Biology Approach (biology + approach)

Distribution by Scientific Domains

Kinds of Biology Approach

  • molecular biology approach
  • system biology approach


  • Selected Abstracts


    A Molecular Biology Approach to Parkinson's Disease

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2001
    K A Jellinger
    No abstract is available for this article. [source]


    Computational Biology Approaches to Plant Metabolism and Photosynthesis: Applications for Corals in Times of Climate Change and Environmental Stress

    JOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 8 2010
    M. James C. Crabbe
    Knowledge of factors that are important in reef resilience helps us to understand how reef ecosystems react following major anthropogenic and environmental disturbances. The symbiotic relationship between the photosynthetic zooxanthellae algal cells and corals is that the zooxanthellae provide the coral with carbon, while the coral provides protection and access to enough light for the zooxanthellae to photosynthesise. This article reviews some recent advances in computational biology relevant to photosynthetic organisms, including Beyesian approaches to kinetics, computational methods for flux balances in metabolic processes, and determination of clades of zooxanthallae. Application of these systems will be important in the conservation of coral reefs in times of climate change and environmental stress. [source]


    Causal mapping as a tool to mechanistically interpret phenomena in cell motility: Application to cortical oscillations in spreading cells

    CYTOSKELETON, Issue 9 2006
    Gabriel E. Weinreb
    Abstract Biological processes that occur at the cellular level and consist of large numbers of interacting elements are highly nonlinear and generally involve multiple time and spatial scales. The quantitative description of these complex systems is of great importance but presents large challenges. We outline a new systems biology approach, causal mapping (CMAP), which is a coarse-grained biological network tool that permits description of causal interactions between the elements of the network and overall system dynamics. On one hand, the CMAP is an intermediate between experiments and physical modeling, describing major requisite elements, their interactions and paths of causality propagation. On the other hand, the CMAP is an independent tool to explore the hierarchical organization of cell and the role of uncertainties in the system. It appears to be a promising easy-to-use technique for cell biologists to systematically probe verbally formulated qualitative hypotheses. We apply the CMAP to study the phenomenon of contractility oscillations in spreading cells in which microtubules have been depolymerized. The precise mechanism by which these oscillations are governed by a complex mechano-chemical system is not known but the data observed in experiments can be described by a CMAP. The CMAP suggests that the source of the oscillations results from the opposing effects of Rho activation leading to a decreased level of myosin light chain phosphatase and a cyclic calcium influx caused by increased membrane tension and leading to a periodically enhanced activation of myosin light chain kinase. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source]


    Development of three-dimensional architecture of the neuroepithelium: Role of pseudostratification and cellular ,community'

    DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2008
    Takaki Miyata
    This review discusses the development of the neuroepithelium (NE) and its derivative ventricular zone (VZ), from which the central nervous system (CNS) is formed. First, the histological features of the NE and VZ are summarized, highlighting the phenomenon of pseudostratification, which is achieved by polarization and interkinetic nuclear migration (INM) of neural progenitor cells. Next, our current understanding of the cellular and molecular mechanisms and biological significance of INM and pseudostratification are outlined. The recent three-dimensional time-lapse observations revealing heterogeneity in cell lineages within the NE and VZ are also described, focusing on the neuronal lineage. Finally, the necessity of comprehensive studies on cell-cell interactions in the NE/VZ is discussed, as well as the importance of electrophysiological and biomechanical approaches. In particular, we suggest that a systems biology approach to the NE/VZ as a cellular ,community' may be fruitful. [source]


    A systems biology approach to understanding atherosclerosis

    EMBO MOLECULAR MEDICINE, Issue 3 2010
    Stephen A. Ramsey
    Abstract Atherosclerosis, a chronic inflammatory disease of the vascular system, presents significant challenges to developing effective molecular diagnostics and novel therapies. A systems biology approach integrating data from large-scale measurements (e.g. transcriptomics, proteomics and genomics) is successfully contributing to deciphering regulatory networks underlying the response of many different cellular systems to perturbations. Such a network analysis strategy using pathway information and data from multiple measurement platforms, tissues and species is a promising approach to elucidate the mechanistic underpinnings of complex diseases. Here, we present our views on the contributions that a systems approach can bring to the study of atherosclerosis, propose ways to tackle the complexity of the disease in a systems manner and review recent systems-level studies of the disease. [source]


