Lysosomal proteomics and disease

A recent trend in proteomic studies has been to analyze macromolecular complexes such as subcellular organelles instead of complete cells or tissues. This "divide and conquer" approach circumvents some of the formidable problems associated with whole proteome analyses and allows focus on a subset of proteins that may be involved in a particular process or disease of interest. One organelle that has been the focus of considerable attention in proteomic studies is the lysosome, an acidic, membrane-delimited compartment that plays an essential role in the degradation and recycling of biological macromolecules. Lysosomal proteomics have been driven in part by the well-established involvement of this organelle in numerous human diseases, but also by the availability of approaches to selectively visualize and/or isolate subsets of lysosomal proteins. In terms of clinical application, proteomic studies of the lysosome have led to the identification of gene defects in three human hereditary diseases. This review summarizes past progress, current limitations and future directions in the field of lysosomal proteomics.     

Human and organizational issues in information systems development

The paper describes the first phase of a project funded in the UK by the Department of Trade and Industry and the Science and Engineering Research Council (Project I ED 1249). The paper reviews a number of systems development methods, examines the extent to which they incorporate consideration of a set of relevant human and organizational issues, and describes the findings of an exploratory study of the ways in which systems analysts work, including their use of methods.     

Human and organizational issues in information systems development

Abstract

The paper describes the first phase of a project funded in the UK by the Department of Trade and Industry and the Science and Engineering Research Council (Project I ED 1249). The paper reviews a number of systems development methods, examines the extent to which they incorporate consideration of a set of relevant human and organizational issues, and describes the findings of an exploratory study of the ways in which systems analysts work, including their use of methods.     

Degradative proteomics and disease mechanisms

Protein degradation is a fundamental biological process, which is essential for the maintenance and regulation of normal cellular function. In humans and animals, proteins can be degraded by a number of mechanisms: the ubiquitin-proteasome system, autophagy and intracellular proteases. The advances in contemporary protein analysis means that proteomics is increasingly being used to explore these key pathways and as a means of monitoring protein degradation. The dysfunction of protein degradative pathways has been associated with the development of a number of important diseases including cancer, muscle wasting disorders and neurodegenerative diseases. This review will focus on the role of proteomics to study cellular degradative processes and how these strategies are being applied to understand the molecular basis of diseases arising from disturbances in protein degradation.     

The role of Human Factors in system development

The application of Human Factors or ergonomics principles to American system development occurs in a highly unstructured, problem-solving environment in which inputs compete with each other for acceptance. Factors determining whether human engineering inputs will be accepted include: the specification (or lack thereof) of personnel performance requirements; the advantages supplied by the human engineering recommendation; the costs involved in implementing it; the funding supplied by the customer for the new system; and his oversight of human engineering efforts. Human Factors efforts are required in at least five of the six major phases of system development: System Planning; Predesign; Detail Design; Production; Test and Evaluation; and Operations. Each phase introduces behavioural questions that must be answered if the system is to be designed properly. Each question demands specific techniques and skills of the human engineer.     

Colorectal cancer proteomics, molecular characterization and biomarker discovery

Colorectal cancer (CRC) is a widespread disease, whose major genetic changes and mutations have been well characterized in the sporadic form. Much less is known at the protein and proteome level. Still, CRC has been the subject of multiple proteomic studies due to the urgent necessity of finding clinically relevant markers and to elucidate the molecular mechanisms underlying the progression of the disease. These proteomic approaches have been limited by different technical issues, mainly related with sensitivity and reproducibility. However, recent advances in proteomic techniques and MS systems have rekindled the quest for new biomarkers in CRC and an improved molecular characterization. In this review, we will discuss the application of different proteomic approaches to the identification of differentially expressed proteins in CRC. In particular, we will make a critical assessment about the use of 2-D DIGE, MS and protein microarray technologies, in their different formats, to identify up- or downregulated proteins and/or autoantibodies profiles that could be useful for CRC characterization and diagnosis. Despite a wide list of potential biomarkers, it is clear that more scientific efforts and technical advances are still needed to cover the range of low-abundant proteins, which may play a key role in CRC diagnostics and progression.     

Cartilage proteomics: Challenges, solutions and recent advances

The mammalian skeleton is largely composed of cartilage and bone. The major functions of cartilage are first to provide a transient template for development of the axial and appendicular skeleton and secondly to provide permanent articulating joint surfaces. The unique cartilage extracellular matrix (ECM) is essential for the load-bearing and viscoelastic properties of cartilage tissues. Maintained by the chondrocytes, the ECM contains a myriad of proteins and proteoglycans organized into precise networks. Many cartilage disorders result from genetic disruption of cartilage ECM components, their interactions and/or degradation. Although technically challenging, the proteomic analysis of cartilage in development and disease is now emerging as a clinically important research area. In this article, we will review progress in the proteomic characterization of cartilage-related samples.     

