排序方式: 共有30条查询结果,搜索用时 15 毫秒
1.
The most common genetic cause for amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) is repeat expansion of a hexanucleotide sequence (GGGGCC) within the C9orf72 genomic sequence. To elucidate the functional role of C9orf72 in disease pathogenesis, we identified certain molecular interactors of this factor. We determined that C9orf72 exists in a complex with SMCR8 and WDR41 and that this complex acts as a GDP/GTP exchange factor for RAB8 and RAB39, 2 RAB GTPases involved in macroautophagy/autophagy. Consequently, C9orf72 depletion in neuronal cultures leads to accumulation of unresolved aggregates of SQSTM1/p62 and phosphorylated TARDBP/TDP-43. However, C9orf72 reduction does not lead to major neuronal toxicity, suggesting that a second stress may be required to induce neuronal cell death. An intermediate size of polyglutamine repeats within ATXN2 is an important genetic modifier of ALS-FTD. We found that coexpression of intermediate polyglutamine repeats (30Q) of ATXN2 combined with C9orf72 depletion increases the aggregation of ATXN2 and neuronal toxicity. These results were confirmed in zebrafish embryos where partial C9orf72 knockdown along with intermediate (but not normal) repeat expansions in ATXN2 causes locomotion deficits and abnormal axonal projections from spinal motor neurons. These results demonstrate that C9orf72 plays an important role in the autophagy pathway while genetically interacting with another major genetic risk factor, ATXN2, to contribute to ALS-FTD pathogenesis. 相似文献
2.
Dian J. Chiang Sanjoy Roychowdhury Katelyn Bush Megan R. McMullen Sorana Pisano Kathryn Niese Mitchell A. Olman Michele T. Pritchard Laura E. Nagy 《PloS one》2013,8(7)
The effect of moderate alcohol consumption on liver fibrosis is not well understood, but evidence suggests that adenosine may play a role in mediating the effects of moderate ethanol on tissue injury. Ethanol increases the concentration of adenosine in the liver. Adenosine 2A receptor (A2AR) activation is known to enhance hepatic stellate cell (HSC) activation and A2AR deficient mice are protected from fibrosis in mice. Making use of a novel mouse model of moderate ethanol consumption in which female C57BL/6J mice were allowed continued access to 2% (vol/vol) ethanol (11% calories) or pair-fed control diets for 2 days, 2 weeks or 5 weeks and superimposed with exposure to CCl4, we tested the hypothesis that moderate ethanol consumption increases fibrosis in response to carbon tetrachloride (CCl4) and that treatment of mice with an A2AR antagonist prevents and/or reverses this ethanol-induced increase in liver fibrosis. Neither the expression or activity of CYP2E1, required for bio-activation of CCl4, nor AST and ALT activity in the plasma were affected by ethanol, indicating that moderate ethanol did not increase the direct hepatotoxicity of CCl4. However, ethanol feeding enhanced HSC activation and exacerbated liver fibrosis upon exposure to CCl4. This was associated with an increased sinusoidal angiogenic response in the liver. Treatment with A2AR antagonist both prevented and reversed the ability of ethanol to exacerbate liver fibrosis.
Conclusion
Moderate ethanol consumption exacerbates hepatic fibrosis upon exposure to CCl4. A2AR antagonism may be a potential pharmaceutical intervention to decrease hepatic fibrosis in response to ethanol. 相似文献3.
4.
The binding of ofloxacin (OFLX) to human serum albumin (HSA) was investigated by fluorescence and circular dichroism (CD) techniques. The binding parameters have been evaluated by a fluorescence quenching method. Competitive binding measurements were performed in the presence of warfarin and ibuprofen and suggest binding to the warfarin site I of HSA. The distance r between donor (HSA) and acceptor (OFLX) was estimated according to the Forster's theory of non‐radiatiative energy transfer. CD spectra revealed that the binding of OFLX to HSA induced conformational changes in HSA. Molecular docking was performed and shows that for the lowest energy complex OFLX is located in site I of HSA, which correlate to the competitive binding experiments. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
5.
Livia Garzia Noriyuki Kijima A. Sorana Morrissy Pasqualino De Antonellis Ana Guerreiro-Stucklin Borja L. Holgado Xiaochong Wu Xin Wang Michael Parsons Kory Zayne Alex Manno Claudia Kuzan-Fischer Carolina Nor Laura K. Donovan Jessica Liu Lei Qin Alexandra Garancher Kun-Wei Liu Michael D. Taylor 《Cell》2018,172(5):1050-1062.e14
6.
Alina Asandei Sorana Iftemi Loredana Mereuta Irina Schiopu Tudor Luchian 《The Journal of membrane biology》2014,247(6):523-530
One of the prevailing paradigms regarding the onset of Alzheimer’s disease endows metal ions with key roles in certain steps of the amyloid-β (Aβ) peptide aggregation cascade, through peptide conformational changes induced by metal binding. Herein, we focused on the truncated, more soluble Aβ1–16 peptide fragment from the human Aβ1–40, and demonstrated the utility of a sensing element based on the α-hemolysin (α-HL) protein to examine and compare at single-molecule level the interactions between such peptides and various metals. By using the same approach, we quantified Cu2+ and Zn2+ binding affinities to the Aβ1–16 fragment, whereas the statistical analysis of blockages induced by a single Aβ1–16 peptide on the current flow through an open α-HL pore show that the metal propensity to interacting with the peptide and entailing conformational changes obey the following order: Cu2+ > Zn2+ > Fe3+ > Al3+. 相似文献
7.
Sorana Toma 《Ethnic and racial studies》2016,39(4):593-613
Research on the role of co-ethnic ties in immigrants’ labour market outcomes has reached mixed conclusions. Some argue they are a valuable resource, increasing immigrants’ labour force participation and wages; others find negative effects such as trapping workers in low-quality employment. Thus far very few quantitative studies have investigated systematically the circumstances under which migrant networks work. Taking advantage of unique data on Senegalese men in France, Italy and Spain, this paper shows that the receiving context shapes the role of pre-migration ties. In France, where the Senegalese community is well-established and socio-economically diverse, networks lead to better economic prospects. In contrast, pre-migration ties in Italy and Spain mostly lead to the perpetuation of ethnic niches developed by the Senegalese in small and precarious trade activities. The article emphasizes the benefits of adopting a comparative and diachronic approach and calls for future work on the factors shaping the role of networks. 相似文献
8.
Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma 总被引:1,自引:0,他引:1
Daniel J. Merk Jasmin Ohli Natalie D. Merk Venu Thatikonda Sorana Morrissy Melanie Schoof Susanne N. Schmid Luke Harrison Severin Filser Julia Ahlfeld Serap Erkek Kaamini Raithatha Thomas Andreska Marc Weißhaar Michael Launspach Julia E. Neumann Mehdi Shakarami Dennis Plenker Ulrich Schüller 《Developmental cell》2018,44(6):709-724.e6
9.
Chen Cao Jingni He Lauren Mak Deshan Perera Devin Kwok Jia Wang Minghao Li Tobias Mourier Stefan Gavriliuc Matthew Greenberg A Sorana Morrissy Laura K Sycuro Guang Yang Daniel C Jeffares Quan Long 《Molecular biology and evolution》2021,38(6):2660
DNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or “haplotypes.” However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics, and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here, we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools tailored to specific organismal systems, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of within-patient HIV populations previously unobserved in single position-based analysis. 相似文献
10.