基于USB数据采集器的膜片钳系统软件设计

为了控制新的基于USB总线的数据采集器进行膜片钳实验,设计和实现了能应用于Windows 2000／XP操作系统的膜片钳系统软件。软件运用面向对象程序设计方法和统一建模语言,实现了封接测试．电压门控和配体门控等实验模式。实验结果表明,该系统软件能够精确控制数据采集器进行高速数据采集,满足细胞生理实验的要求。     

“门控-弹簧”模型及其在果蝇机械力信号转导中的分子基础北大核心CSCD

机械力是生物体生命活动中普遍存在的一种物理刺激,高等生物对机械力的感受是听觉、触觉、压觉以及平衡觉等重要生理过程的生物学基础。生物体中的感受器细胞对机械力信号的转导是上述感受的关键,这一信号转导过程可将细胞外机械力刺激转换为细胞的电信号或者化学信号。"门控-弹簧"模型("Gating-Spring"model)在细胞水平定量地描述了机械力信号转导的原理,但是其分子基础(包括机械力信号转导通路的分子组分,结构基础以及力学原理)依然有待探索。近年来,人们以果蝇为模式生物对上述问题进行了系统的研究,取得了重要的进展。本文对"门控-弹簧"理论进行了概述,并对在果蝇系统中取得的研究进展以及有待解决的问题进行综述和展望。     

“门控-弹簧”模型及其在果蝇机械力信号转导中的分子基础

机械力是生物体生命活动中普遍存在的一种物理刺激,高等生物对机械力的感受是听觉、触觉、压觉以及平衡觉等重要生理过程的生物学基础。生物体中的感受器细胞对机械力信号的转导是上述感受的关键,这一信号转导过程可将细胞外机械力刺激转换为细胞的电信号或者化学信号。"门控-弹簧"模型("Gating-Spring"model)在细胞水平定量地描述了机械力信号转导的原理,但是其分子基础(包括机械力信号转导通路的分子组分,结构基础以及力学原理)依然有待探索。近年来,人们以果蝇为模式生物对上述问题进行了系统的研究,取得了重要的进展。本文对"门控-弹簧"理论进行了概述,并对在果蝇系统中取得的研究进展以及有待解决的问题进行综述和展望。     

长期给予吗啡降低大鼠的听觉惊跳反射和惊跳反射弱刺激抑制

在药物成瘾过程中,多巴胺系统起着至关重要的作用,大多数成瘾性药物都是通过影响多巴胺系统使机体产生依赖性.而多巴胺系统也同样是感觉运动门控功能的主要神经基础.尤其是中脑边缘系统的多巴胺系统在这两种行为中都起很重要的作用.但是这两种行为是如何相互作用、相互影响的还不是很清楚.本实验室曾报道了吗啡如何影响海马区的感觉门控功能.本文研究了吗啡如何影响大鼠的感觉运动门控功能.在吗啡给予前,吗啡给予期间(10天)以及吗啡戒断期间,我们检测了大鼠的感觉运动门控功能.用到的指标为惊跳反射和惊跳前脉冲抑制,这两种指标也是研究精神分裂症的重要手段.其中惊跳反射的声音强度为115分贝,前脉冲声音强度测试了3个水平,分别为70,75,80分贝.研究发现,在吗啡给予期间,惊跳反射的强度降低,而戒断期间不受影响.前脉冲抑制功能在吗啡给予的后2天显著降低,而在吗啡戒断后恢复.     

N-甲基-D-门冬氨酸受体通道复合体

N-甲基-D门冬氨酸(NMDA)受体通道复合体不同于一般的递质门控或电压门控的离子通道,而是兼有递质门控与电压门控双重特征。该受体通道有四种以上不同的电导水平,因而可能是多个受体亚型结合的一个复合的分子实体。NMDA受体通道的开放可引起钠、钾、钙离子内流。已经发现NMDA受体通道与长时程突触增强,癫痫等脑活动有关。     

PC12细胞钾离子通道门控动力学随机建模与参数估计(Ⅰ)

