CMR Assessment of endothelial damage and angiogenesis in porcine coronary arteries using gadofosveset

<p>Abstract</p> <p>Background</p> <p>Endothelial damage and angiogenesis are essential for atherosclerotic plaque development and destabilization. We sought to examine whether contrast enhanced cardiovascular magnetic resonance (CMR) using gadofosveset could show endothelial damage and neovessel formation in balloon injured porcine coronary arteries.</p> <p>Methods and Results</p> <p>Data were obtained from seven pigs that all underwent balloon injury of the left anterior descending coronary artery (LAD) to induce endothelial damage and angiogenesis. Between one - 12 days (average four) after balloon injury, in vivo and ex vivo T1-weighted coronary CMR was performed after intravenous injection of gadofosveset. Post contrast, CMR showed contrast enhancement of the coronary arteries with a selective and time-dependent average expansion of the injured LAD segment area of 45% (p = 0.04; CI₉₅= [15%-75%]), indicating local extravasation of gadofosveset. Vascular and perivascular extravasation of albumin (marker of endothelial leakiness) and gadofosveset was demonstrated with agreement between Evans blue staining and ex vivo CMR contrast enhancement (p = 0.026). Coronary MRI contrast enhancement and local microvessel density determined by microscopic examination correlated (ρ = 0.82, p < 0.001).</p> <p>Conclusion</p> <p>Contrast enhanced coronary CMR with gadofosveset can detect experimentally induced endothelial damage and angiogenesis in the porcine coronary artery wall.</p

Seasonal and annual fluxes of nutrients and organic matter from large rivers to the Arctic Ocean and surrounding seas

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 35 (2012): 369-382, doi:10.1007/s12237-011-9386-6.River inputs of nutrients and organic matter impact the biogeochemistry of arctic estuaries and the Arctic Ocean as a whole, yet there is considerable uncertainty about the magnitude of fluvial fluxes at the pan-arctic scale. Samples from the six largest arctic rivers, with a combined watershed area of 11.3 x 106 km2, have revealed strong seasonal variations in constituent concentrations and fluxes within rivers as well as large differences among the rivers. Specifically, we investigate fluxes of dissolved organic carbon, dissolved organic nitrogen, total dissolved phosphorus, dissolved inorganic nitrogen, nitrate, and silica. This is the first time that seasonal and annual constituent fluxes have been determined using consistent sampling and analytical methods at the pan arctic scale, and consequently provide the best available estimates for constituent flux from land to the Arctic Ocean and surrounding seas. Given the large inputs of river water to the relatively small Arctic Ocean, and the dramatic impacts that climate change is having in the Arctic, it is particularly urgent that we establish the contemporary river fluxes so that we will be able to detect future changes and evaluate the impact of the changes on the biogeochemistry of the receiving coastal and ocean systems.This work was supported by the National Science Foundation through grants OPP-0229302, OPP-0519840, OPP-0732522, and OPP-0732944. Additional support was provided by the U. S. Geological Survey (Yukon River) and the Department of Indian and Northern Affairs (Mackenzie River)

Evidence for Antisense Transcription Associated with MicroRNA Target mRNAs in Arabidopsis

Antisense transcription is a pervasive phenomenon, but its source and functional significance is largely unknown. We took an expression-based approach to explore microRNA (miRNA)-related antisense transcription by computational analyses of published whole-genome tiling microarray transcriptome and deep sequencing small RNA (smRNA) data. Statistical support for greater abundance of antisense transcription signatures and smRNAs was observed for miRNA targets than for paralogous genes with no miRNA cleavage site. Antisense smRNAs were also found associated with MIRNA genes. This suggests that miRNA-associated “transitivity” (production of small interfering RNAs through antisense transcription) is more common than previously reported. High-resolution (3 nt) custom tiling microarray transcriptome analysis was performed with probes 400 bp 5′ upstream and 3′ downstream of the miRNA cleavage sites (direction relative to the mRNA) for 22 select miRNA target genes. We hybridized RNAs labeled from the smRNA pathway mutants, including hen1-1, dcl1-7, hyl1-2, rdr6-15, and sgs3-14. Results showed that antisense transcripts associated with miRNA targets were mainly elevated in hen1-1 and sgs3-14 to a lesser extent, and somewhat reduced in dcl11-7, hyl11-2, or rdr6-15 mutants. This was corroborated by semi-quantitative reverse transcription PCR; however, a direct correlation of antisense transcript abundance in MIR164 gene knockouts was not observed. Our overall analysis reveals a more widespread role for miRNA-associated transitivity with implications for functions of antisense transcription in gene regulation. HEN1 and SGS3 may be links for miRNA target entry into different RNA processing pathways