New Invertebrate Vectors of Okadaic Acid from the North Atlantic Waters—Portugal (Azores and Madeira) and Morocco

PubMed Central

Silva, Marisa; Rodriguez, Inés; Barreiro, Aldo; Kaufmann, Manfred; Neto, Ana Isabel; Hassouani, Meryem; Sabour, Brahim; Alfonso, Amparo; Botana, Luis M.; Vasconcelos, Vitor

2015-01-01

Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP) through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, São Miguel Island (Azores archipelago) and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp., and Stramonita haemostoma. Differences in toxin contents among the species were found. Even though low concentrations were detected, the levels of toxins that were present, especially in edible species, indicate the importance of these types of studies. Routine monitoring should be extended to comprise a wider number of vectors other than for bivalves of okadaic acid and its analogues. PMID:26670254

Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene plus okadaic acid class tumor promoters.

PubMed

Fujiki, H; Suganuma, M; Yoshizawa, S; Kanazawa, H; Sugimura, T; Manam, S; Kahn, S M; Jiang, W; Hoshina, S; Weinstein, I B

1989-01-01

Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin-1, and calyculin A, have potent tumor-promoting activity in two-stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and each of these tumor promoters revealed the same mutation at the second nucleotide of codon 61 (CAA----CTA) in the c-Ha-ras gene, determined by the polymerase chain reaction procedure and DNA sequencing. Three potent 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, TPA, teleocidin, and aplysiatoxin, showed the same effects. These results provide strong evidence that this mutation in the c-Ha-ras gene is due to a direct effect of DMBA rather than a selective effect of specific tumor promoters.

Evaluation of the glycemic indices of three commonly eaten mixed meals in Okada, Edo State.

PubMed

Omage, Kingsley; Omage, Sylvia O

2018-01-01

People do not generally eat single or individual meals; rather they eat mixed meals, consisting of two or more individual meals. These mixed meals usually have glycemic indices which differ from that of the individual food type. This study was aimed at evaluating the glycemic indices of three commonly consumed mixed meals eaten in Okada; rice and beans (test food 1), rice and plantain (test food 2), beans and plantain (test food 3). Two hundred and forty healthy subjects aged between 18 and 30 participated in this study. They were randomized into three groups of eighty persons each, and fed with the standard food (50 g glucose) on day one and one of the test foods on day two, after an overnight fast. Blood samples were taken at 0, 30, 60, 90, and 120 min after the food had been eaten. The results showed that the Glycemic Index (GI) values for the test foods were high: 86.60 (test food 1), 89.74 (test food 2), 86.93(test food 3). The incremental increase in blood glucose was monitored and calculated for each food and when compared with that of the standard food (glucose), there was significant differences ( p  < .036) for test food 1 and ( p  < .068) for test food 3; both at 30 min. At 120 min, no significant differences in blood glucose levels were observed ( p  > .05). The results from this study indicated that the GI of the mixed meals was affected by the constituent nutrient and the response is also affected by the proportion of each nutrient. Our findings show that the selected test foods (mixed meals) consumed in Okada have high GI values.

SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

PubMed

Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

2016-01-01

In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

Spatial memory deficit and neurodegeneration induced by the direct injection of okadaic acid into the hippocampus in rats.

PubMed

He, J; Yamada, K; Zou, L B; Nabeshima, T

2001-01-01

We investigated the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, on spatial memory and neuronal survival in rats. Rats were initially trained on a spatial memory task in an eight arm radial maze. Spatial reference and working memory was impaired 1 day after the unilateral microinjection of OA into the dorsal hippocampus. The impairment was transient, and had disappeared by the following day. In contrast, neurodegeneration induced by OA was persistent and extended to the contralateral side 13 days after the injection. These results suggest that OA causes spatial memory impairment and neurodegeneration when injected directly into the hippocampus. Our findings also indicate dissociation between memory impairment and neurodegeneration induced by OA.

Assessment of the hydrolysis process for the determination of okadaic acid-group toxin ester: presence of okadaic acid 7-O-acyl-ester derivates in Spanish shellfish.

PubMed

Villar-González, A; Rodríguez-Velasco, M L; Ben-Gigirey, B; Yasumoto, T; Botana, L M

2008-04-01

The contamination of different types of shellfish by okadaic acid (OA)-group toxin esters is an important problem that presents serious risk for human health. During previous investigations carried out in our laboratory by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS), the occurrence of a high percentage of esters in relation to the total OA equivalents has been observed in several shellfish species. The determination of these kinds of toxins using LC/MS or other chemical methods requires a hydrolysis step in order to convert the sterified compounds into the parent toxins, OA, dinophysistoxins-1 (DTX-1) and dinophysistoxins-2 (DTX-2). Most of the hydrolysis procedures are based on an alkaline hydrolysis reaction. However, despite hydrolysis being a critical step within the analysis, it has not been studied in depth up to now. The present paper reports the results obtained after evaluating the hydrolysis process of an esterified form of OA by using a standard of 7-O-acyl ester with palmitoyl as the fatty acid (palOA). Investigations were focused on checking the effectiveness of the hydrolysis for palOA using methanol as solvent standard and matrices matched standards. From the results obtained, no matrix influence on the hydrolysis process was observed and the quantity of palOA converted into OA was always above 80%. The analyses of different Spanish shellfish samples showed percentages of palOA in relation to the total OA esters ranging from 27% to 90%, depending on the shellfish specie.

Identification of okadaic acid binding protein 2 in reconstituted sponge cell clusters from Halichondria okadai and its contribution to the detoxification of okadaic acid.

PubMed

Konoki, Keiichi; Okada, Kayo; Kohama, Mami; Matsuura, Hiroki; Saito, Kaori; Cho, Yuko; Nishitani, Goh; Miyamoto, Tomofumi; Fukuzawa, Seketsu; Tachibana, Kazuo; Yotsu-Yamashita, Mari

2015-12-15

Okadaic acid (OA) and OA binding protein 2 (OABP2) were previously isolated from the marine sponge Halichondria okadai. Because the amino acid sequence of OABP2 is completely different from that of protein phosphatase 2A, a well-known target of OA, we have been investigating the production and function of OABP2. In the present study, we hypothesized that OABP2 plays a role in the detoxification of OA in H. okadai and that the OA concentrations are in proportional to the OABP2 concentrations in the sponge specimens. Based on the OA concentrations and the OABP2 concentrations in the sponge specimens collected in various places and in different seasons, however, we could not determine a positive correlation between OA and OABP2. We then attempted to determine distribution of OA and OABP2 in the sponge specimen. When the mixture of dissociated sponge cells and symbiotic species were separated with various pore-sized nylon meshes, most of the OA and OABP2 was detected from the same 0-10 μm fraction. Next, when sponge cell clusters were prepared from a mixture of dissociated sponge cells and symbiotic species in the presence of penicillin and streptomycin, we identified the 18S rDNA of H. okadai and the gene of OABP2 in the analysis of genomic DNA but could not detect OA by LC-MS/MS. We thus concluded that the sponge cells express OABP2, and that OA was not apparently present in the sponge cells but could be colocalized with OABP2 in the sponge cells at a concentration less than the limit of detection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Okadaic Acid Meet and Greet: An Insight into Detection Methods, Response Strategies and Genotoxic Effects in Marine Invertebrates

PubMed Central

Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Méndez, Josefina; Eirín-López, José M.

2013-01-01

Harmful Algal Blooms (HABs) constitute one of the most important sources of contamination in the oceans, producing high concentrations of potentially harmful biotoxins that are accumulated across the food chains. One such biotoxin, Okadaic Acid (OA), is produced by marine dinoflagellates and subsequently accumulated within the tissues of filtering marine organisms feeding on HABs, rapidly spreading to their predators in the food chain and eventually reaching human consumers causing Diarrhetic Shellfish Poisoning (DSP) syndrome. While numerous studies have thoroughly evaluated the effects of OA in mammals, the attention drawn to marine organisms in this regard has been scarce, even though they constitute primary targets for this biotoxin. With this in mind, the present work aimed to provide a timely and comprehensive insight into the current literature on the effect of OA in marine invertebrates, along with the strategies developed by these organisms to respond to its toxic effect together with the most important methods and techniques used for OA detection and evaluation. PMID:23939476

Intracerebroventricular administration of okadaic acid induces hippocampal glucose uptake dysfunction and tau phosphorylation.

PubMed

Broetto, Núbia; Hansen, Fernanda; Brolese, Giovana; Batassini, Cristiane; Lirio, Franciane; Galland, Fabiana; Dos Santos, João Paulo Almeida; Dutra, Márcio Ferreira; Gonçalves, Carlos-Alberto

2016-06-01

Intraneuronal aggregates of neurofibrillary tangles (NFTs), together with beta-amyloid plaques and astrogliosis, are histological markers of Alzheimer's disease (AD). The underlying mechanism of sporadic AD remains poorly understood, but abnormal hyperphosphorylation of tau protein is suggested to have a role in NFTs genesis, which leads to neuronal dysfunction and death. Okadaic acid (OKA), a strong inhibitor of protein phosphatase 2A, has been used to induce dementia similar to AD in rats. We herein investigated the effect of intracerebroventricular (ICV) infusion of OKA (100 and 200ng) on hippocampal tau phosphorylation at Ser396, which is considered an important fibrillogenic tau protein site, and on glucose uptake, which is reduced early in AD. ICV infusion of OKA (at 200ng) induced a spatial cognitive deficit, hippocampal astrogliosis (based on GFAP increment) and increase in tau phosphorylation at site 396 in this model. Moreover, we observed a decreased glucose uptake in the hippocampal slices of OKA-treated rats. In vitro exposure of hippocampal slices to OKA altered tau phosphorylation at site 396, without any associated change in glucose uptake activity. Taken together, these findings further our understanding of OKA neurotoxicity, in vivo and vitro, particularly with regard to the role of tau phosphorylation, and reinforce the importance of the OKA dementia model for studying the neurochemical alterations that may occur in AD, such as NFTs and glucose hypometabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

Okadaic acid and microcystin insensitive PPP-family phosphatases may represent novel biotechnology targets.

PubMed

Uhrig, R Glen; Moorhead, Greg B

2011-12-01

Reversible protein phosphorylation is of central importance to the proper cellular functioning of all living organisms. Catalyzed by the opposing reactions of protein kinases and phosphatases, dysfunction in reversible protein phosphorylation can result in a wide variety of cellular aberrations. In eukaryotic organisms there exists four classes of protein phosphatases, of which the PPP-family protein phosphatases have documented susceptibility to a range of protein and small molecule inhibitors. These inhibitors have been of great importance to the biochemical characterization of PPP-family protein phosphatases since their discovery, but also maintain in natura biological significance with their endogenous regulatory properties (protein inhibitors) and toxicity (small molecule inhibitors). Recently, two unique PPP-family protein phosphatases, named the Shewanella-like protein phosphatases (SLP phosphatases), from Arabidopsis thaliana were characterized and found to be phylogenetically similar to the PPP-family protein phosphatases protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), while completely lacking sensitivity to the classic PPP-family phosphatase small molecule inhibitors okadaic acid and microcystin-LR. SLP phosphatases were also found to be absent in metazoans, but present in a wide range of bacteria, fungi and protozoa responsible for human disease. The unique biochemical properties and evolutionary heritage of SLP phosphatases suggests they could not only be potential biotechnology targets for agriculture, but may also prove to be of interest for future therapeutic drug development. © 2011 Landes Bioscience

Structure–Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins

PubMed Central

Twiner, Michael J.; Doucette, Gregory J.; Pang, Yucheng; Fang, Chao; Forsyth, Craig J.; Miles, Christopher O.

2016-01-01

Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure–activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2-epi-DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 >> 2-epi-DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs’ activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors. PMID:27827901

Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice.

PubMed

Rajasekar, N; Dwivedi, Subhash; Tota, Santosh Kumar; Kamat, Pradeep Kumar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

2013-09-05

Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment. © 2013 Elsevier B.V. All rights reserved.

Structure-Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins.

PubMed

Twiner, Michael J; Doucette, Gregory J; Pang, Yucheng; Fang, Chao; Forsyth, Craig J; Miles, Christopher O

2016-11-04

Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2- epi -DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 > 2- epi -DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs' activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors.

Cdk1 and okadaic acid-sensitive phosphatases control assembly of nuclear pore complexes in Drosophila embryos.

PubMed

Onischenko, Evgeny A; Gubanova, Natalia V; Kiseleva, Elena V; Hallberg, Einar

2005-11-01

Disassembly and reassembly of the nuclear pore complexes (NPCs) is one of the major events during open mitosis in higher eukaryotes. However, how this process is controlled by the mitotic machinery is not clear. To investigate this we developed a novel in vivo model system based on syncytial Drosophila embryos. We microinjected different mitotic effectors into the embryonic cytoplasm and monitored the dynamics of disassembly/reassembly of NPCs in live embryos using fluorescently labeled wheat germ agglutinin (WGA) or in fixed embryos using electron microscopy and immunostaining techniques. We found that in live embryos Cdk1 activity was necessary and sufficient to induce disassembly of NPCs as well as their cytoplasmic mimics: annulate lamellae pore complexes (ALPCs). Cdk1 activity was also required for keeping NPCs and ALPCs disassembled during mitosis. In agreement recombinant Cdk1/cyclin B was able to induce phosphorylation and dissociation of nucleoporins from the NPCs in vitro. Conversely, reassembly of NPCs and ALPCs was dependent on the activity of protein phosphatases, sensitive to okadaic acid (OA). Our findings suggest a model where mitotic disassembly/reassembly of the NPCs is regulated by a dynamic equilibrium of Cdk1 and OA-sensitive phosphatase activities and provide evidence that mitotic phosphorylation mediates disassembly of the NPC.

PP2A inhibition assay using recombinant enzyme for rapid detection of okadaic acid and its analogs in shellfish.

PubMed

Ikehara, Tsuyoshi; Imamura, Shihoko; Yoshino, Atsushi; Yasumoto, Takeshi

2010-01-01

Okadaic acid and its analogs (OAs) responsible for diarrhetic shellfish poisoning (DSP) strongly inhibit protein phosphatase 2A (PP2A) and thus are quantifiable by measuring the extent of the enzyme inhibition. In this study, we evaluated the suitability of the catalytic subunit of recombinant human PP2A (rhPP2Ac) for use in a microplate OA assay. OA, dinophysistoxin-1(DTX1), and hydrolyzate of 7-O-palmitoyl-OA strongly inhibited rhPP2Ac activity with IC(50) values of 0.095, 0.104, and 0.135 nM, respectively. The limits of detection and quantitation for OA in the digestive gland of scallops and mussels were 0.0348 μg/g and 0.0611 μg/g respectively, and, when converted to the whole meat basis, are well below the regulation level proposed by EU (0.16 μg/g whole meat). A good correlation with LC-MS data was demonstrated, the correlation coefficient being 0.996 with the regression slope of 1.097.

GENE EXPRESSION PROFILING OF HUMAN LIVER CARCINOMA (HepG2) CELLS EXPOSED TO THE MARINE TOXIN OKADAIC ACID

PubMed Central

Fieber, Lynne A.; Greer, Justin B.; Guo, Fujiang; Crawford, Douglas C.; Rein, Kathleen S.

2012-01-01

The marine toxin, okadaic acid (OA) is produced by dinoflagellates of the genera Prorocentrum and Dinophysis and is the causative agent of the syndrome known as diarrheic shellfish poisoning (DSP). In addition, OA acts as both a tumor promoter, attributed to OA-induced inhibition of protein phosphatases as well as an inducer of apoptosis. To better understand the potentially divergent toxicological profile of OA, the concentration dependent cytotoxicity and alterations in gene expression on the human liver tumor cell line HepG2 upon OA exposure were determined using RNA microarrays, DNA fragmentation, and cell proliferation assays as well as determinations of cell detachment and cell death in different concentrations of OA. mRNA expression was quantified for approximately 15,000 genes. Cell attachment and proliferation were both negatively correlated with OA concentration. Detached cells displayed necrotic DNA signatures but apoptosis also was broadly observed. Data suggest that OA has a concentration dependent effect on cell cycle, which might explain the divergent effects that at low concentration OA stimulates genes involved in the cell cycle and at high concentrations it stimulates apoptosis. PMID:23172983

MEMANTINE ATTENUATES THE OKADAIC ACID INDUCED SHORT-TERM SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS IN RATS.

PubMed

Dashniani, M; Chighladze, M; Burjanadze, M; Beselia, G; Kruashvili, L

2016-03-01

In the present study, the possible beneficial effect of memantine on the Okadaic Acid (OA) induced spatial short-term memory impairment was examined in spatial alternation task, and the neuroprotective potential of memantine on OA-induced structural changes in the hippocampus was evaluated by Nissl staining. OA was dissolved in artificial cerebrospinal fluid (aCSF) and injected intracerebroventriculary (ICV) 200 ng in a volume of 10 μl bilaterally. Vehicle control received aCSF ICV bilaterally. Control and OA injected rats were divided into 2 subgroups injected i.p. with saline or memantine (5 mg/kg). Memantine or saline were given daily for 13 days starting from the day of OA injection. Behavioral study showed that bilateral ICV microinjection of OA induced impairment in spatial short-term memory. Nissl staining in the present study showed that the ICV microinjection of OA significantly decreased the number of surviving pyramidal neurons in the CA1 region of the hippocampus. Chronic administration of memantine effectively attenuated OA induced spatial short-term memory impairment and the OA-induced neuropathological changes in the hippocampus. Therefore, ICV injection of OA can be used as an experimental model to study mechanisms of neurodegeneration and define novel therapeutics targets for AD pathology.

Does the phycotoxin Okadaic acid cause oxidative stress damages and histological alterations to seabream (Sparus aurata)?

PubMed

Souid, Ghada; Souayed, Nouha; Haouas, Zohra; Maaroufi, Khira

2018-03-15

Okadaic Acid (OA) is a marine toxin responsible for DSP (Diarrheic Shellfish Poisoning) in humans produced by dinoflagellate. The genotoxic and cytotoxic effects of OA have been well reported in mammalian experimental animals and in vitro cultured cells. However, there are no available investigations regarding the involvement of the oxidative stress pathways in OA toxicity, especially on aquatic animals such as fish. In this context, we aimed in the present work to demonstrate whether OA (7.5 μg/ml) induces oxidative stress and histopathological damages in the fish species Sparus aurata under short term exposure (2 h, 4 h and 24 h). To this end, we have assessed lipid peroxidation and anti-oxidative stress response in liver tissue, and finally ultrastructural changes were investigated in hepatic and gills tissues. Our results clearly showed that OA induced significant enhancement in all tested parameters in a time dependent manner and seems to be a strong inducer of oxidative stress in aquatic animals. The data of the present study indicate also that histology is a successful tool to reveal OA impact on liver and gill tissues of Sparus aurata since the animal showed vascular dilation and hepatocellular membrane disintegration in liver and hypertrophy in secondary lamellae and necrotic aspect in the primary lamellae in gill tissue. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of the phosphatase inhibitors, okadaic acid, ATPgammaS, and calyculin A on the dividing sand dollar egg.

PubMed

Hamaguchi, Yukihisa; Kuriyama, Ryoko

2002-06-01

The effects of the phosphatase inhibitors, okadaic acid (OA), adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), and calyculin A (CL-A) on anaphase chromosome movement, cytokinesis, and cytoskeletal structures at cell division were examined by being microinjected into mitotic sand dollar eggs. When OA was injected, chromosome movement was inhibited and, moreover, chromosomes were ejected from the polar regions of the mitotic apparatus. By immunofluorescence, microtubules were observed to be severed in the OA-injected eggs, causing the smooth cell surface to be changed to an irregular surface. When ATPgammaS and CL-A were injected, the effect on cell shape was remarkable: In dividing eggs, furrowing stopped within several seconds after injection, small blebs appeared on the cell surface and became large, spherical or dumbbell cell shapes then changed to irregular forms, and subsequently cytoplasmic flow occurred. Microfilament detection revealed that actin accumulation in the cortex, which was not limited to the furrow cortex, occurred shortly after injection. Cortical accumulation of actin is thought to induce force generation and random cortical contraction, and accordingly to result in bleb extrusion from the cortex. Consequently, the phosphatase inhibitors inhibited the transition from mitosis to interphase by mediating cortical accumulation of actin filaments and/or fragmentation of microtubules.

Label-free okadaic acid detection using growth of gold nanoparticles in sensor gaps as a conductive tag.

PubMed

Pan, Yuxiang; Wan, Zijian; Zhong, Longjie; Li, Xueqin; Wu, Qi; Wang, Jun; Wang, Ping

2017-06-01

Okadaic acid (OA) is a marine toxin ingested by shellfish. In this work, a simple, sensitive and label-free gap-based electrical competitive bioassay has been developed for this biotoxin detection. The gap-electrical biosensor is constructed by modifying interdigitated microelectrodes with gold nanoparticles (AuNPs) and using the self-catalytic growth of AuNPs as conductive bridges. In this development, the AuNPs growth is realized in the solution of glucose and chloroauric acid, with glucose oxidation used as the catalysis for growth of the AuNPs. The catalytic reaction product H 2 O 2 in turn reduces chloroauric acid to make the AuNPs grow. The conductance signal amplification is directly determined by the growth efficiency of AuNPs and closely related to the catalytic activity of AuNPs upon their interaction with OA molecule and OA aptamer. In the absence of OA molecule, the OA aptamer can absorb onto the surfaces of AuNPs due to electrostatic interaction, and the catalytically active sites of AuNPs are fully blocked. Thus the AuNPs growth would not happen. In contrast, the presence of OA molecule can hinder the interaction of OA aptamer and AuNPs. Then the AuNPs sites are exposed and the catalytic growth induces the conductance signal change. The results demonstrated that developed biosensor was able to specifically respond to OA ranging from 5 ppb to 80 ppb, providing limit of detection of 1 ppb. The strategy is confirmed to be effective for OA detection, which indicates the label-free OA biosensor has great potential to offer promising alternatives to the traditional analytical and immunological methods for OA detection.

Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2/HO-1 Antioxidant Pathway.

PubMed

Dwivedi, Subhash; Rajasekar, N; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

2016-10-01

Okadaic acid (OKA) causes memory impairment and attenuates nuclear factor erythroid 2-related factor 2 (Nrf2) along with oxidative stress and neuroinflammation in rats. Sulforaphane (dietary isothiocyanate compound), an activator of Nrf2 signaling, exhibits neuroprotective effects. However, the protective effect of sulforaphane in OKA-induced neurotoxicity remains uninvestigated. Therefore, in the present study, the role of sulforaphane in OKA-induced memory impairment in rats was explored. A significant increased Nrf2 expression in the hippocampus and cerebral cortex was observed in trained (Morris water maze) rats, and a significant decreased Nrf2 expression in memory-impaired (OKA, 200 ng icv) rats indicated its involvement in memory function. Sulforaphane administration (5 and 10 mg/kg, ip, days 1 and 2) ameliorates OKA-induced memory impairment in rats. The treatment also restored Nrf2 and its downstream antioxidant protein expression (GCLC, HO-1) and attenuated oxidative stress (ROS, nitrite, GSH), neuroinflammation (NF-κB, TNF-α, IL-10), and neuronal apoptosis in the cerebral cortex and hippocampus of OKA-treated rats. Further, to determine whether modulation of Nrf2 signaling is responsible for the protective effect of sulforaphane, in vitro, Nrf2 siRNA and its downstream HO-1 inhibition studies were carried out in a rat astrocytoma cell line (C6). The protective effects of sulforaphane were abolished with Nrf2 siRNA and HO-1 inhibition in astrocytes. The results suggest that Nrf2-dependent activation of cellular antioxidant machinery results in sulforaphane-mediated protection against OKA-induced memory impairment in rats. Graphical Abstract ᅟ.

Stimulation of hepatocytic AMP-activated protein kinase by okadaic acid and other autophagy-suppressive toxins

PubMed Central

2004-01-01

Autophagic activity in isolated rat hepatocytes is strongly suppressed by OA (okadaic acid) and other PP (protein phosphatase)-inhibitory toxins as well as by AICAR (5-aminoimidazole-4-carboxamide riboside), a direct activator of AMPK (AMP-activated protein kinase). To investigate whether AMPK is a mediator of the effects of the toxin, a phosphospecific antibody directed against the activation of phosphorylation of the AMPK α (catalytic)-subunit at Thr172 was used to assess the activation status of this enzyme. AICAR as well as all the toxins tested (OA, microcystin-LR, calyculin A, cantharidin and tautomycin) induced strong, dose-dependent AMPKα phosphorylation, correlating with AMPK activity in situ (in intact hepatocytes) as measured by the AMPK-dependent phosphorylation of acetyl-CoA carboxylase at Ser79. All treatments induced the appearance of multiple, phosphatase-sensitive, low-mobility forms of the AMPK α-subunit, consistent with phosphorylation at several sites other than Thr172. The flavonoid naringin, an effective antagonist of OA-induced autophagy suppression, inhibited the AMPK phosphorylation and mobility shifting induced by AICAR, OA or microcystin, but not the changes induced by calyculin A or cantharidin. AMPK may thus be activated both by a naringin-sensitive and a naringin-resistant mechanism, probably involving the PPs PP2A and PP1 respectively. Neither the Thr172-phosphorylating protein kinase LKB1 nor the Thr172-dephosphorylating PP, PP2C, were mobility-shifted after treatment with toxins or AICAR, whereas a slight mobility shifting of the regulatory AMPK β-subunit was indicated. Immunoblotting with a phosphospecific antibody against pSer108 at the β-subunit revealed a naringin-sensitive phosphorylation induced by OA, microcystin and AICAR and a naringin-resistant phosphorylation induced by calyculin A and cantharidin, suggesting that β-subunit phosphorylation could play a role in AMPK activation. Naringin antagonized the autophagy

High-dispersion spectroscopy of the probable microlensing event TCP J05074264+2447555

NASA Astrophysics Data System (ADS)

Maehara, Hiroyuki

2017-11-01

We report the spectroscopic observation of TCP J05074264+2447555 which was discovered by Tadashi Kojima at 10.8 mag on 2017-10-31.7340 (http://www.cbat.eps.harvard.edu/unconf/followups/J05074264+2447555.html).

Maintained activity of glycogen synthase kinase-3{beta} despite of its phosphorylation at serine-9 in okadaic acid-induced neurodegenerative model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Yong-Whan; Yoon, Seung-Yong, E-mail: ysy@amc.seoul.kr; Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul

2010-04-30

Glycogen synthase kinase-3{beta} (GSK3{beta}) is recognized as one of major kinases to phosphorylate tau in Alzheimer's disease (AD), thus lots of AD drug discoveries target GSK3{beta}. However, the inactive form of GSK3{beta} which is phosphorylated at serine-9 is increased in AD brains. This is also inconsistent with phosphorylation status of other GSK3{beta} substrates, such as {beta}-catenin and collapsin response mediator protein-2 (CRMP2) since their phosphorylation is all increased in AD brains. Thus, we addressed this paradoxical condition of AD in rat neurons treated with okadaic acid (OA) which inhibits protein phosphatase-2A (PP2A) and induces tau hyperphosphorylation and cell death. Interestingly,more » OA also induces phosphorylation of GSK3{beta} at serine-9 and other substrates including tau, {beta}-catenin and CRMP2 like in AD brains. In this context, we observed that GSK3{beta} inhibitors such as lithium chloride and 6-bromoindirubin-3'-monoxime (6-BIO) reversed those phosphorylation events and protected neurons. These data suggest that GSK3{beta} may still have its kinase activity despite increase of its phosphorylation at serine-9 in AD brains at least in PP2A-compromised conditions and that GSK3{beta} inhibitors could be a valuable drug candidate in AD.« less

Materials Research Society Symposium on the Electrical, Optical and Magnetic Properties of Organic Solid State Materials Held in Boston Massachusetts on 27 November-2 December 1989

DTIC Science & Technology

1989-12-01

Hiroshi Kawarada, Yusuke OF THE HYDROGEN ENVIRONMENTS IN DIAMOND AND Mori, and Akio Hiraki , Osaka University, DIAMOND-LIKE FILMS. Y.M. LeGrice, E.C...Canon Inc. Tamura, Hiratsuka, Kanagawa, Japan; Y. SYMPOSIUM F presentations Yokota, Y. Mori, J. Wei, and A. Hiraki , may be viewed simultaneously Osaka...INTERFACE, Yusuke Mor, Hiroshi Kawarada, Yoshihiro Yokota, and Akio Hiraki , Osaka University, Department of Electrical Engineering, Facul- ty of

Study of cytoskeletal changes induced by okadaic acid in BE(2)-M17 cells by means of a quantitative fluorimetric microplate assay.

PubMed

Leira, F; Alvarez, C; Vieites, J M; Vieytes, M R; Botana, L M

2001-01-01

The diarrhogenic activity of the marine toxin okadaic acid (OA) has been associated to its actin-disrupting effect, which could reflect the loosening of tight junctions in vivo. In this report, we present results obtained using a fluorimetric microplate assay for quantitative measurements of OA-induced changes on F-actin pools in BE(2)-M17 cells. The proposed method shows important advantages over classical methods in terms of rapidity, sensitivity (less than 5000 cells per well) and reproducibility, thus providing a very useful tool for studying F-actin levels in living cells. Results obtained demonstrate a time- and dose-dependent decrease of F-actin pools (IC(50)=100 nM at 1 h) in OA-treated cells, which was partly counteracted by TPA, H89, forskolin, wortmannin, ionomycin and orthovanadate at early stages, but remained unaffected after 24 h of incubation. Cells exposed for 1 h to 1 nM OA showed a slight increase of F-actin pools (1.5-fold), which was blocked by genistein and lavendustin A, thus suggesting a role for tyrosine kinases-dependent pathways in OA-induced polymerization at low concentrations. These results suggest direct interactions of Ser/Thr protein phosphatases with actin-binding proteins in the regulation of actin polymerization, thus indicating that disruption of cytoskeletal structure may be a key mechanism of OA-induced diarrhea.

GSK-3 mediates the okadaic acid-induced modification of collapsin response mediator protein-2 in human SK-N-SH neuroblastoma cells.

PubMed

Ni, Mei-Hui; Wu, Chih-Ching; Chan, Wen-Hsiung; Chien, Kun-Yi; Yu, Jau-Song

2008-04-15

Collapsin response mediator protein-2 (CRMP-2), a phosphoprotein involved in axonal outgrowth and microtubule dynamics, is aberrantly phosphorylated in Alzheimer's disease (AD) brain. Alteration of glycogen synthase kinase-3 (GSK-3) activity is associated with the pathogenesis of AD. Here, we show that CRMP-2 is one of the major substrates for GSK-3 in pig brain extracts. Both GSK-3alpha and 3beta phosphorylate purified pig brain CRMP-2 and significantly alter its mobility in SDS-gels, resembling the CRMP-2 modification observed in AD brain. Interestingly, this modification can be detected in SK-N-SH neuroblastoma cells treated with a phosphatase inhibitor, okadaic acid (OA), and GSK-3 inhibitors completely block this OA-induced event. Knockdown of both GSK-3alpha and 3beta, but not either kinase alone, impairs OA-induced modification of CRMP-2. Mutation of Ser-518 or Ser-522 of CRMP-2, which are highly phosphorylated in AD brain, to Ala blocks the OA-induced modification of CRMP-2 in SK-N-SH cells. Ser-522 prephosphorylated by Cdk5 is required for subsequent GSK-3alpha-mediated phosphorylation of CRMP-2 in vitro. Collectively, our results demonstrate for the first time that OA can induce phosphorylation of CRMP-2 in SK-N-SH cells at sites aberrantly phosphorylated in AD brain, and both GSK-3alpha and 3beta and Ser-522 kinase(s) are involved in this process.

Protective Effect of Tat PTD-Hsp27 Fusion Protein on Tau Hyperphosphorylation Induced by Okadaic Acid in the Human Neuroblastoma Cell Line SH-SY5Y.

PubMed

Choi, Sunghyun; Oh, Jae Hoon; Kim, Hyeseon; Nam, So Hee; Shin, Jeehae; Park, Jong-Sang

2015-10-01

Alzheimer's disease (AD) is an age-related disorder that causes a loss of brain function. Hyperphosphorylation of tau and the subsequent formation of intracellular neurofibrillary tangles (NFTs) are implicated in the pathogenesis of AD. Hyperphosphorylated tau accumulates into insoluble paired helical filaments that aggregate into NFTs; therefore, regulation of tau phosphorylation represents an important treatment approach for AD. Heat shock protein 27 (Hsp27) plays a specific role in human neurodegenerative diseases; however, few studies have examined its therapeutic effect. In this study, we induced tau hyperphosphorylation using okadaic acid, which is a protein phosphatase inhibitor, and generated a fusion protein of Hsp27 and the protein transduction domain of the HIV Tat protein (Tat-Hsp27) to enhance the delivery of Hsp27. We treated Tat-Hsp27 to SH-SY5Y neuroblastoma cells for 2 h; the transduction level was proportional to the Tat-hsp27 concentration. Additionally, Tat-Hsp27 reduced the level of hyperphosphorylated tau and protected cells from apoptotic cell death caused by abnormal tau aggregates. These results reveal that Hsp27 represents a valuable protein therapeutic for AD.

Expanding Possibilities of Periodicals for Children in Asia and the Pacific. Report of the 1997 Training Course on Production of Periodicals for Children (Tokyo, October 1-15, 1997).

ERIC Educational Resources Information Center

Asia/Pacific Cultural Centre for UNESCO, Tokyo (Japan).

Following the proceedings of the training course on children's periodicals held in 1997 in Tokyo, this report contains the following articles: (1) "Children's Life and Magazines" (Jiro Saito); (2) "Periodical Picture Books to Develop Reading Skills of Children" (Tadashi Matsui); (3) "How to Produce Attractive Educational…

Okadaic acid overcomes the blocked cell cycle caused by depleting Cdc2-related kinases in Trypanosoma brucei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Ziyin; Tu Xiaoming; Wang, Ching C.

2006-11-01

Mitosis and cytokinesis are highly coordinated in eukaryotic cells. But procyclic-form Trypanosoma brucei under G1 or mitotic arrest is still capable of dividing, resulting in anucleate daughter cells (zoids). Okadaic acid (OKA), an inhibitor of protein phosphatases PP1 and PP2A, is known to inhibit kinetoplast replication and cell division yielding multinucleate cells with single kinetoplasts. However, when OKA was applied to cells arrested in G1 or G2/M phase via RNAi knockdown of specific cdc2-related kinases (CRKs), DNA synthesis and nuclear division were resumed without kinetoplast replication or cell division, resulting in multinucleate cells as in the wild type. Cells arrestedmore » in G2/M via depleting the mitotic cyclin CycB2 or an aurora B kinase homologue TbAUK1 were, however, not released by OKA treatment. The phenomenon is thus similar to the OKA activation of Cdc2 in Xenopus oocyte by inhibiting PP2A [Maton, et al., Differential regulation of Cdc2 and Aurora-A in Xenopus oocytes: a crucial role of phosphatase 2A. J. Cell Sci. 118 (2005) 2485-2494]. A simultaneous knockdown of the seven PP1s or the PP2A catalytic subunit in T. brucei by RNA interference did not, however, result in multinucleate cells. This could be explained by assuming a negative regulation, either directly or indirectly, of CRK by an OKA-sensitive phosphatase, which could be a PP2A as in the Xenopus oocyte and a positive regulation of kinetoplast replication by an OKA-susceptible protein(s). Test of a PP2A-specific inhibitor, fostriecin, on cells arrested in G2/M via CRK depletion or a knockdown of the PP2A catalytic subunit from the CRK-depleted cells both showed a partial lift of the G2/M block without forming multinucleate cells. These observations support the abovementioned assumption and suggest the presence of a novel OKA-sensitive protein(s) regulating kinetoplast replication that still remains to be identified.« less

Production of monoclonal antibody for okadaic acid and its utilization in an ultrasensitive enzyme-linked immunosorbent assay and one-step immunochromatographic strip.

PubMed

Liu, Biing-Hui; Hung, Chun-Tse; Lu, Chuan-Chen; Chou, Hong-Non; Yu, Feng-Yih

2014-02-12

Okadaic acid (OA) is a common marine biotoxin that accumulates in bivalves and causes diarrhetic shellfish poisoning (DSP). This study generated a monoclonal antibody (mAb) specific to OA from a hybridoma cell line, 6B1A3, which was obtained by fusion of myeloma cells (P3/NS1/1-AG4-1) with spleen cells isolated from a BALB/c mouse immunized with OA-γ-globulin. The 6B1A3 mAb belongs to the immunoglobulin G1 (κ chain) isotype. Both competitive direct and indirect enzyme-linked immunosorbent assays (ELISAs) were established for characterization of the antibody. The concentrations causing 50% inhibition of binding of OA-horseradish peroxidase to the antibody by OA were calculated to be 0.077 ng/mL in the cdELISA. A rapid and sensitive mAb-based gold nanoparticle immunochromatographic strip was also established. This proposed strip has a detection limit of 5 ng/mL for OA and can be finished in 10 min. Extensive analyses of 20 seafood samples with ELISA revealed that 10 were slightly contaminated with OA, with a mean concentration of 0.892 ng/g. Analysis of OA in shellfish samples showed that data acquired by the immunochromatographic strip agreed well with those acquired by the ELISA. The mAb-based ELISA and immunochromatographic strip assay developed in this study have adequate sensitivity and accuracy for rapid screening of OA in shellfish samples.

In Vitro Analysis of Early Genotoxic and Cytotoxic Effects of Okadaic Acid in Different Cell Types of the Mussel Mytilus galloprovincialis.

PubMed

Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Eirín-López, José M; Méndez, Josefina

2015-01-01

Okadaic acid (OA) is the predominant biotoxin responsible for diarrhetic shellfish poisoning (DSP) syndrome in humans. While its harmful effects have been extensively studied in mammalian cell lines, the impact on marine organisms routinely exposed to OA is still not fully known. Few investigations available on bivalve molluscs suggest less genotoxic and cytotoxic effects of OA at high concentrations during long exposure times. In contrast, no apparent information is available on how sublethal concentrations of OA affect these organisms over short exposure times. In order to fill this gap, this study addressed for the first time in vitro analysis of early genotoxic and cytotoxic effects attributed to OA in two cell types of the mussel Mytilus galloprovincialis. Accordingly, hemocytes and gill cells were exposed to low OA concentrations (10, 50, 100, 200, or 500 nM) for short periods of time (1 or 2 h). The resulting DNA damage, as apoptosis and necrosis, was subsequently quantified using the comet assay and flow cytometry, respectively. Data demonstrated that (1) mussel hemocytes seem to display a resistance mechanism against early genotoxic and cytotoxic OA-induced effects, (2) mussel gill cells display higher sensitivity to early OA-mediated genotoxicity than hemocytes, and (3) mussel gill cells constitute more suitable systems to evaluate the genotoxic effect of low OA concentrations in short exposure studies. Taken together, this investigation provides evidence supporting the more reliable suitability of mussel gill cells compared to hemocytes to evaluate the genotoxic effect of low short-duration exposure to OA.

Cytoplasmic dynein undergoes intracellular redistribution concomitant with phosphorylation of the heavy chain in response to serum starvation and okadaic acid.

PubMed

Lin, S X; Ferro, K L; Collins, C A

1994-11-01

Cytoplasmic dynein is a microtubule-binding protein which is considered to serve as a motor for retrograde organelle movement. In cultured fibroblasts, cytoplasmic dynein localizes primarily to lysosomes, membranous organelles whose movement and distribution in the cytoplasm have been shown to be dependent on the integrity of the microtubule cytoskeleton. We have recently identified conditions which lead to an apparent dissociation of dynein from lysosomes in vivo, indicating that alterations in membrane binding may be involved in the regulation of retrograde organelle movement (Lin, S. X. H., and C. A. Collins. 1993. J. Cell Sci. 105:579-588). Both brief serum withdrawal and low extracellular calcium levels induced this alteration, and the effect was reversed upon addition of serum or additional calcium. Here we demonstrate that the phosphorylation state of the dynein molecule is correlated with changes in its intracellular distribution in normal rat kidney fibroblasts. Dynein heavy chain phosphorylation level increased during serum starvation, and decreased back to control levels upon subsequent addition of serum. We found that okadaic acid, a phosphoprotein phosphatase inhibitor, mimicked the effects of serum starvation on both phosphorylation and the intracellular redistribution of dynein from a membrane-associated pool to one that was more soluble, with similar dose dependence for both phenomena. Cell fractionation by differential detergent extraction revealed that a higher proportion of dynein was present in a soluble pool after serum starvation than was found in comparable fractions from control cells. Our data indicate that cytoplasmic dynein is phosphorylated in vivo, and changes in phosphorylation state may be involved in a regulatory mechanism affecting the distribution of this protein among intracellular compartments.

Survey of the distribution of red tide toxins (okadaic acid and dinophytoxin-1) in the Dalian Bay sea area of China by micellar electrokinetic capillary chromatography.

PubMed

Li, D; Sun, L; Chen, Z; He, X; Lin, B

2001-10-01

Two kinds of diarrhoetic shellfish toxins, okadaic acid (OA) and dinophytoxin-1 (DTX-1) were determined by micellar electrokinetic capillary chromatography (MEKC) with ultraviolet detection. A detection limit of 3.25 microg/mL for both of them was achieved. The UV absorbance of these toxins measured at 200 nm showed good linearity in the range of 6.25-200 microg/mL with R = 0.992 for OA and 0.997 for DTX-1. Three kinds of shellfish (Chlamys farreri, Mytilus edulis and Ruditaps philippinarum) collected from eight locations (sampling in the intertidal zone) along the Dalian Bay sea area of China were surveyed in February and May of 2000. Results indicated that three kinds of shellfish were contaminated by OA and DTX-1. Based on per gram of hepatopancreas in February, the contamination contents ranged from 0 to 1.26 microg for OA and from 0 to 1.82 microg for DTX-1, and in May, the contents ranged from 0 to 1.45 microg for OA and 0 to 2.56 microg for DTX-1. Among the eight locations, Hei Shi Jiao and Long Wang Tang were the most contaminated areas. Of the three kinds of shellfish, Mytilus edulis was the most significant species in accumulating OA and DTX-1.

Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.

PubMed

Jiang, Wei; Luo, Tao; Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

2016-01-01

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.

Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

PubMed Central

Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

2016-01-01

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD. PMID:27050422

Okadaic acid mediates p53 hyperphosphorylation and growth arrest in cells with wild-type p53 but increases aberrant mitoses in cells with non-functional p53.

PubMed

Milczarek, G J; Chen, W; Gupta, A; Martinez, J D; Bowden, G T

1999-06-01

The protein phosphatase inhibitor and tumor promoting agent okadaic acid (OA), has been shown previously to induce hyperphosphorylation of p53 protein, which in turn correlated with increased transactivation or apoptotic function. However, how the tumor promotion effects of OA relate to p53 tumor supressor function (or dysfunction) remain unclear. Rat embryonic fibroblasts harboring a temperature-sensitive mouse p53 transgene were treated with 50 nM doses of OA. At the wild-type permissive temperature this treatment resulted in: (i) the hyperphosphorylation of sites within tryptic peptides of the transactivation domain of p53; (ii) an increase in p53 affinity for a p21(waf1) promotor oligonucleotide; (iii) an increase in cellular steady state levels of p21(waf1) message; (iv) a G2/M cell cycle blockage in addition to the G1/S arrest previously associated with p53; and (v) no increased incidence of apoptosis. On the other hand, OA treatment at the mutated p53 permissive temperature resulted in a relatively high incidence of aberrant mitosis with no upregulation of p21(waf1) message. These results suggest that while wild-type p53 blocks the proliferative effects of OA through p21(waf1)-mediated growth arrest, cells with non-functional p53 cannot arrest and suffer relatively high levels of OA-mediated aberrant mitoses.

A fluorescent microplate assay for diarrheic shellfish toxins.

PubMed

Vieytes, M R; Fontal, O I; Leira, F; Baptista de Sousa, J M; Botana, L M

1997-06-01

A fluorescent enzyme inhibition assay for okadaic acid using 4-methylumbelliferyl phosphate and fluorescein diphosphate as substrates for the enzyme phosphatase 2A was developed. In the inhibition assay, performed in a microtiter plate, the PP2A was inhibited by adding okadaic acid and the resulting fluorescence enhancement derived from enzymatic hydrolysis of the substrate was quantified in a fluorescence plate reader. The measurable range of okadaic acid was 3.2 to 3200 pg/ml with an IC50 = 0.1 nM. The detection limit of okadaic acid was 2.56 pg/well in buffer solutions and 12.8 ng/g hepatopancreas in shellfish extracts. The coefficient of variation (CV, n = 22) for each point ranged from 18.80 to 37.90% (mean 28.35%). The proposed method is very convenient, rapid, and sensitive by using the enzyme inhibition assay system and fluorescent reaction as a detection system. This work demonstrates that the fluorescent assay can be used to quantify the amount of okadaic acid in shellfish samples and also is valid for very dilute samples, such as phytoplankton samples.

Regulation of Breast Carcinoma Growth and Neovascularization by Peptide Sequences in Thromospondin

DTIC Science & Technology

1999-10-01

buffer [0.5 ml; containing 5 m guanidine thiocyanate, 25 Okadaic acid, TPA, fumonisin B I, herbimycin A, and sodium vanadate mM sodium citrate (pH 7.0...of okadaic acid, phorbol, promote cell adhesion, were used instead of free peptides in the herbimycin, fumonisin BI, or TPA on proliferation, the...KRFKQDGGWSHWSPWSSC-conj. (pM) /lM vanadate (narrow stripes), 5 nM okadaic acid (wide stripes), or 25 nM fumonisin B1 (D). The indicated peptides or

Production of monoclonal antibody and application in indirect competitive ELISA for detecting okadaic acid and dinophytoxin-1 in seafood.

PubMed

Lu, Shi-Ying; Zhou, Yu; Li, Yan-Song; Lin, Chao; Meng, Xian-Mei; Yan, Dong-Ming; Li, Zhao-Hui; Yu, Shi-Yu; Liu, Zeng-Shan; Ren, Hong-Lin

2011-08-01

Okadaic acid (OA) and analogues of dinophysistoxin (DTX) are key diarrheic shellfish poisoning (DSP) toxins, which possibly arouse DSP symptoms by consuming the contaminated shellfish. Because of the stable toxicity in high temperature and the long-term carcinogenicity, the outbreaks of DSP related to consumption of bivalve mollusks contaminated by DSP toxins pose a hazard to public health. Therefore, it is worth developing a fast and reliable analytical method for the detection of OA and analogues in shellfish. In this paper, an indirect competitive enzyme-linked immunosorbent assay (ELISA) (icELISA) for detecting OA and DTX-1 in seafood was developed based on monoclonal antibody (McAb). The OA was conjugated to human immunoglobulin G (IgG) and bovine serum albumin (BSA) by the active ester method as the immune antigen and the detective antigen. The spleen cells from BALB/c mice immunized with OA-IgG were fused with SP2/0 myeloma cells. A hybridoma cell line, which secreted McAb against OA, was selected by "limiting dilution" cloning. An icELISA was developed based on immobilized conjugate (OA-BSA) competing the McAb with the free OA in seafood sample. A hybridoma cell line, which secreted IgG1 subclass monoclonal antibody (McAb) against OA, was selected. The IC(50) of the McAb for OA and dinophytoxin-1 (DTX-1) were 4.40 and 3.89 ng/mL, respectively. Based on the McAb, an indirect competitive ELISA for detection of OA and DTX-1 in seafood was developed. The regression equation was y = 54.713x - 25.879 with a coefficient correlation of R (2) = 0.9729. The linear range and the limit of detection were 0.4-12.5 and 0.45 ng/mL, respectively. The average recovery of OA and DTX-1 spiked shellfish was 82.29% with the coefficient of variation of 7.67%. The developed icELISA is a fast, sensitive, and convenient assay for detecting of total amount of OA and DTX-1 in seafood.

Circulatory Shock. Volume 34. Number 1. May 1991. International Conference on Shock (2nd), Meeting of European Shock Society (5th), Annual Meeting of the Shock Society (USA) (14th), Vienna Shock Form (3rd) Held in Vienna, Austria on 2-6 June 1991

DTIC Science & Technology

1991-06-06

OCTADECENOATE, AS A BURN TOXIN Takayuki Ozawa, Mika Hayakawa, Kazuhiro Kosaka, Satoru Sugiyama, Kazuhisa Yokoo, Hisashi Aoyama, and Yohei Izawa Department...shock. 41 CARDIOPULMONARY HEMODYNAMIC AND PERIPHERAL CIRCULATORY RESPONSES IN SHOCK T. Muteki, N. Kaku. T. Fukushige, I. Kohno and T. Hiraki Department...Tadashi, 242 Machleidt, Werner, 213 Ozawa, Takayuki , 11 Kawarada, Yoshifumi, 442 Mackie, D.P., 348 Ozawa, Kazue, 268 Keser, Claudia, 380 Maitra, Subir R

A Computationally Efficient Filter for Reducing Shot Noise in Low S/N Data

PubMed Central

Okada, Mami; Ishikawa, Tomoe; Ikegaya, Yuji

2016-01-01

Functional multineuron calcium imaging (fMCI) provides a useful experimental platform to simultaneously capture the spatiotemporal patterns of neuronal activity from a large cell population in situ. However, fMCI often suffers from low signal-to-noise ratios (S/N). The main factor that causes the low S/N is shot noise that arises from photon detectors. Here, we propose a new denoising procedure, termed the Okada filter, which is designed to reduce shot noise under low S/N conditions, such as fMCI. The core idea of the Okada filter is to replace the fluorescence intensity value of a given frame time with the average of two values at the preceding and following frames unless the focused value is the median among these three values. This process is iterated serially throughout a time-series vector. In fMCI data of hippocampal neurons, the Okada filter rapidly reduces background noise and significantly improves the S/N. The Okada filter is also applicable for reducing shot noise in electrophysiological data and photographs. Finally, the Okada filter can be described using a single continuous differentiable equation based on the logistic function and is thus mathematically tractable. PMID:27304217

Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells.

PubMed

Bodero, Marcia; Hoogenboom, Ron L A P; Bovee, Toine F H; Portier, Liza; de Haan, Laura; Peijnenburg, Ad; Hendriksen, Peter J M

2018-02-01

A study with DNA microarrays was performed to investigate the effects of two diarrhetic and one azaspiracid shellfish poison, okadaic acid (OA), dinophysistoxin-1 (DTX-1) and azaspiracid-1 (AZA-1) respectively, on the whole-genome mRNA expression of undifferentiated intestinal Caco-2 cells. Previously, the most responding genes were used to develop a dedicated array tube test to screen shellfish samples on the presence of these toxins. In the present study the whole genome mRNA expression was analyzed in order to reveal modes of action and obtain hints on potential biomarkers suitable to be used in alternative bioassays. Effects on key genes in the most affected pathways and processes were confirmed by qPCR. OA and DTX-1 induced almost identical effects on mRNA expression, which strongly indicates that OA and DTX-1induce similar toxic effects. Biological interpretation of the microarray data indicates that both compounds induce hypoxia related pathways/processes, the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. The gene expression profile of AZA-1 is different and shows increased mRNA expression of genes involved in cholesterol synthesis and glycolysis, suggesting a different mode of action for this toxin. Future studies should reveal whether identified pathways provide suitable biomarkers for rapid detection of DSPs in shellfish. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modulation of vinblastine cytotoxicity by dilantin (phenytoin) or the protein phosphatase inhibitor okadaic acid involves the potentiation of anti-mitotic effects and induction of apoptosis in human tumour cells.

PubMed Central

Kawamura, K. I.; Grabowski, D.; Weizer, K.; Bukowski, R.; Ganapathi, R.

1996-01-01

Cellular insensitivity to vinca alkaloids is suggested to be primarily due to drug efflux by P-glycoprotein (P-gp). The anti-epileptic phenytoin (DPH), which does not bind to P-gp, can selectively enhance vincristine (VCR) cytotoxicity in wild-type (WT) or multidrug-resistant (MDR) cells. We now demonstrate that the protein phosphatase inhibitor okadaic acid (OKA) can mimic the effect of DPH by selectively enhancing cytotoxicity of vinblastine (VBL), but not taxol and doxorubicin, in human leukaemia HL-60 cells. Both DPH and OKA potentiate the anti-mitotic effects of VBL by enhanced damage to the mitotic spindle, resulting in prolonged growth arrest. Also, unlike VBL alone, in human leukaemia or non-small-cell lung carcinoma cells treated with VBL plus DPH, recovery from damage to the mitotic spindle is compromised in drug-free medium and cell death by apoptosis in interphase ensues. Since protein phosphatases are involved with the regulation of metaphase to anaphase transit of cells during the mitotic cycle, enhanced VBL cytotoxicity in the presence of DPH or OKA may involve effects during metaphase on the mitotic spindle tubulin leading to growth arrest and apoptosis in interphase. These novel results suggest that DPH or OKA could be powerful tools to study cellular effects of vinca alkaloids and possibly for the development of novel therapeutic strategies. Images Figure 6 PMID:8546904

Swift observations of SDSS J141118.31+481257.6 during its first detected outburst

NASA Astrophysics Data System (ADS)

Sandoval, L. E. Rivera; Maccarone, T.

2018-05-01

We report Swift observations of the AM CVn-type system SDSS J141118.31+481257.6 (RA=14:11:18.31, Dec=+48:12:57.6) during its first ever recorded outburst. The system was detected by Tadashi Kojima on 2018-May-20 with a V magnitude of 12.6 +- 0.2 (http://ooruri.kusastro.kyoto-u.ac.jp/mailarchive/vsnet-alert/22176), an increase of 7 mags compared to any previous measurement in the same filter.

Acceptance of the 2014 Geochemical Journal Award by Hiroshi Amakawa

NASA Astrophysics Data System (ADS)

Amakawa, Hiroshi

2015-06-01

I thank Professor Hisayoshi Yurimoto for generous citation. I also would like to extend my gratitude to the people who supported me and to the members of editorial board of Geochemical Journal for the nomination. I also would like to thank the organizing committee of the Goldschmidt Conference for giving an opportunity for this acceptance speech.

Sphingolipid-Mediated Apoptosis and Tumor Suppression in Breast Carcinoma.

DTIC Science & Technology

1996-10-01

diacylglycerol and ceramide. The radioactive spots corresponding to phosphatidic acid and ceramide-phosphate, the phosphorylated products of diacylglycerol (DAG...threonine protein phosphatase (7). This phosphatase is inhibited by okadaic acid , and okadaic acid appears to inhibit the effects of ceramide on...Arg to Thr at amino acid 291 in the reactive site loop. In MCF-7 cells expressing this mutant, there was no significant inhibition of ceramide

Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis

DTIC Science & Technology

2001-07-01

and hepatocellular carcinoma patients have been shown to exhibit elevated somatic mutation frequencies with the GPA assay (Okada et al., 1997...T, Kyogoku A, Yoshimori M (1997) Evidence for increased somatic cell mutations in patients with hepatocellular carcinoma . Carcinogenesis 18: 445-449...significant increase in mutation at the GPA locus has been reported for a population of hepatocellular carcinoma patients (Okada et al., 1997

A 2D Rods-in-Air Square-Lattice Photonic Crystal Optical Switch

DTIC Science & Technology

2009-03-01

4] Tao Chu, Hirohito Yamada, Satomi Ishida, Yasuhiko Arakawa, Thermooptic switch based on photonic-crystal line-defect waveguides, IEEE Photon...Ishida, Yasuhiko Arakawa, Hiroyuki Fujita, Hiroshi Toshiyoshi, Design and fabrication on MEMS optical mod- ulators integrated with Phc waveguide, in

IFLA General Conference, 1986. Bibliographic Control Division. Section: Classification and Indexing. Papers.

ERIC Educational Resources Information Center

International Federation of Library Associations and Institutions, The Hague (Netherlands).

Papers on classification and indexing presented at the 1986 International Federation of Library Associations (IFLA) conference include: (1) "Profile on Chinese Cataloguing and Subject Cataloguing" (Yan Lizhong, China); (2) "The Trend of Classification in Japan" (Hiroshi Ishiyama, Japan); (3) "Classification in Online…

The State of Continuing Education in Japan.

ERIC Educational Resources Information Center

Masatoshi, Nagashima, Ed.; And Others

This book contains the following articles about the state of continuing education and occupational training in Japan: "Funabashi City University of Sports Health" (Abe Nobuhiro); "Public Halls in Omiya City" (Kawamoto Koji); "Setagaya Senior Citizens College (Setagaya Rojin Daigaku)" (Sawamura Hiroshi); "Lifelong…

IFLA General Conference, 1986. Education and Research Division. Section: Library History and Library Theory and Research. Papers.

ERIC Educational Resources Information Center

International Federation of Library Associations and Institutions, The Hague (Netherlands).

Papers on library history and library theory and research presented at the 1986 International Federation of Library Associations (IFLA) conference include: (1) "The History of Western Literature Library Collections in Japan" (Yoshitomi Okazaki, Japan); (2) "Trends of Library History Research in Japan" (Hiroshi Kawai, Yukio…

On JALT 95: Curriculum and Evaluation. Proceedings of the JALT International Conference on Language Teaching/Learning (22nd, Nagoya, Japan, November 1995). Section Two: Curriculum Design.

ERIC Educational Resources Information Center

Harrison, Ian; And Others

Texts of conference papers and summaries of colloquia on second language curriculum design are presented, including: "Competency Assessment in Curriculum Renewal" (summary of session with Ian Harrison, Francis Johnson, Christopher Candlin, Anthony Green, David Nunan, Charles Smith); "The Evolving of a Curriculum" (Hiroshi Abe,…

EphB4 Receptor Tyrosine Kinase in Prostate Cancer

DTIC Science & Technology

2011-09-01

San Diego, La Jolla, CA, USAAbbreviations: MAP kinase, mitogen-activated prote tidylinositol 4,5-bisphosphate; PI(3,4,5)P3, phosphatid PI3K...okadaic acid (MP Biomedicals, 150 μM stock in DMSO), LY294002, PD98059, rapamycin (see previous section), dasatinib (LC Laboratories; 50 μM stock in DMSO...the phosphatase inhibitor tautomycin, which preferentially inhibits PP1 over PP2A. The cells were stimulated and analyzed as in (D). (F) Okadaic acid

Collective Security in Europe and Asia

DTIC Science & Technology

1992-03-02

Minister Hisashi Owada carried by Kyodo, November 18, 1991, in Foreign Broadcast Information Service, (FBIS), Daily Report-East Asia, November 18, 1991...Report-Soviet Union, December 5, 1991, p. 54. For a Japanese view, see Hiroshi Kimura , "Gorbachev’s Japan Policy: The Northern Territories Issue

Regulation of 2-5A Dependent RNase at the Level of its Phosphorylation

DTIC Science & Technology

1991-06-26

extract as follows: 25 ul wheat germ extract 10 ul H2O 1 ul RNasin ribonuclease inhibitor (40 u/ml) 7 ul ImM amino acid mixture 1 ul IM...diacylglycerol (DAG) 2. TPA 3. Indolactam Figure 6. Chemical structure of: 1. H-7 (A kinase inhibitor) 2. okadaic acid (A phosphatase inhibitor) Figure 7...elevating agents: Forskolin and Cholera toxin Figure 17. Down-regulation of 2-5A-depRNase by Okadaic 77 acid : A phosphatase inhibitor Figure 18

Progress in Mathematical Programming.

DTIC Science & Technology

1987-03-04

Philip Gill, Neal Glassman, Donald Goldfarb, Clovis Gonzaga, Harvey Greenberg , Peter Gritzmann, James K. Ho, Alan Hoffman, T. C. Hu, Hiroshi Imai...polar polytope P’ if 0 E P. The image trajectories are geodesics of a projectively invariant geometry on P 0 , Hilbert geometry. This work relates

The Structure of Optimum Interpolation Functions.

DTIC Science & Technology

1983-02-01

Daniel F. Merriam, ed., Plenum Press, 1970. 2. Hiroshi Akima, "Comments on ’Optimal Contour Mapping Using Universal Kriging’ by Ricardo 0. Olea ," (with...Kriging," Mathematical Geology 14 (1982), 249-257. 21 27. Ricardo 0. Olea , "Optimal Contour Mapping Using Universal Kriging," J. of Geophysical Res. 79

Research and Clinical Center for Child Development Annual Report, 1998-1999. No. 22.

ERIC Educational Resources Information Center

Chen, Shing-Jen, Ed.; Furutsuka, Takashi, Ed.; Shirotani, Yukari, Ed.

This annual report presents several articles related to the work of the Clinical Center for Child Development at Hokkaido University in Sapporo, Japan. The articles are: (1) "Maternal Speech and Behavior during Mother-Infant Play: Comparison between the United States and Japan" (Sueko Toda, Marc H. Bornstein, and Hiroshi Azuma); (2)…

National Standards and School Reform in Japan and the United States.

ERIC Educational Resources Information Center

DeCoker, Gary, Ed.

This book is a collection of works that explore the implications of a national U.S. curriculum through the study of Japanese education. It consists of 10 chapters: (1) "The Development of the Course of Study and the Structure of Educational Reform in Japan" (Hiroshi Azuma); (2) "Setting National Standards: Educational Reform, Social…

BMP7 Induces Dormancy of Prostatic Tumor Stem Cell in Bone

DTIC Science & Technology

2013-07-01

Watabe, Shigeru Hirota, Sudha K. Pai, Wen Liu, Koji Fukuda, Christopher Chambers, Andrew Wilber and Kounosuke Watabe “Bone Figure 7. Expression of BMP7...Hiroshi Okuda,1 Fei Xing,1 Puspa R. Pandey,1 Misako Watabe,1 Shigeru Hirota,2 Sudha K. Pai,1 Wen Liu,1 Koji Fukuda,1 Christopher Chambers,1 Andrew

PREFACE: International Workshop on Statistical-Mechanical Informatics 2007 (IW-SMI 2007)

NASA Astrophysics Data System (ADS)

Hukushima, Koji; Kabashima, Yoshiyuki; Nishimori, Hidetoshi; Tanaka, Toshiyuki

2007-06-01

. We would like to thank the contributors of the workshop as well as all the participants, who have enjoyed the workshop as well as their stay in Kyoto, one of the most historic cities in Japan. This successful workshop will stimulate further development of the interdisciplinary research field of informatics and statistical mechanics. Koji Hukushima Yoshiyuki Kabashima Hidetoshi Nishimori Toshiyuki Tanaka Editors The IW-SMI 2007 Organizing Committee Toshiyuki Tanaka, General Chair (Kyoto University) Yoshiyuki Kabashima, Vice-General Chair (Tokyo Institute of Technology) Koji Hukushima, Program Chair (University of Tokyo) Hidetoshi Nishimori (Tokyo Institute of Technology) Masato Okada (University of Tokyo) Kazuyuki Tanaka (Tohoku University) Tadashi Wadayama (Nagoya Institute of Technology)

Characterization of 9H-(1,3-dichlor-9, 9-dimethylacridin-2-ona-7-yl)-phosphate (DDAO) as substrate of PP-2A in a fluorimetric microplate assay for diarrhetic shellfish toxins (DSP).

PubMed

Leira, F; Vieites, J M; Vieytes, M R; Botana, L M

2000-12-01

Specific inhibition of protein-phosphatases by diarrhetic shellfish toxins (DSP) of the okadaic acid group, has led to the development of a fluorescent enzyme inhibition assay for these toxins using protein-phosphatase 2A (PP-2A) and fluorogenic substrates of the enzyme. Two different substrates of PP-2A have been previously used in this microplate assay: 4-methylumbelliferyl phosphate and fluorescein diphosphate (FDP). In this report, we present the results obtained using a new fluorogenic substrate of PP-2A, the compound dimethylacridinone phosphate (DDAO). A linear relationship between PP-2A concentration and DDAO-induced fluorescence was observed. Okadaic acid (0.0157-9.43 nM)-dependent inhibition of phosphatase activity showed similar results using FDP and DDAO. Recovery percentages obtained with FDP and DDAO in spiked mussel samples (both raw and canned) were very similar and reproducible. Comparative analysis of DSP-contaminated mussel samples by HPLC and FDP/DDAO-PP-2A showed a good correlation among all methods, thus demonstrating that DDAO can be used as a fluorogenic substrate to quantify okadaic acid and related toxins in bivalve molluscs with optimum reliability.

The possible involvement of protein phosphatase 1 in thrombin-induced Ca2+ influx of human platelets.

PubMed

Murata, K; Sakon, M; Kambayashi, J; Yukawa, M; Yano, Y; Fujitani, K; Kawasaki, T; Shiba, E; Mori, T

1993-04-01

Protein phosphatase 1 is considered to be involved in thrombin-induced platelet activation (Murata et al., Biochem Int 26:327-334, 1992). To clarify the mechanism, we examined the effects of protein phosphatase 1 and 2A inhibitors (calyculin A, tautomycin, okadaic acid) on Ca2+ influx. In the presence of 1 mM Ca2+, thrombin- (0.1 U/ml) induced platelet aggregation and ATP release were inhibited by calyculin A, while this inhibitory effect was abolished in the absence of Ca2+ (EGTA 1 mM). Furthermore, thrombin-induced Mn2+ influx but not intracellular Ca2+ mobilization was inhibited by calyculin A in a dose-related manner. Calyculin A also blocked the ongoing Ca2+ influx when added 3 min after thrombin stimulation. Similar inhibitory effects were observed with okadaic acid and tautomycin in the same potency sequence as the reported one for protein phosphatase 1 (calyculin A > tautomycin > okadaic acid). These results suggest that the anti-platelet effects of phosphatase inhibitors are due to the inhibition of Ca2+ influx and that protein phosphatase 1 plays a key role in the regulation of receptor operated Ca2+ channel of human platelets.

Inhibitors of protein phosphorylation including the retinoblastoma protein induce germination of Candida albicans.

PubMed

Cho, T; Hamatake, H; Hagihara, Y; Kaminishi, H

2000-02-01

It has been previously shown that the induction of germination in Candida albicans occurs following its cessation of growth as a yeast. Similarly, mammalian cells undergo a differentiation process that is preceded by a growth cessation associated with a hypophosphorylation of proteins of the retinoblastoma gene family. It is postulated that a similar type of mechanism may be operative in C. albicans and protein phosphorylation inhibitors: forskolin (stimulates cyclic adenosine monophosphate production), okadaic acid (phosphatase inhibitor) and D-erythro-sphingosine (retinoblastoma protein phosphorylation inhibitor) have been used to further strengthen this hypothesis. Okadaic acid (1-1000 nM) and D-erythro-sphingosine (100 microM) significantly inhibited the growth of yeast cells of C. albicans. D-Erythro-sphingosine at 1000 microM was candidicidal. Forskolin did not significantly affect growth. Exponentially grown C. albicans pretreated with forskolin (10 microM), okadaic acid (1000 nM) or D-erythro-sphingosine (100 microM) readily germinated. In comparison, when these inhibitors were incorporated in the same medium, germination of exponentially grown cells did not occur. These results suggest that protein dephosphorylation may be necessary at an early stage of the yeast-hyphae transition in C. albicans.

A Bioinformatic Approach to Inter Functional Interactions within Protein Sequences

DTIC Science & Technology

2009-02-23

AFOSR/AOARD Reference Number: USAFAOGA07: FA4869-07-1-4050 AFOSR/AOARD Program Manager : Hiroshi Motoda, Ph.D. Period of...Conference on Knowledge Discovery and Data Mining.) In a separate study we have applied our approaches to the problem of whole genome alignment. We have...SIGKDD Conference on Knowledge Discovery and Data Mining Attached. Interactions: Please list: (a) Participation/presentations at meetings

Dynamic Scheduling for Web Monitoring Crawler

DTIC Science & Technology

2009-02-27

researches on static scheduling methods , but they are not included in this project, because this project mainly focuses on the event-driven...pages from public search engines. This research aims to propose various query generation methods using MCRDR knowledge base and evaluates them to...South Wales Professor Hiroshi Motoda/Osaka University Dr. John Salerno, Air Force Research Laboratory/Information Directorate Report

The new indirubin derivative inhibitors of glycogen synthase kinase-3, 6-BIDECO and 6-BIMYEO, prevent tau phosphorylation and apoptosis induced by the inhibition of protein phosphatase-2A by okadaic acid in cultured neurons.

