Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model

Characterization of a pandemic 2009 H1N1 influenza virus isolated from a fatal case patient (F-IAV), showed the presence of three different mutations; potential determinants of its high pathogenicity that were located in the polymerase subunits (PB2 A221T and PA D529N) and the hemagglutinin (HA S110L). Recombinant viruses containing individually or in combination the polymerase mutations in the backbone of A/California/04/09 (CAL) showed that PA D529N was clearly involved in the increased pathogenicity of the F-IAV virus. Here, we have evaluated the contribution of HA S110L to F-IAV pathogenicity, through introduction of this point mutation in CAL recombinant virus (HA mut). The HA S110L protein has similar pH stability, comparable mobility, and entry properties both in human and mouse cultured cells that wild type HA. The change HA S110L leads to a non-significant trend to reduce the replication capacity of influenza virus in tissue culture, and HA mut is better neutralized than CAL virus by monoclonal and polyclonal antibodies against HA from CAL strain. In addition, recombinant viruses containing HA S110L alone or in combination with polymerase mutations considerably increased the LD50 in infected mice. Characterization of the lungs of HA mut infected animals showed reduced lung damage and inflammation compared with CAL infected mice. Accordingly, lower virus replication, decreased presence in bronchioli and parenchyma and lower leukocytes and epithelial infected cells were found in the lungs of HA mut-infected animals. Our results indicate that, mutation HA S110L constitutes a determinant of attenuation and suggest that its interaction with components of the respiratory tract mucus and lectins, that play an important role on influenza virus outcome, may constitute a physical barrier impeding the infection of the target cells, thus compromising the infection outcome

Gene variation at immunomodulatory and cell adhesion molecules Loci impacts primary Sjögren's Syndrome

Primary Sjögren's syndrome (pSS) is an autoimmune disease triggered by a combination of environmental and host genetic factors, which results in the focal lymphocytic infiltration of exocrine glands causing eye and mouth dryness. Glandular infiltrates include T and B cell subsets positive for CD5 and/or CD6, two surface scavenger receptors involved in the fine-tuning of intracellular signals mediated by the antigen-specific receptor complex of T (TCR) and B (BCR) cells. Moreover, the epithelial cells of inflamed glands overexpress CD166/ALCAM, a CD6 ligand involved in homo and heterotypic cell adhesion interactions. All this, together with the reported association of functionally relevant single nucleotide polymorphisms (SNPs) of CD5, CD6, and CD166/ALCAM with the risk or prognosis of some immune-mediated inflammatory disorders, led us to investigate similar associations in a local cohort of patients with pSS. The logistic regression analyses of individual SNPs showed the association of CD5 rs2241002T with anti-Ro/La positivity, CD6 rs17824933C with neutropenia, and CD6 rs11230563T with increased leukopenia and neutropenia but decreased peripheral nervous system EULAR Sjögren's syndrome disease activity index (ESSDAI). Further analyses showed the association of haplotypes from CD5 (rs2241002T-rs2229177C) with anemia and thrombocytopenia, CD6 (rs17824933G-rs11230563C-rs12360861G) with cutaneous ESSDAI, and CD166/ALCAM (rs6437585C-rs579565A-rs1044243C and rs6437585C-rs579565G-rs1044243T) with disease susceptibility and several analytical parameters (anti-nuclear antibodies, neurological ESSDAI, and hematologic cytopenias). These results support the relevance of gene variation at loci coding for cell surface receptors involved in the modulation of T and B lymphocyte activation (CD5, CD6) and epithelial-immune cell adhesion (CD166/ALCAM) in modulating the clinical and analytical outcomes in patients with pSS.Peer ReviewedPostprint (published version

Gene variation at immunomodulatory and cell adhesion molecules loci impacts primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is an autoimmune disease triggered by a combination of environmental and host genetic factors, which results in the focal lymphocytic infiltration of exocrine glands causing eye and mouth dryness. Glandular infiltrates include T and B cell subsets positive for CD5 and/or CD6, two surface scavenger receptors involved in the fine-tuning of intracellular signals mediated by the antigen-specific receptor complex of T (TCR) and B (BCR) cells. Moreover, the epithelial cells of inflamed glands overexpress CD166/ALCAM, a CD6 ligand involved in homo and heterotypic cell adhesion interactions. All this, together with the reported association of functionally relevant single nucleotide polymorphisms (SNPs) of CD5, CD6, and CD166/ALCAM with the risk or prognosis of some immune-mediated inflammatory disorders, led us to investigate similar associations in a local cohort of patients with pSS. The logistic regression analyses of individual SNPs showed the association of CD5 rs2241002T with anti-Ro/La positivity, CD6 rs17824933C with neutropenia, and CD6 rs11230563T with increased leukopenia and neutropenia but decreased peripheral nervous system EULAR Sjögren's syndrome disease activity index (ESSDAI). Further analyses showed the association of haplotypes from CD5 (rs2241002T-rs2229177C) with anemia and thrombocytopenia, CD6 (rs17824933G-rs11230563C-rs12360861G) with cutaneous ESSDAI, and CD166/ALCAM (rs6437585C-rs579565A-rs1044243C and rs6437585C-rs579565G-rs1044243T) with disease susceptibility and several analytical parameters (anti-nuclear antibodies, neurological ESSDAI, and hematologic cytopenias). These results support the relevance of gene variation at loci coding for cell surface receptors involved in the modulation of T and B lymphocyte activation (CD5, CD6) and epithelial-immune cell adhesion (CD166/ALCAM) in modulating the clinical and analytical outcomes in patients with pS