    Nutrigenomics,new approaches for human nutrition research

    JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 8 2006
    Helen M Roche
    Abstract Food intake and nutrient exposure are key environmental factors involved in the pathogenesis and progression of the common polygenic, diet-related diseases. An individual's phenotype represents a complex interaction between the human genome and environmental factors during an individual's lifetime. This review explores the concept that there is a dynamic, two-way interaction between nutrition and the human genome which determines gene expression, the metabolic response and an individual's health status. It addresses the relevance of new high-throughput genomic, transcriptomic, proteomic and metabolomic technologies within human nutrition research. Common, polygenic, diet-related diseases (CVD, obesity, T2DM, etc.) reflect multiple genetic variants interacting with numerous environmental factors, each combination making a relatively small contribution to overall cellular homeostasis, whole body metabolism and health. This review highlights the value of a nutrigenomics-based systems biology approach to understanding human nutrition and identifying new biomarkers of nutrition and health. The challenge will be to develop and apply robust nutritional genomics research initiatives that are sensitive enough to take account of both human genetic heterogeneity and diverse nutrient exposure. If nutrigenomic approaches enhance our understanding of human nutrition at the molecular level, then it may be possible to apply a more targeted and effective personalized nutrition approach to attenuate the effect of risk factors associated with diet-related diseases. Indeed it could be proposed that a personalized nutrition approach may assist in improving the effectiveness of dietary guidelines/recommendations in general. Copyright © 2006 Society of Chemical Industry [source]


    Proopiomelanocortin gene expression and ,-endorphin localization in the pituitary, testis, and epididymis of stallion

    MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2006
    L. Soverchia
    Abstract Proopiomelanocortin (POMC) is a precursor protein that contains the sequences of several bioactive peptides including adrenocorticotropin (ACTH), ,-endorphin (,-EP), and melanocyte-stimulating-hormone (MSH). POMC is synthesized in the pituitary gland, brain, and many peripheral tissues. Immunoreactive POMC-derived peptides as well as POMC-like mRNA have been evidenced in several nonpituitary tissues, thus suggesting that POMC is actively synthesized by these tissues. The present study was aimed at evaluating if also in the case of stallion POMC-derived peptide, ,-EP, is produced locally in the testis, thus playing effects in a paracrine/autocrine fashion. To investigate this hypothesis the POMC gene expression was analyzed using 3, RACE-PCR and Northern Blot approaches in the testis and epididimys of stallion; moreover, immunocytochemical localization for ,-EP was also performed through confocal laser microscopy. The immunofluorescence results showed a positive ,-EP reaction not only in cellular nest of pituitary but also in the testis and genital tract of stallion, which function could be related with sperm mobility. Such role seem not to be no dependent on the peptide synthesized locally, because the molecular biology approach demonstrated the presence of POMC transcript in the pituitary only. In fact the Northern Blot analysis showed the presence of a single POMC transcript in the pituitary while no signal was detected in the testis and epididimys. The same results were obtained by applied 3, RACE-PCR analysis. In conclusion, opioid-derived peptide ,-EP is present in the genital tract of stallion, but is not locally produced as in other mammalian, and nonmammalian models; its possible biological function at testicular level could be linked to a long-loop feed-back mechanisms. Mol. Reprod. Dev. © 2005 Wiley-Liss, Inc. [source]


    Moss Systems Biology en Route: Phytohormones in Physcomitrella Development

    PLANT BIOLOGY, Issue 3 2006
    E. L. Decker
    Abstract: The moss Physcomitrella patens has become a powerful model system in modern plant biology. Highly standardized cell culture techniques, as well as the necessary tools for computational biology, functional genomics and proteomics have been established. Large EST collections are available and the complete moss genome will be released soon. A simple body plan and the small number of different cell types in Physcomitrella facilitate the study of developmental processes. In the filamentous juvenile moss tissue, developmental decisions rely on the differentiation of single cells. Developmental steps are controlled by distinct phytohormones and integration of environmental signals. Especially the phytohormones auxin, cytokinin, and abscisic acid have distinct effects on early moss development. In this article, we review current knowledge about phytohormone influences on early moss development in an attempt to fully unravel the complex regulatory signal transduction networks underlying the developmental decisions of single plant cells in a holistic systems biology approach. [source]