PubMed

Martin, Ludovic; Magnaudeix, Amandine; Wilson, Cornelia M; Yardin, Catherine; Terro, Faraj

2011-11-01

Alterations in glycogen synthase kinase-3β (GSK3β) and protein phosphatase-2A (PP2A) have been proposed to be involved in the abnormal tau phosphorylation and aggregation linked to Alzheimer's disease (AD). Interconnections between GSK3β and PP2A signaling pathways are well established. Targeting tau kinases was proposed to represent a therapeutic strategy for AD. However, which tau kinases should be blocked and to what extent, keeping in mind that kinases have physiological roles? Because most kinase inhibitors are relatively specific and many of them interfere with the cell cycle, it is necessary to develop more specific tau kinase inhibitors devoid of cell toxicity. Here, we used the PP2A inhibition by okadaic acid (OKA) in primary cultured cortical neurons as an in vitro model of increased tau phosphorylation and apoptosis. We tested the effects of two newly characterized indirubin derivative inhibitors of GSK3, 6-BIDECO (6-bromoindirubin-3'-[O-(N,N-diethylcarbamyl)-oxime] and 6-BIMYEO (6-bromoindirubin-3'-[O-(2-morpholin-1-ylethyl)-oxime] hydrochloride) on OKA-induced tau phosphorylation and neuronal apoptosis. Both compounds exhibit higher selectivity toward GSK3 compared with other tau kinases (for 6-BIDECO, IC50 is 0.03 μM for GSK3, >10 μM for CDK1, and 10 μM for CDK5; for 6-BIMYEO, IC50 is 0.11 μM for GSK3, 1.8 μM for CDK1, and 0.9 μM for CDK5). We show that 6-BIDECO and 6-BIMYEO used at micromolar concentrations are not neurotoxic and potently reversed tau phosphorylation and apoptosis induced by OKA. The neuroprotection by these compounds should be further validated in animal models of AD. Copyright © 2011 Wiley-Liss, Inc.

A novel protein phosphatase 2A (PP2A) is involved in the transformation of human protozoan parasite Trypanosoma cruzi.

PubMed Central

González, Jorge; Cornejo, Alberto; Santos, Marcia R M; Cordero, Esteban M; Gutiérrez, Bessy; Porcile, Patricio; Mortara, Renato A; Sagua, Hernán; Da Silveira, José Franco; Araya, Jorge E

2003-01-01

Here we provide evidence for a critical role of PP2As (protein phosphatase 2As) in the transformation of Trypanosoma cruzi. In axenic medium at pH 5.0, trypomastigotes rapidly transform into amastigotes, a process blocked by okadaic acid, a potent PP2A inhibitor, at concentrations as low as 0.1 microM. 1-Norokadaone, an inactive okadaic acid analogue, did not affect the transformation. Electron microscopy studies indicated that okadaic acid-treated trypomastigotes had not undergone ultrastructural modifications, reinforcing the idea that PP2A inhibits transformation. Using a microcystin-Sepharose affinity column we purified the native T. cruzi PP2A. The enzyme displayed activity against 32P-labelled phosphorylase a that was inhibited in a dose-dependent manner by okadaic acid. The protein was also submitted to MS and, from the peptides obtained, degenerate primers were used to clone a novel T. cruzi PP2A enzyme by PCR. The isolated gene encodes a protein of 303 amino acids, termed TcPP2A, which displayed a high degree of homology (86%) with the catalytic subunit of Trypanosoma brucei PP2A. Northern-blot analysis revealed the presence of a major 2.1-kb mRNA hybridizing in all T. cruzi developmental stages. Southern-blot analysis suggested that the TcPP2A gene is present in low copy number in the T. cruzi genome. These results are consistent with the mapping of PP2A genes in two chromosomal bands by pulsed-field gel electrophoresis and chromoblot hybridization. Our studies suggest that in T. cruzi PP2A is important for the complete transformation of trypomastigotes into amastigotes during the life cycle of this protozoan parasite. PMID:12737627

Phosphatase inhibition leads to histone deacetylases 1 and 2 phosphorylation and disruption of corepressor interactions.

PubMed

Galasinski, Scott C; Resing, Katheryn A; Goodrich, James A; Ahn, Natalie G

2002-05-31

The regulation of histone deacetylases (HDACs) by phosphorylation was examined by elevating intracellular phosphorylation in cultured cells with the protein phosphatase inhibitor okadaic acid. After fractionation of extracts from treated versus untreated cells, HDAC 1 and 2 eluted in several peaks of deacetylase activity, assayed using mixed acetylated histones or acetylated histone H4 peptide. Stimulation of cells with okadaic acid led to hyperphosphorylation of HDAC 1 and 2 as well as changes in column elution of both enzymes. Hyperphosphorylated HDAC2 was also observed in cells synchronized with nocodazole or taxol, demonstrating regulation of HDAC phosphorylation during mitosis. Phosphorylated HDAC1 and 2 showed a gel mobility retardation that correlated with a small but significant increase in activity, both of which were reversed upon phosphatase treatment in vitro. However, the most pronounced effect of HDAC phosphorylation was to disrupt protein complex formation between HDAC1 and 2 as well as complex formation between HDAC1 and corepressors mSin3A and YY1. In contrast, interactions between HDAC1/2 and RbAp46/48 were unaffected by okadaic acid. These results establish a novel link between HDAC phosphorylation and the control of protein-protein interactions and suggest a mechanism for relief of deacetylase-catalyzed transcriptional repression by phosphorylation-dependent signaling.

Toxicity of Thiophenes from Echinops transiliensis (Asteraceae) against Aedes aegypti (Diptera: Culicidae) Larvae

DTIC Science & Technology

2014-01-01

Toxicity of Thiophenes from Echinops transiliensis (Asteraceae) against Aedes aegypti (Diptera: Culicidae) Larvae by Hiroshi Nakano*a)b)c), Abbas...larvicides against Aedes aegypti. Structural differences among compounds 3, 5, and 8 consisted in differing AcO and OH groups attached to C(3’’) and C(4...serious human diseases including malaria, Japanese encephalitis, yellow fever, dengue, and filariasis. The urban-adapted Aedes aegypti mosquito has become

Proceedings of the International Symposium on Diamond Materials Held in Washington, DC on 5-10 May 1991. Volume 91-8

DTIC Science & Technology

1991-05-01

J. S. Ma, H. Kawarada, T. Yonehara, & A. Hiraki DIAMOND ON SILICON: A HOT FILAMENT CVD STUDY OF 266 NUCLEATION P. Ascarelli, S. Fontana, E. Molinari...BORON-DOPED CVD DIAMONDS H. Ka warada, Y. Yokota, H. Matsuyama T. Sogi, & A. Hiraki SPATIALLY AND SPECTALLY RESOLVED 427 CATHODOLUMINESCENCE...Sheng Ma, *Hiroshi Kawarada, "Takao Yonehara, and Akio Hiraki Department of Electrical Engineering, Osaka University, Suita-shi, Osaka 565, Japan

The Theory of Canonical Perturbations Applied to Attitude Dynamics and to the Earth Rotation. Osculating and Nonosculating Andoyer Variables

DTIC Science & Technology

2007-06-21

Hiroshi Kinoshita for his extremely valuable consultations on some subtleties of his theory. ME is also grateful to Pini Gurfil , George Kaplan, Jean...that the Andoyer elements are introduced 20 It can be shown ( Gurfil et al. 2007) that the body-frame-related components gi of the angular momentum are...oblate precessing planet. Astron. J. 70, 5–9 (1965) Goldstein, H.: Classical Mechanics. 2nd ed. Addison-Wesley, Reading MA (1981) Gurfil , P., Elipe

Characteristic Functional of a Probability Measure Absolutely Continuous with Respect to a Gaussian Radon Measure

DTIC Science & Technology

1984-08-01

12. PERSONAL AUTHORISI Hiroshi Sato 13* TYPE OF REPORT TECHNICAL 13b. TIME COVERED PROM TO 14. OATE OF REPORT (Yr. Mo., Day) Aug. 1984...nectuary and identify by bloc* number) Let p and p.. be probability measures on a locally convex Hausdorff real topological linear space E. C.R. Baker [1...THIS PAGE ABSTRACT Let y and y1 be probability measures on a locally convex Hausdorff real topological linear space E. C.R. Baker [1] posed the

Global regulation of post-translational modifications on core histones.

PubMed

Galasinski, Scott C; Louie, Donna F; Gloor, Kristen K; Resing, Katheryn A; Ahn, Natalie G

2002-01-25

Full-length masses of histones were analyzed by mass spectrometry to characterize post-translational modifications of bulk histones and their changes induced by cell stimulation. By matching masses of unique peptides with full-length masses, H4 and the variants H2A.1, H2B.1, and H3.1 were identified as the main histone forms in K562 cells. Mass changes caused by covalent modifications were measured in a dose- and time-dependent manner following inhibition of phosphatases by okadaic acid. Histones H2A, H3, and H4 underwent changes in mass consistent with altered acetylation and phosphorylation, whereas H2B mass was largely unchanged. Unexpectedly, histone H4 became almost completely deacetylated in a dose-dependent manner that occurred independently of phosphorylation. Okadaic acid also partially blocked H4 hyperacetylation induced by trichostatin-A, suggesting that the mechanism of deacetylation involves inhibition of H4 acetyltransferase activity, following perturbation of cellular phosphatases. In addition, mass changes in H3 in response to okadaic acid were consistent with phosphorylation of methylated, acetylated, and phosphorylated forms. Finally, kinetic differences were observed with respect to the rate of phosphorylation of H2A versus H4, suggesting differential regulation of phosphorylation at sites on these proteins, which are highly related by sequence. These results provide novel evidence that global covalent modifications of chromatin-bound histones are regulated through phosphorylation-dependent mechanisms.

Simulation of Earthquake-Generated Sea-Surface Deformation

NASA Astrophysics Data System (ADS)

Vogl, Chris; Leveque, Randy

2016-11-01

Earthquake-generated tsunamis can carry with them a powerful, destructive force. One of the most well-known, recent examples is the tsunami generated by the Tohoku earthquake, which was responsible for the nuclear disaster in Fukushima. Tsunami simulation and forecasting, a necessary element of emergency procedure planning and execution, is typically done using the shallow-water equations. A typical initial condition is that using the Okada solution for a homogeneous, elastic half-space. This work focuses on simulating earthquake-generated sea-surface deformations that are more true to the physics of the materials involved. In particular, a water layer is added on top of the half-space that models the seabed. Sea-surface deformations are then simulated using the Clawpack hyperbolic PDE package. Results from considering the water layer both as linearly elastic and as "nearly incompressible" are compared to that of the Okada solution.

Regulated internalization of caveolae

PubMed Central

1994-01-01

Caveolae are specialized invaginations of the plasma membrane which have been proposed to play a role in diverse cellular processes such as endocytosis and signal transduction. We have developed an assay to determine the fraction of internal versus plasma membrane caveolae. The GPI-anchored protein, alkaline phosphatase, was clustered in caveolae after antibody-induced crosslinking at low temperature and then, after various treatments, the relative amount of alkaline phosphatase on the cell surface was determined. Using this assay we were able to show a time- and temperature-dependent decrease in cell-surface alkaline phosphatase activity which was dependent on antibody-induced clustering. The decrease in cell surface alkaline phosphatase activity was greatly accelerated by the phosphatase inhibitor, okadaic acid, but not by a protein kinase C activator. Internalization of clustered alkaline phosphatase in the presence or absence of okadaic acid was blocked by cytochalasin D and by the kinase inhibitor staurosporine. Electron microscopy confirmed that okadaic acid induced removal of caveolae from the cell surface. In the presence of hypertonic medium this was followed by the redistribution of groups of caveolae to the center of the cell close to the microtubule-organizing center. This process was reversible, blocked by cytochalasin D, and the centralization of the caveolar clusters was shown to be dependent on an intact microtubule network. Although the exact mechanism of internalization remains unknown, the results show that caveolae are dynamic structures which can be internalized into the cell. This process may be regulated by kinase activity and require an intact actin network. PMID:7962085

PREFACE: Nanospintronics design and realization

NASA Astrophysics Data System (ADS)

Akai, Hisazumi; Katayama-Yoshida, Hiroshi; Kasai, Hideaki

2004-12-01

This special issue of Journal of Physics: Condensed Matter contains selected papers from the 1st International Conference on Nanospintronics Design and Realization (ICNDR 2004), which was held in Kyoto, Japan, 24--28 May 2004. This conference was organized by the Nanospintronics Design and Realization project members: Hideaki Kasai, Osaka (Chair of the Conference) Hisazumi Akai, Osaka Hajime Asahi, Osaka Wilson Agerico Diño, Osaka Hiroshi Harima, Kyoto Tomoyuki Kakeshita, Osaka Junjiro Kanamori, Kyoto Hiroshi Katayama-Yoshida, Osaka Koichi Kusakabe, Osaka Hiroshi Nakanishi, Osaka (Secretary) Tamio Oguchi, Hiroshima Teruo Ono, Osaka Naoshi Suzuki, Osaka Hitoshi Tabata, Osaka under the auspices of the Japan Ministry of Education, Culture, Sports, Science and Technology (MEXT) Special Coordination Funds for Promoting Science and Technology, and the sponsorship of Osaka University and the International Institute for Advanced Studies (IIAS). The conference is intended to provide an international forum for experimental and theoretical researchers, in the rapidly developing field of nanospintronics. It aims to: provide an overview of our current understanding of the physics of spin transport in (magnetic) semiconductors and hybrid magnetic/semiconductor structures; provide a venue to present and discuss the latest developments in using spin-dependent phenomena in nano-(opto-) electronics and computing applications; provide a venue for discussion and assessment of other possible means of exploiting the spin-dependent phenomena in future nano-(opto-) electronic and computing applications; address current (and foreseeable future) problems, of fundamental and applied nature, in an effort to bridge the physics and technology gap between semiconducting and magnetic materials. All of these being geared towards bringing about the realization of a functioning nanospintronics. A total of 127 delegates from 15 countries took part in ICNDR 2004, which was comprised of 62 invited

77 FR 30320 - National Park Service Alaska Region's Subsistence Resource Commission

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... testimony. The public is welcome to present written or oral comments to the SRC. This meeting will be... inspection approximately six weeks after the meeting. Before including your address, telephone number, email.... Teleconference meeting participants should contact Marcy Okada, Subsistence Manager, via email ( [email protected

X Chromosome Inactivation and Breast Cancer: Epigenetic Alteration in Tumor Initiation and Progression

DTIC Science & Technology

2007-09-01

Okada, Y., Sugihara, H., Hattori, T., Reeve, A.E., Ogawa, O., and Okamoto, K. (2004). Char- acterization of loss-of-inactive X in Klinefelter ... syndrome and female- derived cancer cells. Oncogene 23, 6163–6169. Marahrens, Y., Panning, B., Dausman, J., Strauss, W., and Jaenisch, R. (1997). Xist

Analysis of lipophilic marine biotoxins by liquid chromatography coupled with high-resolution mass spectrometry in seawater from the Catalan Coast.

PubMed

Bosch-Orea, Cristina; Sanchís, Josep; Farré, Marinella; Barceló, Damià

2017-09-01

Marine biotoxins regularly occur along the coast, with several consequences for the environment as well as the food industry. Monitoring of these compounds in seawater is required to assure the safety of marine resources for human consumption, providing a means for forecasting shellfish contamination events. In this study, an analytical method was developed for the detection of ten lipophilic marine biotoxins in seawater: azaspiracids 1, 2, 3, 4 and 5, classified as azaspiracid shellfish poisoning toxins, and pectenotoxin 2, okadaic acid and the related dinophysistoxin 1, yessotoxin and homoyessotoxin, classified as diarrheic shellfish poisoning toxins. The method is based on the application of solid-liquid ultrasound-assisted extraction and solid-phase extraction, followed by high-performance liquid chromatography coupled with high-resolution mass spectrometry. The limits of detection of this method are in the range of nanograms per litre and picograms per litre for most of the compounds, and recoveries range from 20.5% to 97.2%. To validate the effectiveness of this method, 36 samples of surface water from open coastal areas and marinas located along the Catalan coast on the Mediterranean Sea were collected and analysed. Eighty-eight per cent of these samples exhibited okadaic acid in particulate and aqueous phases in concentrations ranging from 0.11 to 560 μg/g and from 2.1 to 1780 ng/L respectively. Samples from open coastal areas exhibited higher concentrations of okadaic acid in particulate material, whereas in samples collected in sportive ports, the particulate material exhibited lower levels than the aqueous phase. Graphical Abstract Biotoxins investigated in seawater of the Catalan coast.

Contact Sensing from Force Measurements

DTIC Science & Technology

1990-10-01

themselves. Their approach has been reconsidered bv Tsujimura and Yabuta [1C)8,8]. OkadA 1100(l prQent#,A a suspension-cell based tactile sensor, very...with an intrinsic tactile sensor. and the reconstruction of their surface profile has been described by Brock and Chiu [1985], and later by Tsujimura and

Identification of pectenotoxins in plankton, filter feeders, and isolated cells of a Dinophysis acuminata with an atypical toxin profile, from Chile.

PubMed

Blanco, Juan; Alvarez, Gonzalo; Uribe, Eduardo

2007-04-01

A bloom of Dinophysis acuminata produced, in autumn of 2005, a closure of the scallop harvesting in Bahía Inglesa, in the Chilean III region. Isolated cells of this Dinophysis species were shown to contain 180 pg cell(-1) of pectenotoxin 2 but neither okadaic acid nor any of its analogs or derivatives (at least at a detectable level). Examination of plankton and filter-feeder samples covering an area of ca. 350 km, from the location where the toxicity was recorded to Bahía Tongoy, showed that the unique toxin profile found in the first bloom was widespread over that part of Chile and persisted for months. The analysis were carried out by HPLC-ESI-MS using positive ionization mode, with a detection limit below 2 ng of OA mL(-1) of methanolic extract. This is the first report of the presence of pectenotoxins in the plankton of the Pacific coast of America and in the studied filter feeders. This is also the first report of a Dinophysis species containing pectenotoxins and not any toxin of the okadaic acid group.

Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death.

PubMed

Sierra, Saleta; Ramos, Maria C; Molina, Pilar; Esteo, Cynthia; Vázquez, Jose Antonio; Burgos, Javier S

2011-01-01

There is growing evidence to support the hypothesis that statins may act as neuroprotectants in several neuropathological conditions, including Alzheimer's disease. The mechanisms for neuroprotection are only partially understood, however, and pleiotropic phenomena could be involved. We have made a comparative study of 9 statins (lovastatin, mevastatin, pravastatin, simvastatin, cerivastatin, atorvastatin, fluvastatin, pitavastatin, and rosuvastatin), analyzing several parameters that could be related to neuroprotection, such as chemical structure, lipophilicity, potential blood-brain-barrier penetration (BBB), 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibition, cholesterol modulation in neurons, glia, and human hepatocyte cell lines, and protection against neurodegeneration caused by tau hyperphosphorylation induced by okadaic acid. Our results indicate that monacolin J derivatives (natural and semi-synthetic statins) are the best candidates for the prevention of neurodegenerative conditions due to their higher potential BBB penetration capacity, cholesterol lowering effect on neurons with a satisfactory safety profile, and in vitro protection against cell death caused by okadaic acid in culture. Among the nine statins studied, simvastatin presented the best characteristics for preventing neurodegenerative conditions.

Lorazepam v. diazepam for pediatric status epilepticus.

PubMed

Pinto, Rovina Fiona; Turnbull, Jennifer

2016-05-01

Clinical question Is intravenous (IV) lorazepam superior to IV diazepam in the treatment of pediatric status epilepticus? Article chosen Chamberlain JM, Okada P, Holsti M, et al. Lorazepam v. diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA 2014;311(16):1652-60. To determine whether lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus.

Microcystins Alter Chemotactic Behavior in Caenorhabditis elegans by Selectively Targeting the AWA Sensory Neuron

PubMed Central

Moore, Caroline E.; Lein, Pamela J.; Puschner, Birgit

2014-01-01

Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model and the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure on AWA versus AWC sensory neuron function were determined using a chemotaxis assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC-LF was more potent than MC-LR. To probe a potential role for protein phosphatases (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h. Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect on function of either neuronal cell type at the concentrations tested. These findings suggest that MCs alter the AWA neuron at concentrations that do not cause AWC toxicity via mechanisms other than PP inhibition. PMID:24918360

Dinophysis Toxins: Causative Organisms, Distribution and Fate in Shellfish

PubMed Central

Reguera, Beatriz; Riobó, Pilar; Rodríguez, Francisco; Díaz, Patricio A.; Pizarro, Gemita; Paz, Beatriz; Franco, José M.; Blanco, Juan

2014-01-01

Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells·L−1). They are the main threat, in terms of days of harvesting bans, to aquaculture in Northern Japan, Chile, and Europe. Toxicity and toxin profiles are very variable, more between strains than species. The distribution of DSP events mirrors that of shellfish production areas that have implemented toxin regulations, otherwise misinterpreted as bacterial or viral contamination. Field observations and laboratory experiments have shown that most of the toxins produced by Dinophysis are released into the medium, raising questions about the ecological role of extracelular toxins and their potential uptake by shellfish. Shellfish contamination results from a complex balance between food selection, adsorption, species-specific enzymatic transformations, and allometric processes. Highest risk areas are those combining Dinophysis strains with high cell content of okadaates, aquaculture with predominance of mytilids (good accumulators of toxins), and consumers who frequently include mussels in their diet. Regions including pectenotoxins in their regulated phycotoxins will suffer from much longer harvesting bans and from disloyal competition with production areas where these toxins have been deregulated. PMID:24447996

Conceptural Study of Gyroscopic Damping Systems for Structural Indentification

NASA Astrophysics Data System (ADS)

Furuya, H.; Senba, A.

2002-01-01

the system by using the response amplitude, and for the optimum momentum inertia by using the natural frequency. References [1] Hiroshi FURUYA, Masanori TAKAHASHI, and Tatsuo OHMACHI: Concept of Adaptive Gyroscopic Damper and Vibration Suppression of Flexible Structures, 8th International Conference on Adaptive Structures and Technologies, Wakayama, Oct. 29-31, 1997, eds. Y. Murotsu, C.A. Rogers, P. Santini, and H. Okubo, Technomic Publishing, pp.247-254, 1998. [2] Hiroshi FURUYA, Masanori TAKAHASHI, and Tatsuo OHMACHI: Pseudo Feedback Control of Adaptive Gyroscopic Damper for Vibration Suppression, 39th AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics and Material Conference, AIAA 98-1796, Long Beach, CA, April 20-23, pp.830-834, 1998. [3] Hiroshi FURUYA and Atsuo KOBORI: Suppression of Multiple Modes Vibration of Flexible Structures with Adaptive Gyroscopic Damper System, 10th International Conference on Adaptive Structures and Technologies, Paris, Oct. 13-15, 1999, eds. R. Ohayon, and M. Bernadou, Technomic Publishing, pp. 127-134, 1999.

Investigation of Material Problems for High Temperature, High Power Space Energy-Conversion Systems.

DTIC Science & Technology

1986-07-01

Microplastic Deformation in Molybdenum with Grain-Boundary Segregations of Nickel, Phys. Met. Metall. 54, 180, 1982. 76. C. Lea, B. Muddle and D...8217-- *. ~a.-. ~ ~ ~ .. . ~ . ~ . .*.. -- ~ .. 25 93. T. Noda, T. Kainuma and M. Okada: Oxygen Desorption from Grain Boundaries of Molybdenum During Vacuu...behavior of this work function climb was explained by the desorption of atoms adsorbed or, the surface. The test result of the present W-Re samples showed

A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.

PubMed

Kurz, J E; Sheets, D; Parsons, J T; Rana, A; Delorenzo, R J; Churn, S B

2001-07-01

This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.

Development of a Low cost Ultra tiny Line Laser Range Sensor

DTIC Science & Technology

2016-12-01

Development of a Low-cost Ultra-tiny Line Laser Range Sensor Xiangyu Chen∗, Moju Zhao∗, Lingzhu Xiang†, Fumihito Sugai∗, Hiroaki Yaguchi∗, Kei Okada...and Masayuki Inaba∗ Abstract— To enable robotic sensing for tasks with require- ments on weight, size, and cost, we develop an ultra-tiny line laser ...view customizable using different laser lenses. The optimal measurement range of the sensor is 0.05[m] ∼ 2[m]. Higher sampling rates can be achieved

Cognitive and Neural Bases of Skilled Performance

DTIC Science & Technology

1990-08-09

torso. The only significant source of noise was a slow variation of the ambient field, which produces a drift of the baseline. The first depended upon...brief survey. Scand. J. of Psychology, Suppl. 1:170-174, 1982. [25] S. A. Hillyard, R. F. Hink , V. L. Schwent, and T. W. Picton. Electrical signs of...Okada, L. Kaufman, and S. J. Williamson. The hippocampal formation as a source of the slow endogenous potentials. Electroencepk. Clin. Neurophysiol

Prevalence of psychoactive substance use among commercial motorcyclists and its health and social consequences in Zaria, Nigeria.

PubMed

Alti-Muazu, M; Aliyu, A A

2008-06-01

In recent years commercial motorcyclists (Okada riders) have come to bridge the huge public transport gap in most cities across the country. However, this is not without the dangers they pose to themselves, passengers and to other road users. It is claimed that some of these Okada riders operate under the influence of drugs and other substances. But there are few community-based studies that have investigated the problem in this part of Nigeria. Therefore, this study was conducted to determine the prevalence, health and social consequences of psychoactive substance use among commercial motorcyclists (Okada) in Zaria, northern Nigeria. Multi-stage sampling technique was used to sample commercial motorcyclists registered with commercial motorcyclists union in Zaria city, Kaduna state, Nigeria. Structured, closed ended and interviewer administered questionnaires were used to collect information on socio-demographic characteristics, factors influencing psychoactive substance use, impact on health status, motor cycle riding experience and work performance. Two hundred commercial motor cyclists were intervi ewed, majority of them were in the age group 21-25 years (55.5%) with a mean age of 25.4 +/- 3.9 years. All the motorcyclists were male, (60.5%), had no formal education, (79.5%) are of Hausa extraction and (69%) worked for more than 10 hours per day. A high prevalence of 59.5% of road traffic accident that was associated with the use of psychoactive drugs was found among the motorcyclists. Commonly identified psychoactive substance/drugs used were: marijuana [Indian hemp] 25.8%, solution 24.5%, caffeine (Kola) 15.8%, and coffee 4.8%. Keeping awake, suppression of fatigue, and peer group effect were the identified factors influencing psychoactive substance use. The commonest types of injuries sustained were bruises and lacerations (62.5%) and fractures of upper and lower limbs (10.5%). Road traffic accidents among commercial motorcyclists are a frequent occurrence in

On precisely modelling surface deformation due to interacting magma chambers and dykes

NASA Astrophysics Data System (ADS)

Pascal, Karen; Neuberg, Jurgen; Rivalta, Eleonora

2014-01-01

Combined data sets of InSAR and GPS allow us to observe surface deformation in volcanic settings. However, at the vast majority of volcanoes, a detailed 3-D structure that could guide the modelling of deformation sources is not available, due to the lack of tomography studies, for example. Therefore, volcano ground deformation due to magma movement in the subsurface is commonly modelled using simple point (Mogi) or dislocation (Okada) sources, embedded in a homogeneous, isotropic and elastic half-space. When data sets are too complex to be explained by a single deformation source, the magmatic system is often represented by a combination of these sources and their displacements fields are simply summed. By doing so, the assumption of homogeneity in the half-space is violated and the resulting interaction between sources is neglected. We have quantified the errors of such a simplification and investigated the limits in which the combination of analytical sources is justified. We have calculated the vertical and horizontal displacements for analytical models with adjacent deformation sources and have tested them against the solutions of corresponding 3-D finite element models, which account for the interaction between sources. We have tested various double-source configurations with either two spherical sources representing magma chambers, or a magma chamber and an adjacent dyke, modelled by a rectangular tensile dislocation or pressurized crack. For a tensile Okada source (representing an opening dyke) aligned or superposed to a Mogi source (magma chamber), we find the discrepancies with the numerical models to be insignificant (<5 per cent) independently of the source separation. However, if a Mogi source is placed side by side to an Okada source (in the strike-perpendicular direction), we find the discrepancies to become significant for a source separation less than four times the radius of the magma chamber. For horizontally or vertically aligned pressurized

Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A.

PubMed

Han, Min; Pendem, Suresh; Teh, Suet Ling; Sukumaran, Dinesh K; Wu, Feng; Wilson, John X

2010-01-01

Endothelial barrier dysfunction contributes to morbidity in sepsis. We tested the hypothesis that raising the intracellular ascorbate concentration protects the endothelial barrier from septic insult by inhibiting protein phosphatase type 2A. Monolayer cultures of microvascular endothelial cells were incubated with ascorbate, dehydroascorbic acid (DHAA), the NADPH oxidase inhibitors apocynin and diphenyliodonium, or the PP2A inhibitor okadaic acid and then were exposed to septic insult (lipopolysaccharide and interferon-gamma). Under standard culture conditions that depleted intracellular ascorbate, septic insult stimulated oxidant production and PP2A activity, dephosphorylated phosphoserine and phosphothreonine residues in the tight junction-associated protein occludin, decreased the abundance of occludin at cell borders, and increased monolayer permeability to albumin. NADPH oxidase inhibitors prevented PP2A activation and monolayer leak, showing that these changes required reactive oxygen species. Okadaic acid, at a concentration that inhibited PP2A activity and monolayer leak, prevented occludin dephosphorylation and redistribution, implicating PP2A in the response of occludin to septic insult. Incubation with ascorbate or DHAA raised intracellular ascorbate concentrations and mitigated the effects of septic insult. In conclusion, ascorbate acts within microvascular endothelial cells to inhibit septic stimulation of oxidant production by NADPH oxidase and thereby prevents PP2A activation, PP2A-dependent dephosphorylation and redistribution of occludin, and disruption of the endothelial barrier. Copyright 2009 Elsevier Inc. All rights reserved.

In Vitro Reconstitution of Microtubule Plus End-directed, GTPγS-sensitive Motility of Golgi MembranesV⃞

PubMed Central

Fullerton, Aaron T.; Bau, Mu-Yeh; Conrad, Patricia A.; Bloom, George S.

1998-01-01

Purified Golgi membranes were mixed with cytosol and microtubules (MTs) and observed by video enhanced light microscopy. Initially, the membranes appeared as vesicles that moved along MTs. As time progressed, vesicles formed aggregates from which membrane tubules emerged, traveled along MTs, and eventually generated extensive reticular networks. Membrane motility required ATP, occurred mainly toward MT plus ends, and was inhibited almost completely by the H1 monoclonal antibody to kinesin heavy chain, 5′-adenylylimidodiphosphate, and 100 μM but not 20 μM vanadate. Motility was also blocked by GTPγS or AlF4− but was insensitive to AlCl3, NaF, staurosporin, or okadaic acid. The targets for GTPγS and AlF4− were evidently of cytosolic origin, did not include kinesin or MTs, and were insensitive to several probes for trimeric G proteins. Transport of Golgi membranes along MTs mediated by a kinesin has thus been reconstituted in vitro. The motility is regulated by one or more cytosolic GTPases but not by protein kinases or phosphatases that are inhibited by staurosporin or okadaic acid, respectively. The pertinent GTPases are likely to be small G proteins or possibly dynamin. The in vitro motility may correspond to Golgi-to-ER or Golgi-to-cell surface transport in vivo. PMID:9763438

Sp1 transcriptional activity is up-regulated by phosphatase 2A in dividing T lymphocytes.

PubMed

Lacroix, Isabelle; Lipcey, Carol; Imbert, Jean; Kahn-Perlès, Brigitte

2002-03-15

We have followed Sp1 expression in primary human T lymphocytes induced, via CD2 plus CD28 costimulation, to sustained proliferation and subsequent return to quiescence. Binding of Sp1 to wheat germ agglutinin lectin was not modified following activation, indicating that the overall glycosylation of the protein was unchanged. Sp1 underwent, instead, a major dephosphorylation that correlated with cyclin A expression and, thus, with cell cycle progression. A similar change was observed in T cells that re-entered cell cycle following secondary interleukin-2 stimulation, as well as in serum-induced proliferating NIH/3T3 fibroblasts. Phosphatase 2A (PP2A) appears involved because 1) treatment of dividing cells with okadaic acid or cantharidin inhibited Sp1 dephosphorylation and 2) PP2A dephosphorylated Sp1 in vitro and strongly interacted with Sp1 in vivo. Sp1 dephosphorylation is likely to increase its transcriptional activity because PP2A overexpression potentiated Sp1 site-driven chloramphenicol acetyltransferase expression in dividing Kit225 T cells and okadaic acid reversed this effect. This increase might be mediated by a stronger affinity of dephosphorylated Sp1 for DNA, as illustrated by the reduced DNA occupancy by hyperphosphorylated Sp factors from cantharidin- or nocodazole-treated cells. Finally, Sp1 dephosphorylation appears to occur throughout cell cycle except for mitosis, a likely common feature to all cycling cells.

Panel established to revise position statement on climate change

NASA Astrophysics Data System (ADS)

President Robert Dickinson has appointed a panel to review the current AGU position statement on climate change and greenhouse gases, and to consider revising the statement to reflect scientific progress over the last four years. Marvin Geller of the State University of New York-Stonybrook chairs the panel.Other panel members include: Andre Berger, George Lemaître Catholic University of Louvain, Belgium; Anny Cazenave, Observatoire Midi-Pyrénées, Toulouse, France; John Christy, University of Alabama, Huntsville; Ellen Druffel, University of California, Irvine; Jack Fellows, University Consortium for Atmospheric Research, Boulder; Hiroshi Kanzawa, Nagoya University, Japan; William Schlesinger, Duke University, Durham; William (Jim) Shuttleworth, University of Arizona; Eric Sundquist, U.S. Geological Survey, Woods Hole; Richard Turco, University of California, Los Angeles; Ilana Wainer, Universidade Cidade Sao Paulo, Brazil.

Regulation of the Two Delta Crystallin Genes during Lens Development in the Chicken Embryo

DTIC Science & Technology

1991-08-22

Stabilization of tubulin mRNA by inhibition of protein synthesis sea 148 urchin embryos. Mol. Cell. Biol. 8, 3518-3525. Goto, K., Okada, T.S...counts from twenty lens epithelia. Error bars are ± SEM . Symbols: control lens tissue, (square), 0.5 ng/ml actinomycin D, (inverted triangle), 30 ng...Ŝ]-methionine for 5 hr in the absence or presence of actinomycin D (0.5 or 30 M-g/̂ iD • Values are the means ± SEM for ten groups of three lens

Regulation of Breast Carcinoma Growth and Neovascularization by Novel Peptide Sequences in Thromospondin

DTIC Science & Technology

1997-10-01

containing 10% FCS. complete medium. Lysis buffer [0.5 ml; containing 5 m guanidine thiocyanate, 25 Okadaic acid, TPA, fumonisin B1, herbimycin A, and sodium...promote cell adhesion, were used instead of free peptides in the herbimycin, fumonisin BI, or TPA on proliferation, the reagents were current studies...stripes), or 25 nam fumonisin B1 (0i). The indicated peptides or proteins (4 gaM 407f or 450f, 50 nM TSP1, and 0.4 nam Fig. 8. Endothelial cell density

Estimating Tsunami Runup with Fault Plane Parameters

NASA Astrophysics Data System (ADS)

Sepulveda, I.; Liu, P. L. F.

2016-12-01

The forecasting of tsunami runup has often been done by solving numerical models. The execution times, however, make them unsuitable for the purpose of warning. We offer an alternative method that provides analytical relationship between the runup height, the fault plane parameters and the characteristic of coastal bathymetry. The method uses the model of Okada (1985) to estimate the coseismic deformation and the corresponding sea surface displacement (η(x,0)). Once the tsunami waves are generated, Carrier & Greenspan (1958) solution (C&G) is adopted to yield analytical expressions for the shoreline elevation and velocity. Two types of problems are investigated. In the first, the bathymetry is modeled as a constant slope that is connected to a constant depth region, where a seismic event occurs. This is a boundary value problem (BVP). In the second, the bathymetry is further simplified as a constant slope, on which a seismic event occurs. This is an initial value problem (IVP). Both problems are depicted in Figure 1. We derive runup solutions in terms of the fault parameters. The earthquake is associated with vertical coseismic seafloor displacements by using Okada's elastic model. In addition to the simplifications considered in Okada's model, we further assume (1) a strike parallel to the shoreline, (2) a very long rupture area and (3) a fast earthquake so surface elevation mimics the seafloor displacements. Then the tsunami origin is modeled in terms of the fault depth (d), fault width (W), fault slip (s) and dip angle (δ). We describe the solution for the BVP. Madsen & Schaeffer (2010) utilized C&G to derive solutions for the shoreline elevation of sinusoidal waves imposed in the offshore boundary. A linear superposition of this solution represents any arbitrary incident wave. Furthermore, we can prescribe the boundary condition at the toe of sloping beach by adopting the linear shallow wave equations in the constant depth area. By means of a dimensional

KCl stimulation increases norepinephrine transporter function in PC12 cells.

PubMed

Mandela, Prashant; Ordway, Gregory A

2006-09-01

The norepinephrine transporter (NET) plays a pivotal role in terminating noradrenergic signaling and conserving norepinephrine (NE) through the process of re-uptake. Recent evidence suggests a close association between NE release and regulation of NET function. The present study evaluated the relationship between release and uptake, and the cellular mechanisms that govern these processes. KCl stimulation of PC12 cells robustly increased [3H]NE uptake via the NET and simultaneously increased [3H]NE release. KCl-stimulated increases in uptake and release were dependent on Ca2+. Treatment of cells with phorbol-12-myristate-13-acetate (PMA) or okadaic acid decreased [3H]NE uptake but did not block KCl-stimulated increases in [3H]NE uptake. In contrast, PMA increased [3H]NE release and augmented KCl-stimulated release, while okadaic acid had no effects on release. Inhibition of Ca2+-activated signaling cascades with KN93 (a Ca2+ calmodulin-dependent kinase inhibitor), or ML7 and ML9 (myosin light chain kinase inhibitors), reduced [3H]NE uptake and blocked KCl-stimulated increases in uptake. In contrast, KN93, ML7 and ML9 had no effect on KCl-stimulated [3H]NE release. KCl-stimulated increases in [3H]NE uptake were independent of transporter trafficking to the plasma membrane. While increases in both NE release and uptake mediated by KCl stimulation require Ca2+, different intracellular mechanisms mediate these two events.

Reactions of tobacco genotypes with different antioxidant capacities to powdery mildew and Tobacco mosaic virus infections.

PubMed

Gullner, Gábor; Juhász, Csilla; Németh, Adél; Barna, Balázs

2017-10-01

The interactions of powdery mildew (Golovinomyces orontii) and Tobacco mosaic virus (TMV) with tobacco lines having down or upregulated antioxidants were investigated. Xanthi-nc, its salicylic acid-deficient NahG mutant, a paraquat-sensitive Samsun (PS) and its paraquat tolerant (PT) mutant were used. Cell membrane damage caused by H 2 O 2 was significantly higher in NahG than Xanthi, whereas it was lower in PT than in PS. Leakage of ions from PT was reduced by the powdery mildew infection. On the other hand TMV inoculation led to a 6-fold and 2-fold elevation of ion leakage from hypersensitive resistant NahG and Xanthi leaves, respectively, whereas ion leakage increased slightly from susceptible PS leaves. G. orontii infection induced ribonuclease (RNase) enzyme activity in extracts from Xanthi and NahG (about 200-250% increase) and weakly (about 20-30% increase) from PS and PT lines. Pre-treatment with protein kinase inhibitor staurosporine or protein phosphatase inhibitor okadaic acid very strongly inhibited mildew development on tobacco lines. Our experiments suggest that protein kinases inhibited by staurosporine seem to be important factors, while protein phosphatases inhibited by okadaic acid play less significant role in TMV-induced lesion development. Both powdery mildew and TMV infections up-regulated the expression of PR-1b, PR-1c and WRKY12 genes in all tobacco lines to various extents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex

PubMed Central

Nunbhakdi-Craig, Viyada; Machleidt, Thomas; Ogris, Egon; Bellotto, Dennis; White, Charles L.; Sontag, Estelle

2002-01-01

Tight junctions (TJs) play a crucial role in the establishment of cell polarity and regulation of paracellular permeability in epithelia. Here, we show that upon calcium-induced junction biogenesis in Madin-Darby canine kidney cells, ABαC, a major protein phosphatase (PP)2A holoenzyme, is recruited to the apical membrane where it interacts with the TJ complex. Enhanced PP2A activity induces dephosphorylation of the TJ proteins, ZO-1, occludin, and claudin-1, and is associated with increased paracellular permeability. Expression of PP2A catalytic subunit severely prevents TJ assembly. Conversely, inhibition of PP2A by okadaic acid promotes the phosphorylation and recruitment of ZO-1, occludin, and claudin-1 to the TJ during junctional biogenesis. PP2A negatively regulates TJ assembly without appreciably affecting the organization of F-actin and E-cadherin. Significantly, inhibition of atypical PKC (aPKC) blocks the calcium- and serum-independent membrane redistribution of TJ proteins induced by okadaic acid. Indeed, PP2A associates with and critically regulates the activity and distribution of aPKC during TJ formation. Thus, we provide the first evidence for calcium-dependent targeting of PP2A in epithelial cells, we identify PP2A as the first serine/threonine phosphatase associated with the multiprotein TJ complex, and we unveil a novel role for PP2A in the regulation of epithelial aPKC and TJ assembly and function. PMID:12196510

JPRS Report, Science & Technology, Japan, Powder Metallurgy Technology

DTIC Science & Technology

1988-12-13

100 mO« 132 Hz i i i i -K H JL x’ c-p’an« (film) ! f • j 0 60 70 M TOO 90 1C Figure 3. Real and...necessary to develop a new manufacturing process focusing on the control of grain orientation. References 1. M . Okada, et al., Jpn. J. Appl. Phys. 27...Tc drops as the amount of Sr added is increased. References 1. M . Oda, et al., Jpn. J. Phys., 26, L804, 1987. 2. Z. Qi-rui, et al., Solid State

Quantifying the errors due to the superposition of analytical deformation sources

NASA Astrophysics Data System (ADS)

Neuberg, J. W.; Pascal, K.

2012-04-01

The displacement field due to magma movement in the subsurface is often modelled using a Mogi point source or a dislocation Okada source embedded in a homogeneous elastic half-space. When the magmatic system cannot be modelled by a single source it is often represented by several sources, their respective deformation fields are superimposed. However, in such a case the assumption of homogeneity in the half-space is violated and the interaction between sources in an elastic medium is neglected. In this investigation we have quantified the effects of neglecting the interaction between sources on the surface deformation field. To do so, we calculated the vertical and horizontal displacements for models with adjacent sources and we tested them against the solutions of corresponding numerical 3D finite element models. We implemented several models combining spherical pressure sources and dislocation sources, varying the pressure or dislocation of the sources and their relative position. We also investigated three numerical methods to model a dike as a dislocation tensile source or as a pressurized tabular crack. We found that the discrepancies between simple superposition of the displacement field and a fully interacting numerical solution depend mostly on the source types and on their spacing. The errors induced when neglecting the source interaction are expected to vary greatly with the physical and geometrical parameters of the model. We demonstrated that for certain scenarios these discrepancies can be neglected (<5%) when the sources are separated by at least 4 radii for two combined Mogi sources and by at least 3 radii for juxtaposed Mogi and Okada sources

Monitoring and inversion on land subsidence over mining area with InSAR technique

USGS Publications Warehouse

Wang, Y.; Zhang, Q.; Zhao, C.; Lu, Z.; Ding, X.

2011-01-01

The Wulanmulun town, located in Inner Mongolia, is one of the main mining areas of Shendong Company such as Shangwan coal mine and Bulianta coal mine, which has been suffering serious mine collapse with the underground mine withdrawal. We use ALOS/PALSAR data to extract land deformation under these regions, in which Small Baseline Subsets (SBAS) method was applied. Then we compared InSAR results with the underground mining activities, and found high correlations between them. Lastly we applied Distributed Dislocation (Okada) model to invert the mine collapse mechanism. ?? 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Total cylindrospermopsins, microcystins/nodularins, and saxitoxins data for the 2007 United States Environmental Protection Agency National Lake Assessment

USGS Publications Warehouse

Loftin, Keith A.; Dietze, Julie E.; Meyer, Michael T.; Graham, Jennifer L.; Maksimowicz, Megan M.; Toyne, Kathryn D.

2016-05-26

At least one microcystin congener was detected by LC/MS/MS in 52 percent of the 27 samples analyzed at a concentration greater than the LC/MS/MS minimum reporting level (MRL) of 0.010 μg/L and included detections for microcystin-LA, microcystin-LR, microcystin-LY, microcystin-RR, and microcystin-YR. Anatoxin-a, cylindrospermopsin, and nodularin-R were detected in 15 percent, 7 percent, and 4 percent of samples, respectively, at concentrations above 0.010 μg/L. Deoxycylindrospermopsin, domoic acid, lyngbyatoxin-a, microcystin-LF, microcystin-LW, and okadaic acid were not detected in the LC/MS/MS subset.

Economic dynamics with financial fragility and mean-field interaction: A model

NASA Astrophysics Data System (ADS)

Di Guilmi, C.; Gallegati, M.; Landini, S.

2008-06-01

Following Aoki’s statistical mechanics methodology [Masanao Aoki, New Approaches to Macroeconomic Modeling, Cambridge University Press, 1996; Masanao Aoki, Modeling Aggregate Behaviour and Fluctuations in Economics, Cambridge University Press, 2002; Masanao Aoki, and Hiroshi Yoshikawa, Reconstructing Macroeconomics, Cambridge University Press, 2006], we provide some insights into the well-known works of [Bruce Greenwald, Joseph Stiglitz, Macroeconomic models with equity and credit rationing, in: R. Hubbard (Ed.), Information, Capital Markets and Investment, Chicago University Press, Chicago, 1990; Bruce Greenwald, Joseph Stiglitz, Financial markets imperfections and business cycles, Quarterly journal of Economics (1993)]. Specifically, we reach analytically a closed form solution of their models overcoming the aggregation problem. The key idea is to represent the economy as an evolving complex system, composed by heterogeneous interacting agents, that can be partitioned into a space of macroscopic states. This meso level of aggregation permits to adopt mean-field interaction modeling and master equation techniques.

Insect peptide CopA3-induced protein degradation of p27Kip1 stimulates proliferation and protects neuronal cells from apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nam, Seung Taek; Kim, Dae Hong; Lee, Min Bum

2013-07-19

Highlights: •CopA3 peptide isolated from the Korean dung beetle has antimicrobial activity. •Our study reported that CopA3 has anticancer and immunosuppressive effects. •We here demonstrated that CopA3 has neurotropic and neuroprotective effects. •CopA3 degrades p27Kip1 protein and this mediates effects of CopA3 on neuronal cells. -- Abstract: We recently demonstrated that the antibacterial peptide, CopA3 (a D-type disulfide dimer peptide, LLCIALRKK), inhibits LPS-induced macrophage activation and also has anticancer activity in leukemia cells. Here, we examined whether CopA3 could affect neuronal cell proliferation. We found that CopA3 time-dependently increased cell proliferation by up to 31 ± 2% in human neuroblastomamore » SH-SY5Y cells, and up to 29 ± 2% in neural stem cells isolated from neonatal mouse brains. In both cell types, CopA3 also significantly inhibited the apoptosis and viability losses caused by 6-hydroxy dopamine (a Parkinson disease-mimicking agent) and okadaic acid (an Alzheimer’s disease-mimicking agent). Immunoblotting revealed that the p27Kip1 protein (a negative regulator of cell cycle progression) was markedly degraded in CopA3-treated SH-SY5Y cells. Conversely, an adenovirus expressing p27Kip1 significantly inhibited the antiapoptotic effects of CopA3 against 6-hydroxy dopamine- and okadaic acid-induced apoptosis, and decreased the neurotropic effects of CopA3. These results collectively suggest that CopA3-mediated protein degradation of p27Kip1 may be the main mechanism through which CopA3 exerts neuroprotective and neurotropic effects.« less

Finite Element modelling of deformation induced by interacting volcanic sources

NASA Astrophysics Data System (ADS)

Pascal, Karen; Neuberg, Jürgen; Rivalta, Eleonora

2010-05-01

The displacement field due to magma movements in the subsurface is commonly modelled using the solutions for a point source (Mogi, 1958), a finite spherical source (McTigue, 1987), or a dislocation source (Okada, 1992) embedded in a homogeneous elastic half-space. When the magmatic system comprises more than one source, the assumption of homogeneity in the half-space is violated and several sources are combined, their respective deformation field being summed. We have investigated the effects of neglecting the interaction between sources on the surface deformation field. To do so, we calculated the vertical and horizontal displacements for models with adjacent sources and we tested them against the solutions of corresponding numerical 3D finite element models. We implemented several models combining spherical pressure sources and dislocation sources, varying their relative position. Furthermore we considered the impact of topography, loading, and magma compressibility. To quantify the discrepancies and compare the various models, we calculated the difference between analytical and numerical maximum horizontal or vertical surface displacements.We will demonstrate that for certain conditions combining analytical sources can cause an error of up to 20%. References: McTigue, D. F. (1987), Elastic Stress and Deformation Near a Finite Spherical Magma Body: Resolution of the Point Source Paradox, J. Geophys. Res. 92, 12931-12940. Mogi, K. (1958), Relations between the eruptions of various volcanoes and the deformations of the ground surfaces around them, Bull Earthquake Res Inst, Univ Tokyo 36, 99-134. Okada, Y. (1992), Internal Deformation Due to Shear and Tensile Faults in a Half-Space, Bulletin of the Seismological Society of America 82(2), 1018-1040.

Matrix effect and correction by standard addition in quantitative liquid chromatographic-mass spectrometric analysis of diarrhetic shellfish poisoning toxins.

PubMed

Ito, Shinya; Tsukada, Katsuo

2002-01-11

An evaluation of the feasibility of liquid chromatography-mass spectrometry (LC-MS) with atmospheric pressure ionization was made for quantitation of four diarrhetic shellfish poisoning toxins, okadaic acid, dinophysistoxin-1, pectenotoxin-6 and yessotoxin in scallops. When LC-MS was applied to the analysis of scallop extracts, large signal suppressions were observed due to coeluting substances from the column. To compensate for these matrix signal suppressions, the standard addition method was applied. First, the sample was analyzed and then the sample involving the addition of calibration standards is analyzed. Although this method requires two LC-MS runs per analysis, effective correction of quantitative errors was found.

Sensitivity of Tsunami Waves and Coastal Inundation/Runup to Seabed Displacement Models: Application to the Cascadia Subduction zone

NASA Astrophysics Data System (ADS)

Jalali Farahani, R.; Fitzenz, D. D.; Nyst, M.

2015-12-01

Major components of tsunami hazard modeling include earthquake source characterization, seabed displacement, wave propagation, and coastal inundation/run-up. Accurate modeling of these components is essential to identify the disaster risk exposures effectively, which would be crucial for insurance industry as well as policy makers to have tsunami resistant design of structures and evacuation planning (FEMA, 2008). In this study, the sensitivity and variability of tsunami coastal inundation due to Cascadia megathrust subduction earthquake are studied by considering the different approaches for seabed displacement model. The first approach is the analytical expressions that were proposed by Okada (1985, 1992) for the surface displacements and strains of rectangular sources. The second approach was introduced by Meade (2006) who introduced analytical solutions for calculating displacements, strains, and stresses on triangular sources. In this study, the seabed displacement using triangular representation of geometrically complex fault surfaces is compared with the Okada rectangular representations for the Cascadia subduction zone. In the triangular dislocation algorithm, the displacement is calculated using superposition of two angular dislocations for each of the three triangle legs. The triangular elements could give a better and gap-free representation of the fault surfaces. In addition, the rectangular representation gives large unphysical vertical displacement along the shallow-depth fault edge that generates unrealistic short-wavelength waves. To study the impact of these two different algorithms on the final tsunami inundation, the initial tsunami wave as well as wave propagation and the coastal inundation are simulated. To model the propagation of tsunami waves and coastal inundation, 2D shallow water equations are modeled using the seabed displacement as the initial condition for the numerical model. Tsunami numerical simulation has been performed on high

Effect of ethanol on hydrogen peroxide-induced AMPK phosphorylation.

PubMed

Liangpunsakul, Suthat; Wou, Sung-Eun; Zeng, Yan; Ross, Ruth A; Jayaram, Hiremagalur N; Crabb, David W

2008-12-01

AMP-activated protein kinase (AMPK) responds to oxidative stress. Previous work has shown that ethanol treatment of cultured hepatoma cells and of mice inhibited the activity of AMPK and reduced the amount of AMPK protein. Ethanol generates oxidative stress in the liver. Since AMPK is activated by reactive oxygen species, it seems paradoxical that ethanol would inhibit AMPK in the hepatoma cells. In an attempt to understand the mechanism whereby ethanol inhibits AMPK, we studied the effect of ethanol on AMPK activation by exogenous hydrogen peroxide. The effects of ethanol, hydrogen peroxide, and inhibitors of protein phosphatase 2A (PP2A) [either okadaic acid or PP2A small interference RNA (siRNA)] on AMPK phosphorylation and activity were examined in rat hepatoma cells (H4IIEC3) and HeLa cells. In H4IIEC3 cells, hydrogen peroxide (H(2)O(2), 1 mM) transiently increased the level of phospho-AMPK to 1.5-fold over control (P < 0.05). Similar findings were observed in HeLa cells, which do not express the upstream AMPK kinase, LKB1. H(2)O(2) markedly increased the phosphorylation of LKB1 in H4IIEC3 cells. Ethanol significantly inhibited the phosphorylation of PKC-zeta, LKB1, and AMPK caused by exposure to H(2)O(2). This inhibitory effect of ethanol required its metabolism. More importantly, the inhibitory effects of ethanol on H(2)O(2)-induced AMPK phosphorylation were attenuated by the presence of the PP2A inhibitor, okadaic acid, or PP2A siRNA. The inhibitory effect of ethanol on AMPK phosphorylation is exerted through the inhibition of PKC-zeta and LKB1 phosphorylation and the activation of PP2A.

Diarrhetic Shellfish Toxins and Other Lipophilic Toxins of Human Health Concern in Washington State

PubMed Central

Trainer, Vera L.; Moore, Leslie; Bill, Brian D.; Adams, Nicolaus G.; Harrington, Neil; Borchert, Jerry; da Silva, Denis A. M.; Eberhart, Bich-Thuy L.

2013-01-01

The illness of three people in 2011 after their ingestion of mussels collected from Sequim Bay State Park, Washington State, USA, demonstrated the need to monitor diarrhetic shellfish toxins (DSTs) in Washington State for the protection of human health. Following these cases of diarrhetic shellfish poisoning, monitoring for DSTs in Washington State became formalized in 2012, guided by routine monitoring of Dinophysis species by the SoundToxins program in Puget Sound and the Olympic Region Harmful Algal Bloom (ORHAB) partnership on the outer Washington State coast. Here we show that the DSTs at concentrations above the guidance level of 16 μg okadaic acid (OA) + dinophysistoxins (DTXs)/100 g shellfish tissue were widespread in sentinel mussels throughout Puget Sound in summer 2012 and included harvest closures of California mussel, varnish clam, manila clam and Pacific oyster. Concentrations of toxins in Pacific oyster and manila clam were often at least half those measured in blue mussels at the same site. The primary toxin isomer in shellfish and plankton samples was dinophysistoxin-1 (DTX-1) with D. acuminata as the primary Dinophysis species. Other lipophilic toxins in shellfish were pectenotoxin-2 (PTX-2) and yessotoxin (YTX) with azaspiracid-2 (AZA-2) also measured in phytoplankton samples. Okadaic acid, azaspiracid-1 (AZA-1) and azaspiracid-3 (AZA-3) were all below the levels of detection by liquid chromatography tandem mass spectrometry (LC-MS/MS). A shellfish closure at Ruby Beach, Washington, was the first ever noted on the Washington State Pacific coast due to DSTs. The greater than average Fraser River flow during the summers of 2011 and 2012 may have provided an environment conducive to dinoflagellates and played a role in the prevalence of toxigenic Dinophysis in Puget Sound. PMID:23760013

Diarrhetic shellfish toxins and other lipophilic toxins of human health concern in Washington State.

PubMed

Trainer, Vera L; Moore, Leslie; Bill, Brian D; Adams, Nicolaus G; Harrington, Neil; Borchert, Jerry; da Silva, Denis A M; Eberhart, Bich-Thuy L

2013-05-28

The illness of three people in 2011 after their ingestion of mussels collected from Sequim Bay State Park, Washington State, USA, demonstrated the need to monitor diarrhetic shellfish toxins (DSTs) in Washington State for the protection of human health. Following these cases of diarrhetic shellfish poisoning, monitoring for DSTs in Washington State became formalized in 2012, guided by routine monitoring of Dinophysis species by the SoundToxins program in Puget Sound and the Olympic Region Harmful Algal Bloom (ORHAB) partnership on the outer Washington State coast. Here we show that the DSTs at concentrations above the guidance level of 16 μg okadaic acid (OA) + dinophysistoxins (DTXs)/100 g shellfish tissue were widespread in sentinel mussels throughout Puget Sound in summer 2012 and included harvest closures of California mussel, varnish clam, manila clam and Pacific oyster. Concentrations of toxins in Pacific oyster and manila clam were often at least half those measured in blue mussels at the same site. The primary toxin isomer in shellfish and plankton samples was dinophysistoxin-1 (DTX-1) with D. acuminata as the primary Dinophysis species. Other lipophilic toxins in shellfish were pectenotoxin-2 (PTX-2) and yessotoxin (YTX) with azaspiracid-2 (AZA-2) also measured in phytoplankton samples. Okadaic acid, azaspiracid-1 (AZA-1) and azaspiracid-3 (AZA-3) were all below the levels of detection by liquid chromatography tandem mass spectrometry (LC-MS/MS). A shellfish closure at Ruby Beach, Washington, was the first ever noted on the Washington State Pacific coast due to DSTs. The greater than average Fraser River flow during the summers of 2011 and 2012 may have provided an environment conducive to dinoflagellates and played a role in the prevalence of toxigenic Dinophysis in Puget Sound.

Cytokinins and auxins control the expression of a gene in Nicotiana plumbaginifolia cells by feedback regulation.

PubMed Central

Dominov, J A; Stenzler, L; Lee, S; Schwarz, J J; Leisner, S; Howell, S H

1992-01-01

Both cytokinin (N6-benzyladenine [BA]) and auxin (2,4-dichlorophenoxyacetic acid [2,4-D]) stimulate the accumulation of an mRNA, represented by the cDNA pLS216, in Nicotiana plumbaginifolia suspension culture cells. The kinetics of RNA accumulation were different for the two hormones; however, the response to both was transient, and the magnitude of the response was dose dependent. Runoff transcription experiments demonstrated that the transient appearance of the RNA could be accounted for by feedback regulation of transcription and not by the induction of an RNA degradation system. The feedback mechanism appeared to desensitize the cells to further exposure of the hormone. In particular, cells became refractory to the subsequent addition of 2,4-D after the initial RNA accumulation response subsided. A very different response was observed when the second hormone was added to cells that had been desensitized to the first hormone. Under such conditions, BA produced a heightened response in cells desensitized to 2,4-D and vice versa. These findings support a model in which cytokinin further enhances the auxin response or prevents its feedback inhibition. The hormone-induced RNA accumulation was blocked by the protein kinase inhibitor staurosporin. On the other hand, the protein phosphatase inhibitor okadaic acid stimulated expression, and, in particular, okadaic acid was able to stimulate RNA accumulation in cells desensitized to auxin. This suggests that hormone activation involves phosphorylation of critical proteins on the hormone signaling pathway, whereas feedback inhibition may involve dephosphorylation of these proteins. The sequence of pLS216 is similar to genes in other plants that are stimulated by multiple agonists such as auxins, elicitors, and heavy metals, and to the gene encoding the stringent starvation protein in Escherichia coli. It is proposed that this gene family in various plants be called multiple stimulus response (msr) genes. PMID:1498603

[Validation Study for Analytical Method of Diarrhetic Shellfish Poisons in 9 Kinds of Shellfish].

PubMed

Yamaguchi, Mizuka; Yamaguchi, Takahiro; Kakimoto, Kensaku; Nagayoshi, Haruna; Okihashi, Masahiro; Kajimura, Keiji

2016-01-01

A method was developed for the simultaneous determination of okadaic acid, dinophysistoxin-1 and dinophysistoxin-2 in shellfish using ultra performance liquid chromatography with tandem mass spectrometry. Shellfish poisons in spiked samples were extracted with methanol and 90% methanol, and were hydrolyzed with 2.5 mol/L sodium hydroxide solution. Purification was done on an HLB solid-phase extraction column. This method was validated in accordance with the notification of Ministry of Health, Labour and Welfare of Japan. As a result of the validation study in nine kinds of shellfish, the trueness, repeatability and within-laboratory reproducibility were 79-101%, less than 12 and 16%, respectively. The trueness and precision met the target values of notification.

Saxitoxins and okadaic acid group: accumulation and distribution in invertebrate marine vectors from Southern Chile.

PubMed

García, Carlos; Pérez, Francisco; Contreras, Cristóbal; Figueroa, Diego; Barriga, Andrés; López-Rivera, Américo; Araneda, Oscar F; Contreras, Héctor R

2015-01-01

Harmful algae blooms (HABs) are the main source of marine toxins in the aquatic environment surrounding the austral fjords in Chile. Huichas Island (Aysén) has an history of HABs spanning more than 30 years, but there is limited investigation of the bioaccumulation of marine toxins in the bivalves and gastropods from the Region of Aysén. In this study, bivalves (Mytilus chilenses, Choromytilus chorus, Aulacomya ater, Gari solida, Tagelus dombeii and Venus antiqua) and carnivorous gastropods (Argobuccinum ranelliformes and Concholepas concholepas) were collected from 28 sites. Researchers analysed the accumulation of STX-group toxins using a LC with a derivatisation post column (LC-PCOX), while lipophilic toxins (OA-group, azapiracids, pectenotoxins and yessotoxins) were analysed using LC-MS/MS with electrospray ionisation (+/-) in visceral (hepatopancreas) and non-visceral tissues (mantle, adductor muscle, gills and foot). Levels of STX-group and OA-group toxins varied among individuals from the same site. Among all tissue samples, the highest concentrations of STX-group toxins were noted in the hepatopancreas in V. antiqua (95 ± 0.1 μg STX-eq 100 g(-1)), T. dombeii (148 ± 1.4 μg STX-eq 100 g(-1)) and G. solida (3232 ± 5.2 μg STX-eq 100 g(-1); p < 0.05); in the adductor muscle in M. chilensis (2495 ± 6.4 μg STX-eq 100 g(-1); p < 0.05) and in the foot in C. concholepas (81 ± 0.7 μg STX-eq 100 g(-1)) and T. dombeii (114 ± 1.2 μg STX-eq 100 g(-1)). The highest variability of toxins was detected in G. solida, where high levels of carbamate derivatives were identified (GTXs, neoSTX and STX). In addition to the detected hydrophilic toxins, OA-group toxins were detected (OA and DTX-1) with an average ratio of ≈1:1. The highest levels of OA-group toxins were in the foot of C. concholepas, with levels of 400.3 ± 3.6 μg OA eq kg(-1) (p < 0.05) and with a toxic profile composed of 90% OA. A wide range of OA-group toxins was detected in M. chilensis with a toxicity < 80 μg OA eq kg(-1), but with 74% of those toxins detected in the adductor muscle. In all evaluated species, there was no detection of lipophilic toxins associated with biotransformation in molluscs and carnivorous gastropods. In addition, the STX-group and OA-group toxin concentrations in shellfish was not associated with the presence of HAB. The ranking of toxin concentration in the tissues of most species was: digestive glands > mantle > adductor muscle for the STX-group toxins and foot > digestive gland for the OA-group toxins. These results gave a better understanding of the variability and compartmentalisation of STX-group and OA-group toxins in different bivalve and gastropod species from the south of Chile, and the analyses determined that tissues could play an important role in the biotransformation of STX-group toxins and the retention of OA-group toxins.

[Neurology in Japan before World War II].

PubMed

Takahashi, Akira

2013-01-01

Modern Western medicine was introduced into Japan by a Dutch doctor Pompe van Meerdervoort in 1855. A German physician EOE von Balz devoted himself to educating medicine at Tokyo Medical School, the predecessor of the present University of Tokyo for 25 years. Hiroshi Kawahara and Kinnosuke Miura, pioneers of Japan Neurology, received their education by him. Kawahara first described X-linked bulvo-spinal muscular atrophy, and published the first Japanese textbook of clinical neurology in 1897. In 1902, Miura and others founded the Japanese Society of Neuro-Psychiatry, the forerunner of the present " Japanese Society of Neurology ". Both Seizo Katsunuma, Professor of Nagoya University, and Junnjiro Kato, Professor of Tohoku University, succeeded Miura's neurology. Miura investigated into the cause of beriberi, but ended in failure. Hasegawa's proposal at the Diet in 1894 that the Japan Government should found an independent department of neurology in the University of Tokyo was unfortunately rejected. There was no foundation of independent institute, department and clinic of neurology before World War II. Consequently Japanese neurology was on the ebb at that time.

Impact of Sleeping Altitude on Symptoms of Acute Mountain Sickness on Mt. Fuji.

PubMed

Horiuchi, Masahiro; Uno, Tadashi; Endo, Junko; Handa, Yoko; Hasegawa, Tatsuya

2018-05-09

Horiuchi, Masahiro, Tadashi Uno, Junko Endo, Yoko Handa, and Tatsuya Hasegawa. Impact of sleeping altitude on symptoms of acute mountain sickness on Mt. Fuji. High Alt Med Biol. 00:000-000, 2018. We sought to investigate the factors influencing acute mountain sickness (AMS) on Mt. Fuji in Japan, in particular, to assess the effects of sleeping altitude, by means of a questionnaire survey. This study involved 1932 participants who climbed Mt. Fuji, and obtained information regarding sex, age, and whether participants stayed at the mountain lodges. The AMS survey excluded the perceived sleep difficulties assessed with the Lake Louise Scoring (LLS) system for all climbers. The overall prevalence of AMS was 31.6% for all participants (LLS score ≥3 with headache, excluding sleep difficulties). A univariate analysis revealed that overnight stay at Mt. Fuji was associated with an increased prevalence of AMS, but that sex and age were not. For overnight lodgers, the mean sleeping altitude in participants with AMS was slightly higher than that in participants without AMS (p < 0.05). Moreover, participants who stayed above 2870 m were more likely to experience AMS than those who stayed below 2815 m (p < 0.001), but sex and age were not significantly associated with the probability of experiencing AMS. Staying overnight at a mountain lodge, especially one above 2870 m, may be associated with an increased prevalence of AMS on Mt. Fuji.

