Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery

Macrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype. In contrast, ramified macrophages emerged in the contracted ECM of recovering colons and mainly expressed M2 macrophage markers. These contracted structures were not observed in the inflamed colons of AKAP12 knockout (KO) mice. Consequently, the proportion of M2 macrophages in inflamed colons was lower in AKAP12 KO mice than in WT mice. In addition, clinical symptoms and histological damage were more severe in AKAP12 KO mice than in WT mice. In experimentally remodeled collagen gels, WT CMCs drove the formation of a more compacted structure than AKAP12 KO CMCs, which promoted the polarization of macrophages toward an M2 phenotype. These results demonstrated that tissue contraction during recovery provides macrophages with the physical cues that drive M2 polarization

AKAP12 Mediates Barrier Functions of Fibrotic Scars during CNS Repair

The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process

Retrospective study of canine cutaneous tumors in Korea

Over the 42 month period from January 2003 to June 2006, a total of 2,952 canine biopsy specimens were received from the Veterinary Medical Teaching Hospital of Seoul National University and from veterinary practitioners across the nation. Out of these, 748 (25.34%) cases were diagnosed as canine cutaneous tumors in the Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Korea. Thirty-eight different types of cutaneous tumors were identified and categorized into epithelial and melanocytic tumors (56.95%), mesenchymal tumors (38.90%), and hematopoietic tumors (4.14%) located in the skin. Among these, 69.25% were benign and 30.74% were malignant. The top ten most frequently diagnosed cutaneous tumors were epidermal and follicular cysts (12.70%), lipoma (11.36%), mast cell tumors (8.82%), cutaneous histiocytoma (7.49%), basal cell tumors (6.82%), sebaceous gland adenoma (6.68%), sebaceous gland hyperplasia (5.08%), hepatoid gland adenoma (3.61%), apocrine adenocarcinoma (3.07%), and fibroma (2.81%), in order of prevalence. They comprised 68.45% of all cutaneous tumors. These top ten cutaneous tumors were distributed on the trunk (30.08%), head and neck (20.9%), extremities (19.14%), anal and perianal area (8.59%), and tail (3.91%). The age of the dogs with the ten most frequent tumors had a mean age of 8.3 years, with a range of 2 months to 19 years. When all types of tumors were considered together in the entire population, there was no difference in incidence according to sex.This study was supported by the Brain Korea 21 Program for Veterinary Science

Dense dislocation arrays embedded in grain boundaries for high-performance bulk thermoelectrics

The widespread use of thermoelectric technology is constrained by a relatively low conversion efficiency of the bulk alloys, which is evaluated in terms of a dimensionless figure of merit (zT). The zT of bulk alloys can be improved by reducing lattice thermal conductivity through grain boundary and point-defect scattering, which target low- and high-frequency phonons. Dense dislocation arrays formed at low-energy grain boundaries by liquid-phase compaction in Bi_(0.5)Sb_(1.5)Te_3 (bismuth antimony telluride) effectively scatter midfrequency phonons, leading to a substantially lower lattice thermal conductivity. Full-spectrum phonon scattering with minimal charge-carrier scattering dramatically improved the zT to 1.86 ± 0.15 at 320 kelvin (K). Further, a thermoelectric cooler confirmed the performance with a maximum temperature difference of 81 K, which is much higher than current commercial Peltier cooling devices

Copy Number Deletion Has Little Impact on Gene Expression Levels in Racehorses

Copy number variations (CNVs), important genetic factors for study of human diseases, may have as large of an effect on phenotype as do single nucleotide polymorphisms. Indeed, it is widely accepted that CNVs are associated with differential disease susceptibility. However, the relationships between CNVs and gene expression have not been characterized in the horse. In this study, we investigated the effects of copy number deletion in the blood and muscle transcriptomes of Thoroughbred racing horses. We identified a total of 1,246 CNVs of deletion polymorphisms using DNA re-sequencing data from 18 Thoroughbred racing horses. To discover the tendencies between CNV status and gene expression levels, we extracted CNVs of four Thoroughbred racing horses of which RNA sequencing was available. We found that 252 pairs of CNVs and genes were associated in the four horse samples. We did not observe a clear and consistent relationship between the deletion status of CNVs and gene expression levels before and after exercise in blood and muscle. However, we found some pairs of CNVs and associated genes that indicated relationships with gene expression levels: a positive relationship with genes responsible for membrane structure or cytoskeleton and a negative relationship with genes involved in disease. This study will lead to conceptual advances in understanding the relationship between CNVs and global gene expression in the horse