本文以PC12细胞钾离子通门控机理分析为例证,探索离子通道门控动力学马尔科夫模型的建模方法,并详述建模过程,为通过研究者提供启示与借鉴．在此基础上提出PC12细胞钾离子通道门控动力学的三个备择方案,然后试用Ball等人建议的适用于片膜中只含一个通道记录的极大似然算法估计速率参数,根据AIC及SC准则将模型作了比较,选择较适宜的模型刻划PC12细胞钾离子通道门控动力学．     

震惊反射系统在研究小鼠感觉运动门控功能中的应用

感觉运动门控功能异常与多种精神疾病相关,前脉冲抑制是常用的测量感觉运动门控的重要行为学参数。该文介绍了用震惊反射系统测定C57BL/6J品系小鼠前脉冲抑制的实验方法,并用N-甲基-D-天冬氨酸受体非竞争拮抗剂MK-801(Dizocilpine,地卓西平)成功构建了药物诱发前脉冲抑制缺失的小鼠模型。     

植物环核苷酸门控离子通道基因的功能及其调控

环核苷酸(cAMP/cGMP)是生命体重要的信号分子,环核苷酸门控离子通道(CNGC)是环核苷酸主要的受体之一,目前已在植物中克隆并鉴定了多个环核苷酸门控离子通道基因,它们参与调控植物的生长、发育以及抗病等反应.这些通道既可通过一价阳离子,也可通过二价阳离子,其活性受Ca2+/Calmodulin调控.本文概括了近年来植物环核苷酸门控离子通道(CNGC)基因的克隆、植物CNGC对离子的选择特性、CNGC的生物学功能与调控等方面的研究进展.     

一个改进的马尔科夫模型

离子通道是细胞膜里的大分子孔道,是跨越细胞膜里的蛋白质大分子,是神经、肌肉等细胞膜兴奋性的基础。人体细胞均具有完成特殊功能的离子通道,构建离子通道,尤其其门控行为的动力学模型,对于研究离子通道的相关课题具有重要意义。离子通道的开关反映了蛋白质构象变化的动力学过程。本文介绍了细胞膜离子通道的基本内容和几种常用模型,并根据Markov链对离子通道门控行为的一个二态（闭、开）模型的Markov过程进行了改进,得到了包含失活状态的离子通道门控行为的Markov模型。     

超极化激活的环核苷酸门控性阳离子通道（HCN）与疾病的相关性

超极化激活的环核苷酸门控的阳离子通道(hyperpolarization-activated cyclic nucleotide-gate cation channel,HCN)是一种特殊的阳离子通道,存在于神经细胞、小肠间质细胞、窦房结细胞或心脏细胞等具有自律性的细胞膜上,是产生过度激活正离子电流的结构基础,被认为是起搏细胞的重要特征。HCN离子蛋白通道不但与细胞凋亡以及电流传导有着密切关系,而且还与多种生命活动过程密切相关,近年来,已涉及到疼痛、癫痫、心律失常、消化道系统等许多疾病,特别是有关神经系统方面的疾病,下面将超极化激活的环核苷酸门控性阳离子通道(HCN)与疾病的关系综述如下。     

Combined confocal and wide-field high-resolution cytometry of fluorescent in situ hybridization-stained cells

BACKGROUND: The recently developed technique of high-resolution cytometry (HRCM) enables automated acquisition and analysis of fluorescent in situ hybridization (FISH)-stained cell nuclei using conventional wide-field fluorescence microscopy. The method has now been extended to confocal imaging and offers the opportunity to combine the advantages of confocal and wide-field modes. METHODS: We have automated image acquisition and analysis from a standard inverted fluorescence microscope equipped with a confocal module with Nipkow disk and a cooled digital CCD camera. The system is fully controlled by a high-performance computer that performs both acquisition and related on-line image analysis. The system can be used either for an automatic two (2D) and three-dimensional (3D) analysis of FISH- stained interphase nuclei or for a semiautomatic 3D analysis of FISH-stained cells in tissues. The user can select which fluorochromes are acquired using wide-field mode and which using confocal mode. The wide-field and confocal images are overlaid automatically in computer memory. The developed software compensates automatically for both chromatic color shifts and spatial shifts caused by switching to a different imaging mode. RESULTS: Using the combined confocal and wide-field HRCM technique, it is possible to take advantage of both imaging modes. Images of some dyes (such as small hybridization dots or counterstain images of individual interphase nuclei) do not require confocal quality and can be acquired quickly in wide-field mode. On the contrary, images of other dyes (such as chromosome territories or counterstain images of cells in tissues) do require improved quality and are acquired in confocal mode. The dual-mode approach is two to three times faster compared with the single-mode confocal approach and the spectrum of its applications is much broader compared with both single-mode confocal and single-mode wide-field systems. CONCLUSIONS: The combination of high speed specific to the wide-field mode and high quality specific to the confocal mode gives optimal system performance.     

