55,362 research outputs found

    Metabolic Patterning on a Chip: Towards in vitro Liver Zonation of Primary Rat and Human Hepatocytes

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    An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the liver sinusoid is termed as “zonation” of the liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers. Using this platform, we were able to create continuous liver tissues of both rat and human origin with gradually changing metabolic activities. The gradients we have created in nitrogen, carbohydrate and xenobiotic metabolisms recapitulated an in vivo like zonation and zonal toxic response. Beyond its application in recapitulation of liver zonation in vitro as we demonstrate here, the MPOC platform can be used and expanded for a variety of purposes including better understanding of heterogeneity in many different tissues during developmental and adult stages

    Rapid Inventory of Earthquake Damage (RIED)

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    The 25 January 1999 Quindío earthquake in Colombia was a major disaster for the coffee-growing region in Colombia. Most of the damage occurred in the city of Armenia and surrounding villages. Damage due to earthquakes is strongly related to topographic and subsurface geotechnical conditions underneath structures and houses. The RIED project used aerial photographs to obtain a rapid inventory of the earthquake damage right after the seismic event. This inventory was subsequently used to identify any existing relation with subsurface- and topographic conditions. Hazard zonation maps were made on the basis of seismic response analysis of a three-dimensional model of the subsurface that has been created in the GIS. Also indicative zonation maps were created outlining potential areas where topographic amplification may occur. These seismic zonation maps delineate those areas that are most likely affected by subsurface and topographic resonance effects during a future and similar earthquake. The maps have been presented to the city planning authorities of Armenia so that reconstruction of the damaged areas can be carried out in such a way that high risk areas will be avoided or that structures and houses will be built according to the standards for high seismic risk areas

    Recovery trends of commercial fish: the case of an underperforming Mediterranean marine protected area

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    Temporal trends in the recovery of exploited species in marine protected areas (MPAs) are useful for a proper assessment of the efficacy of protection measures. The effects of protection on the fish assemblages of the sublittoral rocky reefs in the \u201cPenisola del Sinis-Isola di Mal di Ventre\u201d MPA (W. Sardinia, Italy) were evaluated using a multi-year series of data. Four surveys, conducted 7, 10, 13 and 15 years after the area was designated as an MPA and carried out in the period spanning June and July, were used to estimate the abundance and biomass of commercial species. The surveys were carried out in zones with decreasing levels of fishing restrictions within the MPA (zones A, B, C) and in unprotected zones (OUT1 and OUT2), and underwater video visual census techniques were used. Protected zones only occasionally showed higher levels of abundance or biomass, and the trajectories of those metrics were not consistent across the years. In addition, the zone with the highest level of protection (zone A) never presented levels of abundance and biomass higher than those in zones B and C. This study shows that even 15 years after designation, protection has had no appreciable effect in the MPA studied. It is argued that this is emblematic of several shortcomings in the planning, regulation and enforcement frameworks of the MPA

    Convergence of Wnt signalling on the HNF4a-driven transcription in controlling liver zonation

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    BACKGROUND & AIMS: In each hepatocyte, the specific repertoire of gene expression is influenced by its exact location along the portocentrovenular axis of the hepatic lobule and provides a reason for the liver functions compartmentalization defined "metabolic zonation." So far, few molecular players controlling genetic programs of periportal (PP) and perivenular (PV) hepatocytes have been identified; the elucidation of zonation mechanisms remains a challenge for experimental hepatology. Recently, a key role in induction and maintenance of the hepatocyte heterogeneity has been ascribed to Wnt/beta-catenin pathway. We sought to clarify how this wide-ranging stimulus integrates with hepatocyte specificity. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) allowed the transcriptional profiling of hepatocytes derived from in vitro differentiation of liver stem cells. The GSK3beta inhibitor 6-bromoindirubin-3'-oxime (BIO) was used for beta-catenin stabilization. Co-immunoprecipitations were used to study biochemical protein interactions while ChIP assays allowed the in vivo inspection of PV and PP genes regulatory regions. RESULTS: We found that spontaneous differentiation of liver stem cells gives rise to PP hepatocytes that, after Wnt pathway activation, switch into PV hepatocytes. Next, we showed that the Wnt downstream player LEF1 interacts with the liver-enriched transcriptional factor HNF4alpha. Finally, we unveiled that the BIO induced activation of PV genes correlates with LEF1 binding to both its own and HNF4alpha consensus, and the repression of PP genes correlates with HNF4alpha displacement from its own consensus. CONCLUSION: Our data show a direct and hitherto unknown convergence of the canonical Wnt signaling on the HNF4alpha-driven transcription providing evidences of a mechanism controlling liver zonated gene expression

    Dynamics of agrarian landscapes in Western Thailand : Agro-ecological zonation and agricultural transformations in Kanjanaburi Province: hypotheses for improving farming systems sustainability

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    Ce document traite de la zonation agroécologique à petite échelle, comme outil essentiel dans la recherche orientée sur les systèmes agraires en vue du développement. Ces systèmes sont définis comme modes d'exploitation adaptés à l'environnement (naturel et humain) y compris échanges de produit et patrimoine culturel; l'étude comprend systèmes de production et de culture, et types d'utilisation des sols. Les diverses relations entre éléments sont analysées dans l'espace et le temps de façon à dégager la dynamique des transformations. Le projet a fait intervenir des équipes pluridisciplinaires comprenant agronomes et spécialistes des ressources naturelles en sociologie et télédétection; le tout aux niveaux de la parcelle et de l'exploitation agricole. Le texte, qui comporte un glossaire technique précis, est illustré de six clichés en couleurs (cultures de maïs, cotonnier, manioc, manguiers) et d'une image digitale en couleurs d'une partie de l'ouest de la Thaïlande vue du satellite Landsat-T

    Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

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    The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well

    Rocky shore biotic assemblages of the Maltese Islands (Central Mediterranean) : a conservation perspective

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    Limestone rocky shores constitute ca 90.5% of the 272km coastline of the Maltese islands. Only some 40% of this rocky coastline is gently sloping and easily accessible. Such shores are heavily impacted with 96% of the accessible coastline dominated by tourist-related or by maritime activities. We characterized the biotic assemblages of lowland Maltese rocky shores and tested the popularly held view that given the scarce variation in physical characteristics, such shores form a homogenous habitat. Belt transects were laid perpendicular to the shoreline from biological zero to the adlittoral zone on seven Coralline Limestone and one Globigerina Limestone shores. Cover (for algae and encrusting species) or population density (for animals except sponges) were estimated using 0.5m X 0.05m quadrats placed contiguously for the first few metres and then at regularly spaced intervals. Overall, 19 faunal and 47 floral species, and 10 faunal and 8 floral species were recorded from the Coralline and Globigerina transects respectively, with 60.8% faunal and 25.6% floral species common to the two substrata. Hierarchical clustering showed that the Coralline and Globigerina transects harboured distinct biotic assemblages and identified an upper shore assemblage dominated by the littorinid Melarhaphe neritoides and barnacles, and a lower shore assemblage dominated by algae and molluscs; a mid-shore transition zone where certain species from both assemblages reached peaks of abundance was present in almost all Coralline and the majority of Globigerina transects. Differences in biota between the two types of shore are most likely primarily related to differences in microtopography and, to a lesser degree, to exposure. It is concluded that in spite of gross physical similarity, Maltese lowland rocky shores are biotically inhomogeneous, making conservation of individual sites much more important than previously thought.peer-reviewe
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