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81.
Jembrana disease virus Tat can regulate human immunodeficiency virus (HIV) long terminal repeat-directed gene expression and can substitute for HIV Tat in viral replication 下载免费PDF全文
Jembrana disease virus (JDV) is a bovine lentivirus genetically similar to bovine immunodeficiency virus; it causes an acute and sometimes fatal disease in infected animals. This virus carries a very potent Tat that can strongly activate not only its own long terminal repeat (LTR) but also the human immunodeficiency virus (HIV) LTR. In contrast, HIV Tat cannot reciprocally activate the JDV LTR (H. Chen, G. E. Wilcox, G. Kertayadnya, and C. Wood, J. Virol. 73:658-666, 1999). This indicates that in transactivation JDV Tat may utilize a mechanism similar to but not the same as that of the HIV Tat. To further study the similarity of JDV and HIV tat in transactivation, we first tested the responses of a series of HIV LTR mutants to the JDV Tat. Cross-transactivation of HIV LTR by JDV Tat was impaired by mutations that disrupted the HIV type 1 transactivation response element (TAR) RNA stem-loop structure. Our results demonstrated that JDV Tat, like HIV Tat, transactivated the HIV LTR at least partially in a TAR-dependent manner. However, the sequence in the loop region of TAR was not as critical for the function of JDV Tat as it was for HIV Tat. The competitive inhibition of Tat-induced transactivation by the truncated JDV or HIV Tat, which consisted only of the activation domain, suggested that similar cellular factors were involved in both JDV and HIV Tat-induced transactivation. Based on the one-round transfection assay with HIV tat mutant proviruses, the cotransfected JDV tat plasmid can functionally complement the HIV tat defect. To further characterize the effect of JDV Tat on HIV, a stable chimeric HIV carrying the JDV tat gene was generated. This chimeric HIV replicated in a T-cell line, C8166, and in peripheral blood mononuclear cells, which suggested that JDV Tat can functionally substitute for HIV Tat. Further characterization of this chimeric virus will help to elucidate how JDV Tat functions and to explain the differences between HIV and JDV Tat transactivation. 相似文献
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John N. Kittinger Lida T. Teneva Haruko Koike Kostantinos A. Stamoulis Daniela S. Kittinger Kirsten L. L. Oleson Eric Conklin Mahana Gomes Bart Wilcox Alan M. Friedlander 《PloS one》2015,10(8)
Ocean and coastal ecosystems provide critical fisheries, coastal protection, and cultural benefits to communities worldwide, but these services are diminishing due to local and global threats. In response, place-based strategies involve communities and resource users in management have proliferated. Here, we present a transferable community-based approach to assess the social and ecological factors affecting resource sustainability and food security in a small-scale, coral reef fishery. Our results show that this small-scale fishery provides large-scale benefits to communities, including 7,353 ± 1547 kg yr-1 (mean ± SE) of seafood per year, equating to >30,000 meals with an economic value of $78,432. The vast majority of the catch is used for subsistence, contributing to community food security: 58% is kept, 33.5% is given away, and 8.5% is sold. Our spatial analysis assesses the geographic distribution of community beneficiaries from the fishery (the “food shed” for the fishery), and we document that 20% of seafood procured from the fishery is used for sociocultural events that are important for social cohesion. This approach provides a method for assessing social, economic, and cultural values provided by small-scale food systems, as well as important contributions to food security, with significant implications for conservation and management. This interdisciplinary effort aims to demonstrate a transferable participatory research approach useful for resource-dependent communities as they cope with socioeconomic, cultural, and environmental change. 相似文献
85.
Tompson SW Bacino CA Safina NP Bober MB Proud VK Funari T Wangler MF Nevarez L Ala-Kokko L Wilcox WR Eyre DR Krakow D Cohn DH 《American journal of human genetics》2010,87(5):708-712
Fibrochondrogenesis is a severe, autosomal-recessive, short-limbed skeletal dysplasia. In a single case of fibrochondrogenesis, whole-genome SNP genotyping identified unknown ancestral consanguinity by detecting three autozygous regions. Because of the predominantly skeletal nature of the phenotype, the 389 genes localized to the autozygous intervals were prioritized for mutation analysis by correlation of their expression with known cartilage-selective genes via the UCLA Gene Expression Tool, UGET. The gene encoding the α1 chain of type XI collagen (COL11A1) was the only cartilage-selective gene among the three candidate intervals. Sequence analysis of COL11A1 in two genetically independent fibrochondrogenesis cases demonstrated that each was a compound heterozygote for a loss-of-function mutation on one allele and a mutation predicting substitution for a conserved triple-helical glycine residue on the other. The parents who were carriers of missense mutations had myopia. Early-onset hearing loss was noted in both parents who carried a loss-of-function allele, suggesting COL11A1 as a locus for mild, dominantly inherited hearing loss. These findings identify COL11A1 as a locus for fibrochondrogenesis and indicate that there might be phenotypic manifestations among carriers. 相似文献
86.
