Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE2 Production

Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE₂, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE₂ inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE₂ confirmed an association between PGE₂ inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.     

Brain Transcriptional and Epigenetic Associations with Autism

BackgroundAutism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic.Conclusions/SignificanceThis work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.     

Differentiation of Human Umbilical Cord Matrix Mesenchymal Stem Cells into Neural-Like Progenitor Cells and Maturation into an Oligodendroglial-Like Lineage

Mesenchymal stem cells (MSCs) are viewed as safe, readily available and promising adult stem cells, which are currently used in several clinical trials. Additionally, their soluble-factor secretion and multi-lineage differentiation capacities place MSCs in the forefront of stem cell types with expected near-future clinical applications. In the present work MSCs were isolated from the umbilical cord matrix (Wharton''s jelly) of human umbilical cord samples. The cells were thoroughly characterized and confirmed as bona-fide MSCs, presenting in vitro low generation time, high proliferative and colony-forming unit-fibroblast (CFU-F) capacity, typical MSC immunophenotype and osteogenic, chondrogenic and adipogenic differentiation capacity. The cells were additionally subjected to an oligodendroglial-oriented step-wise differentiation protocol in order to test their neural- and oligodendroglial-like differentiation capacity. The results confirmed the neural-like plasticity of MSCs, and suggested that the cells presented an oligodendroglial-like phenotype throughout the differentiation protocol, in several aspects sharing characteristics common to those of bona-fide oligodendrocyte precursor cells and differentiated oligodendrocytes.     

Modelling the influence of nutrient loads on Portuguese estuaries

The effects of implementing Directive 91/271/EEC of 21 May 1991 (Waste Water Treatment Plan Directive) and Directive 91/676/EEC of 12 December (Nitrates Directive) are analysed in 7 Portuguese estuaries (Minho, Lima, Douro, Mondego, Tagus, Sado and Guadiana) and two coastal lagoons (Ria de Aveiro and Ria Formosa), with a modelling approach. MOHID Water Modelling System was used to perform simulations with three nitrogen load scenarios for each system: a reference scenario, a 50% nitrate removal by agriculture scenario and another with a 100% nutrients removal by waste water treatment plants (WWTP). It is shown that the interaction between hydrodynamic and ecological processes is an important feature to study trophic problems in estuaries. Ecological processes such as primary production only occur inside the system if the residence time of water is high enough to enable organismal activity and if the adequate conditions are found (e.g. light, nutrients, temperature). From the model results it is possible to conclude: (i) in systems with short residence time a reduction in nutrient load will only produce a decrease in nutrient transit and will not affect the system’s global ecological status (e.g. Douro Estuary); (ii) in systems with long residence time the effects will range from significant, when primary production is mostly limited by nutrients (e.g. Ria de Aveiro), to non-significant, when primary production in the system is light-limited (e.g. Tagus Estuary).     

Exposure to food advertising on television: Associations with children's fast food and soft drink consumption and obesity

There is insufficient research on the direct effects of food advertising on children's diet and diet-related health, particularly in non-experimental settings. We employ a nationally-representative sample from the Early Childhood Longitudinal Survey–Kindergarten Cohort (ECLS-K) and the Nielsen Company data on spot television advertising of cereals, fast food restaurants and soft drinks to children across the top 55 designated-market areas to estimate the relation between exposure to food advertising on television and children's food consumption and body weight. Our results suggest that soft drink and fast food television advertising is associated with increased consumption of soft drinks and fast food among elementary school children (Grade 5). Exposure to 100 incremental TV ads for sugar-sweetened carbonated soft drinks during 2002–2004 was associated with a 9.4% rise in children's consumption of soft drinks in 2004. The same increase in exposure to fast food advertising was associated with a 1.1% rise in children's consumption of fast food. There was no detectable link between advertising exposure and average body weight, but fast food advertising was significantly associated with body mass index for overweight and obese children (≥85th BMI percentile), revealing detectable effects for a vulnerable group of children. Exposure to advertising for calorie-dense nutrient-poor foods may increase overall consumption of unhealthy food categories.