Stimulation of immature lung macrophages with intranasal interferon gamma in a novel neonatal mouse model of respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral death in infants. Reduced CD8 T-cells and negligible interferon gamma (IFNγ) in the airway are associated with severe infant RSV disease, yet there is an abundance of alveolar macrophages (AM) and neutrophils. However, it is unclear, based on our current understanding of macrophage functional heterogeneity, if immature AM improve viral clearance or contribute to inflammation and airway obstruction in the IFNγ-deficient neonatal lung environment. The aim of the current study was to define the age-dependent AM phenotype during neonatal RSV infection and investigate their differentiation to classically activated macrophages (CAM) using i.n. IFNγ in the context of improving viral clearance. Neonatal and adult BALB/cJ mice were infected with 1×106 plaque forming units (PFU)/gram (g) RSV line 19 and their AM responses compared. Adult mice showed a rapid and robust CAM response, indicated by increases in major histocompatibility complex class II (MHC II), CD86, CCR7, and a reduction in mannose receptor (MR). Neonatal mice showed a delayed and reduced CAM response, likely due to undetectable IFNγ production. Intranasal (i.n.) treatment with recombinant mouse IFNγ (rIFNγ) increased the expression of CAM markers on neonatal AM, reduced viral lung titers, and improved weight gain compared to untreated controls with no detectable increase in CD4 or CD8 T-cell infiltration. In vitro infection of J774A.1 macrophages with RSV induced an alternatively activated macrophage (AAM) phenotype however, when macrophages were first primed with IFNγ, a CAM phenotype was induced and RSV spread to adjacent Hep-2 cells was reduced. These studies demonstrate that the neonatal AM response to RSV infection is abundant and immature, but can be exogenously stimulated to express the antimicrobial phenotype, CAM, with i.n. rIFNγ. © 2012 Empey et al

Extremal inverse eigenvalue problem for bordered diagonal matrices

AbstractThe following inverse eigenvalue problem was introduced and discussed in [J. Peng, X.Y. Hu, L. Zhang, Two inverse eigenvalue problems for a special kind of matrices, Linear Algebra Appl. 416 (2006) 336–347]: to construct a real symmetric bordered diagonal matrix A from the minimal and maximal eigenvalues of all its leading principal submatrices. However, the given formulae in [4, Theorem 1] to compute the matrix A may lead us to a matrix, which does not satisfy the requirements of the problem. In this paper, we rediscuss the problem to give a sufficient condition for the existence of such a matrix and necessary and sufficient conditions for the existence of a nonnegative such a matrix. Results are constructive and generate an algorithmic procedure to construct the matrices

Quercetin Protects Primary Human Osteoblasts Exposed to Cigarette Smoke through Activation of the Antioxidative Enzymes HO-1 and SOD-1

Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS). The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM) rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers

Alveolar macrophages support interferon gamma-mediated viral clearance in RSVinfected neonatal mice

Background: Poor interferon gamma (IFNγ) production during respiratory syncytial virus (RSV) is associated with prolonged viral clearance and increased disease severity in neonatal mice and humans. We previously showed that intra-nasal delivery of IFNγ significantly enhances RSV clearance from neonatal lungs prior to observed T-lymphocyte recruitment or activation, suggesting an innate immune mechanism of viral clearance. We further showed that alveolar macrophages dominate the RSV-infected neonatal airways relative to adults, consistent with human neonatal autopsy data. Therefore, the goal of this work was to determine the role of neonatal alveolar macrophages in IFNγ-mediated RSV clearance. Methods: Clodronate liposomes, flow cytometry, viral plaque assays, and histology were used to examine the role of alveolar macrophages (AMs) and the effects of intra-nasal IFNγ in RSV infected neonatal Balb/c mice. The functional outcomes of AM depletion were determined quantitatively by viral titers using plaque assay. Illness was assessed by measuring reduced weight gain. Results: AM activation during RSV infection was age-dependent and correlated tightly with IFNγ exposure. Higher doses of IFNγ more efficiently stimulated AM activation and expedited RSV clearance without significantly affecting weight gain. The presence of AMs were independently associated with improved RSV clearance, whereas AM depletion but not IFNγ exposure, significantly impaired weight gain in RSV-infected neonates. Conclusion: We show here for the first time, that IFNγ is critical for neonatal RSV clearance and that it depends, in part, on alveolar macrophages (AMs) for efficient viral clearing effects. Early reductions in viral burden are likely to have profound short- and long-term immune effects in the vulnerable post-natally developing lung environment. Studies are ongoing to elucidate the pathologic effects associated with early versus delayed RSV clearance in developing neonatal airways

Preferencias matrimoniales en el área de los Cerrillos Canelones–Uruguay

El objetivo de la investigación es estudiar las preferencias matrimoniales de la segunda y tercera generación de descendientes de inmigrantes canarios en el área de influencia de Los Cerrillos, Departamento de Canelones, Uruguay. A partir de 105 entrevistas realizadas a los descendientes canarios establecidos en la zona, se realizó la reconstrucción genealógica a través del programa GenoPro (2095 individuos en total, 67 ancestros fundadores), con el fin de estimar las preferencias matrimoniales de los mismos. Los resultados obtenidos muestran una tendencia a uniones dentro del grupo de pertenencia, encontrándose valores altos de endogamia y consanguinidad; los cuales se mantienen a través de varias generaciones. Se discute si las causas que contribuyen a mantener esta conducta en la elección del cónyuge, son de carácter cultural (la búsqueda de reafirmar la identidad como elemento unificador), geográfico (la existencia de barreras naturales que aislan a las familias) o económicas (mantener dentro de la familia los bienes y la tierra adquiridas).Sesión de posters.Asociación de Antropología Biológica de la República Argentina (AABRA

Preferencias matrimoniales en el área de los Cerrillos Canelones–Uruguay

El objetivo de la investigación es estudiar las preferencias matrimoniales de la segunda y tercera generación de descendientes de inmigrantes canarios en el área de influencia de Los Cerrillos, Departamento de Canelones, Uruguay. A partir de 105 entrevistas realizadas a los descendientes canarios establecidos en la zona, se realizó la reconstrucción genealógica a través del programa GenoPro (2095 individuos en total, 67 ancestros fundadores), con el fin de estimar las preferencias matrimoniales de los mismos. Los resultados obtenidos muestran una tendencia a uniones dentro del grupo de pertenencia, encontrándose valores altos de endogamia y consanguinidad; los cuales se mantienen a través de varias generaciones. Se discute si las causas que contribuyen a mantener esta conducta en la elección del cónyuge, son de carácter cultural (la búsqueda de reafirmar la identidad como elemento unificador), geográfico (la existencia de barreras naturales que aislan a las familias) o económicas (mantener dentro de la familia los bienes y la tierra adquiridas).Sesión de posters.Asociación de Antropología Biológica de la República Argentina (AABRA

Development of a vehicle track interaction model to predict the vibratory benefits of rail grinding in the time domain

