Cripto-1 localizes to dynamic and shed filopodia associated with cellular migration in glioblastoma cells

Cripto-1 is a protein participating in tissue orientation during embryogenesis but has also been implicated in a wide variety of cancers, such as colon, lung and breast cancer. Cripto-1 plays a role in the regulation of different pathways, including TGF-β/Smad and Wnt/β-catenin, which are highly associated with cell migration both during embryonal development and cancer progression. Little is known about the detailed subcellular localization of cripto-1 and how it participates in the directional movement of cells. In this study, the subcellular localization of cripto-1 in glioblastoma cells was investigated in vitro with high-resolution microscopy techniques. Cripto-1 was found to be localized to dynamic and shed filopodia and transported between cells through tunneling nanotubes. Our results connect the refined subcellular localization of cripto-1 to its functions in cellular orientation and migration.     

TRAIL Receptors Serve as Stress-Associated Molecular Patterns to Promote ER-Stress-Induced Inflammation

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The spinal cord supports of vertebrae in the crown‐group salamanders (Caudata,Urodela)

The development of spinal cord supports (bony thickenings which extend into the vertebral canal of vertebrae) in primitive (Salamandrella keyserlingii) and derived (Lissotriton vulgaris) salamanders were described. The spinal cord supports develop as the protuberances of periostal bone of the neural arches in the anteroproximal part of the septal collagenous fibers which connect a transverse myoseptum with the notochord and spinal cord, in the septal bundle inside the vertebral canal. Spinal cord supports were also found in some teleostean (Salmo salar, Oncorhynchus mykiss) and dipnoan (Protopterus sp.) fishes. The absence of the spinal cord supports in vertebrates with cartilaginous vertebrae (lampreys, chondrichthyan, and chondrostean fishes) corresponds to the fact that the spinal cord supports are bone structures. The absence of the spinal cord supports in frogs correlates with the lack of the well developed septal bundles inside the vertebral canal. The spinal cord supports are, presumably, a synapomorphic character for salamanders which originated independently of those observed in teleostean and dipnoan fishes. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc.     

Impacts of maturation on the micromechanics of the meniscus extracellular matrix

To elucidate how maturation impacts the structure and mechanics of meniscus extracellular matrix (ECM) at the length scale of collagen fibrils and fibers, we tested the micromechanical properties of fetal and adult bovine menisci via atomic force microscopy (AFM)-nanoindentation. For circumferential fibers, we detected significant increase in the effective indentation modulus, E_ind, with age. Such impact is in agreement with the increase in collagen fibril diameter and alignment during maturation, and is more pronounced in the outer zone, where collagen fibrils are more aligned and packed. Meanwhile, maturation also markedly increases the E_ind of radial tie fibers, but not those of intact surface or superficial layer. These results provide new insights into the effect of maturation on the assembly of meniscus ECM, and enable the design of new meniscus repair strategies by modulating local ECM structure and mechanical behaviors.     

Vascular supply of the anterior interventricular epicardial nerves and ventricular Purkinje fibers in the porcine hearts

The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well-developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves.     

Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons

Upregulation of small heat-shock proteins (sHsps) in response to cellular stress is one mechanism to increase cell viability. We previously described that cultured rat hippocampal neurons express five of the 11 family members but only upregulate two of them (HspB1 and HspB5) at the protein level after heat stress. Since neurons have to cope with many other pathological conditions, we investigated in this study the expression of all five expressed sHsps on mRNA and protein level after sublethal sodium arsenite and oxidative and hyperosmotic stress. Under all three conditions, HspB1, HspB5, HspB6, and HspB8 but not HspB11 were consistently upregulated but showed differences in the time course of upregulation. The increase of sHsps always occurred earlier on mRNA level compared with protein levels. We conclude from our data that these four upregulated sHsps (HspB1, HspB5, HspB6, HspB8) act together in different proportions in the protection of neurons from various stress conditions.     

Molecular basis of the Keap1–Nrf2 system

Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes, and Keap1 (Kelch-like ECH-associated protein 1), an adaptor subunit of Cullin 3-based E3 ubiquitin ligase, regulates Nrf2 activity. Keap1 also acts as a sensor for oxidative and electrophilic stresses. Keap1 retains multiple sensor cysteine residues that detect various stress stimuli. Increasing attention has been paid to the roles that Nrf2 plays in the protection of our bodies against drug toxicity and stress-induced diseases. On the other hand, Nrf2 is found to promote both oncogenesis and cancer cell resistance against chemotherapeutic drugs. Thus, although Nrf2 acts to protect our body from deleterious stresses, cancer cells hijack the Nrf2 activity to support their malignant growth. Nrf2 has emerged as a new therapeutic target, and both inducers and inhibitors of Nrf2 are awaited. Studies challenging the molecular basis of the Keap1–Nrf2 system functions are now critically important to improve translational studies of the system. Indeed, recent studies identified cross talk between Nrf2 and other signaling pathways, which provides new insights into the mechanisms by which the Keap1–Nrf2 system serves as a potent regulator of our health and disease.     

Characterization of the passive mechanical properties of spine muscles across species

Passive mechanical properties differ between muscle groups within a species. Altered functional demands can also shift the passive force-length relationship. The extent that passive mechanical properties differ within a muscle group (e.g. spine extensors) or between homologous muscles of different species is unknown. It was hypothesized that multifidus, believed to specialize in spine stabilization, would generate greater passive tensile stresses under isometric conditions than erector spinae, which have more generalized functions of moving and stabilizing the spine; observing greater multifidus moduli in different species would strengthen this hypothesis. Permeabilized fibre bundles (n = 337) from the multifidus and erector spinae of mice, rats, and rabbits were mechanically tested. A novel logistic function was fit to the experimental data to fully characterize passive stress and modulus. Species had the greatest effect on passive muscle parameters with mice having the largest moduli at all lengths. Rats generated less passive stress than rabbits due to a shift of the passive force-length relationship towards longer muscle lengths. Rat multifidus generated slightly greater stresses than erector spinae, but no differences were observed between mouse muscles. The secondary objective was to determine the parameters required to simulate the passive force-length relationship. Experimental data were compared to the passive muscle model in OpenSim. The default OpenSim model, optimized for hindlimb muscles, did not fit any of the spine muscles tested; however, the model could accurately simulate experimental data after adjusting the input parameters. The optimal parameters for modelling the passive force-length relationships of spine muscles in OpenSim are presented.     

Comparative responses of Achillea millefolium ecotypes to competition and soil type

Summary Achillea millefolium populations from adjacent sites with zonal and serpentime soil were used to test predictions about the relation between growth and the competitive ability of plants in productive and unproductive environments. Under greenhouse conditions, individually-grown plants from both sources grew larger in serpentine soil than in zonal soil; serpentine plants accumulated 72% more biomass than zonal plants. In zonal soil, zonal plants were 71% larger than serpentine plants, although these differences were not statistically significant, and plants from both sources accumulated much less biomass and were shorter than plants growing in serpentine soil. In a high density, fertilized replacement series, zonal plants were taller and heavier but exhibited no more competitive ability than serpentine plants. The predictions that rapid height growth and biomass accumulation contribute significantly to competitive ability are not supported by our results. Although ecotypic differentiation has occurred between these A. millefolium populations, apparently in response to different soil types, the expression of these heritable differences can be masked by other environmental effects. There has been no apparent trade-off in these ecotypes between their response to the physical environment and their competitive ability.