Lung microbiota promotes tolerance to allergens in neonates via PD-L1.

Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease. The neonatal immune system matures during this period, although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (Treg) cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) Treg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.

Restoration of a lost geological reference point: the loggingstone of Pedralta (Girona, Spain)

The Pedralta is a loggingstone formed of monzonitic leucogranites, which has a volume of about 38 m3 and weighs 101 tons. After its fall in December 1996, a public subscription was opened to meet the expenses of the restoration work, which was completed in May 1999

The OCBI Tipping Point, July 10, 2007, Vol. 1

This is the weekly e-Newsletter called “The OCBI Tipping Point.” We hope that you find it very informative as we explore all possibilities to keep our constituency and the general public informed about all matters that affect Blacks in the state of Iowa.

The OCBI Tipping Point, August 7, 2007, Vol. 2

This is the weekly e-Newsletter called “The OCBI Tipping Point.” We hope that you find it very informative as we explore all possibilities to keep our constituency and the general public informed about all matters that affect Blacks in the state of Iowa.

The OCBI Tipping Point, August 23, 2007, Vol. 1, no.3

This is the weekly e-Newsletter called “The OCBI Tipping Point.” We hope that you find it very informative as we explore all possibilities to keep our constituency and the general public informed about all matters that affect Blacks in the state of Iowa.

The OCBI Tipping Point, August 29, 2007, Vol. 1, no.4

This is the weekly e-Newsletter called “The OCBI Tipping Point.” We hope that you find it very informative as we explore all possibilities to keep our constituency and the general public informed about all matters that affect Blacks in the state of Iowa.

The OCBI Tipping Point, December 7, 2007, Vol. 1, no.5

This is the weekly e-Newsletter called “The OCBI Tipping Point.” We hope that you find it very informative as we explore all possibilities to keep our constituency and the general public informed about all matters that affect Blacks in the state of Iowa.

Toxic effects of brake wear particles on epithelial lung cells in vitro

Background: Fine particulate matter originating from traffic correlates with increased morbidity and mortality. An important source of traffic particles is brake wear of cars which contributes up to 20% of the total traffic emissions. The aim of this study was to evaluate potential toxicological effects of human epithelial lung cells exposed to freshly generated brake wear particles. Results: An exposure box was mounted around a car's braking system. Lung cells cultured at the air-liquid interface were then exposed to particles emitted from two typical braking behaviours ("full stop" and "normal deceleration"). The particle size distribution as well as the brake emission components like metals and carbons was measured on-line, and the particles deposited on grids for transmission electron microscopy were counted. The tight junction arrangement was observed by laser scanning microscopy. Cellular responses were assessed by measurement of lactate dehydrogenase (cytotoxicity), by investigating the production of reactive oxidative species and the release of the pro-inflammatory mediator interleukin-8. The tight junction protein occludin density decreased significantly (p < 0.05) with increasing concentrations of metals on the particles (iron, copper and manganese, which were all strongly correlated with each other). Occludin was also negatively correlated with the intensity of reactive oxidative species. The concentrations of interleukin-8 were significantly correlated with increasing organic carbon concentrations. No correlation was observed between occludin and interleukin-8, nor between reactive oxidative species and interleukin-8. Conclusion: These findings suggest that the metals on brake wear particles damage tight junctions with a mechanism involving oxidative stress. Brake wear particles also increase pro-inflammatory responses. However, this might be due to another mechanism than via oxidative stress. [Authors]

Low density polyethylene (LDPE) passive samplers for the investigation of polychlorinated biphenyl (PCB) point sources in rivers

This study aims to provide a passive sampling approach which can be routinely used to investigate polychlorinated biphenyl (PCB) sources in rivers. The approach consists of deploying low density polyethylene (LDPE) strips downstream and upstream of potential PCB sources as well as in their water discharges. Concentrations of indicator PCBs (iPCBs) absorbed in samplers (Cs) from upstream and downstream sites are compared with each other to reveal increases of PCB levels. Cs measured in water discharges are used to determine if released amounts of PCBs are compatible with increases revealed in the river. As water velocity can greatly vary along a river stretch and influences the uptake at each site in a different way, differences in velocity have to be taken into account to correctly interpret Cs. LDPE strips were exposed to velocities between 1.6 and 37 cm s−1 using a channel system built in the field. Relationships between velocity and Cs were established for each iPCB to determine the expected change in Cs due to velocity variations. For PCBs 28 and 52, this change does not exceed a factor 2 for velocity variations in the range from 1.6 to 100 cm s−1 (extrapolated data above 37 cm s−1). For PCBs 101, 138, 153 and 180, this change only exceeds a factor 2 in the case of large velocity variations. The approach was applied in the Swiss river Venoge to first conduct a primary investigation of potential PCB sources and then conduct thorough investigations of two suspected sources.

Clúster de alta disponibilidad y balanceo de carga sobre un servidor web

El present projecte neix degut a la necessitat de dotar a un pàgina web de una estructura sòlida així com una millor resposta als usuaris. El projecte es pot fraccionar en 2 blocs, els quals son: -La creació de un clúster de alta disponibilitat de manera que assegurem que en cas de fallida de un dels servidors físics la web seguirà sent visible per al públic. -La creació de un clúster de balanceig de càrrega que s’encarrega de redirigir les peticions per a veure la web al node del clúster que sigui més ociós en aquell.

Complex interplay between LPS and IL-10 in dendritic cells: uncoupling of inflammatory chemokine receptors and positive effects on B cell chemokines

Abstract: Protective immune responses against pathogen invasion and transformed cells requires the coordinated action of distinct leukocyte subsets and soluble factors, overall termed immunological network. Among antigen-presenting cells (APC), a crucial role is played by dendritic cells (DC), which initiate, amplify and determine the outcome of the immune response. Micro-environmental conditions profoundly influence DC in such ways that the resulting immune response ranges from successful immune stimulation to abortive response or immune suppression. For instance, the presence in the milieu of anti-inflammatory cytokine interleukin-10 (IL-10) reverts most of the effects mediated on DC by even strong pro-inflammatory agents such as bacterial Lipopolysaccharide (LPS), in terms of differentiation, activation and functions. In an environment containing both LPS and IL-10, uncoupling of receptors for inflammatory chemokines already occurs after a few hours and in a reversible manner on DC, allowing scavenging of chemokines and, consequently, attenuation of the inflammatory process which could be deleterious to the organism. By studying the effects on DC of concomitant stimulation by LPS and IL-10 from the gene expression point of view, we were able to define four distinct transcriptional programs: A. the inhibition of inflammation and immunity, B. the regulation of tissue remodeling, C. the tuning of cytokine/growth factor receptors and G protein-coupled receptors, D. the stimulation of B cell function and lymphoid tissue neogenesis. Among the latter genes, we further demonstrated that IL-10 synergizes with Toll-like receptor ligands for the production of functionally active B cell attracting chemokine CXCL13. Our data provide evidence that the combined exposure of APC to LPS and IL-10, via the production of CXCL13, involves humoral immunity by attracting antibody-producing cells. It is well known that the persistent release of CXCL13 leads to the development of ectopic lymphoid tissue aggregates and production of high levels of antibodies, thus favoring the induction of auto-immunity. Our findings suggest that the IL-10 produced in chronic inflammatory conditions may promote lymphoid tissue neogenesis through increased release of CXCL13. IL-10 is an anti-inflammatory cytokine inhibiting cellular-mediated TH 1-polarized immune responses. In this study we demonstrate that IL- 10 strongly supports the development of humoral immunity. IL-10 and CXCL13 can thus be targets for specific therapies in auto-immune diseases.