PREFACE: IUMRS-ICA 2008 Symposium, Sessions 'X. Applications of Synchrotron Radiation and Neutron Beam to Soft Matter Science' and 'Y. Frontier of Polymeric Nano-Soft-Materials - Precision Polymer Synthesis, Self-assembling and Their Functionalization'

NASA Astrophysics Data System (ADS)

Takahara, Atsushi; Kawahara, Seiichi

2009-09-01

Tashiro (Toyota Technological Institute) Professor Kazuo Sakurai(Kitakyushu University) Professor Keiji Tanaka (Kyushu University) Dr Sono Sasaki (JASRI/Spring-8) Professor Naoya Torikai (KENS) Professor Moonhor Ree (POSTECH) Professor Kookheon Char (Seoul National University) Professor Charles C Han (CAS) Professor Atsushi Takahara(Kyushu University) Frontier of Polymeric Nano-Soft-Materials, Precision Polymer Synthesis, Self-assembling and Their Functionalization (Symposium Y of IUMRS-ICA2008) Seiichi Kawahara, Rong-Ming Ho, Hiroshi Jinnai, Masami Kamigaito, Takashi Miyata, Hiroshi Morita, Hideyuki Otsuka, Daewon Sohn, Keiji Tanaka It is our great pleasure and honor to publish peer-reviewed papers, presented in Symposium Y 'Frontier of Polymeric Nano-Soft-Materials Precision Polymer Synthesis, Self-assembling and Their Functionalization' at the International Union of Materials Research Societies International Conference in Asia 2008 (IUMRS-ICA2008), which was held on 9-13 December 2008, at Nagoya Congress Center, Nagoya, Japan. 'Polymeric nano-soft-materials' are novel outcomes based on a recent innovative evolution in polymer science, i.e. precision polymer synthesis, self-assembling and functionalization of multi-component systems. The materials are expected to exhibit specific functions and unique properties due to their hierarchic morphologies brought either by naturally-generated ordering or by artificial manipulation of the systems, e.g., crystallization and phase-separation. The emerging precision synthesis has brought out new types of polymers with well-controlled primary structures. Furthermore, the surface and interface of the material are recognized to play an important role in the outstanding mechanical, electrical and optical properties, which are required for medical and engineering applications. In order to understand structure-property relationships in the nano-soft-materials, it is indispensable to develop novel characterization techniques. Symposium Y

EDITORIAL: Focus on Heavy Ions in Biophysics and Medical Physics FOCUS ON HEAVY IONS IN BIOPHYSICS AND MEDICAL PHYSICS

NASA Astrophysics Data System (ADS)

Durante, Marco

2008-07-01

include carcinogenesis, late degenerative tissue effects (including damage to the central nervous system), and hereditary effects. For these studies, microbeams represent an essential tool, considering that in space each cell in the human body will not experience more than one heavy-ion traversal. Both NASA and ESA are investing important resources in ground-based space radiation research programs, to reduce risk uncertainty and to develop countermeasures. For both cancer therapy and space radiation protection a better understanding of the effects of energetic heavy ions is needed. Physics should be improved, especially the measurements of nuclear fragmentation cross-sections, and the transport calculations. Biological effects need to be studied in greater detail, and clearly only understanding the mechanisms of heavy-ion induced biological damage will reduce the uncertainty on late effects in humans. This focus issue of New Journal of Physics aims to provide the state-of-the-art of the biophysics of energetic heavy ions and to highlight the areas where more research is urgently needed for therapy and the space program. Focus on Heavy Ions in Biophysics and Medical Physics Contents Heavy ion microprobes: a unique tool for bystander research and other radiobiological applications K O Voss, C Fournier and G Taucher-Scholz Heavy ions light flashes and brain functions: recent observations at accelerators and in spaceflight L Narici Clinical advantages of carbon-ion radiotherapy Hirohiko Tsujii, Tadashi Kamada, Masayuki Baba, Hiroshi Tsuji, Hirotoshi Kato, Shingo Kato, Shigeru Yamada, Shigeo Yasuda, Takeshi Yanagi, Hiroyuki Kato, Ryusuke Hara, Naotaka Yamamoto and Junetsu Mizoe Heavy-ion effects: from track structure to DNA and chromosome damage F Ballarini, D Alloni, A Facoetti and A Ottolenghi Shielding experiments with high-energy heavy ions for spaceflight applications C Zeitlin, S Guetersloh, L Heilbronn, J Miller, N Elkhayari, A Empl, M LeBourgeois, B W Mayes, L Pinsky

Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

PubMed

Mantani, Akio; Kato, Tadashi; Furukawa, Toshi A; Horikoshi, Masaru; Imai, Hissei; Hiroe, Takahiro; Chino, Bun; Funayama, Tadashi; Yonemoto, Naohiro; Zhou, Qi; Kawanishi, Nao

2017-11-03

on BDI-II and 0.76 points (95% CI -0.05 to 1.58, P=.07) lower on FIBSER. In the per-protocol sample (comfortable with the smartphone app, still symptomatic, and adherent to medication with mild or less side effects after run-in), the intervention group (n=60) scored 1.72 points (95% CI 0.25-3.18, P=.02) lower on PHQ-9, 3.2 points (95% CI -0.01 to 6.3, P=.05) lower on BDI-II, and 0.75 points (95% CI 0.03-1.47, P=.04) lower on FIBSER than the control (n=57). The treatment benefits were maintained up to week 17. This is the first study to demonstrate the effectiveness of a smartphone CBT in the treatment of clinically diagnosed depression. Given the merits of the mobile mental health intervention, including accessibility, affordability, quality control, and effectiveness, it is clinically worthwhile to consider adjunctive use of a smartphone CBT app when treating patients with antidepressant-resistant depression. Research into its effectiveness in wider clinical contexts is warranted. Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik). ©Akio Mantani, Tadashi Kato, Toshi A Furukawa, Masaru Horikoshi, Hissei Imai, Takahiro Hiroe, Bun Chino, Tadashi Funayama, Naohiro Yonemoto, Qi Zhou, Nao Kawanishi. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 03.11.2017.

Monitoring of DSP toxins in small-sized plankton fraction of seawater collected in Mutsu Bay, Japan, by ELISA method: relation with toxin contamination of scallop.

PubMed

Imai, Ichiro; Sugioka, Hikaru; Nishitani, Goh; Mitsuya, Tadashi; Hamano, Yonekazu

2003-01-01

Monitorings were conducted on DSP toxins in mid-gut gland of scallop (mouse assay), cell numbers of toxic dinoflagellate species of Dinophysis, and diarrhetic shellfish poisoning (DSP) toxins in small-sized (0.7-5 microm) plankton fraction of seawater collected from surface (0 m) and 20 m depth at a station in Mutsu Bay, Aomori Prefecture, Japan, in 2000. A specific enzyme-linked immunosorbent assay (ELISA) was employed for the analysis of DSP toxins in small-sized plankton fraction using a mouse monoclonal anti-okadaic acid antibody which recognizes okadaic acid, dinophysistoxin-1, and dinophysistoxin-3. DSP toxins were detected twice in the mid-gut gland of scallops at 1.1-2.3 MU (mouse units) g(-1) on 26 June and at 0.6-1.2 MU g(-1) on 3 July, respectively. Relatively high cell densities of D. fortii were observed on 26 June and 11 September, and may only contribute to the bivalve toxicity during late June to early July. D. acuminata did not appear to be responsible for the toxicity of scallops in Mutsu Bay in 2000. ELISA monitoring of small-sized plankton fraction in seawater could detect DSP toxins two weeks before the detection of the toxin in scallops, and could do so two weeks after the loss of the bivalve toxicity by mouse assay. On 17 July, toxic D. fortii was detected at only small number, <10 cells l(-1), but DSP toxins were detected by the ELISA assay, suggesting a presence of other toxic small-sized plankton in seawater. For the purpose of reducing negative impacts of DSP occurrences, monitorings have been carried out hitherto on DSP toxins of bivalve tissues by mouse assay and on cell densities of "toxic" species of Dinophysis. Here we propose a usefulness of ELISA monitoring of plankton toxicity, especially in small-sized fraction, which are possible foods of mixotrophic Dinophysis, as a practical tool for detecting and predicting DSPs in coastal areas of fisheries grounds of bivalve aquaculture.

Multiple Signals Regulate PLC beta 3 in Human Myometrial Cells

PubMed Central

Zhong, Miao; Murtazina, Dilyara A.; Phillips, Jennifer; Ku, Chun-Ying; Sanborn, Barbara M.

2008-01-01

Summary The regulation of PLCB3-Serine1105 phosphorylation by both negative feedback and negative crosstalk facilitates the integration of multiple signaling pathways in myometrial cells. Phospholipase CB3 (PLCB3) Serine1105, a substrate for multiple protein kinases, represents a potential point of convergence of several signaling pathways in the myometrium. To explore this hypothesis, the regulation of PLCB3-Serine1105 phosphorylation (P-S1105) was studied in immortalized and primary human myometrial cells. CPT-cAMP and calcitonin gene-related peptide (CALCA) transiently increased P-S1105. Relaxin also stimulated P-S1105; this effect was partially blocked by the protein kinase A (PRKA) inhibitor Rp-8-CPT-cAMPS. Oxytocin, which stimulates Gαq-mediated pathways, also rapidly increased P-S1105, as did PGF2α and ATP. Oxytocin-stimulated phosphorylation was blocked by the protein kinase C (PRKC) inhibitor Go6976 and by pretreatment overnight with a phorbol ester. Cypermethrin, a PP2B phosphatase inhibitor, but not okadaic acid, a PP1/PP2A inhibitor, prolonged the effect of CALCA on P-S1105, whereas the reverse was the case for the oxytocin-stimulated increase in P-S1105. PLCB3 was the predominant PLC isoform expressed in the myometrial cells and PLCB3 shRNA constructs significantly attenuated oxytocin-stimulated increases in intracellular calcium. Oxytocin-induced phosphatidylinositol (PI) turnover was inhibited by CPT-cAMP and okadaic acid but enhanced by pretreatment with Go6976. CPT-cAMP inhibited oxytocin-stimulated PI turnover in the presence of overexpressed PLCB3, but not overexpressed PLCB3-S1105A. These data demonstrate that both negative crosstalk from the cAMP/PRKA pathway and a negative feedback loop in the oxytocin/G protein/PLCB pathway involving PRKC operate in myometrial cells and suggest that different protein phosphatases predominate in mediating P-S1105 dephosphorylation in these pathways. The integration of multiple signal components at the level

Determination of the variability of both hydrophilic and lipophilic toxins in endemic wild bivalves and carnivorous gastropods from the southern part of Chile.

PubMed

Zamorano, Ruben; Marín, Michelle; Cabrera, Fabiola; Figueroa, Diego; Contreras, Cristóbal; Barriga, Andrés; Lagos, Néstor; García, Carlos

2013-01-01

The aim of this study was to analyse and determine the composition of paralytic shellfish poisoning (PSP) toxins and lipophilic toxins in the Region of Aysén, Chile, in wild endemic mussels (Mytilus chilensis, Venus antiqua, Aulacomya ater, Choromytilus chorus, Tagelus dombeii and Gari solida) and in two endemic carnivorous molluscs species (Concholepas concholepas and Argobuccinum ranelliforme). PSP-toxin contents were determined by using HPLC with fluorescence detection, while lipophilic toxins were determined by using LC-MS/MS. Mean concentrations for the total of PSP toxins were in the range 55-2505 μg saxitoxin-equivalent/100 g. The two most contaminated samples for PSP toxicity were bivalve Gari solida and carnivorous Argobuccinum ranelliforme with 2505 ± 101 and 1850 ± 137 μg saxitoxin-equivalent/100 g, respectively (p < 0.05). The lipophilic toxins identified were okadaic acid, dinophysistoxin-1 (DTX-1), azaspiracid-1 (AZA-1), pectenotoxin-2 (PTX-2) and yessotoxins (YTX). All analysed molluscs contained lipophilic toxins at levels ranging from 56 ± 4.8 to 156.1 ± 8.2 μg of okadaic acid-equivalent/kg shellfish together with YTX at levels ranging from 1.0 ± 0.1 to 18 ± 0.9 μg of YTX-equivalent/kg shellfish and AZA at levels ranging from 3.6 ± 0.2 to 31 ± 2.1 μg of AZA-equivalent/kg shellfish. Furthermore, different bivalves and gastropods differ in their capacity of retention of lipophilic toxins, as shown by the determination of their respective lipophilic toxins levels. In all the evaluated species, the presence of lipophilic toxins associated with biotransformation in molluscs and carnivorous gastropods was not identified, in contrast to the identification of PSP toxins, where the profiles identified in the different species are directly related to biotransformation processes. Thus, this study provides evidence that the concentration of toxins in the food intake of the evaluated species (Bivalvia and Gastropoda class) determines the degree of

Curcumin Modulates the NMDA Receptor Subunit Composition Through a Mechanism Involving CaMKII and Ser/Thr Protein Phosphatases.

PubMed

Mallozzi, Cinzia; Parravano, Mariacristina; Gaddini, Lucia; Villa, Marika; Pricci, Flavia; Malchiodi-Albedi, Fiorella; Matteucci, Andrea

2018-05-30

Curcumin is one of the major compounds contained in turmeric, the powdered rhizome of Curcuma longa. Results obtained in various experimental models indicate that curcumin has the potential to treat a large variety of neuronal diseases. Excitotoxicity, the toxicity due to pathological glutamate receptors stimulation, has been considered to be involved in several ocular pathologies including ischemia, glaucoma, and diabetic retinopathy. The NMDA receptor (NMDAR), a heteromeric ligand-gated ion channel, is composed of GluN1 and GluN2 subunits. There are four GluN2 subunits (GluN2A-D), which are major determinants of the functional properties of NMDARs. It is widely accepted that GluN2B has a pivotal role in excitotoxicity while the role of GluN2A remains controversial. We previously demonstrated that curcumin is neuroprotective against NMDA-induced excitotoxicity with a mechanism involving an increase of GluN2A subunit activity. In this paper, we investigate the mechanisms involved in curcumin-induced GluN2A increase in retinal cultures. Our results show that curcumin treatment activated CaMKII with a time-course that paralleled those of GluN2A increase. Moreover, KN-93, a CaMKII inhibitor, was able to block the effect of curcumin on GluN2A expression. Finally, in our experimental model, curcumin reduced ser/thr phosphatases activity. Using okadaic acid, a specific PP1 and PP2A blocker, we observed an increase in GluN2A levels in cultures. The ability of okadaic acid to mimic the effect of curcumin on GluN2A expression suggests that curcumin might regulate GluN2A expression through a phosphatase-dependent mechanism. In conclusion, our findings indicate curcumin modulation of CaMKII and/or ser/thr phosphatases activities as a mechanism involved in GluN2A expression and neuroprotection against excitotoxicity.

The potential role of natural tumor promoters in marine turtle fibropapillomatosis

USGS Publications Warehouse

Landsberg, Jan H.; Balazs, G.H.; Steidinger, K.A.; Baden, D.G.; Work, Thierry M.; Russel, D.J.

1999-01-01

Fibropapillomatosis (FP) in green turtles Chelonia mydas is a debilitating, neoplastic disease that has reached worldwide epizootic levels. The etiology of FP is unknown but has been linked to oncogenic viruses. Toxic benthic dinoflagellates (Prorocentrum spp.) are not typically considered tumorigenic agents, yet they have a worldwide distribution and produce a tumor promoter, okadaic acid (OA). Prorocentrum spp. are epiphytic on macroalgae and seagrasses that are normal components of green turtle diets. Here we show that green turtles in the Hawaiian Islands consume Prorocentrum and that high-risk FP areas are associated with areas where P. lima and P. concavum are both highly prevalent and abundant. The presence of presumptive OA in the tissues of Hawaiian green turtles further suggests exposure and a potential role for this tumor promoter in the etiology of FP.

Flavonoids from Potentilla parvifolia Fisch. and Their Neuroprotective Effects in Human Neuroblastoma SH-SY5Y Cells in vitro.

PubMed

Yuan, Zhenzhen; Luan, Guangxiang; Wang, Zhenhua; Hao, Xueyan; Li, Ji; Suo, Yourui; Li, Gang; Wang, Honglun

2017-06-01

Potentilla parvifolia Fisch. (Rosaceae) is a traditional medicinal plant in P. R. China. In this study, seven flavonoids, ayanin (1), tricin (2), quercetin (3), tiliroside (4), miquelianin (5), isoquercitrin (6), and astragalin (7), were separated and purified from ethyl acetate extractive fractions from ethanol extracts of P. parvifolia using a combination of sevaral chromatographic methods. The human neuroblastoma SH-SY5Y cells were differentiated with all trans-retinoic acid and treated with okadaic acid to induce tau protein phosphorylation and synaptic atrophy, which could establish an Alzheimer's disease cell model. The neuroprotective effects of these flavonoids in cellular were evaluated in vitro by this cell model. Results from the Western blot and morphology analysis suggested that compounds 3 and 4 had the better neuroprotective effects. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Legionella pneumophila effector WipA, a bacterial PPP protein phosphatase with PTP activity.

PubMed

Jia, Qian; Lin, Yun; Gou, Xuejing; He, Lei; Shen, Dong; Chen, Dongni; Xie, Wei; Lu, Yongjun

2018-04-26

The gram-negative bacterium Legionella pneumophila invades human's lung and causes Legionnaires' disease. To benefit its survival and replication in cellular milieu, L. pneumophila secrets at least 330 effector proteins into host cells. We found that the effector WipA has the protein tyrosine phosphatase (PTP) activity but does not depend on the classical CX5R motif for activity, suggesting that WipA is an unconventional PTP. Meanwhile, the presence of three other highly conserved motifs typically seen in protein serine/threonine phosphatases and the poor inhibition of WipA activity by okadaic acid led us to propose that WipA is a bacterial protein phosphatase. In addition, the determination of the 2.55-Å crystal structure of WipA revealed that WipA resembles cold-active protein tyrosine phosphatase (CAPTPase), and therefore very likely shares the same catalytic mechanism.

Protein phosphatase 2A in stretch-induced endothelial cell proliferation

NASA Technical Reports Server (NTRS)

Murata, K.; Mills, I.; Sumpio, B. E.

1996-01-01

We previously proposed that activation of protein kinase C is a key mechanism for control of cell growth enhanced by cyclic strain [Rosales and Sumpio (1992): Surgery 112:459-466]. Here we examined protein phosphatase 1 and 2A activity in bovine aortic endothelial cells exposed to cyclic stain. Protein phosphatase 2A activity in the cytosol was decreased by 36.1% in response to cyclic strain for 60 min, whereas the activity in the membrane did not change. Treatment with low concentration (0.1 nM) of okadaic acid enhanced proliferation of both static and stretched endothelial cells in 10% fetal bovine serum. These data suggest that protein phosphatase 2A acts as a growth suppressor and cyclic strain may enhance cellular proliferation by inhibiting protein phosphatase 2A as well as stimulating protein kinase C.

Shear-wave polarization anisotropy in the mantle wedge beneath the southern part of Tohoku, Japan

NASA Astrophysics Data System (ADS)

Shimizu, J.; Nakajima, J.; Hasegawa, A.

2003-12-01

We investigated shear-wave polarization anisotropy in the mantle wedge beneath the southern part of Tohoku, Japan, by using waveform data of intermediate depth earthquakes with M>2.5 recorded by the seismic networks of Tohoku University and Japan Meteorological Agency (JMA). We selected waveform data with ray paths whose incident angles to the surface are 35 degrees or less to avoid contamination of particle motions by converted phases. All the seismograms thus selected were filtered with bandpassed ranges of 2-8 Hz. Cross-correlation method [Ando et al., 1983] was used for determining delay time between the leading and following shear-waves (delay time) and the leading shear-wave polarization direction (fast direction). Two horizontal components of observed seismograms were rotated with the direction from 0 to 180 degrees with an interval of 5 degrees, and shifted one horizontal component by a time lag. The time lag varied from 0 to 1 s with an interval of 0.01 s. The length of time window used to calculate correlation coefficient was set to be nearly equal to one cycle of the shear-wave. We do not use the data whose maximum correlation coefficient is less than 0.8. Obtained results show that most of the fast directions at stations in the back-arc side are nearly E-W, whereas those at stations in the fore-arc side are N-S. We infer that the anisotropy caused by lattice-preferred orientation of olivine, which is probably produced by flow in the mantle wedge, is a likely candidate for the observed shear-wave splitting with E-W trend fast directions in the back-arc side. Although it is not certain what causes the N-S trend fast directions in the for-arc side, the same trend is seen in the previous studies of other areas in Tohoku [Okada et al.,1995; Nakajima, 2002]. Observed delay times are mostly 0.1-0.3 s, which is consistent with the results of Okada et al. [1995] and Nakajima [2002]. Acknowledgments: We are grateful to the staff of the JMA for allowing us to use

Checking the validity of superimposing analytical deformation models and implications for numerical modelling of dikes and magma chambers

NASA Astrophysics Data System (ADS)

Pascal, K.; Neuberg, J. W.; Rivalta, E.

2011-12-01

The displacement field due to magma movements in the subsurface is commonly modelled using the solutions for a point source (Mogi, 1958), a finite spherical source (McTigue, 1987), or a dislocation source (Okada, 1992) embedded in a homogeneous elastic half-space. When the magmatic system is represented by several sources, their respective deformation fields are summed, and the assumption of homogeneity in the half-space is violated. We have investigated the effects of neglecting the interaction between sources on the surface deformation field. To do so, we calculated the vertical and horizontal displacements for models with adjacent sources and we tested them against the solutions of corresponding numerical 3D finite element models. We implemented several models combining spherical pressure sources and dislocation sources, varying the pressure or opening of the sources and their relative position. We also investigated various numerical methods to model a dike as a dislocation tensile source or as a pressurized tabular crack. In the former case, the dike opening was either defined as two boundaries displaced from a central location, or as one boundary displaced relative to the other. We finally considered two case studies based on Soufrière Hills Volcano (Montserrat, West Indies) and the Dabbahu rift segment (Afar, Ethiopia) magmatic systems. We found that the discrepancies between simple superposition of the displacement field and a fully interacting numerical solution depend mostly on the source types and on their spacing. Their magnitude may be comparable with the errors due to neglecting the topography, the inhomogeneities in crustal properties or more realistic rheologies. In the models considered, the errors induced when neglecting the source interaction can be neglected (<5%) when the sources are separated by at least 4 radii for two combined Mogi sources and by at least 3 radii for juxtaposed Mogi and Okada sources. Furthermore, this study underlines

The effect of material heterogeneities in long term multiscale seismic cycle simulations

NASA Astrophysics Data System (ADS)

Kyriakopoulos, C.; Richards-Dinger, K. B.; Dieterich, J. H.

2016-12-01

A fundamental part of the simulation of the earthquake cycles in large-scale multicycle earthquake simulators is the pre-computation of elastostatic Greens functions collected into the stiffness matrix (K). The stiffness matrices are typically based on the elastostatic solutions of Okada (1992), Gimbutas et al. (2012), or similar. While these analytic solutions are computationally very fast, they are limited to modeling a homogeneous isotropic half-space. It is thus unknown how such simulations may be affected by material heterogeneity characterizing the earth medium. We are currently working on the estimation of the effects of heterogeneous material properties in the earthquake simulator RSQSim (Richards-Dinger and Dieterich, 2012). In order to do that we are calculating elastostatic solutions in a heterogeneous medium using the Finite Element (FE) method instead of any of the analytical solutions. The investigated region is a 400 x 400 km area centered on the Anza zone in southern California. The fault system geometry is based on that of the UCERF3 deformation models in the area of interest, which we then implement in a finite element mesh using Trelis 15. The heterogeneous elastic structure is based on available tomographic data (seismic wavespeeds and density) for the region (SCEC CVM and Allam et al., 2014). For computation of the Greens functions we are using the open source FE code Defmod (https://bitbucket.org/stali/defmod/wiki/Home) to calculate the elastostatic solutions due to unit slip on each patch. Earthquake slip on the fault plane is implemented through linear constraint equations (Ali et al., 2014, Kyriakopoulos et al., 2013, Aagard et al, 2015) and more specifically with the use of Lagrange multipliers adjunction. The elementary responses are collected into the "heterogeneous" stiffness matrix Khet and used in RSQSim instead of the ones generated with Okada. Finally, we compare the RSQSim results based on the "heterogeneous" Khet with results from

Effects of Short-Term Acclimatization at the Summit of Mt. Fuji (3776 m) on Sleep Efficacy, Cardiovascular Responses, and Ventilatory Responses.

PubMed

Horiuchi, Masahiro; Oda, Shiro; Uno, Tadashi; Endo, Junko; Handa, Yoko; Fukuoka, Yoshiyuki

2017-06-01

Horiuchi, Masahiro, Shiro Oda, Tadashi Uno, Junko Endo, Yoko Handa, and Yoshiyuki Fukuoka. Effects of short-term acclimatization at the summit of Mt. Fuji (3776 m) on sleep efficacy, cardiovascular responses, and ventilatory responses. High Alt Med Biol. 18:171-178, 2017.-We investigated the effects of a short period of acclimatization, at 3776 m on Mt. Fuji, on sleep parameters and related physiological responses. Physiological responses were assessed in seven healthy lowlander men during both daytime and sleep while at sea level (SL), as well as for three consecutive nights at high altitude (HA; 3776 m, day 1 [D1], D2, D3, and morning only of D4). Blood pressure variables, heart rate (HR), pulmonary ventilation (V E ), and breathing frequency (Bf) progressively increased each day, with significant differences between SL and HA (p < 0.05, respectively). In contrast, end-tidal PCO 2 (P ET CO 2 ) progressively decreased each day with statistical differences between SL and D3 at HA (p < 0.05). During sleep at HA, mean arterial pressure (MAP) was stable, whereas it decreased during sleep at SL. Sleep efficacy, which was assessed by actigraphy, was linearly impaired with statistical differences between SL and D3 (p < 0.05). These impairments in sleep efficacy at HA were associated with higher MAP and HR, as well as lower Bf and P ET CO 2 during the daytime (pooled data, p < 0.05, respectively). These results suggest that hypoxia-induced cardiovascular and ventilatory responses may be crucial contributors to changes in sleep efficacy at HA.

PREFACE: International Conference on High Pressure Science and Technology, Joint AIRAPT-22 & HPCJ-50

NASA Astrophysics Data System (ADS)

Viña, Luis; Tejedor, Carlos; Calleja, José M.

2010-01-01

The International Joint AIRAPT-22 & HPCJ-50 Conference was held in Odaiba, Tokyo, on 26-31 July 2009. About 480 scientists from 24 countries attended the conference and 464 papers, including 3 plenary lectures, 39 invited talks, and 156 oral presentations, were presented. It is my great pleasure to present this proceedings volume, which is based on the high quality scientific works presented at the conference. The International AIRAPT conference has been held every two years in various countries around the world since 1965, while High Pressure Conference of Japan (HPCJ) has been held annually since 1959 in various Japanese cities. Pressure is a fundamental parameter to control the property of matter. As a result, both AIRAPT and HPCJ have become highly multidisciplinary, and cover Physics, Chemistry, Materials Science, Earth and Planetary Sciences, Biosciences, Food Science, and Technology. Although each discipline has a unique target, they all have high-pressure research in common. This proceedings volume includes about 200 papers of state-of-the-art studies from numerous fields. I hope this proceedings volume provides excellent pieces of information in various fields to further advance high-pressure research. Conference logo Takehiko Yagi Conference Chairman Institute for Solid State Physics The University of Tokyo 7 December 2009 Conference photograph Participants at the conference venue, Tokyo International Exchange Center, Odaiba, Tokyo, Japan. Editor in Chief TAKEMURA Kenichi National Institute for Materials Science, Japan Editorial board Tadashi KONDO Osaka University, Japan Hitoshi MATSUKI The University of Tokushima, Japan Nobuyuki MATUBAYASI Kyoto University, Japan Yoshihisa MORI Okayama University of Science, Japan Osamu OHTAKA Osaka University, Japan Chihiro SEKINE Muroran Institute of Technology, Japan

Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation.

PubMed

Amsailale, Rachid; Beyaert, Maxime; Smal, Caroline; Janssens, Veerle; Van Den Neste, Eric; Bontemps, Françoise

2014-03-03

Deoxycytidine kinase (dCK) is a critical enzyme for activation of anticancer nucleoside analogs. Its activity is controlled via Ser-74 phosphorylation. Here, we investigated which Ser/Thr phosphatase dephosphorylates Ser-74. In cells, the PP1/PP2A inhibitor okadaic acid increased both dCK activity and Ser-74 phosphorylation at concentrations reported to specifically target PP2A. In line with this, purified PP2A, but not PP1, dephosphorylated recombinant pSer-74-dCK. In cell lysates, the Ser-74-dCK phosphatase activity was found to be latent, Mn(2+)-activated, responsive to PP2A inhibitors, and diminished after PP2A-immunodepletion. Use of siRNAs allowed concluding definitively that PP2A constitutively dephosphorylates dCK in cells and negatively regulates its activity. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

[Effect of inhibitors serine/threonine protein kinases and protein phosphatases on mitosis progression of synchronized tobacco by-2 cells].

PubMed

Sheremet, Ia A; Emets, A I; Azmi, A; Vissenberg, K; Verbelen, J-P; Blium, Ia B

2012-01-01

In order to investigate the role of various serine/ threonine protein kinases and protein phosphatases in the regulation of mitosis progression in plant cells the influence of cyclin-dependent (olomoucine) and Ca2+ -calmodulin-dependent (W7) protein kinases inhibitors, as well as protein kinase C inhibitors (H7 and staurosporine) and protein phosphatases inhibitor (okadaic acid) on mitosis progression in synchronized tobacco BY-2 cells has been studied. It was found that BY-2 culture treatment with inhibitors of cyclin dependent protein kinases and protein kinase C causes prophase delay, reduces the mitotic index and displaces of mitotic peak as compare with control cells. Inhibition of Ca2+ -calmodulin dependent protein kinases enhances the cell entry into prophase and delays their exit from mitosis. Meanwhile inhibition of serine/threonine protein phosphatases insignificantly enhances of synchronized BY-2 cells entering into all phases of mitosis.

Graphene oxide-assisted non-immobilized SELEX of okdaic acid aptamer and the analytical application of aptasensor

NASA Astrophysics Data System (ADS)

Gu, Huajie; Duan, Nuo; Wu, Shijia; Hao, Liling; Xia, Yu; Ma, Xiaoyuan; Wang, Zhouping

2016-02-01

Okadaic acid (OA) is a low-molecular-weight marine toxin from shellfish that causes abdominal pain, vomiting and diarrhea, i.e., diarrheic shellfish poisoning. In this study, a ssDNA aptamer that specifically binds to OA with high affinity was obtained via Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assisted by graphene oxide (GO). This aptamer was then applied to fabricate a novel direct competitive enzyme-linked aptamer assay (ELAA). At the optimized conditions, this ELAA method showed a low detection limit (LOD of 0.01 ng/mL), wide linear range (from 0.025 to 10 ng/mL), good recovery rate (92.86-103.34% in OA-spiked clam samples) and repeatability (RSD of 2.28-4.53%). The proposed method can be used to detect OA in seafood products with high sensitivity and can potentially be adapted for the determination of other small molecular analytes.

Conference Committees: Conference Committees

NASA Astrophysics Data System (ADS)

2009-09-01

International Programm Committee (IPC) Harald Ade NCSU Sadao Aoki University Tsukuba David Attwood Lawrence Berkeley National Laboratory/CXRO Christian David Paul Scherrer Institut Peter Fischer Lawrence Berkeley National Laboratory Adam Hitchcock McMaster University Chris Jacobsen SUNY, Stony Brook Denis Joyeux Lab Charles Fabry de l'Institut d'Optique Yasushi Kagoshima University of Hyogo Hiroshi Kihara Kansai Medical University Janos Kirz SUNY Stony Brook Maya Kiskinova ELETTRA Ian McNulty Argonne National Lab/APS Alan Michette Kings College London Graeme Morrison Kings College London Keith Nugent University of Melbourne Zhu Peiping BSRF Institute of High Energy Physics Francois Polack Soleil Christoph Quitmann Paul Scherrer Institut Günther Schmahl University Göttingen Gerd Schneider Bessy Hyun-Joon Shin Pohang Accelerator Lab Jean Susini ESRF Mau-Tsu Tang NSRRC Tony Warwick Lawrence Berkeley Lab/ALS Local Organizing Committee Christoph Quitmann Chair, Scientific Program Charlotte Heer Secretary Christian David Scientific Program Frithjof Nolting Scientific Program Franz Pfeiffer Scientific Program Marco Stampanoni Scientific Program Robert Rudolph Sponsoring, Financials Alfred Waser Industry Exhibition Robert Keller Public Relation Markus Knecht Computing and WWW Annick Cavedon Proceedings and Excursions and Accompanying Persons Program Margrit Eichler Excursions and Accompanying Persons Program Kathy Eikenberry Excursions and Accompanying Persons Program Marlies Locher Excursions and Accompanying Persons Program

Effect of the industrial canning on the toxicity of mussels contaminated with diarrhetic shellfish poisoning (DSP) toxins.

PubMed

Blanco, Juan; Arévalo, Fabiola; Correa, Jorge; Porro, M Corina; Cabado, Ana G; Vieites, Juan M; Moroño, Angeles

2016-03-15

The effect of canning in pickled sauce and autoclaving on weight, toxin content, toxin concentration and toxicity of steamed mussels was studied. Weight decreased by 25.5%. Okadaic acid (OA) and DTX2 content of mussel meat decreased by 24.1 and 42.5%, respectively. The estimated toxicity of the mussel remained nearly unchanged (increased by 2.9%). A part of the toxins lost by the mussels was leached to the sauce but the remaining part should have been thermally degraded. DTX2 underwent more degradation than OA and, in both toxins, free forms more than conjugated ones. This process, therefore, cannot be responsible for the large increments of toxicity of processed mussels -relative to the raw ones-sometimes detected by food processing companies. The final product could be monitored in several ways, but analysing the whole can content or the mussel meat once rehydrated seems to be the most equivalents to the raw mussel controls. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of internal structure on equilibrium of field-reversed configuration plasma sustained by rotating magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yambe, Kiyoyuki; Inomoto, Michiaki; Okada, Shigefumi

The effects of an internal structure on the equilibrium of a field-reversed configuration (FRC) plasma sustained by rotating magnetic field is investigated by using detailed electrostatic probe measurements in the FRC Injection Experiment apparatus [S. Okada, et al., Nucl. Fusion. 45, 1094 (2005)]. An internal structure installed axially on the geometrical axis, which simulates Ohmic transformer or external toroidal field coils on the FRC device, brings about substantial changes in plasma density profile. The internal structure generates steep density-gradients not only on the inner side but on the outer side of the torus. The radial electric field is observed tomore » sustain the ion thermal pressure-gradient in the FRC without the internal structure; however, the radial electric field is not sufficient to sustain the increased ion thermal pressure-gradient in the FRC with the internal structure. Spontaneously driven azimuthal ion flow will be accountable for the imbalance of the radial pressure which is modified by the internal structure.« less

Short term memory bowing effect is consistent with presentation rate dependent decay.

PubMed

Tarnow, Eugen

2010-12-01

I reanalyze the free recall data of Murdock, J Exp Psychol 64(5):482-488 (1962) and Murdock and Okada, J Verbal Learn and Verbal Behav 86:263-267 (1970) which show the famous bowing effect in which initial and recent items are recalled better than intermediate items (primacy and recency effects). Recent item recall probabilities follow a logarithmic decay with time of recall consistent with the tagging/retagging theory. The slope of the decay increases with increasing presentation rate. The initial items, with an effectively low presentation rate, decay with the slowest logarithmic slope, explaining the primacy effect. The finding that presentation rate limits the duration of short term memory suggests a basis for memory loss in busy adults, for the importance of slow music practice, for long term memory deficiencies for people with attention deficits who may be artificially increasing the presentation rates of their surroundings. A well-defined, quantitative measure of the primacy effect is introduced.

[Plants as a source of natural harmful substances].

PubMed

Czerwiecki, Ludwik

2005-01-01

In this review the several data concerning phytotoxins as natural harmful substances of plants and phycotoxins--toxicants of algae were described. For example plants are source of pyrrolizidine alkaloids, glycoalkaloids, glucosinolates as well as glycosides, saponine and psolarens. Possible adverse effects of phytoestrogens as endocrine disruptors versus beneficial influence these substances on human organism were mentioned. About lectins as possible factors of some diseases was reported, as well as some proteins as allergens of soy and peanuts was mentioned. Accumulated by shellfish and fish the most important phycotoxins such as saxitoxin, okadaic acid, brevetoxins and ciguatoxins were described. Phycotoxins produced several poisoning symptoms. Microcystins and nodularin--cyanobacterial phycotoxins of freshwater, was mentioned. In conclusion, the need of limitation of permissible levels of some plant toxicants, development of analytical methods as well as knowledge of influence of some technological processes on toxic plant substances was highlighted. The importance of balanced diet as a tool of defense against plant toxicants was concluded.

[Medical support on human resources and clinical laboratory in Myanmar].

PubMed

Koide, Norio

2012-03-01

I have been involved in medical cooperation programs between Myanmar and Japan for over 10 years. The purpose of the first visit to Myanmar was the investigation of hepatitis C spreading among thalassemia patients. I learned that the medical system was underdeveloped in this country, and have initiated several cooperation programs together with Professor Shigeru Okada, such as the "Protection against hepatitis C in Myanmar", "Scientist exchange between the Ministry of Health, Myanmar and Okayama University", and "Various activities sponsored by a Non-Profit Organization". As for clinical laboratories, the laboratory system itself is pre-constructed and the benefit of a clinical laboratory in modern medicine is not given to patients in Myanmar. The donation of drugs and reagents for laboratory tests is helpful, but it will be more helpful to assist the future leaders to learn modern medicine and develop their own various systems to support modern medicine. Our activity in the cooperation program is described.

Plant Defense Response to Fungal Pathogens (Activation of Host-Plasma Membrane H+-ATPase by Elicitor-Induced Enzyme Dephosphorylation).

PubMed Central

Vera-Estrella, R.; Barkla, B. J.; Higgins, V. J.; Blumwald, E.

1994-01-01

Elicitor preparations containing the avr5 gene products from race 4 of Cladosporium fulvum and tomato (Lycopersicon esculentum L.) cells near isogenic for the resistance gene Cf5 were used to investigate events following the treatment of host plasma membranes with elicitor. A 4-fold increase in H+-ATPase activity, coincident with the acidification of the extracellular medium, was detected immediately after elicitor treatment. The elicitor-induced stimulation of the plasma membrane H+-ATPase was inhibited by okadaic acid but not by staurosporine, suggesting that protein dephosphorylation was required for increased H+-ATPase activity. This observation was confirmed by [gamma]-32P labeling and immunodetection of the plasma membrane H+-ATPase. Effects of guanidine nucleotide analogs and mastoparan on the ATPase activity suggested the role of GTP-binding proteins in mediating the putative elicitor-receptor binding, resulting in activation of a phosphatase(s), which in turn stimulates the plasma membrane H+-ATPase by dephosphorylation. PMID:12232073

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rong-Nan Huang; I-Ching Ho; Ling-Hui Yih

Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 {mu}M) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplicationmore » in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity. 61 refs., 6 figs., 2 tabs.« less

Recent work of decay spectroscopy at RIBF

NASA Astrophysics Data System (ADS)

Söderström, Pär-Anders

2014-09-01

β- and isomer-decay spectroscopy are sensitive probes of nuclear structure, and are often the only techniques capable of providing data for exotic nuclei that are producted with very low rates. Decay properties of exotic nuclei are also essential to model astrophysical events responible for the evolution of the universe such as the rp- and r-process. The EURICA project (EUROBALL RIKEN Cluster Array) has been launched in 2012 with the goal of performing spectroscopy of very exotic nuclei. Since 2012, four experimental campaigns have been successfully completed using fragmentation of 124Xe beam and in-flight-fission of 238U beam, approaching for example the key nuclei 78Ni, 110Zr, 100Sn, 128Pd, and 138Sn. This contribution highlights the experiments performed, results obtained, and discusses the future perspective of the EURICA project. In collaboration with Shunji Nishimura, Hidetada Baba, RIKEN Nishina Center; Frank Browne, Brighton University; Pieter Doornenbal, RIKEN Nishina Center; Guillaume Gey, Universite Joseph Fourier Grenoble; Tadaaki Isobe and Giuseppe Lorusso, RIKEN Nishina Center; Daniel Lubos, Technische Universitat Munchen; Kevin Mochner, University of Cologne; Zena Patel and Simon Rice, University of Surrey; Hiroyoshi Sakurai, RIKEN Nishina Center; Laura Sinclair, University of York; Toshiyuki Sumikama, Tohoku University; Jan Taprogge, Universidad Autonoma de Madrid; Zsolt Vajta, MTA Atomki; Hiroshi Watanabe, Beihang University; Jin Wu, Peking University; and Zhengyu Xu, University of Tokyo.

Astrobiology: The Search for Life in the Universe

NASA Technical Reports Server (NTRS)

Pacchioli, David

2003-01-01

Each of the 11 lead members of NASA's Astrobiology Institute has a specific mission. According to Hiroshi Ohmoto, director of Penn State s Astrobiology Research Center, Here we are mainly concerned with the origin of life and the evolution and extinction of important organisms. These include bacteria that live on methane, cyanobacteria (the inventors of photosynthesis), eukaryotes (a big category, covering anything with a nucleus, from single-celled organisms to humans), land-dwelling organisms, and early animals. Penn State astrobiologists are studying the environment before there was life on Earth, the origin of oxygen in the atmosphere, the chemical and thermal structures of oceans, and the role of metals in the evolution of life. Overall, they want to understand the connection between changes in environment and changes in life forms in the early Earth. PSARC offers research assistantships for graduate and undergraduate students, fellowships for graduate students and post-doctoral fellows, and an undergraduate minor in astrobiology. The minor covers 18 credits in earth sciences, geochemistry, geophysics, astronomy, biology, biochemistry, meteorology, and microbiology. The goal, says Ohmoto, is to teach students to critically evaluate claims related to this field that they encounter well after their college education has ended. Under a scanning electron microscope, Martian meteorite ALH84001 yields tube-like structures that look a lot like remnants of Earthly bacteria except smaller by a factor of ten.

Toxicity and Growth Assessments of Three Thermophilic Benthic Dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) Developing in the Southern Mediterranean Basin.

PubMed

Ben-Gharbia, Hela; Yahia, Ons Kéfi-Daly; Amzil, Zouher; Chomérat, Nicolas; Abadie, Eric; Masseret, Estelle; Sibat, Manoella; Zmerli Triki, Habiba; Nouri, Habiba; Laabir, Mohamed

2016-10-15

Harmful benthic dinoflagellates, usually developing in tropical areas, are expanding to temperate ecosystems facing water warming. Reports on harmful benthic species are particularly scarce in the Southern Mediterranean Sea. For the first time, three thermophilic benthic dinoflagellates ( Ostreopsis cf. ovata , Prorocentrum lima and Coolia monotis ) were isolated from Bizerte Bay (Tunisia, Mediterranean) and monoclonal cultures established. The ribotyping confirmed the morphological identification of the three species. Maximum growth rates were 0.59 ± 0.08 d -1 for O. cf. ovata , 0.35 ± 0.01 d -1 for C. monotis and 0.33 ± 0.04 d -1 for P. lima. Toxin analyses revealed the presence of ovatoxin-a and ovatoxin-b in O. cf. ovata cells. Okadaic acid and dinophysistoxin-1 were detected in P. lima cultures. For C. monotis , a chromatographic peak at 5.6 min with a mass m / z = 1061.768 was observed, but did not correspond to a mono-sulfated analogue of the yessotoxin. A comparison of the toxicity and growth characteristics of these dinoflagellates, distributed worldwide, is proposed.

Failure to recall.

PubMed

Laming, Donald

2009-01-01

Mathematical analysis shows that if the pattern of rehearsal in free-recall experiments (of necessity, the pattern observed when participants rehearse aloud) be continued without any further interruption by stimuli (as happens during recall), it terminates with the retrieval of the same 1 word over and over again. Such a terminal state is commonly reached before some of the words in the list have been retrieved even once; those words are not recalled. The 1 minute frequently allowed for recall in free-recall experiments is ample time for retrieval to seize up in this way. The author proposes a model that represents the essential features of the pattern of rehearsal; validates that model by reference to the overt rehearsal data from B. B. Murdock, Jr., and J. Metcalfe (1978) and the recall data from B. B. Murdock, Jr., and R. Okada (1970); demonstrates the long-term properties of continued sequences of retrievals and, also, a fundamental relation linking recall to the total time of presentation; and, finally, compares failure to recall in free-recall experiments with forgetting in general.

Purification and characterization of protein phosphatase 2A from petals of the tulip Tulipa gesnerina.

PubMed

Azad, Md Abul Kalam; Sawa, Yoshihiro; Ishikawa, Takahiro; Shibata, Hitoshi

2006-11-30

The holoenzyme of protein phosphatase (PP) from tulip petals was purified by using hydrophobic interaction, anion exchange and microcystin affinity chromatography to analyze activity towards p-nitrophenyl phosphate (p-NPP). The catalytic subunit of PP was released from its endogenous regulatory subunits by ethanol precipitation and further purified. Both preparations were characterized by immunological and biochemical approaches to be PP2A. On SDS-PAGE, the final purified holoenzyme preparation showed three protein bands estimated at 38, 65, and 75 kDa while the free catalytic subunit preparation showed only the 38 kDa protein. In both preparations, the 38 kDa protein was identified immunologically as the catalytic subunit of PP2A by using a monoclonal antibody against the PP2A catalytic subunit. The final 623- and 748- fold purified holoenzyme and the free catalytic preparations, respectively, exhibited high sensitivity to inhibition by 1 nM okadaic acid when activity was measured with p-NPP. The holoenzyme displayed higher stimulation in the presence of ammonium sulfate than the free catalytic subunit did by protamine, thereby suggesting different enzymatic behaviors.

Microcystins from tap water could be a risk factor for liver and colorectal cancer: a risk intensified by global change.

PubMed

Martínez Hernández, Juan; López-Rodas, V; Costas, E

2009-05-01

An increasing number of people drink water from fresh water supply reservoirs. However, with the global change a lot of reservoirs become eutrophic, which facilitates the occurrence of toxin-producing cyanobacterial blooms. Microcystins (powerful hepatotoxic water-soluble heptapeptides) are the most important cyanobacterial toxins affecting humans. High doses of microcystins produce hepatic necrosis. Consequently, WHO Guidelines limit microcystins to 1 ppb in drinking waters. However, microcystins are present frequently in tap water at lower doses. Here, we hypothesized that chronic consume of tap water containing low doses of microcystins may be a risk factor for liver and colorectal cancer. Two kinds of evidences support this hypothesis. On one hand some epidemiological data (mainly in China). On the other hand, the molecular mechanism of microcystins toxicity (inhibition of protein phosphatases PP1 and PP2) is just like okadaic acid (a potent tumor promoter). Cancer risk from drinking water is certainly less than smoking, occupational exposures or some foods. But it is significant and with a rapid increase of toxic cyanobacterial blooms by eutrophycation, become more frequent.

Toxicity and Growth Assessments of Three Thermophilic Benthic Dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) Developing in the Southern Mediterranean Basin

PubMed Central

Ben-Gharbia, Hela; Yahia, Ons Kéfi-Daly; Amzil, Zouher; Chomérat, Nicolas; Abadie, Eric; Masseret, Estelle; Sibat, Manoella; Zmerli Triki, Habiba; Nouri, Habiba; Laabir, Mohamed

2016-01-01

Harmful benthic dinoflagellates, usually developing in tropical areas, are expanding to temperate ecosystems facing water warming. Reports on harmful benthic species are particularly scarce in the Southern Mediterranean Sea. For the first time, three thermophilic benthic dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) were isolated from Bizerte Bay (Tunisia, Mediterranean) and monoclonal cultures established. The ribotyping confirmed the morphological identification of the three species. Maximum growth rates were 0.59 ± 0.08 d−1 for O. cf. ovata, 0.35 ± 0.01 d−1 for C. monotis and 0.33 ± 0.04 d−1 for P. lima. Toxin analyses revealed the presence of ovatoxin-a and ovatoxin-b in O. cf. ovata cells. Okadaic acid and dinophysistoxin-1 were detected in P. lima cultures. For C. monotis, a chromatographic peak at 5.6 min with a mass m/z = 1061.768 was observed, but did not correspond to a mono-sulfated analogue of the yessotoxin. A comparison of the toxicity and growth characteristics of these dinoflagellates, distributed worldwide, is proposed. PMID:27754462

LibHalfSpace: A C++ object-oriented library to study deformation and stress in elastic half-spaces

NASA Astrophysics Data System (ADS)

Ferrari, Claudio; Bonafede, Maurizio; Belardinelli, Maria Elina

2016-11-01

The study of deformation processes in elastic half-spaces is widely employed for many purposes (e.g. didactic, scientific investigation of real processes, inversion of geodetic data, etc.). We present a coherent programming interface containing a set of tools designed to make easier and faster the study of processes in an elastic half-space. LibHalfSpace is presented in the form of an object-oriented library. A set of well known and frequently used source models (Mogi source, penny shaped horizontal crack, inflating spheroid, Okada rectangular dislocation, etc.) are implemented to describe the potential usage and the versatility of the library. The common interface given to library tools enables us to switch easily among the effects produced by different deformation sources that can be monitored at the free surface. Furthermore, the library also offers an interface which simplifies the creation of new source models exploiting the features of object-oriented programming (OOP). These source models can be built as distributions of rectangular boundary elements. In order to better explain how new models can be deployed some examples are included in the library.

Residual Life and Strength Predictions and Life-Enhancement of Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okada, H.; Atluri, S.N.

1998-09-01

In this paper, a method to quantitatively evaluate the T{sub {var_epsilon}}* integral directly from the measured near-tip displacement field for laboratory specimens made of metallic materials, is presented. This is the first time that such an attempt became a success. In order to develop the procedure, we carefully examine the nature of T{sub {var_epsilon}}* Hence, the nature of T{sub {var_epsilon}}* is further revealed. Following Okada and Atluri (1997), the relationship between energy balance statements for a cracked plate and the T{sub {var_epsilon}}* is discussed. It is concluded that T{sub {var_epsilon}}* quantifies the deformation energy dissipated near crack tip region [anmore » elongating strip of height e] per unit crack extension. In the evaluation of T{sub {var_epsilon}}* integral directly from measured displacement field, the use of deformation theory plasticity (J2-D theory) and the truncation of the near crack integral path on the experimental studies of Omori et el. (1995) are presented, and these show a good agreement with the results of finite element analysis.« less

PDGF activates K-Cl cotransport through phosphoinositide 3-kinase and protein phosphatase-1 in primary cultures of vascular smooth muscle cells.

PubMed

Zhang, Jing; Lauf, Peter K; Adragna, Norma C

2005-07-15

K-Cl cotransport (K-Cl COT, KCC) is an electroneutrally coupled movement of K and Cl present in most cells. In this work, we studied the pathways of regulation of K-Cl COT by platelet-derived growth factor (PDGF) in primary cultures of vascular smooth muscle cells (VSMCs). Wortmannin and LY 294002 blocked the PDGF-induced K-Cl COT activation, indicating that the phosphoinositide 3-kinase (PI 3-K) pathway is involved. However, PD 98059 had no effect on K-Cl COT activation by PDGF, suggesting that the mitogen-activated protein kinase pathway is not involved under the experimental conditions tested. Involvement of phosphatases was also examined. Sodium orthovanadate, cyclosporin A and okadaic acid had no effect on PDGF-stimulated K-Cl COT. Calyculin A blocked the PDGF-stimulated K-Cl COT by 60%, suggesting that protein phosphatase-1 (PP-1) is a mediator in the PDGF signaling pathway/s. In conclusion, our results indicate that the PDGF-mediated pathways of K-Cl COT regulation involve the signaling molecules PI 3-K and PP-1.

Analytic crack solutions for tilt fields around hydraulic fractures

NASA Astrophysics Data System (ADS)

Warpinski, Norman R.

2000-10-01

The recent development of downhole tiltmeter arrays for monitoring hydraulic fractures has provided new information on fracture growth and geometry. These downhole arrays offer the significant advantages of being close to the fracture (large signal) and being unaffected by the free surface. As with surface tiltmeter data, analysis of these measurements requires the inversion of a crack or dislocation model. To supplement the dislocation models of Davis [1983], Okada [1992], and others, this work has extended several elastic crack solutions to provide tilt calculations. The solutions include constant-pressure two-dimensional (2-D), penny-shaped, and 3-D-elliptic cracks and a 2-D-variable-pressure crack. Equations are developed for an arbitrary inclined fracture in an infinite elastic space. Effects of fracture height, fracture length, fracture dip, fracture azimuth, fracture width, and monitoring distance on the tilt distribution are given, as well as comparisons with the dislocation model. The results show that the tilt measurements are very sensitive to the fracture dimensions but also that it is difficult to separate the competing effects of the various parameters.

Analytic crack solutions for tilt fields around hydraulic fractures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warpinski, N.R.

The recent development of downhole tiltmeter arrays for monitoring hydraulic fractures has provided new information on fracture growth and geometry. These downhole arrays offer the significant advantages of being close to the fracture (large signal) and being unaffected by the free surface. As with surface tiltmeter data, analysis of these measurements requires the inversion of a crack or dislocation model. To supplement the dislocation models of Davis [1983], Okada [1992] and others, this work has extended several elastic crack solutions to provide tilt calculations. The solutions include constant-pressure 2D, penny-shaped, and 3D-elliptic cracks and a 2D-variable-pressure crack. Equations are developedmore » for an arbitrary inclined fracture in an infinite elastic space. Effects of fracture height, fracture length, fracture dip, fracture azimuth, fracture width and monitoring distance on the tilt distribution are given, as well as comparisons with the dislocation model. The results show that the tilt measurements are very sensitive to the fracture dimensions, but also that it is difficult to separate the competing effects of the various parameters.« less

SCOP/PHLPP and its functional role in the brain.

PubMed

Shimizu, Kimiko; Mackenzie, Scott M; Storm, Daniel R

2010-01-01

SCOP (suprachiasmatic nucleus (SCN) circadian oscillatory protein) was originally identified in 1999 in a differential display screen of the rat SCN for genes whose expression were regulated in a circadian manner (K. Shimizu, M. Okada, A. Takano and K. Nagai, FEBS Lett., 1999, 458, 363-369). The SCN is the principle pacemaker of the circadian clock, and expression of SCOP protein in the SCN was found to oscillate, increasing during the subjective night, even when animals were housed in constant darkness. SCOP interacts with and inhibits multiple proteins important for intracellular signaling, either by directly binding to K-Ras or by dephosphorylating p-Akt and p-PKC. Since the functions of K-Ras, Akt, and PKC are considerably divergent, SCOP may have several roles. We recently discovered that SCOP participates in the formation of long-term hippocampus-dependent memories, and other investigators have examined its role in cell proliferation and survival. In this review, we introduce SCOP from its molecular structure to its physiological functions, focusing mainly on its role in ERK1/2 activation and memory consolidation.

SCOP/PHLPP and its functional role in the brain

PubMed Central

Shimizu, Kimiko; Mackenzie, Scott M.; Storm, Daniel R.

2012-01-01

SCOP (suprachiasmatic nucleus (SCN) circadian oscillatory protein) was originally identified in 1999 in a differential display screen of the rat SCN for genes whose expression were regulated in a circadian manner (K. Shimizu, M. Okada, A. Takano and K. Nagai, FEBS Lett., 1999, 458, 363–369). The SCN is the principle pacemaker of the circadian clock, and expression of SCOP protein in the SCN was found to oscillate, increasing during the subjective night, even when animals were housed in constant darkness. SCOP interacts with and inhibits multiple proteins important for intracellular signaling, either by directly binding to K-Ras or by dephosphorylating p-Akt and p-PKC. Since the functions of K-Ras, Akt, and PKC are considerably divergent, SCOP may have several roles. We recently discovered that SCOP participates in the formation of long-term hippocampus-dependent memories, and other investigators have examined its role in cell proliferation and survival. In this review, we introduce SCOP from its molecular structure to its physiological functions, focusing mainly on its role in ERK1/2 activation and memory consolidation. PMID:20024065

Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan.

PubMed

Miyata, Shinji; Kitagawa, Hiroshi

2017-10-01

The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration. Here, we review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity, with a particular focus on the mechanism that regulates PV cell function through specific interactions between CS chains and their binding partners. We also discuss how the barrier function of the brain ECM restricts dendritic spine dynamics and limits axon regeneration after injury. The brain ECM not only forms physical barriers that modulate neural plasticity and axon regeneration, but also forms molecular brakes that actively controls maturation of PV cells and synapse plasticity in which sulfation patterns of CS chains play a key role. Structural remodeling of the brain ECM modulates neural function during development and pathogenesis. Genetic or enzymatic manipulation of the brain ECM may restore neural plasticity and enhance recovery from nerve injury. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. Copyright © 2017 Elsevier B.V. All rights reserved.

Glycosylation with ribitol-phosphate in mammals: New insights into the O-mannosyl glycan.

PubMed

Manya, Hiroshi; Endo, Tamao

2017-10-01

O-mannosyl glycans have been found in a limited number of glycoproteins of the brain, nerves, and skeletal muscles, particularly in α-dystroglycan (α-DG). Defects in O-mannosyl glycan on α-DG are the primary cause of a group of congenital muscular dystrophies, which are collectively termed α-dystroglycanopathy. Recent studies have revealed various O-mannosyl glycan structures, which can be classified as core M1, core M2, and core M3 glycans. Although many dystroglycanopathy genes are involved in core M3 processing, the structure and biosynthesis of core M3 glycan remains only partially understood. This review presents recent findings about the structure, biosynthesis, and pathology of O-mannosyl glycans. Recent studies have revealed that the entire structure of core M3 glycan, including ribitol-5-phosphate, is a novel structure in mammals; its unique biosynthetic pathway has been elucidated by the identification of new causative genes for α-dystroglycanopathies and their functions. O-mannosyl glycan has a novel, unique structure that is important for the maintenance of brain and muscle functions. These findings have opened up a new field in glycoscience. These studies will further contribute to the understanding of the pathomechanism of α-dystroglycanopathy and the development of glycotherapeutics. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. Copyright © 2017 Elsevier B.V. All rights reserved.

WHO still reeling from racism charges.

PubMed

1995-06-01

The World Health Organization (WHO) is not as prestigious as it used to be. It operates on a relatively small annual budget of $1.8 billion, the WHO 1995 audit suggested irregularities in the way contracts were awarded and criticized a lack of control over funds at the WHO's African headquarters in the Congo, and its director, Hiroshi Nakajima, has been accused of being a racist against Africans. Nakajima complained during a January 1995 WHO board meeting that some African members had poor English skills. Delegates from several African nations to the annual World Health Assembly, which began in Geneva on May 1, subsequently raised the issue and called for the Japanese director to resign. The release of the recent WHO health report, "Bridging the Gaps," was an attempt by the organization to regain some its international respect, but little new was reported. Basic messages were that poverty is the most important cause of ill health, 60% of all new HIV infections occur among people aged 15-24 in many countries, 50% of people with HIV globally are younger than 25 years old, 60% of infections in women occur by age 20, and life expectancy is increasing in all countries except Cote d'Ivoire, Central African Republic, Congo, Uganda, and Zambia, all countries hard-hit by HIV/AIDS. For now, Nakajima has retained his position, although British and US donors stress that they will keep closer watch over the organization and that reforms must be made.

Conformations and Barriers to Methyl Group Internal Rotation in Two Asymmetric Ethers: Propyl Methyl Ether and Butyl Methyl Ether

NASA Astrophysics Data System (ADS)

Long, B. E.; Dechirico, F.; Cooke, S. A.

2012-06-01

The conformational preferences of the O-C-C-C unit are important in many biological systems with the unit generally preferring a gauche configuration compared to an anti configuration. Butyl methyl ether and propyl methyl ether provide very simple systems for this phenomenom to manifest. Pure rotational spectra of the title molecules have been recorded using chirped pulse Fourier transform microwave spectroscopy (CP-FTMW). In the case of butyl methyl ether, only one conformer has been observed. This conformer has torsional angles of COCC = 180°, OCCC = 62° and CCCC = 180° (anti-gauche-anti) and rotational constants of A = 10259.4591(33) MHz, B = 1445.6470(13) MHz, and C = 1356.2944(14) MHz. The rotational spectrum was doubled and has been analyzed to produce an effective barrier to methyl group internal rotation of 780(35) cm-1. A prior rotational spectroscopic study on propyl methyl ether had focused only on the high energy anti-anti conformer. We have analyzed spectra from the lowest energy anti-gauche conformer and the spectroscopic constants will be presented. A summary of the differences in conformational energies and methyl group internal rotation barriers for the class of aliphatic asymmetric ethers will be presented. K. N. Houk, J. E. Eksterowicz, Y.-D. Wu, C. D. Fuglesang, D. B. Mitchell. J. Am. Chem. Soc. 115 (4170), 1993. Hiroshi Kato, Jun Nakagawa, Michiro Hayashi. J. Mol. Spectrosc. 80 (272), 1980.

An angle encoder for super-high resolution and super-high accuracy using SelfA

NASA Astrophysics Data System (ADS)

Watanabe, Tsukasa; Kon, Masahito; Nabeshima, Nobuo; Taniguchi, Kayoko

2014-06-01

Angular measurement technology at high resolution for applications such as in hard disk drive manufacturing machines, precision measurement equipment and aspherical process machines requires a rotary encoder with high accuracy, high resolution and high response speed. However, a rotary encoder has angular deviation factors during operation due to scale error or installation error. It has been assumed to be impossible to achieve accuracy below 0.1″ in angular measurement or control after the installation onto the rotating axis. Self-calibration (Lu and Trumper 2007 CIRP Ann. 56 499; Kim et al 2011 Proc. MacroScale; Probst 2008 Meas. Sci. Technol. 19 015101; Probst et al Meas. Sci. Technol. 9 1059; Tadashi and Makoto 1993 J. Robot. Mechatronics 5 448; Ralf et al 2006 Meas. Sci. Technol. 17 2811) and cross-calibration (Probst et al 1998 Meas. Sci. Technol. 9 1059; Just et al 2009 Precis. Eng. 33 530; Burnashev 2013 Quantum Electron. 43 130) technologies for a rotary encoder have been actively discussed on the basis of the principle of circular closure. This discussion prompted the development of rotary tables which achieve reliable and high accuracy angular verification. We apply these technologies for the development of a rotary encoder not only to meet the requirement of super-high accuracy but also to meet that of super-high resolution. This paper presents the development of an encoder with 221 = 2097 152 resolutions per rotation (360°), that is, corresponding to a 0.62″ signal period, achieved by the combination of a laser rotary encoder supplied by Magnescale Co., Ltd and a self-calibratable encoder (SelfA) supplied by The National Institute of Advanced Industrial Science & Technology (AIST). In addition, this paper introduces the development of a rotary encoder to guarantee ±0.03″ accuracy at any point of the interpolated signal, with respect to the encoder at the minimum resolution of 233, that is, corresponding to a 0.0015″ signal period after

Tsunami Impact in Morocco due to Most Credible Tsunami Scenarios in the Gulf of Cadiz.

NASA Astrophysics Data System (ADS)

Omira, R.; Baptista, M. A.; Miranda, J. M.; Toto, E. A.

2009-04-01

In the Gulf of Cadiz, the tsunami risk should be considered major due to the peculiar geological context close to the Nubia-Eurasia plate boundary and also to the high vulnerability of the coastlines in the region. The extensive occupation of coastal areas in the surrounding countries - Portugal, Spain and Morocco, the enormous influxes of tourists during high season and the large economic value of harbors and other coastal facilities increase considerably the vulnerability to tsunami impact. In order to establish the Most Credible Tsunami Scenarios we used the earthquake scenarios in the Gulf of Cadiz area. Each scenario has an associated typical fault/or faults and a set of fault parameters that are used as input to compute the sea bottom deformation using Okada's equations. Tsunami propagation uses COMCOT-LX, modified version of the COMCOT Cornnell University code. Maximum wave height (MWH) and tsunami energy direction are computed, for each tsunamigenic scenario for the north Atlantic coast of Morocco. Finally we selected the harbor of Casablanca for the production of inundation maps for Casablanca This research was funded by NEAREST and TRANSFER, 6FP-European Union.

Effects of marine toxins on the reproduction and early stages development of aquatic organisms.

PubMed

Vasconcelos, Vítor; Azevedo, Joana; Silva, Marisa; Ramos, Vítor

2010-01-19

Marine organisms, and specially phytoplankton species, are able to produce a diverse array of toxic compounds that are not yet fully understood in terms of their main targets and biological function. Toxins such as saxitoxins, tetrodotoxin, palytoxin, nodularin, okadaic acid, domoic acid, may be produced in large amounts by dinoflagellates, cyanobacteria, bacteria and diatoms and accumulate in vectors that transfer the toxin along food chains. These may affect top predator organisms, including human populations, leading in some cases to death. Nevertheless, these toxins may also affect the reproduction of aquatic organisms that may be in contact with the toxins, either by decreasing the amount or quality of gametes or by affecting embryonic development. Adults of some species may be insensitive to toxins but early stages are more prone to intoxication because they lack effective enzymatic systems to detoxify the toxins and are more exposed to the toxins due to a higher metabolic growth rate. In this paper we review the current knowledge on the effects of some of the most common marine toxins on the reproduction and development of early stages of some organisms.

Regulation of tyrosine hydroxylase activity and phosphorylation at Ser(19) and Ser(40) via activation of glutamate NMDA receptors in rat striatum.

PubMed

Lindgren, N; Xu, Z Q; Lindskog, M; Herrera-Marschitz, M; Goiny, M; Haycock, J; Goldstein, M; Hökfelt, T; Fisone, G

2000-06-01

The activity of tyrosine hydroxylase, the rate-limiting enzyme in the biosynthesis of dopamine, is stimulated by phosphorylation. In this study, we examined the effects of activation of NMDA receptors on the state of phosphorylation and activity of tyrosine hydroxylase in rat striatal slices. NMDA produced a time-and concentration-dependent increase in the levels of phospho-Ser(19)-tyrosine hydroxylase in nigrostriatal nerve terminals. This increase was not associated with any changes in the basal activity of tyrosine hydroxylase, measured as DOPA accumulation. Forskolin, an activator of adenylyl cyclase, stimulated tyrosine hydroxylase phosphorylation at Ser(40) and caused a significant increase in DOPA accumulation. NMDA reduced forskolin-mediated increases in both Ser(40) phosphorylation and DOPA accumulation. In addition, NMDA reduced the increase in phospho-Ser(40)-tyrosine hydroxylase produced by okadaic acid, an inhibitor of protein phosphatase 1 and 2A, but not by a cyclic AMP analogue, 8-bromo-cyclic AMP. These results indicate that, in the striatum, glutamate decreases tyrosine hydroxylase phosphorylation at Ser(40) via activation of NMDA receptors by reducing cyclic AMP production. They also provide a mechanism for the demonstrated ability of NMDA to decrease tyrosine hydroxylase activity and dopamine synthesis.

Biodegradation of polyether algal toxins--isolation of potential marine bacteria.

PubMed

Shetty, Kateel G; Huntzicker, Jacqueline V; Rein, Kathleen S; Jayachandran, Krish

2010-12-01

Marine algal toxins such as brevetoxins, okadaic acid, yessotoxin, and ciguatoxin are polyether compounds. The fate of polyether toxins in the aqueous phase, particularly bacterial biotransformation of the toxins, is poorly understood. An inexpensive and easily available polyether structural analog salinomycin was used for enrichment and isolation of potential polyether toxin degrading aquatic marine bacteria from Florida bay area, and from red tide endemic sites in the South Florida Gulf coast. Bacterial growth on salinomycin was observed in most of the enrichment cultures from both regions with colony forming units ranging from 0 to 6×10(7) per mL. The salinomycin biodegradation efficiency of bacterial isolates determined using LC-MS ranged from 22% to 94%. Selected bacterial isolates were grown in media with brevetoxin as the sole carbon source to screen for brevetoxin biodegradation capability using ELISA. Out of the two efficient salinomycin biodegrading isolates MB-2 and MB-4, maximum brevetoxin biodegradation efficiency of 45% was observed with MB-4, while MB-2 was unable to biodegrade brevetoxin. Based on 16S rRNA sequence similarity MB-4 was found have a match with Chromohalobacter sp.

Biodegradation of polyether algal toxins–Isolation of potential marine bacteria

PubMed Central

SHETTY, KATEEL G.; HUNTZICKER, JACQUELINE V.; REIN, KATHLEEN S.; JAYACHANDRAN, KRISH

2012-01-01

Marine algal toxins such as brevetoxins, okadaic acid, yessotoxin, and ciguatoxin are polyether compounds. The fate of polyether toxins in the aqueous phase, particularly bacterial biotransformation of the toxins, is poorly understood. An inexpensive and easily available polyether structural analog salinomycin was used for enrichment and isolation of potential polyether toxin degrading aquatic marine bacteria from Florida bay area, and from red tide endemic sites in the South Florida Gulf coast. Bacterial growth on salinomycin was observed in most of the enrichment cultures from both regions with colony forming units ranging from 0 to 6 × 107 per mL. The salinomycin biodegradation efficiency of bacterial isolates determined using LC-MS ranged from 22% to 94%. Selected bacterial isolates were grown in media with brevetoxin as the sole carbon source to screen for brevetoxin biodegradation capability using ELISA. Out of the two efficient salinomycin biodegrading isolates MB-2 and MB-4, maximum brevetoxin biodegradation efficiency of 45% was observed with MB-4, while MB-2 was unable to biodegrade brevetoxin. Based on 16S rRNA sequence similarity MB-4 was found have a match with Chromohalobacter sp. PMID:20954040

Determination of lipophilic toxins by LC/MS/MS: single-laboratory validation.