    From proteomics to systems biology of bacterial pathogens: Approaches, tools, and applications

    PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2007
    Uwe Plikat Dr.
    Abstract The hallmark of a systems biology approach is the integration of computational tools with experimental data encompassing multiple classes of biomolecules across different functional levels. Equally important as the availability of reasonably comprehensive information at the gene, protein, and metabolite levels is the development of adequate analysis and visualization tools to reduce the inherent complexity to interpretable dimensions. In this paper, we describe the integration of a 2-D gel-based proteome map of Staphylococcus aureus Mu50 with genomic and transcriptomic information through a customized data integration and user interface built on the Ensembl genome browser. We illustrate its application and potential through the analysis of a defined system perturbation caused by a mutation in the formyltransferase gene. We envision that this software package, which we called Insieme, can support the development of novel antibiotics by allowing a systems-based view of the bacterial response pathways. [source]


    Mathematical modeling of the circadian rhythm of key neuroendocrine,immune system players in rheumatoid arthritis: A systems biology approach

    ARTHRITIS & RHEUMATISM, Issue 9 2009
    Michael Meyer-Hermann
    Objective Healthy subjects and patients with rheumatoid arthritis (RA) exhibit circadian rhythms of the neuroendocrine,immune system. Understanding circadian dynamics is complex due to the nonlinear behavior of the neuroendocrine,immune network. This study was undertaken to seek and test a mathematical model for studying this network. Methods We established a quantitative computational model to simulate nonlinear interactions between key factors in the neuroendocrine,immune system, such as plasma tumor necrosis factor (TNF), plasma cortisol (and adrenal cholesterol store), and plasma noradrenaline (NA) (and presynaptic NA store). Results The model was nicely fitted with measured reference data on healthy subjects and RA patients. Although the individual circadian pacemakers of cortisol, NA, and TNF were installed without a phase shift, the relative phase shift between these factors evolved as a consequence of the modeled network interactions. Combined long-term and short-term TNF increase (the "RA model") increased cortisol plasma levels for only a few days, and cholesterol stores started to become markedly depleted. This nicely demonstrated the phenomenon of inadequate cortisol secretion relative to plasma TNF levels, as a consequence of adrenal deficiency. Using the RA model, treatment with glucocorticoids between midnight and 2:00 AM was found to have the strongest inhibitory effect on TNF secretion, which supports recent studies on RA therapy. Long-term reduction of TNF levels by simulation of anti-TNF therapy normalized cholesterol stores under "RA" conditions. Conclusion These first in silico studies of the neuroendocrine,immune system in rheumatology demonstrate that computational biology in medicine, making use of large collections of experimental data, supports understanding of the pathophysiology of complex nonlinear systems. [source]


    The meaning of clinical remission in polyarticular juvenile idiopathic arthritis: Gene expression profiling in peripheral blood mononuclear cells identifies distinct disease states

    ARTHRITIS & RHEUMATISM, Issue 3 2009
    Nicholas Knowlton
    Objective The development of biomarkers to predict response to therapy in polyarticular juvenile idiopathic arthritis (JIA) is an important issue in pediatric rheumatology. A critical step in this process is determining whether there is biologic meaning to clinically derived terms such as "active disease" and "remission." The aim of this study was to use a systems biology approach to address this question. Methods We performed gene transcriptional profiling on children who fulfilled the criteria for specific disease states as defined by the consensus criteria developed by Wallace and colleagues. The study group comprised children with active disease (n = 14), children with clinical remission on medication (CRM; n = 9), children with clinical remission off medication (CR; n = 6), and healthy control children (n = 13). Transcriptional profiles in peripheral blood mononuclear cells (PBMCs) were obtained using Affymetrix U133 Plus 2.0 arrays. Results Hierarchical cluster analysis and predictive modeling demonstrated that the clinically derived criteria represent biologically distinct states. Minimal differences were seen between children with active disease and those with disease in CRM. Thus, underlying immune/inflammatory abnormalities persist despite a response to therapy. The PBMC transcriptional profiles of children whose disease was in remission did not return to normal but revealed networks of proinflammatory and antiinflammatory genes, suggesting that remission is a state of homeostasis, not a return to a normal state. Conclusion Gene transcriptional profiling of PBMCs revealed that clinically derived criteria for JIA disease states reflect underlying biology. We also demonstrated that neither CRM nor CR status results in resolution of the underlying inflammatory process, but that these conditions are more likely to be states of balanced homeostasis between proinflammatory and antiinflammatory mechanisms. [source]


