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171.
Pranav Kumar Robert Lodge Frédéric Raymond Jean‐François Ritt Pascal Jalaguier Jacques Corbeil Marc Ouellette Michel J. Tremblay 《Molecular microbiology》2013,89(3):565-582
Drug resistance is a major public health challenge in leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV‐1 co‐infections. We have delineated the mechanism of cell death induced by the HIV‐1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to further study Nelfinavir–Leishmania interactions, we selected Nelfinavir‐resistant axenic amastigotes in vitro and characterized them. RNA expression profiling analyses and comparative genomic hybridizations of closely related Leishmania species were used as a screening tool to compare Nelfinavir‐resistant and ‐sensitive parasites in order to identify candidate genes involved in drug resistance. Microarray analyses of Nelfinavir‐resistant and ‐sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters. Transporter assays using radiolabelled Nelfinavir suggest a greater drug accumulation in the resistant parasites and in a time‐dependent manner. Furthermore, high‐resolution electron microscopy and measurements of intracellular polyphosphate levels showed an increased number of cytoplasmic vesicular compartments known as acidocalcisomes in Nelfinavir‐resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in drug‐induced intracellular vesicles. 相似文献
172.
Caroline Michot Asmaa Mamoune Joseph Vamecq Mai Thao Viou Lu-Sheng Hsieh Eric Testet Jeanne Lainé Laurence Hubert Anne-Frédérique Dessein Monique Fontaine Chris Ottolenghi Laetitia Fouillen Karim Nadra Etienne Blanc Jean Bastin Sophie Candon Mario Pende Arnold Munnich Pascale de Lonlay 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):2103-2114
173.
Rujuan?DaiEmail author Savannah?McReynolds Tanya?LeRoith Bettina?Heid Zhihong?Liang Sattar?Ansar?AhmedEmail author 《Biology of sex differences》2013,4(1):19
<div class="AbstractSection" id="ASec1">
Background
A majority of autoimmune diseases, including systemic lupus erythematosus (SLE), occur predominantly in females. Recent studies have identified specific dysregulated microRNAs (miRNAs) in both human and murine lupus, implying an important contribution of these miRNAs to lupus pathogenesis. However, to date, there is no study that examined sex differences in miRNA expression in immune cells as a plausible basis for sex differences in autoimmune disease. This study addresses this aspect in NZB/WF1 mice, a classical murine lupus model with marked female bias, and further investigates estrogen regulation of lupus-associated miRNAs.div><div class="AbstractSection" id="ASec2">Methods
The Taqman miRNA assay system was used to quantify the miRNA expression in splenocytes from male and female NZB/WF1 mice at 17–18, 23, and 30 weeks (wks) of age. To evaluate potential estrogen's effect on lupus-associated miRNAs, 6-wk-old NZB/WF1 male mice were orchidectomized and surgically implanted with empty (placebo) or estrogen implants for 4 and 26 wks, respectively. To assess the lupus status in the NZB/WF1 mice, serum anti-dsDNA autoantibody levels, proteinuria, and renal histological changes were determined.div><div class="AbstractSection" id="ASec3">Results
The sex differences in the expression of lupus-associated miRNAs, including the miR-182-96-183 cluster, miR-155, miR-31, miR-148a, miR-127, and miR-379, were markedly evident after the onset of lupus, especially at 30 wks of age when female NZB/WF1 mice manifested moderate to severe lupus when compared to their male counterparts. Our limited data also suggested that estrogen treatment increased the expression of aforementioned lupus-associated miRNAs, with the exception of miR-155, in orchidectomized male NZB/WF1 mice to a similar level in age-matched intact female NZB/WF1 mice. It is noteworthy that orchiectomy, itself, did not affect the expression of lupus-associated miRNAs.div><div class="AbstractSection" id="ASec4">Conclusion
To our knowledge, this is the first study that demonstrated sex differences in the expression of lupus-associated miRNAs in splenocytes, especially in the context of autoimmunity. The increased expression of lupus-associated miRNA in female NZB/WF1 mice and conceivably in estrogen-treated orchidectomized male NZB/WF1 mice was associated with lupus manifestation. The notable increase of lupus-associated miRNAs in diseased, female NZB/WF1 mice may be a result of both lupus manifestation and the female gender.div> 相似文献174.
Moh’d A Salameh Evette S Radisky 《International Journal of Biochemistry and Molecular Biology》2013,4(3):129-139
Thirty five years ago mesotrypsin was first isolated from the human pancreas. It was described as a minor trypsin isoform with the remarkable property of near total resistance to biological trypsin inhibitors. Another unusual feature of mesotrypsin was discovered later, when it was found that mesotrypsin has defective affinity toward many protein substrates of other trypsins. As the younger sibling of the two major trypsins secreted by the pancreas, cationic and the anionic trypsin, it has been speculated to represent an evolutionary waste with no apparent function. We know now that mesotrypsin is functionally very different from the other trypsins, with novel substrate specificity that hints at distinct physiological functions. Recently, evidence has begun to emerge implicating mesotrypsin in direct involvement in cancer progression. This review will explore the biochemical characteristics of mesotrypsin and structural insights into its specificity, function, and inhibition. 相似文献
175.