The state of the art of Xyalidae (Nematoda, Monhysterida) with reference to the Brazilian records

In the current study we provide a reviewed list of valid genera and species of Xyalidae, a widespread family of mostly marine free-living nematodes. Comments are added about the historic background and taxonomic situation of the family, all valid genera and, when necessary, diagnostic characters are given. Additionally, information about distribution and geographical location of species recorded along the Brazilian coast is provided. Our review recognized 46 valid genera, 450 valid species and 73 descriptions without enough morphological information for identification (species inquerendae). Nearly 80 % of the species inquerendae belong to Daptonema and Theristus. To avoid homonymies, two Daptonema species were renamed, Daptonema biwaensis (Tsalolikhin, 2002) new name (former Mongolotheristus timoshkini) and Daptonema vietnamensis (Gagarin and Thu, 2008) new name (former D. curvatum sensu Gagarin and Thu, 2008). Cenolaimus sapeloensis is transferred to Xyala sapeloensis comb. nov. Along the Brazilian coast 28 genera and 41 species have been recorded. The species Elzalia floresi, Metadesmolaimus tersus, Paramonohystera stricta, Pseudosteineria scopae, Rhynchonema cemae, R. veronicae, Steineria ericia, S. marcorum, S. pavo, S. tripartita, Theristus acribus, T. flevensis, T. macroflevensis, T. pertenuis, T. stranus, Trichotheristus heterus, T. setosus and Zygonemella striata have the Brazilian coast as the type locality. Among all species, three occurred across three geographic regions, while the large majority was restricted to one. Xyalidae is typically encountered in oceanic sandy beaches, with only the species belonging to Daptonema, Theristus, Trichotheristus and Zygonemella being recorded in estuarine sediments. This observation suggests that the colonization of inland waters occurred multiple times along the evolutionary history

Thermophilic anaerobic digestion of the screened solid fraction of dairy manure in a solid-phase percolating reactor system

An increase in volatile solids (VS) content from solid fraction of dairy manure would reduce the size of biogas on-farm facilities and could be of greater interest to farmers than manure slurry biogas plants. This study examined the technical feasibility of a solid-phase batch thermophilic anaerobic digestion system for the screened solid fraction (SF) of dairy manure using the digested liquid fraction of dairy manure as inoculum. Inoculum to substrate ratio (I/S) and percolate recirculation strategy were the parameters studied. The manure slurry separation process resulted in a solid fraction that represented 16.8% of total manure mass; this aforementioned fraction showed an ultimate methane yield of 61.5 L CH4 kg−1 SF (265 L CH4 kg−1 VS) which represented 48% of methane potential from raw manure slurry. Five comparative experiments with 40 kg SF and different I/S ratios and percolate recirculation rates revealed that higher I/S ratios provide more security against inhibition states due to high VFA levels and low pH in percolate. The results of the present work have shown that increasing the percolate recirculation rate in intermittent and short recirculation operations improves the stability and speed of the process. Under this percolate recirculation strategy dry batch operation was possible with a I/S ratio of 0.6 obtaining methane yields of 145, 175, 204 and 220 L CH4 kg−1 VS after 15, 20, 30 and 60 days of operation

Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients

OBJECTIVE: CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. METHODS: The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. RESULTS: T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis. CONCLUSION: The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Diseño y construccion de una vivienda unifamiliar de 2 niveles en la urbanizacion de Santa Catalina – Barranca, 2019

Objetivo: Determinar la relación entre el diseño y construcción de una vivienda unifamiliar de 2 niveles en la urbanización Santa Catalina - Barranca, 2019. Método: El diseño de la investigación es relacional de tipo cualitativo, la población fue de 12 colaboradores involucradas nuestra muestra fue censal 12 colaboradores. Resultados: se realizó la construcción de una vivienda de 2 niveles, el cual tuvo un área de 33.80 metros cuadrados, el costo de la mano de obra solo casco de toda la estructura fue de 11500.00 soles y en temas de acabado ascendió ascendieron lo 8000,00 soles y en materiales promediar 20000.00 soles. Se realizó la contratación de hipótesis con el software SSPS v23.0, donde se procesó los datos del cuestionario mediante la escala de Likert con la prueba de hipótesis de chi cuadrada, puesto que el grado de libertad fue de 2 (problema principal X -Y) gl= (r-1)(k-1) y el nivel de significancia de 5% el valor en tabla resultó 5,991 el cual fue mayor al chi cuadrados calculado en las variables y dimensiones, por lo tanto, se afirma que existe un grado de relación entre sí. Conclusión: El modelo de investigación que explica la relación del diseño y construcción de una vivienda unifamiliar – Barranca, 2019, es: Diseño = 1,5 + 0,5 (construcción ) Al aplicar la prueba de hipótesis chi cuadrada a los resultados cualitativo se obtiene que = 6,000a es mayor a x2 crítica =5,991 y cae en la región de rechazo, entonces rechazamos la H0 y aceptamos H1 a un nivel de significancia del 5%, es decir; El diseño tiene relación con la construcción de una vivienda unifamiliar de 2 niveles en la urbanización Santa Catalina - Barranca, 2019Tesi