Lung resident mesenchymal stem cells isolated from human lung allografts inhibit T cell proliferation via a soluble mediator

Development of allograft rejection continues to be the major determinant of morbidity and mortality postlung transplantation. We have recently demonstrated that a population of donor-derived mesenchymal stem cells is present in human lung allografts and can be isolated and expanded ex vivo. In this study, we investigated the impact of lung resident mesenchymal stem cells (LR-MSCs), derived from allografts of human lung transplant recipients, on T cell activation in vitro. Similar to bone marrow-derived MSCs, LR-MSCs did not express MHC II or the costimulatory molecules CD80 or CD86. In vitro, LR-MSCs profoundly suppressed the proliferative capacity of T cells in response to a mitogenic or an allogeneic stimulus. The immunosuppressive function of LR-MSCs was also noted in the absence of direct cell contact, indicating that LR-MSCs mediated their effect predominantly via a soluble mediator. LR-MSCs isolated from lung transplant recipients demonstrated PGE(2) secretion at baseline (385 +/- 375 pg/ml), which increased in response to IL-1beta (1149 +/- 1081 pg/ml). The addition of PG synthesis inhibitors (indomethacin and NS-398) substantially abrogated LR-MSC-mediated immunosuppression, indicating that PGE(2) may be one of the major soluble mediators impacting T cell activity. This is the first report to demonstrate that human tissue-derived MSCs isolated from an allogeneic environment have the potential to mediate immunological responses in vitro.     

Sinorhizobium meliloti genes involved in tolerance to the antimicrobial peptide protamine

The innate resistance of plants and animals to microbial infection is mediated in part by small cationic peptides with antimicrobial activity. We assessed the susceptibility of the alfalfa symbiont Sinorhizobium meliloti to the model antimicrobial peptide protamine. Twenty-one Tn5-induced mutants showing increased sensitivity to protamine were isolated, and nine were further characterized in detail. These nine mutants carried distinct transposon insertions that affected a total of seven different genes. Three of these genes are involved in exopolysaccharide and beta-(1,2)-glucan biosynthesis (exoT, exoU and ndvB), three other genes are implicated in nitrogen metabolism, such as a putative dyhidropyrimidinase, hutU and ureF, and the last gene exhibited similarity to the ATP binding cassette family of membrane transporters. Symbiotic defects ranging from severe to moderate were displayed by some of the protamine-hypersensitive mutants suggesting that S. meliloti possess active mechanisms to counteract hypothetical cationic peptides that may be produced by its host plant.     

In silico predicted robustness of viroid RNA secondary structures. II. Interaction between mutation pairs

Viroids are plant subviral pathogens whose genomes are constituted by a single-stranded and covalently closed small RNA molecule that does not encode for any protein. Most of the 29 described viroid species fold into a rodlike or quasi-rodlike structure, whereas a few of them fold as highly branched structures. In a previous study, we used RNA thermodynamic secondary structure prediction algorithms to compare the mutational robustness of all viroid species. Here we used the same approach to explore the sign and strength of epistasis among pairs of random mutations. We found that antagonistic interactions were more abundant than synergistic ones. However, despite their lower frequency, synergistic interactions tended to be more intense. Mutational robustness and the intensity of epistasis were correlated such that viroid species with large average mutational effects showed stronger antagonistic epistasis, whereas viroids with mild average mutational effects showed weaker antagonistic interactions. The strength of antagonistic epistasis decreased with genome complexity as a consequence of the gained robustness of duplicated genomes. In good agreement with our previous finding of an evolutionary trend toward increased robustness, we now found a trend toward reduced antagonistic epistasis.     

A network model for the correlation between epistasis and genomic complexity

The study of genetic interactions (epistasis) is central to the understanding of genome organization and evolution. A general correlation between epistasis and genomic complexity has been recently shown, such that in simpler genomes epistasis is antagonistic on average (mutational effects tend to cancel each other out), whereas a transition towards synergistic epistasis occurs in more complex genomes (mutational effects strengthen each other). Here, we use a simple network model to identify basic features explaining this correlation. We show that, in small networks with multifunctional nodes, lack of redundancy, and absence of alternative pathways, epistasis is antagonistic on average. In contrast, lack of multi-functionality, high connectivity, and redundancy favor synergistic epistasis. Moreover, we confirm the previous finding that epistasis is a covariate of mutational robustness: in less robust networks it tends to be antagonistic whereas in more robust networks it tends to be synergistic. We argue that network features associated with antagonistic epistasis are typically found in simple genomes, such as those of viruses and bacteria, whereas the features associated with synergistic epistasis are more extensively exploited by higher eukaryotes.     