    Systems biology analysis of sjögren's syndrome and mucosa-associated lymphoid tissue lymphoma in parotid glands

    ARTHRITIS & RHEUMATISM, Issue 1 2009
    Shen Hu
    Objective To identify key target genes and activated signaling pathways associated with the pathogenesis of Sjögren's syndrome (SS) by conducting a systems analysis of parotid glands manifesting primary SS or primary SS/mucosa-associated lymphoid tissue (MALT) lymphoma phenotypes. Methods A systems biology approach was used to analyze parotid gland tissue samples obtained from patients with primary SS, patients with primary SS/MALT lymphoma, and subjects without primary SS (non,primary SS controls). The tissue samples were assessed concurrently by gene-expression microarray profiling and proteomics analysis, followed by weighted gene-coexpression network analysis. Results Gene-coexpression modules related to primary SS and primary SS/MALT lymphoma were significantly enriched with genes known to be involved in the immune/defense response, apoptosis, cell signaling, gene regulation, and oxidative stress. Detailed functional pathway analyses indicated that primary SS,associated modules were enriched with genes involved in proteasome degradation, apoptosis, signal peptides of the class I major histocompatibility complex (MHC), complement activation, cell growth and death, and integrin-mediated cell adhesion, while primary SS/MALT lymphoma,associated modules were enriched with genes involved in translation, ribosome biogenesis and assembly, proteasome degradation, class I MHC signal peptides, the G13 signaling pathway, complement activation, and integrin-mediated cell adhesion. Combined analyses of gene expression and proteomics data implicated 6 highly connected "hub" genes for distinguishing primary SS from non,primary SS, and 8 hub genes for distinguishing primary SS/MALT lymphoma from primary SS. Conclusion Systems biology analyses of the parotid glands from patients with primary SS and those with primary SS/MALT lymphoma revealed pathways and molecular targets associated with disease pathogenesis. The identified gene modules/pathways provide further insights into the molecular mechanisms of primary SS and primary SS/MALT lymphoma. The identified disease-hub genes represent promising targets for therapeutic intervention, diagnosis, and prognosis. [source]


    Abiotic stress and plant responses from the whole vine to the genes

    AUSTRALIAN JOURNAL OF GRAPE AND WINE RESEARCH, Issue 2010
    G.R. CRAMER
    Abstract Drought, salinity and extreme temperatures significantly limit the distribution of grapes around the world. In this review, the literature of grape responses to abiotic stress with particular reference to whole plant and molecular responses observed in recent studies is discussed. A number of short-term and long-term studies on grapevine shoots and berries have been conducted using a systems biology approach. Transcripts, proteins and metabolites were profiled. Water deficit, salinity and chilling altered the steady-state abundance of a large number of transcripts. Common responses to these stresses included changes in hormone metabolism, particularly abscisic acid (ABA), photosynthesis, growth, transcription, protein synthesis, signalling and cellular defences. Some of the transcriptional changes induced by stress were confirmed by proteomic and metabolomic analyses. More than 2000 genes were identified whose transcript abundance was altered by both water deficit and ABA. Different gene sets were used to map molecular pathways regulated by ABA, water deficit, salinity and chilling in grapevine. This work supports the hypothesis that ABA is a central regulator of abiotic stress tolerance mechanisms. ABA affects signalling pathways that trigger important molecular activities involving metabolism, transcription, protein synthesis, and cellular defence and also regulates important physiological responses such as stomatal conductance, photoprotection and growth. Systems biology approaches are providing more comprehensive understanding of the complex plant responses to abiotic stress. The molecular sets generated from mapping the ABA-inducible stress responses provide numerous targets for genetic and cultural manipulation for improved plant protection and grape quality. [source]