PubMed

Villar-González, Adriano; Rodríguez-Velasco, María Luisa; Gago-Martínez, Ana

2011-01-01

An LC/MS/MS method has been developed, assessed, and intralaboratory-validated for the analysis of the lipophilic toxins currently regulated by European Union legislation: okadaic acid (OA) and dinophysistoxins 1 and 2, including their ester forms; azaspiracids 1, 2, and 3; pectenotoxins 1 and 2; yessotoxin (YTX), and the analogs 45 OH-YTX, Homo YTX, and 45 OH-Homo YTX; as well as for the analysis of 13-desmetil-spirolide C. The method consists of duplicate sample extraction with methanol and direct analysis of the crude extract without further cleanup or concentration. Ester forms of OA and dinophysistoxins are detected as the parent ions after alkaline hydrolysis of the extract. The validation process of this method was performed using both fortified and naturally contaminated samples, and experiments were designed according to International Organization for Standardization, International Union of Pure and Applied Chemistry, and AOAC guidelines. With the exception of YTX in fortified samples, RSDr below 15% and RSDR were below 25%. Recovery values were between 77 and 95%, and LOQs were below 60 microg/kg. These data together with validation experiments for recovery, selectivity, robustness, traceability, and linearity, as well as uncertainty calculations, are presented in this paper.

Phosphatidic acid induces decidualization by stimulating Akt-PP2A binding in human endometrial stromal cells.

PubMed

Lee, So Young; Lee, Yun Young; Choi, Joong Sub; Yoon, Mee-Sup; Han, Joong-Soo

2016-11-01

Decidualization of human endometrial stromal cells (hESCs) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 (PLD1) is required for cAMP-induced decidualization of hESCs. However, the mechanism by which phosphatidic acid (PA), the product of PLD1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESCs by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP1 and prolactin transcripts (P < 0.05). Treatment with PA reduced phosphorylation of Akt and consequently that of FoxO1, which led to the increased IGFBP1 and prolactin mRNA levels (P < 0.05). Conversely, PLD1 knockdown rescued Akt phosphorylation. Binding of PP2A and Akt increased in response to cAMP or PA, suggesting that their binding is directly responsible for the inactivation of Akt during decidualization. Consistent with this observation, treatment with okadaic acid, a PP2A inhibitor, also inhibited cAMP-induced decidualization by blocking Akt dephosphorylation. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Comparison of frailty of primary neurons, embryonic, and aging mouse cortical layers.

PubMed

Fugistier, Patrick; Vallet, Philippe G; Leuba, Geneviève; Piotton, Françoise; Marin, Pascale; Bouras, Constantin; Savioz, Armand

2014-02-01

Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and superficial layers, were treated either with Aβ(1-42), okadaic acid, or kainic acid. Second, whole E14 and E17 embryonic cortices, and third, in vitro separated deep and superficial layers of young and old C57BL/6J mice, were treated identically. We observed that E14 and E17 neurons in culture were prone to death after the Aβ and particularly the kainic acid treatment. This was also the case for the superficial layers of the aged cortex, but not for the embryonic, the young cortex, and the deep layers of the aged cortex. Thus, the aged superficial layers appeared to be preferentially vulnerable against Aβ and kainic acid. This pattern of vulnerability corresponds to enhanced accumulation of senile plaques in the superficial cortical layers with aging and Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Protein kinase and phosphatase modulation of quail brain GABA(A) and non-NMDA receptors co-expressed in Xenopus oocytes.

PubMed

Moon, C; Fraser, S P; Djamgoz, M B

2000-02-01

The GABA(A) receptor and the non-NMDA subtype of the ionotropic glutamate receptor were co-expressed in Xenopus oocytes by injection of quail brain mRNA. The oocytes were treated with various protein kinase (PK) and protein phosphatase (PP) activators and inhibitors and the effects on receptor functioning were monitored. Two phorbol esters, 4-beta-phorbol 12-myristate-13-acetate (PMA) and 4-beta-phorbol 12,13-dibutyrate (PDBu); the cGMP-dependent PK activators sodium nitroprusside (SNP) and S-nitrosoglutathione (SNOG); and the PP inhibitor okadaic acid (OA) reduced the amplitude of the GABA-induced currents, whilst the PK inhibitor staurosporine potentiated it. In addition, PMA, PDBu, SNP, and OA reduced the desensitization of the GABA-induced response. Identical treatments generally had similar but less pronounced effects on responses generated by kainate (KA) but the desensitization characteristic of the non-NMDA receptor was not affected. None of the treatments had any effect on the reversal potentials of the induced currents. Immunoblots revealed that the oocytes express endogenous PKG and guanylate cyclase. The results are discussed in terms of the molecular structures of GABA(A) and non-NMDA receptors and the potential functional consequences of phosphorylation/dephosphorylation.

Protein kinase antagonists inhibit invasion of mammalian cells by Fonsecaea pedrosoi.

PubMed

Limongi, Cristiana L; De Souza, Wanderley; Rozental, Sonia

2003-03-01

The phosphorylation process is an important mechanism of cell signalling and regulation. It has been implicated recently in defence strategies against a variety of pathogens that alter host signalling pathways in order to facilitate their invasion and survival within host cells. In this study, the involvement of protein kinases (PKs) has been investigated in attachment and invasion by the pathogenic fungus Fonsecaea pedrosoi within epithelial cells and macrophages. The use of the PK inhibitors staurosporine, genistein and calphostin C prior to infection provided significant information about the role played by PKs in the F. pedrosoi-host cell interaction. All three PK inhibitors could reduce cell invasion by F. pedrosoi significantly. Pre-treatment of macrophages, epithelial cells or conidia with PK inhibitors decreased fungus invasion, and this effect could be overcome by okadaic acid, a phosphatase inhibitor. Immunofluorescence assays showed that tyrosine residues were phosphorylated in the first step of the interaction, while serine residues were phosphorylated in the subsequent step of entry of the parasite into the host cell. These results suggest that both host-cell and conidium PK activities are important in the interaction process, playing a significant role in cell invasion.

Sphingosine regulates the NLRP3-inflammasome and IL-1β release from macrophages

PubMed Central

Luheshi, Nadia M; Giles, James A; Lopez-Castejon, Gloria; Brough, David

2012-01-01

Abstract Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that regulates inflammatory responses to injury and infection. IL-1β secretion requires the protease caspase-1, which is activated following recruitment to inflammasomes. Endogenous danger-associated molecular patterns (DAMPs) released from necrotic cells activate caspase-1 through an NLRP3-inflammasome. Here, we show that the endogenous lipid metabolite sphingosine (Sph) acts as a DAMP by inducing the NLRP3-inflammasome-dependent secretion of IL-1β from macrophages. This process was dependent upon serine/threonine protein phosphatases since the PP1/PP2A inhibitors okadaic acid and calyculin A inhibited Sph-induced IL-1β release. IL-1β release induced by other well-characterized NLRP3-inflammasome activators, such as ATP and uric acid crystals, in addition to NLRC4 and AIM2 inflammasome activators was also blocked by these inhibitors. Thus, we propose Sph as a new DAMP, and that a serine/threonine phosphatase (PP1/PP2A)-dependent signal is central to the endogenous host mechanism through which diverse stimuli regulate inflammasome activation. PMID:22105559

Programmed death-1 controls T cell survival by regulating oxidative metabolism1

PubMed Central

Tkachev, Victor; Goodell, Stefanie; Opipari, Anthony W.; Hao, Ling-Yang; Franchi, Luigi; Glick, Gary D.; Ferrara, James L.M.; Byersdorfer, Craig A.

2015-01-01

The co-inhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity of graft-versus-host disease (GVHD), but the interplay between PD-1 inhibition and T cell metabolism is not well studied. We found that both murine and human alloreactive T cells concomitantly up-regulated PD-1 expression and increased levels of reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1HiROSHi phenotype was specific to alloreactive T cells and was not observed in syngeneic T cells during homeostatic proliferation. Blockade of PD-1 signaling decreased both mitochondrial H2O2 and total cellular ROS levels and PD-1 driven increases in ROS were dependent upon the oxidation of fatty acids, as treatment with etomoxir nullified changes in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels impaired T cell survival in a process reversed by anti-oxidants. Furthermore, PD-1 driven changes in ROS were fundamental to establishing a cell’s susceptibility to subsequent metabolic inhibition, as blockade of PD-1 decreased the efficacy of later F1F0-ATP synthase modulation. These data indicate that PD-1 facilitates apoptosis in alloreactive T cells by increasing reactive oxygen species in a process dependent upon the oxidation of fat. In addition, blockade of PD-1 undermines the potential for subsequent metabolic inhibition, an important consideration given the increasing use of anti-PD-1 therapies in the clinic. PMID:25972478

Development of a F actin-based live-cell fluorimetric microplate assay for diarrhetic shellfish toxins.

PubMed

Leira, F; Alvarez, C; Cabado, A G; Vieites, J M; Vieytes, M R; Botana, L M

2003-06-15

A new cytotoxicity assay for detection and quantitation of diarrhetic shellfish toxins (DSP) is presented. This assay is based upon fluorimetric determination of F-actin depolymerization induced by okadaic acid (OA)-class compounds in the BE(2)-M17 neuroblastoma cell line. No interferences were observed with other marine toxins such as saxitoxin, domoic acid, or yessotoxin, thus indicating a good specificity of the assay as expected by the direct relationship between protein phosphatase inhibition and cytoskeletal changes. The proposed method is rapid (<2h) and shows a linear response in the range of 50-300 nM OA. The detection limit of the assay for crude methanolic extracts of bivalves lies between 0.2 and 1.0 microg OA per gram of digestive glands, depending on the type of samples (fresh or canned), thus being similar to that of the mouse bioassay. The performance of this assay has been evaluated by comparative analysis of 32 toxic mussel samples by the F-actin assay, mouse bioassay, HPLC and PP2A inhibition assay. Results obtained by the F-actin method showed no differences with HPLC and significant correlation with PP2A inhibition assay (r(2)=0.71). No false negative results were obtained with this new cell assay, which also showed optimum reproducibility.

Retrieving Precise Three-Dimensional Deformation on the 2014 M6.0 South Napa Earthquake by Joint Inversion of Multi-Sensor SAR.

PubMed

Jo, Min-Jeong; Jung, Hyung-Sup; Yun, Sang-Ho

2017-07-14

We reconstructed the three-dimensional (3D) surface displacement field of the 24 August 2014 M6.0 South Napa earthquake using SAR data from the Italian Space Agency's COSMO-SkyMed and the European Space Agency's Sentinel-1A satellites. Along-track and cross-track displacements produced with conventional SAR interferometry (InSAR) and multiple-aperture SAR interferometry (MAI) techniques were integrated to retrieve the east, north, and up components of surface deformation. The resulting 3D displacement maps clearly delineated the right-lateral shear motion of the fault rupture with a maximum surface displacement of approximately 45 cm along the fault's strike, showing the east and north components of the trace particularly clearly. These maps also suggested a better-constrained model for the South Napa earthquake. We determined a strike of approximately 338° and dip of 85° by applying the Okada dislocation model considering a single patch with a homogeneous slip motion. Using the distributed slip model obtained by a linear solution, we estimated that a peak slip of approximately 1.7 m occurred around 4 km depth from the surface. 3D modelling using the retrieved 3D maps helps clarify the fault's nature and thus characterize its behaviour.

Lander and rover exploration on the lunar surface: A study for SELENE-B mission

NASA Astrophysics Data System (ADS)

Selene-B Rover Science Group; Sasaki, S.; Sugihara, T.; Saiki, K.; Akiyama, H.; Ohtake, M.; Takeda, H.; Hasebe, N.; Kobayashi, M.; Haruyama, J.; Shirai, K.; Kato, M.; Kubota, T.; Kunii, Y.; Kuroda, Y.

The SELENE-B, a lunar landing mission, has been studied in Japan, where a scientific investigation plan is proposed using a robotic rover and a static lander. The main theme to be investigated is to clarify the lunar origin and evolution, especially for early crustal formation process probably from the ancient magma ocean. The highest priority is placed on a direct in situ geology at a crater central peak, “a window to the interior”, where subcrustal materials are exposed and directly accessed without drilling. As a preliminary study was introduced by Sasaki et al. [Sasaki, S., Kubota, T., Okada, T. et al. Scientific exploration of lunar surface using a rover in Japanse future lunar mission. Adv. Space Res. 30, 1921 1926, 2002.], the rover and lander are jointly used, where detailed analyses of the samples collected by the rover are conducted at the lander. Primary scientific instruments are a multi-band stereo imager, a gamma-ray spectrometer, and a sampling tool on the rover, and a multi-spectral telescopic imager, a sampling system, and a sample analysis package with an X-ray spectrometer/diffractometer, a multi-band microscope as well as a sample cleaning and grinding device on the lander.

Rhizobiales-like Phosphatase 2 from Arabidopsis thaliana Is a Novel Phospho-tyrosine-specific Phospho-protein Phosphatase (PPP) Family Protein Phosphatase.

PubMed

Uhrig, R Glen; Labandera, Anne-Marie; Muhammad, Jamshed; Samuel, Marcus; Moorhead, Greg B

2016-03-11

Cellular signaling through protein tyrosine phosphorylation is well established in mammalian cells. Although lacking the classic tyrosine kinases present in humans, plants have a tyrosine phospho-proteome that rivals human cells. Here we report a novel plant tyrosine phosphatase from Arabidopsis thaliana (AtRLPH2) that, surprisingly, has the sequence hallmarks of a phospho-serine/threonine phosphatase belonging to the PPP family. Rhizobiales/Rhodobacterales/Rhodospirillaceae-like phosphatases (RLPHs) are conserved in plants and several other eukaryotes, but not in animals. We demonstrate that AtRLPH2 is localized to the plant cell cytosol, is resistant to the classic serine/threonine phosphatase inhibitors okadaic acid and microcystin, but is inhibited by the tyrosine phosphatase inhibitor orthovanadate and is particularly sensitive to inhibition by the adenylates, ATP and ADP. AtRLPH2 displays remarkable selectivity toward tyrosine-phosphorylated peptides versus serine/threonine phospho-peptides and readily dephosphorylates a classic tyrosine phosphatase protein substrate, suggesting that in vivo it is a tyrosine phosphatase. To date, only one other tyrosine phosphatase is known in plants; thus AtRLPH2 represents one of the missing pieces in the plant tyrosine phosphatase repertoire and supports the concept of protein tyrosine phosphorylation as a key regulatory event in plants. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Study of Adsorption and Flocculation Properties of Natural Clays to Remove Prorocentrum lima

PubMed Central

Louzao, Maria Carmen; Abal, Paula; Fernández, Diego A.; Vieytes, Mercedes R.; Legido, José Luis; Gómez, Carmen P.; Pais, Jesus; Botana, Luis M.

2015-01-01

High accumulations of phytoplankton species that produce toxins are referred to as harmful algal blooms (HABs). HABs represent one of the most important sources of contamination in marine environments, as well as a serious threat to public health, fisheries, aquaculture-based industries, and tourism. Therefore, methods effectively controlling HABs with minimal impact on marine ecology are required. Marine dinoflagellates of the genera Dinophysis and Prorocentrum are representative producers of okadaic acid (OA) and dinophysistoxins responsible for the diarrhetic shellfish poisoning (DSP) which is a human intoxication caused by the consumption of shellfish that bioaccumulate those toxins. In this work we explore the use of natural clay for removing Prorocentrum lima. We evaluate the adsorption properties of clays in seawater containing the dinoflagellates. The experimental results confirmed the cell removal through the flocculation of algal and mineral particles leading to the formation of aggregates, which rapidly settle and further entrain cells during their descent. Moreover, the microscopy images of the samples enable one to observe the clays in aggregates of two or more cells where the mineral particles were bound to the outer membranes of the dinoflagellates. Therefore, this preliminary data offers promising results to use these clays for the mitigation of HABs. PMID:26426051

Cascadia Slow Earthquakes: Strategies for Time Independent Inversion of Displacement Fields

NASA Astrophysics Data System (ADS)

Szeliga, W. M.; Melbourne, T. I.; Miller, M. M.; Santillan, V. M.

2004-12-01

Continuous observations using Global Positioning System geodesy (CGPS) have revealed periodic slow or silent earthquakes along the Cascadia subduction zone with a spectrum of timing and periodicity. These creep events perturb time series of GPS observations and yield coherent displacement fields that relate to the extent and magnitude of fault displacement. In this study, time independent inversions of the surface displacement fields that accompany eight slow earthquakes characterize slip distributions along the plate interface for each event. The inversions employed in this study utilize Okada's elastic dislocation model and a non- negative least squares approach. Methodologies for optimizing the slip distribution smoothing parameter for a particular station distribution have also been investigated, significantly reducing the number of possible slip distributions and the range of estimates for total moment release for each event. The discretized slip distribution calculated for multiple creep events identifies areas of the Cascadia plate interface where slip persistently recurs. The current hypothesis, that slow earthquakes are modulated by forced fluid flow, leads to the possibility that some regions of the Cascadia plate interface may display fault patches preferentially exploited by fluid flow. Thus, the identification of regions of the plate interface that repeatedly slip during slow events may yield important information regarding the identification of these fluid pathways.

Yessotoxins, a Group of Marine Polyether Toxins: an Overview

PubMed Central

Paz, Beatriz; Daranas, Antonio H.; Norte, Manuel; Riobó, Pilar; Franco, José M.; Fernández, José J.

2008-01-01

Yessotoxin (YTX) is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish poisoning (DSP) because they are often simultaneously extracted with DSP toxins, and give positive results when tested in the conventional mouse bioassay for DSP toxins. However, recent evidence suggests that YTXs should be excluded from the DSP toxins group, because unlike okadaic acid (OA) and dinophyisistoxin-1 (DTX-1), YTXs do not cause either diarrhea or inhibition of protein phosphatases. In spite of the increasing number of molecular studies focused on the toxicity of YTX, the precise mechanism of action is currently unknown. Since the discovery of YTX, almost forty new analogues isolated from both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS techniques. These studies indicate a wide variability in the profile and the relative abundance of YTXs in both, bivalves and dinoflagellates. This review covers current knowledge on the origin, producer organisms and vectors, chemical structures, metabolism, biosynthetic origin, toxicological properties, potential risks to human health and advances in detection methods of YTXs. PMID:18728761

Yessotoxins, a group of marine polyether toxins: an overview.

PubMed

Paz, Beatriz; Daranas, Antonio H; Norte, Manuel; Riobó, Pilar; Franco, José M; Fernández, José J

2008-05-07

Yessotoxin (YTX) is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish poisoning (DSP) because they are often simultaneously extracted with DSP toxins, and give positive results when tested in the conventional mouse bioassay for DSP toxins. However, recent evidence suggests that YTXs should be excluded from the DSP toxins group, because unlike okadaic acid (OA) and dinophyisistoxin-1 (DTX-1), YTXs do not cause either diarrhea or inhibition of protein phosphatases. In spite of the increasing number of molecular studies focused on the toxicity of YTX, the precise mechanism of action is currently unknown. Since the discovery of YTX, almost forty new analogues isolated from both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS techniques. These studies indicate a wide variability in the profile and the relative abundance of YTXs in both, bivalves and dinoflagellates. This review covers current knowledge on the origin, producer organisms and vectors, chemical structures, metabolism, biosynthetic origin, toxicological properties, potential risks to human health and advances in detection methods of YTXs.

Temperature and base requirements for the alkaline hydrolysis of okadaite's esters.

PubMed

Rodrigues, Susana M; Vale, Paulo

2009-06-01

Portuguese bivalves are recurrently contaminated with okadaic acid (OA) and dinophysistoxin-2 (DTX2), found mainly in esterified forms. Throughout the years different conditions have been reported in the literature for releasing the parent toxins through an alkaline hydrolysis step, in order to simplify their detection by HPLC-FLD or LC-MS. In order to clearly understand toxin stability and reaction end-point the binominous temperature/time course and base concentration were studied using naturally contaminated bivalve samples. The results showed a strong temperature dependence of the reaction. At 60 degrees C and 70 degrees C the hydrolysis was fast, and 40min were sufficient for maximal recovery of OA and DTX2, while at 40 degrees C and 50 degrees C it was only complete after 100min and 60min, respectively. At room temperature the reaction was slow and incomplete even after 2h. Stability of OA and DTX2 in semi-purified bivalve matrix at 70 degrees C for 2h was demonstrated. Concentrations of sodium hydroxide lower than 2.5M, corresponding to a final incubation concentration of 0.23M, resulted in incomplete release of parent toxins, demonstrating that high concentrations are needed when taking into account the dilution in the supernatant extract.

The c-mos proto-oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell-free extracts of Xenopus oocytes and eggs.

PubMed Central

Nebreda, A R; Hunt, T

1993-01-01

During studies of the activation and inactivation of the cyclin B-p34cdc2 protein kinase (MPF) in cell-free extracts of Xenopus oocytes and eggs, we found that a bacterially expressed fusion protein between the Escherichia coli maltose-binding protein and the Xenopus c-mos protein kinase (malE-mos) activated a 42 kDa MAP kinase. The activation of MAP kinase on addition of malE-mos was consistent, whereas the activation of MPF was variable and failed to occur in some oocyte extracts in which cyclin A or okadaic acid activated both MPF and MAP kinase. In cases when MPF activation was transient, MAP kinase activity declined after MPF activity was lost, and MAP kinase, but not MPF, could be maintained at a high level by the presence of malE-mos. When intact oocytes were treated with progesterone, however, the activation of MPF and MAP kinase occurred simultaneously, in contrast to the behaviour of extracts. These observations suggest that one role of c-mos may be to maintain high MAP kinase activity in meiosis. They also imply that the activation of MPF and MAP kinase in vivo are synchronous events that normally rely on an agent that has still to be identified. Images PMID:8387916

Isoflurane unveils a critical role of glutamate transporter type 3 in regulating hippocampal GluR1 trafficking and context-related learning and memory in mice.

PubMed

Cao, J; Wang, Z; Mi, W; Zuo, Z

2014-07-11

Glutamate transporter type 3 (EAAT3) may play a role in cognition. Isoflurane enhances EAAT3 trafficking to the plasma membrane. Thus, we used isoflurane to determine how EAAT3 might regulate learning and memory and the trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, such as GluR1, to the plasma membrane, a fundamental biochemical process for learning and memory. Here, isoflurane increased EAAT3 but did not change GluR1 levels in the plasma membrane of wild-type mouse hippocampus. Isoflurane increased protein phosphatase activity in the wild-type and EAAT3(-/-) mouse hippocampus. Also, isoflurane reduced GluR1 in the plasma membrane and decreased phospho-GluR1 in EAAT3(-/-) mice. The phosphatase inhibitor okadaic acid attenuated these effects. Finally, isoflurane inhibited context-related fear conditioning in EAAT3(-/-) mice but not in wild-type mice. Thus, isoflurane may increase GluR1 trafficking to the plasma membrane via EAAT3 and inhibit GluR1 trafficking via protein phosphatase. Lack of EAAT3 effects leads to decreased GluR1 trafficking and impaired cognition after isoflurane exposure in EAAT3(-/-) mice. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

YASEIS: Yet Another computer program to calculate synthetic SEISmograms for a spherically multi-layered Earth model

NASA Astrophysics Data System (ADS)

Ma, Yanlu

2013-04-01

those from YASEIS. Finally the static displacements in the source region are computed by choosing a very small frequency value in YASEIS which is designed for computing the dynamic response, and compared with the results in a homogeneous half-space model (Okada 1992). [1] Friederich, W. and J. Dalkolmo (1995). Complete synthetic seismograms for a spherically symmetric Earth a numerical computation of the Green's function in the frequency domain, Geophys. J. Int., vol. 122, 537-550. [2] Kawai, K., N. Takeuchi, and R.J. Geller (2006). Complete synthetic seismograms up to 2Hz for transversely isotropic spherically symmetric media, Geophys. J. Int., vol. 164, 411-424. [3] Okada, Y. (1992). Internal deformation due to shear and tensile faults in a half space, Bull. Seismol. Soc. Am., vol. 82, no. 2, 1018-1040. [4] Takeuchi, H. and M. Saito (1972). Seismic surface waves, Methods in computational physics, vol. II, 217-295. [5] Wang, R. (1999). A simple orthonormalization method for stable and efficient computation of Green's functions, Bull. Seismol. Soc. Am., vol. 89, no. 3, 733-741.

A low molecular weight protein tyrosine phosphatase from Synechocystis sp. strain PCC 6803: enzymatic characterization and identification of its potential substrates

PubMed Central

Mukhopadhyay, Archana; Kennelly, Peter J.

2011-01-01

The predicted protein product of open reading frame slr0328 from Synechocystis sp. PCC 6803, SynPTP, possesses significant amino acid sequence similarity with known low molecular weight protein tyrosine phosphatases (PTPs). To determine the functional properties of this hypothetical protein, open reading frame slr0328 was expressed in Escherichia coli. The purified recombinant protein, SynPTP, displayed its catalytic phosphatase activity towards several tyrosine, but not serine, phosphorylated exogenous protein substrates. The protein phosphatase activity of SynPTP was inhibited by sodium orthovanadate, a known inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor for many serine/threonine phosphatases. Kinetic analysis indicated that the Km and Vmax values for SynPTP towards p-nitrophenyl phosphate are similar to those of other known bacterial low molecular weight PTPs. Mutagenic alteration of the predicted catalytic cysteine of PTP, Cys7, to serine abolished enzyme activity. Using a combination of immunodetection, mass spectrometric analysis and mutagenically altered Cys7SerAsp125Ala-SynPTP, we identified PsaD (photosystem I subunit II), CpcD (phycocyanin rod linker protein) and phycocyanin-α and -β subunits as possible endogenous substrates of SynPTP in this cyanobacterium. These results indicate that SynPTP might be involved in the regulation of photosynthesis in Synechocystis sp. PCC 6803. PMID:21288886

Elevated levels of placental growth factor represent an adaptive host response in sepsis.

PubMed

Yano, Kiichiro; Okada, Yoshiaki; Beldi, Guido; Shih, Shou-Ching; Bodyak, Natalya; Okada, Hitomi; Kang, Peter M; Luscinskas, William; Robson, Simon C; Carmeliet, Peter; Karumanchi, S Ananth; Aird, William C

2008-10-27

Recently, we demonstrated that circulating levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are increased in sepsis (Yano, K., P.C. Liaw, J.M. Mullington, S.C. Shih, H. Okada, N. Bodyak, P.M. Kang, L. Toltl, B. Belikoff, J. Buras, et al. 2006. J. Exp. Med. 203:1447-1458). Moreover, enhanced VEGF/Flk-1 signaling was shown to contribute to sepsis morbidity and mortality. We tested the hypothesis that PlGF also contributes to sepsis outcome. In mouse models of endotoxemia and cecal ligation puncture, the genetic absence of PlGF or the systemic administration of neutralizing anti-PlGF antibodies resulted in higher mortality compared with wild-type or immunoglobulin G-injected controls, respectively. The increased mortality associated with genetic deficiency of PlGF was reversed by adenovirus (Ad)-mediated overexpression of PlGF. In the endotoxemia model, PlGF deficiency was associated with elevated circulating levels of VEGF, induction of VEGF expression in the liver, impaired cardiac function, and organ-specific accentuation of barrier dysfunction and inflammation. Mortality of endotoxemic PlGF-deficient mice was increased by Ad-mediated overexpression of VEGF and was blocked by expression of soluble Flt-1. Collectively, these data suggest that up-regulation of PlGF in sepsis is an adaptive host response that exerts its benefit, at least in part, by attenuating VEGF signaling.

Determination of the toxic variability of lipophilic biotoxins in marine bivalve and gastropod tissues treated with an industrial canning process.

PubMed

García, Carlos; Oyaneder-Terrazas, Javiera; Contreras, Cristóbal; Del Campo, Miguel; Torres, Rafael; Contreras, Héctor R

2016-11-01

Contamination of shellfish with lipophilic marine biotoxins (LMB), pectenotoxins (PTXs), yessotoxins (YTXs) and okadaic acid (OA) toxin groups in southern Chile is a constant challenge for the development of miticulture considering the high incidence of toxic episodes that tend to occur. This research is focused on using methodologies for assessing the decrease in toxins of natural resources in Chile with high value, without altering the organoleptic properties of the shellfish. The species were processed through steaming (1 min at 121°C) and subsequent canning (5 min at 121°C). Changes in the profiles of toxins and total toxicity levels of LMB in endemic bivalves and gastropods were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total reduction of toxicity (≈ 15%) was not related to the destruction of the toxin, but rather to the loss of LMB on removing the shells and packing media of canned products (***p < 0.001). Industrial processing of shellfish reduces LMB contents by up to 15% of the total initial contents, concomitant only with the interconversion of PTX-group toxins into PTX-2sa. In soft bottom-dwelling species with toxicities beyond the standard for safe human consumption (≥ 160 μg OA-eq kg - 1 ), toxicity can be reduced to safe levels through industrial preparation procedures.

Cyanotoxin bioaccumulation in freshwater fish, Washington State, USA.

PubMed

Hardy, F Joan; Johnson, Art; Hamel, Kathy; Preece, Ellen

2015-11-01

Until recently, exposure pathways of concern for cyanotoxins have focused on recreational exposure, drinking water, and dermal contact. Exposure to cyanotoxins through fish consumption is a relatively new area of investigation. To address this concern, microcystins and other cyanotoxins were analyzed in fish collected from nine Washington lakes with recurrent toxic blooms using two types of enzyme-linked immunosorbent assays (ELISAs) and liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS). Microcystins or microcystin-like compounds were elevated in fish liver relative to muscle and other tissues (liver>gut>muscle). Microcystin concentrations in fish fillet samples using anti-Adda ELISA (range 6.3-11 μg/kg wet weight) were consistently higher in all fish species than concentrations using anti-microcystin (MC)-leucine-arginine (LR) ELISA (range 0.25-2.4 μg/kg wet weight). MC-leucine-alanine (LA) was the only variant detected in fish (2.5-12 μg/kg in four livers) among the nine variants analyzed by LC-MS/MS. Fish fillets showed no accumulation of the MCs targeted by LC-MS/MS. Other cyanotoxins analyzed (anatoxin-a, saxitoxin, domoic acid, and okadaic acid) were not detected in fish. Based on this and evidence from other studies, we believe that people can safely consume two 8-oz fish fillet meals per week from lakes with blooms producing MCs (clean the fish and discard viscera).

Phosphorylation and subcellular redistribution of high mobility group proteins 14 and 17, analyzed by mass spectrometry.

PubMed Central

Louie, D. F.; Gloor, K. K.; Galasinski, S. C.; Resing, K. A.; Ahn, N. G.

2000-01-01

High mobility group (HMG) proteins 14 and 17 are nonhistone nuclear proteins that have been implicated in control of transcription and chromatin structure. To examine the posttranslational modifications of HMG-14 and -17 in vivo, HMG proteins were prepared from nuclear vs. cytosolic fractions of human K562 cells treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or okadaic acid (OA) and examined by electrospray mass spectrometry. Analysis of full-length masses demonstrated mono-, di-, and triphosphorylation of HMG-14 and mono- and diphosphorylation of HMG-17 from OA treated cells, whereas HMG-14 and -17 from TPA treated cells were monophosphorylated. Peptide mass and sequence analysis showed major and minor phosphorylation sites, respectively, at Ser24 and Ser28 in HMG-17, and Ser20 and Ser24 in HMG-14. These sites were found in the consensus sequence RRSARLSAK, within the nucleosomal binding domain of each protein. A third phosphorylation site in HMG-14 was located at either Ser6 or Ser7. Interestingly, the proportion of HMG-14 and -17 found in cytosolic pools increased significantly after 1 h of treatment compared to control cells and showed preferential phosphorylation compared with proteins from nuclear fractions. These results suggest that phosphorylation of HMG-14 and -7 interferes with nuclear localization mechanisms in a manner favoring release from nuclei. PMID:10739259

Phosphorylation and subcellular redistribution of high mobility group proteins 14 and 17, analyzed by mass spectrometry.

PubMed

Louie, D F; Gloor, K K; Galasinski, S C; Resing, K A; Ahn, N G

2000-01-01

High mobility group (HMG) proteins 14 and 17 are nonhistone nuclear proteins that have been implicated in control of transcription and chromatin structure. To examine the posttranslational modifications of HMG-14 and -17 in vivo, HMG proteins were prepared from nuclear vs. cytosolic fractions of human K562 cells treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or okadaic acid (OA) and examined by electrospray mass spectrometry. Analysis of full-length masses demonstrated mono-, di-, and triphosphorylation of HMG-14 and mono- and diphosphorylation of HMG-17 from OA treated cells, whereas HMG-14 and -17 from TPA treated cells were monophosphorylated. Peptide mass and sequence analysis showed major and minor phosphorylation sites, respectively, at Ser24 and Ser28 in HMG-17, and Ser20 and Ser24 in HMG-14. These sites were found in the consensus sequence RRSARLSAK, within the nucleosomal binding domain of each protein. A third phosphorylation site in HMG-14 was located at either Ser6 or Ser7. Interestingly, the proportion of HMG-14 and -17 found in cytosolic pools increased significantly after 1 h of treatment compared to control cells and showed preferential phosphorylation compared with proteins from nuclear fractions. These results suggest that phosphorylation of HMG-14 and -7 interferes with nuclear localization mechanisms in a manner favoring release from nuclei.

Urea inhibits NaK2Cl cotransport in human erythrocytes.

PubMed Central

Lim, J; Gasson, C; Kaji, D M

1995-01-01

We examined the effect of urea on NaK2Cl cotransport in human erythrocytes. In erythrocytes from nine normal subjects, the addition of 45 mM urea, a concentration commonly encountered in uremic subjects, inhibited NaK2Cl cotransport by 33 +/- 7%. Urea inhibited NaK2Cl cotransport reversibly, and in a concentration-dependent fashion with half-maximal inhibition at 63 +/- 10 mM. Acute cell shrinkage increased, and acute cell swelling decreased NaK2Cl cotransport in human erythrocytes. Okadaic acid (OA), a specific inhibitor of protein phosphatase 1 and 2A, increased NaK2Cl cotransport by nearly 80%, suggesting an important role for these phosphatases in the regulation of NaK2Cl cotransport. Urea inhibited bumetanide-sensitive K influx even when protein phosphatases were inhibited with OA, suggesting that urea acted by inhibiting a kinase. In cells subjected to shrinking and OA pretreatment, maneuvers expected to increase the net phosphorylation, urea inhibited cotransport only minimally, suggesting that urea acted by causing a net dephosphorylation of the cotransport protein, or some key regulatory protein. The finding that concentrations of urea found in uremic subjects inhibited NaK2Cl cotransport, a widespread transport pathway with important physiological functions, suggests that urea is not only a marker for accumulation of other uremic toxins, but may be a significant uremic toxin itself. PMID:7593597

Carfilzomib induces leukaemia cell apoptosis via inhibiting ELK1/KIAA1524 (Elk-1/CIP2A) and activating PP2A not related to proteasome inhibition.

PubMed

Liu, Chun-Yu; Hsieh, Feng-Shu; Chu, Pei-Yi; Tsai, Wen-Chun; Huang, Chun-Teng; Yu, Yuan-Bin; Huang, Tzu-Ting; Ko, Po-Shen; Hung, Man-Hsin; Wang, Wan-Lun; Shiau, Chung-Wai; Chen, Kuen-Feng

2017-06-01

Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib. Ectopic expression of KIAA1524, or pretreatment with the PP2A inhibitor, okadaic acid, suppressed carfilzomib-induced apoptosis and KIAA1524 downregulation in sensitive cells, whereas co-treatment with the PP2A agonist, forskolin, enhanced carfilzomib-induced apoptosis in resistant cells. Mechanistically, carfilzomib affected KIAA1524 transcription through disturbing ELK1 (Elk-1) binding to the KIAA1524 promoter. Moreover, the drug sensitivity and mechanism of carfilzomib in xenograft mouse models correlated well with the effects of carfilzomib on KIAA1524 and p-Akt expression, as well as PP2A activity. Our data disclosed a novel drug mechanism of carfilzomib in leukaemia cells and suggests the potential therapeutic implication of KIAA1524 in leukaemia treatment. © 2017 John Wiley & Sons Ltd.

Development of Certified Reference Materials for Diarrhetic Shellfish Poisoning Toxins, Part 1: Calibration Solutions.

PubMed

Beach, Daniel G; Crain, Sheila; Lewis, Nancy; LeBlanc, Patricia; Hardstaff, William R; Perez, Ruth A; Giddings, Sabrina D; Martinez-Farina, Camilo F; Stefanova, Roumiana; Burton, Ian W; Kilcoyne, Jane; Melanson, Jeremy E; Quilliam, Michael A; McCarron, Pearse

2016-09-01

Okadaic acid (OA) and its analogs dinophysistoxins-1 (DTX1) and -2 (DTX2) are lipophilic polyethers produced by marine dinoflagellates. These toxins accumulate in shellfish and cause diarrhetic shellfish poisoning (DSP) in humans. Regulatory testing of shellfish is essential to safeguard public health and for international trade. Certified reference materials (CRMs) play a key role in analytical monitoring programs. This paper presents an overview of the interdisciplinary work that went into the planning, production, and certification of calibration-solution CRMs for OA, DTX1, and DTX2. OA and DTX1 were isolated from large-scale algal cultures and DTX2 from naturally contaminated mussels. Toxins were isolated by a combination of extraction and chromatographic steps with processes adapted to suit the source and concentration of each toxin. New 19-epi-DSP toxin analogs were identified as minor impurities. Once OA, DTX1, and DTX2 were established to be of suitable purity, solutions were prepared and dispensed into flame-sealed glass ampoules. Certification measurements were carried out using quantitative NMR spectroscopy and LC-tandem MS. Traceability of measurements was established through certified external standards of established purity. Uncertainties were assigned following standards and guidelines from the International Organization for Standardization, with components from the measurement, stability, and homogeneity studies being propagated into final combined uncertainties.

Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB-F344 cells.

PubMed

Hirane, Miku; Ishii, Shuhei; Tomimatsu, Ayaka; Fukushima, Kaori; Takahashi, Kaede; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

2016-11-01

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA 1 to LPA 6 ) mediates a variety of cellular functions, including cell motility. In the present study, we investigated the effects of LPA receptors on cell motile activity during multi-stage hepatocarcinogenesis in rat liver epithelial WB-F344 cells treated with chemical liver carcinogens. Cells were treated with a initiator (N-nitrosodiethylamine (DEN)) and three promoters (phenobarbital (PB), okadaic acid (OA) and clofibrate) every 24 h for 2 days. Cell motile activity was elevated by DEN, correlating with Lpar3 expression. PB, OA, and clofibrate elevated Lpar1 expression and inhibited cell motile activity. To evaluate the effects of long-term treatment on cell motility, cells were treated with DEN and/or PB for at least 6 months. Lpar3 expression and cell motile activity were significantly elevated by the long-term DEN treatment with or without further PB treatment. In contrast, long-term PB treatment with or without further DEN elevated Lpar1 expression and inhibited cell motility. When the synthesis of extracellular LPA was blocked by a potent ATX inhibitor S32826 before cell motility assay, the cell motility induced by DEN and PB was markedly suppressed. These results suggest that activation of the different LPA receptors may regulate the biological functions of cells treated with chemical carcinogens. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Isolation, Cloning, and Expression of an Acid Phosphatase Containing Phosphotyrosyl Phosphatase Activity from Prevotella intermedia

PubMed Central

Chen, Xiaochi; Ansai, Toshihiro; Awano, Shuji; Iida, Toshiya; Barik, Sailen; Takehara, Tadamichi

1999-01-01

A novel acid phosphatase containing phosphotyrosyl phosphatase (PTPase) activity, designated PiACP, from Prevotella intermedia ATCC 25611, an anaerobe implicated in progressive periodontal disease, has been purified and characterized. PiACP, a monomer with an apparent molecular mass of 30 kDa, did not require divalent metal cations for activity and was sensitive to orthovanadate but highly resistant to okadaic acid. The enzyme exhibited substantial activity against tyrosine phosphate-containing peptides derived from the epidermal growth factor receptor. On the basis of N-terminal and internal amino acid sequences of purified PiACP, the gene coding for PiACP was isolated and sequenced. The PiACP gene consisted of 792 bp and coded for a basic protein with an Mr of 29,164. The deduced amino acid sequence exhibited striking similarity (25 to 64%) to those of members of class A bacterial acid phosphatases, including PhoC of Morganella morganii, and involved a conserved phosphatase sequence motif that is shared among several lipid phosphatases and the mammalian glucose-6-phosphatases. The highly conservative motif HCXAGXXR in the active domain of PTPase was not found in PiACP. Mutagenesis of recombinant PiACP showed that His-170 and His-209 were essential for activity. Thus, the class A bacterial acid phosphatases including PiACP may function as atypical PTPases, the biological functions of which remain to be determined. PMID:10559178

Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein.

PubMed

Jeon, Yeong Ha; Park, Yong Hwan; Lee, Jea Hwang; Hong, Jeong-Ho; Kim, Ick Young

2014-07-01

Selenoprotein W (SelW) is expressed in various tissues, particularly in skeletal muscle. We have previously reported that SelW is up-regulated during C2C12 skeletal muscle differentiation and inhibits binding of 14-3-3 to its target proteins. 14-3-3 reduces myogenic differentiation by inhibiting nuclear translocation of transcriptional co-activator with PDZ-binding motif (TAZ). Phosphorylation of TAZ at Ser89 is required for binding to 14-3-3, leading to cytoplasmic retention of TAZ and a delay in myogenic differentiation. Here, we show that myogenic differentiation was delayed in SelW-knockdown C2C12 cells. Down-regulation of SelW also increased TAZ binding to 14-3-3, which eventually resulted in decreasing translocation of TAZ to the nucleus. However, phosphorylation of TAZ at Ser89 was not affected. Although phosphorylation of TAZ at Ser89 was sustained by the phosphatase inhibitor okadaic acid, nuclear translocation of TAZ was increased by ectopic expression of SelW. This result was due to decreased binding of TAZ to 14-3-3. We also found that the interaction between TAZ and MyoD was increased by ectopic expression of SelW. Taken together, these findings strongly demonstrate that SelW enhances C2C12 cell differentiation by inhibiting TAZ binding to 14-3-3. Copyright © 2014 Elsevier B.V. All rights reserved.

Determination of lipophilic marine toxins in mussels. Quantification and confirmation criteria using high resolution mass spectrometry.

PubMed

Domènech, Albert; Cortés-Francisco, Nuria; Palacios, Oscar; Franco, José M; Riobó, Pilar; Llerena, José J; Vichi, Stefania; Caixach, Josep

2014-02-07

A multitoxin method has been developed for quantification and confirmation of lipophilic marine biotoxins in mussels by liquid chromatography coupled to high resolution mass spectrometry (HRMS), using an Orbitrap-Exactive HCD mass spectrometer. Okadaic acid (OA), yessotoxin, azaspiracid-1, gymnodimine, 13-desmethyl spirolide C, pectenotoxin-2 and Brevetoxin B were analyzed as representative compounds of each lipophilic toxin group. HRMS identification and confirmation criteria were established. Fragment and isotope ions and ion ratios were studied and evaluated for confirmation purpose. In depth characterization of full scan and fragmentation spectrum of the main toxins were carried out. Accuracy (trueness and precision), linearity, calibration curve check, limit of quantification (LOQ) and specificity were the parameters established for the method validation. The validation was performed at 0.5 times the current European Union permitted levels. The method performed very well for the parameters investigated. The trueness, expressed as recovery, ranged from 80% to 94%, the precision, expressed as intralaboratory reproducibility, ranged from 5% to 22% and the LOQs range from 0.9 to 4.8pg on column. Uncertainty of the method was also estimated for OA, using a certified reference material. A top-down approach considering two main contributions: those arising from the trueness studies and those coming from the precision's determination, was used. An overall expanded uncertainty of 38% was obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

Two simple models for accounting mussel contamination with diarrhoetic shellfish poisoning toxins at Aveiro lagoon: Control by rainfall and atmospheric forcing

NASA Astrophysics Data System (ADS)

Vale, Paulo

2012-02-01

At Aveiro lagoon (Portuguese northwest coast) bivalve contamination with diarrhoetic shellfish poisoning toxins (DSTs), okadaic acid (OA) and dinophysistoxin-2 (DTX2), is a recurrent annual phenomenon seriously affecting seafood safety. The influence of meteorological parameters was studied to understand accumulation of DSTs in mussels, related to the blooming of the causative toxic microalgae, belonging to genus Dinophysis. Two simplified models were useful in predicting the accumulation of DSTs in blue mussels from this lagoon. Either the May river drainage or the rainfall accumulated from January through May could adequately predict the severity of OA accumulated from predation upon Dinophysis acuminata during June/July. In both cases a linear relationship was obtained, with correlation coefficients of 0.85 or greater. Winds with a west direction favour coastal concentration of Dinophysis acuta in Aveiro region. Both OA and DTX2 contamination increased exponentially in September/October with the cumulative number of days with W-wind orientation in the preceding August (correlation coefficients greater than 0.92). This relationship was attributed to the quadratic effect of wind stress on surface currents. August is a transitional month, when the continental runoff effect upon Dinophysis acuminata can still be observed and Dinophysis acuta advection may be promoted by westerly winds occurring in July. The frequency of periods with northerly winds in July can halt accumulation of toxins derived from Dinophysis acuta.

Modeling of February 1993 Intrusion Seen by JERS-1 Satellite, Kilauea Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Moore, S.; Wauthier, C.; Fukushima, Y.; Poland, M. P.

2016-12-01

Interferometric Synthetic Aperture Radar (InSAR) is a valuable means of remotely assessing deformation on the surface of the earth. At Kilauea Volcano, Hawai'i many InSAR deformation maps (interferograms) have been studied in recent years to monitor deformation on the volcano. In February 1993, a diking event occurred that could be one of the first intrusions seen by InSAR satellites at Kilauea. This event has not received much attention due to little geodetic data spanning the event. Between October 1992 and March 1993, SAR images from the JERS-1 satellite captured 30 centimeters of surface deformation occurring along the East Rift Zone (ERZ) near Makaopuhi crater. Seismic activity was similar to other intrusions with more than 5,000 shallow (<5 km) earthquakes occurred in the area between the summit caldera and Makaopuhi crater from February 7-9, 1993 [Okubo & Nakata, 2003]. We used simple analytical half-space solutions (e.g., Mogi [1958], Okada [1992)]), as well as a more complex and mechanically robust numerical approach (3D-MBEM [Cayol and Cornet, 1997]) to model deformation sources active between October 1992 and March 1993. Non-linear inversions of the JERS-1 Interferogram show that the most likely source to account for the February 1993 observed deformation is a subvertical rectangular dike with an opening of 1.5 m reaching depths of 1.5 to 3 km.

PREFACE: The International Conference on Science of Friction

NASA Astrophysics Data System (ADS)

Miura, Kouji; Matsukawa, Hiroshi

2007-07-01

The first international conference on the science of friction in Japan was held at Irago, Aichi on 9-13 September 2007. The conference focused on the elementary process of friction phenomena from the atomic and molecular scale view. Topics covered in the conference are shown below.:

Multi Hazard Assessment: The Azores Archipelagos (PT) case

NASA Astrophysics Data System (ADS)

Aifantopoulou, Dorothea; Boni, Giorgio; Cenci, Luca; Kaskara, Maria; Kontoes, Haris; Papoutsis, Ioannis; Paralikidis, Sideris; Psichogyiou, Christina; Solomos, Stavros; Squicciarino, Giuseppe; Tsouni, Alexia; Xerekakis, Themos

2016-04-01

) and earthquake (475 years return period) was used. Topography, lithology, soil moisture and LU/LC were also accounted for. Soil erosion risk was assessed through the empirical model RUSLE (Renard et al. 1991b). Rainfall erosivity, topography and vegetation cover are the main parameters which were used for predicting the proneness to soil loss. Expected, maximum tsunami wave heights were estimated for a specific earthquake scenario at designated forecast points along the coasts. Deformation at the source was calculated by utilizing the Okada code (Okada, 1985). Tsunami waves' generation and propagation is based on the SWAN model (JRC/IPSC modification). To estimate the wave height (forecast points) the Green's Law function was used (JRC Tsunami Analysis Tool). Storm tracks' historical data indicate a return period of 17 /41 years for H1 /H2 hurricane categories respectively. NOAA WAVEWATCH III model hindcast reanalysis was used to estimate the maximum significant wave height (wind and swell) along the coastline during two major storms. The associated storm-surge risk assessment accounted also for the coastline morphology. Seven empirical (independent) indicators were used to express the erosion susceptibility of the coasts. Each indicator is evaluated according to a semi?quantitative score that represents low, medium and high level of erosion risk or impact. The estimation of the coastal erosion hazard was derived through aggregating the indicators in a grid scale.

Lattice preferred orientation development in lower mantle minerals: Implications for seismic anisotropy

NASA Astrophysics Data System (ADS)

Miyagi, L. M.

2011-12-01

Seismic anisotropy in the deep earth likely results from deformation induced texturing (lattice preferred orientation) of polycrystalline rocks in the Earth's interior. Interpreting these anisotropies in terms of the dynamics and deformation structure of the deep earth requires an understanding of the mechanisms that lead to texturing. In high pressure experiments texture can develop during phase transformations, recrystallization, and deformation. Active deformation mechanisms can be constrained by modeling experimental deformation textures with polycrystal plasticity codes. Once the dominant deformation mechanisms are established for the relevant mineral phases, this information can be combined with geodynamic modeling to predict texture and anisotropy development in the Earth's interior. In (Mg,Fe)SiO3 perovskite (Pv), the major mineral phase of the lower mantle, diamond anvil cell deformation textures are consistent with dominant slip on (001) planes in [100], [010] and/or <110> direction (e.g. Wenk et al. 2006; Miyagi et al. 2010a). (Mg,Fe)O magnesiowüstite (Mw) the second most abundant phase in the lower mantle, produces textures consistent with slip on {110}<-110> (e.g. Merkel et al 2002; Long et al. 2009). Although these two phases develop significant texture during deformation experiments, interestingly, the bulk of the lower mantle exhibits very little anisotropy. This lack of anisotropy may be due to deformation by diffusion processes which do not produce texture (e.g. Karato et al. 1995), or to the fact that deformation textures in Pv and Mw produce opposite anisotropies which cancel each other, yielding a nearly isotropic aggregate (Wenk et al. 2006). In the D" region, (Mg,Fe)SiO3 post-perovskite (pPv) is thought to be the major mineral phase. High pressure deformation experiments on MgGeO3 pPv (Okada et al. 2010; Miyagi et al. 2011) and MgSiO3 pPv (Miyagi et al. 2010b) at ambient temperature, as well as MnGeO3 pPv at 2000 K (Hirose et al. 2010), all

Complex regulation of Arabidopsis AGR1/PIN2-mediated root gravitropic response and basipetal auxin transport by cantharidin-sensitive protein phosphatases

NASA Technical Reports Server (NTRS)

Shin, Heungsop; Shin, Hwa-Soo; Guo, Zibiao; Blancaflor, Elison B.; Masson, Patrick H.; Chen, Rujin

2005-01-01

Polar auxin transport, mediated by two distinct plasma membrane-localized auxin influx and efflux carrier proteins/complexes, plays an important role in many plant growth and developmental processes including tropic responses to gravity and light, development of lateral roots and patterning in embryogenesis. We have previously shown that the Arabidopsis AGRAVITROPIC 1/PIN2 gene encodes an auxin efflux component regulating root gravitropism and basipetal auxin transport. However, the regulatory mechanism underlying the function of AGR1/PIN2 is largely unknown. Recently, protein phosphorylation and dephosphorylation mediated by protein kinases and phosphatases, respectively, have been implicated in regulating polar auxin transport and root gravitropism. Here, we examined the effects of chemical inhibitors of protein phosphatases on root gravitropism and basipetal auxin transport, as well as the expression pattern of AGR1/PIN2 gene and the localization of AGR1/PIN2 protein. We also examined the effects of inhibitors of vesicle trafficking and protein kinases. Our data suggest that protein phosphatases, sensitive to cantharidin and okadaic acid, are likely involved in regulating AGR1/PIN2-mediated root basipetal auxin transport and gravitropism, as well as auxin response in the root central elongation zone (CEZ). BFA-sensitive vesicle trafficking may be required for the cycling of AGR1/PIN2 between plasma membrane and the BFA compartment, but not for the AGR1/PIN2-mediated root basipetal auxin transport and auxin response in CEZ cells.

Microvascular dysfunction with increased vascular leakage response in mice systemically exposed to arsenic.

PubMed

Chen, Shih-Chieh; Huang, Shin-Yin; Lu, Chi-Yu; Hsu, Ya-Hung; Wang, Dean-Chuan

2014-09-01

The mechanisms underlying cardiovascular disease induced by arsenic exposure are not completely understood. The objectives of this study were to investigate whether arsenic-fed mice have an increased vascular leakage response to vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity is involved in mustard oil-induced leakage. ICR mice were fed water or sodium arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents was quantified using the Evans blue (EB) technique or vascular labeling with carbon particles. Increased EB leakage and high density of carbon-labeled microvessels were detected in arsenic-fed mice treated with mustard oil. Histamine induced significantly higher vascular leakage in arsenic-fed mice than in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil-induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and NK1R were similar in both groups. PP2A activity was significantly higher in the arsenic-fed mice compared with the control group. These findings indicate that microvessels generally respond to vasoactive agents, and that the increased PP2A activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice. Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in response to vasoactive agents.

Sugar-mediated semidian oscillation of gene expression in the cassava storage root regulates starch synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jansson, Christer; Baguma, Yona; Sun, Chuanxin

Starch branching enzyme (SBE) activity in the cassava storage root exhibited a diurnal fluctuation, dictated by a transcriptional oscillation of the corresponding SBE genes. The peak of SBE activity coincided with the onset of sucrose accumulation in the storage, and we conclude that the oscillatory mechanism keeps the starch synthetic apparatus in the storage root sink in tune with the flux of sucrose from the photosynthetic source. When storage roots were uncoupled from the source, SBE expression could be effectively induced by exogenous sucrose. Turanose, a sucrose isomer that cannot be metabolized by plants, mimicked the effect of sucrose, demonstratingmore » that downstream metabolism of sucrose was not necessary for signal transmission. Also glucose and glucose-1-P induced SBE expression. Interestingly, induction by sucrose, turanose and glucose but not glucose-1-P sustained an overt semidian (12-h) oscillation in SBE expression and was sensitive to the hexokinase (HXK) inhibitor glucosamine. These results suggest a pivotal regulatory role for HXK during starch synthesis. Abscisic acid (ABA) was another potent inducer of SBE expression. Induction by ABA was similar to that of glucose-1-P in that it bypassed the semidian oscillator. Both the sugar and ABA signaling cascades were disrupted by okadaic acid, a protein phosphatase inhibitor. Based on these findings, we propose a model for sugar signaling in regulation of starch synthesis in the cassava storage root.« less

Role of membrane cholesterol in spontaneous exocytosis at frog neuromuscular synapses: reactive oxygen species–calcium interplay

PubMed Central

Petrov, Alexey M; Yakovleva, Anastasiya A; Zefirov, Andrey L

2014-01-01

Using electrophysiological and optical techniques, we studied the mechanisms by which cholesterol depletion stimulates spontaneous transmitter release by exocytosis at the frog neuromuscular junction. We found that methyl-β-cyclodextrin (MCD, 10 mm)-mediated exhaustion of cholesterol resulted in the enhancement of reactive oxygen species (ROS) production, which was prevented by the antioxidant N-acetyl cysteine (NAC) and the NADPH oxidase inhibitor apocynin. An increase in ROS levels occurred both extra- and intracellularly, and it was associated with lipid peroxidation in synaptic regions. Cholesterol depletion provoked a rise in the intracellular Ca2+ concentration, which was diminished by NAC and transient receptor potential vanilloid (TRPV) channel blockers (ruthenium red and capsazepine). By contrast, the MCD-induced rise in [Ca2+]i remained unaffected if Ca2+ release from endoplasmic stores was blocked by TMB8 (8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride). The effects of cholesterol depletion on spontaneous release and exocytosis were significantly reduced by the antioxidant, intracellular Ca2+ chelation with BAPTA-AM and blockers of TRPV channels. Bath application of the calcineurin antagonist cyclosporine A blocked MCD-induced enhancement of spontaneous release/exocytosis, whereas okadaic acid, an inhibitor of phosphatases PP1 and PP2A, had no effect. Thus, our findings indicate that enhancement of spontaneous exocytosis induced by cholesterol depletion may depend on ROS generation, leading to an influx of Ca2+ via TRPV channels and, subsequently, activation of calcineurin. PMID:25326454

The Computation of Global Viscoelastic Co- and Post-seismic Displacement in a Realistic Earth Model by Straightforward Numerical Inverse Laplace Integration

NASA Astrophysics Data System (ADS)

Tang, H.; Sun, W.

2016-12-01

The theoretical computation of dislocation theory in a given earth model is necessary in the explanation of observations of the co- and post-seismic deformation of earthquakes. For this purpose, computation theories based on layered or pure half space [Okada, 1985; Okubo, 1992; Wang et al., 2006] and on spherically symmetric earth [Piersanti et al., 1995; Pollitz, 1997; Sabadini & Vermeersen, 1997; Wang, 1999] have been proposed. It is indicated that the compressibility, curvature and the continuous variation of the radial structure of Earth should be simultaneously taken into account for modern high precision displacement-based observations like GPS. Therefore, Tanaka et al. [2006; 2007] computed global displacement and gravity variation by combining the reciprocity theorem (RPT) [Okubo, 1993] and numerical inverse Laplace integration (NIL) instead of the normal mode method [Peltier, 1974]. Without using RPT, we follow the straightforward numerical integration of co-seismic deformation given by Sun et al. [1996] to present a straightforward numerical inverse Laplace integration method (SNIL). This method is used to compute the co- and post-seismic displacement of point dislocations buried in a spherically symmetric, self-gravitating viscoelastic and multilayered earth model and is easy to extended to the application of geoid and gravity. Comparing with pre-existing method, this method is relatively more straightforward and time-saving, mainly because we sum associated Legendre polynomials and dislocation love numbers before using Riemann-Merlin formula to implement SNIL.

A generic approach for the development of short-term predictions of Escherichia coli and biotoxins in shellfish

PubMed Central

Schmidt, Wiebke; Evers-King, Hayley L.; Campos, Carlos J. A.; Jones, Darren B.; Miller, Peter I.; Davidson, Keith; Shutler, Jamie D.

2018-01-01

Microbiological contamination or elevated marine biotoxin concentrations within shellfish can result in temporary closure of shellfish aquaculture harvesting, leading to financial loss for the aquaculture business and a potential reduction in consumer confidence in shellfish products. We present a method for predicting short-term variations in shellfish concentrations of Escherichia coli and biotoxin (okadaic acid and its derivates dinophysistoxins and pectenotoxins). The approach was evaluated for 2 contrasting shellfish harvesting areas. Through a meta-data analysis and using environmental data (in situ, satellite observations and meteorological nowcasts and forecasts), key environmental drivers were identified and used to develop models to predict E. coli and biotoxin concentrations within shellfish. Models were trained and evaluated using independent datasets, and the best models were identified based on the model exhibiting the lowest root mean square error. The best biotoxin model was able to provide 1 wk forecasts with an accuracy of 86%, a 0% false positive rate and a 0% false discovery rate (n = 78 observations) when used to predict the closure of shellfish beds due to biotoxin. The best E. coli models were used to predict the European hygiene classification of the shellfish beds to an accuracy of 99% (n = 107 observations) and 98% (n = 63 observations) for a bay (St Austell Bay) and an estuary (Turnaware Bar), respectively. This generic approach enables high accuracy short-term farm-specific forecasts, based on readily accessible environmental data and observations. PMID:29805719

A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage.

PubMed

Carlessi, Luigi; Buscemi, Giacomo; Fontanella, Enrico; Delia, Domenico

2010-10-01

The checkpoint kinase Chk2 is an effector component of the ATM-dependent DNA damage response (DDR) pathway. The activation of Chk2 by genotoxic stress involves its phosphorylation on T68 by ATM and additional auto/transphosphorylations. Here we demonstrate that in unperturbed cells, chemical inhibition of Chk2 by VRX0466617 (VRX) enhances the phosphorylation of Chk2-T68 throughout the cell cycle phases. This event, dependent on the presence of ATM and catalytically functional Chk2, is not consequential to DNA damage, as neither gamma-H2AX nuclear foci nor increased ATM activation is detected in VRX-treated cells, suggesting the involvement of other regulatory proteins. As serine/threonine protein phosphatases (PPs) regulate the phosphorylation and deactivation of proteins of the DDR pathway, we analyzed their role in phospho-T68-Chk2 regulation. We found that intracellular inhibition of PP1 and PP2A-like activities by okadaic acid markedly raised the accumulation of Chk2-pT68 without DNA damage induction, and this phenomenon was also seen when PP1-C, PP2A-C, and Wip1/PPM1D were simultaneously knockdown by siRNA. Altogether, these data indicate a novel mechanism in undamaged cells where PPs function to maintain the balance between ATM and its direct substrate Chk2 through a regulatory circuit. Copyright © 2010 Elsevier B.V. All rights reserved.

Two ancient bacterial-like PPP family phosphatases from Arabidopsis are highly conserved plant proteins that possess unique properties.

PubMed

Uhrig, R Glen; Moorhead, Greg B

2011-12-01

Protein phosphorylation, catalyzed by the opposing actions of protein kinases and phosphatases, is a cornerstone of cellular signaling and regulation. Since their discovery, protein phosphatases have emerged as highly regulated enzymes with specificity that rivals their counteracting kinase partners. However, despite years of focused characterization in mammalian and yeast systems, many protein phosphatases in plants remain poorly or incompletely characterized. Here, we describe a bioinformatic, biochemical, and cellular examination of an ancient, Bacterial-like subclass of the phosphoprotein phosphatase (PPP) family designated the Shewanella-like protein phosphatases (SLP phosphatases). The SLP phosphatase subcluster is highly conserved in all plants, mosses, and green algae, with members also found in select fungi, protists, and bacteria. As in other plant species, the nucleus-encoded Arabidopsis (Arabidopsis thaliana) SLP phosphatases (AtSLP1 and AtSLP2) lack genetic redundancy and phylogenetically cluster into two distinct groups that maintain different subcellular localizations, with SLP1 being chloroplastic and SLP2 being cytosolic. Using heterologously expressed and purified protein, the enzymatic properties of both AtSLP1 and AtSLP2 were examined, revealing unique metal cation preferences in addition to a complete insensitivity to the classic serine/threonine PPP protein phosphatase inhibitors okadaic acid and microcystin. The unique properties and high conservation of the plant SLP phosphatases, coupled to their exclusion from animals, red algae, cyanobacteria, archaea, and most bacteria, render understanding the function(s) of this new subclass of PPP family protein phosphatases of particular interest.

Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint.

PubMed

Diril, M Kasim; Bisteau, Xavier; Kitagawa, Mayumi; Caldez, Matias J; Wee, Sheena; Gunaratne, Jayantha; Lee, Sang Hyun; Kaldis, Philipp

2016-09-01

The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL) MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of Mastl for robust spindle assembly checkpoint (SAC) maintenance since the duration of mitotic arrest caused by microtubule poisons in MastlNULL MEFs is shortened, which correlates with premature disappearance of the essential SAC protein Mad1 at the kinetochores. Notably, MastlNULL MEFs display reduced phosphorylation of a number of proteins in mitosis, which include the essential SAC kinase MPS1. We further demonstrate that Mastl is required for multi-site phosphorylation of MPS1 as well as robust MPS1 kinase activity in mitosis. In contrast, treatment of MastlNULL cells with the phosphatase inhibitor okadaic acid (OKA) rescues the defects in MPS1 kinase activity, mislocalization of phospho-MPS1 as well as Mad1 at the kinetochore, and premature SAC silencing. Moreover, using in vitro dephosphorylation assays, we demonstrate that Mastl promotes persistent MPS1 phosphorylation by inhibiting PP2A/B55-mediated MPS1 dephosphorylation rather than affecting Cdk1 kinase activity. Our findings establish a key regulatory function of the Greatwall kinase/Mastl->PP2A/B55 pathway in preventing premature SAC silencing.

Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint

PubMed Central

Kitagawa, Mayumi; Caldez, Matias J.; Gunaratne, Jayantha; Lee, Sang Hyun

2016-01-01

The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL) MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of Mastl for robust spindle assembly checkpoint (SAC) maintenance since the duration of mitotic arrest caused by microtubule poisons in MastlNULL MEFs is shortened, which correlates with premature disappearance of the essential SAC protein Mad1 at the kinetochores. Notably, MastlNULL MEFs display reduced phosphorylation of a number of proteins in mitosis, which include the essential SAC kinase MPS1. We further demonstrate that Mastl is required for multi-site phosphorylation of MPS1 as well as robust MPS1 kinase activity in mitosis. In contrast, treatment of MastlNULL cells with the phosphatase inhibitor okadaic acid (OKA) rescues the defects in MPS1 kinase activity, mislocalization of phospho-MPS1 as well as Mad1 at the kinetochore, and premature SAC silencing. Moreover, using in vitro dephosphorylation assays, we demonstrate that Mastl promotes persistent MPS1 phosphorylation by inhibiting PP2A/B55-mediated MPS1 dephosphorylation rather than affecting Cdk1 kinase activity. Our findings establish a key regulatory function of the Greatwall kinase/Mastl->PP2A/B55 pathway in preventing premature SAC silencing. PMID:27631493

Ultrafast superresolution fluorescence imaging with spinning disk confocal microscope optics.

PubMed

Hayashi, Shinichi; Okada, Yasushi

2015-05-01

Most current superresolution (SR) microscope techniques surpass the diffraction limit at the expense of temporal resolution, compromising their applications to live-cell imaging. Here we describe a new SR fluorescence microscope based on confocal microscope optics, which we name the spinning disk superresolution microscope (SDSRM). Theoretically, the SDSRM is equivalent to a structured illumination microscope (SIM) and achieves a spatial resolution of 120 nm, double that of the diffraction limit of wide-field fluorescence microscopy. However, the SDSRM is 10 times faster than a conventional SIM because SR signals are recovered by optical demodulation through the stripe pattern of the disk. Therefore a single SR image requires only a single averaged image through the rotating disk. On the basis of this theory, we modified a commercial spinning disk confocal microscope. The improved resolution around 120 nm was confirmed with biological samples. The rapid dynamics of micro-tubules, mitochondria, lysosomes, and endosomes were observed with temporal resolutions of 30-100 frames/s. Because our method requires only small optical modifications, it will enable an easy upgrade from an existing spinning disk confocal to a SR microscope for live-cell imaging. © 2015 Hayashi and Okada. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach.

PubMed

Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

2015-01-01

Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades.

Suggested Involvement of PP1/PP2A Activity and De Novo Gene Expression in Anhydrobiotic Survival in a Tardigrade, Hypsibius dujardini, by Chemical Genetic Approach

PubMed Central

Kondo, Koyuki; Kubo, Takeo; Kunieda, Takekazu

2015-01-01

Upon desiccation, some tardigrades enter an ametabolic dehydrated state called anhydrobiosis and can survive a desiccated environment in this state. For successful transition to anhydrobiosis, some anhydrobiotic tardigrades require pre-incubation under high humidity conditions, a process called preconditioning, prior to exposure to severe desiccation. Although tardigrades are thought to prepare for transition to anhydrobiosis during preconditioning, the molecular mechanisms governing such processes remain unknown. In this study, we used chemical genetic approaches to elucidate the regulatory mechanisms of anhydrobiosis in the anhydrobiotic tardigrade, Hypsibius dujardini. We first demonstrated that inhibition of transcription or translation drastically impaired anhydrobiotic survival, suggesting that de novo gene expression is required for successful transition to anhydrobiosis in this tardigrade. We then screened 81 chemicals and identified 5 chemicals that significantly impaired anhydrobiotic survival after severe desiccation, in contrast to little or no effect on survival after high humidity exposure only. In particular, cantharidic acid, a selective inhibitor of protein phosphatase (PP) 1 and PP2A, exhibited the most profound inhibitory effects. Another PP1/PP2A inhibitor, okadaic acid, also significantly and specifically impaired anhydrobiotic survival, suggesting that PP1/PP2A activity plays an important role for anhydrobiosis in this species. This is, to our knowledge, the first report of the required activities of signaling molecules for desiccation tolerance in tardigrades. The identified inhibitory chemicals could provide novel clues to elucidate the regulatory mechanisms underlying anhydrobiosis in tardigrades. PMID:26690982

Interaction between fault systems in a complex tectonic setting: Insights from InSAR and Teleseismic analysis of the 2015 Lake Saurez and 2016 Muji fault earthquake sequence

NASA Astrophysics Data System (ADS)

Nanjundiah, P.; Barbot, S.; Wei, S.; Tapponnier, P.; Feng, W.; Wang, T.