植物ms 级叶绿素荧光动力学数据采集和分析软件

本文介绍了一套可在IBM PC(兼容)微机上运行的植物ms级荧光动力学数据采集和分析软件。本软件用C语言写成,具有汉化界面、菜单驱动、彩色人机对话窗口、操作简便、灵活,兼容性好等优点。本文着重讨论了本软件如何减少荧光动力学测量中的误差、在不过分占用内存的情况下扩大采样时间范围以及如何精确测量固定荧光(Fo)和偏转荧光(Fi)等问题。本软件和我们自行组装的植物ms级动力学荧光计——植物产量荧光计PFM-101型可广泛应用于农业、植物生态学及植物生理学的光合测量和研究。     

植物ms级叶绿素荧光动力学数据采集和分析软件

本文介绍了一套可在ＩＢＭＰＣ（兼容）微机上运行的植物ｍｓ级荧光动力学数据采集和分析软件。本软件用Ｃ语言写成,具有汉化界面、菜单驱动、彩色人机对话窗口、操作简便、灵活,兼容性好等优点。本文着重讨论了本软件如何减少荧光动力学测量中的误差、在不过分占用内存的情况下扩大采样时间范围以及如何精确测量固定荧光（Ｆｏ）和偏转荧光（Ｆｉ）等问题。本软件和我们自行组装的植物ｍｓ级动力学荧光计———植物产量荧光计ＰＦＭ１０１型可广泛应用于农业、植物生态学及植物生理学的光合测量和研究     

MethylCoder: software pipeline for bisulfite-treated sequences

MOTIVATION: MethylCoder is a software program that generates per-base methylation data given a set of bisulfite-treated reads. It provides the option to use either of two existing short-read aligners, each with different strengths. It accounts for soft-masked alignments and overlapping paired-end reads. MethylCoder outputs data in text and binary formats in addition to the final alignment in SAM format, so that common high-throughput sequencing tools can be used on the resulting output. It is more flexible than existing software and competitive in terms of speed and memory use. AVAILABILITY: MethylCoder requires only a python interpreter and a C compiler to run. Extensive documentation and the full source code are available under the MIT license at: https://github.com/brentp/methylcode. CONTACT: bpederse@gmail.com.     

Efficient clustering of large EST data sets on parallel computers

Clustering expressed sequence tags (ESTs) is a powerful strategy for gene identification, gene expression studies and identifying important genetic variations such as single nucleotide polymorphisms. To enable fast clustering of large-scale EST data, we developed PaCE (for Parallel Clustering of ESTs), a software program for EST clustering on parallel computers. In this paper, we report on the design and development of PaCE and its evaluation using Arabidopsis ESTs. The novel features of our approach include: (i) design of memory efficient algorithms to reduce the memory required to linear in the size of the input, (ii) a combination of algorithmic techniques to reduce the computational work without sacrificing the quality of clustering, and (iii) use of parallel processing to reduce run-time and facilitate clustering of larger data sets. Using a combination of these techniques, we report the clustering of 168 200 Arabidopsis ESTs in 15 min on an IBM xSeries cluster with 30 dual-processor nodes. We also clustered 327 632 rat ESTs in 47 min and 420 694 Triticum aestivum ESTs in 3 h and 15 min. We demonstrate the quality of our software using benchmark Arabidopsis EST data, and by comparing it with CAP3, a software widely used for EST assembly. Our software allows clustering of much larger EST data sets than is possible with current software. Because of its speed, it also facilitates multiple runs with different parameters, providing biologists a tool to better analyze EST sequence data. Using PaCE, we clustered EST data from 23 plant species and the results are available at the PlantGDB website.     

