Colloidal properties of biodegradable nanoparticles influence interaction with amyloid-β peptide

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the extracellular deposition of amyloid-β peptides (Aβ). During the past few years, promising approaches based on nanotechnologies have emerged to alter Aβ aggregation and its related toxicity. This study aims to investigate the influence of the nanoparticle colloidal properties over the interaction with Aβ peptide 1–42 (Aβ_1–42). Using capillary electrophoresis with laser-induced fluorescence detection, it was shown that biodegradable poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanoparticles were able to interact with Aβ_1–42 peptide leading to its uptake in rather short time periods. In addition, we highlighted the crucial role of the nanocarrier colloidal properties on the uptake kinetics. Whereas nanoparticles stabilized by sodium cholate (lower size and higher negative surface charge) gave optimum uptake kinetics, nanoparticles stabilized with others surfactants presented lower interactions. In contrast, PEG density seemed to have no influence on the interaction when sodium cholate was used for the preparation. This study intends to give new insights into Aβ_1–42 peptide interaction with nanoparticulate systems by helping to determine suitable nanoparticle characteristics regarding forthcoming therapeutic strategies against AD.     

The complex interplay between mitochondrial dynamics and cardiac metabolism

Mitochondria are highly dynamic organelles, capable of undergoing constant fission and fusion events, forming networks. These dynamic events allow the transmission of chemical and physical messengers and the exchange of metabolites within the cell. In this article we review the signaling mechanisms controlling mitochondrial fission and fusion, and its relationship with cell bioenergetics, especially in the heart. Furthermore we also discuss how defects in mitochondrial dynamics might be involved in the pathogenesis of metabolic cardiac diseases.     

Six-year study of meiofaunal dynamics in fish farms in Tenerife (Canary Islands,NE Atlantic Ocean)

In our six-year study, we investigated the dynamics of the meiofaunal community directly under the influence of a fish farm, in adjacent areas and in control areas outside the fish farm influence. Our data showed spatial, seasonal and annual variation in the meiofaunal community under the influence of the fish farm; however, no clear trend is discernible. Copepods are positively associated with mud and very fine sands, which seem to increase with time under the fish farm and adjacent areas, particularly in summer. As shown throughout the study period, copepods could soon take over other components of the community, resulting in a community shift. Our approach to investigate the dynamics of a community with a quick response to environmental changes proves useful to detect early-stage deviations from non-affected areas, which could be critical to distinguish environmental impacts before they cause major shifts in the environment.     

Phenotypic characteristics of human type II alveolar epithelial cells suitable for antigen presentation to T lymphocytes

Background

Type II alveolar epithelial cells (AECII) are well known for their role in the innate immune system. More recently, it was proposed that they could play a role in the antigen presentation to T lymphocytes but contradictory results have been published both concerning their surface expressed molecules and the T lymphocyte responses in mixed lymphocyte cultures. The use of either AECII cell line or fresh cells could explain the observed discrepancies. Thus, this study aimed at defining the most relevant model of accessory antigen presenting cells by carefully comparing the two models for their expression of surface molecules necessary for efficient antigen presentation.

Methods

We have compared by flow cytometry the surface expression of the major markers involved in the immunological synapse on the A549 cell line, the most popular model of type II alveolar epithelial cells, and freshly isolated cells. HLA-DR, CD80, CD86, ICOS-L, CD54, CD58 surface expression were studied in resting conditions as well as after IFN-γ/TNF-α treatment, two inflammatory cytokines, known to modulate some of these markers.

Results

The major difference found between the two cells types was the very low surface expression of HLA-DR on the A549 cell line compared to its constitutive expression on freshly isolated AECII. The surface expression of co-stimulatory molecules from the B7 family was very low for the CD86 (B7-2) and ICOS-L (B7-H2) and absent for CD80 (B7-1) on both freshly isolated cells and A549 cell line. Neither IFN-γ nor TNF-α could increase the expression of these classical co-stimulatory molecules. However CD54 (ICAM-1) and CD58 (LFA-3) adhesion molecules, known to be implicated in B7 independent co-stimulatory signals, were well expressed on the two cell types.

Conclusions

Constitutive expression of MHC class I and II molecules as well as alternative co-stimulatory molecules by freshly isolated AECII render these cells a good model to study antigen presentation.     

Relevance of Nitrospira for nitrite oxidation in a marine recirculation aquaculture system and physiological features of a Nitrospira marina-like isolate

In biofilters of recirculation aquaculture systems (RAS), nitrification by lithoautotrophic microorganisms is essential to prevent the cultivated organisms from intoxication with ammonium and nitrite. In moving-bed biofilters nitrifying microorganisms are immobilized together with heterotrophic bacteria in dense biofilms on carrier elements like plastic beads. Analyses of fatty acid profiles of these biofilms from a marine biofilter revealed a high abundance of Nitrospira-related lipid markers (8-12% of total fatty acids). Further results of a labeling experiment with (13) C-bicarbonate in mineral salts medium with 3 mM nitrite confirmed that Nitrospira is the major autotrophic nitrite oxidizer in the biofilter system. According to 16S rRNA gene sequence analyses the nitrite-oxidizing community in the biofilter consisted of at least two different representatives of Nitrospira, one of which could be successfully isolated. The marine isolate 'Ecomares 2.1' belongs to cluster IVa and showed 98.8% 16S rRNA gene sequence similarity to Nitrospira marina, whereas the enrichment 'M1 marine' is only distantly related (94.0% 16S rRNA gene sequence similarity to N. marina). In laboratory experiments, the isolate exhibited remarkable tolerances against high substrate and product concentrations (30 mM nitrite and 80 mM nitrate) as well as ammonium (50 mM). During the isolation process a strong tendency of this strain to develop biofilms became apparent. Thus, Ecomares 2.1 seems to be well adapted to the attached lifestyle in biofilters and the nitrogenous load prevailing in the effluent waters of RAS. Both members of Nitrospira could be detected by PCR-based methods in environmental samples of marine and brackish RAS biofilters and are therefore considered to be characteristic for these engineered ecosystems.     

A research agenda to underpin malaria eradication

The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda--primarily directed towards reducing morbidity and mortality--with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda.     

Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium

While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations.