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961.
Huiying Zhao Yuedong Yang Hai Lin Xinjun Zhang Matthew Mort David N Cooper Yunlong Liu Yaoqi Zhou 《Genome biology》2013,14(3):R23
Micro-indels (insertions or deletions shorter than 21 bps) constitute the second most frequent class of human gene mutation after single nucleotide variants. Despite the relative abundance of non-frameshifting indels, their damaging effect on protein structure and function has gone largely unstudied. We have developed a support vector machine-based method named DDIG-in (Detecting disease-causing genetic variations due to indels) to prioritize non-frameshifting indels by comparing disease-associated mutations with putatively neutral mutations from the 1,000 Genomes Project. The final model gives good discrimination for indels and is robust against annotation errors. A webserver implementing DDIG-in is available at http://sparks-lab.org/ddig. 相似文献
962.
Ubaldo E Martinez-Outschoorn Joseph M Curry Ying-Hui Ko Zhao Lin Madalina Tuluc David Cognetti Ruth C Birbe Edmund Pribitkin Alessandro Bombonati Richard G Pestell Anthony Howell Federica Sotgia Michael P Lisanti 《Cell cycle (Georgetown, Tex.)》2013,12(16):2580-2597
Here, we developed a model system to evaluate the metabolic effects of oncogene(s) on the host microenvironment. A matched set of “normal” and oncogenically transformed epithelial cell lines were co-cultured with human fibroblasts, to determine the “bystander” effects of oncogenes on stromal cells. ROS production and glucose uptake were measured by FACS analysis. In addition, expression of a panel of metabolic protein biomarkers (Caveolin-1, MCT1, and MCT4) was analyzed in parallel. Interestingly, oncogene activation in cancer cells was sufficient to induce the metabolic reprogramming of cancer-associated fibroblasts toward glycolysis, via oxidative stress. Evidence for “metabolic symbiosis” between oxidative cancer cells and glycolytic fibroblasts was provided by MCT1/4 immunostaining. As such, oncogenes drive the establishment of a stromal-epithelial “lactate-shuttle”, to fuel the anabolic growth of cancer cells. Similar results were obtained with two divergent oncogenes (RAS and NFκB), indicating that ROS production and inflammation metabolically converge on the tumor stroma, driving glycolysis and upregulation of MCT4. These findings make stromal MCT4 an attractive target for new drug discovery, as MCT4 is a shared endpoint for the metabolic effects of many oncogenic stimuli. Thus, diverse oncogenes stimulate a common metabolic response in the tumor stroma. Conversely, we also show that fibroblasts protect cancer cells against oncogenic stress and senescence by reducing ROS production in tumor cells. Ras-transformed cells were also able to metabolically reprogram normal adjacent epithelia, indicating that cancer cells can use either fibroblasts or epithelial cells as “partners” for metabolic symbiosis. The antioxidant N-acetyl-cysteine (NAC) selectively halted mitochondrial biogenesis in Ras-transformed cells, but not in normal epithelia. NAC also blocked stromal induction of MCT4, indicating that NAC effectively functions as an “MCT4 inhibitor”. Taken together, our data provide new strategies for achieving more effective anticancer therapy. We conclude that oncogenes enable cancer cells to behave as selfish “metabolic parasites”, like foreign organisms (bacteria, fungi, viruses). Thus, we should consider treating cancer like an infectious disease, with new classes of metabolically targeted “antibiotics” to selectively starve cancer cells. Our results provide new support for the “seed and soil” hypothesis, which was first proposed in 1889 by the English surgeon, Stephen Paget. 相似文献
963.
Plastic mulching with drip irrigation is a new water-saving rice cultivation technology, but little is known on its productivity and water-saving capacity. This study aimed to assess the production potential, performance, and water use efficiency (WUE) of rice under plastic mulching with drip irrigation. Field experiments were conducted over 2 years with two rice cultivars under different cultivation systems: conventional flooding (CF), non-flooded irrigation incorporating plastic mulching with furrow irrigation (FIM), non-mulching with furrow irrigation (FIN), and plastic mulching with drip irrigation (DI). Compared with the CF treatment, grain yields were reduced by 31.76–52.19% under the DI treatment, by 57.16–61.02% under the FIM treatment, by 74.40–75.73% under the FIN treatment, which were mainly from source limitation, especially a low dry matter accumulation during post-anthesis, in non-flooded irrigation. WUE was the highest in the DI treatment, being 1.52–2.12 times higher than with the CF treatment, 1.35–1.89 times higher than with the FIM treatment, and 2.37–3.78 times higher than with the FIN treatment. The yield contribution from tillers (YCFTs) was 50.65–62.47% for the CF treatment and 12.07–20.62% for the non-flooded irrigation treatments. These low YCFTs values were attributed to the poor performance in tiller panicles rather than the total tiller number. Under non-flooded irrigation, root length was significantly reduced with more roots distributed in deep soil layers compared with the CF treatment; the DI treatment had more roots in the topsoil layer than the FIM and FIN treatments. The experiment demonstrates that the DI treatment has greater water saving capacity and lower yield and economic benefit gaps than the FIM and FIN treatments compared with the CF treatment, and would therefore be a better water-saving technology in areas of water scarcity. 相似文献
964.
Robotic Partial Nephrectomy for Renal Tumors Larger than 4 cm: A Systematic Review and Meta-analysis
Liangkuan Bi Caixia Zhang Kaiwen Li Xinxiang Fan Kewei Xu Jinli Han Hai Huang Hao Liu Wen Dong Xiangyun Yang Jian Huang Tianxin Lin 《PloS one》2013,8(10)
Background
With the establishment of minimally invasive surgery in society, the robot has been increasingly widely used in the urologic field, including in partial nephrectomy. This study aimed to comprehensively summarize the currently available evidence on the feasibility and safety of robotic partial nephrectomy for renal tumors of >4 cm.Method and Findings
An electronic database search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed. This systematic review and meta-analysis was based on all relevant studies that assessed robotic partial nephrectomy for renal tumors of >4 cm. Five studies were included. The meta-analysis involved 3 studies from 11 institutions including 154 patients, while the narrative review involved the remaining 2 studies from 5 institutions including 64 patients. In the meta-analysis, the mean ischemic time, operation time, and console time was 28, 319, and 189 minutes, respectively. The estimated blood loss and length of stay was 317 ml and 3.8 days, respectively. The rates of conversion, positive margins, intraoperative complications, postoperative complications, hilar clamping, and collecting system repair were 7.0%, 3.5%, 7.0%, 9.8%, 93.9%, and 47.5%, respectively. The narrative review showed results similar to those of the meta-analysis.Conclusions
Robotic partial nephrectomy is feasible and safe for renal tumors of >4 cm with an acceptable warm ischemic time, positive margin rate, conversion rate, complication rate, operation time, estimated blood loss, and length of stay. 相似文献965.
Ching-Hui Huang Chia-Chu Chang Ching-Shan Huang Chen-Ling Kuo Ching-Pei Chen Chien-Hsun Hsia Yung-Ming Chang Hung-Te Chen Chih-Chung Feng Lee-Shin Lin Po-Ta Yang Chen-Dao Tsai Chih-Sheng Lin Chin-San Liu 《PloS one》2013,8(10)
Objectives
Oxidized low-density lipoproteins (oxLDL) and oxidized low-density lipoprotein autoantibodies (OLAB) have been detected in human plasma and atherosclerotic lesions. OLAB appear to play a role in the clearance of oxLDL from circulation. Higher levels of OLAB appear to be associated with a reduced risk of a wide range of cardiovascular diseases. We investigated the prognostic value of plasma oxLDL and OLAB in patients undergoing primary coronary balloon angioplasty for acute ST-elevation myocardial infarction (STEMI).Methods
Plasma oxLDL and OLAB concentrations were measured in 56 patients with acute STEMI before primary angioplasty, and then 3 days, 7 days and 1 month after the acute event. Follow-up angiography was repeated 6 months later to detect the presence of restensosis (defined as >50% luminal diameter stenosis). The thrombolysis in myocardial infarction (TIMI) risk score was calculated to determine the relationship between OLAB/oxLDL ratio and TIMI risk scores.Results
Of the 56 patients, 18 (31%) had angiographic evidence of restenosis. Plasma OLAB concentrations were significantly lower in the restenosis group before angioplasty (181±114 vs. 335±257 U/L, p = 0.003), and at day 3 (155±92 vs. 277±185 U/L, p<0.001) and day 7 (177±110 vs. 352±279 U/L, p<0.001) after the acute event. There was no difference in oxLDL concentration between the two groups. The ratio of OLAB/oxLDL positively correlated with TIMI risk scores before angioplasty (p for trend analysis, p = 0.004), at day 3 (p = 0.008) and day 7 (p<0.001) after STEMI.Significance
A relative deficit of OLAB, and hence likely impaired clearance of oxLDL, is associated with the risk of arterial restenosis after primary angioplasty for acute STEMI. 相似文献966.
