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111.
Pin Lu Sandrine Prost Helen Caldwell Jonathan D. Tugwood Graham R. Betton David J. Harrison 《Mammalian genome》2007,18(9):617-626
Polyploidisation in hepatocytes has been associated with many physiologic and pathologic processes such as proliferation, metabolism, regeneration, aging, and cancer. We studied gene expression patterns in hepatocytes of different ploidy. Primary hepatocytes were obtained from mice of different ages: young (4-6 weeks old), adult (8-10 weeks old), and older (22-24 weeks old). Diploid (2N), tetraploid (4N), and octoploid (8N) hepatocytes were isolated for studies using a high-density mouse genome microarray. No major changes of gene expression patterns between hepatocytes of different ploidy were found. Fifty genes were identified as differentially expressed in the diploid and tetraploid populations, but the changes were less than twofold either way. Four genes (Gas2, Igfbp2, Nr1i3, and Ccne2) were differentially expressed in tetraploid and octoploid cells. This was confirmed in two age groups, "adult" and "older," but once again the factors were less than twofold and the expressions of Gas2 and Igfbp2 were more different between age groups than between ploidy classes. Our results show that polyploid hepatocytes are stable and "normal" without aberrant gene expression, unlike what is thought for cancer cells. By contrast to megakaryocytes, hepatocyte polyploidisation is not a differentiation step associated with major changes in gene expression. Our data support the hypothesis that hepatocyte polyploidisation is a protective mechanism against oxidative stress that occurs via a controlled process throughout growth and aging where binucleation is important. 相似文献
112.
Ágnes Baross Allen D Delaney H Irene Li Tarun Nayar Stephane Flibotte Hong Qian Susanna Y Chan Jennifer Asano Adrian Ally Manqiu Cao Patricia Birch Mabel Brown-John Nicole Fernandes Anne Go Giulia Kennedy Sylvie Langlois Patrice Eydoux JM Friedman Marco A Marra 《BMC bioinformatics》2007,8(1):1-18
Background
Genomic deletions and duplications are important in the pathogenesis of diseases, such as cancer and mental retardation, and have recently been shown to occur frequently in unaffected individuals as polymorphisms. Affymetrix GeneChip whole genome sampling analysis (WGSA) combined with 100 K single nucleotide polymorphism (SNP) genotyping arrays is one of several microarray-based approaches that are now being used to detect such structural genomic changes. The popularity of this technology and its associated open source data format have resulted in the development of an increasing number of software packages for the analysis of copy number changes using these SNP arrays.Results
We evaluated four publicly available software packages for high throughput copy number analysis using synthetic and empirical 100 K SNP array data sets, the latter obtained from 107 mental retardation (MR) patients and their unaffected parents and siblings. We evaluated the software with regards to overall suitability for high-throughput 100 K SNP array data analysis, as well as effectiveness of normalization, scaling with various reference sets and feature extraction, as well as true and false positive rates of genomic copy number variant (CNV) detection.Conclusion
We observed considerable variation among the numbers and types of candidate CNVs detected by different analysis approaches, and found that multiple programs were needed to find all real aberrations in our test set. The frequency of false positive deletions was substantial, but could be greatly reduced by using the SNP genotype information to confirm loss of heterozygosity. 相似文献113.
Schilders G Raijmakers R Malmegrim KC Vande Walle L Saelens X Vree Egberts W van Venrooij WJ Vandenabeele P Pruijn GJ 《Arthritis research & therapy》2007,9(1):R12
Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive
systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'→5' exoribonucleases that
functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly
in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75,
is cleaved during apoptosis. PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75
cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by
caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal
part of the protein at Asp369 (IILD369↓G), and at least a fraction of the resulting N-terminal fragments of PM/Scl-75 remains associated with the exosome. Finally,
the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed. 相似文献
114.
Protein optimization is a major focus of the biotech and pharmaceutical industry. Various in vitro technologies have been developed to accelerate protein evolution and to achieve protein optimization of functional characteristics such as substrate specificity, enzymatic activity and thermostability. The chicken B cell line DT40 diversifies its immunoglobulin (Ig) gene by gene conversion and somatic hypermutation. This machinery can be directed to almost any gene inserted into the Ig locus. Enormously diverse protein libraries of any gene of interest can be quickly generated in DT40 by utilizing random shuffling of complex genetic domains (gene conversion) and by the introduction of novel non-templated genetic information (random mutagenesis). The unique characteristics of the chicken cell line DT40 make it a powerful in-cell diversification system to improve proteins of interest within living cells. One essential advantage of the DT40 protein optimization approach is the fact that variants are generated within an in-cell system thus allowing the direct screening for desired features in the context of intracellular networks. Utilizing specially designed selection strategies, such as the powerful fluorescent protein technology, enables the reliable identification of protein variants exhibiting the most desirable traits. Thus, DT40 is well positioned as a biotechnological tool to generate optimized proteins by applying a powerful combination of gene specific hypermutation, gene conversion and mutant selection. 相似文献
115.