2017-12-01

The Pamir Plateau is a complex and important component of the India-Eurasia Collision zone. Despite being similar to the Tibetan plateau in elevation and collision processes, quite a bit is still unknown about the structure and the tectonic processes occurring in this region. We aim to better understand the structure, stress and deformation patterns in the northern and central Pamir plateau by analysing InSAR, teleseismic, and optical data for two large earthquakes that occurred in this region between December 2015 (Mw 7.2, Lake Saurez) and November 2016 (Mw 6.6 Muji Fault). We constrain the fault geometry by precisely relocating aftershocks using the double difference technique implemented in HypoDD (Waldhauser & Ellsworth 2000). We used Okada's (1992) Green Functions to invert for slip on the fault with a rectangular dislocation and edgreen to numerically invert for the slip in a layered medium (Wang et al. 2005). The combined datasets highlight the existence of an oblique fault between two major thrust fault systems i.e. the Darwas & the Karakoram faults. The December 2015 event highlights complexity in this fault system. The combination of data sets used in this study highlights the existence of a seismic gap south of Lake Karakul as well as coupling between the Muji and Darwas-Karakoram fault systems. We emphasise the role of smaller faults and their interactions in accommodating the overall strain and tectonics in the Pamir region and their effect on estimating local seismic hazard.

Basal protein phosphatase 2A activity restrains cytokine expression: role for MAPKs and tristetraprolin.

PubMed

Rahman, Md Mostafizur; Rumzhum, Nowshin N; Morris, Jonathan C; Clark, Andrew R; Verrills, Nicole M; Ammit, Alaina J

2015-05-18

PP2A is a master controller of multiple inflammatory signaling pathways. It is a target in asthma; however the molecular mechanisms by which PP2A controls inflammation warrant further investigation. In A549 lung epithelial cells in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the anti-inflammatory protein - tristetraprolin (TTP), a destabilizing RNA binding protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition increases TTP mRNA expression, resultant TTP protein builds up in the hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro-inflammatory cytokines increase and anti-inflammatory proteins are rendered inactive. Importantly, these effects can be reversed by the PP2A activators FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression in cells stimulated with TNFα; as inhibition of PP2A with OA or PP2A-C siRNA results in significant increases in cytokine production. Collectively, these data reveal the molecular mechanisms of PP2A regulation and highlight the potential of boosting the power of endogenous phosphatases as novel anti-inflammatory strategies to combat asthmatic inflammation.

Characterizing Volumetric Strain at Brady Hot Springs, Nevada, USA Using Geodetic Data, Numerical Models, and Prior Information

NASA Astrophysics Data System (ADS)

Reinisch, E. C.; Feigl, K. L.; Cardiff, M. A.; Morency, C.; Kreemer, C.; Akerley, J.

2017-12-01

Time-dependent deformation has been observed at Brady Hot Springs using data from the Global Positioning System (GPS) and interferometric synthetic aperture radar (InSAR) [e.g., Ali et al. 2016, http://dx.doi.org/10.1016/j.geothermics.2016.01.008]. We seek to determine the geophysical process governing the observed subsidence. As two end-member hypotheses, we consider thermal contraction and a decrease in pore fluid pressure. A decrease in temperature would cause contraction in the subsurface and subsidence at the surface. A decrease in pore fluid pressure would allow the volume of pores to shrink and also produce subsidence. To simulate these processes, we use a dislocation model that assumes uniform elastic properties in a half space [Okada, 1985]. The parameterization consists of many cubic volume elements (voxels), each of which contracts by closing its three mutually orthogonal bisecting square surfaces. Then we use linear inversion to solve for volumetric strain in each voxel given a measurement of range change. To differentiate between the two possible hypotheses, we use a Bayesian framework with geostatistical prior information. We perform inversion using each prior to decide if one leads to a more geophysically reasonable interpretation than the other. This work is part of a project entitled "Poroelastic Tomography by Adjoint Inverse Modeling of Data from Seismology, Geodesy, and Hydrology" and is supported by the Geothermal Technology Office of the U.S. Department of Energy [DE-EE0006760].

Numerical Investigation of Plasma Detachment in Magnetic Nozzle Experiments

NASA Technical Reports Server (NTRS)

Sankaran, Kamesh; Polzin, Kurt A.

2008-01-01

At present there exists no generally accepted theoretical model that provides a consistent physical explanation of plasma detachment from an externally-imposed magnetic nozzle. To make progress towards that end, simulation of plasma flow in the magnetic nozzle of an arcjet experiment is performed using a multidimensional numerical simulation tool that includes theoretical models of the various dispersive and dissipative processes present in the plasma. This is an extension of the simulation tool employed in previous work by Sankaran et al. The aim is to compare the computational results with various proposed magnetic nozzle detachment theories to develop an understanding of the physical mechanisms that cause detachment. An applied magnetic field topology is obtained using a magnetostatic field solver (see Fig. I), and this field is superimposed on the time-dependent magnetic field induced in the plasma to provide a self-consistent field description. The applied magnetic field and model geometry match those found in experiments by Kuriki and Okada. This geometry is modeled because there is a substantial amount of experimental data that can be compared to the computational results, allowing for validation of the model. In addition, comparison of the simulation results with the experimentally obtained plasma parameters will provide insight into the mechanisms that lead to plasma detachment, revealing how they scale with different input parameters. Further studies will focus on modeling literature experiments both for the purpose of additional code validation and to extract physical insight regarding the mechanisms driving detachment.

Discovery of a protein phosphatase activity encoded in the genome of bacteriophage lambda. Probable identity with open reading frame 221.

PubMed

Cohen, P T; Cohen, P

1989-06-15

Infection of Escherichia coli with phage lambda gt10 resulted in the appearance of a protein phosphatase with activity towards 32P-labelled casein. Activity reached a maximum near the point of cell lysis and declined thereafter. The phosphatase was stimulated 30-fold by Mn2+, while Mg2+ and Ca2+ were much less effective. Activity was unaffected by inhibitors 1 and 2, okadaic acid, calmodulin and trifluoperazine, distinguishing it from the major serine/threonine-specific protein phosphatases of eukaryotic cells. The lambda phosphatase was also capable of dephosphorylating other substrates in the presence of Mn2+, although activity towards 32P-labelled phosphorylase was 10-fold lower, and activity towards phosphorylase kinase and glycogen synthase 25 50-fold lower than with casein. No casein phosphatase activity was present in either uninfected cells, or in E. coli infected with phage lambda gt11. Since lambda gt11 lacks part of the open reading frame (orf) 221, previously shown to encode a protein with sequence similarity to protein phosphatase-1 and protein phosphatase-2A of mammalian cells [Cohen, Collins, Coulson, Berndt & da Cruz e Silva (1988) Gene 69, 131-134], the results indicate that ORF221 is the protein phosphatase detected in cells infected with lambda gt10. Comparison of the sequence of ORF221 with other mammalian protein phosphatases defines three highly conserved regions which are likely to be essential for function. The first of these is deleted in lambda gt11.

The Pathways for Intelligible Speech: Multivariate and Univariate Perspectives

PubMed Central

Evans, S.; Kyong, J.S.; Rosen, S.; Golestani, N.; Warren, J.E.; McGettigan, C.; Mourão-Miranda, J.; Wise, R.J.S.; Scott, S.K.

2014-01-01

An anterior pathway, concerned with extracting meaning from sound, has been identified in nonhuman primates. An analogous pathway has been suggested in humans, but controversy exists concerning the degree of lateralization and the precise location where responses to intelligible speech emerge. We have demonstrated that the left anterior superior temporal sulcus (STS) responds preferentially to intelligible speech (Scott SK, Blank CC, Rosen S, Wise RJS. 2000. Identification of a pathway for intelligible speech in the left temporal lobe. Brain. 123:2400–2406.). A functional magnetic resonance imaging study in Cerebral Cortex used equivalent stimuli and univariate and multivariate analyses to argue for the greater importance of bilateral posterior when compared with the left anterior STS in responding to intelligible speech (Okada K, Rong F, Venezia J, Matchin W, Hsieh IH, Saberi K, Serences JT,Hickok G. 2010. Hierarchical organization of human auditory cortex: evidence from acoustic invariance in the response to intelligible speech. 20: 2486–2495.). Here, we also replicate our original study, demonstrating that the left anterior STS exhibits the strongest univariate response and, in decoding using the bilateral temporal cortex, contains the most informative voxels showing an increased response to intelligible speech. In contrast, in classifications using local “searchlights” and a whole brain analysis, we find greater classification accuracy in posterior rather than anterior temporal regions. Thus, we show that the precise nature of the multivariate analysis used will emphasize different response profiles associated with complex sound to speech processing. PMID:23585519

New record of Japanese snake blenny Xiphasia matsubarai (Perciformes: Blenniidae) from South China Sea

NASA Astrophysics Data System (ADS)

Yi, Murong; Zhao, Chunxu; Su, Xin; Tao, Yajin; Yan, Yunrong

2017-11-01

Specimens belonging to the family Blenniidae were collected in a fishery resource investigation from the coastal waters of Xisha Islands and Hainan Island, South China Sea in 2016. Combining morphological results with sequence analysis, we identified one specimen as Xiphasia matsubarai Okada & Suzuki, 1952. This represents a new record in the South China Sea. In morphology, the specimen has the following traits: body elongated, eel-like or ribbon-like in shape; flanks medium flat; the head small bluntly rounded anteriorly and without a moustache; eyes is slightly smaller, on upper lateral position of head, which is about equal to 1/5 of the length of the head; body without scales, lateral line has been degraded; both sides of the upper and lower jaws with a canine; gill is opening at the top of the pectoral fin base, approximately equal to the length of eye diameter. Dorsal fin XI, 96; pectoral fin 10; anal fin II, 95. Head and body grey-brown, including 26 dark grey-brown bands; abdomen and lower operculum yellowish grey and colour lighter; and dorsal base long with dark grey. Origin of dorsal is located over the anterior margin of pupil; black blotch on dorsal fin between 8th and 10th dorsal spine; anal and caudal fins dark grey, pectoral and ventral fins pale yellow. Sequence analysis of cytochrome oxidase subunit I gene (COI) strongly supports the identity of the specimen as X. matsubarai.

The limit of irrigation adaption due to the inter-crop conflict of water use under changing climate and landuse

NASA Astrophysics Data System (ADS)

Okada, M.; Iizumi, T.; Sakamoto, T.; Kotoku, M.; Sakurai, G.; Nishimori, M.

2017-12-01

Replacing rainfed cropping system by irrigated one is assumed to be an effective measure for climate change adaptation in agriculture. However, in many agricultural impact assessments, future irrigation scenarios are externally given and do not consider variations in the availability of irrigation water under changing climate and land use. Therefore, we assess the potential effects of adaption measure expanding irrigated area under climate change by using a large-scale crop-river coupled model, CROVER [Okada et al. 2015, JAMES]. The CROVER model simulates the large-scale terrestrial hydrological cycle and crop growth depending on climate, soil properties, landuse, crop cultivation management, socio-economic water demand, and reservoir operation management. The bias-corrected GCMs outputs under the RCP 8.5 scenario were used. The future expansion of irrigation area was estimated by using the extrapolation method based on the historical change in irrigated and rainfed areas. As the results, the irrigation adaptation has only a limited effect on the rice production in East Asia due to the conflict of water use for irrigation with the other crops, whose farmlands require unsustainable water extraction with the excessively expanding irrigated area. In contrast, the irrigation adaptation benefits maize production in Europe due to the little conflict of water use for irrigation. Our findings suggest the importance of simulating the river water availability and crop production in a single model for the more realistic assessment in the irrigation adaptation potential effects of crop production under changing climate and land use.

Effect of complete protein 4.1R deficiency on ion transportproperties of murine erythrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivera, Alicia; De Franceschi, Lucia; Peters, Luanne L.

2006-06-02

), with an abnormal dependence onosmolarity, (K0.5=417 +- 42 in 4.1 -/- vs. 460 +- 35 mOsm in controlmice) suggestive of an up-regulated functional state. While the affinityfor internal protons was not altered (K0.5= 489.7 +- 0.7 vs. 537.0 +-0.56 nM in control mice), the Vmax of the H-induced Na/H exchangeactivity was markedly elevated in 4.1-/- erythrocytes (Vmax 91.47+-7.2compared to 46.52+-5.4 mmol/1013 cell x h in control mice). Na/H exchangeactivation by okadaic acid was absent in 4.1-/- erythrocytes. Altogether,these results suggest that erythroid protein 4.1 plays a major role involume regulation and physiologically down-regulates Na/H exchange inmouse erythrocytes. Up-regulation of the Na/H exchange is an importantcontributor to the elevated cell Na content of 4.1 -/- erythrocytes.-7.2compared to 46.52+-5.4 mmol/1013 cell x h in control mice). Na/H exchangeactivation by okadaic acid was absent in 4.1-/- erythrocytes. Altogether,these results suggest that erythroid protein 4.1 plays a major role involume regulation and physiologically down-regulates Na/H exchange inmouse erythrocytes. Up-regulation of the Na/H exchange is an importantcontributor to the elevated cell Na content of 4.1 -/-erythrocytes.« less

The 2011 Tohoku-oki Earthquake related to a large velocity gradient within the Pacific plate

NASA Astrophysics Data System (ADS)

Matsubara, Makoto; Obara, Kazushige

2015-04-01

We conduct seismic tomography using arrival time data picked by the high sensitivity seismograph network (Hi-net) operated by National Research Institute for Earth Science and Disaster Prevention (NIED). We used earthquakes off the coast outside the seismic network around the source region of the 2011 Tohoku-oki Earthquake with the centroid depth estimated from moment tensor inversion by NIED F-net (broadband seismograph network) as well as earthquakes within the seismic network determined by Hi-net. The target region, 20-48N and 120-148E, covers the Japanese Islands from Hokkaido to Okinawa. A total of manually picked 4,622,346 P-wave and 3,062,846 S-wave arrival times for 100,733 earthquakes recorded at 1,212 stations from October 2000 to August 2009 is available for use in the tomographic method. In the final iteration, we estimate the P-wave slowness at 458,234 nodes and the S-wave slowness at 347,037 nodes. The inversion reduces the root mean square of the P-wave traveltime residual from 0.455 s to 0.187 s and that of the S-wave data from 0.692 s to 0.228 s after eight iterations (Matsubara and Obara, 2011). Centroid depths are determined using a Green's function approach (Okada et al., 2004) such as in NIED F-net. For the events distant from the seismic network, the centroid depth is more reliable than that determined by NIED Hi-net, since there are no stations above the hypocenter. We determine the upper boundary of the Pacific plate based on the velocity structure and earthquake hypocentral distribution. The upper boundary of the low-velocity (low-V) oceanic crust corresponds to the plate boundary where thrust earthquakes are expected to occur. Where we do not observe low-V oceanic crust, we determine the upper boundary of the upper layer of the double seismic zone within high-V Pacific plate. We assume the depth at the Japan Trench as 7 km. We can investigate the velocity structure within the Pacific plate such as 10 km beneath the plate boundary since the

Integrated bio-magnetostratigraphy of ODP Site 709 (equatorial Indian Ocean).

NASA Astrophysics Data System (ADS)

Villa, Giuliana; Fioroni, Chiara; Florindo, Fabio

2015-04-01

Over the last decade, calcareous nannofossil biostratigraphy of the lower Eocene-Oligocene sediments has shown great potential, through identification of several new nannofossil species and bioevents (e.g. Fornaciari et al., 2010; Bown and Dunkley Jones, 2012; Toffanin et al., 2013). These studies formed the basis for higher biostratigraphic resolution leading to definition of a new nannofossil biozonation (Agnini et al., 2014). In this study, we investigate the middle Eocene-lower Oligocene sediments from ODP Hole 709C (ODP Leg 115) by means of calcareous nannofossils and magnetostratigraphy. Ocean Drilling Program (ODP) Site 709 was located in the equatorial Indian Ocean and biostratigraphy has been investigated in the nineties (Okada, 1990; Fornaciari et al., 1990) while paleomagnetic data from the Initial Report provided only a poorly constrained magnetostratigraphic interpretation, thus the cored succession was dated only by means of biostratigraphy. Our goal is to test the reliability in the Indian Ocean of the biohorizons recently identified at Site 711 (Fioroni et al., in press), by means of high resolution sampling, new taxonomic updates, quantitative analyses on calcareous nannofossils allowed to increase the number of useful bioevents and to compare their reliability and synchroneity. The new magnetostratigraphic analyses and integrated stratigraphy allow also to achieve an accurate biochronology of the time interval spanning Chrons C20 (middle Eocene) and C12 (early Oligocene). In addition, this equatorial site represents an opportunity to study the carbonate accumulation history and the large fluctuations of the carbonate compensation depth (CCD) during the Eocene (e.g. Pälike et al., 2012). The investigated interval encompasses the Middle Eocene Climatic Optimum (MECO), and the long cooling trend that leads to the Oligocene glacial state. By means of our new bio-magnetostratigraphic data and paleoecological results we provide further insights on

Introduction to the Proceedings of the 9th ISDH

NASA Astrophysics Data System (ADS)

Bove, V. Michael, Jr.; Riskin, Seth

2013-02-01

The Proceedings As co-chairs of the 9th International Symposium on Display Holography, we welcome readers of this collection of papers and posters presented at the event. We hope that both attendees of the event and others pursuing the art, science, and business of holography and 3D imaging will find the authors' contributions of lasting interest and importance. The Event Since its creation at Lake Forest College in 1982 by Professor Tung H Jeong, ISDH has followed a model that differentiates it from other scientific conferences. The 9th ISDH continued this history, fully occupying a floor of the MIT Media Lab for five days. The single-track conference opened with reports on the state of holography in the various nations represented by the attendees, followed by a series of presentations on Education and Holography. One and one-half days of papers on Art and Holography followed, then sessions on Techniques and Materials, Digital Techniques, and Commercial and Applied Holography. A poster session permitted more in-depth discussion between authors and the audience. Two exhibitions of holographic works opened at ISDH: an informal display area at the symposium, and a 15-month-long MIT Museum exhibition, The Jeweled Net: Views of Contemporary Holography. The success of an event of this sort requires the help of many people and organizations. We wish especially to recognize our Honorary Conference Chairs: Tung H Jeong and Joseph W Goodman; our Technical Program Committee: Hans I Bjelkhagen, Frank Fan, Nasser Peyghambarian, and Hiroshi Yoshikawa; and our Arts and Exhibition Committee: Betsy Connors-Chen, Melissa Crenshaw, John Durant, Dieter Jung, Linda Law, Martin Richardson, Jonathan Ross, and Sally Weber. Betsy also coordinated the on-site exhibition. Kristin Hall at the MIT Media Lab made local arrangements, while registration was handled by MIT Conference Services. We also gratefully acknowledge support from Lake Forest College, holographer.org, and authentibrand

Representatives of countries participating in the International Space Station toured KSC's Space Sta

NASA Technical Reports Server (NTRS)

1998-01-01

Senior government officials from 15 countries participating in the International Space Station (ISS) signed agreements in Washington D.C. on Jan. 29 to establish the framework of cooperation among the partners on the design, development, operation and utilization of the Space Station. Acting Secretary of State Strobe Talbott signed the 1998 Intergovernmental Agreement on Space Station Cooperation with representatives of Russia, Japan, Canada, and participating countries of the European Space Agency (ESA), including Belgium, Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. Some of these officials then toured KSC's Space Station Processing Facility (SSPF) with NASA Administrator Daniel Goldin, at front, sixth from the left. They are, left to right, front to back: Hidetoshi Murayama, National Space Development Agency of Japan (NASDA); Louis Laurent, Embassy of France; Haakon Blankenborg, Norwegian Parliament Standing Committee on Foreign Affairs; His Excellency Joris Vos, ambassador of the Netherlands; His Excellency Tom Vraalsen, ambassador of Norway; Daniel Goldin; Luigi Berlinguer, Italian minister for education, scientific, and technological research; Antonio Rodota, director general, European Space Agency (ESA); Yvan Ylieff, Belgian minister of science and chairman of the ESA Ministerial Council; Jacqueline Ylieff; Masaaki Komatsu, KSC local NASDA representative and interpreter; Serge Ivanets, space attache, Embassy of Russia; Hiroshi Fujita, Science and Technology Agency of Japan; Akira Mizutani, Japanese Ministry of Foreign Affairs; Peter Grognard, science attache, Royal Embassy of Belgium; Michelangelo Pipan, Italian diplomatic counselor to the minister; His Excellency Gerhard Fulda, German Federal Foreign Office; Jorg Feustel-Buechl, ESA director of manned space flight and microgravity; A. Yakovenko, Russian Ministry of Foreign Affairs; JoAnn Morgan, KSC associate director for Advanced Development

Ethanol Reversal of Cellular Tolerance to Morphine in Rat Locus Coeruleus Neurons

PubMed Central

Llorente, Javier; Withey, Sarah; Rivero, Guadalupe; Cunningham, Margaret; Cooke, Alex; Saxena, Kunal; McPherson, Jamie; Oldfield, Sue; Dewey, William L.; Bailey, Chris P.; Kelly, Eamonn; Henderson, Graeme

2013-01-01

Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala2,N-MePhe4,Gly-ol]-enkephalin was not reversed by ethanol. Previous studies in LC neurons have revealed a role for protein kinase C (PKC)α in μ-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance, but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKCα. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor okadaic acid, indicating that dephosphorylation is involved. In human embryonic kidney 293 cells expressing the MOPr, ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by guanosine 5′-O-(3-[35S]thio)triphosphate binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance. PMID:23716621

A fluorescence microplate screen assay for the detection of neurite outgrowth and neurotoxicity using an antibody against βIII-tubulin.

PubMed

Popova, Dina; Jacobsson, Stig O P

2014-04-01

The majority of environmental and commercial chemicals have not been evaluated for their potential to cause neurotoxicity. We have investigated if neuron specific anti-βIII-tubulin antibodies are useful in a microplate assay of neurite outgrowth of retinoic acid-induced neurons from mouse P19 embryonal carcinoma cells. By incubating the P19-derived neurons with the primary anti-βIII-tubulin antibody and a secondary Alexa Fluor 488-conjugated antibody, followed by measuring the fluorescence in a microplate reader, a time-dependent increase in anti-βIII-tubulin immunofluorescence was observed. The relative fluorescence units increased by 4.3-fold from 2 to 10 days in culture. The results corresponded well with those obtained by semi-automatic tracing of neurites in fluorescence microscopy images of βIII-tubulin-labeled neurons. The sensitivity of the neurite outgrowth assay using a microplate reader to detect neurotoxicity produced by nocodazole, methyl mercury chloride and okadaic acid was significantly higher than for a cell viability assay measuring intracellular fluorescence of calcein-AM. The microplate-based method to measure toxicity targeting neurites using anti-βIII-tubulin antibodies is however less sensitive than the extracellular lactate dehydrogenase activity assay to detect general cytotoxicity produced by high concentrations of clomipramine, or glutamate-induced excitotoxicity. In conclusion, the fluorescence microplate assay for the detection of neurite outgrowth by measuring changes in βIII-tubulin immunoreactivity is a rapid and sensitive method to assess chemical- or toxin-induced neurite toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of seawater salinity on pore-size distribution on a poly(styrene)-based HP20 resin and its adsorption of diarrhetic shellfish toxins.

PubMed

Fan, Lin; Sun, Geng; Qiu, Jiangbing; Ma, Qimin; Hess, Philipp; Li, Aifeng

2014-12-19

In the present study, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were spiked into artificial seawater at low, medium and high estuarine salinities (9‰, 13.5‰ and 27‰). Passive samplers (HP20 resin) used for solid phase adsorption toxin tracking (SPATT) technology were exposed in these seawaters for 12-h periods. Adsorption curves well fitted a pseudo-secondary kinetics model. The highest initial sorption rates of both toxins occurred in the seawater of medium salinity, followed by seawater of low and high estuarine salinity. Pore volumes of micropores (<2 nm) and small mesopores (2 nm

Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling.

PubMed

Gürsel, Demirkan B; Banu, Matei A; Berry, Nicholas; Marongiu, Roberta; Burkhardt, Jan-Karl; Kobylarz, Keith; Kaplitt, Michael G; Rafii, Shahin; Boockvar, John A

2015-01-01

Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.

Hyperphosphorylation of PP2A in colorectal cancer and the potential therapeutic value showed by its forskolin-induced dephosphorylation and activation.

PubMed

Cristóbal, Ion; Rincón, Raúl; Manso, Rebeca; Madoz-Gúrpide, Juan; Caramés, Cristina; del Puerto-Nevado, Laura; Rojo, Federico; García-Foncillas, Jesús

2014-09-01

The tumor suppressor protein phosphatase 2A (PP2A) is frequently inactivated in human cancer and phosphorylation of its catalytic subunit (p-PP2A-C) at tyrosine-307 (Y307) has been described to inhibit this phosphatase. However, its molecular and clinical relevance in colorectal cancer (CRC) remains unclear. p-PP2A-C Y307 was determined by immunoblotting in 7 CRC cell lines and 35 CRC patients. CRC cells were treated with the PP2A activator forskolin alone or combined with the PP2A inhibitor okadaic acid, 5-fluorouracil and oxaliplatin. We examined cell growth, colonosphere formation, caspase activity and AKT and ERK activation. PP2A-C was found hyperphosphorylated in CRC cell lines. Forskolin dephosphorylated and activated PP2A, impairing proliferation and colonosphere formation, and inducing activation of caspase 3/7 and changes in AKT and ERK phosphorylation. Moreover, forskolin showed additive effects with 5-fluorouracil and oxaliplatin treatments. Analysis of p-PP2A-C Y307 in primary tumors confirmed the presence of this alteration in a subgroup of CRC patients. Our data show that PP2A-C hyperphosphorylation is a frequent event that contributes to PP2A inhibition in CRC. Antitumoral effects of forskolin-mediated PP2A activation suggest that the analysis of p-PP2A-C Y307 status could be used to identify a subgroup of patients who would benefit from treatments based on PP2A activators. Copyright © 2014 Elsevier B.V. All rights reserved.

A PP2A-mediated feedback mechanism controls Ca2+-dependent NO synthesis under physiological oxygen.

PubMed

Keeley, Thomas P; Siow, Richard C M; Jacob, Ron; Mann, Giovanni E

2017-12-01

Intracellular O 2 is a key regulator of NO signaling, yet most in vitro studies are conducted in atmospheric O 2 levels, hyperoxic with respect to the physiologic milieu. We investigated NO signaling in endothelial cells cultured in physiologic (5%) O 2 and stimulated with histamine or shear stress. Culture of cells in 5% O 2 (>5 d) decreased histamine- but not shear stress-stimulated endothelial (e)NOS activity. Unlike cells adapted to a hypoxic environment (1% O 2 ), those cultured in 5% O 2 still mobilized sufficient Ca 2+ to activate AMPK. Enhanced expression and membrane targeting of PP2A-C was observed in 5% O 2 , resulting in greater interaction with eNOS in response to histamine. Moreover, increased dephosphorylation of eNOS in 5% O 2 was Ca 2+ -sensitive and reversed by okadaic acid or PP2A-C siRNA. The present findings establish that Ca 2+ mobilization stimulates both NO synthesis and PP2A-mediated eNOS dephosphorylation, thus constituting a novel negative feedback mechanism regulating eNOS activity not present in response to shear stress. This, coupled with enhanced NO bioavailability, underpins differences in NO signaling induced by inflammatory and physiologic stimuli that are apparent only in physiologic O 2 levels. Furthermore, an explicit delineation between physiologic normoxia and genuine hypoxia is defined here, with implications for our understanding of pathophysiological hypoxia.-Keeley, T. P., Siow, R. C. M., Jacob, R., Mann, G. E. A PP2A-mediated feedback mechanism controls Ca 2+ -dependent NO synthesis under physiological oxygen. © The Author(s).

Human cytomegalovirus carries serine/threonine protein phosphatases PP1 and a host-cell derived PP2A.

PubMed Central

Michelson, S; Turowski, P; Picard, L; Goris, J; Landini, M P; Topilko, A; Hemmings, B; Bessia, C; Garcia, A; Virelizier, J L

1996-01-01

Human cytomegalovirus (CMV), a herpesvirus, is an important cause of morbidity and mortality in immunocompromised patients. When studying hyper-immediate-early events after contact between CMV virions and the cell membrane, we observed a hypophosphorylation of cellular proteins within 10 min. This can be explained in part by our finding that purified CMV contains serine/threonine protein phosphatase activities. Biochemical analyses indicate that this protein phosphatase activity has all characteristics of type 1 and 2A protein phosphatases (PP1 and PP2A). Specifically, PP1 accounts for approximately 30% and PP2A accounts for the remaining 70% of the phosphorylase phosphatase activity found. CMV produced in astrocytoma cells stably expressing an amino-terminally tagged PP2A catalytic subunit contained tagged enzyme, thus demonstrating the cellular origin of CMV-associated PP2A. PP2A is specifically found inside the virus, associated with the nucleocapsid fraction. Western blot (immunoblot) analysis of purified virus revealed the presence of the catalytic subunits of PP2A and PP1. Furthermore, the catalytic subunit of PP2A appears to be complexed to the regulatory subunits PR65 and PR55, which is also the most abundant configuration of this enzyme found in the host cells. Incubation of virus with okadaic acid before contact of CMV with cells prevented hypophosphorylation of cellular proteins, thus demonstrating the role of CMV-associated phosphatases in this phenomenon. CMV can thus transport an active enzyme from one cell to another. PMID:8627658

InSAR Surface Deformation and Source Modelling at Semisopochnoi Island During the 2014 and 2015 Seismic Swarms with Constraints from Geochemical and Seismic Analysis

NASA Astrophysics Data System (ADS)

DeGrandpre, K.; Pesicek, J. D.; Lu, Z.

2017-12-01

During the summer of 2014 and the early spring of 2015 two notable increases in seismic activity at Semisopochnoi Island in the western Aleutian islands were recorded on AVO seismometers on Semisopochnoi and neighboring islands. These seismic swarms did not lead to an eruption. This study employs interferometric synthetic aperture radar (InSAR) techniques using TerraSAR-X images in conjunction with more accurately relocating the recorded seismic events through simultaneous inversion of event travel times and a three-dimensional velocity model using tomoDD. The InSAR images exhibit surprising coherence and an island wide spatial distribution of inflation that is then used in Mogi, Okada, spheroid, and ellipsoid source models in order to define the three-dimensional location and volume change required for a source at the volcano to produce the observed surface deformation. The tomoDD relocations provide a more accurate and realistic three-dimensional velocity model as well as a tighter clustering of events for both swarms that clearly outline a linear seismic void within the larger group of shallow (<10 km) seismicity. The source models are fit to this void and pressure estimates from geochemical analysis are used to verify the storage depth of magmas at Semisopochnoi. Comparisons of calculated source cavity, magma injection, and surface deformation volumes are made in order to assess the reality behind the various modelling estimates. Incorporating geochemical and seismic data to provide constraints on surface deformation source inversions provides an interdisciplinary approach that can be used to make more accurate interpretations of dynamic observations.

Mechanisms of hyposmotic volume regulation in isolated nematocytes of the anthozoan Aiptasia diaphana.

PubMed

Marino, Angela; Morabito, Rossana; La Spada, Giuseppina; Adragna, Norma C; Lauf, Peter K

2010-01-01

The nature and role of potassium (K) and water transport mediating hyposmotically-induced regulatory volume decrease (RVD) were studied in nematocytes dissociated with 605 mM thiocyanate from acontia of the Anthozoan Aiptasia diaphana. Cell volume and hence RVD were calculated from the inverse ratios of the cross sectional areas of nematocytes (A/A(o)) measured before (A(o)) and after (A) challenge with 65% artificial sea water (ASW). To distinguish between K channels and K-Cl cotransport (KCC), external sodium (Na) and chloride (Cl) were replaced by K and nitrate (NO(3)), respectively. Inhibitors were added to identify K channels (barium, Ba), and putative kinase (N-ethylmaleimide, NEM) and phosphatase (okadaic acid, OA) regulation of KCC. In 65% NaCl ASW, nematocytes displayed a biphasic change in A/A(o), peaking within 4 min due to osmotic water entry and thereafter declining within 6 min due to RVD. Changing NaCl to KCl or NaNO(3) ASW did not affect the osmotic phase but attenuated RVD, consistent with K channel and KCC mechanisms. Ba (3 mM) inhibited RVD. NEM and OA, applied separately, inhibited the osmotic phase and muted RVD suggesting primary action on water transport (aquaporins). NEM and OA together reduced the peak A/A(o) ratio during the osmotic phase whereas RVD was inhibited when OA preceded NEM. Thus, both K channels and KCC partake in the nematocyte RVD, the extent of which is determined by functional thiols and dephosphorylation of putative aquaporins facilitating the preceding osmotic water shifts. Copyright 2010 S. Karger AG, Basel.

Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells.

PubMed

Knoepp, Stewart M; Chahal, Manpreet S; Xie, Yuhuan; Zhang, Zhihong; Brauner, Daniel J; Hallman, Mark A; Robinson, Stephanie A; Han, Shujie; Imai, Masaki; Tomlinson, Stephen; Meier, Kathryn E

2008-09-01

The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectable endogenous PLD1 or PLD2. The overall goal of the study was to examine the roles of PLD2 in cellular signal transduction and cell phenotype. HA-PLD2 confers PLD activity that is activated by phorbol ester, ionomycin, and okadaic acid. Proliferation and Erk activation are unchanged in cells transfected with active PLD2; proliferation rate is decreased in cells expressing inactive PLD2. Basal tyrosine phosphorylation of focal adhesion kinase (FAK) is increased in cells expressing active PLD2, as is phosphorylation of Akt; inactive PLD2 has no effect. Expression of active PLD2 is associated with increased spreading and elongation of cells on tissue culture plastic, whereas inactive PLD2 inhibits cell spreading. Inactive PLD2 also inhibits cell adhesion, migration, and serum-induced invasion. Cells expressing active PLD2 form metastases in syngeneic mice, as do the parental cells; cells expressing inactive PLD2 form fewer metastases than parental cells. In summary, active PLD2 enhances FAK phosphorylation, Akt activation, and cell invasion in EL4 lymphoma cells, whereas inactive PLD2 exerts inhibitory effects on adhesion, migration, invasion, and tumor formation. Overall, expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis.

Statistical inference in comparing DInSAR and GPS data in fault areas

NASA Astrophysics Data System (ADS)

Barzaghi, R.; Borghi, A.; Kunzle, A.

2012-04-01

DInSAR and GPS data are nowadays currently used in geophysical investigation, e.g. for estimating slip rate over the fault plane in seismogenic areas. This analysis is usually done by mapping the surface deformation rates as estimated by GPS and DInSAR over the fault plane using suitable geophysical models (e.g. the Okada model). Usually, DInSAR vertical velocities and GPS horizontal velocities are used for getting an integrated slip estimate. However, it is sometimes critical to merge the two kinds of information since they may reflect a common undergoing geophysical signal plus different disturbing signals that are not related to the fault dynamic. In GPS and DInSAR data analysis, these artifacts are mainly connected to signal propagation in the atmosphere and to hydrological phenomena (e.g. variation in the water table). Thus, some coherence test between the two information must be carried out in order to properly merge the GPS and DInSAR velocities in the inversion procedure. To this aim, statistical tests have been studied to check for the compatibility of the two deformation rate estimates coming from GPS and DInSAR data analysis. This has been done according both to standard and Bayesian testing methodology. The effectiveness of the proposed inference methods has been checked with numerical simulations in the case of a normal fault. The fault structure is defined following the Pollino fault model and both GPS and DInSAR data are simulated according to real data acquired in this area.

Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29.

PubMed

Law, Alice Y S; Yeung, B H Y; Ching, L Y; Wong, Chris K C

2011-08-01

Our previous study demonstrated that, stanniocalcin-1 (STC1) was a target of histone deacetylase (HDAC) inhibitors and was involved in trichostatin A (TSA) induced apoptosis in the human colon cancer cells, HT29. In this study, we reported that the transcriptional factor, specificity protein 1 (Sp1) in association with retinoblastoma (Rb) repressed STC1 gene transcription in TSA-treated HT29 cells. Our data demonstrated that, a co-treatment of the cells with TSA and Sp1 inhibitor, mithramycin A (MTM) led to a marked synergistic induction of STC1 transcript levels, STC1 promoter (1 kb)-driven luciferase activity and an increase of apoptotic cell population. The knockdown of Sp1 gene expression in TSA treated cells, revealed the repressor role of Sp1 in STC1 transcription. Using a protein phosphatase inhibitor okadaic acid (OKA), an increase of Sp1 hyperphosphorylation and so a reduction of its transcriptional activity, led to a significant induction of STC1 gene expression. Chromatin immunoprecipitation (ChIP) assay revealed that Sp1 binding on STC1 proximal promoter in TSA treated cells. The binding of Sp1 to STC1 promoter was abolished by the co-treatment of MTM or OKA in TSA-treated cells. Re-ChIP assay illustrated that Sp1-mediated inhibition of STC1 transcription was associated with the recruitment of another repressor molecule, Rb. Collectively our findings identify STC1 is a downstream target of Sp1. Copyright © 2011 Wiley-Liss, Inc.

Tau-Induced Ca2+/Calmodulin-Dependent Protein Kinase-IV Activation Aggravates Nuclear Tau Hyperphosphorylation.

PubMed

Wei, Yu-Ping; Ye, Jin-Wang; Wang, Xiong; Zhu, Li-Ping; Hu, Qing-Hua; Wang, Qun; Ke, Dan; Tian, Qing; Wang, Jian-Zhi

2018-04-01

Hyperphosphorylated tau is the major protein component of neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). However, the mechanism underlying tau hyperphosphorylation is not fully understood. Here, we demonstrated that exogenously expressed wild-type human tau40 was detectable in the phosphorylated form at multiple AD-associated sites in cytoplasmic and nuclear fractions from HEK293 cells. Among these sites, tau phosphorylated at Thr205 and Ser214 was almost exclusively found in the nuclear fraction at the conditions used in the present study. With the intracellular tau accumulation, the Ca 2+ concentration was significantly increased in both cytoplasmic and nuclear fractions. Further studies using site-specific mutagenesis and pharmacological treatment demonstrated that phosphorylation of tau at Thr205 increased nuclear Ca 2+ concentration with a simultaneous increase in the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase IV (CaMKIV) at Ser196. On the other hand, phosphorylation of tau at Ser214 did not significantly change the nuclear Ca 2+ /CaMKIV signaling. Finally, expressing calmodulin-binding protein-4 that disrupts formation of the Ca 2+ /calmodulin complex abolished the okadaic acid-induced tau hyperphosphorylation in the nuclear fraction. We conclude that the intracellular accumulation of phosphorylated tau, as detected in the brains of AD patients, can trigger nuclear Ca 2+ /CaMKIV signaling, which in turn aggravates tau hyperphosphorylation. Our findings provide new insights for tauopathies: hyperphosphorylation of intracellular tau and an increased Ca 2+ concentration may induce a self-perpetuating harmful loop to promote neurodegeneration.

Morphotaxonomy and seasonal distribution of planktonic and benthic Prorocentrales in Karachi waters, Pakistan Northern Arabian Sea

NASA Astrophysics Data System (ADS)

Munir, Sonia; Burhan, Zaib-un-nisa; Naz, Tahira; Siddiqui, P. J. A.; Morton, Steve L.

2013-03-01

Morphotaxonomy and seasonal abundance of dinoflagellates of the genera Prorocentrum and Mesoporos (Prorocentrales) were studied from nutrient-rich waters, Karachi Harbor and the mouth of the Manora Channel, Pakistan during May 2002-July 2003. Using both light and scanning electron microscopy, 13 species of Prorocentrales were identified according to cell shape, size, ornamentation of thecal plates, and architecture of apical platelets, apical pore area, marginal pores, and intercalary bands. P. sigmoides, P. arcuatum, P. scutellum, P. donghaiense, P. balticum, P. minimum, P. emarginatum, P. lima, P. faustiae, and Mesoporos perforatus constitute new records for sindh coast of Pakistan. The most abundant species were P. minimum/P. balticum (4.5×103 cells/L), P. micans (1.1×103 cells/L), P. gracile / P. sigmoides (2.5×10 2 cells/L) and P. donghaiense (6.6×103 cells/L) at temperatures of 29-31°C and salinities of 35-40. Maximum abundance was observed in winter and lower abundance in summer. There was no significant change in the distribution of species between stations except for the benthic species which occurred close to Karachi Harbor waters. Significant positive correlations were observed between Prorocentrum spp. and temperature ( R 2 =0.27) and negative correlations with salinity ( R 2 =-0.32) except for P. minimum and P. emarginatum which has negative correlation with temperature ( R 2 =-0.24) and positive with salinity ( R 2 =0.08, 0.19). The finding of potential okadaic-acid producing species of benthic Prorocentrum call for monitoring for possible human health problems in this region.

Human cancer stem cells are a target for cancer prevention using (-)-epigallocatechin gallate.

PubMed

Fujiki, Hirota; Sueoka, Eisaburo; Rawangkan, Anchalee; Suganuma, Masami

2017-12-01

Our previous experiments show that the main constituent of green-tea catechins, (-)-epigallocatechin gallate (EGCG), completely prevents tumor promotion on mouse skin initiated with 7,12-dimethylbenz(a)anthracene followed by okadaic acid and that EGCG and green tea extract prevent cancer development in a wide range of target organs in rodents. Therefore, we focused our attention on human cancer stem cells (CSCs) as targets of cancer prevention and treatment with EGCG. The numerous reports concerning anticancer activity of EGCG against human CSCs enriched from cancer cell lines were gathered from a search of PubMed, and we hope our review of the literatures will provide a broad selection for the effects of EGCG on various human CSCs. Based on our theoretical study, we discuss the findings as follows: (1) Compared with the parental cells, human CSCs express increased levels of the stemness markers Nanog, Oct4, Sox2, CD44, CD133, as well as the EMT markers, Twist, Snail, vimentin, and also aldehyde dehydrogenase. They showed decreased levels of E-cadherin and cyclin D1. (2) EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs. (3) EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs. (4) The inhibition of EGCG of the stemness of CSCs was weaker compared with parental cells. (5) The weak inhibitory activity of EGCG increased synergistically in combination with anticancer drugs. Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.

Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease.

PubMed

Wang, Feixiang; Jia, Yali; Liu, Jiajing; Zhai, Jinglei; Cao, Ning; Yue, Wen; He, Huixia; Pei, Xuetao

2017-06-01

Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs-treated cells were found to restore gradually with re-elongation of retracted dendrites. Meanwhile, Cell Counting Kit-8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs-treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α-tubulin and F-actin demonstrated that the hDPSCs-treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD. © 2017 International Federation for Cell Biology.

Mouse fibroblasts homozygous for c-Src oncogene disruption shows dramatic suppression of expression of the gene encoding osteopontin, and adhesive phosphoprotein implicated in bone differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chackalaparampil, I.; Mukherjee, B.B.; Peri, A.

1994-09-01

Osteopetrosis, affecting mice and humans alike, arises from reduced or impaired bone resorption, causing abnormally dense bone formation. Normal bone differentiation requires continuous resorption and remodeling by osteoclasts which are derived from monocyte/macrophage lineage in the bone marrow. It has been reported that targeted homozygous disruption of c-src proto-oncogene in mice results in the development of osteopetrosis due to impaired bone-resorbing function of osteoclast cells. However, the molecular mechanism(s) which leads to osteoclast dysfunction in c-src deficient (src{sup -/-}) mice remains unclear. Here, we report that in embryonic fibroblasts derived from homozygous Src{sup -/-} mice, the expression of the genemore » coding for osteopontin (OP), a phosphorylated glycoprotein involved in bone differentiation, is drastically repressed. OP gene expression is not, however, affected in the heterozygous (Src{sup +/-}) mutant cells of identical origin, or in the c-src expression and OP production. Moreover, OP expression in c-src-deficient cells could be rescued upon treatment with 12-0-tetradecanoyl phorbol-13-myristate-acetate or okadaic acid. These observations indicate that OP expression is regulated via an src-mediated protein kinase C signaling pathway. Since it is known that OP mediates osteoclast adherence to the bone matrix, a key event in bone differentiation, our data is most significant in that they strongly suggest that drastic inhibition of synthesis of OP prevents osteoclasts in Src{sup -/-} mice from anchoring to the bone matrix. Consequently, this disruption of osteoclast adherence impairs their ability to form bone-resorbing ruffled border, causing osteopetrosis.« less

Stevioside improves pancreatic beta-cell function during glucotoxicity via regulation of acetyl-CoA carboxylase.

PubMed

Chen, Jianguo; Jeppesen, Per Bendix; Nordentoft, Iver; Hermansen, Kjeld

2007-06-01

Chronic hyperglycemia is detrimental to pancreatic beta-cells, causing impaired insulin secretion and beta-cell turnover. The characteristic secretory defects are increased basal insulin secretion (BIS) and a selective loss of glucose-stimulated insulin secretion (GSIS). Several recent studies support the view that the acetyl-CoA carboxylase (ACC) plays a pivotal role for GSIS. We have shown that stevioside (SVS) enhances insulin secretion and ACC gene expression. Whether glucotoxicity influences ACC and whether this action can be counteracted by SVS are not known. To investigate this, we exposed isolated mouse islets as well as clonal INS-1E beta-cells for 48 h to 27 or 16.7 mM glucose, respectively. We found that 48-h exposure to high glucose impairs GSIS from mouse islets and INS-1E cells, an effect that is partly counteracted by SVS. The ACC dephosphorylation inhibitor okadaic acid (OKA, 10(-8) M), and 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR, 10(-4) M), an activator of 5'-AMP protein kinase that phosphorylates ACC, eliminated the beneficial effect of SVS. 5-Tetrade-cyloxy-2-furancarboxylic acid (TOFA), the specific ACC inhibitor, blocked the effect of SVS as well. During glucotoxity, ACC gene expression, ACC protein, and phosphorylated ACC protein were increased in INS-1E beta-cells. SVS pretreatment further increased ACC gene expression with strikingly elevated ACC activity and increased glucose uptake accompanied by enhanced GSIS. Our studies show that glucose is a potent stimulator of ACC and that SVS to some extent counteracts glucotoxicity via increased ACC activity. SVS possesses the potential to alleviate negative effects of glucotoxicity in beta-cells via a unique mechanism of action.

PP2A activity is controlled by methylation and regulates oncoprotein expression in melanoma cells: a mechanism which participates in growth inhibition induced by chloroethylnitrosourea treatment.

PubMed

Guénin, Samuel; Schwartz, Laurent; Morvan, Daniel; Steyaert, Jean Marc; Poignet, Amandine; Madelmont, Jean Claude; Demidem, Aicha

2008-01-01

Protein phosphatase 2A (PP2A), an Akt pathway inhibitor, is considered to be activated by methylation of its catalytic subunit. Also PP2A downregulation was proposed to take part in carcinogenesis. Recently, PP2A activation was shown to be activated in response to DNA damage. To obtain further information on the role of PP2A in tumors and response to DNA damage, we investigated the relationship between PP2A methylation and activity, cell proliferation, Akt activation, c-Myc expression and PTEN activity in B16 melanoma cells untreated and after chloroethylnitrosourea (CENU) treatment. In untreated cells, okadaic acid, an antagonist of PP2A methylation, inhibited PP2A activity, stimulated cell proliferation, increased Akt activation and c-Myc expression. Xylulose-5-phosphate, an agonist of PP2A methylation, increased PP2A activity, decreased cell proliferation, Akt activation and c-Myc expression. However, both PP2A methylation modulators increased PTEN activity. During the response to CENU treatment, PP2A methylation and activity were strongly increased, Akt activation and c-Myc expression were decreased. However PTEN activity was increased. After tumor cell growth recovery, these modifications were moderately decreased. PP2A methylation was quantified and correlated positively with PP2A activity, and negatively with criteria for cell aggressiveness (cell proliferation, Akt activation, c-Myc expression). Based on these data, PP2A methylation status controls PP2A activity and oncoproteins expression and PP2A is strongly activated after CENU treatment thus partly explaining the growth inhibition in response to this agent. It follows that PP2A promethylating agents are potential candidates for anticancer drugs.

Dinophysis caudata generated lipophilic shellfish toxins in bivalves from the Nanji Islands, East China Sea

NASA Astrophysics Data System (ADS)

Jiang, Tao; Xu, Yixiao; Li, Yang; Qi, Yuzao; Jiang, Tianjiu; Wu, Feng; Zhang, Fan

2014-01-01

A 12-month program of monitoring potentially toxic microalgae (that produce lipophilic shellfish toxins; LSTs) and their toxins in bivalves was conducted from April 2006 to March 2007 in the Nanji Islands, East China Sea. Two Dinophysis species, D. caudata and D. acuminata, were identified, and D. caudata was found to be the dominant species. D. caudata was detected in water samples between April and June 2006, and between February and March 2007. It reached its highest abundances in May, with a mean abundance of 1.38×102 cells/L in surface water and 1.25×102 cells/L in bottom water (<10 m deep). The temporal distribution of D. caudata was associated with the occurrence of LSTs in bivalve samples, which mostly occurred at the same time as D. caudata blooms, between April and July 2006. All of the cultured bivalves sampled between April and June were contaminated with LSTs, with an average toxicity of 85 μg okadaic acid (OA) eq./100 g meat, which was four times higher than the Chinese regulatory limit (20 μg OA eq./100 g meat). Ten out of fifteen wild samples (66.7%) collected during the same period were positive for LSTs, and contained an average LST toxicity of 45 μg OA eq./100 g meat (more than twice the regulatory value). Cultured Patinopecten yessoensis collected on 15 May 2006 had the highest toxicity, 320 μg OA eq./100 g meat, and relatively high toxicities (80 to 160 μg OA eq./100 g meat) were found in bivalves until the end of July.

PP2A regulates SCF-induced cardiac stem cell migration through interaction with p38 MAPK.

PubMed

Wang, Ying; Xia, Yanli; Kuang, Dong; Duan, Yaqi; Wang, Guoping

2017-12-15

Previous studies have shown that stem cell factor (SCF) induces the migration of cardiac stem cells (CSCs) and helps to repair myocardial infarctions. Earlier studies on the migration mechanism only focused on the activation of kinases; here, we aimed to explore the functional role of protein phosphatase 2A (PP2A) in SCF-induced CSC migration. CSCs were treated with SCF, PP2A enzymatic activity was measured, the phosphorylation levels of PP2A, p38 MAPK and cofilin were evaluated using western blot. Transwell assay was used to determine the migratory ability of CSCs. In vitro, SCF induced the phosphorylation of p38 MAPK and cofilin, leading to the migration of CSCs. Cofilin acted as a downstream signal of p38 MAPK. PP2A was involved in this process. Further studies revealed that PP2A was inactivated via phosphorylation at Tyr307 by SCF and the inactivation/phosphorylation was mediated by activated p38 MAPK, as p38 MAPK inhibitor SB203580 or siRNA prevented SCF-induced inactivation and phosphorylation of PP2A. When CSCs were pretreated with PP2A inhibitor (okadaic acid, OA), SCF-induced CSC migration and the downstream signals were enhanced, and the enhancement was reversed when p38 MAPK was blocked. Additionally, co-immunoprecipitation showed a direct interaction of PP2A with p38 MAPK. Our results indicated that PP2A regulated the SCF-induced activation of p38 MAPK/cofilin signaling pathway and subsequent migration of CSCs by interaction with p38 MAPK. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human cytomegalovirus phosphoproteins are hypophosphorylated and intrinsically disordered.

PubMed

Rieder, Franz J J; Kastner, Marie-Theres; Hartl, Markus; Puchinger, Martin G; Schneider, Martina; Majdic, Otto; Britt, William J; Djinović-Carugo, Kristina; Steininger, Christoph

2017-03-01

Protein phosphorylation has important regulatory functions in cell homeostasis and is tightly regulated by kinases and phosphatases. The tegument of human cytomegalovirus (CMV) contains not only several proteins reported to be extensively phosphorylated but also cellular protein phosphatases (PP1 and PP2A). To investigate this apparent inconsistency, we evaluated the phosphorylation status of the tegument proteins pUL32 and pp65 by enzymatic dephosphorylation and MS. Enzymatic dephosphorylation with bacterial λ phosphatase, but not with PP1, shifted the pUL32-specific signal on reducing SDS-PAGE from ~150 to ~148 kDa, a mass still much larger than the ~118 kDa obtained from our diffusion studies and from the calculated protein mass of ~113 kDa. Remarkably, inhibition of phosphatases through treatment with the phosphatase inhibitors calyculin A and okadaic acid resulted in a shift to ~190 or ~180 kDa, respectively, indicating that a considerable number of potential phosphorylated residues on pUL32 are not phosphorylated under normal conditions. MS revealed a general state of hypophosphorylation of CMV phosphoproteins with only 17 phosphorylated residues detected on pUL32 and 19 on pp65, respectively. Moreover, bioinformatics analysis shows that the C-terminal two-thirds of pUL32 are intrinsically disordered and that most phosphorylations map to this region. In conclusion, we show that important CMV tegument proteins are indeed phosphorylated, though to a lesser extent than previously reported, and the difference in mobility on SDS-PAGE and calculated mass of pUL32 may not be attributed to phosphorylation but more likely due to the partially intrinsically disordered nature of pUL32.

Protein Phosphatase 1-α Regulates AS160 Ser588 and Thr642 Dephosphorylation in Skeletal Muscle.

PubMed

Sharma, Pragya; Arias, Edward B; Cartee, Gregory D

2016-09-01

Akt substrate of 160 kDa (AS160) phosphorylation on Thr(642) and Ser(588) by Akt is essential for insulin's full effect on glucose transport. However, protein phosphorylation is determined by the balance of actions by kinases and phosphatases, and the specific phosphatase(s) controlling AS160 dephosphorylation is (are) unknown. Accordingly, we assessed roles of highly expressed skeletal muscle serine/threonine phosphatases (PP1, PP2A, PP2B, and PP2C) on AS160 dephosphorylation. Preliminary screening of candidate phosphatases used an AS160 dephosphorylation assay. Lysates from insulin-stimulated skeletal muscle were treated with pharmacological phosphatase inhibitors and assessed for AS160 Ser(588) and Thr(642) dephosphorylation. AS160 dephosphorylation on both phosphorylation sites was unaltered by PP2B or PP2C inhibitors. Okadaic acid (low dose inhibits PP2A; high dose inhibits PP1) delayed AS160 Ser(588) (both doses) and Thr(642) (high dose only) dephosphorylation concomitant with greater Akt phosphorylation (both doses). AS160 was coimmunoprecipitated with PP1-α but not with PP1-β, PP1-γ1, or PP2A. Recombinant inhibitor-2 protein (a selective PP1 inhibitor) delayed AS160 dephosphorylation on both phosphorylation sites without altering Akt phosphorylation. Furthermore, knockdown of PP1-α but not PP1-β or PP1-γ1 by small interfering RNA caused greater AS160 Ser(588) and Thr(642) phosphorylation concomitant with unaltered Akt phosphorylation. Together, these results identified PP1-α as a regulator of AS160 Thr(642) and Ser(588) dephosphorylation in skeletal muscle. © 2016 by the American Diabetes Association.

The RCN1-encoded A subunit of protein phosphatase 2A increases phosphatase activity in vivo

NASA Technical Reports Server (NTRS)

Deruere, J.; Jackson, K.; Garbers, C.; Soll, D.; Delong, A.; Evans, M. L. (Principal Investigator)

1999-01-01

Protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine-specific protein phosphatase, comprises a catalytic C subunit and two distinct regulatory subunits, A and B. The RCN1 gene encodes one of three A regulatory subunits in Arabidopsis thaliana. A T-DNA insertion mutation at this locus impairs root curling, seedling organ elongation and apical hypocotyl hook formation. We have used in vivo and in vitro assays to gauge the impact of the rcn1 mutation on PP2A activity in seedlings. PP2A activity is decreased in extracts from rcn1 mutant seedlings, and this decrease is not due to a reduction in catalytic subunit expression. Roots of mutant seedlings exhibit increased sensitivity to the phosphatase inhibitors okadaic acid and cantharidin in organ elongation assays. Shoots of dark-grown, but not light-grown seedlings also show increased inhibitor sensitivity. Furthermore, cantharidin treatment of wild-type seedlings mimics the rcn1 defect in root curling, root waving and hypocotyl hook formation assays. In roots of wild-type seedlings, RCN1 mRNA is expressed at high levels in root tips, and accumulates to lower levels in the pericycle and lateral root primordia. In shoots, RCN1 is expressed in the apical hook and the basal, rapidly elongating cells in etiolated hypocotyls, and in the shoot meristem and leaf primordia of light-grown seedlings. Our results show that the wild-type RCN1-encoded A subunit functions as a positive regulator of the PP2A holoenzyme, increasing activity towards substrates involved in organ elongation and differential cell elongation responses such as root curling.

RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.

PubMed

Uchida, Hitoshi; Matsumura, Shinji; Okada, Shunpei; Suzuki, Tsutomu; Minami, Toshiaki; Ito, Seiji

2017-05-01

Transcriptional and post-translational regulations are important in peripheral nerve injury-induced neuropathic pain, but little is known about the role of post-transcriptional modification. Our objective was to determine the possible effect of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyze post-transcriptional RNA editing, in tactile allodynia, a hallmark of neuropathic pain. Seven days after L5 spinal nerve transection (SNT) in adult mice, we found an increase in ADAR2 expression and a decrease in ADAR3 expression in the injured, but not in the uninjured, dorsal root ganglions (DRGs). These changes were accompanied by elevated levels of editing at the D site of the serotonin (5-hydroxytryptamine) 2C receptor (5-HT 2C R), at the I/V site of coatomer protein complex subunit α (COPA), and at the R/G site of AMPA receptor subunit GluA2 in the injured DRG. Compared to Adar2 +/+ /Gria2 R/R littermate controls, Adar2 -/- /Gria2 R/R mice completely lacked the increased editing of 5-HT 2C R, COPA, and GluA2 transcripts in the injured DRG and showed attenuated tactile allodynia after SNT. Furthermore, the antidepressant fluoxetine inhibited neuropathic allodynia after injury and reduced the COPA I/V site editing in the injured DRG. These findings suggest that ADAR2 is a mediator of injury-induced tactile allodynia and thus a potential therapeutic target for the treatment of neuropathic pain.-Uchida, H., Matsumura, S., Okada, S., Suzuki, T., Minami, T., Ito, S. RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury. © FASEB.

A novel bicistronic sensor vector for detecting caspase-3 activation.

PubMed

Vagner, Tatyana; Mouravlev, Alexandre; Young, Deborah

2015-01-01

Apoptosis is involved in pathological cell death of a wide range of human diseases. One of the most important biochemical markers of apoptosis is activation of caspase-3. Ability to detect caspase-3 activation early in the pathological process is important for determining the timing for interfering with apoptosis initiation and prevention of cell damage. Techniques allowing detection of caspase-3 activity at a single cell level show increased sensitivity, compared to biochemical assays; therefore, we developed a novel bicistronic caspase-3 sensor vector enabling detection of caspase-3 activity in individual cells. We employed green fluorescent protein (GFP) as a reporter for caspase-3 activation in our constructs and assessed the functionality of the generated constructs in transiently transfected Neuro2A and HEK293 cells under basal conditions and following application of okadaic acid (OA) or staurosporine (STS) to induce apoptosis. To ensure responsiveness of the new sensor vector to active caspase-3, we co-transfected the sensor with plasmid(s) overexpressing active caspase-3 and quantified GFP fluorescence using a plate reader. We observed an increase in GFP expression in cells transfected with the new bicistronic caspase-3 sensor in response to both OA and STS. We also showed a significant increase in GFP fluorescence intensity in cells co-expressing the sensor with the plasmid(s) encoding active caspase-3. We generated a novel bicistronic caspase-3 sensor vector which relies on a transcription factor/response element system. The obtained sensor combines high sensitivity of the single cell level detection with the possibility of automated quantification. Copyright © 2015 Elsevier Inc. All rights reserved.

Thalidomide suppresses NF-kappa B activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysaccharides, or phorbol ester.

PubMed

Majumdar, Sekhar; Lamothe, Betty; Aggarwal, Bharat B

2002-03-15

Thalidomide ([+]-alpha-phthalimidoglutarimide), a psychoactive drug that readily crosses the blood-brain barrier, has been shown to exhibit anti-inflammatory, antiangiogenic, and immunosuppressive properties through a mechanism that is not fully established. Due to the central role of NF-kappaB in these responses, we postulated that thalidomide mediates its effects through suppression of NF-kappaB activation. We investigated the effects of thalidomide on NF-kappaB activation induced by various inflammatory agents in Jurkat cells. The treatment of these cells with thalidomide suppressed TNF-induced NF-kappaB activation, with optimum effect occurring at 50 microg/ml thalidomide. These effects were not restricted to T cells, as other hematopoietic and epithelial cell types were also inhibited. Thalidomide suppressed H(2)O(2)-induced NF-kappaB activation but had no effect on NF-kappaB activation induced by PMA, LPS, okadaic acid, or ceramide, suggesting selectivity in suppression of NF-kappaB. The suppression of TNF-induced NF-kappaB activation by thalidomide correlated with partial inhibition of TNF-induced degradation of an inhibitory subunit of NF-kappaB (IkappaBalpha), abrogation of IkappaBalpha kinase activation, and inhibition of NF-kappaB-dependent reporter gene expression. Thalidomide abolished the NF-kappaB-dependent reporter gene expression activated by overexpression of TNFR1, TNFR-associated factor-2, and NF-kappaB-inducing kinase, but not that activated by the p65 subunit of NF-kappaB. Overall, our results clearly demonstrate that thalidomide suppresses NF-kappaB activation specifically induced by TNF and H(2)O(2) and that this may contribute to its role in suppression of proliferation, inflammation, angiogenesis, and the immune system.

Treatment with direct-current stimulation against cingulate seizure-like activity induced by 4-aminopyridine and bicuculline in an in vitro mouse model.

PubMed

Chang, Wei-Pang; Lu, Hsiang-Chin; Shyu, Bai-Chuang

2015-03-01

Clinical studies have shown that cathodal transcranial direct-current stimulation (tDCS) application can produce long-term suppressive effects on drug-resistant seizures. Whether this long-term effect produced by cathodal tDCS can counterbalance the enhancement of synaptic transmission during seizures requires further investigation. Our hypothesis was that the long-term effects of DCS on seizure suppression by the application of cathodal DCS occur through a long-term depression (LTD)-like mechanism. We used a thalamocingulate brain slice preparation combined with a multielectrode array and patch recording to investigate the underlying mechanism of the suppressive effect of DCS on anterior cingulate cortex (ACC) seizures. Patch-clamp recordings showed that cathodal DCS significantly decreased spontaneous excitatory postsynaptic currents (EPSCs) and epileptic EPSCs caused by the 4-aminopyridine. Fifteen minutes of DCS application reliably induced LTD, and the synaptic activation frequency was an important factor in LTD formation. The application of DCS alone without continuous synaptic activation did not induce LTD. Direct-current stimulation-induced LTD appeared to be N-methyl-d-aspartate (NMDA)-dependent, in which the application of the NMDA receptor antagonist D-1-2-amino-5-phosphonopentanoic acid (APV) abolished DCS-induced LTD, and the immediate effect remained. Direct-current stimulation-induced LTD and the long-term effects of DCS on seizure-like activities were also abolished by okadaic acid, a protein phosphatase 1 inhibitor. The long-term effects of DCS on seizures were not influenced by the depotentiation blocker FK-506. Therefore, we conclude that the long-term effects of DCS on seizure-like activities in brain slice occur through an LTD-like mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells.

PubMed

Gause, K C; Homma, M K; Licciardi, K A; Seger, R; Ahn, N G; Peterson, M J; Krebs, E G; Meier, K E

1993-08-05

Phorbol ester-sensitive and -resistant EL4 thymoma cell lines differ in their ability to activate mitogen-activated protein kinase (MAPK) in response to phorbol ester. Treatment of wild-type EL4 cells with phorbol ester results in the rapid activations of MAPK and pp90rsk kinase, a substrate for MAPK, while neither kinase is activated in response to phorbol ester in variant EL4 cells. This study examines the activation of MAPK kinase (MAPKK), an activator of MAPK, in wild-type and variant EL4 cells. Phosphorylation of a 40-kDa substrate, identified as MAPK, was observed following in vitro phosphorylation reactions using cytosolic extracts or Mono Q column fractions prepared from phorbol ester-treated wild-type EL4 cells. MAPKK activity coeluted with a portion of the inactive MAPK upon Mono Q anion-exchange chromatography, permitting detection of the MAPKK activity in fractions containing both kinases. This MAPKK activity was present in phorbol ester-treated wild-type cells, but not in phorbol ester-treated variant cells or in untreated wild-type or variant cells. The MAPKK from wild-type cells was able to activate MAPK prepared from either wild-type or variant cells. MAPKK activity could be stimulated in both wildtype and variant EL4 cells in response to treatment of cells with okadaic acid. These results indicate that the failure of variant EL4 cells to activate MAP kinase in response to phorbol ester is due to a failure to activate MAPKK. Therefore, the step that confers phorbol ester resistance to variant EL4 cells lies between the activation of protein kinase C and the activation of MAPKK.

Selective Extraction and Purification of Azaspiracids from Blue Mussels ( Mytilus edulis) Using Boric Acid Gel.

PubMed

Miles, Christopher O; Kilcoyne, Jane; McCarron, Pearse; Giddings, Sabrina D; Waaler, Thor; Rundberget, Thomas; Samdal, Ingunn A; Løvberg, Kjersti E

2018-03-21

Azaspiracids belong to a family of more than 50 polyether toxins originating from marine dinoflagellates such as Azadinium spinosum. All of the azaspiracids reported thus far contain a 21,22-dihydroxy group. Boric acid gel can bind selectively to compounds containing vic-diols or α-hydroxycarboxylic acids via formation of reversible boronate complexes. Here we report use of the gel to selectively capture and release azaspiracids from extracts of blue mussels. Analysis of the extracts and fractions by liquid chromatography-tandem mass spectrometry (LC-MS) showed that this procedure resulted in an excellent cleanup of the azaspiracids in the extract. Analysis by enzyme-linked immunoasorbent assay (ELISA) and LC-MS indicated that most azaspiracid analogues were recovered in good yield by this procedure. The capacity of boric acid gel for azaspiracids was at least 50 μg/g, making this procedure suitable for use in the early stages of preparative purification of azaspiracids. In addition to its potential for concentration of dilute samples, the extensive cleanup provided by boric acid gel fractionation of azaspiracids in mussel samples almost eliminated matrix effects during subsequent LC-MS and could be expected to reduce matrix effects during ELISA analysis. The method may therefore prove useful for quantitative analysis of azaspiracids as part of monitoring programs. Although LC-MS data showed that okadaic acid analogues also bound to the gel, this was much less efficient than for azaspiracids under the conditions used. The boric acid gel methodology is potentially applicable to other important groups of natural toxins containing diols including ciguatoxins, palytoxins, pectenotoxins, tetrodotoxin, trichothecenes, and toxin glycosides.

G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity through PDZ motif-dependent and -independent mechanisms.

