102,056 research outputs found
Genetic epidemiology of susceptibility to malaria: not only academic exercises.
No full textDescriptive genetic epidemiology represents the initial step of a logical procedure of linked and consequential phases spanning from the identification of genes involved in the resistance/susceptibility to diseases, to the determination of the underlying mechanisms and finally to the possible translation of the acquired knowledge in new control tools. In malaria, the rational development and potential of this pathway is based on complementary interactions of heterogeneus disciplines going from epidemiology (the transmission, the infection, the disease) to vaccinology passing through genetics, pathogenesis, and immunology. Several epidemiological approaches can be applied in the study of the genetic susceptibility to Plasmodium falciparum malaria: intra-ethnic case-control studies comparing genetic candidates of resistance/susceptibility between subjects with different presentation of malaria (from severe disease to asymptomatic infection) and the general healthy population is the classic approach; inter-ethnic comparative analyses among populations with different genetic backgrounds, exposed to the same epidemiological context and showing different susceptibility to the disease is a further, complementary, strategy
Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria.
No full textHaemoglobin S (HbS; beta6Glu-->Val) and HbC (beta6Glu-->Lys) strongly protect against clinical Plasmodium falciparum malaria. HbS, which is lethal in homozygosity, has a multi-foci origin and a widespread geographic distribution in sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational load, occurs only in a small area of central West-Africa. To address this apparent paradox, we adopted two partially independent haplotypic approaches in the Mossi population of Burkina Faso where both the local S (S(Benin)) and the C alleles are common (0.05 and 0.13). Here we show that: both C and S(Benin) are monophyletic; C has accumulated a 4-fold higher recombinational and DNA slippage haplotypic variability than the S(Benin) allele (P = 0.003) implying higher antiquity; for a long initial lag period, the C alleles did apparently remain very few. These results, consistent with epidemiological evidences, imply that the C allele has been accumulated mainly through a recessive rather than a semidominant mechanism of selection. This evidence explains the apparent paradox of the uni-epicentric geographic distribution of HbC, representing a 'slow but gratis' genetic adaptation to malaria through a transient polymorphism, compared to the polycentric 'quick but costly' adaptation through balanced polymorphism of HbS
Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung
No full textDieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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3346: Samuel G. Freedman, author, 2013
No full textPhotograph of author Samuel G. Freedman, at NT Daily Slash meeting in the Mayborn School of Journalism at UNT
The science of BAV aortopathy
No full textThe aortopathy associated with bicuspid aortic valve (BAV) is an epidemiologically relevant source of chronic and acute aortic disease (aneurysm and dissection). However, its pathogenesis is still the object of scientific uncertainties and debates. Indeed, the mechanisms determining the diseases of the ascending aorta in BAV patients are most likely complex and multifactorial, i.e. resulting from variable modes of interplay between genetic and hemodynamic factors. Although few scientific studies have so far taken into adequate account this complexity, leaving the precise sequence of pathogenetic events still undiscovered, the accumulated evidence from previous research approaches have at least brought about important insights. While genetic studies have so far identified variants relevant to either valve malformation or aortic complications (including those in the genes NOTCH1, TGFBR2, ACTA2, GATA5, NKX2.5, SMAD6, ROBO4), however each explaining not more than 5% of the study population, other investigations have thoroughly described both the flow features, with consequent forces acting on the arterial wall (including skewed flow jet direction, rotational flow, wall shear stress), and the main changes in the molecular and cellular wall structure (including extracellular matrix degradation, smooth muscle cell changes, oxidative stress, unbalance of TGF-beta signaling, aberrant endothelia l-tomesenchymal transition). All of this evidence, together with the recognition of the diverse phenotypes that the aortopathy can assume in BAV patients, holding possible prognostic significance, is reviewed in this chapter. The complex and multifaceted body of knowledge resulting from clinical and basic science studies on BAV aortopathy has the potential to importantly influence modes of clinical management of this disease in the near future. Crown Copyright (c) 2020 Published by Elsevier Inc. All rights reserved
Epithelial-mesenchymal transition of epicardial cells requires specific signals from microenvironment and constitutes the source of cardiac primitive cells in the adult human heart
No full textDuring heart morphogenesis a subset of epicardial cells undergoes an epithelial-mesenchymal transition and invades myocardium contributing to the formation of myofibroblasts, vascular endothelium and smooth muscle cells. Recently, the presence of resident stem cells able to give rise to the cells of cardiac lineages was observed in the adult human heart, raising questions concerning their origin and biology. The scope of the present study was to investigate whether the epithelial-mesenchymal transition takes place in the adult human heart, generating the population of cardiac stem cells, and which molecular factors are involved in its initiation and progression.
Since the subepicardial space is rich in extracellular matrix components and cytokines, constituting the specific environment for epicardially derived cells, cardiac fibroblasts obtained from the subepicardium layer of adult human atrium were cultured to create the most appropriate conditions for the in vitro study. After the non-enzymatic removal of cells, the presence of extracellular matrix proteins - fibronectin, collagen III and IV, tenascin and laminin - was confirmed by immunofluorescence. This substrate was used to obtain and culture the sheets of epithelial cells from the epicardium of normal adult human atria. The epithelial phenotype of the cells was confirmed by the positive immunolabeling of E-cadherin and β-catenin at the intercellular junctions and cytokeratin in the cytoplasm. While in the presence of basic fibroblast growth factor (10 ng/ml) or platelet-derived growth factor-BB (40 ng/ml) the epithelial sheets remained intact, the addition of epidermal growth factor (40 ng/ml), hepatocyte growth factor (40 ng/ml) or transforming growth factor beta (0,5 ng/ml) resulted in the change of cell characteristics. The intercellular contacts were lost and the cells acquired spindle-like shape and vimentin expression. When induced to differentiate into endothelial, smooth muscle cells or cardiomyocytes, these cells expressed factor VIII, smooth muscle actin or myosin heavy chain α/β, respectively.
The results of our study indicate that in the specific conditions epithelial-mesenchymal transition takes place in the adult human epicardial cells. We suggest that epicardially derived cells enrich the pool of cardiac primitive cells and contribute to the regenerative properties of the heart. A better understanding of complex interactions of the extracellular matrix proteins and growth factors with their specific receptors on the cell surface will be pivotal for progressing therapeutic cardiac regeneration
Early graft failure after heart transplant: risk factors andimplications for improved donor-recipient matching.
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