Locational memory of macrovessel vascular cells is transcriptionally imprinted

Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems

Systematic analysis of chromatin interactions at disease associated loci links novel candidate genes to inflammatory bowel disease

BACKGROUND: Genome-wide association studies (GWAS) have revealed many susceptibility loci for complex genetic diseases. For most loci, the causal genes have not been identified. Currently, the identification of candidate genes is predominantly based on genes that localize close to or within identified loci. We have recently shown that 92 of the 163 inflammatory bowel disease (IBD)-loci co-localize with non-coding DNA regulatory elements (DREs). Mutations in DREs can contribute to IBD pathogenesis through dysregulation of gene expression. Consequently, genes that are regulated by these 92 DREs are to be considered as candidate genes. This study uses circular chromosome conformation capture-sequencing (4C-seq) to systematically analyze chromatin-interactions at IBD susceptibility loci that localize to regulatory DNA. RESULTS: Using 4C-seq, we identify genomic regions that physically interact with the 92 DRE that were found at IBD susceptibility loci. Since the activity of regulatory elements is cell-type specific, 4C-seq was performed in monocytes, lymphocytes, and intestinal epithelial cells. Altogether, we identified 902 novel IBD candidate genes. These include genes specific for IBD-subtypes and many noteworthy genes including ATG9A and IL10RA. We show that expression of many novel candidate genes is genotype-dependent and that these genes are upregulated during intestinal inflammation in IBD. Furthermore, we identify HNF4α as a potential key upstream regulator of IBD candidate genes. CONCLUSIONS: We reveal many novel and relevant IBD candidate genes, pathways, and regulators. Our approach complements classical candidate gene identification, links novel genes to IBD and can be applied to any existing GWAS data

Formal asymptotic limit of a diffuse-interface tumor-growth model

We consider a diffuse-interface tumor-growth model which has the form of a phase-field system. We characterize the singular limit of this problem. More precisely, we formally prove that as the coefficient of the reaction term tends to infinity, the solution converges to the solution of a novel free boundary problem. We present numerical simulations which illustrate the convergence of the diffuse-interface model to the identified sharp-interface limit

Binary metal oxides for composite ultrafiltration membranes

A new ultrafiltration membrane was developed by the incorporation of binary metal oxides inside polyethersulfone. Physico-chemical characterization of the binary metal oxides demonstrated that the presence of Ti in the TiO2?ZrO2 system results in an increase of the size of the oxides, and also their dispersity. The crystalline phases of the synthesized binary metal oxides were identified as srilankite and zirconium titanium oxide. The effect of the addition of ZrO2 can be expressed in terms of the inhibition of crystal growth of anocrystalline TiO2 during the synthesis process. For photocatalytic applications the band gap of the synthesized semiconductors was determined, confirming a gradual increase (blue shift) in the band gap as the amount of Zr loading increases. Distinct distributions of binary metal oxides were found along the permeation axis for the synthesized membranes. Particles with Ti are more uniformly dispersed throughout the membrane cross-section. The physico-chemical characterization of membranes showed a strong correlation between some key membrane properties and the spatial particle distribution in the membrane structure. The proximity of metal oxide fillers to the membrane surface determines the hydrophilicity and porosity of modified membranes. Membranes incorporating binary metal oxides were found to be promising candidates for wastewater treatment by ultrafiltration, considering the observed improvement influx and anti-fouling properties of doped membranes. Multi-run fouling tests of doped membranes confirmed the stability of permeation through membranes embedded with binary TiO2?ZrO2 particles

Using a system dynamics framework to assess disease risks of pig value chains in Vietnam

In Vietnam, there are more than 4 million households producing pigs and pork. This accounts for 57% of quantity of meat consumed. One of the most critical constraints to pig production is the presence of animal disease. Pig disease outbreaks are a regular occurrence in various parts of the country, with the industry affected by diseases such as foot and mouth disease, porcine reproductive and respiratory syndrome, classical swine fever, porcine high fever disease, and swine influenza. In addition, food safety issues related to pig diseases and pork-borne diseases have also increasingly become more important concerns for consumers. Recent studies have shown significant changes in consumption behaviour in response to disease outbreaks. For instance, at least half of urban consumers stop consuming pork in times of pig disease epidemics and/or shift consumption to other meat substitutes such as poultry or fish. Disease risks thus have both public health and livelihoods impacts that are important to understand for appropriate policy and practice response. A proposed methodology for investigating disease risks uses a system dynamics analysis framework. System dynamics models are particularly relevant in the study of livestock systems, as they capture the diverse actors and feedbacks present in value chains and their interface with disease risk and behaviour. A system dynamics model is developed that will describe different scenarios of disease risks and the consequences of different interventions to mitigate these risks. Data from a sample of 1000 farmers and value chain actors including all actors in the pig value chain in Vietnam was collected with support from an ACIAR-funded project on Reducing Disease Risks and Improving Food Safety in Smallholder Pig Value Chains in Vietnam. We propose to test the hypotheses that disease risk is affected by type of production system, feeding system and types of feed uses, access to inputs and services, and selected socio-demographic variables associated with farmers and location

Market-based approaches to food safety and animal health interventions: Lessons from smallholder pig value chains in Vietnam

Food safety and animal health issues are increasingly important constraints to smallholder pig production in Viet Nam. Recent studies have highlighted the significant prevalence of animal disease and food‐borne pathogens inherent within the Vietnamese pig sector. These in turn have important negative livelihoods effects on smallholder pig producers and other value chain actors, as well as important public health impacts. An important research gap is in identifying ex‐ante appropriate market‐based policy responses that take into account the tradeoffs between improved animal health and food safety outcomes and their associated costs for different value chain actors as a means of developing chain‐level solutions for their control. In this paper, we constructed a system dynamics model of the pig value chain that combines a detailed model of herd production and marketing with modules on short‐ and long‐term investment in pig capacity, and decisions by value chain actors to adopt different innovations. The model further highlights the feedbacks between different actors in the chain to identify both the potential entry points for upgrading food safety and animal health as well as potential areas of tension within the chain that may undermine uptake. Model results demonstrate that interventions at nodal levels (e.g. only at farm or slaughterhouse level) are less cost‐effective and sustainable than those that jointly enhance incentives for control across the value chain, as weak links downstream undermine the ability of producers to sustain good health practices