The anti-inflammatory properties of intravenous immunoglobulin in a murine model of allergic airway disease ; effects on the development of regulatory T-cells

Les immunoglobulines intraveineuses (IVIg) constituent une préparation polyclonale d’IgG isolée et regroupée à partir du plasma sanguin de multiples donneurs. Initialement utilisé comme traitement de remplacement chez les patients souffrant d’immunodéficience primaire ou secondaire, les IVIg sont maintenant largement utilisées dans le traitement de plusieurs conditions auto-immunes, allergiques ou inflammatoires à une dose élevée, dite immunomodulatrice. Différents mécanismes d’action ont été postulés au fil des années pour expliquer l’effet thérapeutique des IVIg dans les maladies auto-immunes et inflammatoires. Entre autre, un nombre grandissant de données issues de modèles expérimentaux chez l’animal et l’humain suggère que les IVIg induisent l’expansion et augmentent l’action suppressive des cellules T régulatrices (Tregs), par un mécanisme qui demeure encore inconnu. Également, les patients atteints de maladies auto-immunes ou inflammatoires présentent souvent un nombre abaissé de Tregs par rapport aux individus sains. Ainsi, une meilleure compréhension des mécanismes par lesquels les IVIg modulent les cellules T régulatrices est requise afin de permettre un usage plus rationnel de ce produit sanguin en tant qu’alternative thérapeutique dans le traitement des maladies auto-immunes et inflammatoires. Par le biais d’un modèle expérimental d’allergie respiratoire induite par un allergène, nous avons démontré que les IVIg diminuaient significativement l’inflammation au niveau des voies aériennes ce, en association avec une différenciation des Tregs à partir des cellules T non régulatrices du tissu pulmonaire. Nous avons également démontré qu’au sein de notre modèle expérimental, l’effet anti-inflammatoire des IVIg était dépendant des cellules dendritiques CD11c+ (CDs) pulmonaires, puisque cet effet pouvait être complètement reproduit par le transfert adoptif de CDs provenant de souris préalablement traitées par les IVIg. À cet effet, il est déjà établi que les IVIg peuvent moduler l’activation et les propriétés des CDs pour favoriser la tolérance immunitaire et que ces cellules seraient cruciales pour l’induction périphérique des Tregs. C’est pourquoi, nous avons cherché à mieux comprendre comment les IVIg exercent leur effet sur ces cellules. Pour la première fois, nous avons démontré que la fraction d’IgG riche en acide sialique (SA-IVIg) (constituant 2-5% de l’ensemble des IgG des donneurs) interagit avec un récepteur dendritique inhibiteur de type lectine C (DCIR) et active une cascade de signalement intracellulaire initiée par la phosphorylation du motif ITIM qui est responsable des changements observés en faveur de la tolérance immunitaire auprès des cellules dendritiques et des Tregs. L’activité anti-inflammatoire de la composante SA-IVIg a déjà été décrite dans des études antérieures, mais encore une fois le mécanisme par lequel ce traitement modifie la fonction des CDs n’a pas été établi. Nous avons finalement démontré que le récepteur DCIR facilite l’internalisation des molécules d’IgG liées au récepteur et que cette étape est cruciale pour permettre l’induction périphérique des Tregs. En tant que produit sanguin, les IVIg constitue un traitement précieux qui existe en quantité limitée. La caractérisation des mécanismes d’action des IVIg permettra une meilleure utilisation de ce traitement dans un vaste éventail de pathologies auto-immunes et inflammatoires.

The effects of administration of a nuclear factor kappa-B inhibitor on pulmonary endothelial dysfunction after cardiopulmonary bypass: impact on oxygenation and hemodynamics and development of therapeutic and preventive modalities in a porcine model

Introduction: La circulation extracorporelle (CEC) peut entraîner une dysfonction endothéliale pulmonaire et l’hypertension pulmonaire. Le SN50 agit au niveau de la signalisation cellulaire pour prévenir ces réactions à la CEC et pourrait renverser la dysfonction endothéliale pulmonaire post-CEC sans effets néfastes sur l’hémodynamie. Méthodes: Quatre groups de porcs ont reçu un parmi quatre traîtements avant de subir 90 minutes de CEC et 60 minutes de reperfusion: (1) milrinone nébulisé; (2) sildenafil nébulisé; (3) placebo nébulisé; et (4) SN-50 intraveineux. Un monitoring hémodynamique invasif a été utilisé. La réactivité vasculaire des artères pulmonaires de deuxième ordre a été évaluée face à l’acétylcholine et la bradykinine. Résultats: Le sildénafil produit une augmentation significative de la pression de l’artère pulmonaire (PAP) moyenne à 60 minutes de reperfusion par rapport au début de la chirurgie. Les relaxations dépendantes de l’endothélium face à la bradykinine étaient meilleurs dans les groupes milrinone et SN-50 et surtout dans le groupe sildénafil par rapport au groupe placébo. Le SN-50 produisait de moins bonnes relaxations dépendantes de l’endothélium face à l’acétylcholine que les autres traitements incluant placébo. Conclusion: Le sildénafil prévient mieux la dysfonction endothéliale pulmonaire que les autres traitements. Les bénéfices du SN-50 sont possiblement sous-estimés vu que la dose n’a pas pu être ajustée à la durée de CEC. Le sildenafil inhalé mérite une étude plus importante chez l’humain et le SN-50 dans un model de CEC animal.

