Encephalomyocarditis virus may use different pathways to initiateinfection of primary human cardiomyocytes

Encephalomyocarditis virus (EMCV) caninfect a wide range of vertebrate species including swineand non-human primates, but few data are available forhumans. We therefore wanted to gain further insight intothe mechanisms involved in EMCV infection of humancells. For this purpose, we analyzed the permissiveness ofprimary human cardiomyocytes towards two strains ofEMCV; a pig myocardial strain (B279/95) and a rat strain(1086C). In this study, we show that both strains productivelyinfect primary human cardiomyocytes and inducecomplete cytolysis. Binding and infection inhibitionexperiments indicated that attachment and infection areindependent of sialic acid and heparan sulfate for B279/95and dependent for 1086C. Sequence comparison betweenthe two strains and three-dimensional analysis of the capsidrevealed that six of the seven variable residues are surfaceexposed,suggesting a role for these amino acids in binding.Moreover, analysis of variants isolated from the 1086Cstrain revealed the importance of lysine 231 of VP1 in theattachment of EMCV to cell-surface sialic acid residues.Together, these results show a potential for EMCV strainsto use at least two different binding possibilities to initiateinfection and provide new insights into the mechanismsinvolved in primary human cell recognition by EMCV

CD98 Increases Renal Epithelial Cell Proliferation by Activating MAPKs

CD98 heavy chain (CD98hc) is a multifunctional transmembrane spanning scaffolding protein whose extracellular domain binds with light chain amino acid transporters (Lats) to form the heterodimeric amino acid transporters (HATs). It also interacts with β1 and β3 integrins by its transmembrane and cytoplasmic domains. This interaction is proposed to be the mechanism whereby CD98 mediates cell survival and growth via currently undefined signaling pathways. In this study, we determined whether the critical function of CD98-dependent amino acid transport also plays a role in cell proliferation and defined the signaling pathways that mediate CD98-dependent proliferation of murine renal inner medullary collecting duct (IMCD) cells. We demonstrate that downregulating CD98hc expression resulted in IMCD cell death. Utilizing overexpression studies of CD98hc mutants that either lacked a cytoplasmic tail or were unable to bind to Lats we showed that CD98 increases serum-dependent cell proliferation by a mechanism that requires the CD98hc cytoplasmic tail. We further demonstrated that CD98-dependent amino acid transport increased renal tubular epithelial cell proliferation by a mechanism that does not require the CD98hc cytoplasmic tail. Both these mechanisms of increased renal tubular epithelial cell proliferation are mediated by Erk and p38 MAPK signaling. Although increased amino transport markedly activated mTor signaling, this pathway did not alter cell proliferation. Thus, these studies demonstrate that in IMCD cells, the cytoplasmic and extracellular domains of CD98hc regulate cell proliferation by distinct mechanisms that are mediated by common MAPK signaling pathways

Ευρετικές προσεγγίσεις του μοναδιάστατου προβλήματος πακετοποίησης

Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and non-pleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data

Use of clinical characteristics to predict spirometric classification of obstructive lung disease

Steven J Pascoe,1 Wei Wu,2,3 Kathryn A Collison,1 Linda M Nelsen,4 Keele E Wurst,5 Laurie A Lee6 1Respiratory Medicines Development Center, GSK, Research Triangle Park, NC, USA; 2Biostatistics, PAREXEL International, Research Triangle Park, NC, USA; 3Clinical Statistics, GSK, Research Triangle Park, NC, USA; 4Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 5Epidemiology, GSK, Collegeville, PA, USA; 6Research and Development, GSK, Stevenage, UK Background: There is no consensus on how to define patients with symptoms of asthma and chronic obstructive pulmonary disease (COPD). A diagnosis of asthma–COPD overlap (ACO) syndrome has been proposed, but its value is debated. This study (GSK Study 201703 [NCT02302417]) investigated the ability of statistical modeling approaches to define distinct disease groups in patients with obstructive lung disease (OLD) using medical history and spirometric data.Methods: Patients aged ≥18 years with diagnoses of asthma and/or COPD were categorized into three groups: 1) asthma (nonobstructive; reversible), 2) ACO (obstructive; reversible), and 3) COPD (obstructive; nonreversible). Obstruction was defined as a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7, and reversibility as a post-albuterol increase in FEV1 ≥200 mL and ≥12%. A primary model (PM), based on patients’ responses to a health care practitioner-administered questionnaire, was developed using multinomial logistic regression modeling. Other multivariate statistical analysis models for identifying asthma and COPD as distinct entities were developed and assessed using receiver operating characteristic (ROC) analysis. Partial least squares discriminant analysis (PLS-DA) assessed the degree of overlap between groups.Results: The PM predicted spirometric classifications with modest sensitivity. Other analysis models performed with high discrimination (area under the ROC curve: asthma model, 0.94; COPD model, 0.87). PLS-DA identified distinct phenotypic groups corresponding to asthma and COPD.Conclusion: Within the OLD spectrum, patients with asthma or COPD can be identified as two distinct groups with a high degree of precision. Patients outside these classifications do not constitute a homogeneous group. Keywords: asthma–COPD overlap syndrome, asthma, COPD, differential diagnosis, surveys and questionnaire

Rethinking Competence Systems for Knowledge-Based Organizations

Existing competence systems are based on a rationalistic view of competence. While these competence systems might work in job-based organizations, we argue that in more dynamic settings, such as in knowledge-based organizations, the interest-informed actions that capture the emergent competencies of tomorrow require different types of information technology support. The main objective of this paper is to elaborate on the possibilities and implications of using interest-activated technology as a design rationale for competence systems. This paper is based on an action case study of an implemented interest-activated Intranet recommender system prototype at Volvo Information Technology AB in Gothenburg, Sweden. On the basis of how organizational members used this prototype to find information they were interested in, our research team was able to inquire into how personal interest, embodied in information-seeking activities, could be a means for identifying competence. Building on the relation between personal interest and competence, we discuss competence systems design and spell out explicit implications for managerial practice in knowledge-based organizations