Novel pathways in the pathobiology of human abdominal aortic aneurysms.

OBJECTIVES: Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs. METHODS: A custom-designed 'AAA-chip' was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes. RESULTS: Altogether 38 of the 43 genes on the 'AAA-chip' showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings. CONCLUSION: The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways.

Role of complement cascade in abdominal aortic aneurysms.

OBJECTIVE: The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs). METHODS AND RESULTS: Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues. CONCLUSIONS: These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.

Offspring size at weaning affects survival to recruitment and reproductive performance of primiparous gray seals.

Offspring size affects survival and subsequent reproduction in many organisms. However, studies of offspring size in large mammals are often limited to effects on juveniles because of the difficulty of following individuals to maturity. We used data from a long-term study of individually marked gray seals (Halichoerus grypus; Fabricius, 1791) to test the hypothesis that larger offspring have higher survival to recruitment and are larger and more successful primiparous mothers than smaller offspring. Between 1998 and 2002, 1182 newly weaned female pups were branded with unique permanent marks on Sable Island, Canada. Each year through 2012, all branded females returning to the breeding colony were identified in weekly censuses and a subset were captured and measured. Females that survived were significantly longer offspring than those not sighted, indicating size-selective mortality between weaning and recruitment. The probability of female survival to recruitment varied among cohorts and increased nonlinearly with body mass at weaning. Beyond 51.5 kg (mean population weaning mass) weaning mass did not influence the probability of survival. The probability of female survival to recruitment increased monotonically with body length at weaning. Body length at primiparity was positively related to her body length and mass at weaning. Three-day postpartum mass (proxy for birth mass) of firstborn pups was also positively related to body length of females when they were weaned. However, females that were longer or heavier when they were weaned did not wean heavier firstborn offspring.

Probability of detecting marine predator-prey and species interactions using novel hybrid acoustic transmitter-receiver tags.

Understanding the nature of inter-specific and conspecific interactions in the ocean is challenging because direct observation is usually impossible. The development of dual transmitter/receivers, Vemco Mobile Transceivers (VMT), and satellite-linked (e.g. GPS) tags provides a unique opportunity to better understand between and within species interactions in space and time. Quantifying the uncertainty associated with detecting a tagged animal, particularly under varying field conditions, is vital for making accurate biological inferences when using VMTs. We evaluated the detection efficiency of VMTs deployed on grey seals, Halichoerus grypus, off Sable Island (NS, Canada) in relation to environmental characteristics and seal behaviour using generalized linear models (GLM) to explore both post-processed detection data and summarized raw VMT data. When considering only post-processed detection data, only about half of expected detections were recorded at best even when two VMT-tagged seals were estimated to be within 50-200 m of one another. At a separation of 400 m, only about 15% of expected detections were recorded. In contrast, when incomplete transmissions from the summarized raw data were also considered, the ratio of complete transmission to complete and incomplete transmissions was about 70% for distances ranging from 50-1000 m, with a minimum of around 40% at 600 m and a maximum of about 85% at 50 m. Distance between seals, wind stress, and depth were the most important predictors of detection efficiency. Access to the raw VMT data allowed us to focus on the physical and environmental factors that limit a transceiver's ability to resolve a transmitter's identity.