Basic and clinical proteomics from the EU Health Research perspective

The European Union (EU) is one of the main public funders of research in Europe and its major instrument for funding is the Seventh Framework Programme for research and technological development (FP7). The bulk of funding in FP7 goes to collaborative research, with the objective of establishing excellent research projects and networks. Understanding the functions of proteins is essential for the rational development of disease prevention, diagnosis and treatment, therefore the EU has largely invested in proteomics, in particular for technology development, data standardisation and sharing efforts, and the application of proteomics in the clinic. The scientific community, including both academia and industry, is encouraged to apply for FP7 funding so that the EU can even more efficiently support innovative health research and ultimately, bring better healthcare to patients.     

Clinical application of tear proteomics: Present and future prospects

Human tear fluid is charactered with very small volume and complex protein constitutes with a very large orders of magnitude. The tear proteome analysis provides a unique dataset (i.e., specific protein markers or protein patterns) that may be correlated to more effective diagnosis, prognosis, and response to therapy. Compared to less than 100 tear proteins obtained by the traditional methods, more than 400 proteins have been found in human tear fluid by current proteomic technologies. Many proteomics techniques, such as 2-DE, MALDI-TOF-MS, LC-MS, SELDI-TOF-MS, protein arrays, have been used to perform tear proteome analysis in healthy and/or disease subjects. The clinical application of tear proteomics needs suitable tear collection methods, standard tear handling procedures, and more sensitive and reliable proteomic technologies.     

Combining laser capture microdissection and proteomics: methodologies and clinical applications

Laser capture microdissection (LCM) has become an important tool for biomedical research. Various molecular biology techniques have been combined with LCM to reveal molecular profiles at an unprecedented tissue resolution. Proteomics is among those techniques that have proved fruitful in combination with LCM. This review provides an overview of the various proteomic techniques that have been developed for analyzing cells obtained using LCM. Methods for analyzing microdissected cells for various proteomic techniques are described and compared. In addition, various applications based on LCM and proteomics are discussed.     

Human resource development,domains of information technology use,and levels of economic prosperity

We report on a research model that was developed and tested to empirically investigate the associations of education quality, on-the-job training, the maturity of information and communications technology (ICT) use by individuals, businesses and governments, and gross domestic product (GDP) per capita across 122 countries. Overall, the findings indicate that education quality is positively associated with GDP per capita, while on-the-job training is not. Education quality is positively associated with ICT use by individuals and governments, but weakly with ICT use by business. On-the-job training, however, is positively associated with all three domains of ICT use. We then separately analyze countries with higher and lower levels of GDP per capita and find both similarities and differences. Healthy composite reliabilities and R²s are obtained in all analyses. The research model, its analysis, and discussion of the results are presented. © 2008 Wiley Periodicals, Inc.     

数字人与人体仿真

20世纪末提出的数字人研究如今已经成为生命与信息科学领域的一个热点问题.数字人结合了医学和计算机科学的最新成果,试图运用信息技术建立数字化人体各层次的计算机模型.其数据反映了人体真实结构和物理、生理特征,使其在涉及人体仿真的许多方面,如航空航天、军事、医学、汽车等领域具有潜在应用价值.该文介绍了国内外这一研究的进展及相关技术,并根据数字人发展的不同阶段,探讨了它在人体仿真领域的应用.     

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Protein oxidation mechanisms result in a wide array of modifications, from backbone cleavage or protein crosslinking to more subtle modifications such as side chain oxidations. Protein oxidation occurs as part of normal regulatory processes, as a defence mechanism against oxidative stress, or as a deleterious processes when antioxidant defences are overcome. Because blood is continually exposed to reactive oxygen and nitrogen species, blood proteomics should inherently adopt redox proteomic strategies. In this review, we recall the biochemical basis of protein oxidation, review the proteomic methodologies applied to analyse redox modifications, and highlight some physiological and in vitro responses to oxidative stress of various blood components.     

新型生物传感器在蛋白质组学研究中应用进展

微技术和毫微技术的进展,使新技术的广泛领域包括具有毫微大小的机械设计成为可能．这类设计的新型传感器及其分析是蛋白质组学研究中的重要分析仪器和分析方法之一。文章讨论了新型生物传感器的类型,各种不同类型的生物传感器及非传感器生物检测技术对蛋白质敏感的检出限度和分析时间。综述了新型生物传感器在蛋白质分析鉴定、蛋白质组学研究中的应用进展。