bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic analysis of differential protein expression induced by ultraviolet light radiation in HeLa cells
Authors: Decker Emily D. , Zhang Yinong , Cocklin Ross R. , Witzmann Frank A. , Wang Mu 
Published: November 2003

AbstractCells treated with ultraviolet (UV) radiation undergo cell cycle arrest at the S‐phase and G1/S boundary, allowing DNA repair to occur. Several proteins such as replication protein A and DNA‐dependent protein kinase have been suggested to be involved in UV‐induced inhibition of DNA replication. However, the role of these proteins in inhibiting DNA replication remains unknown. Other proteins may play important roles in modulating functions of these proteins in response to UV‐irradiation. To understand the broad range of proteins involved in this inhibition, we carried out a systematic study to identify specific proteins involved in UV‐induced replication arrest using two‐dimensional gel electrophoresis and mass spectrometry. Unique changes in protein expression level for 31 proteins were observed over a 24‐hour time course, including calgizzarin, cyclophilin A, and macrophage migration inhibitory factor. The expression level changes of these proteins are dynamically correlated to DNA replication activity, suggesting involvement of these proteins in modulating DNA replication and repair activities. This proteomic approach provides opportunities to gain insights into the mechanism by which DNA replication is inhibited.
GLYCO‐FRAGMENT: A web tool to support the interpretation of mass spectra of complex carbohydrates
Authors: Lohmann Klaus K. , von der Lieth Claus‐W. 
Published: November 2003

AbstractMass spectrometry is frequently used to analyze complex oligosaccharides and glycopeptides. The spectra of glycans can be complicated and difficult to interpret without reference data. Unfortunately, no libraries of suitably pure and homogeneous standards have so far been compiled. The web‐based tool GLYCO‐FRAGMENT allows the generation of all theoretically possible MS relevant fragments of oligosaccharides as defined using the extended IUPAC nomenclature. The main focus of GLYCO‐FRAGMENT is to support the manual assignment of all peaks contained in mass spectra of complex carbohydrates. The service is available at http://www.dkfz.de/spec/projekte/fragments/.
Overcoming technical variation and biological variation in quantitative proteomics
Authors: Molloy Mark P. , Brzezinski Erin E. , Hang Junqi , McDowell Michael T. , VanBogelen Ruth A. 
Published: November 2003

AbstractQuantitative proteomics investigates physiology at the molecular level by measuring relative differences in protein expression between samples under different experimental conditions. A major obstacle to reliably determining quantitative changes in protein expression is to overcome error imposed by technical variation and biological variation. In drug discovery and development the issue of biological variation often rises in concordance with the developmental stage of research, spanning from in vitro assays to clinical trials. In this paper we present case studies to raise awareness to the issues of technical variation and biological variation and the impact this places on applying quantitative proteomics. We defined the degree of technical variation from the process of two‐dimensional electrophoresis as 20–30% coefficient of variation. On the other hand, biological variation observed experiment‐to‐experiment showed a broader degree of variation depending upon the sample type. This was demonstrated with case studies where variation was monitored across experiments with bacteria, established cell lines, primary cultures, and with drug treated human subjects. We discuss technical variation and biological variation as key factors to consider during experimental design, and offer insight into preparing experiments that overcome this challenge to provide statistically significant outcomes for conducting quantitative proteomic research.
Functional proteomics of neurokinin B in the placenta indicates a novel role in regulating cytotrophoblast antioxidant defences
Authors: Sawicki Grzegorz , Dakour Jamal , Morrish Donald W. 
Published: November 2003

AbstractNeurokinin B (NKB) has recently been demonstrated to be secreted from the placenta in abnormally high amounts in preeclampsia (PE) and to cause hypertension in rats, suggesting it may be a mediator of some pathophysiological features of PE. It is also known that NKB receptors exist in the placenta. To determine the effect of high levels of NKB on the placenta, we have performed proteomics on five separate preparations of cultured purified human term cytotrophoblast cells. The results showed a statistically significant decrease in 20 proteins, of which five were unknown proteins. Proteins important in antioxidant defenses that decreased were thioredoxin, cyclophilin A, cytokeratin 1, and peroxiredoxin 5. Two proteins that inhibit intravascular anticoagulation, cytokeratin 1 and annexin 11 were also decreased. Pathways involving pro‐inflammatory cytokine activation of NF‐κB are opposed by Raf kinase inhibitor protein, which was also decreased. Cofilin 1, a protein involved in defense against bacteria, was also decreased. Among other proteins that were suppressed by NKB were proteasome proteins, desmoplakin, and calgizzarin. Western blots confirmed the decrease in cytokeratin 1 and cyclophilin A protein after NKB exposure. In PE, there is reduced antioxidant activity and increased intravascular coagulation. The findings that high levels of NKB, similar to those observed in PE, can impair these two classes of activity support the hypothesis that high NKB levels may contribute to the pathogenesis of PE.
Carbon starvation survival of Listeria monocytogenes in planktonic state and in biofilm: A proteomic study
Authors: Helloin Emmanuelle , Jänsch Lothar , Phan‐Thanh Luu 
Published: November 2003