PubMed

Gonzalez de Valdivia, Ernesto; Broselid, Stefan; Kahn, Robin; Olde, Björn; Leeb-Lundberg, L M Fredrik

2017-06-16

G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor 1 (GPER1), is thought to play important roles in breast cancer and cardiometabolic regulation, but many questions remain about ligand activation, effector coupling, and subcellular localization. We showed recently that GPR30 interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive decrease in cAMP production independently of G i/o Here, we show that GPR30 also constitutively increases ERK1/2 activity. Removing the receptor PDZ motif or knocking down specifically AKAP5 inhibited the increase, showing that this increase also requires the PDZ interaction. However, the increase was inhibited by pertussis toxin as well as by wortmannin but not by AG1478, indicating that G i/o and phosphoinositide 3-kinase (PI3K) mediate the increase independently of epidermal growth factor receptor transactivation. FK506 and okadaic acid also inhibited the increase, implying that a protein phosphatase is involved. The proposed GPR30 agonist G-1 also increased ERK1/2 activity, but this increase was only observed at a level of receptor expression below that required for the constitutive increase. Furthermore, deleting the PDZ motif did not inhibit the G-1-stimulated increase. Based on these results, we propose that GPR30 increases ERK1/2 activity via two G i/o -mediated mechanisms, a PDZ-dependent, apparently constitutive mechanism and a PDZ-independent G-1-stimulated mechanism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Profiling of Extracellular Toxins Associated with Diarrhetic Shellfish Poison in Prorocentrum lima Culture Medium by High-Performance Liquid Chromatography Coupled with Mass Spectrometry.

PubMed

Pan, Lei; Chen, Junhui; Shen, Huihui; He, Xiuping; Li, Guangjiu; Song, Xincheng; Zhou, Deshan; Sun, Chengjun

2017-09-30

Extracellular toxins released by marine toxigenic algae into the marine environment have attracted increasing attention in recent years. In this study, profiling, characterization and quantification of extracellular toxin compounds associated with diarrhetic shellfish poison (DSP) in the culture medium of toxin-producing dinoflagellates were performed using high-performance liquid chromatography-high-resolution mass spectrometry/tandem mass spectrometry for the first time. Results showed that solid-phase extraction can effectively enrich and clean the DSP compounds in the culture medium of Prorocentrum lima ( P. lima ), and the proposed method achieved satisfactory recoveries (94.80%-100.58%) and repeatability (relative standard deviation ≤9.27%). Commercial software associated with the accurate mass information of known DSP toxins and their derivatives was used to screen and identify DSP compounds. Nine extracellular DSP compounds were identified, of which seven toxins (including OA-D7b, OA-D9b, OA-D10a/b, and so on) were found in the culture medium of P. lima for the first time. The results of quantitative analysis showed that the contents of extracellular DSP compounds in P. lima culture medium were relatively high, and the types and contents of intracellular and extracellular toxins apparently varied in the different growth stages of P. lima . The concentrations of extracellular okadaic acid and dinophysistoxin-1 were within 19.9-34.0 and 15.2-27.9 μg/L, respectively. The total concentration of the DSP compounds was within the range of 57.70-79.63 μg/L. The results showed that the proposed method is an effective tool for profiling the extracellular DSP compounds in the culture medium of marine toxigenic algae.

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

PubMed Central

Palma, Eleonora; Roseti, Cristina; Maiolino, Francesca; Fucile, Sergio; Martinello, Katiuscia; Mazzuferi, Manuela; Aronica, Eleonora; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Miledi, Ricardo; Simonato, Michele; Eusebi, Fabrizio

2007-01-01

A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (IGABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, IGABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease. PMID:18083839

Ecology of the ciguatera causing dinoflagellates from the Northern Great Barrier Reef: changes in community distribution and coastal eutrophication.

PubMed

Skinner, Mark P; Lewis, Richard J; Morton, Steve

2013-12-15

Ciguatera fish poisoning (CFP) is known to be caused by the ciguatoxins from the dinoflagellate genus Gambierdiscus, however, there is the potential for other toxins such as okadaic acid and dinophysistoxins from the genus Prorocentrum, and palytoxin from the genus Ostreopsis, to contaminate seafood. These genera may also be indicators of ecosystem health and potentially impact on coral reef ecosystems and the role they may play in the succession of coral to macroalgae dominated reefs has not been researched. Sixteen GBR field sites spanning inshore, mid-lagoon and outer lagoon (offshore) regions were studied. Samples were collected from September 2006 to December 2007 and abundance of benthic dinoflagellates on different host macroalgae and concentration of nutrients present in the water column were determined. The maximum abundance of Prorocentrum, Ostreopsis and Gambierdiscus found was 112, 793 and 50 cells per gram wet weight of host macroalgae, respectively. The average level of Dissolved Inorganic Nitrogen (DIN) in the water column across all sites (0.03 mg/L) was found to be more than double the threshold critical value (0.013 mg/L) for healthy coral reefs. Compared to a previous study 1984, there is evidence of a major shift in the distribution and abundance of these dinoflagellates. Inshore reefs have either of Prorocentrum (as at Green Island) or Ostreopsis (as at Magnetic Island) dominating the macroalgal surface niche which was once dominated by Gambierdiscus, whilst at offshore regions Gambierdiscus is still dominant. This succession may be linked to the ongoing eutrophication of the GBR lagoon and have consequences for the sources of toxins for ongoing cases of ciguatera. Published by Elsevier Ltd.

Rover exploration on the lunar surface; a science proposal for SELENE-B mission

NASA Astrophysics Data System (ADS)

Sasaki, S.; Kubota, T.; Akiyama, H.; Hirata, N.; Kunii, Y.; Matsumoto, K.; Okada, T.; Otake, M.; Saiki, K.; Sugihara, T.

LUNARSURFACE:ASCIENCES. Sasaki (1), T. Kubota (2) , H. Akiyama (1) , N. Hirata (3), Y. Kunii (4), K. Matsumoto (5), T. Okada (2), M. Otake (3), K. Saiki (6), T. Sugihara (3) (1) Department of Earth and Planetary Science, Univ. Tokyo, (2) Institute of Space and Astronautical Sciences, (3) National Space Development Agency of Japan, (4) Department of Electrical and Electronic Engineering, Chuo Univ., (5) National Aerospace Laboratory of Japan, (6) Research Institute of Materials and Resources, Akita Univ. sho@eps.s.u -tokyo.ac.jp/Fax:+81-3-5841-4569 A new lunar landing mission (SELENE-B) is now in consideration in Japan. Scientific investigation plans using a rover are proposed. To clarify the origin and evolution of the moon, the early crustal formation and later mare volcanic processes are still unveiled. We proposed two geological investigation plans: exploration of a crater central peak to discover subsurface materials and exploration of dome-cone structures on young mare region. We propose multi-band macro/micro camera using AOTF, X-ray spectrometer/diffractometer and gamma ray spectrometer. Since observation of rock fragments in brecciaed rocks is necessary, the rover should have cutting or scraping mechanism of rocks. In our current scenario, landing should be performed about 500m from the main target (foot of a crater central peak or a cone/dome). After the spectral survey by multi-band camera on the lander, the rover should be deployed for geological investigation. The rover should make a short (a few tens meter) round trip at first, then it should perform traverse observation toward the main target. Some technological investigations on SELENE-B project will be also presented.

Contamination of commercially available seafood by key diarrhetic shellfish poisons along the coast of China.

PubMed

Lin, Chao; Liu, Zeng-Shan; Tan, Cai-Yun; Guo, Yi-Ping; Li, Lin; Ren, Hong-Lin; Li, Yan-Song; Hu, Pan; Gong, Sheng; Zhou, Yu; Lu, Shi-Ying

2015-01-01

With the increasing number of outbreaks of food-borne diseases caused by okadaic acid (OA) and its analogue dinophysistoxin-1 (DTX-1), two key diarrhetic shellfish poison (DSP) toxins, OA and DTX-1, have become a serious threat to public health and have attracted significant public attention in China. The aim of our study was to monitor OA and DTX-1 contamination in commercially available seafood and to provide references for tracking these toxins and preventing disease outbreaks. From 2010 to 2012, 40 species were collected from six coastal cities of four inland seas in China. An enzyme-linked immunosorbent assay (ELISA) and a lateral flow immunochromatographic (LFIC) test strip were used to analyse the samples, and the results were further confirmed using a commercially available ELISA kit. The monitoring results indicated that 23 of 40 species were positive for contamination. In addition, 14 of the positive species were determined to be inedible because the content of OA and DTX-1 was above the regulatory limit. Simultaneously, we verified that the digestive glands of shellfish tended to accumulate toxin, in contrast to the flesh. The highest concentrations of OA and DTX-1 were recorded in Scapharca broughtonii, which was collected from Qing Dao, in relation to the other analysed species. Moreover, the Arca family as well as Mytilus galloprovincialis were severely contaminated by OA and its analogue. The above results indicate that some of the commercially available seafood from the coastal cities in China may be inedible due to serious marine toxin contamination. The results of this study might play an important role in protecting consumer health and safety screening of marine products.

Decreased glucagon responsiveness by bile acids: a role for protein kinase Calpha and glucagon receptor phosphorylation.

PubMed

Ikegami, Tadashi; Krilov, Lada; Meng, Jianping; Patel, Bhumika; Chapin-Kennedy, Kelli; Bouscarel, Bernard

2006-11-01

Dihydroxy bile acids like chenodeoxycholic acid (CDCA) induce heterologous glucagon receptor desensitization. We previously demonstrated that protein kinase C (PKC) was activated by certain bile acids and mediated the CDCA-induced decrease in glucagon responsiveness. The aim of the present study was to explore the role of PKC in the phosphorylation and desensitization of the glucagon receptor by CDCA. Desensitization was evaluated by measuring adenylyl cyclase activity. Receptor phosphorylation was assayed by metabolic labeling with [gamma-(32)P] ATP. Protein kinase C (PKC) translocation and activation was visualized by fluorescence microscopy. CDCA decreased cAMP production induced by glucagon in a dose-dependent manner without affecting cAMP synthesis through stimulation of either stimulatory GTP-binding protein (Gs) by NaF or adenylyl cyclase by forskolin. The CDCA-induced inhibition of adenylyl cyclase activity was potentiated by the phosphatase inhibitor, okadaic acid. The desensitizing effect of CDCA was bile acid-specific and was significantly reduced in the presence of PKC inhibitors and after PKC down-regulation by phorbol 12-myristate 13-acetate. CDCA increased glucagon receptor phosphorylation more than 3-fold at concentrations as low as 25 mum. Furthermore, CDCA significantly stimulated human recombinant PKCalpha autophosphorylation in vitro, as well as PKCalpha translocation to the plasma membrane and phosphorylation in vivo at concentrations as low as 25 mum. CDCA also stimulated PKCdelta translocation to the perinuclear region. Activated PKCalpha, PKCzeta, and to a lesser extent, PKCdelta, phosphorylated the glucagon receptor in vitro. This study demonstrates that certain bile acids, such as CDCA, stimulate phosphorylation and heterologous desensitization of the glucagon receptor, involving at least PKCalpha activation.

The role of spatial organization of Ca2+ release sites in the generation of arrhythmogenic diastolic Ca2+ release in myocytes from failing hearts

PubMed Central

Ho, Hsiang-Ting; Bonilla, Ingrid M.; Terentyeva, Radmila; Schober, Karsten E.; Terentyev, Dmitry; Carnes, Cynthia A.

2018-01-01

In heart failure (HF), dysregulated cardiac ryanodine receptors (RyR2) contribute to the generation of diastolic Ca2+ waves (DCWs), thereby predisposing adrenergically stressed failing hearts to life-threatening arrhythmias. However, the specific cellular, subcellular, and molecular defects that account for cardiac arrhythmia in HF remain to be elucidated. Patch-clamp techniques and confocal Ca2+ imaging were applied to study spatially defined Ca2+ handling in ventricular myocytes isolated from normal (control) and failing canine hearts. Based on their activation time upon electrical stimulation, Ca2+ release sites were categorized as coupled, located in close proximity to the sarcolemmal Ca2+ channels, and uncoupled, the Ca2+ channel-free non-junctional Ca2+ release units. In control myocytes, stimulation of β-adrenergic receptors with isoproterenol (Iso) resulted in a preferential increase in Ca2+ spark rate at uncoupled sites. This site-specific effect of Iso was eliminated by the phosphatase inhibitor okadaic acid, which caused similar facilitation of Ca2+ sparks at coupled and uncoupled sites. Iso-challenged HF myocytes exhibited increased predisposition to DCWs compared to control myocytes. In addition, the overall frequency of Ca2+ sparks was increased in HF cells due to preferential stimulation of coupled sites. Furthermore, coupled sites exhibited accelerated recovery from functional refractoriness in HF myocytes compared to control myocytes. Spatially resolved subcellular Ca2+ mapping revealed that DCWs predominantly originated from coupled sites. Inhibition of CaMK∏ suppressed DCWs and prevented preferential stimulation of coupled sites in Iso-challenged HF myocytes. These results suggest that CaMK∏-(and phosphatase)-dependent dysregulation of junctional Ca2+ release sites contributes to Ca2+-dependent arrhythmogenesis in HF. PMID:28612155

Disrupting Cyclin Dependent Kinase 1 in Spermatocytes Causes Late Meiotic Arrest and Infertility in Mice1

PubMed Central

Clement, Tracy M.; Inselman, Amy L.; Goulding, Eugenia H.; Willis, William D.; Eddy, Edward M.

2015-01-01

While cyclin dependent kinase 1 (CDK1) has a critical role in controlling resumption of meiosis in oocytes, its role has not been investigated directly in spermatocytes. Unique aspects of male meiosis led us to hypothesize that its role is different in male meiosis than in female meiosis. We generated a conditional knockout (cKO) of the Cdk1 gene in mouse spermatocytes to test this hypothesis. We found that CDK1-null spermatocytes undergo synapsis, chiasmata formation, and desynapsis as is seen in oocytes. Additionally, CDK1-null spermatocytes relocalize SYCP3 to centromeric foci, express H3pSer10, and initiate chromosome condensation. However, CDK1-null spermatocytes fail to form condensed bivalent chromosomes in prophase of meiosis I and instead are arrested at prometaphase. Thus, CDK1 has an essential role in male meiosis that is consistent with what is known about the role of CDK1 in female meiosis, where it is required for formation of condensed bivalent metaphase chromosomes and progression to the first meiotic division. We found that cKO spermatocytes formed fully condensed bivalent chromosomes in the presence of okadaic acid, suggesting that cKO chromosomes are competent to condense, although they do not do so in vivo. Additionally, arrested cKO spermatocytes exhibited irregular cell shape, irregular large nuclei, and large distinctive nucleoli. These cells persist in the seminiferous epithelium through the next seminiferous epithelial cycle with a lack of stage XII checkpoint-associated cell death. This indicates that CDK1 is required upstream of a checkpoint-associated cell death as well as meiotic metaphase progression in mouse spermatocytes. PMID:26490841

Thermodynamic and Thermoelastic properties of the NAL Phase

NASA Astrophysics Data System (ADS)

Marcondes, M. L.; Yao, C.; Wu, Z.; Wentzcovitch, R.

2017-12-01

Subduction of Mid Ocean Ridge Basalt (MORB) transports crust elements to the deep Earth. Therefore, it is important to study MORB in order to understand geophysical processes in the mantle. The high Al2O3 content of the MORB gives rise to a new aluminous phase (NAL) that constitutes up to 25% of its composition [1]. Phase equilibrium study of MgAl2O4-CaAl2O4 generated the mineral CaMg2Al6O12 with hexagonal symmetry, which was proposed for the NAL phase [2,3]. The NAL chemical composition, however, shows significantly less calcium [1,4] and several compositions have been considered in previous studies of this phase [5,6]. Here we present an ab initio study of NAL phases at high temperatures with several possible compositions. We used the quasiharmonic approximation to address thermodynamic and thermoelastic properties and seismic velocities of this phase as function of composition. References[1] T. Irifune and A. E. Ringwood, Earth Planet. Sci. Lett. 117, 101 (1993). [2] H. Miura, Y. Hamada, T. Suzuki, M. Akaogi, N. Miyajima, and K. Fujino, Am. Mineral. 85, 1799 (2000). [3] M. Akaogi, Y. Hamada, T. Suzuki, M. Kobayashi, and M. Okada, Phys. Earth Planet. Inter. 115, 67 (1999). [4] A. Ricolleau, J. P. Perrillat, G. Fiquet, I. Daniel, J. Matas, A. Addad, N. Menguy, H. Cardon, M. Mezouar, and N. Guignot, J. Geophys. Res. Solid Earth 115, B08202 (2010). [5] M. Mookherjee, B. B. Karki, L. Stixrude, and C. Lithgow-Bertelloni, Geophys. Res. Lett. 39, L19306 (2012). [6] K. Kawai and T. Tsuchiya, Geophys. Res. Lett. 37, L17302 (2010).

[6]-Gingerol Affects Glucose Metabolism by Dual Regulation via the AMPKα2-Mediated AS160-Rab5 Pathway and AMPK-Mediated Insulin Sensitizing Effects.

PubMed

Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Moon, Ji Wook; Lee, Soo Kyung; Kim, Su Jin; Kim, Joong Kwan; Park, Sun Hwa; Kim, Hyeon Soo

2015-07-01

[6]-Gingerol has been used to control diabetes and dyslipidemia; however, its metabolic role is poorly understood. In this study, [6]-gingerol increased adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation in mouse skeletal muscle C2C12 cells. Stimulation of glucose uptake by [6]-gingerol was dependent on AMPKα2. Moreover, both Inhibition and knockdown of AMPKα2 blocked [6]-gingerol-induced glucose uptake. [6]-Gingerol significantly decreased the activity of protein phosphatase 2A (PP2A). Inhibition of PP2A activity with okadaic acid enhanced the phosphorylation of AMPKα2. Moreover, the interaction between AMPKα2 and PP2A was increased by [6]-gingerol, suggesting that PP2A mediates the effect of [6]-gingerol on AMPK phosphorylation. In addition, [6]-gingerol increased the phosphorylation of Akt-substrate 160 (AS160), which is a Rab GTPase-activating protein. Inhibition of AMPKα2 blocked [6]-gingerol-induced AS160 phosphorylation. [6]-gingerol increased the Rab5, and AMPKα2 knockdown blocked [6]-gingerol-induced expression of Rab5, indicating AMPK play as an upstream of Rab5. It also increased glucose transporter 4 (GLUT4) mRNA and protein expression and stimulated GLUT4 translocation. Furthermore, insulin-mediated glucose uptake and Akt phosphorylation were further potentiated by [6]-gingerol treatment. This potentiation was not observed in the presence of AMPK inhibitor compound C. In summary, our results suggest that [6]-gingerol plays an important role in glucose metabolism via the AMPKα2-mediated AS160-Rab5 pathway and through potentiation of insulin-mediated glucose regulation. © 2015 Wiley Periodicals, Inc.

The Role of Deep Creep in the Timing of Large Earthquakes

NASA Astrophysics Data System (ADS)

Sammis, C. G.; Smith, S. W.

2012-12-01

The observed temporal clustering of the world's largest earthquakes has been largely discounted for two reasons: a) it is consistent with Poisson clustering, and b) no physical mechanism leading to such clustering has been proposed. This lack of a mechanism arises primarily because the static stress transfer mechanism, commonly used to explain aftershocks and the clustering of large events on localized fault networks, does not work at global distances. However, there is recent observational evidence that the surface waves from large earthquakes trigger non-volcanic tremor at the base of distant fault zones at global distances. Based on these observations, we develop a simple non-linear coupled oscillator model that shows how the triggering of such tremor can lead to the synchronization of large earthquakes on a global scale. A basic assumption of the model is that induced tremor is a proxy for deep creep that advances the seismic cycle of the fault. We support this hypothesis by demonstrating that the 2010 Maule Chile and the 2011 Fukushima Japan earthquakes, which have been shown to induce tremor on the Parkfield segment of the San Andreas Fault, also produce changes in off-fault seismicity that are spatially and temporally consistent with episodes of deep creep on the fault. The observed spatial pattern can be simulated using an Okada dislocation model for deep creep (below 20 km) on the fault plane in which the slip rate decreases from North to South consistent with surface creep measurements and deepens south of the "Parkfield asperity" as indicated by recent tremor locations. The model predicts the off-fault events should have reverse mechanism consistent with observed topography.

KSC-98pc246

NASA Image and Video Library

1998-01-30

CAPE CANAVERAL, Fla. -- In the International Space Station Processing Facility at NASA's Kennedy Space Center in Florida, senior government officials from 15 countries participating in the space station program signed agreements in Washington D.C. on Jan. 29 to establish the framework of cooperation among the partners on the design, development, operation and utilization of the space station. Acting Secretary of State Strobe Talbott signed the 1998 Intergovernmental Agreement on Space Station Cooperation with representatives of Russia, Japan, Canada, and participating countries of the European Space Agency ESA -- Belgium, Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. Some of these officials then toured Kennedy's Space Station Processing Facility SSPF with NASA Administrator Daniel Goldin, at front, sixth from the left. They are, left to right, front to back: Hidetoshi Murayama, National Space Development Agency of Japan NASDA Louis Laurent, Embassy of France Haakon Blankenborg, Norwegian Parliament Standing Committee on Foreign Affairs His Excellency Joris Vos, ambassador of the Netherlands His Excellency Tom Vraalsen, ambassador of Norway Goldin Luigi Berlinguer, Italian minister for education, scientific, and technological research Antonio Rodota, director general, ESA Yvan Ylieff, Belgian minister of science and chairman of the ESA Ministerial Council Jacqueline Ylieff Masaaki Komatsu, Kennedy local NASDA representative and interpreter Serge Ivanets, space attache, Embassy of Russia Hiroshi Fujita, Science and Technology Agency of Japan Akira Mizutani, Japanese Ministry of Foreign Affairs Peter Grognard, science attache', Royal Embassy of Belgium Michelangelo Pipan, Italian diplomatic counselor to the minister His Excellency Gerhard Fulda, German Federal Foreign Office Jorg Feustel-Buechl, ESA director of manned space flight and microgravity A. Yakovenko, Russian Ministry of Foreign Affairs Jo

Multi-millennial-scale climate variability in Antarctica during the past seven glacial periods

NASA Astrophysics Data System (ADS)

Kawamura, K.

2009-12-01

Climate variability on 1,000- to 10,000 -year timescales and associated interhemispheric seesaw during the last glacial period have been documented in a variety of paleoclimatic records. However, the frequency, magnitude, cause and prerequisites for the older glacial periods are still uncertain. We here present a new 720,000-year ice core record from Dome Fuji, East Antarctica. The agreement between the Dome Fuji and Dome C isotopic temperature records indicates homogeneous climate variability across the East Antarctic plateau throughout the past 720 kyr. By combining the two temperature proxy records, we identified persistent multi-millennial-scale Antarctic events over the past seven glacial periods. With a fully coupled atmosphere-ocean general circulation model, it is suggested that the prerequisite for the bipolar seesaw is the combination of a cold background climate and freshwater input into the northern North Atlantic. With our identification criteria, the mean repetition period of the large Antarctic events increased from 6 kyr in the older three glacial periods to 8 kyr in the younger four glacial periods. Low frequency variations (repetition period of >10 kyr) occur in the early parts of the last four glacial periods (i.e. after Mid-Brunhes climatic shift), suggesting a role of insolation forcing on the large bipolar events in the recent glacial periods. Dome Fuji Ice Core Project members (listed in alphabetical order): Ayako Abe-Ouchi, Yutaka Ageta, Shuji Aoki, Nobuhiko Azuma, Yoshiyuki Fujii, Koji Fujita, Shuji Fujita, Kotaro Fukui, Teruo Furukawa, Atsushi Furusaki, Kumiko Goto-Azuma, Ralf Greve, Motohiro Hirabayashi, Takeo Hondoh, Akira Hori, Shinichiro Horikawa, Kazuho Horiuchi, Makoto Igarashi, Yoshinori Iizuka, Takao Kameda, Kokichi Kamiyama, Hiroshi Kanda, Kenji Kawamura, Mika Kohno, Takayuki Kuramoto, Yuki Matsushi, Morihiro Miyahara, Takayuki Miyake, Atsushi Miyamoto, Hideaki Motoyama, Yasuo Nagashima, Yoshiki Nakayama, Takakiyo Nakazawa, Fumio

Cross regulation between cGMP-dependent protein kinase and Akt in vasodilatation of porcine pulmonary artery.

PubMed

Liu, Juan; Liu, Huixia; Li, Yanjing; Xu, Xiaojian; Chen, Zhengju; Liu, Limei; Yu, Xiaoxing; Gao, Yuansheng; Dou, Dou

2014-11-01

cGMP-dependent protein kinase (PKG) plays a crucial role in vasodilatation induced by cGMP-elevating agents. Akt has been demonstrated to be involved in modulating vasoreactivity. The present study was to determine the interaction between PKG and Akt and their influences on nitric oxide (NO)-induced vasodilatation. Isolated fourth-generation porcine pulmonary arteries were dissected from the lung and cut into rings in ice-cold modified Krebs-Ringer bicarbonate buffer. The relaxant responses of vessels were determined by organ chamber technique, cGMP was assayed by using enzyme-linked immunosorbent assay kit, the protein levels of phosphorylated Akt were examined by Western blotting, and the activity of phosphodiesterase type 5 (PDE5) was assayed by measuring the rate of cGMP degradation. Incubation with DETA NONOate (a stable NO donor) and 8-Br-cGMP (a cell membrane permeable analog of cGMP) attenuated Akt phosphorylation at Ser-473, which was prevented by Rp-8-Br-PET-cGMPS (a specific inhibitor of PKG) and calyculin A (an inhibitor of protein phosphatase 1 and 2A) but not by okadaic acid (a selective inhibitor of protein phosphatase 2A). Inhibition of Akt enhanced the relaxation and cGMP elevation of porcine pulmonary arteries induced by DETA NONOate or sodium nitroprusside, which was prevented by zaprinast, a specific inhibitor of PDE5. Incubation with LY294002 or Akt inhibitor reduced PDE5 activity in porcine pulmonary arteries. The present study indicates that PKG may attenuate Akt phosphorylation through protein phosphatase 1, which leads to an augmented cGMP elevation by inhibition of PDE5. The increased cGMP in turn activates PKG. Such a positive feedback may play an important role in NO-induced pulmonary vasodilatation.

Profiling of Extracellular Toxins Associated with Diarrhetic Shellfish Poison in Prorocentrum lima Culture Medium by High-Performance Liquid Chromatography Coupled with Mass Spectrometry

PubMed Central

Pan, Lei; Chen, Junhui; Shen, Huihui; He, Xiuping; Li, Guangjiu; Song, Xincheng; Zhou, Deshan; Sun, Chengjun

2017-01-01

Extracellular toxins released by marine toxigenic algae into the marine environment have attracted increasing attention in recent years. In this study, profiling, characterization and quantification of extracellular toxin compounds associated with diarrhetic shellfish poison (DSP) in the culture medium of toxin-producing dinoflagellates were performed using high-performance liquid chromatography–high-resolution mass spectrometry/tandem mass spectrometry for the first time. Results showed that solid-phase extraction can effectively enrich and clean the DSP compounds in the culture medium of Prorocentrum lima (P. lima), and the proposed method achieved satisfactory recoveries (94.80%–100.58%) and repeatability (relative standard deviation ≤9.27%). Commercial software associated with the accurate mass information of known DSP toxins and their derivatives was used to screen and identify DSP compounds. Nine extracellular DSP compounds were identified, of which seven toxins (including OA-D7b, OA-D9b, OA-D10a/b, and so on) were found in the culture medium of P. lima for the first time. The results of quantitative analysis showed that the contents of extracellular DSP compounds in P. lima culture medium were relatively high, and the types and contents of intracellular and extracellular toxins apparently varied in the different growth stages of P. lima. The concentrations of extracellular okadaic acid and dinophysistoxin-1 were within 19.9–34.0 and 15.2–27.9 μg/L, respectively. The total concentration of the DSP compounds was within the range of 57.70–79.63 μg/L. The results showed that the proposed method is an effective tool for profiling the extracellular DSP compounds in the culture medium of marine toxigenic algae. PMID:28974018

Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

NASA Technical Reports Server (NTRS)

Swingle, Mark R.; Ciszak, Ewa M.; Honkanen, Richard E.

2004-01-01

Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

Unique subcellular distribution of phosphorylated Plk1 (Ser137 and Thr210) in mouse oocytes during meiotic division and pPlk1(Ser137) involvement in spindle formation and REC8 cleavage.

PubMed

Du, Juan; Cao, Yan; Wang, Qian; Zhang, Nana; Liu, Xiaoyu; Chen, Dandan; Liu, Xiaoyun; Xu, Qunyuan; Ma, Wei

2015-01-01

Polo-like kinase 1 (Plk1) is pivotal for proper mitotic progression, its targeting activity is regulated by precise subcellular positioning and phosphorylation. Here we assessed the protein expression, subcellular localization and possible functions of phosphorylated Plk1 (pPlk1(Ser137) and pPlk1(Thr210)) in mouse oocytes during meiotic division. Western blot analysis revealed a peptide of pPlk1(Ser137) with high and stable expression from germinal vesicle (GV) until metaphase II (MII), while pPlk1(Thr210) was detected as one large single band at GV stage and 2 small bands after germinal vesicle breakdown (GVBD), which maintained stable up to MII. Immunofluorescence analysis showed pPlk1(Ser137) was colocalized with microtubule organizing center (MTOC) proteins, γ-tubulin and pericentrin, on spindle poles, concomitantly with persistent concentration at centromeres and dynamic aggregation between chromosome arms. Differently, pPlk1(Thr210) was persistently distributed across the whole body of chromosomes after meiotic resumption. The specific Plk1 inhibitor, BI2536, repressed pPlk1(Ser137) accumulation at MTOCs and between chromosome arms, consequently disturbed γ-tubulin and pericentrin recruiting to MTOCs, destroyed meiotic spindle formation, and delayed REC8 cleavage, therefore arresting oocytes at metaphase I (MI) with chromosome misalignment. BI2536 completely reversed the premature degradation of REC8 and precocious segregation of chromosomes induced with okadaic acid (OA), an inhibitor to protein phosphatase 2A. Additionally, the protein levels of pPlk1(Ser137) and pPlk1(Thr210), as well as the subcellular distribution of pPlk1(Thr210), were not affected by BI2536. Taken together, our results demonstrate that Plk1 activity is required for meiotic spindle assembly and REC8 cleavage, with pPlk1(Ser137) is the action executor, in mouse oocytes during meiotic division.

Phosphatase inhibitors remove the run-down of γ-aminobutyric acid type A receptors in the human epileptic brain

PubMed Central

Palma, E.; Ragozzino, D. A.; Di Angelantonio, S.; Spinelli, G.; Trettel, F.; Martinez-Torres, A.; Torchia, G.; Arcella, A.; Di Gennaro, G.; Quarato, P. P.; Esposito, V.; Cantore, G.; Miledi, R.; Eusebi, F.

2004-01-01

The properties of γ-aminobutyric acid (GABA) type A receptors (GABAA receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABAA receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat α1β2γ2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABAA receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABAA receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABAA-receptor β1, β2, β3, and γ2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABAA receptors. Blockage of phosphatases stabilizes the TLE GABAA receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy. PMID:15218107

NO3 −/H+ Antiport in the Tonoplast of Cucumber Root Cells Is Stimulated by Nitrate Supply: Evidence for a Reversible Nitrate-Induced Phosphorylation of Vacuolar NO3 −/H+ Antiport

PubMed Central

Migocka, Magdalena; Warzybok, Anna; Papierniak, Anna; Kłobus, Grażyna

2013-01-01

Studies in the last few years have shed light on the process of nitrate accumulation within plant cells, achieving molecular identification and partial characterization of the genes and proteins involved in this process. However, contrary to the plasma membrane-localized nitrate transport activities, the kinetics of active nitrate influx into the vacuole and its adaptation to external nitrate availability remain poorly understood. In this work, we have investigated the activity and regulation of the tonoplast-localized H+/NO3 − antiport in cucumber roots in response to N starvation and NO3 − induction. The time course of nitrate availability strongly influenced H+/NO3 − antiport activity at the tonoplast of root cells. However, under N starvation active nitrate accumulation within the vacuole still occurred. Hence, either a constitutive H+-coupled transport system specific for nitrate operates at the tonoplast, or nitrate uses another transport protein of broader specificity to different anions to enter the vacuole via a proton-dependent process. H+/NO3 − antiport in cucumber was significantly stimulated in NO3 −-induced plants that were supplied with nitrate for 24 hours following 6-day-long N starvation. The cytosolic fraction isolated from the roots of NO3 −-induced plants significantly stimulated H+/NO3 − antiport in tonoplast membranes isolated from cucumbers growing on nitrate. The stimulatory effect of the cytosolic fraction was completely abolished by EGTA and the protein kinase inhibitor staurosporine and slightly enhanced by the phosphatase inhibitors okadaic acid and cantharidin. Hence, we conclude that stimulation of H+/NO3 − antiport at the tonoplast of cucumber roots in response to nitrate provision may occur through the phosphorylation of a membrane antiporter involving Ca-dependent, staurosporine-sensitive protein kinase. PMID:24040130

α(2) noradrenergic receptor suppressed CaMKII signaling in spinal dorsal horn of mice with inflammatory pain.

PubMed

Wang, Xin-Tai; Lian, Xia; Xu, Ying-Ming; Suo, Zhan-Wei; Yang, Xian; Hu, Xiao-Dong

2014-02-05

Intrathecal application of α2 noradrenergic receptor agonists effectively alleviates the pathological pain induced by peripheral tissue injury. However, the spinal antinociceptive mechanisms of α2 noradrenergic receptors remain to be characterized. The present study performed immunohistochemistry and western blot to elucidate the signaling pathway initiated by α2 noradrenergic receptors in spinal dorsal horn of mice, and identified calcium/calmodulin-dependent protein kinase II (CaMKII) as an important target for noradrenergic suppression of inflammatory pain. Our data showed that intraplantar injection of Complete Freund's Adjuvant (CFA) substantially enhanced CaMKII autophosphorylation at Threonine 286, which could be abolished by intrathecal administration of α2 noradrenergic receptor agonist clonidine. Gi protein-coupled α2 noradrenergic receptor might inhibit cAMP-dependent protein kinase (PKA) to disturb CaMKII signaling. We found that pharmacological activation of PKA in intact mice also enhanced spinal CaMKII autophosphorylation level, which was completely antagonized by clonidine. Moreover, direct PKA inhibition in CFA-injected mice mimicked the suppressive effect of α2 noradrenergic receptors on CaMKII. PKA inhibition has been shown to downregulate CaMKII by enhancing protein phosphatase activity. Consistent with this notion, spinal treatment with protein phosphatase inhibitor okadaic acid ruled out clonidine-mediated CaMKII dephosphorylation in CFA-injected mice. Through PKA/protein phosphatase/CaMKII pathway, clonidine noticeably decreased CFA-evoked phosphorylation of N-methyl-d-aspartate subtype glutamate receptor GluN1 and GluN2B subunit as well as α-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid subtype glutamate receptor GluA1 subunit. These data suggested that interference with CaMKII signaling might represent an important mechanism underlying noradrenergic suppression of inflammatory pain. Copyright © 2013 Elsevier B.V. All rights

Low magnitude earthquakes generating significant subsidence: the Lunigiana case study

NASA Astrophysics Data System (ADS)

Samsonov, S. V.; Polcari, M.; Melini, D.; Cannelli, V.; Moro, M.; Bignami, C.; Saroli, M.; Vannoli, P.; Stramondo, S.

2013-12-01

We applied the Differential Interferometric Synthetic Aperture Radar (DInSAR) technique to investigate and measure surface displacements due to the ML 5.2, June 21, 2013, earthquake occurred in the Apuan Alps (NW Italy) at a depth of about 5 km. The Centroid Moment Tensor (CMT) solution from INGV indicates an almost pure normal fault mechanism. Two differential interferograms showing the coseismic displacement were generated using X- band and C-band data respectively. The X-Band interferogram was obtained from a Cosmo-SkyMed ascending pair (azimuth -7.9° and incidence angle 40°) with a time interval of one day (June 21 - June 22) and 139 m spatial baseline, covering an area of about 40x40 km around the epicenter. The topographic phase component was removed using the 90 m SRTM DEM. The C-Band interferferogram was computed from two RADARSAT-2 Standard-3 (S3) images, characterized by 24 days temporal and 69 m spatial baselines, acquired on June 18 and July 12, 2013 on ascending orbit (azimuth -10.8°) with an incidence angle of 34° and covering 100x100 km area around the epicenter. The topographic phase component was removed using 30 m ASTER DEM. Adaptive filtering, phase unwrapping with Minimum Cost Flow (MCF) algorithm and orbital refinement were also applied to both interferograms. We modeled the observed SAR deformation fields using the Okada analytical formulation within a nonlinear inversion scheme, and found them to be consistent with a fault plane dipping towards NW at an angle of about 45°. In spite of the small magnitude, this earthquake produces a surface subsidence of about 1.5 cm in the Line-Of-Sight (LOS) direction, corresponding to about 3 cm along the vertical axis, that can be observed in both interferograms and appears consistent with the normal fault mechanisms.

The Nrf1 CNC-bZIP protein is regulated by the proteasome and activated by hypoxia.

PubMed

Chepelev, Nikolai L; Bennitz, Joshua D; Huang, Ting; McBride, Skye; Willmore, William G

2011-01-01

Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is a transcription factor mediating cellular responses to xenobiotic and pro-oxidant stress. Nrf1 regulates the transcription of many stress-related genes through the electrophile response elements (EpREs) located in their promoter regions. Despite its potential importance in human health, the mechanisms controlling Nrf1 have not been addressed fully. We found that proteasomal inhibitors MG-132 and clasto-lactacystin-β-lactone stabilized the protein expression of full-length Nrf1 in both COS7 and WFF2002 cells. Concomitantly, proteasomal inhibition decreased the expression of a smaller, N-terminal Nrf1 fragment, with an approximate molecular weight of 23 kDa. The EpRE-luciferase reporter assays revealed that proteasomal inhibition markedly inhibited the Nrf1 transactivational activity. These results support earlier hypotheses that the 26 S proteasome processes Nrf1 into its active form by removing its inhibitory N-terminal domain anchoring Nrf1 to the endoplasmic reticulum. Immunoprecipitation demonstrated that Nrf1 is ubiquitinated and that proteasomal inhibition increased the degree of Nrf1 ubiquitination. Furthermore, Nrf1 protein had a half-life of approximately 5 hours in COS7 cells. In contrast, hypoxia (1% O(2)) significantly increased the luciferase reporter activity of exogenous Nrf1 protein, while decreasing the protein expression of p65, a shorter form of Nrf1, known to act as a repressor of EpRE-controlled gene expression. Finally, the protein phosphatase inhibitor okadaic acid activated Nrf1 reporter activity, while the latter was repressed by the PKC inhibitor staurosporine. Collectively, our data suggests that Nrf1 is controlled by several post-translational mechanisms, including ubiquitination, proteolytic processing and proteasomal-mediated degradation as well as by its phosphorylation status. © 2011 Chepelev et al.

Regulation of human airway ciliary beat frequency by intracellular pH

PubMed Central

Sutto, Zoltan; Conner, Gregory E; Salathe, Matthias

2004-01-01

pHi affects a number of cellular functions, but the influence of pHi on mammalian ciliary beat frequency (CBF) is not known. CBF and pHi of single human tracheobronchial epithelial cells in submerged culture were measured simultaneously using video microscopy (for CBF) and epifluorescence microscopy with the pH-sensitive dye BCECF. Baseline CBF and pHi values in bicarbonate-free medium were 7.2 ± 0.2 Hz and 7.49 ± 0.02, respectively (n = 63). Alkalization by ammonium pre-pulse to pHi 7.78 ± 0.02 resulted in a 2.2 ± 0.1 Hz CBF increase (P < 0.05). Following removal of NH4Cl, pHi decreased to 7.24 ± 0.02 and CBF to 5.8 ± 0.1 Hz (P < 0.05). Removal of extracellular CO2 to change pHi resulted in similar CBF changes. Pre-activation of cAMP-dependent protein kinase (10 μm forskolin), broad inhibition of protein kinases (100 μm H-7), inhibition of PKA (10 μm H-89), nor inhibition of phosphatases (10 μm cyclosporin + 1.5 μm okadaic acid) changed pHi-mediated changes in CBF, nor were they due to [Ca2+]i changes. CBF of basolaterally permeabilized human tracheobronchial cells, re-differentiated at the air–liquid interface, was 3.9 ± 0.3, 5.7 ± 0.4, 7.0 ± 0.3 and 7.3 ± 0.3 Hz at basolateral i.e., intracellular pH of 6.8, 7.2, 7.6 and 8.0, respectively (n = 18). Thus, intracellular alkalization stimulates, while intracellular acidification attenuates human airway CBF. Since phosphorylation and [Ca2+]i changes did not seem to mediate pHi-induced CBF changes, pHi may directly act on the ciliary motile machinery. PMID:15308676

Signalling mechanism for somatostatin receptor 5-mediated suppression of AMPA responses in rat retinal ganglion cells.

PubMed

Deng, Qin-Qin; Sheng, Wen-Long; Zhang, Gong; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

2016-08-01

Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Immunofluorescence double labelling demonstrated the expression of sst5 in rat GCs. Consistent to this, whole cell AMPA currents of GCs were dose-dependently suppressed by SRIF, and the effect was reversed by the sst5 antagonist BIM-23056. Intracellular dialysis of GDP-β-S or pre-incubation with the Gi/o inhibitor pertussis toxin (PTX) abolished the SRIF effect. The SRIF effect was mimicked by the administration of either 8-Br-cAMP or forskolin, but was eliminated by the protein kinase A (PKA) antagonists H-89/KT5720/Rp-cAMP. Moreover, SRIF increased intracellular Ca(2+) levels and did not suppress the AMPA currents when GCs were infused with an intracellular Ca(2+)-free solution or in the presence of ryanodine receptor modulators caffeine/ryanodine. Furthermore, the SRIF effect was eliminated when the activity of calmodulin (CaM), calcineurin and protein phosphatase 1 (PP1) was blocked with W-7, FK-506 and okadaic acid, respectively. SRIF persisted to suppress the AMPA currents when cGMP-protein kinase G (PKG) and phosphatidylinositol (PI)-/phosphatidylcholine (PC)-phospholipase C (PLC) signalling pathways were blocked. In rat flat-mount retinas, SRIF suppressed AMPAR-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) in GCs. We conclude that a distinct Gi/o/cAMP-PKA/ryanodine/Ca(2+)/CaM/calcineurin/PP1 signalling pathway comes into play due to the activation of sst5 to mediate the SRIF effect on GCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ser123 Is Essential for the Water Channel Activity of McPIP2;1 from Mesembryanthemum crystallinum*

PubMed Central

Amezcua-Romero, Julio C.; Pantoja, Omar; Vera-Estrella, Rosario

2010-01-01

The increased expression of McPIP2;1 (MipC), a root-specific aquaporin (AQP) from Mesembryanthemum crystallinum, under salt stress has suggested a role for this AQP in the salt tolerance of the plant. However, whether McPIP2;1 transports water or another solute and how its activity is regulated are so far unknown. Therefore, wild type (wt) or mutated McPIP2;1 protein was expressed in Xenopus laevis oocytes. Then, the osmotic water permeability (Pf) of the oocytes membrane was assessed by hypotonic challenges. Selectivity of McPIP2;1 to water was determined by radiolabeled glycerol or urea uptake assays. Moreover, swelling and in vitro phosphorylation assays revealed that both water permeation and phosphorylation status of McPIP2;1 were significantly increased by the phosphorylation agonists okadaic acid (OA), phorbol myristate acetate (PMA), and 8-Br-cAMP, and markedly decreased by the inhibitory peptides PKI 14-22 and PKC 20-28, inhibitors of protein kinases A (PKA) and C (PKC), respectively. Substitution of Ser123 or both, Ser123 and Ser282, abolished the water channel activity of McPIP2;1 while substitution of Ser282 only partially inhibited it (51.9% inhibition). Despite lacking Ser123 and/or Ser282, the McPIP2;1 mutant forms were still phosphorylated in vitro, which suggests that phosphorylation may have a dual role on this AQP. Our results indicate that McPIP2;1 water permeability depends completely on Ser123 and is positively regulated by PKA- and PKC-mediated phosphorylation. Regulation of the phosphorylation status of McPIP2;1 may contribute to control water transport through root cells when the plant is subjected to high salinity conditions. PMID:20332086

A role for protein phosphatase-2A in p38 mitogen-activated protein kinase-mediated regulation of the c-Jun NH(2)-terminal kinase pathway in human neutrophils.

PubMed

Avdi, Natalie J; Malcolm, Kenneth C; Nick, Jerry A; Worthen, G Scott

2002-10-25

Human neutrophil accumulation in inflammatory foci is essential for the effective control of microbial infections. Although exposure of neutrophils to cytokines such as tumor necrosis factor-alpha (TNFalpha), generated at sites of inflammation, leads to activation of MAPK pathways, mechanisms responsible for the fine regulation of specific MAPK modules remain unknown. We have previously demonstrated activation of a TNFalpha-mediated JNK pathway module, leading to apoptosis in adherent human neutrophils (Avdi, N. J., Nick, J. A., Whitlock, B. B., Billstrom, M. A., Henson, P. M., Johnson, G. L., and Worthen, G. S. (2001) J. Biol. Chem. 276, 2189-2199). Herein, evidence is presented linking regulation of the JNK pathway to p38 MAPK and the Ser/Thr protein phosphatase-2A (PP2A). Inhibition of p38 MAPK by SB 203580 and M 39 resulted in significant augmentation of TNFalpha-induced JNK and MKK4 (but not MKK7 or MEKK1) activation, whereas prior exposure to a p38-activating agent (platelet-activating factor) diminished the TNFalpha-induced JNK response. TNFalpha-induced apoptosis was also greatly enhanced upon p38 inhibition. Studies with a reconstituted cell-free system indicated the absence of a direct inhibitory effect of p38 MAPK on the JNK module. Neutrophil exposure to the Ser/Thr phosphatase inhibitors okadaic acid and calyculin A induced JNK activation. Increased phosphatase activity following TNFalpha stimulation was shown to be PP2A-associated and p38-dependent. Furthermore, PP2A-induced dephosphorylation of MKK4 resulted in its inactivation. Thus, in neutrophils, p38 MAPK, through a PP2A-mediated mechanism, regulates the JNK pathway, thus determining the extent and nature of subsequent responses such as apoptosis.

Epigallocatechin-3-gallate and penta-O-galloyl-β-D-glucose inhibit protein phosphatase-1.

PubMed

Kiss, Andrea; Bécsi, Bálint; Kolozsvári, Bernadett; Komáromi, István; Kövér, Katalin E; Erdődi, Ferenc

2013-01-01

Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) are responsible for the dephosphorylation of the majority of phosphoserine/threonine residues in cells. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), polyphenolic constituents of green tea and tannins, inhibit the activity of the PP1 recombinant δ-isoform of the PP1 catalytic subunit and the native PP1 catalytic subunit (PP1c) with IC(50) values of 0.47-1.35 μm and 0.26-0.4 μm, respectively. EGCG and PGG inhibit PP2Ac less potently, with IC(50) values of 15 and 6.6 μm, respectively. The structure-inhibitory potency relationships of catechin derivatives suggests that the galloyl group may play a major role in phosphatase inhibition. The interaction of EGCG and PGG with PP1c was characterized by NMR and surface plasmon resonance-based binding techniques. Competitive binding assays and molecular modeling suggest that EGCG docks at the hydrophobic groove close to the catalytic center of PP1c, partially overlapping with the binding surface of microcystin-LR or okadaic acid. This hydrophobic interaction is further stabilized by hydrogen bonding via hydroxyl/oxo groups of EGCG to PP1c residues. Comparative docking shows that EGCG binds to PP2Ac in a similar manner, but in a distinct pose. Long-term treatment (24 h) with these compounds and other catechins suppresses the viability of HeLa cells with a relative effectiveness reminiscent of their in vitro PP1c-inhibitory potencies. The above data imply that the phosphatase-inhibitory features of these polyphenols may be implicated in the wide spectrum of their physiological influence. © 2012 The Authors Journal compilation © 2012 FEBS.

Jupiter Trojan's Shallow Subsurface: Direct Observation By Radar Sounding

NASA Astrophysics Data System (ADS)

Herique, A.; Plettemeier, D.; Beck, P.; Michel, P.; Kumamoto, A.; Kofman, W. W.

2017-12-01

Most of the Jupiter's Trojan are classified as spectral type P or D from visible and near-IR observations. Still, major question remain regarding theire origin and geological evolution: What ices are present in their interior, and in what amount? What is the abundance and the nature of the organic fraction? Did they experience some level of differentiation powered by 26Al? Answering theses question is the goal of the Solar-Power Sail JAXA mission [1, 2]. This mission plans to study the surface by remote sensing in the optical in IR domain. This probe will carry a large-sized lander with a drill to sample the constitutive material at meter depth in order to complement physical and chemical properties measured by on-board instruments. The sample return is an option under study.Radar sounding of the shallow subsurface would be envisaged in complement to this payload. Sounding radar could provide the structure of the first tens of meters of the Trojan surface. It will allow identifying layering, ice lens, and embedded block. It also will enable to reconnect the surface with the deep interior in order to identify exogenous / pristine material. For the surface package, the drilling and the sample return, radar sounding is a unique opportunity to support the selection of the landing site and to provide the greater geological context of the samples that will be returned to Earth.In this paper, we will detail the objective of this instrument and then we will outline the proposed instrument, which is inheriting from the radar developed for the AIDA/AIM mission.[1] Mori, O. et al., Science experiments on a Jupiter Trojan Asteroid in the solar powerd sail mission. LPSC 2016 - 1822.[2] Okada, T. et al., Science and Exploration of a Jupiter Trojan Asteroid in the solar-power sail mission. LPSC 2017 - 1828.

Acetaminophen Modulates P-Glycoprotein Functional Expression at the Blood-Brain Barrier by a Constitutive Androstane Receptor–Dependent Mechanism

PubMed Central

Thompson, Brandon J.; Sanchez-Covarrubias, Lucy; Zhang, Yifeng; Laracuente, Mei-Li; Vanderah, Todd W.; Ronaldson, Patrick T.; Davis, Thomas P.

2013-01-01

Effective pharmacologic treatment of pain with opioids requires that these drugs attain efficacious concentrations in the central nervous system (CNS). A primary determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood-brain barrier (BBB) efflux transporter that is involved in brain-to-blood transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor constitutive androstane receptor (CAR) has been identified as a regulator of P-gp functional expression at the BBB. This is critical to pharmacotherapy of pain/inflammation, as patients are often administered acetaminophen (APAP), a CAR-activating ligand, in conjunction with an opioid. Our objective was to investigate, in vivo, the role of CAR in regulation of P-gp at the BBB. Following APAP treatment, P-gp protein expression was increased up to 1.4–1.6-fold in a concentration-dependent manner. Additionally, APAP increased P-gp transport of BODIPY-verapamil in freshly isolated rat brain capillaries. This APAP-induced increase in P-gp expression and activity was attenuated in the presence of CAR pathway inhibitor okadaic acid or transcriptional inhibitor actinomycin D, suggesting P-gp regulation is CAR-dependent. Furthermore, morphine brain accumulation was enhanced by P-gp inhibitors in APAP-treated animals, suggesting P-gp–mediated transport. A warm-water (50°C) tail-flick assay revealed a significant decrease in morphine analgesia in animals treated with morphine 3 or 6 hours after APAP treatment, as compared with animals treated concurrently. Taken together, our data imply that inclusion of APAP in a pain treatment regimen activates CAR at the BBB and increases P-gp functional expression, a clinically significant drug-drug interaction that modulates opioid analgesic efficacy. PMID:24019224

Histamine H2 receptor trafficking: role of arrestin, dynamin, and clathrin in histamine H2 receptor internalization.

PubMed

Fernandez, Natalia; Monczor, Federico; Baldi, Alberto; Davio, Carlos; Shayo, Carina

2008-10-01

Agonist-induced internalization of G protein-coupled receptors (GPCRs) has been implicated in receptor desensitization, resensitization, and down-regulation. In the present study, we sought to establish whether the histamine H2 receptor (H2r) agonist amthamine, besides promoting receptor desensitization, induced H2r internalization. We further studied the mechanisms involved and its potential role in receptor resensitization. In COS7 transfected cells, amthamine induced H2r time-dependent internalization, showing 70% of receptor endocytosis after 60-min exposure to amthamine. Agonist removal led to the rapid recovery of resensitized receptors to the cell surface. Similar results were obtained in the presence of cycloheximide, an inhibitor of protein synthesis. Treatment with okadaic acid, an inhibitor of the protein phosphatase 2A (PP2A) family of phosphatases, reduced the recovery of both H2r membrane sites and cAMP response. Arrestin 3 but not arrestin 2 overexpression reduced both H2r membrane sites and H2r-evoked cAMP response. Receptor cotransfection with dominant-negative mutants for arrestin, dynamin, Eps15 (a component of the clathrin-mediated endocytosis machinery), or RNA interference against arrestin 3 abolished both H2r internalization and resensitization. Similar results were obtained in U937 cells endogenously expressing H2r. Our findings suggest that amthamine-induced H2r internalization is crucial for H2r resensitization, processes independent of H2r de novo synthesis but dependent on PP2A-mediated dephosphorylation. Although we do not provide direct evidence for H2r interaction with beta-arrestin, dynamin, and/or clathrin, our results support their involvement in H2r endocytosis. The rapid receptor recycling to the cell surface and the specific involvement of arrestin 3 in receptor internalization further suggest that the H2r belongs to class A GPCRs.

Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters: A comparison of methods of analysis.

PubMed

McNamee, Sara E; Medlin, Linda K; Kegel, Jessica; McCoy, Gary R; Raine, Robin; Barra, Lucia; Ruggiero, Maria Valeria; Kooistra, Wiebe H C F; Montresor, Marina; Hagstrom, Johannes; Blanco, Eva Perez; Graneli, Edna; Rodríguez, Francisco; Escalera, Laura; Reguera, Beatriz; Dittami, Simon; Edvardsen, Bente; Taylor, Joe; Lewis, Jane M; Pazos, Yolanda; Elliott, Christopher T; Campbell, Katrina

2016-05-01

Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n=256) from European waters, collected 2009-2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (DTX1/DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2×2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray. Copyright © 2016 Elsevier B

Cooling Effects of Wearer-Controlled Vaporization for Extravehicular Activity.

PubMed

Tanaka, Kunihiko; Nagao, Daiki; Okada, Kosuke; Nakamura, Koji

2017-04-01

The extravehicular activity suit currently used by the United States in space includes a liquid cooling and ventilation garment (LCVG) that controls thermal conditions. Previously, we demonstrated that self-perspiration for evaporative cooling (SPEC) garment effectively lowers skin temperature without raising humidity in the garment. However, the cooling effect is delayed until a sufficient dose of water permeates and evaporates. In the present study, we hypothesized that wearer-controlled vaporization improves the cooling effect. Six healthy subjects rode a cycle ergometer under loads of 30, 60, 90, and 120 W for durations of 3 min each. Skin temperature and humidity on the back were measured continuously. Subjects wore and tested three garments: 1) a spandex garment without any cooling device (Normal); 2) a simulated LCVG (s-LCVG) or spandex garment knitted with a vinyl tube for flowing and permeating water; and 3) a garment that allowed wearer-controlled vaporization (SPEC-W). The use of s-LCVG reduced skin temperature by 1.57 ± 0.14°C during 12 min of cooling. Wearer-controlled vaporization of the SPEC-W effectively and significantly lowered skin temperature from the start to the end of cycle exercise. This decrease was significantly larger than that achieved using s-LCVG. Humidity in the SPEC-W was significantly lower than that in s-LCVG. This preliminary study suggests that SPEC-W is effective in lowering skin temperature without raising humidity in the garment. The authors think it would be useful in improving the design of a cooling system for extravehicular activity.Tanaka K, Nagao D, Okada K, Nakamura K. Cooling effects of wearer-controlled vaporization for extravehicular activity. Aerosp Med Hum Perform. 2017; 88(4):418-422.

Investigation of complex slow slip behavior along the Hikurangi subduction zone with earthquake simulator RSQSim

NASA Astrophysics Data System (ADS)

Colella, H.; Ellis, S. M.; Williams, C. A.

2015-12-01

The Hikurangi subduction zone (New Zealand) is one of many subudction zones that exhibit slow slip behavior. Geodetic observations along the Hikurangi subduction zone are unusual in that not only does the subduction zone exhibit periodic slow slip events at "typical" subduction-zone depths of 25-50 km along the southern part of the margin, but also much shallower depths of 8-15 km along the northern part of the margin. Furthermore, there is evidence for interplay between slow slip events at these different depth ranges (between the deep and shallow events) along the central part of the margin, and some of the slow slip behavior is observed along regions of the interface that were previously considered locked, which raises questions about the slip behavior of this region. This study employs the earthquake simulator, RSQSim, to explore variations in the effective normal stress (i.e., stress after the addition of pore fluid pressures) and the frictional instability necessary to generate the complex slow slip events observed along the Hikurangi margin. Preliminary results suggest that to generate slow slip events with similar recurrence intervals to those observed the effective normal stress (MPa) is 3x higher in the south than the north, 6-9MPa versus 2-3MPa, respectively. Results also suggest that, at a minimum, that some overlap along the central margin must exist between the slow slip sections in the north and south to reproduce the types of slip events observed along the Hikurangi subduction zone. To further validate the results from the simulations, Okada solutions for surface displacements will be compared to geodetic solution to more accurately constrain the areas in which slip behavior varies and the cause(s) for the variation(s).

Retinoic Acid Protects Cardiomyocytes from High Glucose-Induced Apoptosis via Inhibition of Sustained Activation of NF-κB Signaling

PubMed Central

Nizamutdinova, Irina T.; Guleria, Rakeshwar S.; Singh, Amar B.; Kendall, Jonathan A.; Baker, Kenneth M.; Pan, Jing

2012-01-01

We have previously shown that retinoic acid (RA) has protective effects on high glucose (HG)-induced cardiomyocyte apoptosis. To further elucidate the molecular mechanisms of RA effects, we determined the interaction between nuclear factor (NF)-κB and RA signaling. HG induced a sustained phosphorylation of IKK/IκBα and transcriptional activation of NF-κB in cardiomyocytes. Activated NF-κB signaling has an important role in HG-induced cardiomyocyte apoptosis and gene expression of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1 (MCP-1). All-trans RA (ATRA) and LGD1069, through activation of RAR/RXR-mediated signaling, inhibited the HG-mediated effects in cardiomyocytes. The inhibitory effect of RA on NF-κB activation was mediated through inhibition of IKK/IκBα phosphorylation. ATRA and LGD1069 treatment promoted protein phosphatase 2A (PP2A) activity, which was significantly suppressed by HG stimulation. The RA effects on IKK and IκBα were blocked by okadaic acid or silencing the expression of PP2Ac-subunit, indicating that the inhibitory effect of RA on NF-κB is regulated through activation of PP2A and subsequent dephosphorylation of IKK/IκBα. Moreover, ATRA and LGD1069 reversed the decreased PP2A activity and inhibited the activation of IKK/IκBα and gene expression of MCP-1, IL-6 and TNF-α in the hearts of Zucker diabetic fatty rats. In summary, our findings suggest that the suppressed activation of PP2A contributed to sustained activation of NF-κB in HG-stimulated cardiomyocytes; and that the protective effect of RA on hyperglycemia-induced cardiomyocyte apoptosis and inflammatory responses is partially regulated through activation of PP2A and suppression of NF-κB-mediated signaling and downstream targets. PMID:22718360

The natural compound cantharidin induces cancer cell death through inhibition of heat shock protein 70 (HSP70) and Bcl-2-associated athanogene domain 3 (BAG3) expression by blocking heat shock factor 1 (HSF1) binding to promoters.

PubMed

Kim, Joo Ae; Kim, Youngmi; Kwon, Byoung-Mog; Han, Dong Cho

2013-10-04

Heat shock factor 1 (HSF1) enhances the survival of cancer cells under various stresses. The knock-out of HSF1 impairs cancer formation and progression, suggesting that HSF1 is a promising therapeutic target. To identify inhibitors of HSF1 activity, we performed cell-based screening with a library of marketed and experimental drugs and identified cantharidin as an HSF1 inhibitor. Cantharidin is a potent antitumor agent from traditional Chinese medicine. Cantharidin inhibited heat shock-induced luciferase activity with an IC50 of 4.2 μm. In contrast, cantharidin did not inhibit NF-κB luciferase reporter activity, demonstrating that cantharidin is not a general transcription inhibitor. When the HCT-116 colorectal cancer cells were exposed to heat shock in the presence of cantharidin, the induction of HSF1 downstream target proteins, such as HSP70 and BAG3 (Bcl-2-associated athanogene domain 3), was suppressed. HSP70 and its co-chaperone BAG3 have been reported to protect cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. As expected, treating HCT-116 cancer cells with cantharidin significantly decreased the amounts of BCL-2, BCL-xL, and MCL-1 protein and induced apoptotic cell death. Chromatin immunoprecipitation analysis showed that cantharidin inhibited the binding of HSF1 to the HSP70 promoter and subsequently blocked HSF1-dependent p-TEFb recruitment. Therefore, the p-TEFb-dependent phosphorylation of the C-terminal domain of RNA polymerase II was blocked, arresting transcription at the elongation step. Protein phosphatase 2A inhibition with PP2CA siRNA or okadaic acid did not block HSF1 activity, suggesting that cantharidin inhibits HSF1 in a protein phosphatase 2A-independent manner. We show for the first time that cantharidin inhibits HSF1 transcriptional activity.

Development of a new code to solve hydro-mechanical coupling, shear failure and tensile failure due to hydraulic fracturing operations.

NASA Astrophysics Data System (ADS)

María Gómez Castro, Berta; De Simone, Silvia; Carrera, Jesús

2016-04-01

Nowadays, there are still some unsolved relevant questions which must be faced if we want to proceed to the hydraulic fracturing in a safe way. How much will the fracture propagate? This is one of the most important questions that have to be solved in order to avoid the formation of pathways leading to aquifer targets and atmospheric release. Will the fracture failure provoke a microseismic event? Probably this is the biggest fear that people have in fracking. The aim of this work (developed as a part of the EU - FracRisk project) is to understand the hydro-mechanical coupling that controls the shear of existing fractures and their propagation during a hydraulic fracturing operation, in order to identify the key parameters that dominate these processes and answer the mentioned questions. This investigation focuses on the development of a new C++ code which simulates hydro-mechanical coupling, shear movement and propagation of a fracture. The framework employed, called Kratos, uses the Finite Element Method and the fractures are represented with an interface element which is zero thickness. This means that both sides of the element lie together in the initial configuration (it seems a 1D element in a 2D domain, and a 2D element in a 3D domain) and separate as the adjacent matrix elements deform. Since we are working in hard, fragile rocks, we can assume an elastic matrix and impose irreversible displacements in fractures when rock failure occurs. The formulation used to simulate shear and tensile failures is based on the analytical solution proposed by Okada, 1992 and it is part of an iterative process. In conclusion, the objective of this work is to employ the new code developed to analyze the main uncertainties related with the hydro-mechanical behavior of fractures derived from the hydraulic fracturing operations.

Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes

PubMed Central

Huang, Shujuan; Huang, Suling; Wang, Xi; Zhang, Qingli; Liu, Jia; Leng, Ying

2017-01-01

Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle. PMID:28123341

Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes.

PubMed

Huang, Shujuan; Huang, Suling; Wang, Xi; Zhang, Qingli; Liu, Jia; Leng, Ying

2017-01-01

Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle.

Protein Phosphatase 2A Antagonizes ATM and ATR in a Cdk2- and Cdc7-Independent DNA Damage Checkpoint

PubMed Central

Petersen, Paris; Chou, Danny M.; You, Zhongsheng; Hunter, Tony; Walter, Johannes C.; Walter, Gernot

2006-01-01

We previously used a soluble cell-free system derived from Xenopus eggs to investigate the role of protein phosphatase 2A (PP2A) in chromosomal DNA replication. We found that immunodepletion of PP2A or inhibition of PP2A by okadaic acid (OA) inhibits initiation of DNA replication by preventing loading of the initiation factor Cdc45 onto prereplication complexes. Evidence was provided that PP2A counteracts an inhibitory protein kinase that phosphorylates and inactivates a crucial Cdc45 loading factor. Here, we report that the inhibitory effect of OA is abolished by caffeine, an inhibitor of the checkpoint kinases ataxia-telangiectasia mutated protein (ATM) and ataxia-telangiectasia related protein (ATR) but not by depletion of ATM or ATR from the extract. Furthermore, we demonstrate that double-strand DNA breaks (DSBs) cause inhibition of Cdc45 loading and initiation of DNA replication and that caffeine, as well as immunodepletion of either ATM or ATR, abolishes this inhibition. Importantly, the DSB-induced inhibition of Cdc45 loading is prevented by addition of the catalytic subunit of PP2A to the extract. These data suggest that DSBs and OA prevent Cdc45 loading through different pathways, both of which involve PP2A, but only the DSB-induced checkpoint implicates ATM and ATR. The inhibitory effect of DSBs on Cdc45 loading does not result from downregulation of cyclin-dependent kinase 2 (Cdk2) or Cdc7 activity and is independent of Chk2. However, it is partially dependent on Chk1, which becomes phosphorylated in response to DSBs. These data suggest that PP2A counteracts ATM and ATR in a DNA damage checkpoint in Xenopus egg extracts. PMID:16479016

Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis.

PubMed

Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E

2015-09-15

Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1. Copyright © 2015 the American Physiological Society.

Molecular Genetics of Root Thigmoresponsiveness in Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Masson, Patrick H.

2002-01-01

The molecular mechanisms that allow plant roots to use gravity and touch as growth guides are investigated. We are using a molecular genetic strategy in Arabidopsis thaliana to study these processes. When Arabidopsis thaliana seedlings grow on tilted hard-agar surfaces, their roots develop a wavy pattern of growth which appears to derive from a succession of left-handed and right-handed circumnutation-like processes triggered by gravity and touch stimulation (Okada and Shimura, 1990; Rutherford et al., 1998; Rutherford and Masson, 1996). Interestingly, mutations that affect root waving on tilted hard-agar surfaces can be identified and characterized. Some of these mutations affect root gravitropism, while others appear to be responsible for the production of abnormal waves (no waves, compressed or square waves, coils) without affecting gravitropism. The specific objectives of this project were to functionally characterize two genes (WVD2 and WVD6) which are required for root waving on tilted agar surfaces, but not for root gravitropism. Specific objectives included a physiological and cytological analysis of the mutants, and molecular cloning and characterization of the corresponding genes. As summarized in this paper, we have reached these objectives. We have also identified and partially characterized other mutations that affect root skewing on hard-agar surfaces (sku5-1 and ago1), and have completed our work on the root-wave phenotype associated with mutations in genes of the tryptophan biosynthesis pathway (Lynn et al., 1999; Rutherford et al., 1998; Sedbrook et al., 2000, 2002). We briefly describe our progress on the cloning and characterization of WVD6, WVD2 and SKU5, and provide a list of papers (published, or in preparation) that derived from this grant. We also discuss the biological implications of our findings, with special emphasis on the analysis of WVD2.

Scenario Based Approach for Multiple Source Tsunami Hazard Assessment for Sines, Portugal

NASA Astrophysics Data System (ADS)

Wronna, Martin; Omira, Rachid; Baptista, Maria Ana

2015-04-01

In this paper, we present a scenario-based approach for tsunami hazard assessment for the city and harbour of Sines, Portugal one the test-sites of project ASTARTE. Sines holds one of the most important deep-water ports which contains oil-bearing, petrochemical, liquid bulk, coal and container terminals. The port and its industrial infrastructures are facing the ocean to the southwest facing the main seismogenic sources. This work considers two different seismic zones: the Southwest Iberian Margin and the Gloria Fault. Within these two regions, a total of five scenarios were selected to assess tsunami impact at the test site. These scenarios correspond to the worst-case credible scenario approach based upon the largest events of the historical and paleo tsunami catalogues. The tsunami simulations from the source area towards the coast is carried out using NSWING a Non-linear Shallow Water Model With Nested Grids. The code solves the non-linear shallow water equations using the discretization and explicit leap-frog finite difference scheme, in a Cartesian or Spherical frame. The initial sea surface displacement is assumed to be equal to the sea bottom deformation that is computed by Okada equations. Both uniform and non-uniform slip conditions are used. The presented results correspond to the models using non-uniform slip conditions. In this study, the static effect of tides is analysed for three different tidal stages MLLW (mean lower low water) MSL (mean sea level) and MHHW (mean higher high water). For each scenario, inundation is described by maximum values of wave height, flow depth, drawdown, run-up and inundation distance. Synthetic waveforms are computed at virtual tide gages at specific locations outside and inside the harbour. The final results consist of Aggregate Scenario Maps presented for the different inundation parameters. This work is funded by ASTARTE - Assessment, Strategy And Risk Reduction for Tsunamis in Europe - FP7-ENV2013 6.4-3, Grant 603839

Continuous Fine-Fault Estimation with Real-Time GNSS

NASA Astrophysics Data System (ADS)

Norford, B. B.; Melbourne, T. I.; Szeliga, W. M.; Santillan, V. M.; Scrivner, C.; Senko, J.; Larsen, D.

