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A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors at this locus that are related to the etiopathology of CRC, we used microarray-based target selection methods, coupled to next-generation sequencing, to study 103 kb at the 11q23 locus. We genotyped 369 putative variants from 1,030 patients with CRC (cases) and 1,061 individuals without CRC (controls) from the Ontario Familial Colorectal Cancer Registry. Two previously uncharacterized genes, COLCA1 and COLCA2, were found to be co-regulated genes that are transcribed from opposite strands. Expression levels of COLCA1 and COLCA2 transcripts correlate with rs3802842 genotypes. In colon tissues, COLCA1 co-localizes with crystalloid granules of eosinophils and granular organelles of mast cells, neutrophils, macrophages, dendritic cells and differentiated myeloid-derived cell lines. COLCA2 is present in the cytoplasm of normal epithelial, immune and other cell lineages, as well as tumor cells. Tissue microarray analysis demonstrates the association of rs3802842 with lymphocyte density in the lamina propria (p = 0.014) and levels of COLCA1 in the lamina propria (p = 0.00016) and COLCA2 (tumor cells, p = 0.0041 and lamina propria, p = 6 × 10(-5)). In conclusion, genetic, expression and immunohistochemical data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. Histologic analyses indicate the involvement of immune pathways.

The article discusses the efforts of the Albertans Heading for Peace to make social justice an expectation. It notes that Albertans Heading for Peace of students at High Park School in Alberta is part of the PeaceJam initiative that aims to empower other students to get involved and promote a more peaceful world. Furthermore, Albertans Heading for Peace is a highly anticipated expectation that continues to open up possibilities for people to take action and make a difference.

Introduction: Human spermatozoa have unique, well-organized nuclear architecture different from somatic cells. Improperly packaged sperm chromatin will have a high probability of disrupting the particularly structured sequence of fertilization. The evaluation of nuclear organization in spermatozoa is challenging due to the extreme compactness of chromatin and the absolute necessity for induced nuclear decondensation (ND), which itself alters native sperm architecture. The purpose of our study was to identify sperm ND protocol that results in minimal disturbance of sperm architecture. Materials and Methods: Three widely used ND protocols for fluorescence in situ hybridization (FISH) were evaluated in this study: protocol 1 was combined denaturation and decondensation with 0.5N NaOH; in protocol 2, decondensation was achieved with 10mM dithiothreitol (DTT) and lithium diiodosalicylate (LIS); in protocol 3, 2.5mM DTT and heparin was used for ND. Protocols 2 and 3 were followed by denaturation with formamide at 75°C. The effect of denaturation and hybridization on spontaneous ND was also evaluated. Samples were counterstained with DAPI. Images were acquired using unbiased sampling and digital image morphometry analysis by Visiopharm Integrator System. Results were compared to neat samples using SPSS 16.0 statistical computer software. Results: Comparison of ND protocols is provided in the table. Mild decondensation was defined as 1.5 3 fold increase in nuclear area. Spontaneous ND occurred in an unexpectedly large proportion of spermatozoa during denaturation (74%) and hybridization (39%). Conclusions: Combined denaturation and decondensation with 0.5N NaOH demonstrated superior results providing uniform mild ND with over 80% of nucleus suitable for FISH sperm architecture assessment. The influence of spontaneous ND should be considered in any FISH preparation protocols. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to analyze MRI contrast-enhancement patterns in arthritic and nonarthritic knees and the relationship of those patterns with clinical, laboratory, and histologic synovium markers., Materials and Methods: Dynamic contrast-enhanced MRI was performed in nine arthritic and three nonarthritic knees of juvenile rabbits. A two-compartment pharmacokinetic model of signal intensity-time data was implemented to generate parametric maps of signal slope, maximal percentage of signal change, capillary permeability, leakage space volume, and time-to-peak. MRI values were compared with clinical, laboratory, and histologic markers for evaluation of synovial changes during the progression of arthritis., Results: Parametric maps of capillary permeability and signal slope depicted significant differences between arthritic and nonarthritic knees. Arthritic knees showed increased capillary permeability (p = 0.006) and signal slope (p = 0.01) with time after onset of disease as opposed to nonarthritic knees (permeability, p = 0.65; slope, p = 0.56). Significant correlations were found between temporal changes in capillary permeability (p = 0.002), signal slope (p = 0.003), and serum concentrations of amyloid A. No relationship was noted between any MRI parameters and histologic scores. The discriminative power of MRI indexes varied according to the stage of arthritis: time-to-peak was most accurate for differentiation of presence versus absence of arthritis in early arthritis (day 1, p = 0.0002), and signal slope was most accurate in midterm arthritis (day 14, p = 0.001)., Conclusion: In vivo capillary permeability and signal slope have distinctive dynamic MRI properties. The accuracy of MRI parameters for diagnostic evaluation of experimental arthritis differs according to the stage of disease.