AbstractThe proteomes of Listeria monocytogenes expressed in suspension and biofilm state, in the presence and absence of a caron source, were analysed by two‐dimensional electrophoresis with the help of computer software. The up‐regulated proteins in each case were identified by peptide sequencing using electrospray ionisation tandem mass spectrometry and a database search against the Listeria genome was performed. Relevant functions could be attributed to a number of the induced proteins which contibute to the understanding of the mechanisms of starvation survival of L. monocytogenes in planktonic state and in biofilm.
Toward the identification of liver toxicity markers: A proteome study in human cell culture and rats
Authors: Thome‐Kromer Birgit , Bonk Ines , Klatt Mathias , Nebrich Grit , Taufmann Marion , Bryant Stewart , Wacker Ulrich , Köpke Andreas 
Published: November 2003

AbstractThe effects of toxic and nontoxic compound treatments were investigated by high resolution custom developed 2–11 pH gradient NEPHGE (non equilibrium pH gradient electrophoresis) two‐dimensional electrophoresis. Two models were compared: (i) in vivo rat and (ii) the human cell line HepG2, to test their suitability in a proteomics based approach to identify a toxicity marker. 163 and 321 proteins were identified from the rat liver and the HepG2 proteome. These represent various isoforms of 113 and 194 different NCBI annotated gene sequences, respectively. Nine compounds were selected to induce proteome variations associated with liver toxicity and metabolism. The rat liver proteome database consists of 78 gels, the HepG2 database of 52 gels. Variant proteins were assessed regarding their usefulness as a toxicity marker by evaluating their treatment specificity against multiple control treatments. Thirteen potential toxicity marker proteins were found in rat liver and eight in HepG2. Catalase and carbamoylphosphate synthetase‐1 isoforms were found to be significantly changed after treatment by 4/4 and 3/4 toxic compounds in rat liver, respectively. Aldo‐keto‐reductase family 1, member C1 was implicated for 3/4 liver cell toxic compounds in HepG2. Our approach was able to differentiate the quality of potential toxicity markers and provided useful information for an ongoing characterization of more compounds in a wider number of toxicity classes.
Proteome of Caulobacter crescentus cell cycle publicly accessible on SWICZ server
Authors: Vohradsky Jiri , Janda Ivan , Grünenfelder Björn , Berndt Peter , Röder Daniel , Langen Hanno , Weiser Jaroslav , Jenal Urs 
Published: November 2003

AbstractHere we present the Swiss‐Czech Proteomics Server (SWICZ), which hosts the proteomic database summarizing information about the cell cycle of the aquatic bacterium Caulobacter crescentus. The database provides a searchable tool for easy access of global protein synthesis and protein stability data as examined during the C. crescentus cell cycle. Protein synthesis data collected from five different cell cycle stages were determined for each protein spot as a relative value of the total amount of [35S]methionine incorporation. Protein stability of pulse‐labeled extracts were measured during a chase period equivalent to one cell cycle unit. Quantitative information for individual proteins together with descriptive data such as protein identities, apparent molecular masses and isoelectric points, were combined with information on protein function, genomic context, and the cell cycle stage, and were then assembled in a relational database with a world wide web interface (http://proteom.biomed.cas.cz), which allows the database records to be searched and displays the recovered information. A total of 1250 protein spots were reproducibly detected on two‐dimensional gel electropherograms, 295 of which were identified by mass spectroscopy. The database is accessible either through clickable two‐dimensional gel electrophoretic maps or by means of a set of dedicated search engines. Basic characterization of the experimental procedures, data processing, and a comprehensive description of the web site are presented. In its current state, the SWICZ proteome database provides a platform for the incorporation of new data emerging from extended functional studies on the C. crescentus proteome.
High‐throughput proteomic analysis of human infiltrating ductal carcinoma of the breast
Authors: Somiari Richard I. , Sullivan Anthony , Russell Stephen , Somiari Stella , Hu Hai , Jordan Rick , George Alisha , Katenhusen Richard , Buchowiecka Alicja , Arciero Cletus , Brzeski Henry , Hooke Jeff , Shriver Craig 
Published: November 2003