Chaotic, memory, and cooling rate effects in spin glasses: Evaluation of the Edwards-Anderson model

We investigate chaotic, memory, and cooling rate effects in the three-dimensional Edwards-Anderson model by doing thermoremanent (TRM) and ac susceptibility numerical experiments and making a detailed comparison with laboratory experiments on spin glasses. In contrast to the experiments, the Edwards-Anderson model does not show any trace of reinitialization processes in temperature change experiments (TRM or ac). A detailed comparison with ac relaxation experiments in the presence of dc magnetic field or coupling distribution perturbations reveals that the absence of chaotic effects in the Edwards-Anderson model is a consequence of the presence of strong cooling rate effects. We discuss possible solutions to this discrepancy, in particular the smallness of the time scales reached in numerical experiments, but we also question the validity of the Edwards-Anderson model to reproduce the experimental results.

“Effects of monospecific and mixed algal diets on survival, development and biochemical composition of Penaeus monodon larvae”

The main objective of the present work is to acquire information regarding the growth responses of P. monodon larvae (from PZ1 upto PL1) to various mono specific and mixed diets. Evaluate the nutritional quality of selected species of micro algae viz. Chaetoceros calcitrans, Dunaliella salina, Isochrysis galbana and Nannochloropsis salina, larvae at three cell concentrations 10x104 cells/ml, 25x104 cells/ml and 50x104 cells/ml. The P. monodon larvae were transported, at the Nauplius stage, to the laboratory. The larvae were stocked at density of 150 larvae per litre in 5 litre FRP tanks with 3 litres of sea water. The algal cell density given to the larvae varied. The larval stages were fed with increasing densities of algae to evaluate the relationship between the food densities, ingestion rates, development and growth of the larvae. The water quality parameters, the percentage of survival rate, the growth estimation and the algal cell count were done. Each experiment was carried out in triplicate with a control group of larvae fed with Chaetoceros calcitrans. For the estimation standard procedures were used.to P. monodon

Multi-site time-trend analysis of soil fertility management effects on crop production in sub-Saharan West Africa

Soil fertility constraints to crop production have been recognized widely as a major obstacle to food security and agro-ecosystem sustainability in sub-Saharan West Africa. As such, they have led to a multitude of research projects and policy debates on how best they should be overcome. Conclusions, based on long-term multi-site experiments, are lacking with respect to a regional assessment of phosphorus and nitrogen fertilizer effects, surface mulched crop residues, and legume rotations on total dry matter of cereals in this region. A mixed model time-trend analysis was used to investigate the effects of four nitrogen and phosphorus rates, annually applied crop residue dry matter at 500 and 2000 kg ha^-1, and cereal-legume rotation versus continuous cereal cropping on the total dry matter of cereals and legumes. The multi-factorial experiment was conducted over four years at eight locations, with annual rainfall ranging from 510 to 1300 mm, in Niger, Burkina Faso, and Togo. With the exception of phosphorus, treatment effects on legume growth were marginal. At most locations, except for typical Sudanian sites with very low base saturation and high rainfall, phosphorus effects on cereal total dry matter were much lower with rock phosphate than with soluble phosphorus, unless the rock phosphate was combined with an annual seed-placement of 4 kg ha^-1 phosphorus. Across all other treatments, nitrogen effects were negligible at 500 mm annual rainfall but at 900 mm, the highest nitrogen rate led to total dry matter increases of up to 77% and, at 1300 mm, to 183%. Mulch-induced increases in cereal total dry matter were larger with lower base saturation, reaching 45% on typical acid sandy Sahelian soils. Legume rotation effects tended to increase over time but were strongly species-dependent.

Model calculations on the influence of quantum electrodynamical effects on the chemistry of superheavy elements.

Using a phenomenological model, the influence of quantum electrodynamical effects on the prediction of the chemical behavior of superheavy elements within a relativistic Dirac-Slater calculation was investigated. This influence will be small and nondetectable for elements up to Z = 114. For elements near Z = 164 some changes in the ground state configurations occur but the chemical behavior will not change. Using this heuristic model, it is also possible to calculate elements beyond Z = 175. As an example we have chosen element E184 and are now able to make more valid speculations about the chemical behavior of the element than Penneman and co-workers could.

