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Parkinson disease (PD) is a common neurodegenerative disorder caused by environmental and genetic factors. We have previously shown linkage of PD to chromosome 8p. Subsequently, fibroblast growth factor 20 (FGF20) at 8p21.3-22 was identified as a risk factor in several association studies. To identify the risk-conferring polymorphism in FGF20, we performed genetic and functional analysis of single-nucleotide polymorphisms within the gene. In a sample of 729 nuclear families with 1089 affected and 1165 unaffected individuals, the strongest evidence of association came from rs12720208 in the 3' untranslated region of FGF20. We show in several functional assays that the risk allele for rs12720208 disrupts a binding site for microRNA-433, increasing translation of FGF20 in vitro and in vivo. In a cell-based system and in PD brains, this increase in translation of FGF20 is correlated with increased alpha-synuclein expression, which has previously been shown to cause PD through both overexpression and point mutations. We suggest a novel mechanism of action for PD risk in which the modulation of the susceptibility gene's translation by common variations interfere with the regulation mechanisms of microRNA. We propose this is likely to be a common mechanism of genetic modulation of individual susceptibility to complex disease.  相似文献   
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Wastewaters generated during mining and processing of metal sulfide ores are often acidic (pH < 3) and can contain significant concentrations of nitrate, nitrite, and ammonium from nitrogen based explosives. In addition, wastewaters from sulfide ore treatment plants and tailings ponds typically contain large amounts of inorganic sulfur compounds, such as thiosulfate and tetrathionate. Release of these wastewaters can lead to environmental acidification as well as an increase in nutrients (eutrophication) and compounds that are potentially toxic to humans and animals. Waters from cyanidation plants for gold extraction will often conjointly include toxic, sulfur containing thiocyanate. More stringent regulatory limits on the release of mining wastes containing compounds such as inorganic sulfur compounds, nitrate, and thiocyanate, along the need to increase production from sulfide mineral mining calls for low cost techniques to remove these pollutants under ambient temperatures (approximately 8 °C). In this study, we used both aerobic and anaerobic continuous cultures to successfully couple inorganic sulfur compound (i.e. thiosulfate and thiocyanate) oxidation for the removal of nitrogenous compounds under neutral to acidic pH at the low temperatures typical for boreal climates. Furthermore, the development of the respective microbial communities was identified over time by DNA sequencing, and found to contain a consortium including populations aligning within Flavobacterium, Thiobacillus, and Comamonadaceae lineages. This is the first study to remediate mining waste waters by coupling autotrophic thiocyanate oxidation to nitrate reduction at low temperatures and acidic pH by means of an identified microbial community.  相似文献   
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Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factorkappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.  相似文献   
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针对目前粮食仓贮熏蒸剂(即磷化氢)防虫不防霉,且施用时对环境和操作人员均存在安全隐患的现状,为将具有自主知识产权的纯天然驱虫抗霉复合精油产品很好地应用于仓储领域,一款新型仓贮超声雾化熏蒸装置被设计研制,并在国家级标准粮库微缩模型(1∶200)中进行相关功能技术参数测定。结果显示,样机在常温下能连续工作48h,远大于实际所需要的工作时间;样品雾化后,工作区中分布的雾滴粒径为几个微米级;GC-MS分析证明雾化后复合精油的组分种类、比例及功效组分浓度没有改变,就整体而言具有一定的纯化作用;雾化的精油量与功率和时间均呈良好线性关系。上述数据说明,所研制的超声雾化装置完全适用于新型防虫抗霉复合精油的雾化,实际应用时若配合仓库鼓风系统雾化效果会更好。  相似文献   
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三峡水库蓄水初期鱼体汞含量及其水生食物链累积特征   总被引:3,自引:0,他引:3  
余杨  王雨春  周怀东  高博  赵高峰 《生态学报》2013,33(13):4059-4067
于2011-2012年在三峡库区干流水域及7条典型支流采集了11种鱼类样品,以稳定同位素(δ13C和δ15N)营养等级分析为基础,研究了三峡水库蓄水后的鱼类汞含量水平及其食物链累积特征.结果表明,库区鱼类(以鲤为例)平均总汞含量为57.1 μg/kg,与蓄水前鱼体总汞水平相当,但在库区不同水域鱼体总汞含量差异显著:干流入库水域(洛碛断面)鱼体总汞含量平均值为88.0μg/kg,显著高于水库腹区水域(巫山断面)的平均值43.1μg/kg.稳定同位素分析表明,库区支流鱼体的δ13C范围为-22.08‰--28.92‰,大于干流鱼体的δ13C范围(-23.11‰--26.87‰),表明支流鱼类的食物来源具有更明显的湖沼型特征.同时,支流鱼类食物链上汞的累积放大效率显著高于干流水域.水文水动力差异可能是库区内汞累积等生态过程存在空间差异的重要原因.  相似文献   
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水浮莲对水稻竞争效应、产量与土壤养分的影响   总被引:1,自引:0,他引:1  
为了解入侵植物水浮莲在稻田生产中的扩散规律和对水稻农业性状的影响,通过田间水稻田实验,按照de Wit 取代试验方法和添加系列设计方法研究水浮莲与水稻(云稻2 号)混种对植株形态和生物量影响、种间竞争效应、水稻产量以及对土壤养分的影响。结果表明,混种条件下水浮莲母株株高、分蘖数、生物量和开花株数均受到水稻的明显抑制,受到的抑制率显著高于其对水稻的抑制率。水浮莲的种间竞争大于种内竞争(RY 小于1.0)而水稻的种内竞争大于种间竞争(RY 大于1.0),水浮莲混种比例大于和等于1:1 时(RYT大于1.0)与水稻不存在竞争作用,而小于1:1时(RYT 小于1.0)其存在着竞争作用,水浮莲对水稻的竞争力(CB 小于0)小于水稻。混种条件下水稻有效穗数和产量有明显提高,增产比例为3.54%-13.38%。生长过程中水浮莲对土壤钾、磷元素消耗大于水稻,而有机质和氮元素消耗小于水稻;混种条件下水稻明显降低水浮莲对土壤养分消耗,且二者在土壤养分上没有竞争关系。所有这些表明,入侵稻田的水浮莲与水稻生长过程中其形态、生物量等方面都处于劣势,而且一定的水浮莲密度有利于抑制水浮莲对土壤养分的消耗和促进水稻生长繁殖及其产量的提高,因此为满足饲料利用和环境净化,建议在正常耕作稻田中可对水浮莲进行适当的应用。  相似文献   
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浙江省植被NDVI动态及其对气候的响应   总被引:14,自引:0,他引:14  
何月  樊高峰  张小伟  柳苗  高大伟 《生态学报》2012,32(14):4352-4362
利用GIMMS和MODIS两种归一化植被指数(NDVI)资料反演了1982—2010年浙江植被覆盖状况,结合同期研究区63个气象站点的气温、降水和湿润指数等气候指标,分析了该地区植被年际变化、月际变化及其对气候要素的响应特征。结果表明:(1)研究期间,浙江气候总体呈暖干化趋势,植被覆盖缓慢下降,主要是由于森林植被遭破坏,农业生产活动受抑制影响所致,其中NDVI显著减少的地区约占全省陆域面积的29.1%,主要发生在6—11月;(2)降水量及干湿程度对浙江植被NDVI年变化起着决定性作用。植被与气候要素年变化相关分析发现,NDVI与湿润指数关系较降水、气温更为密切,两者相关及偏相关系数均通过0.05水平的置信度检验,这表明在年际尺度上,湿度的增加增大了植被的生长势,有利于植被生长;(3)植被与气候要素月变化分析表明冬季的热量供给是影响浙江植被生长的重要因子,而植被变化对夏季降水和干湿程度的最大响应为滞后两个月;(4)农业生产水平的提高使得农作物种植区NDVI有所增加,人类活动对浙江植被覆盖的影响不可忽视。  相似文献   
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