    Physiologically Based Modelling and Prediction of Drug Interactions

    BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2010
    Frédéric Y. Bois
    This article reviews briefly past developments in the area of physiologically based pharmacokinetic (PBPK) modelling of interactions. It also demonstrates a systems biology approach to the question, and the capabilities of new software tools to facilitate that development. Individual Systems Biology Markup Language models of metabolic pathways can now be automatically merged and coupled to a template PBPK pharmacokinetic model, using for example the GNU MCSim software. The global model generated is very efficient and able to simulate the interactions between a theoretically unlimited number of substances. Development time and the number of model parameter increase only linearly with the number of substances considered, even though the number of possible interactions increases exponentially. [source]


    Proteomics: Recent Applications and New Technologies

    BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2006
    Mollisa M. Elrick
    Proteomic analyses have recently been conducted on tissues, biofluids, subcellular components and enzymatic pathways as well as various disease and toxicological states, in both animal models and man. In addition, several recent studies have attempted to integrate proteomics data with genomics and/or metabonomics data in a systems biology approach. The translation of proteomic technology and bioinformatics tools to clinical samples, such as in the areas of disease and toxicity biomarkers, represents one of the major opportunities and challenges facing this field. An ongoing challenge in proteomics continues to be the analysis of the serum proteome due to the vast number and complexity of proteins estimated to be present in this biofluid. Aside from the removal of the most abundant proteins, a number of interesting approaches have recently been suggested that may help reduce the overall complexity of serum analysis. In keeping with the increasing interest in applications of proteomics, the tools available for proteomic analyses continue to improve and expand. For example, enhanced tools (such as software and labeling procedures) continue to be developed for the analysis of 2D gels and protein quantification. In addition, activity-based probes are now being used to tag, enrich and isolate distinct sets of proteins based on enzymatic activity. One of the most active areas of development involves microarrays. Antibody-based microarrays have recently been released as commercial products while numerous additional capture agents (e.g. aptamers) and many additional types of microarrays are being explored. [source]


    Genome-wide analysis of host responses to the Pseudomonas aeruginosa type III secretion system yields synergistic effects

    CELLULAR MICROBIOLOGY, Issue 11 2005
    Jeffrey K. Ichikawa
    Summary The type III secretion system (TTSS) is a dedicated bacterial pathogen protein targeting system that directly affects host cell signalling and response pathways. Our goal was to identify host responses to the Pseudomonas aeruginosa effectors, introduced into target cells utilizing the TTSS. We carried out expression profiling of a human lung pneumocyte cell line A549 exposed to isogenic mutants of P. aeruginosa PAK lacking individual or a combination of TTSS components. We then devised a data analysis method to isolate the key responses to specific secreted bacterial effector proteins as well as components of the TTSS machinery. Individually, the effector proteins elicited host responses consistent with their known functions, many of which were cell cycle-related. However, our analysis has shown that the effector proteins elicit a distinct host transcriptional response when present in combination, suggesting a synergistic effect. Furthermore, the pattern of host transcriptional responses is consistent with the pore forming ability of the TTSS needle complex. This study shows that the individual components of the TTSS define an integrated system and that a systems biology approach is required to fully understand the complex interplay between pathogen and host. [source]


    SPATIAL AND TEMPORAL ASPECTS OF cAMP SIGNALLING IN CARDIAC MYOCYTES

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2008
    Radu V Iancu
    SUMMARY 1,1 -Adrenoceptor and M2 muscarinic receptor regulation of cAMP production plays a pivotal role in autonomic regulation of cardiac myocyte function. However, not all responses are easily explained by a uniform increase or decrease in cAMP activity throughout the entire cell. 2Adenovirus expression of fluorescence resonance energy transfer (FRET)-based biosensors can be used to monitor cAMP activity in protein kinase A (PKA) signalling domains, as well as the bulk cytoplasmic domain of intact adult cardiac myocytes. 3Data obtained using FRET-based biosensors expressed in different cellular microdomains have been used to develop a computational model of compartmentalized cAMP signalling. 4A systems biology approach that uses quantitative computational modelling together with experimental data obtained using FRET-based biosensors has been used to provide evidence for the idea that compartmentation of cAMP signalling is necessary to explain the stimulatory responses to ,1 -adrenoceptor activation as well as the complex temporal responses to M2 muscarinic receptor activation. [source]


