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961.
Yukari Asai-Tajiri Koichiro Matsumoto Satoru Fukuyama Keiko Kan-o Takako Nakano Ken Tonai Tatsukuni Ohno Miyuki Azuma Hiromasa Inoue Yoichi Nakanishi 《Respiratory research》2014,15(1)
Background
CD86-CD28 interaction has been suggested as the principal costimulatory pathway for the activation and differentiation of naïve T cells in allergic inflammation. However, it remains uncertain whether this pathway also has an essential role in the effector phase. We sought to determine the contribution of CD86 on dendritic cells in the reactivation of allergen-specific Th2 cells.Methods
We investigated the effects of the downregulation of CD86 by short interfering RNAs (siRNAs) on Th2 cytokine production in the effector phase in vitro and on asthma phenotypes in ovalbumin (OVA)-sensitized and -challenged mice.Results
Treatment of bone marrow-derived dendritic cells (BMDCs) with CD86 siRNA attenuated LPS-induced upregulation of CD86. CD86 siRNA treatment impaired BMDCs’ ability to activate OVA-specific Th2 cells. Intratracheal administration of CD86 siRNA during OVA challenge downregulated CD86 expression in the airway mucosa. CD86 siRNA treatment ameliorated OVA-induced airway eosinophilia, airway hyperresponsiveness, and the elevations of OVA-specific IgE in the sera and IL-5, IL-13, and CCL17 in the bronchoalveolar lavage fluid, but not the goblet cell hyperplasia.Conclusion
These results suggest that local administration of CD86 siRNA during the effector phase ameliorates lines of asthma phenotypes. Targeting airway dendritic cells with siRNA suppresses airway inflammation and hyperresponsiveness in an experimental model of allergic asthma. 相似文献962.
Signatures of selection in sheep bred for resistance or susceptibility to gastrointestinal nematodes
Background
Gastrointestinal nematodes are one of the most serious causes of disease in domestic ruminants worldwide. There is considerable variation in resistance to gastrointestinal nematodes within and between sheep breeds, which appears to be due to underlying genetic diversity. Through selection of resistant animals, rapid genetic progress has been demonstrated in both research and commercial flocks. Recent advances in genome sequencing and genomic technologies provide new opportunities to understand the ovine host response to gastrointestinal nematodes at the molecular level, and to identify polymorphisms conferring nematode resistance.Results
Divergent lines of Romney and Perendale sheep, selectively bred for high and low faecal nematode egg count, were genotyped using the Illumina® Ovine SNP50 BeadChip. The resulting genome-wide SNP data were analysed for selective sweeps on loci associated with resistance or susceptibility to gastrointestinal nematode infection. Population differentiation using FST and Peddrift revealed sixteen regions, which included candidate genes involved in chitinase activity and the cytokine response. Two of the sixteen regions identified were contained within previously identified QTLs associated with nematode resistance.Conclusions
In this study we identified fourteen novel regions associated with resistance or susceptibility to gastrointestinal nematodes. Results from this study support the hypothesis that host resistance to internal nematode parasites is likely to be controlled by a number of loci of moderate to small effects.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-637) contains supplementary material, which is available to authorized users. 相似文献963.