2017-12-01

Thousands of real-time telemetered GNSS stations operate throughout the circum-Pacific that may be used for rapid earthquake characterization and estimation of local tsunami excitation. We report on the development of a GNSS-based finite-fault inversion system that continuously estimates slip using real-time GNSS position streams from the Cascadia subduction zone and which is being expanded throughout the circum-Pacific. The system uses 1 Hz precise point position streams computed in the ITRF14 reference frame using clock and satellite orbit corrections from the IGS. The software is implemented as seven independent modules that filter time series using Kalman filters, trigger and estimate coseismic offsets, invert for slip using a non-negative least squares method developed by Lawson and Hanson (1974) and elastic half-space Green's Functions developed by Okada (1985), smooth the results temporally and spatially, and write the resulting streams of time-dependent slip to a RabbitMQ messaging server for use by downstream modules such as tsunami excitation modules. Additional fault models can be easily added to the system for other circum-Pacific subduction zones as additional real-time GNSS data become available. The system is currently being tested using data from well-recorded earthquakes including the 2011 Tohoku earthquake, the 2010 Maule earthquake, the 2015 Illapel earthquake, the 2003 Tokachi-oki earthquake, the 2014 Iquique earthquake, the 2010 Mentawai earthquake, the 2016 Kaikoura earthquake, the 2016 Ecuador earthquake, the 2015 Gorkha earthquake, and others. Test data will be fed to the system and the resultant earthquake characterizations will be compared with published earthquake parameters. Seismic events will be assumed to occur on major faults, so, for example, only the San Andreas fault will be considered in Southern California, while the hundreds of other faults in the region will be ignored. Rake will be constrained along each subfault to be

I had a dream… Continuous InSAR measurement and transparent earth, the beauty of analogue modeling to assess direct model uncertainties

NASA Astrophysics Data System (ADS)

Taisne, B.; Pansino, S.; Manta, F.; Tay Wen Jing, C.

2017-12-01

Have you ever dreamed about continuous, high resolution InSAR data? Have you ever dreamed about a transparent earth allowing you to see what is actually going on under a volcano? Well, you likely dreamed about an analogue facility that allows you to scale down the natural system to fit into a room, with a controlled environment and complex visualisation system. Analogue modeling has been widely used to understand magmatic processes and thanks to a transparent analogue for the elastic Earth's crust, we can see, as it evolves with time, the migration of a dyke, the volume change of a chamber or the rise of a bubble in a conduit. All those phenomena are modeled theoretically or numerically, with their own simplifications. Therefore, how well are we really constraining the physical parameters describing the evolution of a dyke or a chamber? Getting access to those parameters, in real time and with high level of confidence is of paramount importance while dealing with unrest at volcanoes. The aim of this research is to estimate the uncertainties of the widely used Okada and Mogi models. To do so, we design a set of analogue experiments allowing us to explore different elastic properties of the medium, the characteristic of the fluid injected into the medium as well as the depth, size and volume change of a reservoir. The associated surface deformation is extracted using an array of synchronised cameras and using digital image correlation and structure from motion for horizontal and vertical deformation respectively. The surface deformation are then inverted to retrieve the controlling parameters (e.g. location and volume change of a chamber, or orientation, position, length, breadth and opening of a dyke). By comparing those results with the known parameters, that we can see and measure independently, we estimate the uncertainties of the models themself, and the associated level of confidence for each of the inverted parameters.

First Results from a Forward, 3-Dimensional Regional Model of a Transpressional San Andreas Fault System

NASA Astrophysics Data System (ADS)

Fitzenz, D. D.; Miller, S. A.

2001-12-01

We present preliminary results from a 3-dimensional fault interaction model, with the fault system specified by the geometry and tectonics of the San Andreas Fault (SAF) system. We use the forward model for earthquake generation on interacting faults of Fitzenz and Miller [2001] that incorporates the analytical solutions of Okada [85,92], GPS-constrained tectonic loading, creep compaction and frictional dilatancy [Sleep and Blanpied, 1994, Sleep, 1995], and undrained poro-elasticity. The model fault system is centered at the Big Bend, and includes three large strike-slip faults (each discretized into multiple subfaults); 1) a 300km, right-lateral segment of the SAF to the North, 2) a 200km-long left-lateral segment of the Garlock fault to the East, and 3) a 100km-long right-lateral segment of the SAF to the South. In the initial configuration, three shallow-dipping faults are also included that correspond to the thrust belt sub-parallel to the SAF. Tectonic loading is decomposed into basal shear drag parallel to the plate boundary with a 35mm yr-1 plate velocity, and East-West compression approximated by a vertical dislocation surface applied at the far-field boundary resulting in fault-normal compression rates in the model space about 4mm yr-1. Our aim is to study the long-term seismicity characteristics, tectonic evolution, and fault interaction of this system. We find that overpressured faults through creep compaction are a necessary consequence of the tectonic loading, specifically where high normal stress acts on long straight fault segments. The optimal orientation of thrust faults is a function of the strike-slip behavior, and therefore results in a complex stress state in the elastic body. This stress state is then used to generate new fault surfaces, and preliminary results of dynamically generated faults will also be presented. Our long-term aim is to target measurable properties in or around fault zones, (e.g. pore pressures, hydrofractures, seismicity

The modulation of the phosphorylation status of NKCC1 in organ cultured bovine lenses: Implications for the regulation of fiber cell and overall lens volume.

PubMed

Vorontsova, Irene; Donaldson, Paul J; Kong, Zhiying; Wickremesinghe, Chiharu; Lam, Leo; Lim, Julie C

2017-12-01

In previous work, we have shown the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to be a key effector of lens fiber cell volume regulation. Since others have shown that the activity of NKCC1 is regulated via its phosphorylation status, the purpose of this study was to investigate whether NKCC1 phosphorylation can be modulated in organ cultured bovine lenses, and to see how this relates to changes in lens wet weight. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level. Changes to NKCC1-P status were then assessed by organ culturing bovine lenses in either isotonic, hypertonic or hypotonic solutions in the presence or absence of the NKCC inhibitor, bumetanide, or phosphatase inhibitors okadaic acid and calyculin A. After 1-22 h of culturing, lenses were weighed, assessed for transparency and the cortical protein fractions analyzed by western blot using antibodies to detect total NKCC1 and NKCC1-P. NKCC1, NKCC1-P, SPAK, PP1 and PP2A were all detected in the membrane fraction of bovine lenses. Under hypertonic conditions, NKCC1 is phosphorylated and activated to mediate a regulatory volume increase. Finally, NKCC1-P signal increased in the presence of phosphatase inhibitors indicating that PP1/PP2A can dephosphorylate NKCC1. These results show that the phosphorylation status and hence activity of NKCC1 is dynamically regulated and that in response to hypertonic stress, NKCC1 activity is increased to effect a regulatory volume increase that limits cell shrinkage. These findings support the view that the lens dynamically regulates ion fluxes to maintain steady state lens volume, and suggest that dysfunction of this regulation maybe an initiating factor in the localized fiber cell swelling that is a characteristic of diabetic lens cataract. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sperm motility development in the epididymis is associated with decreased glycogen synthase kinase-3 and protein phosphatase 1 activity.

PubMed

Vijayaraghavan, S; Stephens, D T; Trautman, K; Smith, G D; Khatra, B; da Cruz e Silva, E F; Greengard, P

1996-03-01

Immotile bovine caput epididymal sperm contain levels of protein phosphatase activity twofold higher than do mature motile caudal sperm. Comparison of the inhibition profiles of endogenous phosphatase activities detected by okadaic acid (OA) and calyculin A (CA) revealed a pattern consistent with the predominance of a type 1 protein phosphatase (PP1). Immunoblot analysis identified PP1 gamma 2 (the testis-specific isoform of PP1) as the only PP1 isoform in sperm and showed little protein phosphatase 2A (PP2A). In addition, of the known PP1 inhibitors, i.e., DARPP-32, inhibitor 1 (I1), and inhibitor 2 (I2), only I2-like activity was detected in sperm. Inhibition of PP1 by the heat-stable I2-like activity purified from sperm could be reversed with purified glycogen synthase kinase-3 (GSK-3). Furthermore, sperm extracts contain an inactive complex of PP1 and I2 (termed PP1I) that could also be activated by purified GSK-3. The presence of GSK-3 in sperm was demonstrated by activation of purified PP1I, and quantitation revealed that immotile caput sperm contained sixfold higher GSK-3 activity than motile caudal sperm. Immunoblot analysis confirmed the expression of GSK-3 in sperm and revealed the occurrence of both the alpha and beta isoforms. Our findings suggest that the higher PP1 activity measured in immotile sperm, presumably due to higher GSK-3 activity, is responsible for holding motility in check. This conclusion was supported by the observation that the phosphatase inhibitors OA and CA, at micromolar and nanomolar levels, respectively, were able to induce motility in completely immotile bovine caput epididymal sperm and to stimulate the kinetic activity of mature caudal sperm. The intrasperm levels of cAMP, pH, and calcium were unaltered by treatment with these inhibitors. The results suggest a biochemical basis for the development and regulation of sperm motility and a possible physiological role for the PP1/I2/GSK-3 system.

Toxin levels and profiles in microalgae from the north-Western Adriatic Sea--15 years of studies on cultured species.

PubMed

Pistocchi, Rossella; Guerrini, Franca; Pezzolesi, Laura; Riccardi, Manuela; Vanucci, Silvana; Ciminiello, Patrizia; Dell'Aversano, Carmela; Forino, Martino; Fattorusso, Ernesto; Tartaglione, Luciana; Milandri, Anna; Pompei, Marinella; Cangini, Monica; Pigozzi, Silvia; Riccardi, Elena

2012-01-01

The Northern Adriatic Sea is the area of the Mediterranean Sea where eutrophication and episodes related to harmful algae have occurred most frequently since the 1970s. In this area, which is highly exploited for mollusk farming, the first occurrence of human intoxication due to shellfish consumption occurred in 1989, nearly 10 years later than other countries in Europe and worldwide that had faced similar problems. Until 1997, Adriatic mollusks had been found to be contaminated mostly by diarrhetic shellfish poisoning toxins (i.e., okadaic acid and dinophysistoxins) that, along with paralytic shellfish poisoning toxins (i.e., saxitoxins), constitute the most common marine biotoxins. Only once, in 1994, a toxic outbreak was related to the occurrence of paralytic shellfish poisoning toxins in the Adriatic coastal waters. Moreover, in the past 15 years, the Adriatic Sea has been characterized by the presence of toxic or potentially toxic algae, not highly widespread outside Europe, such as species producing yessotoxins (i.e., Protoceratium reticulatum, Gonyaulax spinifera and Lingulodinium polyedrum), recurrent blooms of the potentially ichthyotoxic species Fibrocapsa japonica and, recently, by blooms of palytoxin-like producing species of the Ostreopsis genus. This review is aimed at integrating monitoring data on toxin spectra and levels in mussels farmed along the coast of the Emilia-Romagna region with laboratory studies performed on the species involved in the production of those toxins; toxicity studies on toxic or potentially toxic species that have recently appeared in this area are also reviewed. Overall, reviewed data are related to: (i) the yessotoxins producing species P. reticulatum, G. spinifera and L. polyedrum, highlighting genetic and toxic characteristics; (ii) Adriatic strains of Alexandrium minutum, Alexandrium ostenfeldii and Prorocentrum lima whose toxic profiles are compared with those of strains of different geographic origins; (iii) F

Toxin Levels and Profiles in Microalgae from the North-Western Adriatic Sea—15 Years of Studies on Cultured Species

PubMed Central

Pistocchi, Rossella; Guerrini, Franca; Pezzolesi, Laura; Riccardi, Manuela; Vanucci, Silvana; Ciminiello, Patrizia; Dell’Aversano, Carmela; Forino, Martino; Fattorusso, Ernesto; Tartaglione, Luciana; Milandri, Anna; Pompei, Marinella; Cangini, Monica; Pigozzi, Silvia; Riccardi, Elena

2012-01-01

The Northern Adriatic Sea is the area of the Mediterranean Sea where eutrophication and episodes related to harmful algae have occurred most frequently since the 1970s. In this area, which is highly exploited for mollusk farming, the first occurrence of human intoxication due to shellfish consumption occurred in 1989, nearly 10 years later than other countries in Europe and worldwide that had faced similar problems. Until 1997, Adriatic mollusks had been found to be contaminated mostly by diarrhetic shellfish poisoning toxins (i.e., okadaic acid and dinophysistoxins) that, along with paralytic shellfish poisoning toxins (i.e., saxitoxins), constitute the most common marine biotoxins. Only once, in 1994, a toxic outbreak was related to the occurrence of paralytic shellfish poisoning toxins in the Adriatic coastal waters. Moreover, in the past 15 years, the Adriatic Sea has been characterized by the presence of toxic or potentially toxic algae, not highly widespread outside Europe, such as species producing yessotoxins (i.e., Protoceratium reticulatum, Gonyaulax spinifera and Lingulodinium polyedrum), recurrent blooms of the potentially ichthyotoxic species Fibrocapsa japonica and, recently, by blooms of palytoxin-like producing species of the Ostreopsis genus. This review is aimed at integrating monitoring data on toxin spectra and levels in mussels farmed along the coast of the Emilia-Romagna region with laboratory studies performed on the species involved in the production of those toxins; toxicity studies on toxic or potentially toxic species that have recently appeared in this area are also reviewed. Overall, reviewed data are related to: (i) the yessotoxins producing species P. reticulatum, G. spinifera and L. polyedrum, highlighting genetic and toxic characteristics; (ii) Adriatic strains of Alexandrium minutum, Alexandrium ostenfeldii and Prorocentrum lima whose toxic profiles are compared with those of strains of different geographic origins; (iii) F

Inhibition of glycogen synthase kinase-3beta downregulates total tau proteins in cultured neurons and its reversal by the blockade of protein phosphatase-2A.

PubMed

Martin, Ludovic; Magnaudeix, Amandine; Esclaire, Françoise; Yardin, Catherine; Terro, Faraj

2009-02-03

In tauopathies such as Alzheimer's disease (AD), the molecular mechanisms of tau protein aggregation into neurofibrillary tangles (NFTs) and their contribution to neurodegeneration remain not understood. It was recently demonstrated that tau, regardless of its aggregation, might represent a key mediator of neurodegeneration. Therefore, reduction of tau levels might represent a mechanism of neuroprotection. Glycogen synthase kinase-3beta (GSK3beta) and protein phosphatase-2A (PP2A) are key enzymes involved in the regulation of tau phosphorylation, and have been suggested to be involved in the abnormal tau phosphorylation and aggregation in AD. Connections between PP2A and GSK3beta signaling have been reported. We have previously demonstrated that exposure of cultured cortical neurons to lithium decreased tau protein expression and provided neuroprotection against Abeta. Since lithium is not a specific inhibitor of GSK3beta (ID50=2.0 mM), whether or not the lithium-induced tau decrease involves GSK3beta remained to be determined. For that purpose, cultured cortical neurons were exposed to 6-bromo-indirubin-3'-oxime (6-BIO), a more selective and potent GSK3beta inhibitor (ID50=1.5 microM) or to lithium. Analysis of tau levels and phosphorylation by western-blot assays showed that lithium and 6-BIO dose-dependently decreased both tau protein levels and tau phosphorylation. Conversely, inhibition of cyclin-dependent kinase-5 (CDK5) by roscovitine decreased phosphorylated tau but failed to alter tau protein levels. These data indicate that GSK3beta might be selectively involved in the regulation of tau protein levels. Moreover, inhibition of PP2A by okadaic acid, but not that of PP2B (protein phosphatase-2B)/calcineurin by FK506, dose-dependently reversed lithium-induced tau decrease. These data indicate that GSK3beta regulates both tau phosphorylation and total tau levels through PP2A.

Thermal acclimation affects growth and lipophilic toxin production in a strain of cosmopolitan harmful alga Dinophysis acuminata.

PubMed

Basti, Leila; Suzuki, Toshiyuki; Uchida, Hajime; Kamiyama, Takashi; Nagai, Satoshi

2018-03-01

Species of the harmful algal bloom (HAB) genera Dinophysis are causative of one of the most widespread and expanding HAB events associated with the human intoxication, diarrheic shellfish poisoning (DSP). The effects of warming temperature on the physiology and toxinology of these mixotrophic species remain intractable due to their low biomass in nature and difficulties in establishing and maintaining them in culture. Hence, the present study investigated the influence of warming temperature, encompassing present and predicted climate scenarios, on growth and toxin production in a strain of the most cosmopolitan DSP-causative species, Dinophysis acuminata. The strain was isolated from western Japan, acclimated, and cultured over extended time spans. The specific growth and toxin production rates were highest at 20-26 °C and 17-29 °C, respectively, and had significant linear relationships during exponential phase. The cellular toxin production of okadaic acid and pectenotoxin-2 were highest during early exponential growth phase at temperatures ≤17 °C but highest during late stationary phase at temperatures ≥20 °C. The cellular toxin production of Dinophysistoxin-1, however, increased from early exponential to late stationary growth phase independently from temperature. The net toxin productions were not affected by acclimation temperature but significantly affected by growth and were highest during early exponential growth phase. Warming water temperatures increase growth and promote toxin production of D. acuminata, potentially increasing incidence of diarrheic shellfish poisoning events and closures of shellfish production. It is likely that D. acuminata is more toxic at low cell densities during bloom initiation in winter, and at high cell densities during bloom termination in spring-autumn. The results of the present research are also of importance for the mass production of D. acuminata for subsequent studies of the toxicological and

The Size Distribution of Atmospheric Aerosols at Kosan, Korea during ACE-Asia: Changes due to Dust Input and Scavenging by Precipitation

NASA Astrophysics Data System (ADS)

Jung, C.; Kim, J.; Choi, B.; Brechtel, F. J.; Buzorius, G.; Oh, S.

2001-12-01

., Ikegami, M., Okada, K., and Makino, Y. (1995). Aerosol concentration observed at Zhangye in China, J. Meteorological Society in Japan, 73, 891-897.

Regulation of FAK Ser-722 phosphorylation and kinase activity by GSK3 and PP1 during cell spreading and migration.

PubMed

Bianchi, Mariarita; De Lucchini, Stefania; Marin, Oriano; Turner, David L; Hanks, Steven K; Villa-Moruzzi, Emma

2005-10-15

In addition to tyrosine sites, FAK (focal adhesion kinase) is phosphorylated on multiple serine residues. In the present study, the regulation of two of these sites, Ser-722 (S1) and Ser-911 (S4), was investigated. Phosphorylation of S1 (but not S4) decreased in resuspended cells, and recovered during spreading on fibronectin, indicating adhesion-dependent regulation. GSK3 (glycogen synthase kinase 3) inhibitors decreased S1 phosphorylation, and siRNA (short interfering RNA) silencing indicated further the involvement of GSK3beta. Furthermore, GSK3beta was found to become activated during cell spreading on fibronectin, and to physically associate with FAK. S1 phosphorylation was observed to decrease in wounded cell monolayers, while GSK3beta underwent inactivation and later was observed to increase to the original level within 24 h. Direct phosphorylation of S1, requiring pre-phosphorylation of Ser-726 in the +4 position, was demonstrated using purified GSK3 and a synthetic peptide containing FAK residues 714-730. An inhibitory role for S1 phosphorylation in FAK signalling was indicated by findings that both alanine substitution for S1 and dephosphorylation of S1 by PP1 (serine/threonine protein phosphatase type-1) resulted in an increase in FAK kinase activity; likewise, this role was also shown by cell treatment with the GSK3 inhibitor LiCl. The inhibitory role was confirmed by the finding that cells expressing FAK with alanine substitution for S1 displayed improved cell spreading and faster migration in wound-healing and trans-well assays. Finally, the finding that S1 phosphorylation increased in cells treated with the PP1 inhibitor okadaic acid indicated targeting of this site by PP1. These results indicate an additional mechanism for regulation of FAK activity during cell spreading and migration, involving Ser-722 phosphorylation modulated through the competing actions of GSK3beta and PP1.

Determination of source process and the tsunami simulation of the 2013 Santa Cruz earthquake

NASA Astrophysics Data System (ADS)

Park, S. C.; Lee, J. W.; Park, E.; Kim, S.

2014-12-01

In order to understand the characteristics of large tsunamigenic earthquakes, we analyzed the earthquake source process of the 2013 Santa Cruz earthquake and simulated the following tsunami. We first estimated the fault length of about 200 km using 3-day aftershock distribution and the source duration of about 110 seconds using the duration of high-frequency energy radiation (Hara, 2007). Moment magnitude was estimated to be 8.0 using the formula of Hara (2007). From the results of 200 km of fault length and 110 seconds of source duration, we used the initial value of rupture velocity as 1.8 km/s for teleseismic waveform inversions. Teleseismic body wave inversion was carried out using the inversion package by Kikuchi and Kanamori (1991). Teleseismic P waveform data from 14 stations were used and band-pass filter of 0.005 ~ 1 Hz was applied. Our best-fit solution indicated that the earthquake occurred on the northwesterly striking (strike = 305) and shallowly dipping (dip = 13) fault plane. Focal depth was determined to be 23 km indicating shallow event. Moment magnitude of 7.8 was obtained showing somewhat smaller than the result obtained above and that of previous study (Lay et al., 2013). Large slip area was seen around the hypocenter. Using the slip distribution obtained by teleseismic waveform inversion, we calculated the surface deformations using formulas of Okada (1985) assuming as the initial change of sea water by tsunami. Then tsunami simulation was carred out using Conell Multi-grid Coupled Tsunami Model (COMCOT) code and 1 min-grid topographic data for water depth from the General Bathymetric Chart of the Ocenas (GEBCO). According to the tsunami simulation, most of tsunami waves propagated to the directions of southwest and northeast which are perpendicular to the fault strike. DART buoy data were used to verify our simulation. In the presentation, we will discuss more details on the results of source process and tsunami simulation and compare them

Paleomagnetic Results From the Pleistocene Sediments of Lomonosov Ridge, Central Artic Ocean, IODP Leg 302

NASA Astrophysics Data System (ADS)

King, J. W.; Heil, C.; O'Regan, M.; Moran, K.; Gattacecca, J.; Backman, J.; Jakobsson, M.; Moore, T.

2005-12-01

, B. Clement, M. Okada, and T. Williams. 2001. Brunhes chron magnetics excursions recovered from Leg 172 sediments. In Keigwin, L. D., Rio, D., Acton, G. D., and Arnold, E., (eds.) Proc. ODP Sci. Results, v. 172; p. 1-18 (Online)

Thermal Infrared Imager on Hayabusa2: Science and Development

NASA Astrophysics Data System (ADS)

Okada, Tatsuaki

2015-04-01

Thermal Infrared Imager TIR was developed and calibrated for Haya-busa2 asteroid explorer, aiming at the investigation of thermo-physical properties of C-class near-Earth sub-km sized asteroid (162173) 1999JU3. TIR is based on the 2D micro-bolometer array with germani-um lens to image the surface of asteroid in 8 to 12 μm wavelength (1), measuring the thermal emission off the asteroid surface. Its field of view is 16° x 12° with 328 x 248 pixels. At least 40 (up to 100) images will be taken during asteroid rotation once a week, mainly from the Home Position which is about 20km sunward from asteroid surface. Therefore TIR will image the whole asteroid with spatial resolution of < 20m per pixel, and the temperature profile of each site on the asteroid will be traced from dawn to dusk regions by asteroid rotation. The scien-tific objectives of TIR include the mapping of asteroid surface condi-tions (regional distribution of thermal inertia), since the surface physical conditions are strongly correlated with thermal inertia. It is so informa-tive on understanding the re-accretion or surface sedimentation process-es of the asteroid to be the current form. TIR data will be used for searching for those sites having the typical particle size of 1mm for best sample collection, and within the proper thermal condition for space-craft safe operation. After launch of Hayabusa2, TIR has been tested successfully, covering from -100 to 150 °C using a single parameter settings (2). This implies that TIR is actually able to map the surface other than the sunlit areas. Performance of TIR was found basically the same as those in the pre-launch test, when the temperature of TIR is well controlled. References: (1) Fukuhara T. et al., (2011) Earth Planet. Space 63, 1009-1018; (2) Okada T. et al., (2015) Lunar Planet. Sci. Conf. 46, #1331.

Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats.

PubMed

Matsushita, Yumi; Manabe, Miki; Kitamura, Naoki; Shibuya, Izumi

2018-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at -60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α2 antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α2 agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5'- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α2-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway.

Human papilloma virus type16 E6 deregulates CHK1 and sensitizes human fibroblasts to environmental carcinogens independently of its effect on p53

PubMed Central

Chen, Bo; Simpson, Dennis A.; Zhou, Yingchun; Mitra, Amritava; Mitchell, David L.; Cordeiro-Stone, Marila; Kaufmann, William K.

2015-01-01

After treatment with ultraviolet radiation (UV), human fibroblasts that express the HPV type 16 E6 oncoprotein display defects in repair of cyclobutane pyrimidine dimers, hypersensitivity to inactivation of clonogenic survival and an inability to sustain DNA replication. To determine whether these effects are specific to depletion of p53 or inactivation of its function, fibroblast lines were constructed with ectopic expression of a dominant-negative p53 allele (p53-H179Q) to inactivate function or a short-hairpin RNA (p53-RNAi) to deplete expression of p53. Only the expression of HPV16E6 sensitized fibroblasts to UV or the chemical carcinogen, benzo[a]pyrene diolepoxide I (BPDE). Carcinogen-treated cells expressing p53-H179Q or p53-RNAi were resistant to inactivation of colony formation and did not suffer replication arrest. CHK1 is a key checkpoint kinase in the response to carcinogen-induced DNA damage. Control and p53-RNAi-expressing fibroblasts displayed phosphorylation of Ser345 on CHK1 45–120 min after carcinogen treatment with a return to near baseline phosphorylation by 6 h after treatment. HPV16E6-expressing fibroblasts displayed enhanced and sustained phosphorylation of CHK1. This was associated with enhanced phosphorylation of Thr68 on CHK2 and Ser139 on H2AX, both markers of severe replication stress and DNA double strand breaks. Incubation with the phosphatase inhibitor okadaic acid produced more phosphorylation of CHK1 in UV-treated HPV16E6-expressing cells than in p53-H179Q-expressing cells suggesting that HPV16E6 may interfere with the recovery of coupled DNA replication at replication forks that are stalled at [6-4]pyrimidine-pyrimidone photoproducts and BPDE-DNA adducts. The results indicate that HPV16E6 targets a protein or proteins other than p53 to deregulate the activity of CHK1 in carcinogen-damaged cells. PMID:19411857

Modulation of IL-33/ST2-TIR and TLR signalling pathway by fingolimod and analogues in immune cells.

PubMed

Rüger, K; Ottenlinger, F; Schröder, M; Zivković, A; Stark, H; Pfeilschifter, J M; Radeke, H H

2014-12-01

For the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell-based confocal assay and IL-33/ST2-TIR Th2-like response with ST2-transduced EL4-6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR-enhanced antigen presentation assay with OVA-TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy-derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720-P. The IL-33/ST2-TIR Th2-like response in ST2-EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA-TCRtg LPS/TLR-enhanced spleen cell assay, we found that fingolimod inhibited both IL-17 and IFN-γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune-modulating properties of fingolimod, including interference with a prototypical Th2 response via IL-33/ST2-TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR-activated and antigen-dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives. © 2014 John Wiley & Sons Ltd.

Cholinergic and neuroprotective drugs for the treatment of Alzheimer and neuronal vascular diseases. II. Synthesis, biological assessment, and molecular modelling of new tacrine analogues from highly substituted 2-aminopyridine-3-carbonitriles.

PubMed

Samadi, Abdelouahid; Valderas, Carolina; de los Ríos, Cristóbal; Bastida, Agatha; Chioua, Mourad; González-Lafuente, Laura; Colmena, Inés; Gandía, Luis; Romero, Alejandro; Del Barrio, Laura; Martín-de-Saavedra, María D; López, Manuela G; Villarroya, Mercedes; Marco-Contelles, José

2011-01-01

The synthesis, biological assessment, and molecular modelling of new tacrine analogues 11-22 is described. Compounds 11-22 have been obtained by Friedländer-type reaction of 2-aminopyridine-3-carbonitriles 1-10 with cyclohexanone or 1-benzyl-4-piperidone. The biological evaluation showed that some of these molecules were good AChE inhibitors, in the nanomolar range, and quite selective regarding the inhibition of BuChE, the most potent being 5-amino-2-(dimethylamino)-6,7,8,9-tetrahydrobenzo[1,8-b]-naphthyridine-3-carbonitrile (11) [IC(50) (EeAChE: 14nM); IC(50) (eqBuChE: 5.2μM]. Kinetic studies on the easily available and potent anticholinesterasic compound 5-amino-2-(methoxy)-6,7,8,9-tetrahydrobenzo[1,8-b]-naphthyridine-3-carbonitrile (16) [IC(50) (EeAChE: 64nM); IC(50) (eqBuChE: 9.6μM] showed that this compound is a mixed-type inhibitor (K(i)=69.2nM) of EeAChE. Molecular modelling on inhibitor 16 confirms that this compound, as expected and similarly to tacrine, binds at the catalytic active site of EeAChE. The neuroprotective profile of molecules 11-22 has been investigated in SH-SY5Y neuroblastoma cells stressed with a mixture of oligomycin-A/rotenone. Compound 16 was also able to rescue by 50% cell death induced by okadaic acid in SH-SY5Y cells. From these results we conclude that the neuroprotective profile of these molecules is moderate, the most potent being compounds 12 and 17 which reduced cell death by 29%. Compound 16 does not affect ACh- nor K(+)-induced calcium signals in bovine chromaffin cells. Consequently, tacrine analogues 11-22 can be considered attractive therapeutic molecules on two key pharmacological targets playing key roles in the progression of Alzheimer, that is, cholinergic dysfunction and oxidative stress, as well as in neuronal cerebrovascular diseases. Copyright © 2010. Published by Elsevier Ltd.

Atorvastatin Alleviates Experimental Diabetic Cardiomyopathy by Regulating the GSK-3β-PP2Ac-NF-κB Signaling Axis

PubMed Central

Wu, Wen; Luo, Jie; Ye, Peng; Chen, Shao-liang; Hu, Zuo-ying

2016-01-01

Recent studies reported that atorvastatin (ATOR) alleviated progression of experimental diabetic cardiomyopathy (DCM), possibly by protecting against apoptosis. However, the underlying mechanisms of this protective effect remain unclear. Therefore, our study investigated the role of the glycogen synthase kinase (GSK)-3β-protein phosphatase 2A(PP2A)-NF-κB signaling pathway in the anti-apoptotic and cardioprotective effects of ATOR on cardiomyocytes cultured in high glucose (HG) and in DCM. Our results showed that, in HG-cultured cardiomyocytes, phosphorylation of GSK-3β was decreased, while that of the PP2A catalytic subunit C (PP2Ac) and IKK/IкBα was increased, followed by NF-кB nuclear translocation and apoptosis. IKK/IкBα phosphorylation and NF-кB nuclear translocation were also increased by treatment of cells with okadaic acid (OA), a selective PP2A inhibitor, or by silencing PP2Ac expression. The opposite results were obtained by silencing GSK-3β expression, which resulted in PP2Ac activation. Furthermore, IKK/IкBα phosphorylation and NF-кB nuclear translocation were markedly inhibited and apoptosis attenuated in cells treated with ATOR. These effects occurred through inactivation of GSK-3β and subsequent activation of PP2Ac. They were abolished by treatment of cells with OA or PP2Ac siRNA. In mice with type 1 diabetes mellitus, treatment with ATOR, at 10 mg-kg−1-d−1, significantly suppressed GSK-3β activation, IKK/IкBα phosphorylation, NF-кB nuclear translocation and caspase-3 activation, while also activating PP2Ac. Finally, improvements in histological abnormalities, fibrosis, apoptosis and cardiac dysfunction were observed in diabetic mice treated with ATOR. These findings demonstrated that ATOR protected against HG-induced apoptosis in cardiomyocytes and alleviated experimental DCM by regulating the GSK-3β-PP2A-NF-κB signaling pathway. PMID:27851811

[Alkaline phosphatase in Amoeba proteus].

PubMed

Sopina, V A

2005-01-01

In free-living Amoeba proteus (strain B), 3 phosphatase were found after disc-electrophoresis of 10 microg of protein in PAGE and using 1-naphthyl phosphate as a substrate a pH 9.0. These phosphatases differed in their electrophoretic mobilities - "slow" (1-3 bands), "middle" (one band) and "fast" (one band). In addition to 1-naphthyl phosphate, "slow" phosphatases were able to hydrolyse 2-naphthyl phosphate and p-nitrophenyl phosphate. They were slightly activated by Mg2+, completely inhibited by 3 chelators (EDTA, EGTA and 1,10-phenanthroline), L-cysteine, sodium dodecyl sulfate and Fe2+, Zn2+ and Mn2+ (50 mM), considerably inactivated by orthovanadate, molybdate, phosphatase inhibitor cocktail 1, p-nitrophenyl phosphate, Na2HPO4, DL-dithiothreitol and urea and partly inhibited by H2O2, DL-phenylalanine, 2-mercaptoethanol, phosphatase inhibitor cocktail 2 and Ca2+. Imidazole, L-(+)-tartrate, okadaic acid, NaF and sulfhydryl reagents -p-(hydroxy-mercuri)benzoate and N-ethylmaleimide - had no influence on the activity of "slow" phosphatases. "Middle" and "fast" phosphatases, in contrast to "slow" ones, were not inactivated by 3 chelators. The "middle" phosphatase differed from the "fast" one by smaller resistance to urea, Ca2+, Mn2+, phosphates and H2O2 and greater resistance to dithiothreitol and L-(+)-tartrate. In addition, the "fast" phosphatase was inhibited by L-cysteine but the "middle" one was activated by it. Of 5 tested ions (Mg2+, Cu2+, Mn2+, Ca2+ and Zn2+), only Zn2+ reactivated "slow" phosphatases after their inactivation by EDTA treatment. The reactivation of apoenzyme was only partial (about 35 %). Thus, among phosphatases found in amoebae at pH 9.0, only "slow" ones are Zn-metalloenzymes and may be considered as alkaline phosphatases (EC 3.1.3.1). It still remains uncertain, to which particular phosphatase class "middle" and "fast" phosphatases (pH 9.0) may belong.

Relationship between displacement and gravity change of Uemachi faults and surrounding faults of Osaka basin, Southwest Japan

NASA Astrophysics Data System (ADS)

Inoue, N.; Kitada, N.; Kusumoto, S.; Itoh, Y.; Takemura, K.

2011-12-01

The Osaka basin surrounded by the Rokko and Ikoma Ranges is one of the typical Quaternary sedimentary basins in Japan. The Osaka basin has been filled by the Pleistocene Osaka group and the later sediments. Several large cities and metropolitan areas, such as Osaka and Kobe are located in the Osaka basin. The basin is surrounded by E-W trending strike slip faults and N-S trending reverse faults. The N-S trending 42-km-long Uemachi faults traverse in the central part of the Osaka city. The Uemachi faults have been investigated for countermeasures against earthquake disaster. It is important to reveal the detailed fault parameters, such as length, dip and recurrence interval, so on for strong ground motion simulation and disaster prevention. For strong ground motion simulation, the fault model of the Uemachi faults consist of the two parts, the north and south parts, because of the no basement displacement in the central part of the faults. The Ministry of Education, Culture, Sports, Science and Technology started the project to survey of the Uemachi faults. The Disaster Prevention Institute of Kyoto University is carried out various surveys from 2009 to 2012 for 3 years. The result of the last year revealed the higher fault activity of the branch fault than main faults in the central part (see poster of "Subsurface Flexure of Uemachi Fault, Japan" by Kitada et al., in this meeting). Kusumoto et al. (2001) reported that surrounding faults enable to form the similar basement relief without the Uemachi faults model based on a dislocation model. We performed various parameter studies for dislocation model and gravity changes based on simplified faults model, which were designed based on the distribution of the real faults. The model was consisted 7 faults including the Uemachi faults. The dislocation and gravity change were calculated based on the Okada et al. (1985) and Okubo et al. (1993) respectively. The results show the similar basement displacement pattern to the

Inverse agonist abolishes desensitization of a constitutively active mutant of thyrotropin-releasing hormone receptor: role of cellular calcium and protein kinase C

PubMed Central

Grimberg, Hagit; Zaltsman, Ilona; Lupu-Meiri, Monica; Gershengorn, Marvin C; Oron, Yoram

1999-01-01

C335Stop is a constitutively active mutant of the TRH receptor (TRH-R). To investigate the mechanism of the decreased responsiveness of C335Stop TRH-R, we studied cellular Ca2+ concentrations ([Ca2+]i) in AtT20 cells stably transfected with C335Stop TRH-R cDNA, or Ca2+-activated chloride currents in Xenopus laevis oocytes expressing this mutant receptor after injection of cRNA. The competitive TRH-R binding antagonist, chlorodiazepoxide (CDE), was used as an inverse agonist to study the contribution of constitutive activity to desensitization. Acute treatment with CDE resulted in a rapid (within minutes) decrease in [Ca2+]i and an increase in the response amplitude to TRH with no measurable change in receptor density. Conversely, removal of chronically administered CDE caused a rapid increase in [Ca2+]i and a decrease in TRH response amplitude. CDE abolished heterologous desensitization induced by C335Stop TRH-R on muscarinic m1-receptor (m1-R) co-expressed in Xenopus oocytes. Chelation of extracellular calcium with EGTA caused a rapid decrease in [Ca2+]i and a concomitant increase in the response to TRH in AtT20 cells expressing C335Stop TRH-Rs. Chelerythrine, a specific inhibitor of protein kinase C (PKC), reversed the heterologous desensitization of the response to acetylcholine (ACh). The phosphoserine/phosphothreonine phosphatase inhibitor, okadaic acid, abolished the effect of chelerythrine. Down-regulation of PKC by chronic exposure to phorbol 12-myristate 13-acetate (PMA) or acute inhibition with chelerythrine caused a partial resensitization of the response to TRH. Western analysis indicated that the α subtype of protein kinase C was down-regulated in cells expressing C335Stop TRH-Rs. Following a 5 min exposure to PMA, the residual αPKC translocated to the particular fraction. We propose that cells expressing the constitutively active mutant TRH-R rapidly desensitize their response, utilizing a mechanism mediated by an increase in [Ca2+]i and PKC. PMID

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition

PubMed Central

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-01-01

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a (pp2a) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing atherosclerotic

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition.

PubMed

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-11-27

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a ( pp2a ) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing

[Tartrate-resistant acid phosphatase in free-living Amoeba proteus].

PubMed

Sopina, V A

2002-01-01

Tartrate-resistant acid phosphatase (TRAP) of Amoeba proteus (strain B) was represented by 3 of 6 bands (= electromorphs) revealed after disc-electrophoresis in polyacrylamide gels with the use of 2-naphthyl phosphate as a substrate at pH 4.0. The presence of MgCl2, CaCl2 or ZnCl2 (50 mM) in the incubation mixture used for gel staining stimulated activities of all 3 TRAP electromorphs or of two of them (in the case of ZnCl2). When gels were treated with MgCl2, CaCl2 or ZnCl2 (10 and 100 mM, 30 min) before their staining activity of TRAP electromorphs also increased. But unlike 1 M MgCl2 or 1 M CaCl2, 1 M ZnCl2 partly inactivated two of the three TRAP electromorphs. EDTA and EGTA (5 mM), and H2O2 (10 mM) completely inhibited TRAP electromorphs after gel treatment for 10, 20 and 30 min, resp. Of 5 tested ions (Mg2+, Ca2+, Fe2+, Fe3+ and Zn2+), only the latter reactivated the TRAP electromorphs previously inactivated by EDTA or EGTA treatment. In addition, after EDTA inactivation, TRAP electromorphs were reactivated better than after EGTA. The resistance of TRAP electromorphs to okadaic acid and phosphatase inhibitor cocktail 1 used in different concentrations is indicative of the absence of PP1 and PP2A among these electromorphs. Mg2+, Ca2+ and Zn2+ dependence of TRAP activity, and the resistance of its electromorphs to vanadate and phosphatase inhibitor cocktail 2 prevents these electromorphs from being classified as PTP. It is suggested that the active center of A. proteus TRAP contains zinc ion, which is essential for catalytic activity of the enzyme. Thus, TRAP of these amoebae is metallophosphatase showing phosphomonoesterase activity in acidic medium. This metalloenzyme differs from both mammalian tartrate-resistant PAPs and tartrate-resistant metallophosphatase of Rana esculenta.

IT-26IDENTIFICATION OF PSEUDO-PROGRESSION IN NEW DIAGNOSED GLIOBLASTOMA (GBM) IN A RANDOMIZED PHASE 2 OF ICT-107: MRI AND PATHOLOGY CORRELATION

PubMed Central

Phuphanich, Surasak; Yu, John; Bannykh, Serguei; Zhu, Jay-Jiguang

2014-01-01

BACKGROUND: Previously reports of pseudo-progression in patients with brain tumor after therapeutic vaccines in pediatric and adult glioma (Pollack, JCO online on June 2, 2014 and Okada, JCO Jan 20, 2011; 29: 330-336) demonstrated that RANO criteria for tumor progression may not be adequate for immunotherapy trials. Similar observations were also seen in other checkpoint inhibitor in melanoma and NSLSC. METHODS: We identified 2 patients, who developed tumor progression by RANO criteria, underwent surgery following enrollment in a phase 2 randomized ICT-107 (an autologous vaccine consisting of patient dendritic cells pulsed with peptides from AIM-2, TRP-2, HER2/neu, IL-13Ra2, gp100, MAGE1) after radiation and Temozolomide (TMZ). RESULTS: The first case is a 69 years old Chinese male, who underwent 1st surgery of gross total resection right occipital GBM on 10/26/2011. Subsequently he received 19 cycles of TMZ and 9 vaccines/placebo. MRI from 7/2/2013 showed enhancement surrounding surgical cavity. After 2nd surgery, pathology showed only rare residual tumor cells with macrophages and positive CD 8 cells. He continued on this vaccine program and MRI showed more progression with finger-like extension into parietal lobe 4 months later. The 3rd surgery also showed extensive reactive changes with no active tumor cells. For 2nd case, a 62 years old male, who underwent first surgery on 7/11/2011 of right temporal lobe, developed 2 areas of enhancement after 6 cycles of TMZ and 7 vaccines/placebo on 4/18/2012. With 2nd surgery, pathology showed reactive gliosis without active tumor. The subject continued in this trial. CONCLUSION: Pseudo-progression was confirmed by pathology in these 2 patients at 20 and 9 months which were delayed comparing to pseudo-progression observed in patients treated with concurrent XRT/TMZ (3-6 months). Future iRANO criteria development is essential for immunotherapy trials. Accurately identifying and managing such patients is necessary to avoid

On boundary-element models of elastic fault interaction

NASA Astrophysics Data System (ADS)

Becker, T. W.; Schott, B.

2002-12-01

We present the freely available, modular, and UNIX command-line based boundary-element program interact. It is yet another implementation of Crouch and Starfield's (1983) 2-D and Okada's (1992) half-space solutions for constant slip on planar fault segments in an elastic medium. Using unconstrained or non-negative, standard-package matrix routines, the code can solve for slip distributions on faults given stress boundary conditions, or vice versa, both in a local or global reference frame. Based on examples of complex fault geometries from structural geology, we discuss the effects of different stress boundary conditions on the predicted slip distributions of interacting fault systems. Such one-step calculations can be useful to estimate the moment-release efficiency of alternative fault geometries, and so to evaluate the likelihood which system may be realized in nature. A further application of the program is the simulation of cyclic fault rupture based on simple static-kinetic friction laws. We comment on two issues: First, that of the appropriate rupture algorithm. Cellular models of seismicity often employ an exhaustive rupture scheme: fault cells fail if some critical stress is reached, then cells slip once-only by a given amount, and subsequently the redistributed stress is used to check for triggered activations on other cells. We show that this procedure can lead to artificial complexity in seismicity if time-to-failure is not calculated carefully because of numerical noise. Second, we address the question if foreshocks can be viewed as direct expressions of a simple statistical distribution of frictional strength on individual faults. Repetitive failure models based on a random distribution of frictional coefficients initially show irregular seismicity. By repeatedly selecting weaker patches, the fault then evolves into a quasi-periodic cycle. Each time, the pre-mainshock events build up the cumulative moment release in a non-linear fashion. These

Recording Plate Boundary Deformation Processes Around The San Jacinto Fault, California

NASA Astrophysics Data System (ADS)

Hodgkinson, K.; Mencin, D.; Borsa, A.; Fox, O.; Walls, C.; Van Boskirk, E.

2012-04-01

The San Jacinto Fault is one of the major faults which form the San Andreas Fault System in southern California. The fault, which lies to the west of the San Andreas, is one of the most active in the region. While strain rates are higher along the San Andreas, 23-37 mm/yr compared to 12-22 mm/yr along the San Jacinto, there have been 11 earthquakes of M6 and greater along the San Jacinto in the past 150 years while there have been none of this magnitude on the San Andreas in this region. UNAVCO has installed an array of geodetic and seismic instruments along the San Jacinto as part of the Plate Boundary Observatory (PBO). The network includes 25 GPS stations within 20 km of the surface trace with a concentration of borehole instrumentation in the Anza region where there are nine boreholes sites. Most of the borehole sites contain a GTSM21 4-component strainmeter, a Sonde-2 seismometer, a MEMS accelerometer and a pore pressure sensor. Thus, the array has the capability to capture plate boundary deformation processes with periods of milliseconds (seismic) to decades (GPS). On July 7th 2010 a M5.4 earthquake occurred on the Coyote Creek segment of the fault. The event was preceded by a M4.9 earthquake in the same area four weeks earlier and four earthquakes of M5 and greater within a 20 km radius of the epicenter in the past 50 years. In this study we will present the signals recorded by the different instrument types for the July 7th 2010 event and will compare the coseismic displacements recorded by the GPS and strainmeters with the displacement field predicted by Okada [1992]. All data recorded as part of the PBO observatory are publically available from the UNAVCO, the IRIS Data Management Center and the Northern California Earthquake Data Center.

Finite Element Analysis Of Structural And Magmatic Interactions At Mono Basin (California)

NASA Astrophysics Data System (ADS)

La Marra, D.; Manconi, A.; Battaglia, M.

2010-12-01

Mono Basin is a northward trending graben situated east of the Sierra Nevada and west of Cowtrack Mountains, extending from the northern edge of Long Valley Caldera towards the Bodie Hills. From a hydrographic perspective, the Mono Basin is defined by all streams that drain into Mono Lake. The Mono-Inyo Craters forms a prominent 25-km-long volcanic complex from the NW corner of Long Valley caldera to the southern edge of Mono Lake. The late Quaternary Hartley Springs fault occurs along the Sierran range front between June Lake and the northern border of Long Valley Caldera. Recently it has been proposed that the manifestation of the volcanic and of the tectonic activity in this area is likely interrelated. According to Bursik et al (2003), stratigraphic data suggest that during the North Mono-Inyo eruption sequence of ~1350 A.D., a series of strong earthquakes occurred across the end of the North Mono explosive phase and the beginning of the Inyo explosive phase. Moreover, geological and geomorphic features of the Hartley Springs fault are consistent with rupture of the fault during the eruption sequence. We use the Finite Element Method (FEM) to simulate a three-dimensional model and investigate the feedback mechanism between dike intrusion and slip along the Hartley Springs fault. We first validate our numerical model against the Okada (1985) analytical solution for a homogeneous and elastic flat half-space. Subsequently, we evaluate the distribution of local stress changes to study the influence of the Inyo Dike intrusion in ~1350 A.D. on Hartley Springs fault, and how the fault slip may encourage the propagation of dikes towards the surface. To this end, we considered the standard Coulomb stress change as failure criterion. Finally, we analyze the effects of the topography and of vertical and lateral heterogeneities of the crust on the distribution of local and regional stress changes. In this presentation, we highlight the preliminary results of our analysis

Tsunami Source Model of the 2004 Sumatra-Andaman Earthquake inferred from Tide Gauge and Satellite Data

NASA Astrophysics Data System (ADS)

Fujii, Y.; Satake, K.

2005-12-01

The tsunami generation process of the 2004 Sumatra-Andaman earthquake were estimated from the tsunami waveforms recorded on tide gauges and sea surface heights captured by satellite altimetry measurements over the Indian Ocean. The earthquake (0:58:53, 26, Dec., 2004, UTC), the largest in the last 40 years, caused devastating tsunami damages to the countries around the Indian Ocean. One of the important questions is the source length; the aftershocks were distributed along the Sunda trench for 1000 to 1200 km, from off northwestern part of Sumatra island through Nicobar islands to Andaman island, while seismic wave analyses indicate much shorter source length (several hundred km). We used instrumental data of this tsunami, tide gauges and sea surface heights. Tide gauge data have been collected by Global Sea Level Observing System (GLOSS). We have also used another tide gauges data for tsunami simulation analysis. Tsunami propagation was captured as sea surface heights of Jason-1 satellite altimetry measurements over the Indian Ocean for the first time (Gower, 2005). We numerically compute tsunami propagation on actually bathymetry. ETOPO2 (Smith and Sandwell, 1997), the gridded data of global ocean depth from bathymetry soundings and satellite gravity data, are less reliable in the shallow ocean. To improve the accuracy, we have digitized the charts near coasts and merged the digitized data with the ETOPO2 data. The long-wave equation and the equation of motion were numerically solved by finite-difference method (Satake, 1995). As the initial condition, a static deformation of seafloor has been calculated using rectangular fault model (Okada, 1985). The source region is divided into 22 subfaults. We fixed the size and geometry of each subfault, and varied the slip amount and rise time (or slip duration) for each subfault, and rupture velocity. Tsunami waveforms or Greens functions for each subfault were calculated for the rise times of 3, 10, 30 and 60 minutes

Volcanic deformation sources associated with Fogo 2011-2012 unrest, Azores - The first modelling result

NASA Astrophysics Data System (ADS)

Okada, Jun; Araújo, João; Bonforte, Alessandro; Guglielmino, Francesco; Lorenzo, Maria; Ferreira, Teresa

2016-04-01

Volcanic deformation is often observed at many active volcanoes in the world by using space geodesy techniques, namely GNSS and InSAR. More difficulties in judgement if eruptions are imminent or not arise when such phenomenon occurs at dormant volcanoes due to the lack of eruption experiences with monitoring data. The eruption triggering mechanism is still controversial at many cases, but many attempts to image deformation sources beneath volcanoes have been made using geophysical inversion techniques. In this study, we show the case study of Fogo (Água de Pau) volcano, S. Miguel Island, Azores which represents over 450 years of eruption dormancy since 1563-1564. In the recent decades Fogo has exhibited three prominent unrest episodes (1989, 2003-2006, and 2011-2012). The lack of geochemical and hydrothermal evidences for a magmatic intrusion during those episodes does not encourage discussions on resuming volcanic activity of Fogo. However, the inflation/uplift are evident on the edifices at least for the last two unrest episodes based on GPS data by Trota et al. (2009) and Okada et al. (2015), respectively. The preliminary deformation modelling based on repeated GPS campaign data suggested a shallow expanding spheroid (Trota et al. 2009) or a single Mogi sources beneath the summit caldera. We performed a more integrated inversion for the 2011-2012 episode using a genetic algorithm optimizing the source parameters. The best fit model agrees well with the regional/local tectonic lineament suggesting the close relation between the volcanic sources and the regional/local tectonics. The regional extensional stress (between Eurasia and Nubia plates) may play important roles for the ascent of volcanic fluids at Fogo volcano. We do not discard the possibility that Fogo may have been preparing for eruptions by intermittent ascents of magma at shallow crust (i.e. experiencing "failed eruptions") during the apparent dormant period. As a local monitoring agency, CIVISA

AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation.

PubMed

Min, Wang; Lin, Yan; Tang, Shibo; Yu, Luyang; Zhang, Haifeng; Wan, Ting; Luhn, Tricia; Fu, Haian; Chen, Hong

2008-04-11

Previously we have shown that AIP1 (apoptosis signal-regulating kinase [ASK]1-interacting protein 1), a novel member of the Ras-GAP protein family, facilitates dephosphorylation of ASK1 at pSer967 and subsequently 14-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling. However, the phosphatase(s) responsible for ASK1 dephosphorylation at pSer967 has not been identified. In the present study, we identified protein phosphatase (PP)2A as a potential phosphatase in vascular endothelial cells (ECs). Tumor necrosis factor (TNF)-induced dephosphorylation of ASK1 pSer967 in ECs was blocked by PP2A inhibitor okadaic acid. Overexpression of PP2A catalytic subunit induced dephosphorylation of ASK1 pSer967 and activation of c-Jun N-terminal kinase (JNK). In contrast, a catalytic inactive form of PP2A or PP2A small interfering RNA blunted TNF-induced dephosphorylation of ASK1 pSer967 and activation of JNK without effects on NF-kappaB activation. Whereas AIP1, via its C2 domain, binds to ASK1, PP2A binds to the GAP domain of AIP1. Endogenous AIP1-PP2A complex can be detected in the resting state, and TNF induces a complex formation of AIP1-PP2A with ASK1. Furthermore, TNF-induced association of PP2A with ASK1 was diminished in AIP1-knockdown ECs, suggesting a critical role of AIP1 in recruiting PP2A to ASK1. TNF-signaling molecules TRAF2 and RIP1, known to be in complex with AIP1 and activate AIP1 by phosphorylating AIP1 at Ser604, are critical for TNF-induced ASK1 dephosphorylation. Finally, PP2A and AIP1 cooperatively induce activation of ASK1-JNK signaling and EC apoptosis, as demonstrated by both overexpression and small interfering RNA knockdown approaches. Taken together, our data support a critical role of PP2A-AIP1 complex in TNF-induced activation of ASK1-JNK apoptotic signaling.

Role of the nuclear xenobiotic receptors CAR and PXR in induction of cytochromes P450 by non-dioxinlike polychlorinated biphenyls in cultured rat hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gährs, Maike; Roos, Robert; Andersson, Patrik L.

Polychlorinated biphenyls (PCBs) are among the most ubiquitously detectable ‘persistent organic pollutants’. In contrast to ‘dioxinlike’ (DL) PCBs, less is known about the molecular mode of action of the larger group of the ‘non-dioxinlike’ (NDL) PCBs. Owing to the life-long exposure of the human population, a carcinogenic, i.e., tumor-promoting potency of NDL-PCBs has to be considered in human risk assessment. A major problem in risk assessment of NDL-PCBs is dioxin-like impurities that can occur in commercially available NDL-PCB standards. In the present study, we analyzed the induction of CYP2B1 and CYP3A1 in primary rat hepatocytes using a number of highlymore » purified NDL-PCBs with various degrees of chlorination and substitution patterns. Induction of these enzymes is mediated by the nuclear xenobiotic receptors CAR (Constitutive androstane receptor) and PXR (Pregnane X receptor). For CYP2B1 induction, concentration–response analysis revealed a very narrow window of EC{sub 50} estimates, being in the range of 1–4 μM for PCBs 28 and 52, and between 0.4 and 1 μM for PCBs 101, 138, 153 and 180. CYP3A1 induction was less sensitive to NDL-PCBs, the most pronounced induction being achieved at 100 μM with the higher chlorinated congeners. Using okadaic acid and small interfering RNAs targeting CAR and PXR, we could demonstrate that CAR plays a major role and PXR a minor role in NDL-PCB-driven induction of CYPs, both effects showing no stringent structure–activity relationship. As the only obvious relevant determinant, the degree of chlorination was found to be positively correlated with the inducing potency of the congeners. - Highlights: • We analyzed six highly purified NDL-PCBs for CYP2B1 and CYP3A1 expression. • CAR plays a major, PXR a minor role in NDL-PCB-driven induction of CYPs. • The degree of chlorination seems to be the major parameter for the inducing potency. • There exists a competition between CAR and PXR. �

Ground Deformation and Sources geometry of the 2016 Central Italy Earthquake Sequence Investigated through Analytical and Numerical Modeling of DInSAR Measurements and Structural-Geological Data

NASA Astrophysics Data System (ADS)

Solaro, G.; Bonano, M.; Boncio, P.; Brozzetti, F.; Castaldo, R.; Casu, F.; Cirillo, D.; Cheloni, D.; De Luca, C.; De Nardis, R.; De Novellis, V.; Ferrarini, F.; Lanari, R.; Lavecchia, G.; Manunta, M.; Manzo, M.; Pepe, A.; Pepe, S.; Tizzani, P.; Zinno, I.

2017-12-01

The 2016 Central Italy seismic sequence started on 24th August with a MW 6.1 event, where the intra-Apennine WSW-dipping Vettore-Gorzano extensional fault system released a destructive earthquake, causing 300 casualties and extensive damage to the town of Amatrice and surroundings. We generated several interferograms by using ALOS and Sentinel 1-A and B constellation data acquired on both ascending and descending orbits to show that most displacement is characterized by two main subsiding lobes of about 20 cm on the fault hanging-wall. By inverting the generated interferograms, following the Okada analytical approach, the modelling results account for two sources related to main shock and more energetic aftershock. Through Finite Element numerical modelling that jointly exploits DInSAR deformation measurements and structural-geological data, we reconstruct the 3D source of the Amatrice 2016 normal fault earthquake which well fit the main shock. The inversion shows that the co-seismic displacement area was partitioned on two distinct en echelon fault planes, which at the main event hypocentral depth (8 km) merge in one single WSW-dipping surface. Slip peaks were higher along the southern half of the Vettore fault, lower along the northern half of Gorzano fault and null in the relay zone between the two faults; field evidence of co-seismic surface rupture are coherent with the reconstructed scenario. The following seismic sequence was characterized by numerous aftershocks located southeast and northwest of the epicenter which decreased in frequency and magnitude until the end of October, when a MW 5.9 event occurred on 26th October about 25 km to the NW of the previous mainshock. Then, on 30th October, a third large event of magnitude MW 6.5 nucleated below the town of Norcia, striking the area between the two preceding events and filling the gap between the previous ruptures. Also in this case, we exploit a large dataset of DInSAR and GPS measurements to investigate

PREFACE: International Workshop on Statistical-Mechanical Informatics 2010

NASA Astrophysics Data System (ADS)

Inoue, Jun-ichi; Kabashima, Yoshiyuki; Tanaka, Kazuyuki; Tanaka, Toshiyuki

2010-04-01

statistical mechanics and information science. Editors Jun-ichi Inoue Yoshiyuki Kabashima Kazuyuki Tanaka Toshiyuki Tanaka The IW-SMI 2010 Organizing Committee: Masato Okada (University of Tokyo) Yoshiyuki Kabashima, General Chair (Tokyo Institute of Technology) Shin Ishii (Kyoto University) Jun-ichi Inoue, Publications Chair (Hokkaido University) Kazuyuki Tanaka (Tohoku University) Toshiyuki Tanaka, Vice-General Chair (Kyoto University)

Occurrence of marine algal toxins in oyster and phytoplankton samples in Daya Bay, South China Sea.

PubMed

Jiang, Tao; Liu, Lei; Li, Yang; Zhang, Jing; Tan, Zhijun; Wu, Haiyan; Jiang, Tianjiu; Lu, Songhui

2017-09-01

The occurrence and seasonal variations of marine algal toxins in phytoplankton and oyster samples in Daya Bay (DYB), South China Sea were investigated. Two Dinophysis species, namely, D. caudata and D. acuminata complex, were identified as Okadaic acid (OA)/pectenotoxin (PTX) related species. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis demonstrated that 2.04-14.47 pg PTX2 per cell was the predominant toxin in single-cell isolates of D. caudata. D. acuminata was not subjected to toxin analysis. The occurrence of OAs in phytoplankton concentrates of net-haul sample coincided with the presence of D. accuminata complex, suggesting that this species is most likely an OA producer in this sea area. OA, dinophysistoxins-1 (DTX1), PTX2, PTX2sa, gymnodimine (GYM), homoyessotoxin (homoYTX), and domoic acid (DA) demonstrated positive results in net haul samples. To our best knowledge, this paper is the first to report the detection of GYM, DA, and homoYTX in phytoplankton samples in Chinese coastal waters. Among the algal toxins, GYM demonstrated the highest frequency of positive detections in phytoplankton concentrates (13/17). Five compounds of algal toxins, including OA, DTX1, PTX2, PTX2sa, and GYM, were detected in oyster samples. DA and homoYTX were not detected in oysters despite of positive detections for both in the phytoplankton concentrates. However, neither the presence nor absence of DA in oysters can be determined because extraction conditions with 100% methanol used to isolate toxins from oysters (recommended by the EU-Harmonised Standard Operating Procedure, 2015) would likely be unsuitable for this water-soluble toxin. In addition, transformation of DA during the digestion process of oysters may also be involved in the negative detections of this toxin. GYM exhibited the highest frequency of positive results in oysters (14/17). OAs were only detected in the hydrolyzed oyster samples. The detection rates of PTX and PTX2sa in

Empirical Relationships Among Magnitude and Surface Rupture Characteristics of Strike-Slip Faults: Effect of Fault (System) Geometry and Observation Location, Dervided From Numerical Modeling

NASA Astrophysics Data System (ADS)

Zielke, O.; Arrowsmith, J.

2007-12-01

In order to determine the magnitude of pre-historic earthquakes, surface rupture length, average and maximum surface displacement are utilized, assuming that an earthquake of a specific size will cause surface features of correlated size. The well known Wells and Coppersmith (1994) paper and other studies defined empirical relationships between these and other parameters, based on historic events with independently known magnitude and rupture characteristics. However, these relationships show relatively large standard deviations and they are based only on a small number of events. To improve these first-order empirical relationships, the observation location relative to the rupture extent within the regional tectonic framework should be accounted for. This however cannot be done based on natural seismicity because of the limited size of datasets on large earthquakes. We have developed the numerical model FIMozFric, based on derivations by Okada (1992) to create synthetic seismic records for a given fault or fault system under the influence of either slip- or stress boundary conditions. Our model features A) the introduction of an upper and lower aseismic zone, B) a simple Coulomb friction law, C) bulk parameters simulating fault heterogeneity, and D) a fault interaction algorithm handling the large number of fault patches (typically 5,000-10,000). The joint implementation of these features produces well behaved synthetic seismic catalogs and realistic relationships among magnitude and surface rupture characteristics which are well within the error of the results by Wells and Coppersmith (1994). Furthermore, we use the synthetic seismic records to show that the relationships between magntiude and rupture characteristics are a function of the observation location within the regional tectonic framework. The model presented here can to provide paleoseismologists with a tool to improve magnitude estimates from surface rupture characteristics, by incorporating the

BicPAMS: software for biological data analysis with pattern-based biclustering.

PubMed

Henriques, Rui; Ferreira, Francisco L; Madeira, Sara C

2017-02-02

Biclustering has been largely applied for the unsupervised analysis of biological data, being recognised today as a key technique to discover putative modules in both expression data (subsets of genes correlated in subsets of conditions) and network data (groups of coherently interconnected biological entities). However, given its computational complexity, only recent breakthroughs on pattern-based biclustering enabled efficient searches without the restrictions that state-of-the-art biclustering algorithms place on the structure and homogeneity of biclusters. As a result, pattern-based biclustering provides the unprecedented opportunity to discover non-trivial yet meaningful biological modules with putative functions, whose coherency and tolerance to noise can be tuned and made problem-specific. To enable the effective use of pattern-based biclustering by the scientific community, we developed BicPAMS (Biclustering based on PAttern Mining Software), a software that: 1) makes available state-of-the-art pattern-based biclustering algorithms (BicPAM (Henriques and Madeira, Alg Mol Biol 9:27, 2014), BicNET (Henriques and Madeira, Alg Mol Biol 11:23, 2016), BicSPAM (Henriques and Madeira, BMC Bioinforma 15:130, 2014), BiC2PAM (Henriques and Madeira, Alg Mol Biol 11:1-30, 2016), BiP (Henriques and Madeira, IEEE/ACM Trans Comput Biol Bioinforma, 2015), DeBi (Serin and Vingron, AMB 6:1-12, 2011) and BiModule (Okada et al., IPSJ Trans Bioinf 48(SIG5):39-48, 2007)); 2) consistently integrates their dispersed contributions; 3) further explores additional accuracy and efficiency gains; and 4) makes available graphical and application programming interfaces. Results on both synthetic and real data confirm the relevance of BicPAMS for biological data analysis, highlighting its essential role for the discovery of putative modules with non-trivial yet biologically significant functions from expression and network data. BicPAMS is the first biclustering tool offering the

Using the Vertical Component of the Surface Velocity Field to Map the Locked Zone at Cascadia Subduction Zone

NASA Astrophysics Data System (ADS)

Moulas, E.; Brandon, M. T.; Podladchikov, Y.; Bennett, R. A.

2014-12-01

At present, our understanding of the locked zone at Cascadia subduction zone is based on thermal modeling and elastic modeling of horizontal GPS velocities. The thermal model by Hyndman and Wang (1995) provided a first-order assessment of where the subduction thrust might be cold enough for stick-slip behavior. The alternative approach by McCaffrey et al. (2007) is to use a Green's function that relates horizontal surface velocities, as recorded by GPS, to interseismic elastic deformation. The thermal modeling approach is limited by a lack of information about the amount of frictional heating occurring on the thrust (Molnar and England, 1990). The GPS approach is limited in that the horizontal velocity component is fairly insensitive to the structure of the locked zone. The vertical velocity component is much more useful for this purpose. We are fortunate in that vertical velocities can now be measured by GPS to a precision of about 0.2 mm/a. The dislocation model predicts that vertical velocities should range up to about 20 percent of the subduction velocity, which means maximum values of ~7 mm/a. The locked zone is generally entirely offshore at Cascadia, except for the Olympic Peninsula region, where the underlying Juan De Fuca plate has an anomalously low dip. Previous thermal and GPS modeling, as well as tide gauge data and episodic tremors indicate the locked zone there extends about 50 to 75 km onland. This situation provides an opportunity to directly study the locked zone. With that objective in mind, we have constructed a full 3D geodynamic model of the Cascadia subduction zone. At present, the model provides a full representation of the interseismic elastic deformation due to variations of slip on the subduction thrust. The model has been benchmarked against the Savage (2D) and Okada (3D) analytical solutions. This model has an important advantage over traditional dislocation modeling in that we include temperature-sensitive viscosity for the upper and

The 2014 Napa Earthquake Imaged Through A Full Exploitation Of SAR Data

NASA Astrophysics Data System (ADS)

Castaldo, R.; Casu, F.; de Luca, C.; Solaro, G.

2014-12-01

We investigate the co-seismic surface deformation related to the earthquake occurred in Napa area (California) on August 24, 2014. To this aim, we exploit both the phase and the amplitude information of SAR data acquired in Stripmap mode by the Italian COSMO-SkyMed (CSK), the Canadian RADARSAT-2 (RS2), and the recently launched Europena Sentinel-1 satellites, to evaluate and analyze the induced surface displacements through the Differential SAR Interferometry (DInSAR) and Pixel-Offset (PO) techniques. In particular, the SAR images, acquired from descending orbits on 26 July and 27 August 2014 by CSK, and on 07 August and 31 August 2014 by Sentinel-1, as well as the ones acquired on 24 July and 10 September by RS2 from ascending passes were used to generate differential SAR interferograms encompassing the main seismic events. The related deformation map, obtained by performing a complex multi-look operation resulting in a pixel size of about 30 m by 30 m, reveals two main lobes of LOS displacement with a range change decrease of about 11 cm to the NE sector and about 7 cm of range change increase to the SE sector. Moreover, by benefiting from the sensor spatial resolutions (down to 3 meters for both CSK and Sentinel-1 satellites), the Pixel-Offset maps of the same data pairs have been also computed, thus permitting us to retrieve displacement information along the azimuth direction and better describing the deformation field. In order to retrieve the earthquake source location and its geometrical characteristics, the displacement maps were modeled by finite dislocation faults in an elastic and homogeneous half-space [Okada, 1985]. In particular, we searched for all the parameters free the fault by using a nonlinear inversion based on the Levenberg-Marquardt least-squares approach. The best fit solution, consists of a right -lateral NNW-SSE oriented fault. The comparison between the model results and the measured InSAR data show a good fit, with residue values

Toxin profiles of five geographical isolates of Dinophysis spp. from North and South America.