A mixed H2/H∞-based semiactive control for vibration mitigation in flexible structures

In this paper, we address this problem through the design of a semiactive controller based on the mixed H2/H∞ control theory. The vibrations caused by the seismic motions are mitigated by a semiactive damper installed in the bottom of the structure. It is meant by semiactive damper, a device that absorbs but cannot inject energy into the system. Sufficient conditions for the design of a desired control are given in terms of linear matrix inequalities (LMIs). A controller that guarantees asymptotic stability and a mixed H2/H∞ performance is then developed. An algorithm is proposed to handle the semiactive nature of the actuator. The performance of the controller is experimentally evaluated in a real-time hybrid testing facility that consists of a physical specimen (a small-scale magnetorheological damper) and a numerical model (a large-scale three-story building)

The two-way mixed model : A long and winding controversy

Resumen tomado de la publicación

Comparing intergroup contact effects on blatant and subtle prejudice in adolescents : a multivariate multilevel model

Resumen tomado de la publicación

Comparing meta-analysis and ecological-longitudinal analysis in time-series studies: a case study of the effects of air pollution on mortality in three Spanish cities

The objective of this paper is to introduce a diVerent approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches. Design—The approach is illustrated by providing quantitative estimates of the short-termeVects of air pollution on mortality in three Spanish cities, Barcelona,Valencia and Vigo, for the period 1992–1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were nonlinear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models. Main results—The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 μg/m3 and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 μg/m3 of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant,especially those among air pollutants and meteorological variables. Conclusions—Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities

Immunohistochemistry of synergistic effects of kanamycin and furosemide in the murine model

Adult CBA/CaJ mice were injected with large single dose of both kanamycin and furosemide in order to study hair cell lesion and macrophage recruitment within the cochlea.

Effects of Spruce Budworm (Choristoneura fumiferana (Clem.)) Outbreaks on Boreal Mixed-Wood Bird Communities

This study examined the influence of a spruce budworm (Choristoneura fumiferana (Clem.)) outbreak on a boreal mixed-wood bird community in forest stands ranging in age from 0 to 223 yr. We asked if (1) patterns of species response were consistent with the existence of spruce budworm specialists, i.e., species that respond in a stronger quantitative or qualitative way than other species; (2) the superabundance of food made it possible for species to expand their habitat use in age classes that were normally less used; and (3) the response to budworm was limited to specialists or was it more widespread. Results here indicated that three species, specifically the Bay-breasted Warbler (Dendroica castanea), Tennessee Warbler (Vermivora peregrina), and Cape May Warbler (Dendroica tigrina), had a larger numerical response to the budworm outbreak. They responded with increases in density of up to tenfold over 4 or 5 yr. No other species responded with more than a twofold increase in the same time period. These species also showed a functional response by breeding more frequently in young stands aged 1–21 yr and intermediate stands aged 22–36 yr as budworm numbers increased. Our data also suggested that many species profited to a lesser extent from budworm outbreaks, but that this effect may be too subtle to detect in most studies. We found evidence of a positive numerical effect in at least 18 additional species in one or two stand-age categories but never in all three for any one species. Given the numerical response in many species and the potential influence of budworm on bird populations because of the vast extent of outbreaks, we believe that the population cycle of spruce budworm should be considered in any evaluation of population trends in eastern boreal birds.

Coupled simulations of the Indian monsoon intraseasonal oscillation using a fine-resolution mixed-layer ocean model

The intraseasonal variability (ISV) of the Indian summer monsoon is dominated by a 30–50 day oscillation between “active” and “break” events of enhanced and reduced rainfall over the subcontinent, respectively. These organized convective events form in the equatorial Indian Ocean and propagate north to India. Atmosphere–ocean coupled processes are thought to play a key role the intensity and propagation of these events. A high-resolution, coupled atmosphere–mixed-layer-oceanmodel is assembled: HadKPP. HadKPP comprises the Hadley Centre Atmospheric Model (HadAM3) and the K Profile Parameterization (KPP) mixed-layer ocean model. Following studies that upper-ocean vertical resolution and sub-diurnal coupling frequencies improve the simulation of ISV in SSTs, KPP is run at 1 m vertical resolution near the surface; the atmosphere and ocean are coupled every three hours. HadKPP accurately simulates the 30–50 day ISV in rainfall and SSTs over India and the Bay of Bengal, respectively, but suffers from low ISV on the equator. This is due to the HadAM3 convection scheme producing limited ISV in surface fluxes. HadKPP demonstrates little of the observed northward propagation of intraseasonal events, producing instead a standing oscillation. The lack of equatorial ISV in convection in HadAM3 constrains the ability of KPP to produce equatorial SST anomalies, which further weakens the ISV of convection. It is concluded that while atmosphere–ocean interactions are undoubtedly essential to an accurate simulation of ISV, they are not a panacea for model deficiencies. In regions where the atmospheric forcing is adequate, such as the Bay of Bengal, KPP produces SST anomalies that are comparable to the Tropical Rainfall Measuring Mission Microwave Imager (TMI) SST analyses in both their magnitude and their timing with respect to rainfall anomalies over India. HadKPP also displays a much-improved phase relationship between rainfall and SSTs over a HadAM3 ensemble forced by observed SSTs, when both are compared to observations. Coupling to mixed-layer models such as KPP has the potential to improve operational predictions of ISV, particularly when the persistence time of SST anomalies is shorter than the forecast lead time.