Glioma proteomics: Status and perspectives

High grade gliomas are the most common brain tumors in adults and their malignant nature makes them the fourth biggest cause of cancer death. Major efforts in neuro-oncology research are needed to reach similar progress in treatment efficacy as that achieved for other cancers in recent years. In addition to the urgent need to identify novel effective drug targets against malignant gliomas, the search for glioma biomarkers and grade specific protein signatures will provide a much needed contribution to diagnosis, prognosis, treatment decision and assessment of treatment response. Over the past years glioma proteomics has been attempted at different levels, including proteome analysis of patient biopsies and bodily fluids, of glioma cell lines and animal models. Here we provide an extensive review of the outcome of these studies in terms of protein identifications (protein numbers and regulated proteins), with an emphasis on the methods used and the limitations of the studies with regard to biomarker discovery. This is followed by a perspective on novel technologies and on the potential future contribution of proteomics in a broad sense to understanding glioma biology.     

Amyloids and prions in plants: Facts and perspectives

Amyloids represent protein fibrils that have highly ordered structure with unique physical and chemical properties. Amyloids have long been considered lethal pathogens that cause dozens of incurable diseases in humans and animals. Recent data show that amyloids may not only possess pathogenic properties but are also implicated in the essential biological processes in a variety of prokaryotes and eukaryotes. Functional amyloids have been identified in archaea, bacteria, fungi, and animals, including humans. Plants are one of the most poorly studied groups of organisms in the field of amyloid biology. Although amyloid properties have not been shown under native conditions for any plant protein, studies demonstrating amyloid properties for a set of plant proteins in vitro or in heterologous systems in vivo have been published in recent years. In this review, we systematize the data on the amyloidogenic proteins of plants and their functions and discuss the perspectives of identifying novel amyloids using bioinformatic and proteomic approaches.     

Designing biomedical proteomics experiments: state-of-the-art and future perspectives

With the current expanded technical capabilities to perform mass spectrometry-based biomedical proteomics experiments, an improved focus on the design of experiments is crucial. As it is clear that ignoring the importance of a good design leads to an unprecedented rate of false discoveries which would poison our results, more and more tools are developed to help researchers designing proteomic experiments. In this review, we apply statistical thinking to go through the entire proteomics workflow for biomarker discovery and validation and relate the considerations that should be made at the level of hypothesis building, technology selection, experimental design and the optimization of the experimental parameters.     

Concepts and therapeutic perspectives of proteomics

The present paper aims at clarifying some important aspects of proteomics, i.e. the large scale analysis of proteins. To this purpose, the main types of proteomic analyses are presented, i.e. those aiming at determining expression levels and those aiming at unravelling protein-protein interactions networks. Their performances and limitations are outlined, as well as their potential applications in biomedicine, to give an reasoned view of the current state of the art.     

Current perspectives in cancer proteomics

Proteome technology has been used widely in cancer research and is a useful tool for the identification of new cancer markers and treatment-related changes in cancer. This article details the use of proteome technology in cancer research, and laboratory-based and clinical cancer research studies are described. New developments in proteome technology that enable higher sample-throughput are evaluated and methods for enhancing conventional proteome analysis (based on two-dimensional electrophoresis) discussed. The need to couple laboratory-based proteomics research with clinically relevant models of the disease is also considered, as this remains the next main challenge of cancer-related proteome research.     

Lactic acid bacteria and proteomics: current knowledge and perspectives

Lactic acid bacteria (LAB) are widely used in the agro-food industry. Some of the LAB also participate in the natural flora in humans and animals. We review here proteomic studies concerning LAB. Two methods of research can be distinguished. In the first one, a systematic mapping of proteins is attempted, which will be useful for taxonomy and to function assignment of proteins. The second one focuses particularly on proteins whose synthesis is induced by various environmental situations or stresses. However, both approaches are complementary and will give new insights for the use of bacteria in industry, in human health and in the struggle against bacterial pathogens. Interest in LAB is growing, showing thus an increasing concern of their rational use and one can foresee in the near future an increasing use of proteomics as well as genomics.     