AbstractLarge‐scale proteomics will play a critical role in the rapid display, identification and validation of new protein targets, and elucidation of the underlying molecular events that are associated with disease development, progression and severity. However, because the proteome of most organisms are significantly more complex than the genome, the comprehensive analysis of protein expression changes will require an analytical effort beyond the capacity of standard laboratory equipment. We describe the first high‐throughput proteomic analysis of human breast infiltrating ductal carcinoma (IDCA) using OCT (optimal cutting temperature) embedded biopsies, two‐dimensional difference gel electrophoresis (2‐D DIGE) technology and a fully automated spot handling workstation. Total proteins from four breast IDCAs (Stage I, IIA, IIB and IIIA) were individually compared to protein from non‐neoplastic tissue obtained from a female donor with no personal or family history of breast cancer. We detected differences in protein abundance that ranged from 14.8% in stage I IDCA versus normal, to 30.6% in stage IIB IDCA versus normal. A total of 524 proteins that showed ≥ three‐fold difference in abundance between IDCA and normal tissue were picked, processed and identified by mass spectrometry. Out of the proteins picked, ∼ 80% were unambiguously assigned identities by matrix‐assisted laser desorbtion/ionization‐time of flight mass spectrometry or liquid chromatography‐tandem mass spectrometry in the first pass. Bioinformatics tools were also used to mine databases to determine if the identified proteins are involved in important pathways and/or interact with other proteins. Gelsolin, vinculin, lumican, alpha‐1‐antitrypsin, heat shock protein‐60, cytokeratin‐18, transferrin, enolase‐1 and β‐actin, showed differential abundance between IDCA and normal tissue, but the trend was not consistent in all samples. Out of the proteins with database hits, only heat shock protein‐70 (more abundant) and peroxiredoxin‐2 (less abundant) displayed the same trend in all the IDCAs examined. This preliminary study demonstrates quantitative and qualitative differences in protein abundance between breast IDCAs and reveals 2‐D DIGE portraits that may be a reflection of the histological and pathological status of breast IDCA.
Proteomic analysis of mdx skeletal muscle: Great reduction of adenylate kinase 1 expression and enzymatic activity
Authors: Ge Yue , Molloy Mark P. , Chamberlain Jeffrey S. , Andrews Philip C. 
Published: November 2003

AbstractTo investigate the pathophysiological events of Duchenne muscular dystrophy, we analyzed alterations of protein expression in hindlimb muscles of three month old mdx mice using two‐dimensional gel electrophoresis and mass spectrometry. About 40 differentially expressed proteins from the cytosolic fraction and 20 from the microsomal fraction of mdx hindlimb muscles were identified. Among these altered proteins, adenylate kinase 1 (AK 1) was particular interesting because its decrease in abundance was so dramatic (> four‐fold). Enzymatic assays demonstrated that AK 1 activity was also decreased in mdx mice. Furthermore, the expression and enzymatic activity of AK 1 were consistently reduced in mdx mice at one and six months of age, suggesting a direct relationship between the lack of dystrophin and alteration of AK 1. Along with AK 1, creatine kinase (CK) provides a major pathway for regulation of nucleotide ratios and energy metabolism in muscles. To gain a better understanding of mechanisms of energy metabolism, we also investigated CK activities in these mdx mice at different ages. Our results suggested that decreased AK 1 expression and activity might result in redistribution of energy flow through the alternative CK system, thus a compensatory potential might limit cellular energy failure in mdx skeletal muscle.
Differential expression of the liver proteome in senescence accelerated mice
Authors: Cho Young‐Moon , Bae Soo‐Han , Choi Byung‐Kwon , Cho Sang Yun , Song Chang‐Woo , Yoo Je‐Kwon , Paik Young‐Ki 
Published: November 2003

AbstractThe senescence‐accelerated mouse (SAM) is a useful animal model to study aging or age‐associated disorders due to its inherited aging phenotype. To investigate proteins involved in the aging process in liver, we compared the young (4‐ or 20‐week old) and the aged group (50‐week‐old) of SAMP8 (short life span) and SAMR1 (control) mice, and identified 85 differentially expressed distinct proteins comprising antioxidation, glucose/amino acid metabolism, signal transduction and cell cycle systems using proteomics tools. For the antioxidation system, the aged SAMP8 mice showed a large increase in glutathione peroxidase and decreases in glutathione‐S‐transferase and peroxiredoxin, ranging from 2.5‐ to 5‐fold, suggesting lower detoxification potentials for oxidants in the aged SAMP8 liver. Similarly, levels of key glycolytic enzymes decreased greatly in the aged SAMP8 compared to SAMR1, indicating a disturbance in glucose homeostasis that may be closely related to the typical deficits in learning and memory of the aged SAMP8. Protein profiles of amino acid metabolic enzymes suggest that accumulation of glutamine and glutamate in tissues of the aged SAMP8 may be due to hyperexpression of ornithine aminotransferase and/or glutamate dehydrogenase. Decreases in levels of proteins involved in signal transduction/apoptosis (e.g., cathepsin B) in the aged SAMP8 may support the previously proposed negative relationship between apoptosis and aging. However, the changes described above were not markedly seen in the young group of both strains. For cell cycle systems, levels of selenium binding protein increased about four‐fold with age in SAMP8. Yet, almost no change occurred in either the young or the aged SAMR1, which may explain problems associated with cell proliferation and tissue regeneration in the aged SAMP8. In conclusion, composite profiles of key proteins involved in age‐related processes enable assessment of accelerated senescence and the appearance of senescence‐related pathologies in the aged SAMP8.
Turtles all the way down: outlines for a dynamic theory of epistemology
Authors: Neuman Yair 
Published: November 2003