    Research Agenda for Frailty in Older Adults: Toward a Better Understanding of Physiology and Etiology: Summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2006
    Jeremy Walston MD
    Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty. Although social and psychological aspects of frailty are critically important and merit future research, these topics were largely beyond the scope of this meeting. Included in this article are sections on the evolving conceptualization and definitions of frailty; physiological underpinnings of frailty, including the potential contributions of inflammatory, endocrine, skeletal muscle, and neurologic system changes; potential molecular and genetic contributors; proposed animal models; and integrative, system biology approaches that may help to facilitate future frailty research. In addition, several specific recommendations as to future directions were developed from suggestions put forth by participants, including recommendations on definition and phenotype development, methodological development to perform clinical studies of individual-system and multiple-system vulnerability to stressors, development of animal and cellular models, application of population-based studies to frailty research, and the development of large collaborative networks in which populations and resources can be shared. This meeting and subsequent article were not meant to be a comprehensive review of frailty research; instead, they were and are meant to provide a more-targeted research agenda-setting process. [source]


    Endothelial barriers: from hypothetical pores to membrane proteins*

    JOURNAL OF ANATOMY, Issue 6 2002
    J. A. Firth
    Abstract The anatomical counterpart of the physiologically defined small pore system of capillary endothelia has proved difficult to establish. In non-brain continuous capillaries, the contributions of caveolar and transmembrane pathways are likely to be small and paracellular clefts are probably the dominant routes. Analogy with epithelial paracellular pathways suggests that tight junctions may be the most restrictive elements. However, structural features of tight junction-based models are incompatible with physiological data; it is more likely that the tight junction acts as a shutter limiting the available cleft area. Proposed molecular sieves elsewhere in the paracellular pathway include the glycocalyx and the cadherin-based complexes of the adherens junctions. The molecular architecture of tight junctions and adherens junctions is moderately well defined in terms of molecular species, and there are differences at both sites between the endothelial and epithelial spectra of protein expression. However, definition of the size-restricting pore remains elusive and may require structural biology approaches to the spatial arrangements and interactions of the membrane molecular complexes surrounding the endothelial paracellular clefts. [source]


    Systems biology approaches for toxicology,

    JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2007
    William Slikker Jr
    Abstract Systems biology/toxicology involves the iterative and integrative study of perturbations by chemicals and other stressors of gene and protein expression that are linked firmly to toxicological outcome. In this review, the value of systems biology to enhance the understanding of complex biological processes such as neurodegeneration in the developing brain is explored. Exposure of the developing mammal to NMDA (N -methyl- d -aspartate) receptor antagonists perturbs the endogenous NMDA receptor system and results in enhanced neuronal cell death. It is proposed that continuous blockade of NMDA receptors in the developing brain by NMDA antagonists such as ketamine (a dissociative anesthetic) causes a compensatory up-regulation of NMDA receptors, which makes the neurons bearing these receptors subsequently more vulnerable (e.g. after ketamine washout), to the excitotoxic effects of endogenous glutamate: the up-regulation of NMDA receptors allows for the accumulation of toxic levels of intracellular Ca2+ under normal physiological conditions. Systems biology, as applied to toxicology, provides a framework in which information can be arranged in the form of a biological model. In our ketamine model, for example, blockade of NMDA receptor up-regulation by the co-administration of antisense oligonucleotides that specifically target NMDA receptor NR1 subunit mRNA, dramatically diminishes ketamine-induced cell death. Preliminary gene expression data support the role of apoptosis as a mode of action of ketamine-induced neurotoxicity. In addition, ketamine-induced cell death is also prevented by the inhibition of NF- ,B translocation into the nucleus. This process is known to respond to changes in the redox state of the cytoplasm and has been shown to respond to NMDA-induced cellular stress. Although comprehensive gene expression/proteomic studies and mathematical modeling remain to be carried out, biological models have been established in an iterative manner to allow for the confirmation of biological pathways underlying NMDA antagonist-induced cell death in the developing nonhuman primate and rodent. Published in 2007 John Wiley & Sons, Ltd. [source]


    Future Prospects for Biomarkers of Alcohol Consumption and Alcohol-Induced Disorders

