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排序方式: 共有218条查询结果,搜索用时 15 毫秒
211.
Isabelle Thiffault David J. Speca Daniel C. Austin Melanie M. Cobb Kenneth S. Eum Nicole P. Safina Lauren Grote Emily G. Farrow Neil Miller Sarah Soden Stephen F. Kingsmore James S. Trimmer Carol J. Saunders Jon T. Sack 《The Journal of general physiology》2015,146(5):399-410
The epileptic encephalopathies are a group of highly heterogeneous genetic disorders. The majority of disease-causing mutations alter genes encoding voltage-gated ion channels, neurotransmitter receptors, or synaptic proteins. We have identified a novel de novo pathogenic K+ channel variant in an idiopathic epileptic encephalopathy family. Here, we report the effects of this mutation on channel function and heterologous expression in cell lines. We present a case report of infantile epileptic encephalopathy in a young girl, and trio-exome sequencing to determine the genetic etiology of her disorder. The patient was heterozygous for a de novo missense variant in the coding region of the KCNB1 gene, c.1133T>C. The variant encodes a V378A mutation in the α subunit of the Kv2.1 voltage-gated K+ channel, which is expressed at high levels in central neurons and is an important regulator of neuronal excitability. We found that expression of the V378A variant results in voltage-activated currents that are sensitive to the selective Kv2 channel blocker guangxitoxin-1E. These voltage-activated Kv2.1 V378A currents were nonselective among monovalent cations. Striking cell background–dependent differences in expression and subcellular localization of the V378A mutation were observed in heterologous cells. Further, coexpression of V378A subunits and wild-type Kv2.1 subunits reciprocally affects their respective trafficking characteristics. A recent study reported epileptic encephalopathy-linked missense variants that render Kv2.1 a tonically activated, nonselective cation channel that is not voltage activated. Our findings strengthen the correlation between mutations that result in loss of Kv2.1 ion selectivity and development of epileptic encephalopathy. However, the strong voltage sensitivity of currents from the V378A mutant indicates that the loss of voltage-sensitive gating seen in all other reported disease mutants is not required for an epileptic encephalopathy phenotype. In addition to electrophysiological differences, we suggest that defects in expression and subcellular localization of Kv2.1 V378A channels could contribute to the pathophysiology of this KCNB1 variant. 相似文献
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The results of a modelling study to investigate the mechanisms controlling macroalgal growth within the Medway estuary, UK,
are presented. Intertidal zone bathymetry, tidal dynamics and turbidity control the time available for nutrient uptake and
photosynthesis, and were used as a basis for predicting areas where macroalgae will grow. Tidal bed stress was also considered
as a controlling factor for the presence of the less robust green macroalgae species. Two approaches to predicting macroalgal
distributions were applied: (1) a simple ‘suitability index’ method based on tidal flooding and drying, taking account of
the conflict between time available for nutrient uptake and for photosynthesis; and (2) a biological macroalgal growth model
that includes a detailed treatment of nutrient uptake and plant growth. The former approach assigns a value between zero and
one for the suitability of a location for macroalgal occurrence, while the latter predicts the full macroalgal growth dynamics
over an annual cycle. Tidal bed stress was included in both approaches as an independent modifier of macroalgal occurrence/growth.
Results were compared with aerial survey maps of observed vegetation cover and time series of measured biomass density. Both
approaches gave good predictions of non-species-specific vegetation cover in the intertidal zone of the Medway. Tidal bed
stress was found to be a strong predictor of the specific occurrence of Enteromorpha spp. and Ulva spp., with these species favouring areas of low tidal energy. It was concluded that light and a lack of suitable regions
with low tidal bed stress, rather than nutrients, were the main factors limiting excessive growth of Enteromorpha spp. and Ulva spp. in the estuary. Although this study was focussed on the Medway, the results are likely to be applicable to a broad range
of relatively turbid, meso- and macro-tidal estuaries.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Guest editors: J. H. Andersen & D. J. Conley
Eutrophication in Coastal Ecosystems: Selected papers from the Second International Symposium on Research and Management of
Eutrophication in Coastal Ecosystems, 20–23 June 2006, Nyborg, Denmark 相似文献
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Martin P. Meyer James S. Trimmer Jonathan D. Gilthorpe Stephen J Smith 《Developmental neurobiology》2005,63(2):91-105
The PSD‐95 family of membrane‐ associated guanylate kinases (MAGUKs) are thought to act as molecular scaffolds that regulate the assembly and function of the multiprotein signaling complex found at the postsynaptic density of excitatory synapses. Genetic analysis of PSD‐95 family members in the mammalian nervous system has so far been difficult, but the zebrafish is emerging as an ideal vertebrate system for studying the role of particular genes in the developing and mature nervous system. Here we describe the cloning of the zebrafish orthologs of PSD‐95, PSD‐93, and two isoforms of SAP‐97. Using in situ hybridization analysis we show that these zebrafish MAGUKs have overlapping but distinct patterns of expression in the developing nervous system and craniofacial skeleton. Using a pan‐MAGUK antibody we show that MAGUK proteins localize to neurons within the developing hindbrain, cerebellum, visual and olfactory systems, and to skin epithelial cells. In the olfactory and visual systems MAGUK proteins are expressed strongly in synaptic regions, and the onset of expression in these areas coincides with periods of synapse formation. These data are consistent with the idea that PSD‐95 family members are involved in synapse assembly and function, and provide a platform for future functional studies in vivo in a highly tractable model organism. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 相似文献
216.
Differential susceptibility of human cells to transformation by murine and avian sarcoma viruses 总被引:1,自引:0,他引:1
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