Yurixhi Maldonado-López Pablo Cuevas-Reyes Gumersindo Sánchez-Montoya Ken Oyama Mauricio Quesada 《Arthropod-Plant Interactions》2014,8(4):241-251
Frequently, female plants allocate more resources to reproductive structures and defense-related secondary compounds in comparison with male plants that invest more resources to growth, reflecting trade-offs between reproduction, growth and defense. Therefore, differences in herbivory can be expected between genders. In this study, over two years, we analyzed the differences in plant chemical defense, nutritional quality, plant size and herbivory between genders in the dioecious tree, Spondias purpurea in a Mexican tropical dry forest. We estimated the total leaf area and the area consumed by folivory using a digital image of each leaf. The nutritional quality was estimated as water content, and the concentration of chlorophyll and total nonstructural carbohydrates. The secondary metabolites analyzed were total content of soluble phenolics, flavonoids, protein precipitation capacity of tannins, gallotannins, soluble proanthocyanidins, hydrolyzable tannins and ellagitannins. Our results differ from most of studies that analyze the differential herbivory patterns in dioecious plants. We found that female trees had higher levels of herbivory than male trees of S. purpurea. In the same way, female trees showed higher size and nutritional quality than males, while chemical defense was higher in male trees. The higher percentage of folivory in female trees of S. purpurea is associated with greater nutritional quality and lower chemical defenses. Our results show that male-biased herbivory might not be universal in dioecious species. Therefore, studies of fitness components affected by herbivory are necessary to understand the evolution of dioecy and the importance of herbivores as selective agents on breeding system features. 相似文献
964.
965.
966.
Jason Li Maria A. Doyle Isaam Saeed Stephen Q. Wong Victoria Mar David L. Goode Franco Caramia Ken Doig Georgina L. Ryland Ella R. Thompson Sally M. Hunter Saman K. Halgamuge Jason Ellul Alexander Dobrovic Ian G. Campbell Anthony T. Papenfuss Grant A. McArthur Richard W. Tothill 《PloS one》2014,9(4)
Targeted resequencing by massively parallel sequencing has become an effective and affordable way to survey small to large portions of the genome for genetic variation. Despite the rapid development in open source software for analysis of such data, the practical implementation of these tools through construction of sequencing analysis pipelines still remains a challenging and laborious activity, and a major hurdle for many small research and clinical laboratories. We developed TREVA (Targeted REsequencing Virtual Appliance), making pre-built pipelines immediately available as a virtual appliance. Based on virtual machine technologies, TREVA is a solution for rapid and efficient deployment of complex bioinformatics pipelines to laboratories of all sizes, enabling reproducible results. The analyses that are supported in TREVA include: somatic and germline single-nucleotide and insertion/deletion variant calling, copy number analysis, and cohort-based analyses such as pathway and significantly mutated genes analyses. TREVA is flexible and easy to use, and can be customised by Linux-based extensions if required. TREVA can also be deployed on the cloud (cloud computing), enabling instant access without investment overheads for additional hardware. TREVA is available at http://bioinformatics.petermac.org/treva/. 相似文献
967.
Hirotoki Ohkubo Yoshiya Ito Tsutomu Minamino Koji Eshima Ken Kojo Shin-ichiro Okizaki Mitsuhiro Hirata Masabumi Shibuya Masahiko Watanabe Masataka Majima 《PloS one》2014,9(8)
Liver repair after acute liver injury is characterized by hepatocyte proliferation, removal of necrotic tissue, and restoration of hepatocellular and hepatic microvascular architecture. Macrophage recruitment is essential for liver tissue repair and recovery from injury; however, the underlying mechanisms are unclear. Signaling through vascular endothelial growth factor receptor 1 (VEGFR1) is suggested to play a role in macrophage migration and angiogenesis. The aim of the present study was to examine the role of VEGFR1 in liver repair and sinusoidal reconstruction after hepatic ischemia/reperfusion (I/R). VEGFR1 tyrosine kinase knockout mice (VEGFR1 TK-/- mice) and wild-type (WT) mice were subjected to hepatic warm I/R, and the processes of liver repair and sinusoidal reconstruction were examined. Compared with WT mice, VEGFR1 TK-/- mice exhibited delayed liver repair after hepatic I/R. VEGFR1-expressing macrophages recruited to the injured liver showed reduced expression of epidermal growth factor (EGF). VEGFR1 TK-/- mice also showed evidence of sustained sinusoidal functional and structural damage, and reduced expression of pro-angiogenic factors. Treatment of VEGFR1 TK-/- mice with EGF attenuated hepatoceullar and sinusoidal injury during hepatic I/R. VEGFR1 TK-/- bone marrow (BM) chimeric mice showed impaired liver repair and sinusoidal reconstruction, and reduced recruitment of VEGFR1-expressing macrophages to the injured liver. VEGFR1-macrophages recruited to the liver during hepatic I/R contribute to liver repair and sinusoidal reconstruction. VEGFR1 activation is a potential therapeutic strategy for promoting liver repair and sinusoidal restoration after acute liver injury. 相似文献
968.