Prostate cancer proteomics: clinically useful protein biomarkers and future perspectives

Introduction: Although prostate cancer constitutes one of the most important, death-related diseases in the male population, there is still a need for identification of sensitive biomarkers that could precociously detect the disease and differentiate aggressive from indolent cancers, in order to decrease overtreatment. Proteomics research has improved understanding on mechanisms underlying tumorigenesis, cancer cells migration and invasion potential, and castration resistance. This review has focused on proteomic studies of prostate cancer published in the recent years, with a special emphasis on determination of biomarkers for cancer progression and diagnosis.

Areas covered: Shotgun and targeted-proteomic studies of prostate cancer in different matrices are reviewed, i.e., prostate tissue, prostate cell lines, blood (serum and plasma), urine, seminal plasma, and exosomes. The most important biomarkers for cancer diagnosis and aggressiveness characterization are highlighted.

Expert commentary: In general, results demonstrate alteration in cell cycle control, DNA repair, proteasomal degradation, and metabolic activity. However, these studies suffer from low reproducibility due to heterogeneity of the cancer itself, as well as to techniques utilized for protein identification/quantification. Downstream confirmatory studies in separate cohorts are warranted in order to demonstrate accuracy of these results.     

我国蛋白质组学研究现状及展望

蛋白质组学是系统研究分子机器、亚细胞器、细胞、组织、器官乃至整体等生物体系内蛋白质全组成及其活动规律的科学,已成为21世纪生命科学的焦点之一。本文简要介绍了蛋白质组学研究背景,我国蛋白质组学研究现状、存在问题和前景展望。     

New perspectives on an old disease: proteomics in cancer research

A report on the American Association for Cancer Research Conference 'Advances in Proteomics in Cancer Research', Amelia Island, USA, 27 February-2 March 2007.     

Mass spectrometry imaging: Facts and perspectives from a non-mass spectrometrist point of view

Mass Spectrometry Imaging (MSI, also called Imaging Mass Spectrometry) can be used to map molecules according to their chemical abundance and spatial distribution. This technique is not widely used in mass spectrometry circles and is barely known by other scientists. In this review, a brief overview of the mass spectrometer hardware used in MSI and some of the possible applications of this powerful technique are discussed. I intend to call attention to MSI uses from cell biology to histopathology for biological scientists who have little background in mass spectrometry. MSI facts and perspectives are presented from a non-mass spectrometrist point of view.     

ATP-dependent intercellular Ca2+ signaling in the developing cochlea: Facts,fantasies and perspectives

Hearing relies on a sensitive mechanoelectrical transduction process in the cochlea of the inner ear. The cochlea contains sensory, secretory, neural, supporting and epithelial cells which are all essential to the sound transduction process. It is well known that a complex extracellular purinergic signaling system contributes to cochlear homeostasis, altering cochlear sensitivity and neural output via ATP-gated ion channels (P2X receptors) and G protein-coupled P2Y receptors. This review focuses on the emerging roles of ATP that are currently under investigation in the developing sensory epithelium, with particular emphasis on the link between ATP release, Ca²⁺ signaling, the expression and function of gap junction proteins connexin26 and connexin30, and the acquisition of hearing.     