AbstractThe most serious problem facing epistemological research is how to establish solid foundations for epistemology within a recursive system of knowing. The aim of this paper is to respond to this problem by presenting some outlines for a dynamic theory of epistemology. This theory suggests that the most basic unshakeable unit of epistemology is a process of differentiation, which is a self‐referential activity. This paper elaborates on this thesis and illustrates its relevance to solving the problem of embodiment in Piaget's genetic epistemology. Copyright © 2002 John Wiley & Sons, Ltd.
The paradigm of the science of management and of the management science disciplines
Authors: van Gigch John P. 
Published: November 2003

AbstractThis essay explores C. West Churchman's contributions to the development of the paradigm of the science of management and of management science. No other contemporary thinker has contributed more than Churchman to the elaboration of the management paradigm. In his unique way, and throughout his professional life, he has raised our level of consciousness concerning the unfinished business of the discipline. Given the eclectic nature of Churchman's mind, it would be impossible to do him justice and make a complete list of the methodological and epistemological issues that he has studied. In this essay, we illustrate the ideas that, to our mind, will have the greatest impact on the future direction of the discipline. Copyright © 2003 John Wiley & Sons, Ltd.
Identification of normative sources for systems thinking: an inquiry into religious ground‐motives for systems thinking paradigms
Authors: Eriksson Darek M. 
Published: November 2003

AbstractIn celebration of C. West Churchman's work, this article investigates one of the most cherished endeavours of his thinking: to provide a normative meaning for the conduct of human affiars. Churchman has always emphasized ‘What‐Ought‐To‐Be’, at the expense of the ‘What‐Is’. To achieve this purpose, four Systems Thinking paradigms, namely Hard Systems Thinking, Soft Systems Thinking, Critical Systems Thinking, and Multimodal Systems Thinking, are investigated with regard to their foundations for normative guidance. This investigation is made by identifying their respective basic convictions in the form of so‐called ‘religious ground‐motives’, which are based on the assumption that all human thinking and acting starts with a credal conviction, be it Christian, Jew, Islamic, Buddhist, or other. As a result it is found that these systems thinking paradigms are either founded on an inherent contradiction or provide a normative foundation that lacks a social contract for their implementation, and therefore these paradigms do not provide a stable and satisfactory normative guidance for system design.Note: The key claim of this author is that, to be normative, an ethical theory must be grounded in a transcendental justification which is based on some religious faith. The opinions presented in this paper are strictly the author's, who does not claim that his beliefs have more merit or are more ethical than those of any competitive faiths. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of the additional installation of implants in the posterior region on the prognosis of treatment in the edentulous mandibular jaw
Authors: Miyamoto Youji , Fujisawa Kenji , Takechi Masaaki , Momota Yukihiro , Yuasa Tetsuya , Tatehara Seiko , Nagayama Masaru , Yamauchi Eiji 
Published: November 2003

Abstract:The aim of this study was to elucidate the effect of the additional installation of implants in the posterior region on the prognosis of treatment in the edentulous mandibular jaw. Fifteen patients who had received implants (Brånemark system, Nobel Biocare, Gotebörg, Sweden) in the edentulous mandible and completed a 1‐year follow‐up after the fitting of implant‐anchored fixed prostheses were selected. In seven patients (Group A), four or five implants were installed between the mental foramina, and in eight patients (Group P), one or two implants, one on each side, were installed in the posterior regions in addition to the implants between the foramina. All implants of both groups achieved osseointegration. In Group A, there was no implant loss after loading. Six implants were lost in five patients of Group P within 1 year after loading. All of them were located in the posterior region. To elucidate whether or not the failure rate of the implants in the posterior region of Group P after loading was especially high, the failures were also compared with 89 implants, which were installed in the posterior region of the mandibles to support implant‐anchored fixed partial prosthesis, during the same period (Group C). The cumulative survival rate of the implants of Group P was 60%, while that of the implants of Group C was 100% (P<0.001). When the survival rates of posterior implants with the same length of the two groups were compared, there were significant differences for the 7‐ and 10‐mm‐length implants only. These data demonstrate that the posterior implants in Group P are at greater risk. Deformation of the mandible due to jaw movement was thought to be the most likely cause of the implant loss. Therefore, when such modified treatment is chosen, it should be performed with meticulous attention.