Yang R Wilcox DM Haasch DL Jung PM Nguyen PT Voorbach MJ Doktor S Brodjian S Bush EN Lin E Jacobson PB Collins CA Landschulz KT Trevillyan JM Rondinone CM Surowy TK 《The Journal of biological chemistry》2007,282(31):22765-22774
The c-Jun N-terminal kinases (JNKs) have been implicated in the development of insulin resistance, diabetes, and obesity. Genetic disruption of JNK1, but not JNK2, improves insulin sensitivity in diet-induced obese (DIO) mice. We applied RNA interference to investigate the specific role of hepatic JNK1 in contributing to insulin resistance in DIO mice. Adenovirus-mediated delivery of JNK1 short-hairpin RNA (Ad-shJNK1) resulted in almost complete knockdown of hepatic JNK1 protein without affecting JNK1 protein in other tissues. Liver-specific knockdown of JNK1 resulted in significant reductions in circulating insulin and glucose levels, by 57 and 16%, respectively. At the molecular level, JNK1 knockdown mice had sustained and significant increase of hepatic Akt phosphorylation. Furthermore, knockdown of JNK1 enhanced insulin signaling in vitro. Unexpectedly, plasma triglyceride levels were robustly elevated upon hepatic JNK1 knockdown. Concomitantly, expression of proliferator-activated receptor gamma coactivator 1 beta, glucokinase, and microsomal triacylglycerol transfer protein was increased. Further gene expression analysis demonstrated that knockdown of JNK1 up-regulates the hepatic expression of clusters of genes in glycolysis and several genes in triglyceride synthesis pathways. Our results demonstrate that liver-specific knockdown of JNK1 lowers circulating glucose and insulin levels but increases triglyceride levels in DIO mice. 相似文献
87.
The influence of material property and morphological parameters on specimen-specific finite element models of porcine vertebral bodies 总被引:4,自引:0,他引:4
Wilcox RK 《Journal of biomechanics》2007,40(3):669-673
The use of finite element (FE) methods in spinal research is increasing, but there is only limited information available on the influence of different input parameters on the model predictions. The aim of this study was to investigate the role of these parameters in FE models of the vertebral body. Experimental tests were undertaken on porcine lumbar vertebral bodies and scans of the specimens were used to create specimen-specific FE models. Three models were created for each specimen with combinations of generic and specimen-specific parameters. Stiffness and strength predictions were also made directly from the specimen trabecular bone volume fraction (BVF) and cross-sectional area (CSA). The agreement between the experimental results and the FE models with generic morphology was poorer (concordance coefficients = 0.058, 0.125 for stiffness, strength) than those made from the BVF and CSA (concordance coefficients = 0.638, 0.609). The greatest levels of agreement were found with the morphologically specific models including element-specific material properties (concordance coefficients = 0.881, 0.752). This indicates that highly specific models, both in terms of morphology and bone quality, are necessary if the FE tool is to be used effectively for spinal research and clinical practice. 相似文献
88.
Palm F Onozato ML Luo Z Wilcox CS 《American journal of physiology. Heart and circulatory physiology》2007,293(6):H3227-H3245
Asymmetric (N(G),N(G))-dimethylarginine (ADMA) inhibits nitric oxide (NO) synthases (NOS). ADMA is a risk factor for endothelial dysfunction, cardiovascular mortality, and progression of chronic kidney disease. Two isoforms of dimethylarginine dimethylaminohydrolase (DDAH) metabolize ADMA. DDAH-1 is the predominant isoform in the proximal tubules of the kidney and in the liver. These organs extract ADMA from the circulation. DDAH-2 is the predominant isoform in the vasculature, where it is found in endothelial cells adjacent to the cell membrane and in intracellular vesicles and in vascular smooth muscle cells among the myofibrils and the nuclear envelope. In vivo gene silencing of DDAH-1 in the rat and DDAH +/- mice both have increased circulating ADMA, whereas gene silencing of DDAH-2 reduces vascular NO generation and endothelium-derived relaxation factor responses. DDAH-2 also is expressed in the kidney in the macula densa and distal nephron. Angiotensin type 1 receptor activation in kidneys reduces the expression of DDAH-1 but increases the expression of DDAH-2. This rapidly evolving evidence of isoform-specific distribution and regulation of DDAH expression in the kidney and blood vessels provides potential mechanisms for nephron site-specific regulation of NO production. In this review, the recent advances in the regulation and function of DDAH enzymes, their roles in the regulation of NO generation, and their possible contribution to endothelial dysfunction in patients with cardiovascular and kidney diseases are discussed. 相似文献
89.
Sébastien JD Giroux Celmar Alves-Leiva Yann Lécluse Patrick Martin Olivier Albagli Isabelle Godin 《BMC developmental biology》2007,7(1):79
Background
Hematopoietic development in vertebrate embryos results from the sequential contribution of two pools of precursors independently generated. While intra-embryonic precursors harbour the features of hematopoietic stem cells (HSC), precursors formed earlier in the yolk sac (YS) display limited differentiation and self-renewal potentials. The mechanisms leading to the generation of the precursors in both sites are still largely unknown, as are the molecular basis underlying their different potential. A possible approach to assess the role of candidate genes is to transfer or modulate their expression/activity in both sites. We thus designed and compared transduction protocols to target either native extra-embryonic precursors, or hematopoietic precursors. 相似文献90.
Brian S. Roberts Andrew A. Hardigan Marie K. Kirby Meredith B. Fitz-Gerald C.?Mel Wilcox Robert P. Kimberly Richard M. Myers 《Nucleic acids research》2015,43(21):e145
Highly abundant microRNAs (miRNAs) in small RNA sequencing libraries make it difficult to obtain efficient measurements of more lowly expressed species. We present a new method that allows for the selective blocking of specific, abundant miRNAs during preparation of sequencing libraries. This technique is specific with little off-target effects and has no impact on the reproducibility of the measurement of non-targeted species. In human plasma samples, we demonstrate that blocking of highly abundant hsa-miR-16–5p leads to improved detection of lowly expressed miRNAs and more precise measurement of differential expression overall. Furthermore, we establish the ability to target a second abundant miRNA and to multiplex the blocking of two miRNAs simultaneously. For small RNA sequencing, this technique could fill a similar role as do ribosomal or globin removal technologies in messenger RNA sequencing. 相似文献