, might be explained by different underlying genetic mechanisms (dominant negative versus haploinsufficiency) and by consideration of the two main physiological functions of fibrillin-1 (structural versus mediator of TGF beta signalling). Exon 24-32 mutations define a high-risk group for cardiac manifestations associated with severe prognosis at all ages. 相似文献
43.
J. Robins † D. Mayer ‡ J. Staunton-Smith I. Halliday B. Sawynok § M. Sellin 《Journal of fish biology》2006,69(2):379-391
Relationships between freshwater flows and growth rates of the opportunistic predatory finfish barramundi Lates calcarifer in a dry tropical estuary were examined using data from a long-term tag-recapture programme. Lagged effects were not investigated. After accounting for length at release, time at liberty and seasonal variation ( e.g. winter, spring, summer and autumn), growth rates were significantly and positively related to fresh water flowing to the estuary. Effects were present at relatively low levels of freshwater flow ( i.e. 2·15 m3 s−1 , the 5th percentile of the mean flow rate experienced by fish in the study during time at liberty). The analysis, although correlative, provides quantitative evidence to support the hypothesis that freshwater flows are important in driving the productivity of estuaries and can improve growth of species high in the trophic chain. 相似文献
44.
45.
Collins JP Halliday T 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2005,360(1454):309-314
Amphibian population declines and sudden species' extinctions began to be noted at the beginning of the 1980s. Understanding the causes of the losses is hampered by our poor knowledge of the amphibian fauna in many parts of the world. Amphibian taxa are still being described at a high rate, especially in the tropics, which means that even quantifying species lost as a percentage of the current fauna can be a misleading statistic in some parts of the globe. The number of species that have gone missing is only one measure of the loss of biodiversity. Long-term studies of single-species populations are needed, but this approach has its limits. Amphibian populations often show great annual variation in population size making it difficult, if not impossible, to use short-term studies as a basis for deciding if a population is increasing or decreasing in the long term. Aggregating single studies into databases and searching for patterns of variation is a way of overcoming this limitation. Several databases on species and population time series are available or in development. These records show that declines are continuing worldwide with some species and populations, especially in the tropics and at higher elevations, at greater risk of extinction than others. Unfortunately, amphibian databases with population time series have much less information for the tropics compared to the temperate zone, and less for Africa and Asia compared with Europe and North America. Focusing limited resources using comprehensive statistical designs is a way to maximize the efficiency and effectiveness of monitoring efforts. It is clear that, in the first decades of the twenty-first century, the regions of the globe with the highest diversity of amphibian species will experience the greatest rates of decrease of forests and increase in human population size, fertilizer use, agricultural production, creation of new croplands and irrigation. Many of these changes are likely negatively to affect amphibian species diversity, and their influence must be understood before concluding, at least for amphibians, that the 2010 millennium assessment goal of significantly reversing the rate of loss of Earth's biodiversity can be met. 相似文献
46.
Severs NJ Dupont E Coppen SR Halliday D Inett E Baylis D Rothery S 《Biochimica et biophysica acta》2004,1662(1-2):138-148
Different combinations and relative quantities of three connexins-connexin43, connexin40 and connexin45-are expressed in different subsets of cardiomyocyte. In the healthy heart, gap junctions assembled from these different connexin combinations form the cell-to-cell pathways for the precisely orchestrated patterns of current flow that govern the normal heart rhythm. Remodelling of gap junction organization and connexin expression is a conspicuous feature of human heart disease in which there is an arrhythmic tendency. This remodelling may take the form of structural remodelling, involving disturbances in the distribution of gap junctions (i.e., disruption of the normal ordered pathways for cell-to-cell conduction), and remodelling of connexin expression, involving alteration in the amount or type of connexin(s) present. Most notable among quantitative alterations in connexin expression is a reduction in ventricular connexin43 levels in human congestive heart failure. By correlating data from studies in experimental animal models, gap junction and connexin remodelling emerges as a factor to be considered in understanding the pro-arrhythmic substrate characteristic of many forms of heart disease. However, our knowledge of the functional correlates of the specific patterns of multiple connexin expression found in different regions of the heart in health and disease remains rudimentary, and the development of new experimental cell models heralds advances in this area over the next few years. 相似文献
47.
