The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

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

The Regulation of Muscle Structure and Metabolism by Mio/dChREBP in Drosophila.

All cells require energy to perform their specialized functions. Muscle is particularly sensitive to the availability of nutrients due to the high-energy requirement for muscle contraction. Therefore the ability of muscle cells to obtain, store and utilize energy is essential for the function of these cells. Mio, the Drosophila homolog of carbohydrate response element binding protein (ChREBP), has recently been identified as a nutrient responsive transcription factor important for triglyceride storage in the fly fat body. However, the function of Mio in muscle is unknown. In this study, we characterized the role of Mio in controlling muscle function and metabolism. Decreasing Mio levels using RNAi specifically in muscle results in increased thorax glycogen storage. Adult Mio-RNAi flies also have a flight defect due to altered myofibril shape and size in the indirect flight muscles as shown by electron microscopy. Myofibril size is also decreased in flies just before emerging from their pupal cases, suggesting a role for Mio in myofibril development. Together, these data indicate a novel role for Mio in controlling muscle structure and metabolism and may provide a molecular link between nutrient availability and muscle function

Mio affects myofibril size.

<p>Scanning Electron Microscopy of Indirect Flight Muscles of adult Mef2-Gal4>Mio^dsRNA and Mef2-Gal4>Mio-IR females compared to Mef2-Gal4>GFP controls. Panels (A), (B) and (C) show cross sections of the myofibrils; bars indicate 0.5μm. f, myofibril; c, mitochondrion; g, glycogen granules. (D) Average myofibril area of Mef2-Gal4>Mio^dsRNA and Mef2-Gal4>Mio-IR flies compared to Mef2-Gal4>GFP control flies (n = 3–5). All values represent average myofibril area ±SEM. *p<0.05 Kruskal-Wallis One-way ANOVA with post hoc all pairwise multiple comparison pooled sample median test.</p

Mio is not necessary for normal expression of structural genes in adult fly muscle.

<p>Expression of Actin 88F (Act88F, n = 8), Myosin Heavy Chain (MHC, n = 11), and Myosin light chain-2 (Mlc-2, n = 8) was measured by performing quantitative PCR on thorax cDNA from 5–7 day old Mef2-Gal4>Mio^dsRNA and Mef2-Gal4>Mio-IR flies and compared to Mef2-Gal4>GFP controls. mRNA levels of Mef2-Gal4>GFP controls were set to 1.0 and mRNA levels of Mef2-Gal4>Mio^dsRNA and Mef2-Gal4>Mio-IR animals were then normalized to their respective control. Values represent mean±SEM. *p<0.05 by One-way ANOVA with post hoc Tukey test.</p

Decreasing Mio levels results in abnormal myofibril organization.

<p>Scanning Electron Microscopy of longitudinal sections of Indirect Flight Muscles of adult Mef2-Gal4>Mio^dsRNA and Mef2-Gal4>Mio-IR females compared to Mef2-Gal4>GFP controls. f, myofibril; g, glycogen granules. Each arrow points to a single longitudinal myofibril. Scale bar = 20μm.</p

Mio in muscle is necessary for normal flight.

<p>Flight tests were performed on Mef2-Gal4>Mio^dsRNA (n = 144) and Mef2-Gal4>Mio-IR (n = 296) flies and compared to Mef2-Gal4>GFP (n = 179) controls and scored based on flight ability (See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136504#sec002" target="_blank">methods</a>). Values represent average flight score ±SEM. *p<0.05 Kruskal-Wallis One-way ANOVA with post hoc all pairwise multiple comparison pooled sample median test.</p

Mio affects myofibril size in pharate adults.

<p>Transmission Electron Microscopy of Indirect Flight Muscles of Mef2-Gal4>Mio^dsRNA and Mef2-Gal4>Mio-IR pharate adults compared to Mef2-Gal4>GFP controls. Panels (A), (B) and (C) show cross sections of the myofibrils. Bars indicate 0.5μm. f, myofibril; c, mitochondrion; g, glycogen granules. (D) Average myofibril area of Mef2-Gal4>Mio^dsRNA and Mef2-Gal4>Mio-IR pharate adults compared to Mef2-Gal4>GFP controls (n = 3–5). Values represent average myofibril area ±SEM. *p<0.05 by One-way ANOVA with post hoc Tukey test.</p