967.
968.
Lin Li Guoqing Sun Shujia Liang Jianjian Li Tianyi Li Zhe Wang Wei Liu Shaomin Yang Yongjian Liu Xiaolin Wang Jingyun Li 《PloS one》2013,8(10)
Yunnan, Guangxi and Henan are the provinces with the most severe HIV epidemic in China, which were also among the first group of areas providing free ART in 2004. However, little comprehensive data are available on prevalence of HIV subtype and baseline drug resistance in drug-naïve populations. In this study, 1746 treatment-naïve HIV-positive individuals were randomly selected from new-reported cases in Henan, Guangxi and Yunnan. Among of them, subtypes and drug resistance of 1159 strains were determined by amplifying and sequencing full-length pol genes. Significantly different distributions of HIV subtypes prevalent in three provinces were identified (P<0.01). CRF08_BC was found dominant in Yunnan (59.8%), while CRF01_AE was dominant in Guangxi (77.3%) and subtype B was dominant in Henan province (93.9%). The total prevalence of drug resistance was 7.1%. The highest prevalence of HIV drug resistance was found in Henan (12.2%), followed by Yunnan (5.6%) and Guangxi (3.3%). The results of this study suggest that genetic drug-resistance should be tested before initiation of ART in China, especially in Henan province. Furthermore, the prevalence of HIV drug resistant strains should be considered separately in different areas in China before the change of different free ART regimens. 相似文献
969.
Lin Feng Hao Wu Lingling E Dongsheng Wang Fukui Feng Yuwan Dong Hongchen Liu Lili Wang 《PloS one》2013,8(12)
To study the relationship between vascular endothelial growth factor (VEGF) and formation and repair of engineering bone, second-generation bone marrow stromal cells (BMSCs) of New Zealand white rabbits that were separated in vitro were transfected with VEGF 165 gene vectors by adenovirus to detect gene expressions. Transfected BMSCs and β-tricalcium phosphate material were complexed and implanted at the femoral injury sites of the study group (n = 12), and the control group (n = 12) were implanted with engineering bones that were not transfected with VEGF. Femoral recoveries of the two groups were observed on the 15th, 30th, 45th and 60th days, and their vascularization and ossification statuses were observed by immunohistochemical methods. The BMSCs transfected with VEGF highly expressed VEGF genes and excreted VEGF. The two groups both experienced increased vascularization and bone volume after implantation (t = 7.92, P<0.05), and the increases of the study group were significantly higher than those of the control group (t = 6.92, P<0.05). VEGF is clinically applicable because it can accelerate the formation and repair of engineering bone by promoting vascularization and ossification. 相似文献
970.
Fang Lu Lulin Huang Chuntao Lei Guiquan Sha Hong Zheng Xiaoqi Liu Jiyun Yang Yi Shi Ying Lin Bo Gong Xianjun Zhu Shi Ma Lifeng Qiao He Lin Jing Cheng Zhenglin Yang 《PloS one》2013,8(11)