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BACKGROUND: Ulcerative colitis (UC) is a chronic, idiopathic inflammatory condition affecting the colonic epithelium, with the inflammasome, T cells, complement activation, and microbiome dysbiosis contributing to pathogenesis. AIMS: We applied a previously established method of microarray molecular analysis to a set of 71 UC biopsies (from 61 patients), to elucidate the molecular changes associated with active UC, specifically comparing UC to T-cell mediated rejection (TCMR), as a prototype of a sterile, T-cell mediated disease. METHODS: 71 for-cause UC colonic biopsies were collected at the U of A Hospital in Edmonton, AB and Cedars-Sinai Hospital in LA, California. These biopsies were processed using Affymetrix GeneChip microarrays and the data analyzed in R programming language. Gene expression data was displayed using volcano plots (showing the fold change and association between the genes and endoscopic Mayo score) and heatmaps (showing expression of the top 30 genes in a cell panel). We then analyzed overexpression of the top genes using the DAVID tool(1), and compared the results to similar results for top genes overexpressed in TCMR. RESULTS: The volcano plot (Figure 1) showed strong associations between the endoscopic Mayo score and decay accelerating factor (CD55), and moderate associations with calprotectin genes (S100A8/S100A9), with lesser associations for effector T cell transcripts (i.e. CTLA4, interferon gamma (IFNG), and chemokine ligand (CXCL13)), many IFNG inducible transcripts, inflammasome transcripts (CASP1), and toll-like receptors (TLR5). NLRP3 (incriminated in mouse UC models) did not pass the IQR filter and was not significant. Expression of the top genes in a cell panel showed primary expression in monocytes, macrophages, and dendritic cells, with some expression in epithelial and endothelial cells, while minimal expression was found in CD4/CD8 T cells, or in NK cells. Pathway analysis showed major differences between pathway terms. CONCLUSIONS: Our findings show that while transcripts associated with cognate T cell inflammatory processes (TCMR) are expressed in UC, there are substantial differences between the pathogenesis of a pure T cell-mediated disease and UC. In our cohort, the top genes associated with the endoscopic Mayo score in UC were not those associated with effector T cells: T cell-associated transcripts were only moderately associated with the Mayo score, and pathway analysis showed significant differences between TCMR and UC, which is much more an inflammatory environment with strong associations to CD55. This suggests that cognate T cell recognition is present in UC but supplemented by a second source of inflammation. REFERENCES: 1. Huang et al. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols (2009). FUNDING AGENCIES: None

In our model of partially appropriable invention, if the US Plant Variety Protection Act (PVPA) of 1970 succeeded in strengthening intellectual property protection for plant breeders, it should have led to increases in investment in varietal R&D, improved varietal quality, and enhanced royalties. These hypotheses are tested using data on US wheat. We find that the PVPA may have stimulated public (but not private-sector) investment in wheat varietal improvement but that the PVPA did not cause any increase in experimental or commercial wheat yields. These findings indicate that the PVPA had little impact on excludability or appropriability in wheat varieties.

SummaryPreviously, we demonstrated in a rat model of heparin-induced osteoporosis that low molecular weight heparin (LMWH) produces less bone loss than unfractionated heparin, and that only heparin increases osteoclast number and activity. In contrast, both heparin and LMWH were found to decrease osteoblast function to a similar extent, possibly because at the doses tested both agents produced maximal inhibition. To examine the relative effects of heparin and LMWH on osteoblast function more closely we used an in vitro bone nodule assay, together with measurements of alkaline phosphatase (ALP) activity. Both agents inhibited bone nodule formation and ALP activity in a concentration-dependent manner, but 6 to 8-fold higher concentrations of LMWH were required to achieve equivalent effects. The effect of heparin on osteoblast function was both chain-length and negative charge-dependent because the ability of defined heparin fragments to inhibit nodule formation correlated with their molecular weight (r = 0.98), and N-desulfated heparin was less inhibitory than heparin. In contrast, the effect of heparin on osteoblast function was pentasaccharide-independent because heparin with low affinity for antithrombin had similar activity to heparin with high antithrombin activity. These findings help to explain mounting clinical evidence that the risk of osteoporosis is lower with LMWH than with heparin.

Absorption cross-sectional measurements and model predictions of 25 disks with moderate electrical conductivity were made. The disk radii span part of the resonance region, and their thicknesses are an order of magnitude less than the skin depth. A photoacoustic apparatus, with a 35-GHz microwave source, was used to measure the absorption cross sections. The disks tend to be more absorbing when they are edge-on rather than broadside to the incident microwaves. Also they absorb most efficiently near a size parameter of 1. Model predictions generally agree with the measured magnitudes and trends in the data.