Systematically Constructing Kinetic Transition Network in Polypeptide from Top to Down: Trajectory Mapping

Molecular dynamics (MD) simulation is an important tool for understanding bio-molecules in microscopic temporal/spatial scales. Besides the demand in improving simulation techniques to approach experimental scales, it becomes more and more crucial to develop robust methodology for precisely and objectively interpreting massive MD simulation data. In our previous work [J Phys Chem B 114, 10266 (2010)], the trajectory mapping (TM) method was presented to analyze simulation trajectories then to construct a kinetic transition network of metastable states. In this work, we further present a top-down implementation of TM to systematically detect complicate features of conformational space. We first look at longer MD trajectory pieces to get a coarse picture of transition network at larger time scale, and then we gradually cut the trajectory pieces in shorter for more details. A robust clustering algorithm is designed to more effectively identify the metastable states and transition events. We applied this TM method to detect the hierarchical structure in the conformational space of alanine-dodeca-peptide from microsecond to nanosecond time scales. The results show a downhill folding process of the peptide through multiple pathways. Even in this simple system, we found that single common-used order parameter is not sufficient either in distinguishing the metastable states or predicting the transition kinetics among these states.     

Redox proteomics: basic principles and future perspectives for the detection of protein oxidation in plants

The production and scavenging of chemically reactive species, such as ROS/RNS, are central to a broad range of biotic and abiotic stress and physiological responses in plants. Among the techniques developed for the identification of oxidative stress-induced modifications on proteins, the so-called 'redox proteome', proteomics appears to be the best-suited approach. Oxidative or nitrosative stress leaves different footprints in the cell in the form of different oxidatively modified components and, using the redox proteome, it will be possible to decipher the potential roles played by ROS/RNS-induced modifications in stressed cells. The purpose of this review is to present an overview of the latest research endeavours in the field of plant redox proteomics to identify the role of post-translational modifications of proteins in developmental cell stress. All the strategies set up to analyse the different oxidized/nitrosated amino acids, as well as the different reactivities of ROS and RNS for different amino acids are revised and discussed. A growing body of evidence indicates that ROS/RNS-induced protein modifications may be of physiological significance, and that in some cellular stresses they may act causatively and not arise as a secondary consequence of cell damage. Thus, although previously the oxidative modification of proteins was thought to represent a detrimental process in which the modified proteins were irreversibly inactivated, it is now clear that, in plants, oxidatively/nitrosatively modified proteins can be specific and reversible, playing a key role in normal cell physiology. In this sense, redox proteomics will have a central role in the definition of redox molecular mechanisms associated with cellular stresses.     

Proteomics in Argentina ‐ limitations and future perspectives: A special emphasis on meat proteomics

Argentina is one of the most relevant countries in Latin America, playing a major role in regional economics, culture and science. Over the last 80 years, Argentinean history has been characterized by several upward and downward phases that had major consequences on the development of science in the country and most recently on proteomics. In this article, we characterize the evolution of Proteomics sciences in Argentina over the last decade and a half. We describe the proteomics publication output of the country in the framework of the regional and international contexts, demonstrating that Argentina is solidly anchored in a regional context, showing results similar to other emergent and Latin American countries, albeit still far from the European, American or Australian realities. We also provide a case‐study on the importance of Proteomics to a specific sector in the area of food science: the use of bacteria of technological interest, highlighting major achievements obtained by Argentinean proteomics scientists. Finally, we provide a general picture of the endeavors being undertaken by Argentinean Proteomics scientists and their international collaborators to promote the Proteomics‐based research with the new generation of scientists and PhD students in both Argentina and other countries in the Southern cone.     

Effectiveness and limitation of two-dimensional gel electrophoresis in bacterial membrane protein proteomics and perspectives

Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) using isoelectric focusing and SDS-PAGE in the first and second dimensions, respectively, is an established means of simultaneously separating over 1000 proteins and two new types have recently been developed. These procedures have significant shortcomings such as low load ability and poor separation of hydrophobic, acidic and alkaline proteins. We therefore modified the protocols to analyze the Bacillus subtilis membrane proteome. The 2D-PAGE techniques effectively separated membrane proteins having one and two transmembrane segments but not those with more than four. Compared with new LC/MS/MS procedures that are independent of electrophoretic separation, 2D-PAGE can globally analyze and quantify proteins at various stages of the cell cycle when labeled with isotopes such as 35S-methionine or the stable isotope, 15N.