17 research outputs found

    Claudin 13, a Member of the Claudin Family Regulated in Mouse Stress Induced Erythropoiesis

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    Mammals are able to rapidly produce red blood cells in response to stress. The molecular pathways used in this process are important in understanding responses to anaemia in multiple biological settings. Here we characterise the novel gene Claudin 13 (Cldn13), a member of the Claudin family of tight junction proteins using RNA expression, microarray and phylogenetic analysis. We present evidence that Cldn13 appears to be co-ordinately regulated as part of a stress induced erythropoiesis pathway and is a mouse-specific gene mainly expressed in tissues associated with haematopoietic function. CLDN13 phylogenetically groups with its genomic neighbour CLDN4, a conserved tight junction protein with a putative role in epithelial to mesenchymal transition, suggesting a recent duplication event. Mechanisms of mammalian stress erythropoiesis are of importance in anaemic responses and expression microarray analyses demonstrate that Cldn13 is the most abundant Claudin in spleen from mice infected with Trypanosoma congolense. In mice prone to anaemia (C57BL/6), its expression is reduced compared to strains which display a less severe anaemic response (A/J and BALB/c) and is differentially regulated in spleen during disease progression. Genes clustering with Cldn13 on microarrays are key regulators of erythropoiesis (Tal1, Trim10, E2f2), erythrocyte membrane proteins (Rhd and Gypa), associated with red cell volume (Tmcc2) and indirectly associated with erythropoietic pathways (Cdca8, Cdkn2d, Cenpk). Relationships between genes appearing co-ordinately regulated with Cldn13 post-infection suggest new insights into the molecular regulation and pathways involved in stress induced erythropoiesis and suggest a novel, previously unreported role for claudins in correct cell polarisation and protein partitioning prior to erythroblast enucleation

    Circulating microparticles: square the circle

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    Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

    Malaria endemicity and co-infection with tissue-dwelling parasites in Sub-Saharan Africa: a review

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    Seasonal variation in the diversity and abundance of pelagic larvae of Antarctic marine invertebrates

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    Most marine benthic macroinvertebrate species reproduce via a larval phase but attempts to explain the occurrence of different larval strategies (feeding or non-feeding, pelagic or benthic) in different habitats have been largely inconclusive. There have been very few year-round surveys of meroplankton at any latitude and in consequence fundamental data on the diversity, abundance, and timings of larval life history phases are lacking. There has been considerable debate regarding the viability of pelagic larvae in cold waters with highly seasonal primary production but there has been only one year-round study of meroplankton in the Southern Ocean, and that was outside of the Antarctic Circle. We present data from the first year-round survey of meroplankton assemblages at a location within the Antarctic Circle. We surveyed abundances of meroplanktonic larvae over 1.5 year at Rothera Point, West Antarctic Peninsula (67A degrees 34'S, 68A degrees 07'W). Larvae were collected in monthly diver-towed net samples close to the seabed at 20 and 6 m total water depths at each of three locations and were identified and counted live immediately after sampling. A total of 99 operationally defined taxonomic types representing 11 phyla were recorded but this is likely to be an underestimate of true diversity because of inherent difficulties of identification. Larvae were present in all months of the year and although planktotrophic larvae were more abundant in summer, both feeding and non-feeding types were present in all months. Comparisons of seasonal larval abundances with data from a settlement study at the same sites and from the literature show that larvae of mobile adults settle in summer regardless of developmental type, whereas sessile taxa settle in all seasons. We suggest that this is a consequence of differences in the food requirements of mobile and sessile fauna and that the availability of food for post-larval juveniles is more critical for survival than factors affecting the larval stage itself

    Valproic Acid Causes Proteasomal Degradation of DICER and Influences miRNA Expression

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    Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA’s clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER

    Contributions of Bayesian Phylogenetics to Exploring Patterns of Macroevolution in Archaeological Data

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    Archaeology is often defined by our interest in how cultural traditions change over time and generate patterns of material culture diversity. As acknowledged throughout the history of archaeological research, evolutionary biology broadly parallels these interests by also examining patterns of inheritance and diversity. Today, one of the most common frameworks used in evolutionary biology to infer patterns of macroevolution is Bayesian phylogenetic inference. Despite the popularity of this approach across the sciences, few worked examples can be found in the archaeological literature. This chapter closes this gap by providing a step-by-step application of a Bayesian phylogenetic approach to archaeological data from the Great Plains. We conclude that Bayesian methods are not only able to reconstruct evolutionary relationships in a more robust manner but also ask a new generation of questions about the pace of cultural change, periods of cultural divergence, and rates of cultural diversification
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