Characterization of the Fecal Microbiome from Non-Human Wild Primates Reveals Species Specific Microbial Communities

BACKGROUND: Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny. CONCLUSION/SIGNIFICANCE: Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome

Loss of Sex and Age Driven Differences in the Gut Microbiome Characterize Arthritis-Susceptible *0401 Mice but Not Arthritis-Resistant *0402 Mice

<div><h3>Background</h3><p>HLA-DRB1*0401 is associated with susceptibility, while HLA-DRB1*0402 is associated with resistance to developing rheumatoid arthritis (RA) and collagen-induced arthritis in humans and transgenic mice respectively. The influence of gut-joint axis has been suggested in RA, though not yet proven.</p> <h3>Methodology/Principal Findings</h3><p>We have used HLA transgenic mice carrying arthritis susceptible and -resistant HLA-DR genes to explore if genetic factors and their interaction with gut flora gut can be used to predict susceptibility to develop arthritis. Pyrosequencing of the 16S rRNA gene from the fecal microbiomes of DRB1*0401 and DRB1*0402 transgenic mice revealed that the guts of *0401 mice is dominated by a Clostridium-like bacterium, whereas the guts of *0402 mice are enriched for members of the <em>Porphyromonadaceae</em> family and <em>Bifidobacteria</em>. DRB1*0402 mice harbor a dynamic sex and age-influenced gut microbiome while DRB1*0401 mice did not show age and sex differences in gut microbiome even though they had altered gut permeability. Cytokine transcripts, measured by rtPCR, in jejuna showed differential TH17 regulatory network gene transcripts in *0401 and *0402 mice.</p> <h3>Conclusions/Significance</h3><p>We have demonstrated for the first time that HLA genes in association with the gut microbiome may determine the immune environment and that the gut microbiome might be a potential biomarker as well as contributor for susceptibility to arthritis. Identification of pathogenic commensal bacteria would provide new understanding of disease pathogenesis, thereby leading to novel approaches for therapy.</p> </div

City festivals: creativity and control in staged urban experiences

In a global market, cities aim to develop a distinct profile to attract mobile consumers. One means increasingly used to attain distinction is to brand the city as experience space. In particular, the urban festival has become a popular organizational form for creating experience spaces and for marketing cities. Festivals are often strategically conceived with the purpose of promoting a ?distinctive city?, in line with uniqueness being the keystone of success in the experience economy. This paper applies an experience economy framework to analyse city festivals as potentially transformative practices, helping re-imagine urban space and reshape urban identity. Building on empirical studies of the Stockholm Culture Festival and the Nowy Kercelak Fair in Warsaw, it examines the tension between controlled image production and carnivalesque celebration and the extent to which the meanings and flow of urban space can be managed. Using Lef�bvre?s notion of the production of space and Deleuze and Guattari?s concepts of de-territorialization and re-territorialization, this paper critically assesses the possibility of reshaping urban practices through the staging of festivals, and the potential for creativity and expression extant in managed staging of experience

Optimization of functional efficacy of phosphorothioate-modified oligonucleotides in a human CD8+ T-Cell Ex Vivo expansion model

Antisense oligodeoxyribonucleotides (ODNs) can specifically inhibit gene expression, but their application to fresh human CD8+ T cells is limited by poor spontaneous uptake (<2%). We have examined and optimized the uptake of phosphorothioate-modified oligodeoxyribonucleotides (PS-ODNs) into these cells in an ex vivo expansion model. Optimal antisense treatments were found to be, for fresh CD8+ T cells, 1 µm PS-ODNs complexed with lipofectin (LF), which resulted in 35% uptake and 10 µm PS-ODNs in the absence of LF, for cultured cells, which resulted in 95% uptake. The delivered antisenses were functional, as determined by the inhibition of protein expression. In this respect, partially phosphorothioate-modified ODNs (PS-ODNs-P) were twice as effective as completely modified (PS-ODNs-C), and the antisense specific for the cap site showed the highest protein suppression of those tested (68%). Uptake mechanisms were also investigated. To our knowledge, this is the first optimization of the delivery of antisense oligonucleotides into human CD8+ T cells. This protocol could be used to study the function of a particular gene in cytotoxic T lymphocytes and also by those looking for a method to deliver short interfering RNA into cell lines to specifically suppress a gene of interest

Abnormal Early Cleavage Events Predict Early Embryo Demise: Sperm Oxidative Stress and Early Abnormal Cleavage

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors

Liposomes as a gene delivery system

Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer