Peroxiredoxin 2 as a chemotherapy responsiveness biomarker candidate in osteosarcoma revealed by proteomics

Purpose : We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients. Experimental design : Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2‐D DIGE consisted of 2250 protein spots. Results : Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p‐value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2‐D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting. Conclusions and clinical relevance : These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.     

Orientation dependence of fracture toughness measured by indentation methods and its relation to surface energy in single crystal silicon

Fracture toughness of silicon crystals has been investigated using indentation methods, and their surface energies have been calculated by molecular dynamics (MD). In order to determine the most preferential fracture plane at room temperature among the crystallographic planes containing the 〈001〉, 〈110〉 and 〈111〉 directions, a conical indenter was forced into (001), (110) and (111) silicon wafers at room temperature. Dominant {110}, {111} and {110} cracks were introduced from the indents on (001), (011) and (111) wafers, respectively. Fracture occurs most easily along {110}, {111} and {110} planes among the crystallographic planes containing the 〈001〉, 〈011〉 and 〈111〉 directions, respectively. A series of surface energies of those planes were calculated by MD to confirm the orientation dependence of fracture toughness. The surface energy of the {110} plane is the minimum of 1.50 Jm⁻² among planes containing the 〈001〉 and 〈111〉 directions, respectively, and that of the {111} plane is the minimum of 1.19 Jm⁻² among the planes containing the 〈011〉 direction. Fracture toughness of those planes was also derived from the calculated surface energies. It was shown that the K _IC value of the {110} crack plane was the minimum among those for the planes containing the 〈001〉 and 〈111〉 directions, respectively, and that K _IC value of the {111} crack plane was the minimum among those for the planes containing the 〈011〉 direction. These results are in good agreement with that obtained conical indentation.     

Permeation measurements for investigating atomic hydrogen flux and wall pumping/fuelling dynamics in QUEST

In order to investigate the overall atomic hydrogen background and the dynamic characteristics of wall pumping/fuelling phenomenon, a permeation probe system has been developed and applied in the spherical tokamak QUEST. Reliability of measurements, within ±3% accuracy and a positive correlation with the hydrogen line emission over three orders of magnitude have been demonstrated for more than 3000 various plasma discharges. By comparison of the experimental permeation (flux) curves with the numerically simulated curves, the net incident atomic hydrogen flux is evaluated in the range of 1 × 10¹⁹ H m^?2 s^?1 to 4 × 10²⁰ H m^?2 s^?1. The atomic flux has been investigated as a function of various plasma operation parameters like RF power, gas pressure and magnetic configuration. Using the static particle balance and permeation measurements, the progress in wall conditioning has been investigated. An inverse correlation between the atomic hydrogen flux and improvement in wall pumping has been observed over the two campaigns.     

A Technique to Eliminate Redundant Inter-Processor Communication on Parallelizing Compiler TINPAR

Optimizing inter-processor (PE) communication is crucial for parallelizing compilers for message-passing parallel machines to achieve high performance. In this paper, we propose a technique to eliminate redundant inter-PE messages. This technique utilizes data-flow analysis to find a definition point that corresponds to a use point where the definition and the use occur in different PEs. If several read accesses occurred in the same PE use the data defined at the same definition point in another PE, redundant inter-PE messages are eliminated as follows: only one inter-PE communication is performed for the earliest read access and the previously received data are used for the following read. In order to guarantee the consistency of the data, a valid flag and a sent flag are provided for each chunk of received data. The control of these flags is equivalent to the coherence control by the self invalidation on a compiler aided cache coherence scheme.     

Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase

Parkinson’s disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. The synthesis of human NM is regarded to be similar to that of melanin in melanocytes; melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then, synthesized to NM. Intracellular NM accumulation above a specific threshold has been reported to be associated with DA neuron death and PD phenotypes. This review reports recent progress in the biosynthesis and pathophysiology of NM in PD.     

Distribution and behavior of nonylphenol, octylphenol, and nonylphenol monoethoxylate in Tokyo metropolitan area: their association with aquatic particles and sedimentary distributions

Distributions of alkylphenols (APs) [i.e., nonylphenol (NP), octylphenol (OP)], and nonylphenol monoethoxylate (NP1EO) in wastewater effluents, river water, and riverine and bay sediments in the Tokyo metropolitan area were demonstrated. During sewage treatments, NP and OP were efficiently removed from the sewage effluents through activated sludge treatments. Greater removal for NP (93% on average) than OP (84% on average) was consistent with their partitioning behavior to particles in primary and secondary effluents. NP concentrations in the river water samples ranged from 0.051 to 1.08 microg/L with higher concentrations in summer and spring than in colder seasons. In the river water samples, approximately 20% of NP was found in the particulate phase. Organic carbon-normalized apparent partition coefficients (K'OC) for NP (10(5.22 +/- 0.38)) and OP (10(4.65 +/- 0.42)) were 1 order of magnitude higher than those expected from their octanol-water partition coefficients (K(OW)), indicating strong affinity of APs to aquatic particles. Among NP isomers, no significant differences in their K'OC values were suggested. This is consistent with surprisingly uniform isomer peak profiles among the technical standard and all the environmental samples analyzed. NP and OP were widely distributed in the river sediments in Tokyo, and relatively high concentrations (0.5-13.0 microg/g dry) of NP were observed in a long reach (approximately 10 km) in the Sumidagawa River. In situ production of APs in the river sediment was suggested. Seaward decreasing trend in APs concentration was observed from the estuary to the Tokyo Bay. APs were well preserved in a sediment core collected from the bay. The profile shows subsurface maximum of AP concentrations in the layer deposited around the mid-1970s. The recent decrease in AP concentrations can be attributed to the legal regulation of industrial wastewater in the early 1970s.     

Profiling and Imaging of Phospholipids in Brains of Abcd1‐Deficient Mice

ABCD1 is a gene responsible for X‐linked adrenoleukodystrophy (X‐ALD), and is critical for the transport of very long‐chain fatty acids (VLCFA) into peroxisomes and subsequent β‐oxidation. VLCFA‐containing lipids accumulate in X‐ALD patients, although the effect of ABCD1‐deficiency on each lipid species in the central nervous system has not been fully characterized. In this study, each phospholipid and lysophospholipid species in Abcd1‐deficient mice brains were profiled by liquid chromatography‐mass spectrometry. Among the phospholipid and lysophospholipid species that are significantly more enriched in Abcd1‐deficient mice brains, VLCFA were present in 75, 15, 5, 4, and 1 species of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, lysophosphatidylcholine, and lysophosphatidylethanolamine, respectively. Most VLCFA were incorporated at the sn‐1 position of phosphatidylcholine and phosphatidylethanolamine. Among the phospholipid species that are significantly less enriched in Abcd1‐deficient mice brains, odd‐numbered saturated or mono‐unsaturated fatty acyl moieties are contained in all phosphatidylcholine species. In addition, a number of phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine species contained highly unsaturated fatty acyl moieties. Intriguingly, 44:1 phosphatidylcholine with VLCFA was mainly distributed in the gray matter, such as the cortex, but not in the white matter in the cerebrum and cerebellum. These results show that ABCD1‐deficiency causes metabolic alternation of long‐chain fatty acids and VLCFA. Moreover, our results imply a molecular mechanism for the incorporation of saturated or monounsaturated VLCFA into the sn‐1 position of phospholipids, and also indicate that the distribution of phospholipids with VLCFA may correlate with the development of X‐ALD.     

Effects of some calcium-related agents on the protoplast transfection of Lactobacillus casei with phage PL-1 DNA

An audit of the treatment procedures routinely adopted by maxillofacial and oral surgeons for the removal of impacted third molars under general anaesthesia was undertaken in South Africa. Most maxillofacial and oral surgeons agree on the method of bone removal, the prescribing of antibiotics, analgesic agents and mouthwashes, the suturing of the incision wound and the post-operative review of patients. The results were compared to a similar study undertaken by Falcon and Roberts (1992) in the UK. With the exception of the method of bone removal, maxillofacial and oral surgeons in both groups share a similar approach to the treatment procedures adopted in the removal of impacted third molars. Some variability, however, existed in both studies with regard to the use of intra-operative local anaesthetic agents, the administration of peri-operative steroids and the use of non-steroidal anti-inflammatory agents.     

Effects of an antiallergic drug, pemirolast potassium on tyrosine phosphorylation and map kinase activation in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells

Aggregation of high affinity IgE Fc receptors (Fc epsilon RI) on RBL-2H3 cells results in tyrosine phosphorylation of 33-, 42-, 44-, 72-, 80-, 90-, 125-kDa proteins. The 42 and 44 kDa proteins were identified as mitogen-activated protein (MAP) kinases with immunoblotting of anti-MAP kinase antibody. The effects of an antiallergic drug, pemirolast potassium (TBX) on Ag-induced protein tyrosine phosphorylation and MAP kinase activation were investigated. When RBL-2H3 cells were stimulated with Ag in the presence of TBX, tyrosine phosphorylation of three proteins (33, 42 and 44 kDa) was inhibited concentration-dependently (0.1-10 micrograms/ml). Inhibition of Ag-induced tyrosine phosphorylation of 33 kDa protein, which could be a beta subunit of Fc epsilon RI, suggests that TBX may prevent the activation of Fc epsilon RI. TBX suppressed activation of MAP kinases (42 and 44 kDa) in response to Ag as well as phorbol myristate acetate (100 nM) or calcium ionophore A23187 (500 nM), implying that the drug acts on signal transduction component(s) between the second messengers and MAP kinases. However, TBX had no effects on protein tyrosine phosphorylation and MAP kinase activation in MC3T3-E1 osteoblastic cells. These results indicate that TBX may affect Fc epsilon RI and also may act as a step distal of Ca2+ mobilization and protein kinase C activation leading to MAP kinase activation in RBL-2H3 cells.