MUCH OF THE TRADITIONAL analysis of productivity growth in manufacturing industries has been based explicitly or implicitly on a model in which identical, perfectly competitive plants respond in the same way to forces that strike the industry as a whole. The estimates of growth obtained with this framework are then used as the basis for discussions of policy concerning capital accumulation, research and development, trade, or other issues. This contrasts markedly with the literature of industrial organization in which perfect competition is seen as an unusual market structure and in which the differences among firms are examined in detail. The models of oligopoly that are the staple of the industrial organization literature are then used to examine antitrust policy.
Growth faltering of rural Gambian infants is associated with a chronic inflammatory enteropathy of the mucosa of the small intestine that may impair both digestive/absorptive and barrier functions. The aim of this study was to determine whether the enteropathy was associated with a compromised barrier function that allowed translocation of antigenic macromolecules from the gut lumen into the body, with subsequent systemic immunostimulation, resulting in growth retardation. Rural Gambian infants were studied longitudinally at regular intervals between 8 and 64 wk of age. On each study day, each child was medically examined, anthropometric measurements were made, a blood sample was taken and an intestinal permeability test performed. Evidence of chronic immunostimulation was provided by abnormally elevated white blood cell, lymphocyte and platelet counts, and frequently raised plasma concentration of C-reactive protein. Intestinal permeability was abnormal and associated with impaired growth (r = -0.41, P < 0.001). Plasma concentrations of endotoxin and immunoglobulin (Ig)G-endotoxin core antibody were also elevated and related to both growth (r = -0.30, P < 0.02; r = -0.64, P < 0.0001, respectively) and measures of mucosal enteropathy. Plasma IgG, IgA and IgM levels increased rapidly with age toward adult concentrations. Raised values were related to poor growth but also to measures of mucosal enteropathy and the endotoxin antibody titer. The interrelationships among these variables and growth suggested that they were all part of the same growth-retarding mechanism. These data are consistent with the hypothesis of translocation of immunogenic lumenal macromolecules across a compromised gut mucosa, leading to stimulation of systemic immune/inflammatory processes and subsequent growth impairment.
The ability to analyze and understand the mechanisms by which cells process information is a key question of systems biology research. Such mechanisms critically depend on reversible phosphorylation of cellular proteins, a process that is catalyzed by protein kinases and phosphatases. Here, we present PhosphoPep, a database containing more than 10 000 unique high-confidence phosphorylation sites mapping to nearly 3500 gene models and 4600 distinct phosphoproteins of the Drosophila melanogaster Kc167 cell line. This constitutes the most comprehensive phosphorylation map of any single source to date. To enhance the utility of PhosphoPep, we also provide an array of software tools that allow users to browse through phosphorylation sites on single proteins or pathways, to easily integrate the data with other, external data types such as protein-protein interactions and to search the database via spectral matching. Finally, all data can be readily exported, for example, for targeted proteomics approaches and the data thus generated can be again validated using PhosphoPep, supporting iterative cycles of experimentation and analysis that are typical for systems biology research.
To the editorReversible protein phosphorylation is a universal process that is involved in the control of most biological processes. The comprehensive and quantitative analysis of the protein phosphorylation patterns of cells at different states is therefore of considerable and general interest. Over the past years, mass spectrometry has become the method of choice for the analysis of protein phosphorylation and impressive gains have been realized in the isolation of phosphorylated peptides from complex samples as well as their mass spectrometric and computational analysis. In such studies hundreds to thousands of phosphopeptides and phosphorylation sites are now routinely identified.Currently, several databases exist which store and disseminate protein phosphorylation data obtained from large scale studies, however, several factors limit their utility. First, and most importantly, the current phosphopeptide databases are human and/or rodent centric. Examples include the human proteome reference database (HPRD) 1 , PhosphoElm 2 , Phosida 3 and PhosphoSitePlus (www.phosphosite.org). Extensive phosphoproteome data sets for model organisms organized in databases are still missing. Second, the lack of phosphorylation data from diverse species precludes comparative studies, e.g. those that assess whether specific phosphorylation sites or perturbation induced phosphopeptide patterns are conserved between species. For example, the analysis of the evolutionary conservation of the human phosphorylation sites of the Phosida 3 database relies on amino acid sequence conservation, but not on observed phosphorylation sites in other species. Third, none of these databases provides sufficient information to validate, identify and quantify the presented phosphorylation sites by mass spectrometry in independent experiments.To address these issues and to complement existing protein databases for life science research we describe the PhosphoPep v2.0 database (www.phosphopep.org) 4 which is a significant extension of its first version, PhosphoPep v1.0. In its initial implementation the database contained 12,756 assigned phosphorylation sites identified in D. melanogaster Kc167 cells,