    ALCOHOLISM, Issue 6 2010
    Willard M. Freeman
    The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis, treatment, and research of alcohol abuse and alcoholism. Successful development of a biomarker that allows for accurate assessment of alcohol intake and drinking patterns would not only be a major advance in clinical care but also a valuable research tool. A number of advances have been made in testing the validity of proposed biomarkers as well as in identifying potential new biomarkers through systems biology approaches. This commentary will examine the definition of a biomarker of heavy drinking, the types of potential biomarkers, the steps in biomarker development, the current state of biomarker development, and critical obstacles for the field. The challenges in developing biomarkers for alcohol treatment and research are similar to those found in other fields. However, the alcohol research field must reach a competitive level of rigor and organization. We recommend that NIAAA consider taking a leadership role in organizing investigators in the field and providing a common set of clinical specimens for biomarker validation studies. [source]


    Advances in proteomics data analysis and display using an accurate mass and time tag approach

    MASS SPECTROMETRY REVIEWS, Issue 3 2006
    Jennifer S.D. Zimmer
    Abstract Proteomics has recently demonstrated utility for increasing the understanding of cellular processes on the molecular level as a component of systems biology approaches and for identifying potential biomarkers of various disease states. The large amount of data generated by utilizing high efficiency (e.g., chromatographic) separations coupled with high mass accuracy mass spectrometry for high-throughput proteomics analyses presents challenges related to data processing, analysis, and display. This review focuses on recent advances in nanoLC-FTICR-MS-based proteomics approaches and the accompanying data processing tools that have been developed to display and interpret the large volumes of data being produced. © 2006 Wiley Periodicals, Inc., Mass Spec Rev 25:450,482, 2006 [source]


    Next generation of elevated [CO2] experiments with crops: a critical investment for feeding the future world

    PLANT CELL & ENVIRONMENT, Issue 9 2008
    ELIZABETH A. AINSWORTH
    ABSTRACT A rising global population and demand for protein-rich diets are increasing pressure to maximize agricultural productivity. Rising atmospheric [CO2] is altering global temperature and precipitation patterns, which challenges agricultural productivity. While rising [CO2] provides a unique opportunity to increase the productivity of C3 crops, average yield stimulation observed to date is well below potential gains. Thus, there is room for improving productivity. However, only a fraction of available germplasm of crops has been tested for CO2 responsiveness. Yield is a complex phenotypic trait determined by the interactions of a genotype with the environment. Selection of promising genotypes and characterization of response mechanisms will only be effective if crop improvement and systems biology approaches are closely linked to production environments, that is, on the farm within major growing regions. Free air CO2 enrichment (FACE) experiments can provide the platform upon which to conduct genetic screening and elucidate the inheritance and mechanisms that underlie genotypic differences in productivity under elevated [CO2]. We propose a new generation of large-scale, low-cost per unit area FACE experiments to identify the most CO2 -responsive genotypes and provide starting lines for future breeding programmes. This is necessary if we are to realize the potential for yield gains in the future. [source]


    Identification of the proteins present in the bull sperm cytosolic fraction enriched in tyrosine kinase activity: A proteomic approach

    PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 16 2006
    Claudia Lalancette
    Abstract Numerous sperm proteins have been identified on the basis of their increase in tyrosine phosphorylation during capacitation. However, the tyrosine kinases present in spermatozoa that are responsible for this phosphorylation remain unknown. As spermatozoa are devoid of transcriptional and translational activities, molecular biology approaches might not reflect the transcriptional pattern in mature spermatozoa. Working directly with the proteins present in ejaculated spermatozoa is the most reliable approach to identify the tyrosine kinases potentially involved in the capacitation-associated increase in protein tyrosine phosphorylation. A combination of tyrosine kinase assays and proteomic identification tools were used as an approach to identify sperm protein tyrosine kinases. Fractionation by nitrogen cavitation showed that the majority of tyrosine kinase activity is present in the cytosolic fraction of bovine spermatozoa. By the use of Poly-Glu:Tyr(4:1)-agarose affinity chromatography, we isolated a fraction enriched in tyrosine kinase activity. Proteomics approaches permitted the identification of tyrosine kinases from three families: Src (Lyn), Csk, and Tec (Bmx, Btk). We also identified proteins implicated in different cellular events associated with sperm capacitation and acrosome reaction. These results confirm the implication of tyrosine phosphorylation in some aspects of capacitation/acrosome reaction and reveal the identity of new players potentially involved in these processes. [source]


