Molecular signatures of cell migration in C. elegans Q neuroblasts.

Metazoan cell movement has been studied extensively in vitro, but cell migration in living animals is much less well understood. In this report, we have studied the Caenorhabditis elegans Q neuroblast lineage during larval development, developing live animal imaging methods for following neuroblast migration with single cell resolution. We find that each of the Q descendants migrates at different speeds and for distinct distances. By quantitative green fluorescent protein imaging, we find that Q descendants that migrate faster and longer than their sisters up-regulate protein levels of MIG-2, a Rho family guanosine triphosphatase, and/or down-regulate INA-1, an integrin alpha subunit, during migration. We also show that Q neuroblasts bearing mutations in either MIG-2 or INA-1 migrate at reduced speeds. The migration defect of the mig-2 mutants, but not ina-1, appears to result from a lack of persistent polarization in the direction of cell migration. Thus, MIG-2 and INA-1 function distinctly to control Q neuroblast migration in living C. elegans

Detection of Gamma-rays around 1TeV from RX J0852.0-4622 by CANGAROO-II

We have detected gamma-ray emission at the 6sigma level at energies greater than 500GeV from the supernova remnant RX J0852.0-4622 (G266.2-1.2) using the CANGAROO-II Imaging Atmospheric Cherenkov Telescope (IACT). The flux was 0.12 times of that of Crab at 1TeV. The signal centroid is consistent with the peak of the X-ray emission in the north-west rim of the remnant.Comment: 12pages, 4figures, to be published in ApJ

Search for VHE gamma rays from SS433/W50 with the CANGAROO-II telescope

SS433, located at the center of the supernova remnant W50, is a close proximity binary system consisting of a compact star and a normal star. Jets of material are directed outwards from the vicinity of the compact star symmetrically to the east and west. Non-thermal hard X-ray emission is detected from lobes lying on both sides. Shock accelerated electrons are expected to generate sub-TeV gamma rays through the inverse-Compton process in the lobes. Observations of the western X-ray lobe region of SS433/W50 system have been performed to detect sub-TeV gamma-rays using the 10m CANGAROO-II telescope in August and September, 2001, and July and September, 2002. The total observation times are 85.2 hours for ON source, and 80.8 hours for OFF source data. No significant excess of sub-TeV gamma rays has been found at 3 regions of the western X-ray lobe of SS433/W50 system. We have derived 99% confidence level upper limits to the fluxes of gamma rays and have set constraints on the strengths of the magnetic fields assuming the synchrotron/inverse-Compton model for the wide energy range of photon spectrum from radio to TeV. The derived lower limits are 4.3 microgauss for the center of the brightest X-ray emission region and 6.3 microgauss for the far end from SS433 in the western X-ray lobe. In addition, we suggest that the spot-like X-ray emission may provide a major contribution to the hardest X-ray spectrum in the lobe.Comment: 7 pages, 8 figures, to be published in Astroparticle Physic

The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium

Objective Marrow-derived endothelial progenitor cells (EPCs) are important in the neovascularization that occurs in diverse conditions such as cardiovascular disorders, inflammatory diseases, and neoplasms. In rheumatoid arthritis (RA), synovial neovascularization propels disease by nourishing the inflamed and hyperproliferative synovium. This study was undertaken to investigate the hypothesis that EPCs selectively home to inflamed joint tissue and may perpetuate synovial neovascularization. Methods In a collagen-induced arthritis (CIA) model, neovascularization and EPC accumulation in mouse ankle synovium was measured. In an antibody-induced arthritis model, EPC recruitment to inflamed synovium was evaluated. In a chimeric SCID mouse/human synovial tissue (ST) model, mice were engrafted subcutaneously with human ST, and EPC homing to grafts was assessed 2 days later. EPC adhesion to RA fibroblasts and RA ST was evaluated in vitro. Results In mice with CIA, cells bearing EPC markers were significantly increased in peripheral blood and accumulated in inflamed synovial pannus. EPCs were 4-fold more numerous in inflamed synovium from mice with anti–type II collagen antibody–induced arthritis versus controls. In SCID mice, EPC homing to RA ST was 3-fold greater than to normal synovium. Antibody neutralization of vascular cell adhesion molecule 1 (VCAM-1) and its ligand component Α4 integrin potently inhibited EPC adhesion to RA fibroblasts and RA ST cryosections. Conclusion These data demonstrate the selective recruitment of EPCs to inflamed joint tissue. The VCAM-1/very late activation antigen 4 adhesive system critically mediates EPC adhesion to cultured RA fibroblasts and to RA ST cryosections. These findings provide evidence of a possible role of EPCs in the synovial neovascularization that is critical to RA pathogenesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56042/1/22706_ftp.pd

Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers

Arginylation is an emerging post-translational modification mediated by arginyltransferase (ATE1) that is essential for mammalian embryogenesis and regulation of the cytoskeleton. Here, we discovered that Ate1-knockout (KO) embryonic fibroblasts exhibit tumorigenic properties, including abnormally rapid contact-independent growth, reduced ability to form cell-cell contacts and chromosomal aberrations. Ate1-KO fibroblasts can form large colonies in Matrigel and exhibit invasive behavior, unlike wild-type fibroblasts. Furthermore, Ate1-KO cells form tumors in subcutaneous xenograft assays in immunocompromised mice. Abnormal growth in these cells can be partially rescued by reintroduction of stably expressed specific Ate1 isoforms, which also reduce the ability of these cells to form tumors. Tumor array studies and bioinformatics analysis show that Ate1 is downregulated in several types of human cancer samples at the protein level, and that its transcription level inversely correlates with metastatic progression and patient survival. We conclude that Ate1-KO results in carcinogenic transformation of cultured fibroblasts, suggesting that in addition to its previously known activities Ate1 gene is essential for tumor suppression and also likely participates in suppression of metastatic growth. © 2016 Macmillan Publishers Limited, part of Springer Nature

Application of layered poly (L-lactic acid) cell free scaffold in a rabbit rotator cuff defect model

<p>Abstract</p> <p>Background</p> <p>This study evaluated the application of a layered cell free poly (L-lactic acid) (PLLA) scaffold to regenerate an infraspinatus tendon defect in a rabbit model. We hypothesized that PLLA scaffold without cultivated cells would lead to regeneration of tissue with mechanical properties similar to reattached infraspinatus without tendon defects.</p> <p>Methods</p> <p>Layered PLLA fabric with a smooth surface on one side and a pile-finished surface on the other side was used. Novel form of layered PLLA scaffold was created by superimposing 2 PLLA fabrics. Defects of the infraspinatus tendon were created in 32 rabbits and the PLLA scaffolds were transplanted, four rabbits were used as normal control. Contralateral infraspinatus tendons were reattached to humeral head without scaffold implantation. Histological and mechanical evaluations were performed at 4, 8, and 16 weeks after operation.</p> <p>Results</p> <p>At 4 weeks postoperatively, cell migration was observed in the interstice of the PLLA fibers. Regenerated tissue was directly connected to the bone composed mainly of type III collagen, at 16 weeks postoperatively. The ultimate failure load increased in a time-dependent manner and no statistical difference was seen between normal infraspinatus tendon and scaffold group at 8 and 16 weeks postoperatively. There were no differences between scaffold group and reattach group at each time of point. The stiffness did not improve significantly in both groups.</p> <p>Conclusions</p> <p>A novel form of layered PLLA scaffold has the potential to induce cell migration into the scaffold and to bridge the tendon defect with mechanical properties similar to reattached infraspinatus tendon model.</p

Prevalence of Metabolic Syndrome in Iranian Professional Drivers: Results from a Population Based Study of 12,138 Men

It is evident that professional driving is associated with substantial changes in lifestyle habits. Professional drivers are prone to metabolic syndrome (MetS) and its complications because their working environment is characterized by numerous stress factors such as lack of physical activity due to working in a fixed position, disruption in diet, and irregular sleep habits. The aim of the present study was to estimate the prevalence of MetS among long distance drivers residing in West Azerbaijan province in Iran.To assess the prevalence of metabolic syndrome among professional long distance drivers, 12138 participants were enrolled in this cross sectional study. The MetS was defined using International Diabetes Federation criteria.Among12138 participants, 3697 subjects found to be MetS. The crude and age-adjusted rates of MetS were 30.5% and 32.4% respectively. Based on Body mass index (BMI), 5027 subjects (41.4%) were overweight (BMI ≥25.01–30 kg/m2), and 2592 (21.3%) were obese (BMI ≥30.01 kg/m2). The presence of central obesity was more common than other components. The associations of MetS with BMI, pack-year smoking, age, weekly driving duration and driving experiences were significant in the logistic regression. By increasing BMI, pack-year smoking, age, weekly driving duration and driving experiences, odds ratio of MetS was increased.The study suggests that MetS has become a noteworthy health problem among Iranian long distance drivers. This might be due to the following facts: sitting in a fixed position for long hours while working, cigarette smoking, job stress, unhealthy diet and lack of physical activity. Educational programs should be established for promoting healthy lifestyle and also for early detection and appropriate intervention

Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis

Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process

Identification of Genes Required for Neural-Specific Glycosylation Using Functional Genomics

Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, α1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific α1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a neural-specific protein using a Drosophila RNAi library. We obtained 109 genes affecting glycosylation that clustered into nine functional groups. Among them, members of the RNA regulation group were enriched by a secondary screen that identified genes specifically regulating α1,3-fucosylation. Further analyses revealed that an RNA–binding protein, second mitotic wave missing (Swm), upregulates expression of the neural-specific glycosyltransferase FucTA and facilitates its mRNA export from the nucleus. This first large-scale genetic screen for glycosylation-related genes has revealed novel regulation of fucTA mRNA in neural cells