A framework for three-dimensional simulation of morphogenesis

We present COMPUCELL3D, a software framework for three-dimensional simulation of morphogenesis in different organisms. COMPUCELL3D employs biologically relevant models for cell clustering, growth, and interaction with chemical fields. COMPUCELL3D uses design patterns for speed, efficient memory management, extensibility, and flexibility to allow an almost unlimited variety of simulations. We have verified COMPUCELL3D by building a model of growth and skeletal pattern formation in the avian (chicken) limb bud. Binaries and source code are available, along with documentation and input files for sample simulations, at http:// compucell.sourceforge.net.     

Dual N-Back Working Memory Training in Healthy Adults: A Randomized Comparison to Processing Speed Training

Enhancing cognitive ability is an attractive concept, particularly for middle-aged adults interested in maintaining cognitive functioning and preventing age-related declines. Computerized working memory training has been investigated as a safe method of cognitive enhancement in younger and older adults, although few studies have considered the potential impact of working memory training on middle-aged adults. This study investigated dual n-back working memory training in healthy adults aged 30–60. Fifty-seven adults completed measures of working memory, processing speed, and fluid intelligence before and after a 5-week web-based dual n-back or active control (processing speed) training program. Results: Repeated measures multivariate analysis of variance failed to identify improvements across the three cognitive composites, working memory, processing speed, and fluid intelligence, after training. Follow-up Bayesian analyses supported null findings for training effects for each individual composite. Findings suggest that dual n-back working memory training may not benefit working memory or fluid intelligence in healthy adults. Further investigation is necessary to clarify if other forms of working memory training may be beneficial, and what factors impact training-related benefits, should they occur, in this population.     

The Role of Visual Processing Speed in Reading Speed Development

A steady increase in reading speed is the hallmark of normal reading acquisition. However, little is known of the influence of visual attention capacity on children''s reading speed. The number of distinct visual elements that can be simultaneously processed at a glance (dubbed the visual attention span), predicts single-word reading speed in both normal reading and dyslexic children. However, the exact processes that account for the relationship between the visual attention span and reading speed remain to be specified. We used the Theory of Visual Attention to estimate visual processing speed and visual short-term memory capacity from a multiple letter report task in eight and nine year old children. The visual attention span and text reading speed were also assessed. Results showed that visual processing speed and visual short term memory capacity predicted the visual attention span. Furthermore, visual processing speed predicted reading speed, but visual short term memory capacity did not. Finally, the visual attention span mediated the effect of visual processing speed on reading speed. These results suggest that visual attention capacity could constrain reading speed in elementary school children.     

Exact genetic linkage computations for general pedigrees

MOTIVATION: Genetic linkage analysis is a useful statistical tool for mapping disease genes and for associating functionality of genes with their location on the chromosome. There is a need for a program that computes multipoint likelihood on general pedigrees with many markers that also deals with two-locus disease models. RESULTS: In this paper we present algorithms for performing exact multipoint likelihood calculations on general pedigrees with a large number of highly polymorphic markers, taking into account a variety of disease models. We have implemented these algorithms in a new computer program called SUPERLINK which outperforms leading linkage software with regards to functionality, speed, memory requirements and extensibility.     

Automated analysis of courtship suppression learning and memory in Drosophila melanogaster

Study of the fruit fly, Drosophila melanogaster, has yielded important insights into the underlying molecular mechanisms of learning and memory. Courtship conditioning is a well-established behavioral assay used to study Drosophila learning and memory. Here, we describe the development of software to analyze courtship suppression assay data that correctly identifies normal or abnormal learning and memory traits of individual flies. Development of this automated analysis software will significantly enhance our ability to use this assay in large-scale genetic screens and disease modeling. The software increases the consistency, objectivity, and types of data generated.