Vbmp: variational Bayesian Multinomial Probit Regression for multi-class classification in R

SUMMARY: Vbmp is an R package for Gaussian Process classification of data over multiple classes. It features multinomial probit regression with Gaussian Process priors and estimates class posterior probabilities employing fast variational approximations to the full posterior. This software also incorporates feature weighting by means of Automatic Relevance Determination. Being equipped with only one main function and reasonable default values for optional parameters, vbmp combines flexibility with ease of usage as is demonstrated on a breast cancer microarray study. AVAILABILITY: The R library vbmp implementing this method is part of Bioconductor and can be downloaded from http://www.dcs.gla.ac.uk/~girolami     

Olive stone an attractive source of bioactive and valuable compounds

The olive stone and seed are an important byproduct generated in the olive oil extraction and pitted table olive industries. As a lignocellulosic material, the hemicellulose, cellulose and lignin are the main components of olive stone as wells as protein, fat, phenols, free sugars and poliols composition. The main use of this biomass is as combustion to produce electric energy or heat. Other uses such as activated carbon, furfural production, plastic filled, abrasive and cosmetic or other potential uses such as biosorbent, animal feed or resin formation have been cited. In this article, an overview of the characterization and main uses of olive stone and seed are described for the first time. Also, this review discusses the potential use of this material based on each component. In this way, a new approach to the olive stone and seed by pretreating with a steam explosion followed by chemical fractionation is described.     

Enhanced CD4 down-modulation by late stage HIV-1 nef alleles is associated with increased Env incorporation and viral replication

Three viral proteins participate in the down-modulation of CD4 in human immunodeficiency virus type 1 (HIV-1)-infected cells. The underlying mechanisms have been extensively investigated. However, the physiological relevance of this phenomenon remains poorly understood. To address the role of CD4 down-modulation in HIV-1 pathogenesis in vivo, we have characterized the functional properties of nef alleles isolated from seven HIV-1-infected patients at either the stage of AIDS (late alleles) or during the asymptomatic phase of infection (early alleles). HIV-1 variants carrying these nef alleles showed striking differences in CD4 down-modulation, virus infectivity, and replication properties. Infection of T cells with late strains resulted in production of viral particles with enhanced infectivity, as compared with variants carrying early nef alleles. These differences in infectivity were observed only when viruses were produced in cells with high levels of the viral receptor, suggesting a functional link between CD4 levels and the ability of Nef to down-modulate CD4 and to enhance viral infectivity. Similarly, late nef alleles were substantially more active than early nef genes in stimulating HIV-1 replication in high CD4-positive cells, including primary lymphocytes, but not in cells expressing low levels of the CD4 receptor. Single-round assays showed that differences in infectivity between late and early strains are largely reduced when evaluated in target cells with high levels of CD4, suggesting that the inhibitory effect occurs at the entry step. Supporting this, enhanced CD4 down-modulation by late nef alleles was associated with higher levels of envelope incorporation into viral particles, a phenomenon that likely accounted for the augmented infectivity. Our data suggest a mechanistic link between the Nef-mediated CD4 down-modulation and the enhancement of replication in CD4-positive lymphocytes. As progression to disease occurs, HIV-1 Nef variants with enhanced ability to down-modulate CD4 are selected. These strains efficiently overcome the deleterious effects of CD4 and replicate more aggressively in CD4-positive primary lymphocytes. These results highlight the importance of the virus-induced CD4 down-modulation in HIV-1 pathogenesis.     

Genetic variability and level of differentiation among Brazilian pantanal wood stork populations

The Wood Stork (Mycteria americana) is a colonial wading bird of the tropical and lower subtropical zones. We assessed genetic structure within and among five stork colonies from the Brazilian Pantanal and compared our data with those from North American populations. Samples of 234 individuals were studied using protein electrophoresis to evaluate genetic variability and interpopulation differentiation. Of 22 loci examined, 7 were polymorphic (mean heterozygosity = 0.068). The low Fst value (0.005) indicated little intraspecific variation among breeding colonies. Estimated number of migrants per generation based on private alleles (Nm = 11.3) and on Fst (48.8) suggests high gene flow. Nei's genetic distance values among Pantanal colonies ranged from 0.0001 to 0.0034, demonstrating low genetic divergence among populations. Our data can be explained by supposing high gene flow levels among Pantanal colonies, and between North and South American populations, intermediated by a probable interbreeding population in Central America.     

Production of exopolysaccharides from a thermophilic microorganism isolated from a marine hot spring in flegrean areas

A thermophilic strain isolated from sea sand at Maronti, near Sant' Angelo (Ischia), is described. The organism grows well at an optimal temperature of 60 °C at pH 7.0. The thermophilic bacterium, named strain 4004, produces an exocellular polysaccharide (EPS) in yields of 90 mg/l. The EPS fraction was produced with all substrates tested, although a higher yield was obtained with sucrose or trehalose as sole carbon source. During growth, the EPS content was proportional to the biomass. Three fractions (EPS1, EPS2, EPS3) were obtained after purification. Quantitative monosaccharide analysis of the EPSs revealed the presence of mannose:glucose:galactose in a relative ratio of 0.5:1.0:0.3 in EPS1, mannose:glucose:galactose in a relative ratio of 1.0:0.3:trace in EPS2, and galactose:mannose:glucosamine:arabinose in a relative ratio of 1.0:0.8:0.4:0.2 in EPS3. The average molecular mass of EPS3 was determined to be 1×10⁶ Da. From comparison of the chemical shift values in ¹H and ¹³C spectra, we conclude that EPS3 presents a pentasaccharide repeating unit. Electronic Publication