    Abiotic stress and plant responses from the whole vine to the genes

    AUSTRALIAN JOURNAL OF GRAPE AND WINE RESEARCH, Issue 2010
    G.R. CRAMER
    Abstract Drought, salinity and extreme temperatures significantly limit the distribution of grapes around the world. In this review, the literature of grape responses to abiotic stress with particular reference to whole plant and molecular responses observed in recent studies is discussed. A number of short-term and long-term studies on grapevine shoots and berries have been conducted using a systems biology approach. Transcripts, proteins and metabolites were profiled. Water deficit, salinity and chilling altered the steady-state abundance of a large number of transcripts. Common responses to these stresses included changes in hormone metabolism, particularly abscisic acid (ABA), photosynthesis, growth, transcription, protein synthesis, signalling and cellular defences. Some of the transcriptional changes induced by stress were confirmed by proteomic and metabolomic analyses. More than 2000 genes were identified whose transcript abundance was altered by both water deficit and ABA. Different gene sets were used to map molecular pathways regulated by ABA, water deficit, salinity and chilling in grapevine. This work supports the hypothesis that ABA is a central regulator of abiotic stress tolerance mechanisms. ABA affects signalling pathways that trigger important molecular activities involving metabolism, transcription, protein synthesis, and cellular defence and also regulates important physiological responses such as stomatal conductance, photoprotection and growth. Systems biology approaches are providing more comprehensive understanding of the complex plant responses to abiotic stress. The molecular sets generated from mapping the ABA-inducible stress responses provide numerous targets for genetic and cultural manipulation for improved plant protection and grape quality. [source]


    New insights into the pathogenic role of advanced glycation in diabetic retinopathy

    ACTA OPHTHALMOLOGICA, Issue 2008
    AW STITT
    Purpose Retinopathy is the most common microvascular complication of diabetes. The clinicopathology of microvascular lesions and neuroglial dysfunction in the diabetic retina have been extensively studied, although the relative contribution of various biochemical sequelae of hyperglycaemia remains ill-defined. The formation and accumulation of advanced glycation endproducts (AGEs) is an important pathogenic pathway in the progression of diabetic retinopathy although some of the cellular and molecular pathologies initiated by these adducts in retinal cells remain unknown. Methods This presentation will cover several aspects of AGE-linked retinal pathology and demonstrate opportunities for therapeutic intervention. The studies outlined will cover a wide range of molecular cell biology approaches using appropriate in vitro and in vivo model systems. Results It will be demonstrated that AGEs form in vivo in the diabetic retina through the reaction of alpha-oxaloaldehydes leading to significant modifications of retinal proteins. Evidence will be presented to demonstrate that these AGEs act as significant effectors of retinal vascular and neuroglial cell dysfunction, leading to pro-inflammatory responses, growth factor imbalance and, ultimately, neurovascular lesions such as blood retinal barrier dysfunction and microvascular degeneration. The protective role of novel AGE-inhibitors will also be shown. Conclusion Evidence now points towards a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy and this review lecture will outline the current state of knowledge of AGE-related pathology in the retina at a cellular and molecular level. [source]


    When does a protein become an allergen?

    CLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2008
    Searching for a dynamic definition based on most advanced technology tools
    Summary Since the early beginning of allergology as a science considerable efforts have been made by clinicians and researchers to identify and characterize allergic triggers as raw allergenic materials, allergenic sources and tissues, and more recently basic allergenic structures defined as molecules. The last 15,20 years have witnessed many centres focusing on the identification and characterization of allergenic molecules leading to an expanding wealth of knowledge. The need to organize this information leads to the most important question ,when does a protein become an allergen?' In this article, I try to address this question by reviewing a few basic concepts of the immunology of IgE-mediated diseases, reporting on the current diagnostic and epidemiological tools used for allergic disease studies and discussing the usefulness of novel biotechnology tools (i.e. proteomics and molecular biology approaches), information technology tools (i.e. Internet-based resources) and microtechnology tools (i.e. proteomic microarray for IgE testing on molecular allergens). A step-wise staging of the identification and characterization process, including bench, clinical and epidemiological aspects, is proposed, in order to classify allergenic molecules dynamically. This proposal reflects the application and use of all the new tools available from current technologies. [source]