Avanti lipid tools: Connecting lipids,technology, and cell biology

Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein–lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions.     

基于分段线性模板先验的正电子成像重建

正电子发射成像的噪声性能较其它的一些成像方法要差得多,为了提高重建结果的分辨率和噪声特性,一般采用Bayesian重建。Bayesian方法需要选择恰当的先验,这种先验既要能够抑止重建结果的噪声,又要能够保留图像密度的突变信息。分段线性模板图像模型利用从其它模态的形态学成像得到的组织结构信息,构造适合要求的先验分布函数,由于采用的先验函数是非凸的并包含超验参数,一般的优化方法难以处理,采用动态后验模拟的方法可以很好地解决这些问题。     

肝移植术后肝脏淋巴回流淤滞的影像学特征

目的:分析肝移植术后病人肝脏淋巴回流淤滞(intrahepatic lymphatic stasis,IHLS)的计算机断层扫描(Computed Tomography,CT)及磁共振(Magnetic Resonance Imaging,MRI)影像学特征。方法:回顾性收集我院自2004~2012年肝移植术后病人66例,分析其术后CT及MRI图像,对IHLS的阳性次数、持续时间及其影像学特征进行观察分析。结果:66病人中IHLS病人22例。肝移植术后IHLS的直接征象为血管周围项圈征(perivacular collar,PC),CT和MRI可清晰显示且可根据PC的部位分型。结论:肝移植术后IHLS的CT及MRI具有特定的影像学特征,对其识别具有一定的临床意义。     

Dynamic conformational changes due to the ATP hydrolysis in the motor domain of myosin: 10-ns molecular dynamics simulations

Muscle contraction is caused by directed movement of myosin heads along actin filaments. This movement is triggered by ATP hydrolysis, which occurs within the motor domain of myosin. The mechanism for this intramolecular process remains unknown owing to a lack of ways to observe the detailed motions of each atom in the myosin molecule. We carried out 10-ns all-atom molecular dynamics simulations to investigate the types of dynamic conformational changes produced in the motor domain by the energy released from ATP hydrolysis. The results revealed that the thermal fluctuations modulated by perturbation of ATP hydrolysis are biased in one direction that is relevant to directed movement of the myosin head along the actin filament.     

Odours and volatile organic compounds emitted from municipal solid waste at different stage of decomposition and relationship with biological stability

Odours (OU_E) and volatile organic compounds (VOC) emission during biological process used to treat MSW were studied under standardized conditions in order to detect potential risk for workers and population. Results obtained indicated that odours and VOCs emitted depend on the biological stability of waste measured by the dynamic respiration index (DRI) and a very good correlation were found between these parameters (OU_E vs. DRI, r = 0.96, p < 0.001, n = 6; VOC vs. DRI, r = 0.97, p < 0.001, n = 6).GC-MS study of the VOCs indicated the presence of a group of molecules that were degraded during the process. On the other hand, a second group of molecules, i.e. aromatic and halogenated compounds, and furan persisted in the waste sample, although molecule concentrations were always lower than Threshold Limit Value-Time Weighted Average (TLV-TWA).     

Determinants of gait stability while walking on a treadmill: A machine learning approach

Dynamic balance in human locomotion can be assessed through the local dynamic stability (LDS) method. Whereas gait LDS has been used successfully in many settings and applications, little is known about its sensitivity to individual characteristics of healthy adults. Therefore, we reanalyzed a large dataset of accelerometric data measured for 100 healthy adults from 20 to 70 years of age performing 10 min treadmill walking. We sought to assess the extent to which the variations of age, body mass and height, sex, and preferred walking speed (PWS) could influence gait LDS. The random forest (RF) and multiple adaptive regression splines (MARS) algorithms were selected for their good bias-variance tradeoff and their capabilities to handle nonlinear associations. First, through variable importance measure (VIM), we used RF to evaluate which individual characteristics had the highest influence on gait LDS. Second, we used MARS to detect potential interactions among individual characteristics that may influence LDS. The VIM and MARS results indicated that PWS and age correlated with LDS, whereas no associations were found for sex, body height, and body mass. Further, the MARS model detected an age by PWS interaction: on one hand, at high PWS, gait stability is constant across age while, on the other hand, at low PWS, gait instability increases substantially with age. We conclude that it is advisable to consider the participants’ age as well as their PWS to avoid potential biases in evaluating dynamic balance through LDS.     