R Moriggi Jr HS Di Mauro SC Dias JM Matos MB Urtado NF Camar?o IV Sousa Neto DC Nascimento RA Tibana CO Assump??o J Prestes CB Urtado 《Biology of sport / Institute of Sport》2015,32(4):289-294
Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances. 相似文献
116.
JI Priego AG Lucas-Cuevas I Aparicio JV Giménez JM Cortell-Tormo P Pérez-Soriano 《Biology of sport / Institute of Sport》2015,32(3):219-223
The use of graduated compression stockings (GCS) in sport has been increasing in the last years due to their potential positive effects for athletes. However, there is little evidence to support whether these types of garments actually improve cardiorespiratory performance. The aim of this study was to examine the cardiorespiratory responses of GCS during running after three weeks of regular use. Twenty recreational runners performed three tests on different days: test 1) – a 5-min maximal effort run in order to determine the participants’ maximal aerobic speed; and tests 2) and 3) – a fatigue running test of 30 minutes at 80% of their maximal aerobic speed with either GCS or PLACEBO stockings at random. Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen consumption, relative carbon dioxide production, ventilatory equivalents for oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in the laboratory, the participants trained with the randomly assigned stockings (GCS or PLACEBO) for three weeks. No significant differences between GCS and PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the present study provides evidence that running with GCS for three weeks does not influence cardiorespiratory parameters in recreational runners. 相似文献
117.
Lung fibrosis is an ultimate consequence of pulmonary oxygen toxicity in human and animal models. Excessive production and deposition of extracellular matrix proteins, e.g., collagen-I, is the most important feature of pulmonary fibrosis in hyperoxia-induced lung injury. In this study, we investigated the roles of RhoA and reactive oxygen species (ROS) in collagen-I synthesis in hyperoxic lung fibroblasts and in a mouse model of oxygen toxicity. Exposure of human lung fibroblasts to hyperoxia resulted in RhoA activation and an increase in collagen-I synthesis and cell proliferation. Inhibition of RhoA by C3 transferase CT-04, dominant-negative RhoA mutant T19N, or RhoA siRNA prevented hyperoxia-induced collagen-I synthesis. The constitutively active RhoA mutant Q63L mimicked the effect of hyperoxia on collagen-I expression. Moreover, the Rho kinase inhibitor Y27632 inhibited collagen-I synthesis in hyperoxic lung fibroblasts and fibrosis in mouse lungs after oxygen toxicity. Furthermore, the ROS scavenger tiron attenuated hyperoxia-induced increases in RhoA activation and collagen-I synthesis in lung fibroblasts and mouse lungs after oxygen toxicity. More importantly, we found that hyperoxia induced separation of guanine nucleotide dissociation inhibitor (GDI) from RhoA in lung fibroblasts and mouse lungs. Further, tiron prevented the separation of GDI from RhoA in hyperoxic lung fibroblasts and mouse lungs with oxygen toxicity. Together, these results indicate that ROS-induced separation of GDI from RhoA leads to RhoA activation with oxygen toxicity. ROS-dependent RhoA activation is responsible for the increase in collagen-I synthesis in hyperoxic lung fibroblasts and mouse lungs. 相似文献
118.
Protein misfolding and aggregation are key pathological features observed in numerous neurodegenerative diseases, including the misfolding of α-synuclein (α-syn) in Parkinson's disease (PD) and β-amyloid in Alzheimer's disease. While this phenomenon is widely observed, the etiology and progression of these diseases is not fully understood. Furthermore, there is a lack of therapeutic treatments directed at halting the progression and neurodegeneration associated with these diseases. This demands a need for an inexpensive, easy to manipulate multicellular organism to conduct both genetic and chemical screens within to identify factors that may play a pivotal role in the pathology of these diseases. Herein, we describe methodology involved in identifying genetic modifiers of α-syn misfolding and toxicity in the nematode roundworm, Caenorhabditis elegans. Transgenic nematodes engineered to express human α-syn in the body wall muscles or dopaminergic (DA) neurons result in formation of cytoplasmic puncta or DA neurodegeneration, respectively. Using these models, we describe the use of RNA interference (RNAi) and transgenic gene expression to functionally elucidate potential therapeutic gene targets that alter α-syn misfolding and DA neurotoxicity. 相似文献
119.
120.
Christopher B Arena Michael B Sano John H Rossmeisl Jr John L Caldwell Paulo A Garcia Marissa Nichole Rylander Rafael V Davalos 《Biomedical engineering online》2011,10(1):1-21