Differential Response of Heat-Shock-Induced p38 MAPK and JNK Activity in PC12 Mutant and PC12 Parental Cells for Differentiation and Apoptosis

Among the 3 mitogen-activated protein kinases -- ERK, p38 MAPK and JNK -- JNK has been suggested to participate in apoptosis, whereas p38 MAPK is thought to be part of the differentiation response. There are many common inducers of JNK and p38 MAPK, but the mechanisms underlying the differential response to apoptosis and differentiation are poorly understood. We found that heatshock activated p38 MAPK at 3min after exposure to a temperature of 44 in stress-hypersensitive PC12m3 mutant cells, while it activated JNK at 20min after the same heat treatment. However, heat shock activated p38 MAPK 5min after heat treatment and JNK 10min after heat treatment in PC12 parental cells. The extent of phosphorylation of p38 MAPK induced by heat shock in PC12m3 cells was significantly greater than that in PC12 parental cells, and a high level of heat-shock-induced neurite outgrowth was observed only in PC12m3 cells. On the other hand, heat-shock-induced JNK activation appeared more quickly and apoptosis started earlier in PC12 parental cells. These findings indicate that short stress induces p38 MAPK and longer stress induces JNK, and that the response of these kinases to heat shock differs depending on cell type.</p

Design and Performance of Superconducting Magnets for Hybrid Magnets(Part I. Establishment and Tests of Hybrid Magnet System at HFLSM)

Design, construction and performance of three superconducting magnets for the hybrid magnets installed in the High Field Laboratory for Superconducting Materials are described in detail. The compact solenoid, SM-3, without fully cryostable design forms the outer part of the most compact hybrid magnet in the world, HM-3 (32 mm bore, 20 T). Fully cryostable superconducting magnet designed under the Steckly criterion, SM-2, is the outer part of HM-2 (52 mm bore, 23 T), which has been most attractive to many experimentalists. SM-1, the outer part of HM-1 (32/52 mm bore, 31/28 T), with the Williams cryostability criterion is the world largest one of the superconducting magnets which employ Ti-doped Nb_3Sn multifilamentary conductors and can generate more than 12 T

A new tectono-magmatic model for the Lofoten/Vesterålen Margin at the outer limit of the Iceland Plume influence

Highlights • The Lofoten/Vesterålen margin has less Early Cenozoic lava flows than believed. • Breakup of the L/V margin is delayed ∼1 m.y. from the Vøring Plateau to the south. • Late arrival of the Iceland Plume may explain delayed breakup and prolonged extension. The Early Eocene continental breakup was magma-rich and formed part of the North Atlantic Igneous Province. Extrusive and intrusive magmatism was abundant on the continental side, and a thick oceanic crust was produced up to a few m.y. after breakup. However, the extensive magmatism at the Vøring Plateau off mid-Norway died down rapidly northeastwards towards the Lofoten/Vesterålen Margin. In 2003 an Ocean Bottom Seismometer profile was collected from mainland Norway, across Lofoten, and into the deep ocean. Forward/inverse velocity modeling by raytracing reveals a continental margin transitional between magma-rich and magma-poor rifting. For the first time a distinct lower-crustal body typical for volcanic margins has been identified at this outer margin segment, up to 3.5. km thick and ∼50. km wide. On the other hand, expected extrusive magmatism could not be clearly identified here. Strong reflections earlier interpreted as the top of extensive lavas may at least partly represent high-velocity sediments derived from the shelf, and/or fault surfaces. Early post-breakup oceanic crust is moderately thickened (∼8. km), but is reduced to 6. km after 1. m.y. The adjacent continental crystalline crust is extended down to a minimum of 4.5. km thickness. Early plate spreading rates derived from the Norway Basin and the northern Vøring Plateau were used to calculate synthetic magnetic seafloor anomalies, and compared to our ship magnetic profile. It appears that continental breakup took place at ∼53.1. Ma, ∼1. m.y. later than on the Vøring Plateau, consistent with late strong crustal extension. The low interaction between extension and magmatism indicates that mantle plume material was not present at the Lofoten Margin during initial rifting, and that the observed excess magmatism was created by late lateral transport from a nearby pool of plume material into the lithospheric rift zone at breakup time

Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion

Background: Acute coronary syndrome leads to systemic responses, including activation of the sympathetic nervous system, inflammation of atherosclerotic lesions, changes in metabolism and gene expressions of remote organs such as the spleen, bone marrow, and liver. Clinical trials and experimental studies have demonstrated that therapy with adipose-derived regenerative cells (ADRCs) attenuates myocardial ischemia/reperfusion (I/R) injury. The aim of this study is to investigate the role of ADRCs in regulating systemic reactions following I/R.Methods: Isolated ADRCs were obtained from green fluorescent protein transgenic male mice. Flow cytometry revealed that freshly isolated ADRCs expressed stem cell markers CD90 and Sca-1, and mesenchymal lineage marker. These cells exhibited multilineage differentiation into adipogenic, osteogenic, and chondrogenic lineages. Wild-type mice were subjected to 30 min of left ascending coronary ischemia and 24 h reperfusion. Freshly isolated ADRCs (105 cells) or vehicle (VEH), were administered intravenously through the tail at the time of reperfusion.Results: Compared to VEH, administration of ADRCs significantly reduced circulating troponin levels 24 h after I/R. Using quantitative real-time polymerase chain reaction analysis, the present study confirms that I/R-induced increase of factor X mRNA expression in the liver and was significantly inhibited by ADRCs compared to VEH. Administration of ADRCs significantly reduced the I/R-induced increase in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-18 seen in mice receiving VEH.Conclusions: These results suggest that administration of ADRCs could have an important role in reducing myocardial injury and regulating the hepatic gene expression profile following I/R

Heat Shock-Induced Three-Dimensional-Like Proliferation of Normal Human Fibroblasts Mediated by Pressed Silk

The aim of this study was to determine the optimal heat treatment conditions for enhancement of pressed silk-mediated 3D-like proliferation of normal human dermal fibroblasts, as well as to determine the responses to heat shock of cells and intracellular signaling pathways. The beginning of 3D-like pattern formation of cells was observed in the second week after the start of the experiment. The mean rates of beginning of 3D-like pattern formation by cells heat-treated at 40 ºC and 43 ºC for 10 min were significantly higher (3.2- and 8.6-fold, respectively) than that of untreated cells. We found that apoptosis had occurred in 7.5% and 50.0% of the cells at one week after heat treatment for 10 min at 43 ºC and 45 ºC, respectively. Western blot analysis demonstrated that phosphorylation of p38 MAPK and that of Hsp27 were markedly increased by heat treatment at 43 ºC for 10 min. The results of an experiment using a p38 MAPK inhibitor and Hsp27 inhibitor suggest that activation of p38 MAPK by heat shock is associated with 3D-like cell proliferation and that Hsp27 contributes to the inhibition of apoptosis. The results of this study should be useful for further studies aimed at elucidation of the physiologic mechanisms underlying thermotherapy

Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events

Objective: Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. Methods: 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. Results: During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Conclusions: Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. © Published by the BMJ Publishing Group Limited