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排序方式: 共有508条查询结果,搜索用时 125 毫秒
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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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L. J. Farrow E. J. Holborow G. D. Johnson S. G. Lamb J. S. Stewart P. E. Taylor A. J. Zuckerman 《BMJ (Clinical research ed.)》1970,2(5711):693-695
In 39 unselected patients with acute infective hepatitis diagnosed on clinical, epidemiological, and pathological findings, smooth muscle (S.M.) antibody was found in 87% and hepatitis-associated antigen in 33%. The incidence of S.M. antibody was highest during the first month after the onset of symptoms, and the antibody was preponderantly IgM at this stage.S.M. antibody and hepatitis-associated antigen occurred independently, and unlike hepatitis-associated antigen, which was strongly associated with possible parenteral exposure to infection, the incidence of S.M. antibody was not related to the presumed mode of exposure. It is concluded that production of S.M. antibody is more directly related to liver cell damage than to the presence of hepatitis-associated antigen in the serum. 相似文献
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A MODIFIED LIGHT-TRAP FOR OBTAINING LARGE SAMPLES OF NIGHT-FLYING LOCUSTS AND GRASSHOPPERS 总被引:2,自引:2,他引:0
R. A. Farrow 《Australian Journal of Entomology》1974,13(4):357-360
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Christopher R. Farrow Josef D. Ackerman Ralph E. H. Smith Dave Snider 《Freshwater Biology》2020,65(2):289-303
- Rivers often transport phytoplankton to coastal embayments and introduce nutrients that can enrich coastal plankton communities. We investigated the effects of the Nottawasaga River on the nearshore (i.e. within 500 μm of shore) phytoplankton composition along a 10-km transect of Nottawasaga Bay, Lake Huron in 2015 and 2016. Imaging flow cytometry was used to identify and enumerate algal taxa, which were resolved at sizes larger than small nanoplankton (i.e. >5 μm). Multivariate analysis (perMANOVA and redundancy analysis) and a dilution model were used to examine how nutrients and the transport of algal taxa affected community composition in the bay.
- Sampling stations with different percentages of river water had significantly different phytoplankton communities. Phytoplankton community composition was also strongly associated with nutrients, including total phosphorus, which also varied with the percentage of river water. The majority of the 51 phytoplankton taxa identified in 2016 had numerical abundances in the bay that could be explained simply by the dilution of incoming river water.
- Phytoplankton transported from the river had a higher proportion of edible-sized cells (<30 μm), particularly in summer when colonial cyanobacteria were numerically dominant in the bay. Six taxa were more abundant than expected from the dilution of river water and included some cyanobacteria with late summer maxima. Five of the taxa that were transported from the river were less abundant than expected in the bay.
- Whereas impacts of fertilisation due to the characteristically higher nutrient concentration in the river are to be expected, the strong and highly correlated effects of transport within the narrow coastal band of this study largely concealed any distinct fertilisation effects.
- Riverine inputs may strongly influence the nearshore assemblage of phytoplankton in oligotrophic embayments in large lakes, creating hotspots for productivity, species turnover, and trophic dynamics.