A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Sex and Genetic Background Influence Superoxide Dismutase (cSOD)-Related Phenotypic Variation in Drosophila melanogaster

Mutations often have drastically different effects in different genetic backgrounds; understanding a gene’s biological function then requires an understanding of its interaction with genetic diversity. The antioxidant enzyme cytosolic copper/zinc superoxide dismutase (cSOD) catalyzes the dismutation of the superoxide radical, a molecule that can induce oxidative stress if its concentration exceeds cellular control. Accordingly, Drosophila melanogaster lacking functional cSOD exhibit a suite of phenotypes including decreased longevity, hypersensitivity to oxidative stress, impaired locomotion, and reduced NADP(H) enzyme activity in males. To date, cSOD-null phenotypes have primarily been characterized using males carrying one allele, cSodn108red, in a single genetic background. We used ANOVA, and the effect size partial eta squared, to partition the amount of variation attributable to cSOD activity, sex, and genetic background across a series of life history, locomotor, and biochemical phenotypes associated with the cSOD-null condition. Overall, the results demonstrate that the cSOD-null syndrome is largely consistent across sex and genetic background, but also significantly influenced by both. The sex-specific effects are particularly striking and our results support the idea that phenotypes cannot be considered to be fully defined if they are examined in limited genetic contexts

Percent difference of enzyme activities of SOD1-nulls compared to SOD⁺ controls under benign conditions.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024518#pone-0024518-t001" target="_blank">Table 1</a> for mean ± SEM and statistics. Bars not connected by the same letter code are statistically different, as determined by one-way ANOVA Contrast, F1,81 = 26.36, p<0.0001.</p

Enzyme activities, triglyceride and lipid concentrations of SOD1-nulls and SOD⁺ controls before (blue bars) and after 24 hours starvation (green bars).

<p>Activity data (A–F) are presented as mean activity ± SEM. (A) G6PD, F_3,36 = 61.630, p<0.0001, (B) MEN, F_3,36 = 31.615, p<0.0001, (C) HEX, F_3,36 = 20.634, p<0.0001, (D) IDH, F_3,36 = 45.405, p<0.0001, (E) PGI, F_3,36 = 27.415, p<0.0001, (F) ADH, F_3,36 = 33.825, p<0.0001, (G) GLYP, F_3,36 = 16.595, p<0.0001, (H) Triglyceride concentration is expressed as the mean triglyceride concentration (mmol/L) ± SEM, F_3,36 = 1.023, p = 0.3939, (I) Lipid concentration is expressed as mean mg lipid ± SEM, F_3,36 = 32.237, p<0.0001. Significant differences denoted as: ‘*’ indicates p<0.05, and ‘***’ indicates p<0.0001, as determined by one-way ANOVA and Tukey's HSD; black stars indicate differences between genotypes (SOD1-null versus SOD⁺ control), red stars indicate differences between experimental conditions within a genotype (e.g. fed and starved SOD⁺ control flies).</p

Enzyme activities, lipids and triglycerides were assayed every 24 hours for 6 days in SOD1-nulls (red line) and SOD⁺ controls (grey line).

<p>(A) G6PD, F_3,56 = 99.18, p<0.0001 (B) MEN, F_3,56 = 15.60, p<0.0001 (C) HEX, F_3,56 = 32.56, p<0.0001 (D) IDH, F_3,56 = 65.62, p<0.0001 (E) GLYP, F_3,56 = 12.77, p<0.0001 (F) PGI, F_3,56 = 23.0, p<0.0001 (G) ADH, F_3,56 = 22.80, p<0.0001. Each point in the line represents mean activity (OD units) for 5 samples at that time point ± SEM. (H) Triglyceride concentration, each point in the line represents mean triglyceride concentration (mmol/L standardized per mg wet weight) for 5 samples at that time point ± SEM, F_3,56 = 0.3857, p = 0.9854 (I) Lipid concentration, each point in the line represents mean lipid concentration for 10 samples at that time point ± SEM, F_3,117 = 428.90, p<0.0001. Significant differences denoted as: ‘*’ indicates p<0.05, and ‘***’ indicates p<0.0001, as determined by ANCOVA.</p