Imperfections in the wheel-rail contact are one of the main sources of generation of railway vibrations. Consequently, it is essential to take expensive corrective maintenance measures, the results of which may be unknown. In order to assess the effectiveness of these measures, this paper develops a vehicle-track interaction model in the time domain of a curved track with presence of rail corrugation on the inner rail. To characterize the behavior of the track, a numerical finite element model is developed using ANSYS software, while the behavior of the vehicle is characterized by a unidirectional model of two masses developed with VAMPIRE PRO software. The overloads obtained with the dynamic model are applied to the numerical model and then, the vibrational response of the track is obtained. Results are validated with real data and used to assess the effectiveness of rail grinding in the reduction of wheel-rail forces and the vibration generation phenomenon.Real Herráiz, JI.; Zamorano, C.; Velarte, JL.; Blanco, AE. (2015). Development of a vehicle track interaction model to predict the vibratory benefits of rail grinding in the time domain. Journal of Modern Transportation. 23(3):189-201. doi:10.1007/s40534-015-0078-yS189201233Grassie SL, Kalousek J (1993) Rail corrugation: characteristics, causes and treatments. Proc Inst Mech Eng Part F: J Rail Rapid Transit 207:57–68Grassie SL (2005) Rail corrugation: advances in measurement, understanding and treatment. Wear 258:1224–1234Grassie SL (2009) Rail corrugation: characteristics, causes and treatments. Proc Inst Mech Eng Part F: J Rail Rapid Transit 223:581–596Suda Y, Komine H, Iwasa T, Terumichi Y (2002) Experimental study on mechanism of rail corrugation using corrugation simulator. Wear 253:162–171Jin XS, Wen ZF, Wang KY, Zhou ZR, Liu QY, Li CH (2006) Three-dimensional train–track model for study of rail corrugation. J Sound Vib 293(3):830–855Zhao X, Li Z, Esveld C, Dollevoet R (2007) The dynamic stress state of the wheel–rail contact. In: Proceedings of the 2nd IASME/WSEAS international conference on continuum mechanicsTorstensson P, Nielsen J (2011) Simulation of dynamic vehicle-track interaction on small radius curves. Veh Syst Dyn 49(11):1711–1732Hawari HM, Murray MH (2008) Effects of train characteristics on the rate of deterioration of track roughness. J Eng Mech 134(3):234–239Ling L, Li W, Shang H, Xiao X, Wen Z, Jin X (2014) Experimental and numerical investigation of the effect of rail corrugation on the behaviour of rail fastenings. Veh Syst Dyn 52(9):1211–1231Collette C, Horodinca M, Preumont A (2009) Rotational vibration absorber for the mitigation of rail rutting corrugation. Veh Syst Dyn 47:641–659Egaña J, Viñolas J, Gil-Negrete L (2005) Effect of liquid high positive friction (HPF) modifier on wheel-rail contact and rail corrugation. Tribol Int 38:769–774Real Herraiz JI, Galisteo Cabeza A, Real T, Zamorano Martin C (2012) Study of wave barriers design for the mitigation of railway ground vibrations. J Vibroeng 14(1):408–422Real JI, Zamorano C, Hernandez C, Comendador R, Real T (2014) Computational considerations of 3-D finite element method models of railway vibration prediction in ballasted tracks. J Vibroeng 16(4):1709–1722Andersen L, Jones CJ (2001) Three-dimensional elastodynamic analysis using multiple boundary element domains. ISVR Technical Memorandum, University of Southampton, SouthamptonLópez Pita A (2006) Infraestructuras Ferroviarias. Universitat Politècnica de Catalunya, BarcelonaAlves P, Calçada R, Silva A (2011) Vibrations induced by railway traffic: influence of the mechanical properties of the train on the dynamic excitation mechanism. In: Proceedings of the 8th international conference on structural dynamics, EURODYN 2011, Leuven, BelgiumFerrara R, Leonardi G, Jourdan F (2012) Numerical modelling of train induced vibrations. In: SIIV-5th international congress—sustainability of road infrastructures, Rome, ItalyUzzal RU, Ahmed AK, Bhat RB (2013) Modelling, validation and analysis of a three-dimensional railway vehicle–track system model with linear and nonlinear track properties in the presence of wheel flats. Veh Syst Dyn 51(11):1695–1721Eadie DT, Kalousek J, Chiddick KC (2002) The role of high positive friction (HPF) modifier in the control of short pitch corrugations and related phenomena. Wear 253:185–19

Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus

Astroglial type‐1 cannabinoid (CB1) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed by pre‐ and post‐synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB1 receptors. In particular, brain CB1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB1 receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking astroglial CB1 receptor expression specifically in glial fibrillary acidic protein (GFAP)‐containing astrocytes (GFAP‐CB1‐KO mice) and also generated genetic rescue mice to re‐express CB1 receptors exclusively in astrocytes (GFAP‐CB1‐RS). To better identify astroglial structures by immunoelectron microscopy, global CB1 knock‐out (CB1‐KO) mice and wild‐type (CB1‐WT) littermates were intra‐hippocampally injected with an adeno‐associated virus expressing humanized renilla green fluorescent protein (hrGFP) under the control of human GFAP promoter to generate GFAPhrGFP‐CB1‐KO and ‐WT mice, respectively. Furthermore, double immunogold (for CB1) and immunoperoxidase (for GFAP or hrGFP) revealed that CB1 receptors are present in astroglial mitochondria from different hippocampal regions of CB1‐WT, GFAP‐CB1‐RS and GFAPhrGFP‐CB1‐WT mice. Only non‐specific gold particles were detected in mouse hippocampi lacking CB1 receptors. Altogether, we demonstrated the existence of a precise molecular architecture of the CB1 receptor in astrocytes that will have to be taken into account in evaluating the functional activity of cannabinergic signaling at the tripartite synapse.Molecular Physiolog