Previous studies from The Gambia have shown that poor childhood growth is resistant to all but the most intense nutritional intervention and highly dependent on small bowel permeability related to enteropathy. We thus aimed to characterize the mucosal inflammatory response in rural Gambian children in relation to intestinal permeability and nutritional status. Small bowel biopsies were taken from 38 rural Gambian children (age, 0.5-3 y) with a range of nutritional and clinical states (median weight z score, Ϫ4.6; range, 0.5 to Ϫ6.4), 75% of whom had diarrhea. Morphometry was performed with immunohistochemical analysis for a range of lineage and activation markers, including proinflammatory and regulatory cytokines, and related to current clinical status and gut permeability. Comparison was made with 19 age-matched U.K. controls. All Gambian children, regardless of nutritional status, had evidence of chronic cellmediated enteropathy with crypt hyperplasia, villous stunting, and high numbers of intraepithelial lymphocytes. CD25ϩ cells were 20-fold higher than in U.K. controls. Although small bowel architecture was independent of nutritional status, T cell numbers rose and B cell numbers fell with worsening nutrition, and mucosal cytokine production became biased toward a proinflammatory response, with progressive decrease of transforming growth factor- expression. Tropical enteropathy predates the onset of marasmus and is characterized by a cell-mediated T H 1 response. Protein-energy malnutrition is associated with reduction of regulatory immune responses in the mucosal microenvironment, potentially impairing the mechanisms of oral tolerance. Children from The Gambia show a pattern of growth faltering typical of deprived areas of the developing world (1-4). Growth velocity falls from 4 mo onward, so by age 2, the mean weight-for-age lies 2 SD below U.K. standards (z score, Ϫ2). Previous studies from Keneba, rural Gambia, have identified biochemical and dietary deficiencies in these infants. Despite seemingly well-targeted nutritional intervention with macroand micronutrients, growth faltering continues (5-9). Massive dietary supplementation (twice recommended values for energy, 2.5 times for protein) produced short-term catch-up growth after gastroenteritis (5), but growth acceleration reached only the population mean, still 2 SD below the U.K., and reversed as soon as the child left the refeeding study (1, 8).The failure of dietary intervention to restore growth has led to search for other factors. Quantitatively the most important association identified is small bowel enteropathy (2, 4, 10), demonstrated by lactulose:mannitol (L:M) dual sugar permeability testing (11). This assesses both epithelial integrity (exclusion of lactulose entry through intercellular tight junctions) and absorptive capacity (passive absorption of mannitol) (12). During a 1-y period, increased L:M ratio accounted for 0031-3998/03/5403-0306 PEDIATRIC RESEARCH Vol. 54, No. 3, 2003 Copyright © 2003 Printed in U.S.A. ABSTRACT306
Abstract. OzFlux is the regional Australian and New Zealand flux tower network that aims to provide a continental-scale national research facility to monitor and assess trends, and improve predictions, of Australia's terrestrial biosphere and climate. This paper describes the evolution, design, and current status of OzFlux as well as provides an overview of data processing. We analyse measurements from all sites within the Australian portion of the OzFlux network and two sites from New Zealand. The response of the Australian biomes to climate was largely consistent with global studies except that Australian systems had a lower ecosystem water-use efficiency. Australian semi-arid/arid ecosystems are important because of their huge extent (70 %) and they have evolved with common moisture limitations. We also found that Australian ecosystems had a similar radiation-use efficiency per unit leaf area compared to global values that indicates a convergence toward a similar biochemical efficiency. The two New Zealand sites represented extremes in productivity for a moist temperate climate zone, with the grazed dairy farm site having the highest GPP of any OzFlux site (2620 gC m−2 yr−1) and the natural raised peat bog site having a very low GPP (820 gC m−2 yr−1). The paper discusses the utility of the flux data and the synergies between flux, remote sensing, and modelling. Lastly, the paper looks ahead at the future direction of the network and concludes that there has been a substantial contribution by OzFlux, and considerable opportunities remain to further advance our understanding of ecosystem response to disturbances, including drought, fire, land-use and land-cover change, land management, and climate change, which are relevant both nationally and internationally. It is suggested that a synergistic approach is required to address all of the spatial, ecological, human, and cultural challenges of managing the delicately balanced ecosystems in Australasia.
Consistent with the theory that intestinal inflammation in tropical infants may impair growth, fecal neopterin concentrations were inversely associated with growth. Factors other than Giardia are causing enteropathy and growth failure in Gambian infants.
CO 2 production in terrestrial ecosystems is generally assumed to be solely biologically driven while the role of abiotic processes has been largely overlooked. In addition to microbial decomposition, photodegradation -the direct breakdown of organic matter (OM) by solar irradiance -has been found to contribute to litter mass loss in dry ecosystems. Previous small-scale studies have shown that litter degradation by irradiance is accompanied by emissions of CO 2 . However, the contribution of photodegradation to total CO 2 losses at ecosystems scales is unknown. This study determined the proportion of the total CO 2 losses caused by photodegradation in two ecosystems: a bare peatland in New Zealand and a seasonally dry grassland in California. The direct effect of solar irradiance on CO 2 production was examined by comparing daytime CO 2 fluxes measured using eddy covariance (EC) systems with simultaneous measurements made using an opaque chamber and the soil CO 2 gradient technique, and with nighttime EC measurements under the same soil temperature and moisture conditions. In addition, a transparent chamber was used to directly measure CO 2 fluxes from OM caused by solar irradiance. Photodegradation contributed 19% of the annual CO 2 flux from the peatland and almost 60% of the dry season CO 2 flux from the grassland, and up to 62% and 92% of the summer mid-day CO 2 fluxes, respectively. Our results suggest that photodegradation may be important in a wide range of ecosystems with exposed OM. Furthermore, the practice of partitioning daytime ecosystem CO 2 exchange into its gross components by assuming that total daytime CO 2 losses can be approximated using estimates of biological respiration alone may be in error. To obtain robust estimates of global ecosystematmosphere carbon transfers, the contribution of photodegradation to OM decomposition must be quantified for other ecosystems and the results incorporated into coupled carbon-climate models.
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