ABSTRACT
The present study examines a friction stir welded 2017A aluminium alloy. Transmission electron microscope investigations of the weld nugget revealed the average grain size of 5 microm, moderate density of dislocations as well as the presence of nanometric precipitates located mostly in grains interiors. Scanning electron microscope observations of fractures showed the presence of ductile fracture in the region of the weld nugget with brittle precipitates in the lower part. The microhardness analysis performed on the cross-section of the joints showed fairly small changes; however, after the artificial ageing process an increase in hardness was observed. The change of the joint hardness subject to the ageing process indicates partial supersaturation in the material during friction stir welding and higher precipitation hardening of the joint.
ABSTRACT
High HIF-2alpha protein levels in the sympathetic nervous system-derived childhood tumour neuroblastoma as well as immature phenotype correlate to unfavourable outcome. Here we show that a small subset of perivascularly located, strongly HIF-2alpha-positive tumour cells (MYCN amplified) lacks expression of differentiation markers, but expresses neural crest and early sympathetic progenitor marker genes such as Notch-1, HES-1, c-Kit, dHAND, and vimentin. HIF-2alpha- and CD68-positive tumour-associated macrophages were frequently found close to the immature and HIF-2alpha-positive neuroblastoma cells and as VEGF levels are high in the perivascular niche, we hypothesize that neuroblastoma neural crest-like cells and macrophages cooperate to facilitate angiogenesis and thereby contribute to the aggressive neuroblastoma phenotype.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Neural Crest/metabolism , Neuroblastoma/metabolism , Cell Hypoxia , Humans , Macrophages/pathology , N-Myc Proto-Oncogene Protein , Neoplasm Proteins/metabolism , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Neural Crest/pathology , Neuroblastoma/blood supply , Neuroblastoma/pathology , Nuclear Proteins/metabolism , Oncogene Proteins/metabolism , Sympathetic Nervous System/metabolism , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Arsenic trioxide (As(2)O(3)) is toxic to multidrug-resistant neuroblastoma cells in vivo and in vitro. In neuroblastoma, As(2)O(3) does not exert its cell death-promoting effects via a classical apoptotic pathway. A death mechanism involving proteolytic cleavage of Bax to a p18 form seems to be of importance, because inhibition of Bax cleavage coincides with diminished cell death. As existing models of cell death implicate Bax in the intrinsic apoptotic pathway, triggering death after Bax translocation to the mitochondria, we investigated the cellular localization of p18 Bax by subcellular fractionation. After As(2)O(3) treatment, p18 Bax was only present in nuclei-enriched, mitochondria-depleted fractions. Cytoplasmic p21 Bax levels decreased, whereas total (p21 and p18) nuclear Bax increased. Overexpressed p21 Bax localized to the cytoplasm and nuclei, whereas overexpressed p18 Bax localized to extra-nuclear structures only. The inability of overexpressed p18 Bax to locate to the nucleus, and the As(2)O(3)-induced reduction of p21 Bax in the cytosol, suggest an As(2)O(3)-induced mechanism where p18 Bax gets cleaved and 'trapped' in the nucleus. This model is strengthened by the observation that calpain, the protease responsible for p18 Bax generation, is present in the nuclei, and that nuclear calpain is induced by increasing As(2)O(3) and Ca(2+) levels.
Subject(s)
Antineoplastic Agents/toxicity , Cell Nucleus/metabolism , Neuroblastoma/drug therapy , Neuroblastoma/pathology , Oxides/toxicity , Peptide Hydrolases/metabolism , bcl-2-Associated X Protein/metabolism , Arsenic Trioxide , Arsenicals , Cell Death/drug effects , Cell Line, Tumor , Enzyme Activation/drug effects , Humans , Neuroblastoma/enzymologyABSTRACT
The paper presents the behaviour of DNA, RNA and soluble proteins in whole homogenate as well as the nuclear, mitochondrial and postmitochondrial liver fractions in guinea pigs exposed to combustion exhaust gases and the products of their reaction with ammonia. A decrease of RNA level was found in the liver of animals exposed to combustion exhaust gases together with a decrease of soluble proteins in all the studied fractions. On the other hand, in the group of animals subjected to the action of neutralization products of combustion gases by ammonia, the studied components were increased. This increase may be the result of the simultaneous action of industrial noise.