动态心电图在小儿心律失常与心率变异性诊断中的意义

目的：研究动态心电图（DCG）诊断小儿心律失常及心率变异性（HVR）的临床价值。方法：560 例患者均进行常规心电图和动 态心电图的检查,由两组专业人员分别对心电图（ECG）和动态心电图（DCG）的检查结果进行（评价）,比较两种检查手段的不同 类型的心律失常的诊出率;评价不同类型心律失常的HVR。结果：ECG对各型心律失常的总诊出率为25.00%,对不同类型心率失 常的诊出率分别为5.71%、1.43%、9.29%、6.43%和2.14%;DCG 总诊出率为62.85%,对不同类型心率失常的诊出率分别为 16.43%、6.43%、17.86%、14.29%和7.86%,二者具有统计学差异（P＜0.05）。不同类型的心律失常的HVR不同,其中室性心动过速 和室性期前收缩的各项指标均明显低于其他类型（P＜0.05）。结论：DCG对不同心律失常的诊出率明显高于ECG,并能有效反应 不同类型心率失常的HVR,在小儿心律失常的诊断中具有一定的临床价值。     

多模式磁共振指导超时间窗急性缺血性卒中的静脉溶栓治疗研究

目的:评价多模式磁共振指导下超时间窗静脉应用重组组织型纤溶酶原激活剂rt PA治疗急性缺血性卒中的疗效及安全性。方法:将68例急性脑梗塞患者分为rt PA静脉溶栓组A组、强化抗栓治疗组B组,各组按药物干预时间再分为4.5小时亚组及4.5-6小时亚组。A组给予rt PA静脉溶栓治疗和常规治疗,B组给予首剂氯吡格雷300毫克+阿司匹林100毫克和常规治疗。治疗前行急诊头多模式磁共振检查,治疗24小时后复查头CT,分别于治疗前后不同时间点进行NIHSS评分和3个月MRS评分,记录不良事件的发生情况。结果:A组两个亚组治疗后各时间点NIHSS评分均明显低于B组,且A组4.5小时亚组治疗后NIHSS评分低于其4.5-6小时亚组,A组3个月预后良好患者比例显著高于B组,差异均有统计学意义(P0.05)。A组症状性颅内出血的发生率高于B组。结论:多模式头磁共振指导下超时间窗rt PA静脉溶栓治疗安全有效,远期疗效优于强化抗栓治疗,但颅内症状性出血风险略高于强化抗栓治疗。     

Extension of dynamic range of sensitive nanoparticle-based immunoassays

Nanoparticles have successfully been employed in immunometric assays that require high sensitivity. Certain analytes, however, require dynamic ranges (DRs) around a predetermined cut-off value. Here, we have studied the effects that antibody orientation and addition of free solid-phase and detection antibodies have on assay sensitivity and DR in traditional sandwich-type immunoassays. D-dimer and cardiac troponin I (cTnI), both routinely used in critical care testing, were applied as model analytes. The assays were performed in microtitration wells with preimmobilized solid-phase antibody. Inherently fluorescent nanoparticles coated with second antibody were used to detect the analyte. The selection of antibody orientation and addition of free solid-phase or detection antibody, with nanoparticles and calibrator, desensitized the assays and extended the DR. With D-dimer the upper limit of the DR was improved from 50 to 10,000 ng/ml, and with cTnI from 25 to 1000 ng/ml. Regression analysis with the Stago STA Liatest D-dimer assay yielded a slope (95% confidence interval) of 0.09 (0.07–0.11) and a y-intercept of −7.79 (−17.87–2.29) ng/L (n = 65, r = 0.906). Thus it is concluded that Europium(III)-chelate-doped nanoparticles can also be employed in immunoassays that require wide DRs around a certain cut-off limit.     

Cysteine-rich secretory protein 3 inhibits hepatitis C virus at the initial phase of infection

Hepatitis C virus (HCV) affects 2–3% of the global population. Approximately one-quarter of acute infections cause chronic hepatitis that leads to liver cirrhosis or hepatocellular carcinoma. The major obstacle of current research is the extremely narrow host tropism of HCV. A single HCV strain can replicate in the Huh7 human hepatoma cell line. Huh7 cells can be adapted under selective pressure in vitro to identify host factors that influence viral replication. Here, we extended this strategy to the in vivo condition and generated a series of cell lines by multiple rounds of adaptation in immunocompromised mice. Adaptation increased the cellular resistance to HCV infection. Microarray analyses revealed that the expression levels of several genes were associated with HCV resistance. Notably, up-regulation of the mRNA encoding cysteine-rich secretory protein 3 (CRISP3), a glycoprotein with unknown function that is secreted from multiple exocrine glands, was correlated with HCV resistance. The presence of CRISP3 in the culture medium limited HCV replication at the early phase of infection.