Akihito Tsubota Kaoru Mogushi Hideki Aizaki Ken Miyaguchi Keisuke Nagatsuma Hiroshi Matsudaira Tatsuya Kushida Tomomi Furihata Hiroshi Tanaka Tomokazu Matsuura 《PloS one》2014,9(5)
Despite advances in chronic hepatitis C treatment, a proportion of patients respond poorly to treatment. This study aimed to explore hepatic mRNA and microRNA signatures involved in hepatitis C treatment resistance. Global hepatic mRNA and microRNA expression profiles were compared using microarray data between treatment responses. Quantitative real-time polymerase chain reaction validated the gene signatures from 130 patients who were infected with hepatitis C virus genotype 1b and treated with pegylated interferon-alpha and ribavirin combination therapy. The correlation between mRNA and microRNA was evaluated using in silico analysis and in vitro siRNA and microRNA inhibition/overexpression experiments. Multivariate regression analysis identified that the independent variables IL28B SNP rs8099917, hsa-miR-122-5p, hsa-miR-17-5p, and MAP3K8 were significantly associated with a poor virologic response. MAP3K8 and miR-17-5p expression were inversely correlated with treatment response. Furthermore, miR-17-5p repressed HCV production by targeting MAP3K8. Collectively, the data suggest that several molecules and the inverse correlation between mRNA and microRNA contributed to a host genetic refractory hepatitis C treatment response. 相似文献
969.
Ken Murakami Masataka Kohno Masatoshi Kadoya Hidetake Nagahara Wataru Fujii Takahiro Seno Aihiro Yamamoto Ryo Oda Hiroyoshi Fujiwara Toshikazu Kubo Satoshi Morita Hiroshi Nakada Timothy Hla Yutaka Kawahito 《PloS one》2014,9(9)
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cellular processes, including proliferation, migration, and angiogenesis, through interaction with a family of five G protein–coupled receptors (S1P1–5). Some reports have implicated S1P as an important inflammatory mediator of the pathogenesis of airway inflammation, but the role of S1P3 in the pathogenesis of lung diseases is not completely understood. We used S1P3-deficient (knockout (KO)) mice to clarify the role of S1P3 receptor signaling in the pathogenesis of pulmonary inflammation and fibrosis using a bleomycin-induced model of lung injury. On the seventh day after bleomycin administration, S1P3 KO mice exhibited significantly less body weight loss and pulmonary inflammation than wild-type (WT) mice. On the 28th day, there was less pulmonary fibrosis in S1P3 KO mice than in WT mice. S1P3 KO mice demonstrated a 56% reduction in total cell count in bronchoalveolar lavage fluid (BALF) collected on the seventh day compared with WT mice; however, the differential white blood cell profiles were similar. BALF analysis on the seventh day showed that connective tissue growth factor (CTGF) levels were significantly decreased in S1P3 KO mice compared with WT mice, although no differences were observed in monocyte chemotactic protein-1 (MCP-1) or transforming growth factor β1 (TGF-β1) levels. Finally, S1P levels in BALF collected on the 7th day after treatment were not significantly different between WT and S1P3 KO mice. Our results indicate that S1P3 receptor signaling plays an important role in pulmonary inflammation and fibrosis and that this signaling occurs via CTGF expression. This suggests that this pathway might be a therapeutic target for pulmonary fibrosis. 相似文献
970.
Yutaka Terada Nobutaka Matsui Keita Noguchi Ryusei Kuwata Hiroshi Shimoda Takehisa Soma Masami Mochizuki Ken Maeda 《PloS one》2014,9(9)
Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3′-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5′-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently. 相似文献