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51.
Santeri Kiviluoto Tomas Luyten Lars Schneider Dmitrij Lisak Diego Rojas-Rivera Kirsten Welkenhuyzen Ludwig Missaen Humbert De Smedt Jan B. Parys Claudio Hetz Axel Methner Geert Bultynck 《Cell calcium》2013
Bax Inhibitor-1 (BI-1) is an evolutionarily conserved six-transmembrane domain endoplasmic reticulum (ER)-localized protein that protects against ER stress-induced apoptotic cell death. This function is closely connected to its ability to lower steady-state ER Ca2+ levels. Recently, we elucidated BI-1's Ca2+-channel pore in the C-terminal part of the protein and identified the critical amino acids of its pore. Based on these insights, a Ca2+-channel pore-dead mutant BI-1 (BI-1D213R) was developed. We determined whether BI-1 behaves as a bona fide H+/Ca2+ antiporter or as an ER Ca2+-leak channel by investigating the effect of pH on unidirectional Ca2+-efflux rates. At pH 6.8, wild-type BI-1 expression in BI-1−/− cells increased the ER Ca2+-leak rate, correlating with its localization in the ER compartment. In contrast, BI-1D231R expression in BI-1−/−, despite its ER localization, did not increase the ER Ca2+-leak rate. However, at pH < 6.8, the BI-1-mediated ER Ca2+ leak was blocked. Finally, a peptide representing the Ca2+-channel pore of BI-1 promoting Ca2+ flux from the ER was used. Lowering the pH from 6.8 to 6.0 completely abolished the ability of the BI-1 peptide to mediate Ca2+ flux from the ER. We propose that this pH dependence is due to two aspartic acid residues critical for the function of the Ca2+-channel pore and located in the ER membrane-dipping domain, which facilitates the protonation of these residues. 相似文献
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The genus Meira currently contains three recently described species of mite-associated basidiomycete yeasts from Israel and Japan and is placed in the Exobasidiomycetes (Ustilaginomycotina) Incertae sedis. A previously undescribed species of Meira was isolated from the phylloplane of a magnolia leaf in Louisiana, USA. Herein, we describe Meira miltonrushii sp. nov. and include phylogenetic analyses from three rDNA loci to resolve the placement of Meira. This study provides evidence that Meira belongs to the family Brachybasidiaceae in the Exobasidiales and supports the placement of another mite-associated yeast genus, Acaromyces, within Cryptobasidiaceae (Exobasidiales). We also examine sequences produced by numerous environmental studies that suggest Meira species can be found as endophytes of many plant species. To our knowledge, this is the first record of a member of the genus Meira in North America. 相似文献
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Susan M. Gribble Frances K. Wiseman Stephen Clayton Elena Prigmore Elizabeth Langley Fengtang Yang Sean Maguire Beiyuan Fu Diana Rajan Olivia Sheppard Carol Scott Heidi Hauser Philip J. Stephens Lucy A. Stebbings Bee Ling Ng Tomas Fitzgerald Michael A. Quail Ruby Banerjee Kai Rothkamm Victor L. J. Tybulewicz Elizabeth M. C. Fisher Nigel P. Carter 《PloS one》2013,8(4)
Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439. 相似文献
57.
Dana Horakova Robert Zivadinov Bianca Weinstock-Guttman Eva Havrdova Jun Qu Miriam Tama?o-Blanco Darlene Badgett Michaela Tyblova Niels Bergsland Sara Hussein Laura Willis Jan Krasensky Manuela Vaneckova Zdenek Seidl Petra Lelkova Michael G. Dwyer Ming Zhang Haoying Yu Xiaotao Duan Tomas Kalincik Murali Ramanathan 《PloS one》2013,8(1)
Objectives
To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.Methods
We analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.Results
The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.Conclusions
Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy. 相似文献58.
59.
Strejc Jan Kyselova Lucie Cadkova Anna Potocar Tomas Branyik Tomas 《Extremophiles : life under extreme conditions》2019,23(2):219-227
Extremophiles - Acidothermophilic bacteria of the genus Alicyclobacillus are frequent contaminants of fruit-based products. This study is the first attempt to characterize the physico-chemical... 相似文献