176.
Adam Ahanchédé José E. F. Alfaya L. W. Andersen Didier Azam Ma. Anita M. Bautista Anne‐Laure Besnard Gregorio Bigatti Anthony Bouétard Marie‐Agnès Coutellec Eben‐Ezer B. K. Ewédjè Reiko Fuseya Ricardo GarcÍa‐Jiménez M. Haratian Olivier J. Hardy L.‐E. Holm Casey W. Hoy Eriko Koshimizu V. Loeschcke Violeta López‐Márquez Carlos A. Machado Annie Machordom C. Marchi Andrew P. Michel Claire Micheneau Omprakash Mittapalli Takahiro Nagai Nobuaki Okamoto Ying Pan F. Panitz N. Safaie Takashi Sakamoto B. Sharifnabi En‐Wei Tian Hui Yu 《Molecular ecology resources》2013,13(1):158-159
This article documents the addition of 83 microsatellite marker loci and 96 pairs of single‐nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Bembidion lampros, Inimicus japonicus, Lymnaea stagnalis, Panopea abbreviata, Pentadesma butyracea, Sycoscapter hirticola and Thanatephorus cucumeris (anamorph: Rhizoctonia solani). These loci were cross‐tested on the following species: Pentadesma grandifolia and Pentadesma reyndersii. This article also documents the addition of 96 sequencing primer pairs and 88 allele‐specific primers or probes for Plutella xylostella. 相似文献
177.
Karine Loridon Concetta Burgarella Nathalie Chantret Frédéric Martins Jérôme Gouzy Jean‐Marie Prospéri Joëlle Ronfort 《Molecular ecology resources》2013,13(1):84-95
Extensive genomic resources are available in the model legume Medicago truncatula. Here, we present the discovery and design of the first array of single‐nucleotide polymorphism (SNP) markers in M. truncatula through large‐scale Sanger resequencing of genomic fragments spanning the genome, in a diverse panel of 16 M. truncatula accessions. Both anonymous fragments and fragments targeting candidate genes for flowering phenology and symbiosis were surveyed for nucleotide variation in almost 230 kb of unique genomic regions. A set of 384 SNP markers was designed for an Illumina's GoldenGate assay, genotyped on a collection of 192 inbred lines (CC192) representing the geographical range of the species and used to survey the diversity of two natural populations. Finally, 86% of the tested SNPs were of high quality and exhibited polymorphism in the CC192 collection. Even at the population level, we detected polymorphism for more than 50% of the selected SNPs. Analysis of the allele frequency spectrum in the CC192 showed a reduced ascertainment bias, mostly limited to very rare alleles (frequency <0.01). The substantial polymorphism detected at the species and population levels, the high marker quality and the potential to survey large samples of individuals make this set of SNP markers a valuable tool to improve our understanding of the effect of demographic and selective factors that shape the natural genetic diversity within the selfing species Medicago truncatula. 相似文献
178.
Delphine Mirebeau-Prunier Soazig Le Pennec Caroline Jacques Jean-Fred Fontaine Naig Gueguen Nathalie Boutet-Bouzamondo Audrey Donnart Yves Malthièry Frédérique Savagner 《PloS one》2013,8(3)
Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis. 相似文献
179.
The use of antibodies to treat neurodegenerative diseases has undergone rapid development in the past decade. To date, immunotherapeutic approaches to Alzheimer’s disease have mostly targeted amyloid beta as it is a secreted protein that can be found in plasma and CSF and is consequently accessible to circulating antibodies. Few recent publications have suggested the utility of treatment of tau pathology with monoclonal antibodies to tau. Our laboratory has begun a systematic study of different classes of tau monoclonal antibodies using mutant P301L mice. Three or seven months old mutant tau mice were inoculated weekly with tau monoclonal antibodies at a dose of 10 mg/Kg, until seven or ten months of age were reached respectively. Our data strongly support the notion that in P301L animals treated with MC1, a conformational monoclonal antibody specific for PHF-tau, the rate of development of tau pathology is effectively reduced, while injecting DA31, a high affinity tau sequence antibody, does not exert such benefit. MC1 appears superior to DA31 in overall effects, suggesting that specificity is more important than affinity in therapeutic applications. Unfortunately the survival rate of the P301L treated mice was not improved when immunizing either with MC1 or PHF1, a high affinity phospho-tau antibody previously reported to be efficacious in reducing pathological tau. These data demonstrate that passive immunotherapy in mutant tau models may be efficacious in reducing the development of tau pathology, but a great deal of work remains to be done to carefully select the tau epitopes to target. 相似文献
180.
Kayigan Wilson d’Almeida Dominique Pateron Gérald Kierzek Bertrand Renaud Caroline Semaille Pierre de Truchis Fran?ois Simon Judith Leblanc France Lert Stéphane Le Vu Anne-Claude Crémieux 《PloS one》2013,8(4)