An augmented Arabidopsis phenology model reveals seasonal temperature control of flowering time 总被引:1,自引:0,他引:1
Chew YH Wilczek AM Williams M Welch SM Schmitt J Halliday KJ 《The New phytologist》2012,194(3):654-665
? In this study, we used a combination of theoretical (models) and experimental (field data) approaches to investigate the interaction between light and temperature signalling in the control of Arabidopsis flowering. ? We utilised our recently published phenology model that describes the flowering time of Arabidopsis grown under a range of field conditions. We first examined the ability of the model to predict the flowering time of field plantings at different sites and seasons in light of the specific meteorological conditions that pertained. ? Our analysis suggested that the synchrony of temperature and light cycles is important in promoting floral initiation. New features were incorporated into the model that improved its predictive accuracy across seasons. Using both laboratory and field data, our study has revealed an important seasonal effect of night temperatures on flowering time. Further model adjustments to describe phytochrome (phy) mutants supported our findings and implicated phyB in the temporal gating of temperature-induced flowering. ? Our study suggests that different molecular pathways interact and predominate in natural environments that change seasonally. Temperature effects are mediated largely during the photoperiod during spring/summer (long days) but, as days shorten in the autumn, night temperatures become increasingly important. 相似文献
48.
Halliday DC Kennedy GC Hamilton NH Tarmo S Alderman J Siddon NA Robinson AJ 《Gene expression patterns : GEP》2008,8(6):424-432
Metamorphosis, a critical stage in the development of toads and frogs, involves rapid levels of morphological change. In the current study, we have used microarray analysis to identify shifts in gene expression between tadpole and toadlet stages of the cane toad, Bufo (Chaunus) marinus. Here, we report on nine genes that show the greatest induction during metamorphosis; the gut-associated gastrokine and trefoil factor, blood components haemoglobins alpha/beta, apolipoprotein and serum albumin, a nasal gene olfactomedin, a lens gene gamma-crystallin, and a novel gene with low homology to frog harderin. We present both temporal and spatial expression patterns of these genes identified in developing and adult cane toads. This study extends our knowledge of the molecular basis of toad metamorphosis, and not only offers insights to the genes induced during the general remodelling that occurs but also reveals possible targets for control and manipulation of amphibian pest species, for example, the cane toad in Australia. 相似文献
49.
F. Taddei J. A. Halliday I. Matic M. Radman 《Molecular genetics and genomics : MGG》1997,256(3):277-281
Bacteria live in unstructured and structured environments, experiencing feast and famine lifestyles. Bacterial colonies can be viewed as model structured environments. SOS induction and mutagenesis have been observed in aging Escherichia coli colonies, in the absence of exogenous sources of DNA damage. This cAMP-dependent mutagenesis occurring in Resting Organisms in a Structured Environment (ROSE) is unaffected by a umuC mutation and therefore differs from both targeted UV mutagenesis and recA730 (SOS constitutive) untargeted mutagenesis. As a recB mutation has only a minor effect on ROSE mutagenesis it also differs from both adaptive reversion of the lacI33 allele and from iSDR (inducible Stable DNA Replication) mutagenesis. Besides its recA and lexA dependence, ROSE mutagenesis is also uvrB and polA dependent. These genetic requirements are reminiscent of the untargeted mutagenesis in λ phage observed when unirradiated λ infects UV-irradiated E. coli. These mutations, which are not observed in aging liquid cultures, accumulate linearly with the age of the colonies. ROSE mutagenesis might offer a good model for bacterial mutagenesis in structured environments such as biofilms and for mutagenesis of quiescent eukaryotic cells. 相似文献
50.
TANATIN BI 《Mikrobiologiia》1951,20(6):506-511