PubMed

Fux, Elie; Smith, Juliette L; Tong, Mengmeng; Guzmán, Leonardo; Anderson, Donald M

2011-02-01

Marine dinoflagellates of the genus Dinophysis can produce toxins of the okadaic acid (OA) and pectenotoxin (PTX) groups. These lipophilic toxins accumulate in filter-feeding shellfish and cause an illness in consumers called diarrhetic shellfish poisoning (DSP). In 2008, a bloom of Dinophysis led to the closure of shellfish harvesting areas along the Texas coast, one of the first DSP-related closures in the U.S. This event resulted in a broad study of toxin production in isolates of Dinophysis spp. from U.S. waters. In the present study, we compared toxin profiles in geographical isolates of Dinophysis collected in the U.S. (Eel Pond, Woods Hole MA; Martha's Vineyard, MA; and Port Aransas Bay, Texas), and in those from Canada (Blacks Harbour, Bay of Fundy) and Chile (Reloncavi Estuary), when cultured in the laboratory under the same conditions. For each isolate, the mitochondrial cox1 gene was sequenced to assist in species identification. Strains from the northeastern U.S. and Canada were all assigned to Dinophysis acuminata, while those from Chile and Texas were most likely within the D. acuminata complex whereas precise species designation could not be made with this marker. Toxins were detected in all Dinophysis isolates and each isolate had a different profile. Toxin profiles of isolates from Eel Pond, Martha's Vineyard, and Bay of Fundy were most similar, in that they all contained OA, DTX1, and PTX2. The Eel Pond isolate also contained OA-D8 and DTX1-D7, and low levels (unconfirmed structurally) of DTX1-D8 and DTX1-D9. D. acuminata from Martha's Vineyard produced DTX1-D7, along with OA, DTX1, and PTX2, as identified in both the cells and the culture medium. D. acuminata from the Bay of Fundy produced DTX1 and PTX2, as found in both cells and culture medium, while only trace amounts of OA were detected in the medium. The Dinophysis strain from Texas only produced OA, and the one from Chile only PTX2, as confirmed in both cells and culture medium. Published

­Tectonic and geomorphic setting of the Pamir Plateau: Insights from InSAR and teleseismic analysis of the 2015 Lake Saurez and 2016 Muji fault earthquake sequence

NASA Astrophysics Data System (ADS)

Nanjundiah, P.; Barbot, S.; Wei, S.; Tapponnier, P.; Feng, W.; Wang, T.

2017-12-01

The Pamir Plateau lies on the western edge of the India- Eurasia collision zone and has been the sight of complex subduction regime in the past 50 Ma. In our study, we focus on two earthquakes and their aftershocks that occurred between December 2015 and December 2016. The first earthquake (Mw7.2), on 7 December 2015 between the Karakoram and Darwas fault systems, was sinstral strike slip in nature. The earthquake on 25 November (Mw6.6) occurred on the western end of Muji Fault, a dextral strike slip fault with an avg slip rate of 4mm/yr. We aim to better understand the structure, stress and deformation patterns in the northern and central Pamir plateau by analyzing InSAR, teleseismic, and optical data for these events and their aftershocks. We aim to better understand the structure, stress and deformation patterns in the northern and central Pamir plateau by analysing InSAR, teleseismic, and optical data for these events and their aftershocks. We constrain the fault geometry by precisely relocating aftershocks using the double difference technique implemented in HypoDD (Waldhauser & Ellsworth 2000). We used the Green's functions of Okada (1992) to invert for slip on the fault with rectangular dislocation and edgreen to numerically invert for the slip in a layered medium (Wang et al. 2003). The surface rupture of the December 2015 Lake Saurez earthquake shows evidence of multiple segments and step-overs. The combination of data sets used in this study highlights the existence of a seismic gap south of Lake Karakul as well as coupling between the Muji and Darwas-Karakoram fault systems. Mapping of past ruptures shows that the Sarez fault continues along the eastern coast of Lake Karakul almost until the Muji fault. With near field geodetic data in the form of InSAR, we can get a better insight into complex fault structures as well as post seismic slip and strain along the faults and its surroundings. We emphasize the role of smaller faults and their interactions in

Protein phosphatase and kinase activities possibly involved in exocytosis regulation in Paramecium tetraurelia.

PubMed Central

Kissmehl, R; Treptau, T; Hofer, H W; Plattner, H

1996-01-01

In Paramecium tetraurelia cells synchronous exocytosis induced by aminoethyldextran (AED) is accompanied by an equally rapid dephosphorylation of a 63 kDa phosphoprotein (PP63) within 80 ms. In vivo, rephosphorylation occurs within a few seconds after AED triggering. In homogenates (P)P63 can be solubilized in all three phosphorylation states (phosphorylated, dephosphorylated and rephosphorylated) and thus tested in vitro. By using chelators of different divalent cations, de- and rephosphorylation of PP63 and P63 respectively can be achieved by an endogenous protein phosphatase/kinase system. Dephosphorylation occurs in the presence of EDTA, whereas in the presence of EGTA this was concealed by phosphorylation by endogenous kinase(s), thus indicating that phosphorylation of P63 is calcium-independent. Results obtained with protein phosphatase inhibitors (okadaic acid, calyculin A) allowed us to exclude a protein serine/threonine phosphatase of type I (with selective sensitivity in Paramecium). Protein phosphatase 2C is also less likely to be a candidate because of its requirement for high Mg2+ concentrations. According to previous evidence a protein serine/threonine phosphatase of type 2B (calcineurin; CaN) is possibly involved. We have now found that bovine brain CaN dephosphorylates PP63 in vitro. Taking into account the specific requirements of this phosphatase in vitro, with p-nitrophenyl phosphate as a substrate, we have isolated a cytosolic phosphatase of similar characteristics by combined preparative gel electrophoresis and affinity-column chromatography. In Paramecium this phosphatase also dephosphorylates PP63 in vitro (after 32P labelling in vivo). Using various combinations of ion exchange, affinity and hydrophobic interaction chromatography we have also isolated three different protein kinases from the soluble fraction, i.e. a cAMP-dependent protein kinase (PKA), a cGMP-dependent protein kinase (PKG) and a casein kinase. Among the kinases tested, PKA

Tidal modulation of slow slip events in the Nankai trough subduction zone detected by borehole strainmeters

NASA Astrophysics Data System (ADS)

Kikuchi, J.; Ide, S.; Matsumoto, N.

2016-12-01

Slow slip events (SSEs) often occur in the Nankai subduction zone, Japan, within a band-like zone extended from the center of Honshu to western Shikoku. SSEs are believed as shear slip on the plate interface, where the frictional property changes from velocity weakening to strengthening in the dip direction. Therefore the dynamics of SSEs may give some hints on the depth dependent friction and plate subduction. The tidal modulation of SSEs has been identified by statistical analysis using strain data of Plate Boundary Observatory, in the Cascadia subduction zone [Hawthorne & Rubin, 2010]. Here, we perform similar statistical analyses using strain data recorded at borehole stations maintained by National Institute of Advanced Industrial Science and Technology, in western Japan. The correlation between the oscillation in SSEs and tidal stress was confirmed statistically. In Nankai subduction zone, it is known that SSEs are accompanied with high activity of deep tectonic tremors [Hirose & Obara, 2006]. These tremors have been known to be sensitive to tidal stress [Nakata et al., 2008]. Therefore, the tidal modulation of SSEs is another representation of tidal modulation of tremors. To clarify the relation between SSEs and tremors, we investigate whether strain changes corresponding to SSEs can be explained only by tremors activity. For an SSE occurred in Aug. 2010 in Bungo channel, we assume that the seismic moment of the SSE is 1.6 × 1018 Nm (Mw 6.1) based on the inversion of GNSS data [Nishimura et al., 2013], and that this moment is released by 715 tremors that occur during this SSE [Idehara et al., 2014]. In this case, each tremor is assigned with seismic moment of 2.2 × 1015 Nm (Mw 4.2). Then the strain change at the observation station by these tremors is calculated using the Okada [1992] method, assuming a half space and focal mechanism consistent with the regional plate motion. The calculated strain is qualitatively similar with the observed strain

Mechanical loading stimulates chondrogenesis via the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures.

PubMed

Juhász, Tamás; Matta, Csaba; Somogyi, Csilla; Katona, Éva; Takács, Roland; Soha, Rudolf Ferenc; Szabó, István A; Cserháti, Csaba; Sződy, Róbert; Karácsonyi, Zoltán; Bakó, Eva; Gergely, Pál; Zákány, Róza

2014-03-01

Biomechanical stimuli play important roles in the formation of articular cartilage during early foetal life, and optimal mechanical load is a crucial regulatory factor of adult chondrocyte metabolism and function. In this study, we undertook to analyse mechanotransduction pathways during in vitro chondrogenesis. Chondroprogenitor cells isolated from limb buds of 4-day-old chicken embryos were cultivated as high density cell cultures for 6 days. Mechanical stimulation was carried out by a self-designed bioreactor that exerted uniaxial intermittent cyclic load transmitted by the culture medium as hydrostatic pressure and fluid shear to differentiating cells. The loading scheme (0.05 Hz, 600 Pa; for 30 min) was applied on culturing days 2 and 3, when final commitment and differentiation of chondroprogenitor cells occurred in this model. The applied mechanical load significantly augmented cartilage matrix production and elevated mRNA expression of several cartilage matrix constituents, including collagen type II and aggrecan core protein, as well as matrix-producing hyaluronan synthases through enhanced expression, phosphorylation and nuclear signals of the main chondrogenic transcription factor Sox9. Along with increased cAMP levels, a significantly enhanced protein kinase A (PKA) activity was also detected and CREB, the archetypal downstream transcription factor of PKA signalling, exhibited elevated phosphorylation levels and stronger nuclear signals in response to mechanical stimuli. All the above effects were diminished by the PKA-inhibitor H89. Inhibition of the PKA-independent cAMP-mediators Epac1 and Epac2 with HJC0197 resulted in enhanced cartilage formation, which was additive to that of the mechanical stimulation, implying that the chondrogenesis-promoting effect of mechanical load was independent of Epac. At the same time, PP2A activity was reduced following mechanical load and treatments with the PP2A-inhibitor okadaic acid were able to mimic the effects of

Mitochondria-localized caveolin in adaptation to cellular stress and injury

PubMed Central

Fridolfsson, Heidi N.; Kawaraguchi, Yoshitaka; Ali, Sameh S.; Panneerselvam, Mathivadhani; Niesman, Ingrid R.; Finley, J. Cameron; Kellerhals, Sarah E.; Migita, Michael Y.; Okada, Hideshi; Moreno, Ana L.; Jennings, Michelle; Kidd, Michael W.; Bonds, Jacqueline A.; Balijepalli, Ravi C.; Ross, Robert S.; Patel, Piyush M.; Miyanohara, Atsushi; Chen, Qun; Lesnefsky, Edward J.; Head, Brian P.; Roth, David M.; Insel, Paul A.; Patel, Hemal H.

2012-01-01

We show here that the apposition of plasma membrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating the structure and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin specifically in cardiac myocytes (Cav-3 OE), localization of caveolin to mitochondria increases membrane rigidity (4.2%; P<0.05), tolerance to calcium, and respiratory function (72% increase in state 3 and 23% increase in complex IV activity; P<0.05), while reducing stress-induced generation of reactive oxygen species (by 20% in cellular superoxide and 41 and 28% in mitochondrial superoxide under states 4 and 3, respectively; P<0.05) in Cav-3 OE vs. TGneg. By contrast, mitochondrial function is abnormal in caveolin-knockout mice and Caenorhabditis elegans with null mutations in caveolin (60% increase free radical in Cav-2 C. elegans mutants; P<0.05). In human colon cancer cells, mitochondria with increased caveolin have a 30% decrease in apoptotic stress (P<0.05), but cells with disrupted mitochondria-caveolin interaction have a 30% increase in stress response (P<0.05). Targeted gene transfer of caveolin to mitochondria in C57Bl/6 mice increases cardiac mitochondria tolerance to calcium, enhances respiratory function (increases of 90% state 4, 220% state 3, 88% complex IV activity; P<0.05), and decreases (by 33%) cardiac damage (P<0.05). Physical association and apparently the transfer of caveolin between caveolae and mitochondria is thus a conserved cellular response that confers protection from cellular damage in a variety of tissues and settings.—Fridolfsson, H. N., Kawaraguchi, Y., Ali, S. S., Panneerselvam, M., Niesman, I. R., Finley, J. C., Kellerhals, S. E., Migita, M. Y., Okada, H., Moreno, A. L., Jennings, M., Kidd, M. W., Bonds, J. A., Balijepalli, R. C., Ross, R. S., Patel, P. M., Miyanohara, A., Chen, Q., Lesnefsky, E. J., Head, B. P., Roth, D

Geodetic Observations Using GNSS, Tiltmeter, and DInSAR, at Tokachi-dake Volcano, Japan

NASA Astrophysics Data System (ADS)

Miyagi, Y.

2017-12-01

Tokachi-dake volcano is located in central Hokkaido, Japan. Middle sized eruptions occurred in 1926, 1962, and 1988-1989, and several small phreatic eruptions also occurred in the meanwhile. After the latest eruption in 1988-1989, many volcanic tremor and active seismicity were revealed. Active fumarolic activities from Taisho crater and 62-2 crater have been observed. In recent years, Tokachi-dake volcano has been observed by using several geodetic techniques, including DInSAR, GNSS, tiltmeter, and gravimeter, to detect regional and local signals associated with volcanic activities. Continuous GNSS stations in summit area operated by Geological Survey of Hokkaido and Hokkaido University [Okazaki et al., 2015] and DInSAR observations using ALOS-2 and TerraSAR-X data have revealed long-term small deformation after 2006 and transient large deformation in May, 2015. We found that these are quite local deformation, because regional GNSS and tiltmeter network did not detect any obvious signals in same period. The remarkable deformation detected by GNSS and DInSAR in the summit area between May and July, 2015, indicates that horizontal displacements are larger than vertical displacements, and westward displacement are much larger than eastward displacement. First, we try to model the deformation pattern using a simple spherical source model [Mogi, 1958] and a dike source model [Okada, 1985]. However, they cannot explain observed deformation because they do not take into consideration a topographic effect in the deformation area. Kawguchi & Miyagi [2016] tried to model the deformation using a boundary element method considering the topographic effect. Consequently, a deformation source which is vertically prolate spheroid beneath the summit shows a better fit between observed and simulated deformation. Annual campaign gravity observations have carried out by several Japanese university and institutes since 2010 [Takahashi et al., 2016]. These reveal that gravity value

Effect of analgesia on the changes in respiratory parameters in blunt chest injury with multiple rib fractures.

PubMed

Ekpe, Eyo Effiong; Eyo, Catherine

2017-01-01

Blunt chest injury with multiple rib fractures can result in such complications as pneumonia, atelectasis, bronchiectasis, empyema thoracis, acute respiratory distress syndrome, and prolonged Intensive Care Unit and hospital stay, with its concomitant mortality. These may be prevented or reduced by good analgesic therapy which is the subject of this study. This was a prospective study of effects of analgesia on changes in pulmonary functions of patients with traumatic multiple rib fractures resulting from blunt chest injury. There were 64 adult patients who were studied with multiple rib fractures caused by blunt chest trauma. Of these patients, 54 (84.4%) were male and 10 (15.6%) were female. Motorcycle (popularly known as "okada") and tricycle (popularly known as keke napep) accidents significantly accounted for the majority of the multiple rib fractures, that is, in 50 (78.1%) of the patients. Before analgesic administration, no patient had a normal respiratory rate, but at 1 h following the administration of analgesic, 21 (32.8%) of patients recorded normal respiratory rates and there was a significant reduction in the number (10.9% vs. 39.1%) of patients with respiratory rates> 30 breaths/min. Before commencement of analgesic, no patient recorded up to 99% of oxygen saturation (SpO2) as measured by pulse oximeter, while 43.8% recorded SpO2of 96%. This improved after 1 h of administration of analgesics to SpO2of 100% in 18.8% of patients and 99% in 31.3% of patients and none recording SpO2of < 97% (P = 0.006). Before analgesia, no patient was able to achieve peak expiratory flow rate (PEFR) value> 100% of predicted while only 9 (14.1%) patients were able to achieve a PEFR value in the range of 91%-100% of predicted value. One hour after analgesia, a total of 6 (9.4%) patients were able to achieve PEFR values> 100% predicted, while 35 (54.7%) patients achieved PEFR values in the range of 91%-100% predicted. Adequate analgesia is capable of reversing the negative

Study Of The Perovskite to Post-Perovskite Transformation Using Multigrain Crystallography

NASA Astrophysics Data System (ADS)

Merkel, Sébastien; Langrand, Christopher; Hilairet, Nadège; Rosa, Angelika; Svitlyk, Volodymyr; Dobson, David

2017-04-01

At P/T conditions of the D'' layer, Bridgmanite transforms into its high-pressure phase of (Mg,Fe)SiO3 post-perovskite(pPv). Observations of seismic anisotropy in D'' are inferred to arise from textures and microstructures within pPv. Specifically, mantle flow is though to cause pPv to deform, creating lattice-preferred orientations (Merkel et al, 2006, 2007; Miyagi et al, 2010; Nisr et al, 2012). However, debates emerged in the literature whether experimentally observed textures were induced by plastic deformation of the sample or by phase transformation from a previous phase (Walte et al 2009, Okada et al, 2010, Miyagi et al, 2011) and whether this could explain the observed patterns of anisotropy in the lowermost mantle (Dobson et al, 2013). Here, we use multigrain crystallography (Sørensen et al, 2012) to characterize hundreds of crystals in a polycrystalline material in-situ as it is transforming. This technique has been recently adapted for Diamond Anvil Cell (DAC) high pressure experiments (Ice et al, 2005; Nisr et al, 2012, 2014; Barton et al, 2012; Zhang et al, 2013, 2016; Rosa et al, 2015, 2016). Potentially, DAC multigrain crystallography is useful for the determination of the orientation and position of individual grains with an average resolution in grain orientation and position below 0.2° and 5 μm, respectively (Langrand et al, in press). We will presents results on the potential resolution of the method with tests on (Mg,Fe)SiO3 itself and on how the method is now being used for tracking individual grains during the Pv/pPv transition in NaCoF3 up to 25 GPa and at T between 600-900 K. At 600 K, the sample transforms to powder rings and looses the grain microstructure. At 900 K, large grains are preserved as the sample fully transforms to pPv and back to Pv. At the end, the results of such experiments will be used to understand transformation mechanisms between Pv and pPv and the development of microstructures and anisotropy in the Earth's D

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.

Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2)more » after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft

The 2016 central Italy earthquake sequence: surface effects, fault model and triggering scenarios

NASA Astrophysics Data System (ADS)

Chatzipetros, Alexandros; Pavlides, Spyros; Papathanassiou, George; Sboras, Sotiris; Valkaniotis, Sotiris; Georgiadis, George

2017-04-01

The results of fieldwork performed during the 2016 earthquake sequence around the karstic basins of Norcia and La Piana di Castelluccio, at an altitude of 1400 m, on the Monte Vettore (altitude 2476 m) and Vettoretto, as well as the three mapped seismogenic faults, striking NNW-SSW, are presented in this paper. Surface co-seismic ruptures were observed in the Vettore and Vettoretto segment of the fault for several kilometres ( 7 km) in the August earthquakes at high altitudes, and were re-activated and expanded northwards during the October earthquakes. Coseismic ruptures and the neotectonic Mt. Vettore fault zone were modelled in detail using images acquired from specifically planned UAV (drone) flights. Ruptures, typically with displacement of up to 20 cm, were observed after the August event both in the scree and weathered mantle (elluvium), as well as the bedrock, consisting mainly of fragmented carbonate rocks with small tectonic surfaces. These fractures expanded and new ones formed during the October events, typically of displacements of up to 50 cm, although locally higher displacements of up to almost 2 m were observed. Hundreds of rock falls and landslides were mapped through satellite imagery, using pre- and post- earthquake Sentinel 2A images. Several of them were also verified in the field. Based on field mapping results and seismological information, the causative faults were modelled. The model consists of five seismogenic sources, each one associated with a strong event in the sequence. The visualisation of the seismogenic sources follows INGV's DISS standards for the Individual Seismogenic Sources (ISS) layer, while strike, dip and rake of the seismic sources are obtained from selected focal mechanisms. Based on this model, the ground deformation pattern was inferred, using Okada's dislocation solution formulae, which shows that the maximum calculated vertical displacement is 0.53 m. This is in good agreement with the statistical analysis of the

3D Deformation at the Coso Geothermal Field - Observations and Models

NASA Astrophysics Data System (ADS)

Hetland, E. A.; Hager, B. H.; McClusky, S.; King, R. W.

2001-12-01

Over the past decade, rapid ground deformation has been measured over the Coso geothermal field in Eastern CA using InSAR and GPS. InSAR resolves changes in distance along the line-of-sight (LOS) to the satellite with high spatial coverage. In the Coso geothermal field the maximum LOS displacements are up to 35 mm/yr. The inclination of the LOS is acute (about 20 degrees), hence the majority of the deformation resolved with InSAR is vertical, however LOS displacements are also affected by horizontal displacements. The ratio of the sensitivity of LOS displacements to vertical and horizontal displacements is at most 5 to 2, for horizontal displacements inline with the LOS. GPS is able to resolve large horizontal displacements in this area, leading to the conclusion that the InSAR LOS displacement fields are non-trivially affected by horizontal displacements. Additionally, since the horizontal displacements are large, GPS is also able to resolve vertical displacements. Moreover, the GPS three component velocities are fairly consistent with the LOS displacements from InSAR. This deformation has been largely attributed to subsidence as fluid is extracted from the geothermal reservoir. The reservoir has been previously modeled as deflating elliptical volumes and as collapsing sills. The elliptical volumes are described as Mogi sources, which are mathematically given as point forces along a line. The collapsing sills are treated as Okada dislocations for finite area faults with pure tensile displacements across them. In both of these dislocation models of the reservoir, the elastic moduli of the rock remains constant with changing fluid pressure. Actual reservoirs are more likely composed of regions of rock permeated with fluid-filled cracks and pores. In such a composite material, changing the pore-fluid pressure changes the elastic moduli of the region. These moduli changes cause the region to deform under loading, thus resulting in observed surface displacements. The

Complementary Ruptures of Surface Ruptures and Deep Asperity during the 2014 Northern Nagano, Japan, Earthquake (MW 6.3)

NASA Astrophysics Data System (ADS)

Asano, K.; Iwata, T.; Kubo, H.

2015-12-01

A thrust earthquake of MW 6.3 occurred along the northern part of the Itoigawa-Shizuoka Tectonic Line (ISTL) in the northern Nagano prefecture, central Japan, on November 22, 2014. This event was reported to be related to an active fault, the Kamishiro fault belonging to the ISTL (e.g., HERP, 2014). The surface rupture is observed along the Kamishiro fault (e.g., Lin et al., 2015; Okada et al., 2015). We estimated the kinematic source rupture process of this earthquake through the multiple time-window linear waveform inversion method (Hartzell and Heaton, 1983). We used velocity waveforms in 0.05-1 Hz from 12 strong motion stations of K-NET, KiK-net (NIED), JMA, and Nagano prefecture (SK-net, ERI). In order to enhance the reliability in Green's functions, we assumed one-dimensional velocity structure models different for the different stations, which were extracted from the nation-wide three-dimensional velocity structure model, Japan Integrated Velocity Structure Model (JIVSM, Koketsu et al., 2012). Considering the spatial distribution of aftershocks (Sakai et al., 2015) and surface ruptures, the assumed fault model consisted of two dip-bending fault segments with different dip angles between the northern and southern segments. The total length and width of the fault plane is 20 km and 13 km, relatively, and the fault model is divided into 260 subfaults of 1 km × 1 km in space and six smoothed ramp functions in time. An asperity or large slip area with a peak slip of 1.9 m was estimated in the lower plane of the northern segment in the approximate depth range of 4 to 8 km. The depth extent of this asperity is consistent with the seismogenic zone revealed by past studies (e.g., Panayotopoulos et al., 2014). In contrast, the slip in the southern segment is relatively concentrated in the shallow portion of the segment where the surface ruptures were found along the Kamishiro fault. The overall spatial rupture pattern of the source fault, in which the deep asperity

Functional human sperm capacitation requires both bicarbonate-dependent PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases.

PubMed

Battistone, M A; Da Ros, V G; Salicioni, A M; Navarrete, F A; Krapf, D; Visconti, P E; Cuasnicú, P S

2013-09-01

In all mammalian species studied so far, sperm capacitation correlates with an increase in protein tyrosine (Tyr) phosphorylation mediated by a bicarbonate-dependent cAMP/protein kinase A (PKA) pathway. Recent studies in mice revealed, however, that a Src family kinase (SFK)-induced inactivation of serine/threonine (Ser/Thr) phosphatases is also involved in the signaling pathways leading to Tyr phosphorylation. In view of these observations and with the aim of getting a better understanding of the signaling pathways involved in human sperm capacitation, in the present work we investigated the involvement of both the cAMP/PKA and SFK/phosphatase pathways in relation to the capacitation state of the cells. For this purpose, different signaling events and sperm functional parameters were analyzed as a function of capacitation time. Results revealed a very early bicarbonate-dependent activation of PKA indicated by the rapid (1 min) increase in both phospho-PKA substrates and cAMP levels (P < 0.05). However, a complete pattern of Tyr phosphorylation was detected only after 6-h incubation at which time sperm exhibited the ability to undergo the acrosome reaction (AR) and to penetrate zona-free hamster oocytes. Sperm capacitated in the presence of the SFK inhibitor SKI606 showed a decrease in both PKA substrate and Tyr phosphorylation levels, which was overcome by exposure of sperm to the Ser/Thr phosphatase inhibitor okadaic acid (OA). However, OA was unable to induce phosphorylation when sperm were incubated under PKA-inhibitory conditions (i.e. in the absence of bicarbonate or in the presence of PKA inhibitor). Moreover, the increase in PKA activity by exposure to a cAMP analog and a phosphodiesterase inhibitor did not overcome the inhibition produced by SKI606. Whereas the presence of SKI606 during capacitation produced a negative effect (P < 0.05) on sperm motility, progesterone-induced AR and fertilizing ability, none of these inhibitions were observed when sperm

Infrared spectra of interstellar deuteronated PAHs

NASA Astrophysics Data System (ADS)

Buragohain, Mridusmita; Pathak, Amit; Sarre, Peter

2015-08-01

Polycyclic Aromatic Hydrocarbon (PAH) molecules have emerged as a potential constituent of the ISM that emit strong features at 3.3, 6.2, 7.7, 8.6, 11.2 and 12.7 μm with weaker and blended features in the 3-20μm region. These features are proposed to arise from the vibrational relaxation of PAH molecules on absorption of background UV photons (Tielens 2008). These IR features have been observed towards almost all types of astronomical objects; say H II regions, photodissociation regions, reflection nebulae, planetary nebulae, young star forming regions, external galaxies, etc. A recent observation has proposed that interstellar PAHs are major reservoir for interstellar deuterium (D) (Peeters et al. 2004). According to the `deuterium depletion model' as suggested by Draine (2006), some of the Ds formed in the big bang are depleted in PAHs, which can account for the present value of D/H in the ISM. Hence, study of deuterated PAHs (PADs) is essential in order to measure D/H in the ISM.In this work, we consider another probable category of the large PAH family, i.e. Deuteronated PAHs (DPAH+). Onaka et al. have proposed a D/H ratio which is an order of magnitude smaller than the proposed value of D/H by Draine suggesting that if Ds are depleted in PAHs, they might be accommodated in large PAHs (Onaka et al. 2014). This work reports a `Density Functional Theory' calculation of large deuteronated PAHs (coronene, ovalene, circumcoronene and circumcircumcoronene) to determine the expected region of emission features and to find a D/H ratio that is comparable to the observational results. We present a detailed analysis of the IR spectra of these molecules and discuss the possible astrophysical implications.ReferencesDraine B. T. 2006, in ASP Conf. Ser. 348, Proc. Astrophysics in the Far Ultraviolet: Five Years of Discovery with FUSE, ed. G. Sonneborn, H. Moos, B-G Andersson (San Francisco, CA:ASP) 58Onaka T., Mori T. I., Sakon I., Ohsawa R., Kaneda H., Okada Y., Tanaka M

Evaluation of W Phase CMT Based PTWC Real-Time Tsunami Forecast Model Using DART Observations: Events of the Last Decade

NASA Astrophysics Data System (ADS)

Wang, D.; Becker, N. C.; Weinstein, S.; Duputel, Z.; Rivera, L. A.; Hayes, G. P.; Hirshorn, B. F.; Bouchard, R. H.; Mungov, G.

2017-12-01

The Pacific Tsunami Warning Center (PTWC) began forecasting tsunamis in real-time using source parameters derived from real-time Centroid Moment Tensor (CMT) solutions in 2009. Both the USGS and PTWC typically obtain W-Phase CMT solutions for large earthquakes less than 30 minutes after earthquake origin time. Within seconds, and often before waves reach the nearest deep ocean bottom pressure sensor (DARTs), PTWC then generates a regional tsunami propagation forecast using its linear shallow water model. The model is initialized by the sea surface deformation that mimics the seafloor deformation based on Okada's (1985) dislocation model of a rectangular fault with a uniform slip. The fault length and width are empirical functions of the seismic moment. How well did this simple model perform? The DART records provide a very valuable dataset for model validation. We examine tsunami events of the last decade with earthquake magnitudes ranging from 6.5 to 9.0 including some deep events for which tsunamis were not expected. Most of the forecast results were obtained during the events. We also include events from before the implementation of the WCMT method at USGS and PTWC, 2006-2009. For these events, WCMTs were computed retrospectively (Duputel et al. 2012). We also re-ran the model with a larger domain for some events to include far-field DARTs that recorded a tsunami with identical source parameters used during the events. We conclude that our model results, in terms of maximum wave amplitude, are mostly within a factor of two of the observed at DART stations, with an average error of less than 40% for most events, including the 2010 Maule and the 2011 Tohoku tsunamis. However, the simple fault model with a uniform slip is too simplistic for the Tohoku tsunami. We note model results are sensitive to centroid location and depth, especially if the earthquake is close to land or inland. For the 2016 M7.8 New Zealand earthquake the initial forecast underestimated the

What is the fault that has generated the earthquake on 8 September 1905 in Calabria, Italy? Source models compared by tsunami data

NASA Astrophysics Data System (ADS)

Pagnoni, Gianluca; Armigliato, Alberto; Tinti, Stefano; Loreto, Maria Filomena; Facchin, Lorenzo

2014-05-01

-difference technique, while the initial conditions are calculated via Okada's formula. The key-result used to test the models against the data is the maximum height of the tsunami calculated close to the shore at a minimum depth of 5m corrected using the values of the initial coseismic field deformation.

Participation of MAPK, PKA and PP2A in the regulation of MPF activity in Bufo arenarum oocytes.

PubMed

Toranzo, G Sánchez; Bonilla, F; Bühler, M C Gramajo; Bühler, M I

2011-05-01

The objectives of the present paper were to study the involvement and possible interactions of both cAMP-PKA and protein phosphatases in Bufo arenarum oocyte maturation and to determine if these pathways are independent or not of the MAP kinase (MAPK) cascade. Our results indicated that the inhibition of PKA by treatment with H-89, an inhibitor of the catalytic subunit of PKA, was capable of inducing GVBD in a dose-dependent manner by a pathway in which Cdc25 phosphatase but not the MAPK cascade is involved. The injection of 50 nl of H-89 10 μM produced GVBD percentages similar to those obtained with treatment with progesterone. In addition, the assays with okadaic acid (OA), a PP2A inhibitor, significantly enhanced the percentage of oocytes that resumed meiosis by a signal transducing pathway in which the activation of the MEK-MAPK pathway is necessary, but in which Cdc25 phosphatase was not involved. Treatment with H-89, was able to overcome the inhibitory effect of PKA on GVBD; however, the inhibition of Cdc25 activity with NaVO3 was able to overcome the induction of GVBD by H-89. Although the connections between PKA and other signalling molecules that regulate oocytes maturation are still unclear, our results suggest that phosphatase Cdc25 may be the direct substrate of PKA. In Xenopus oocytes it was proposed that PP2A, a major Ser/Thr phosphatase present, is a negative regulator of Cdc2 activation. However, in Bufo arenarum oocytes, inhibition of Cdc25 with NaVO₃ did not inhibit OA-induced maturation, suggesting that the target of PP2A was not the Cdc25 phosphatase. MAPK activation has been reported to be essential in Xenopus oocytes GVBD. In B. arenarum oocytes we demonstrated that the inhibition of MAPK by PD 98059 prevented the activation of MPF induced by OA, suggesting that the activation of the MAPK cascade produced an inhibition of Myt1 and, in consequence, the activation of MPF without participation of the Cdc25 phosphatase. Our results suggest that

Tsunami Hazard in the Algerian Coastline

NASA Astrophysics Data System (ADS)

Amir, L. A.

2008-05-01

The Algerian coastline is located at the border between the African and the Eurasian tectonic plates. The collision between these two plates is approximately 4 to 7 mm/yr. The Alps and the tellian Atlas result from this convergence. Historical and present day data show the occurrence of earthquakes with magnitude up to 7 degrees on Richter scale in the northern part of the country. Cities were destroyed and the number of victims reached millions of people. Recently, small seismic waves generated by a destructive earthquake (Epicenter: 36.90N, 3.71E; Mw=6.8; Algeria, 2003, NEIC) were recorded in the French and Spanish coasts. This event raised again the issue of tsunami hazard in western Mediterranean region. For the Algerian study case, the assessment of seismic and tsunami hazard is a matter of great interest because of fast urban development of cities like Algiers. This study aims to provide scientific arguments to help in the elaboration of the Mediterranean tsunami alert program. This is a real complex issue because (1) the western part of the sea is narrow, (2) constructions on the Algerian coastline do not respect safety standards and (3) the seismic hazard is important. The present work is based on a numerical modeling approach. Firstly, a database is created to gather and list information related to seismology, tectonic, abnormal sea level's variations recorded/observed, submarine and coastal topographic data for the western part of the Mediterranean margin. This database helped to propose series of scenario that could trigger tsunami in the Mediterranean sea. Seismic moment, rake and focal depth are the major parameters that constrain the modeling input seismic data. Then, the undersea earthquakes modeling and the seabed deformations are computed with a program adapted from the rngchn code based on Okada's analytic equations. The last task of this work consisted to calculate the initial water surface displacement and simulate the triggered tsunami

3-D Dynamic Rupture Simulations of the 2016 Kumamoto, Japan, Earthquake

NASA Astrophysics Data System (ADS)

Fukuyama, E.; Urata, Y.; Yoshida, K.

2016-12-01

On April 16, 2016 at 01:25 (JST), an M7.3 main shock of the 2016 Kumamoto, Japan, earthquake sequence occurred along the Futagawa and Hinagu faults. A few days before, three M6-class foreshocks occurred: M6.5 on April 14 at 21:26, M5.8 on April 14 at 22:27, and M6.4 on April 15 at 00:03 (JST). The focal mechanisms of the first and third foreshocks were similar to those of the main shock; therefore, the extensive stress shadow should have been generated on the fault plane of the main shock. The purpose of this study is to illuminate why the rupture of the main shock propagated successfully under such stress conditions by 3-D dynamic rupture simulations, assuming the fault planes estimated by the distributions of aftershocks.First, we investigated time evolution of aftershock hypocenters relocated by the Double Difference method (Waldhauser & Ellsworth, 2000). The result showed that planar distribution of the hypocenters was formed after each M6 event. It allows us to estimate fault planes of the three foreshocks and the main shock.Then, we evaluated stress changes on the fault planes of the main shock due to the three foreshocks. We obtained the slip distributions of the foreshocks by using Eshelby (1957)'s solution, assuming elliptical cracks with constant stress drops on the estimated fault planes. The stress changes on the fault planes of the main shock were calculated by using Okada (1992)'s solution. The obtained stress change distribution showed that the hypocenter of the main shock existed on the region with positive ΔCFF while ΔCFF in the shallower regions than the hypocenter was negative. Therefore, the foreshocks could encourage the initiation of the main shock rupture and could hinder the rupture propagating toward the shallow region.Finally, we conducted 3-D dynamic rupture simulations (Hok and Fukuyama, 2011) of the main shock under the initial stresses, which were the sum of the stress changes by these foreshocks and the regional stress field

Lattice preferred orientation in MnGeO3 post-perovskite at high-temperature

NASA Astrophysics Data System (ADS)

Nagaya, Y.; Hirose, K.; Sata, N.; Ohishi, Y.

2009-12-01

In the Earth’s lowermost mantle which is called D” layer, shear-wave splitting is often observed. The velocity of horizontally polarized S-waves are faster than polarized S-waves in many areas of the D” layer. The D” layer is now recognized as being made up with the post-perovskite (PPv)-type MgSiO3 phase. MgSiO3 PPv has a strong elastic anisotropy because of its layered crystal structure. Therefore, it is expected that a lattice preferred orientation (LPO) of PPv may explain the observed seismic anisotropy. LPOs of PPv have been investigated by the high-pressure experiments using a diamond anvil cell (DAC) (Merkel et al., 2006; 2007; Okada et al., 2009). However, the reported experiments using the DAC were made only at the room temperature. In order to understand the nature of PPv deformation under the lower mantle conditions, it is necessary to operate the deformation experiments at high-temperature (~2500 K). In this study, so as to examine the LPO and the dominant slip plane of PPv at simultaneously high P-T conditions, we conducted the high-temperature plastic deformation experiments in a laser-heated diamond anvil cell (LHDAC) using synchrotron radial X-ray diffraction techniques at the beamline BL10XU, SPring-8. In the radial X-ray diffraction experiments, X-ray was irradiated to the sample perpendicular to the compression axis through gasket. LPO was investigated on the basis of the variations of diffraction intensity. We adopted a cubic boron nitride and beryllium composite gasket to obtain a radial X-ray diffraction pattern. In order to deform a sample at high temperature, we had newly developed a membrane system for the deformation experiments. We are able to regulate the gas pressure in the membrane of the DAC, and therefore compress the sample at high temperature during the laser heating. Starting material was orthopyroxene (OPx) with a composition of MnGeO3, which is an analogue of MgSiO3. First, MnGeO3 PPv was synthesized directly from OPx

4-D Visualization of Seismic and Geodetic Data of the Big Island of Hawai'i

NASA Astrophysics Data System (ADS)

Burstein, J. A.; Smith-Konter, B. R.; Aryal, A.

2017-12-01

For decades Hawai'i has served as a natural laboratory for studying complex interactions between magmatic and seismic processes. Investigating characteristics of these processes, as well as the crustal response to major Hawaiian earthquakes, requires a synthesis of seismic and geodetic data and models. Here, we present a 4-D visualization of the Big Island of Hawai'i that investigates geospatial and temporal relationships of seismicity, seismic velocity structure, and GPS crustal motions to known volcanic and seismically active features. Using the QPS Fledermaus visualization package, we compile 90 m resolution topographic data from NASA's Shuttle Radar Topography Mission (SRTM) and 50 m resolution bathymetric data from the Hawaiian Mapping Research Group (HMRG) with a high-precision earthquake catalog of more than 130,000 events from 1992-2009 [Matoza et al., 2013] and a 3-D seismic velocity model of Hawai'i [Lin et al., 2014] based on seismic data from the Hawaiian Volcano Observatory (HVO). Long-term crustal motion vectors are integrated into the visualization from HVO GPS time-series data. These interactive data sets reveal well-defined seismic structure near the summit areas of Mauna Loa and Kilauea volcanoes, where high Vp and high Vp/Vs anomalies at 5-12 km depth, as well as clusters of low magnitude (M < 3.5) seismicity, are observed. These areas of high Vp and high Vp/Vs are interpreted as mafic dike complexes and the surrounding seismic clusters are associated with shallow magma processes. GPS data are also used to help identify seismic clusters associated with the steady crustal detachment of the south flank of Kilauea's East Rift Zone. We also investigate the fault geometry of the 2006 M6.7 Kiholo Bay earthquake event by analyzing elastic dislocation deformation modeling results [Okada, 1985] and HVO GPS and seismic data of this event. We demonstrate the 3-D fault mechanisms of the Kiholo Bay main shock as a combination of strike-slip and dip

Analysis of Patient Narratives in Disease Blogs on the Internet: An Exploratory Study of Social Pharmacovigilance.

PubMed

Matsuda, Shinichi; Aoki, Kotonari; Tomizawa, Shiho; Sone, Masayoshi; Tanaka, Riwa; Kuriki, Hiroshi; Takahashi, Yoichiro

2017-02-24

observed frequently in the ADR database. We also confirmed the feasibility of using visualization techniques to obtain insights from unstructured text-based tōbyōki blog data. Word clouds described the characteristics of each disorder, such as "sleeping" and "anxiety" in depression and "pain" and "painful" in RA. Pharmacovigilance should maintain a strong focus on patients' actual experiences, concerns, and outcomes, and this approach can be expected to uncover hidden adverse event signals earlier and to help us understand adverse events in a patient-centered way. Patient-generated tōbyōki blogs in the TOBYO database showed unique characteristics that were different from the data in existing sources generated by health care professionals. Analysis of tōbyōki blogs would add value to the assessment of disorders with a high prevalence in women, psychiatric disorders in which subjective symptoms have important clinical meaning, refractory disorders, and other chronic disorders. ©Shinichi Matsuda, Kotonari Aoki, Shiho Tomizawa, Masayoshi Sone, Riwa Tanaka, Hiroshi Kuriki, Yoichiro Takahashi. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 24.02.2017.

Improvements in Patient Acceptance by Hospitals Following the Introduction of a Smartphone App for the Emergency Medical Service System: A Population-Based Before-and-After Observational Study in Osaka City, Japan.

PubMed

Katayama, Yusuke; Kitamura, Tetsuhisa; Kiyohara, Kosuke; Iwami, Taku; Kawamura, Takashi; Izawa, Junichi; Gibo, Koichiro; Komukai, Sho; Hayashida, Sumito; Kiguchi, Takeyuki; Ohnishi, Mitsuo; Ogura, Hiroshi; Shimazu, Takeshi

2017-09-11

control group and 10.93% (32,819/300,395) in the smartphone app group. No change over time in the number of difficulties in hospital acceptance was found before the introduction of the smartphone app (regression coefficient: -2.43, 95% CI -5.49 to 0.64), but after its introduction, the number of difficulties in hospital acceptance gradually decreased by month (regression coefficient: -11.61, 95% CI -14.57 to -8.65). Sharing information between an ambulance and a hospital by using the smartphone app at the scene was associated with decreased difficulty in obtaining hospital acceptance. Our app and findings may be worth considering in other areas of the world where emergency medical information systems with IT are needed. ©Yusuke Katayama, Tetsuhisa Kitamura, Kosuke Kiyohara, Taku Iwami, Takashi Kawamura, Junichi Izawa, Koichiro Gibo, Sho Komukai, Sumito Hayashida, Takeyuki Kiguchi, Mitsuo Ohnishi, Hiroshi Ogura, Takeshi Shimazu. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 11.09.2017.

PREFACE: The 16th International Symposium on Boron, Borides and Related Materials (ISBB 2008)

NASA Astrophysics Data System (ADS)

Tanaka, Takaho

2009-07-01

supported by Tokyo University of Science, Suwa and foundations including, the Kajima Foundation, Foundation for Promotion of Material Science and Technology of Japan and Nippon Sheet Glass Foundation for Materials Science and Engineering, as well as companies including JFE Steel Corporation, Shincron Co, Ltd, Toyo Kohan Co, Ltd, Fukuda Metal Foil and Powder Co, Ltd, Japan New Metals Co, Ltd, H C Starck Ltd and Fritsch Japan Co, Ltd. Editors Chair Takaho Tanaka (National Institute for Materials Science, Japan) Vice chairs Koun Shirai (Osaka University, Japan) Kaoru Kimura (The University of Tokyo, Japan) Ken-ichi Takagi (Tokyo City University, Japan) Touetsu Shishido (Tohoku University, Japan) Shigeru Okada (Kokushikan University) Hideaki Itoh (Nagoya University,Japan) Katsumitsu Nakamura (Nihon University, Japan) Organizing committee of ISBB 2008 K Takagi Chairman (Tokyo City University) T Tanaka Program Committee Chairman (National Institute for Materials Science) K Kimura Secretary (The University of Tokyo) J Akimitsu (Aoyama University)K Shirai (Osaka University) H Itoh (Nagoya University)T Shishido (Tohoku University) K Nakamura (Nihon University)K Soga (Tokyo University of Science) K Nishiyama (Tokyo University of Science, Suwa)M Takeda (Nagaoka University of Technology) S Okada (Kokushikan University)Y Yamazaki (Toyo Kohan Co, Ltd) International Scientific Committee 0f ISBB (2008-2011) K Takagi Chairman (Japan) B Albert (Germany) J-F Halet (France) M Takeda (Japan) M Antadze (Georgia) H Hillebrecht (Germany) T Tanaka (Japan) J Bauer (France) W Jung (Germany) R Telle (Germany) I Boustani (Germany) K Kimura (Japan) M Trenary (USA) D Emin (USA) T Mori (Japan) O Tsagareishvili (Georgia) M Engler (Germany) P D Ownby (USA) H Werheit (Germany) N Frage (Israel) P Rogl (Austria) G Will (Germany) Yu Grin (Germany) S Shalamberidze (Georgia) O Yucel (Turkey) V N Gurin (Russia) N Shitsevalova (Ukraine) G Zhang (China)

PREFACE: Preface

NASA Astrophysics Data System (ADS)

Ye, Chaohui; Wang, Zhong Lin; Zhou, Bingkun

2011-02-01

National Laboratory for Optoelectronics (China)Junqiang Sun, Wuhan National Laboratory for Optoelectronics (China) 4. OPTOELECTRONIC SENSING AND IMAGING (OSI)Editors:Kecheng Yang, Wuhan National Laboratory for Optoelectronics (China)Pengcheng Li, Wuhan National Laboratory for Optoelectronics (China) 5. SOLAR CELLS, SOLID-STATE LIGHTING AND INFORMATION DISPLAY TECHNOLOGIES (SSID)Editors:Hiroshi Amano, Meijo University (Japan)Yibing Cheng, Monash University (Australia)Jinzhong Yu, Institute of Semiconductor, CAS (China)Changqing Chen, Wuhan National Laboratory for Optoelectronics (China)Hongwei Han, Wuhan National Laboratory for Optoelectronics (China)Guoli Tu, Wuhan National Laboratory for Optoelectronics (China) 6. TERA-HERTZ SCIENCE AND TECHNOLOGY (THST)Editors:Jianquan Yao, Tianjin University (China)Shenggang Liu, University of Electronic Science and Technology of China (China)X C Zhang, Rensselaer Polytechnic Institute (USA)Jinsong Liu, Wuhan National Laboratory for Optoelectronics (China) International Advisory Committee:Yibing Cheng, Monash University (Australia)Stephen Z D Cheng, University of Akron (USA)Min Gu, Swinburne University of Technology (Australia)Andrew B Holmes, the University of Melbourne (Australia)Chinlon Lin, Bell Laboratory (retired, USA)Xun Li, McMaster University (Canada)Shenggang Liu, University of Electronic Science and Technology of China (China)Jesper Moerk, Technical University of Denmark (Denmark)Dennis L Matthews, University of California, Davis (USA)Jiacong Shen, Jilin University (China)Ping Shum, Nanyang Technological University (Singapore)Chester C T Shu, Chinese University of Hong Kong (China)Valery V Tuchin, Saratov State University (Russia)Bruce Tromberg, University of California/Irvine (USA)Peiheng Wu, University of Nanjing (China)Alan Willner, University of Southern California (USA)Lihong Wang, Washington University in St. Louis (USA)C P Wong, Georgia Institute of Technology (USA)Jianquan Yao, Tianjin University (China)Xi Zhang

Rapid uplift during 2007-2012 at Laguna del Maule volcanic field, Andean Southern Volcanic Zone, Chile

NASA Astrophysics Data System (ADS)

Le Mevel, H.; Feigl, K.; Ali, T.; Cordova V., M. L.; DeMets, C.; Singer, B. S.

2012-12-01

obtained using a rectangular sill model (Okada, 1985) for which the free parameters include the tensile opening, the location, depth, and dimensions of the source. In total, the volume increase is about 60 million cubic meters since inflation began, for the modeled sill at a depth of approximately 5 km. In early 2012, this trend persists in the InSAR data. Three continuous GPS stations installed in April 2012 around the lake confirm this extraordinarily high vertical uplift rate of more than 280 mm/yr, among the fastest deformation signal measured geodetically for any volcano that is not erupting.

Re-examination of the Present Stress State of the Atera Fault, Central Japan, Based on the Calibrated Crustal Stress Data of Hydraulic Fracturing Test by Measuring the Tensile Strength of Rocks

NASA Astrophysics Data System (ADS)

Yamashita, F.; Mizoguchi, K.; Fukuyama, E.; Omura, K.

2008-12-01

of the Atera fault seems to change from left lateral to right lateral some time ago. The amount of accumulated right lateral dislocation estimated from the stress data with the dislocation model by Okada (1992) is 2.2-2.6 m. Because the current slip rate from the GPS survey is 2.1-2.3 mm/yr, the accumulation period of the dislocation becomes 960-1240 years if the slip rate is stable. This estimation suggests that during the last 1586 Tensho earthquake the Atera fault dislocated right laterally.

Recent Trends in Marine Phycotoxins from  Australian Coastal Waters.

PubMed

Ajani, Penelope; Harwood, D Tim; Murray, Shauna A

2017-02-09

Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the  marine food web, are of growing concern for Australia. These harmful algae pose a threat to  ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest  growing food sectors in the world. With better monitoring, advanced analytical skills and an  increase in microalgal expertise, many phycotoxins have been identified in Australian coastal  waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish  toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The  potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern,  warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012  resulted in an estimated total economic loss of~AUD$23M, indicating that there is an imperative to  improve  toxin  and  organism  detection  methods,  clarify  the  toxin  profiles  of  species  of  phytoplankton and carry out both intra- and inter-species toxicity comparisons. Future work also  includes the application of rapid, real-time molecular assays for the detection of harmful species  and toxin genes. This information, in conjunction with a better understanding of the life histories  and  ecology  of  harmful  bloom  species,  may  lead  to  more  appropriate  management  of  environmental, health and economic resources.

Relocation of the Mw 6.4 July 1, 2009 earthquake to the south of Crete and modeling of its associated small tsunami

NASA Astrophysics Data System (ADS)

Bocchini, Gian Maria; Papadopoulos, Gerassimos A.; Novikova, Tatiana; Karastathis, Vassilis K.; Mouzakiotis, Aggelos; Voulgaris, Nikolaos

2016-04-01

�) and the interplate (dip ~20°) nature of the event. Okada dislocation modeling for the NNE dipping fault plane from the CMT Harvard solution was selected to run the tsunami simulations. The comparison of synthetic and observed tsunami wave heights provided an additional tool to constrain the best hypocentral solution. This research is a contribution to the EU-FP7 ITN research project ZIP (Zooming In between Plates, grant agreement no: 604713, 2013 and ASTARTE (Assessment, Strategy And Risk Reduction for Tsunamis in Europe), grant agreement no: 603839, 2013.

Historical overview of research on the tobacco mosaic virus genome: genome organization, infectivity and gene manipulation.

PubMed Central

Okada, Y

1999-01-01

Early in the development of molecular biology, TMV RNA was widely used as a mRNA [corrected] that could be purified easily, and it contributed much to research on protein synthesis. Also, in the early stages of elucidation of the genetic code, artificially produced TMV mutants were widely used and provided the first proof that the genetic code was non-overlapping. In 1982, Goelet et al. determined the complete TMV RNA base sequence of 6395 nucleotides. The four genes (130K, 180K, 30K and coat protein) could then be mapped at precise locations in the TMV genome. Furthermore it had become clear, a little earlier, that genes located internally in the genome were expressed via subgenomic mRNAs. The initiation site for assembly of TMV particles was also determined. However, although TMV contributed so much at the beginning of the development of molecular biology, its influence was replaced by that of Escherichia coli and its phages in the next phase. As recombinant DNA technology developed in the 1980s, RNA virus research became more detached from the frontier of molecular biology. To recover from this setback, a gene-manipulation system was needed for RNA viruses. In 1986, two such systems were developed for TMV, using full-length cDNA clones, by Dawson's group and by Okada's group. Thus, reverse genetics could be used to elucidate the basic functions of all proteins encoded by the TMV genome. Identification of the function of the 30K protein was especially important because it was the first evidence that a plant virus possesses a cell-to-cell movement function. Many other plant viruses have since been found to encode comparable 'movement proteins'. TMV thus became the first plant virus for which structures and functions were known for all its genes. At the birth of molecular plant pathology, TMV became a leader again. TMV has also played pioneering roles in many other fields. TMV was the first virus for which the amino acid sequence of the coat protein was determined

LC-MS-MS aboard ship: tandem mass spectrometry in the search for phycotoxins and novel toxigenic plankton from the North Sea.

PubMed

Krock, Bernd; Tillmann, Urban; John, Uwe; Cembella, Allan

2008-11-01

Phycotoxins produced by various species of toxigenic microalgae occurring in the plankton are a global threat to the security of seafood resources and the health of humans and coastal marine ecosystems. This has necessitated the development and application of advanced methods in liquid chromatography coupled to mass spectrometry (LC-MS) for monitoring of these compounds, particularly in plankton and shellfish. Most such chemical analyses are conducted in land-based laboratories on stored samples, and thus much information on the near real-time biogeographical distribution and dynamics of phycotoxins in the plankton is unavailable. To resolve this problem, we conducted ship-board analysis of a broad spectrum of phycotoxins collected directly from the water column on an oceanographic cruise along the North Sea coast of Scotland, Norway, and Denmark. We equipped the ship with a triple-quadrupole linear ion-trap hybrid LC-MS-MS system for detection and quantitative analysis of toxins, such as domoic acid, gymnodimine, spirolides, dinophysistoxins, okadaic acid, pectenotoxins, yessotoxins, and azaspiracids (AZAs). We focused particular attention on the detection of AZAs, a group of potent nitrogenous polyether toxins, because the culprit species associated with the occurrence of these toxins in shellfish has been controversial. Marine toxins were analyzed directly from size-fractionated plankton net tows (20 microm mesh size) and Niskin bottle samples from discrete depths, after rapid methanolic extraction but without any further clean-up. Almost all expected phycotoxins were detected in North Sea plankton samples, with domoic acid and 20-methylspirolide G being most abundant. Although AZA was the least abundant of these toxins, the high sensitivity of the LC-MS-MS enabled detailed quantification, indicating that the highest amounts of AZA-1 were present in the southern Skagerrak in the 3-20 microm size-fraction. The direct on-board toxin measurements enabled isolation

Involvement of the dehydroleucodine alpha-methylene-gamma-lactone function in GVBD inhibition in Bufo arenarum oocytes.

PubMed

Sánchez Toranzo, G; López, L A; Martínez, J Zapata; Bühler, M C Gramajo; Bühler, M I

2010-02-01

Dehydroleucodine (DhL), a sesquiterpenic lactone, was isolated and purified from aerial parts of Artemisia douglasiana Besser, a medicinal herb used in Argentina. DhL is an alpha-methylene butyro-gamma-lactone ring connected to a seven-membered ring fused to an exocyclic alpha,beta-unsaturated cyclopentenone ring. It has been previously shown that DhL selectively induces a dose-dependent transient arrest in G2 of both meristematic cells and vascular smooth muscle cells. Treatment with DhL induces an inhibition of spontaneous and progesterone-induced maturation in a dose-dependent manner in Bufo arenarum fully grown oocytes arrested at G2, at the beginning of meiosis I. However, the nature of the mechanisms involved in the process is still unknown. The aim of this work was to analyse whether DhL's alpha-methylene-gamma-lactone function is responsible for the inhibition effect on meiosis reinitiation of Bufo arenarum oocytes as well as some of the transduction pathways that could be involved in this effect using a derivative of DhL inactivated for alpha-methylenelactone, the 11,13-dihydro-dehydroleucodine (2H-DhL). The use of 2H-DhL in the maturation promoting factor (MPF) amplification experiments by injection of both cytoplasm with active MPF and of germinal vesicle content showed results similar to the ones obtained with DhL, suggesting that the hydrogenated derivative would act in a similar way to DhL. Pretreatment with DhL or 2H-DhL did not affect the percentage of germinal vesicle breakdown (GVBD) induced by H89, a protein kinase A (PKA) inhibitor, which suggests that these lactones would act on another step of the signalling pathway that induces MPF activation. The fact that both DhL and 2H-Dhl inhibit GVBD induced by okadaic acid microinjection suggests that they could act on the activity of the Myt1 kinase. This idea is supported by the experiments of injection of GV contents in which an inhibitory effect of these lactones on GVBD was also observed. Our

Generation of deterministic tsunami hazard maps in the Bay of Cadiz, south-west Spain

NASA Astrophysics Data System (ADS)

Álvarez-Gómez, J. A.; Otero, L.; Olabarrieta, M.; González, M.; Carreño, E.; Baptista, M. A.; Miranda, J. M.; Medina, R.; Lima, V.

2009-04-01

free surface elevation, maximum water depth, maximum current speed, maximum Froude number and maximum impact forces (hydrostatic and dynamic forces). The fault rupture and sea bottom displacement has been computed by means of the Okada equations. As result, a set of more than 100 deterministic thematic maps have been created in a GIS environment incorporating geographical data and high resolution orthorectified satellite images. These thematic maps form an atlas of inundation maps that will be distributed to different government authorities and civil protection and emergency agencies. The authors gratefully acknowledge the financial support provided by the EU under the frame of the European Project TRANSFER (Tsunami Risk And Strategies For the European Region), 6th Framework Programme.

Sucrose-mediated transcriptional regulation of sucrose symporter activity in the phloem.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matt Vaughn Greg Harrington Daniel R Bush

2002-08-06

This project was based on our discovery that sucrose acts as a signaling molecule that regulates the activity of a proton-sucrose symporter in sugar beet leaf tissue. A major objective here was determining how sucrose transporter activity is being regulated. When sucrose accumulates in the phloem sucrose transport activity drops dramatically. Western blots of plasma membrane proteins isolated from sucrose treated leaves showed that the loss of sucrose transport activity was proportional to a decline in symporter abundance, demonstrating that sucrose transport is regulated by changes in the amount of BvSUT1 protein. BvSUT1 transcript levels decreased in parallel with themore » loss of sucrose transport activity. Nuclear run-on experiments demonstrated that BvSUT1 gene transcription was repressed significantly in nuclei from leaves fed 100 mM exogenous sucrose, showing that sucrose-dependent modulation of BvSUT1 mRNA levels is mediated by changes in transcription. To identify which secondary messenger systems might be involved in regulating symporter activity, we used a variety of pharmacological agents to probe for a role of calcium or protein phosphorylation in sucrose signaling. In a detailed analysis, only okadaic acid altered sucrose transport activity. These results suggest a protein phosphatase is involved. We hypothesized that protein kinase inhibitors would have a neutral affect or increase symporter transcription. Transpirational feeding of the protein kinase inhibitor staurosporine had no impact on sucrose transport while calphostin C, an inhibitor of protein kinase C, caused a 60% increase. These data provided good evidence that protein phosphorylation plays a central role in regulating sucrose symporter expression and sucrose transport activity. To determine whether protein phosphorylation is involved in sucrose regulation of proton-sucrose symporter activity, we pre-fed leaves with staurosporine for 4 h and then fed the treated leaves water or 100 m

Japan-China Joint Medical Workshop on Drug Discoveries and Therapeutics 2008: The need of Asian pharmaceutical researchers' cooperation.

PubMed

Nakata, M; Tang, W

2008-10-01

-viral drugs: Urgent need to develop effective drugs which cause less resistant virus by Nobuyuki Kobayashi (Nagasaki University, Japan) ● Design, synthesis and antiviral evaluation of novel heterocyclic compounds as HIV-1 NNRTIs by Xinyong Liu (Shandong University, China) ● Antiviral drug screening from microbial products by Eisaku Tsujii (Astellas Pharma Inc., Japan) ● Viral factors that determine the natural course of chronic hepatitis B viral infection by Hiroshi Yotsuyanagi (The University of Tokyo, Japan) ● Effect of andrographolide derivatives having α-glucosidase inhibition, on HBsAg, HBeAg secretion in HepG2 2.2.15 cells by Hongmin Liu (Zhengzhou University, China) ● Current and future antiviral therapy for influenza by Hideki Asanuma (Tokai University, Japan) ● Establishment of an HIV-based pseudotyping system as a safe model for screening inhibitors on bird flu H5N1 entry by Ying Guo (Peking Union Medical Collegee Chinese Academy of Medical Sciences, China) ● Strategy of discovery for novel antibiotics using silkworm infection model by Hiroshi Hamamoto (The University of Tokyo, Japan) ● Potent neuraminidase inhibitors and anti-inflammatory substances from Chaenomeles speciosa by Li Zhang (Chinese Academy of Medical Sciences and Peking Union Medical College, China) ● High-throughput screening assay for hepatitis C virus helicase inhibitors using fluorescence-quenching phenomenon by Hidenori Tani (Waseda University and National Institute of Advanced Industrial Science and Technology, Japan) Session VI. Biochemistry/Molecular Biology/Pharmacology ● A novel conjugate of low-molecular-weight heparin and Cu,Zn-superoxide dismutase: Study on its mechanism in preventing brain reperfusion injury after ischemia in gerbils by Fengshan Wang (Shandong University, China) ● A novel gene fudoh in SCCmec region regulates the colony spreading ability and virulence in Staphylococcus aureus by Chikara Kaito (The University of Tokyo, Japan) ● Water soluble

EDITORIAL: Focus on Iron-Based Superconductors FOCUS ON IRON-BASED SUPERCONDUCTORS

NASA Astrophysics Data System (ADS)

Hosono, Hideo; Ren, Zhi-An

2009-02-01

-L Drechsler, N Kozlova, M Bartkowiak, J E Hamann-Borrero, G Behr, K Nenkov, H-H Klauss, H Maeter, A Amato, H Luetkens, A Kwadrin, R Khasanov, J Freudenberger, A Köhler, M Knupfer, E Arushanov, H Rosner, B Büchner and L Schultz Low-energy spin dynamics in the antiferromagnetic phase of CaFe2As2 N J Curro, A P Dioguardi, N ApRoberts-Warren, A C Shockley and P Klavins Muon spin rotation study of magnetism and superconductivity in BaFe2-xCoxAs2 and Pr1-xSrxFeAsO C Bernhard, A J Drew, L Schulz, V K Malik, M Rössle, Ch Niedermayer, Th Wolf, G D Varma, G Mu, H-H Wen, H Liu, G Wu and X H Chen Magnetic impurities in the pnictide superconductor Ba1-xKxFe2As2 Sutirtha Mukhopadhyay, Sangwon Oh, A M Mounce, Moohee Lee, W P Halperin, N Ni, S L Bud'ko, P C Canfield, A P Reyes and P L Kuhns Neutron scattering investigation of the magnetic order in single crystalline BaFe2As2 M Kofu, Y Qiu, Wei Bao, S-H Lee, S Chang, T Wu, G Wu and X H Chen An NMR study on the F-doping evolution of the iron oxypnictide LaFeAs(O1-xFx) Y Nakai, S Kitagawa, K Ishida, Y Kamihara, M Hirano and H Hosono The peculiar physical properties and phase diagram of BaFe2-xCoxAs2 single crystals X F Wang, T Wu, G Wu, R H Liu, H Chen, Y L Xie and X H Chen Synthesis of LnFeAsO1-y superconductors (Ln=La and Nd) using the high-pressure technique Kiichi Miyazawa, Kunihiro Kihou, Motoyuki Ishikado, Parasharam M Shirage, Chul-Ho Lee, Nao Takeshita, Hiroshi Eisaki, Hijiri Kito and Akira Iyo Correlation effects in the iron pnictides Qimiao Si, Elihu Abrahams, Jianhui Dai and Jian-Xin Zhu Competition/coexisitence of magnetism and superconductivity in iron pnictides probed by muon spin rotation Soshi Takeshita and Ryosuke Kadono Impurity-induced in-gap state and Tc in sign-reversing s-wave superconductors: analysis of iron oxypnictide superconductors Yuko Senga and Hiroshi Kontani Intrinsic magnetic properties of the superconductor NdFeAsO0.9F0.1 from local and global measurements R Prozorov, M E Tillman, E D Mun and P C Canfield

Necessity of using heterogeneous ellipsoidal Earth model with terrain to calculate co-seismic effect

NASA Astrophysics Data System (ADS)

Cheng, Huihong; Zhang, Bei; Zhang, Huai; Huang, Luyuan; Qu, Wulin; Shi, Yaolin

2016-04-01

Co-seismic deformation and stress changes, which reflect the elasticity of the earth, are very important in the earthquake dynamics, and also to other issues, such as the evaluation of the seismic risk, fracture process and triggering of earthquake. Lots of scholars have researched the dislocation theory and co-seismic deformation and obtained the half-space homogeneous model, half-space stratified model, spherical stratified model, and so on. Especially, models of Okada (1992) and Wang (2003, 2006) are widely applied in the research of calculating co-seismic and post-seismic effects. However, since both semi-infinite space model and layered model do not take the role of the earth curvature or heterogeneity or topography into consideration, there are large errors in calculating the co-seismic displacement of a great earthquake in its impacted area. Meanwhile, the computational methods of calculating the co-seismic strain and stress are different between spherical model and plane model. Here, we adopted the finite element method which could well deal with the complex characteristics (such as anisotropy, discontinuities) of rock and different conditions. We use the mash adaptive technique to automatically encrypt the mesh at the fault and adopt the equivalent volume force replace the dislocation source, which can avoid the difficulty in handling discontinuity surface with conventional (Zhang et al., 2015). We constructed an earth model that included earth's layered structure and curvature, the upper boundary was set as a free surface and the core-mantle boundary was set under buoyancy forces. Firstly, based on the precision requirement, we take a testing model - - a strike-slip fault (the length of fault is 500km and the width is 50km, and the slippage is 10m) for example. Because of the curvature of the Earth, some errors certainly occur in plane coordinates just as previous studies (Dong et al., 2014; Sun et al., 2012). However, we also found that: 1) the co

Reconciling Pre- and Co-Seismic Deformation at Megathrusts: Tohoku Informing Cascadia

NASA Astrophysics Data System (ADS)

Furlong, K. P.; Govers, R. M.

2013-12-01

processes along the megathrust and observations regionally - i.e. with such models (e.g. Okada-type solutions) we find reasonable agreement among geodetic and seismologic models. In assessing sensitivities in our preliminary modeling, we find that depending on the strength and rheologic considerations in the model, similar patterns of displacement in the upper plate in the typical observing zones (on-shore, ~ 100+ km from trench) can have significantly different displacement effects in the vicinity of the earthquake rupture and trench - the areas most critical to tsunamigenesis and assessing earthquake magnitude. Also although it is perhaps reassuring to see that there is general agreement between the seismologically determined finite fault models (FFM) and the observed surface deformation; this information after-the-fact does not tell us why the slip deficit accumulated as it did. Here we report on improved (numerical) models of the strain accumulation and release cycle in megathrust zones that better incorporate variations in rheology, the effects of plate boundary character (pre- and co-seismic), and the relationships between pre-earthquakes observed deformation and co-seismic rupture characteristics.

[Frontier of mycobacterium research--host vs. mycobacterium].

PubMed

Okada, Masaji; Shirakawa, Taro

2005-09-01

During the past decade, we have observed advance in tuberculosis research including novel vaccines, innate immunity (TLR), SNIP analysis and molecular mechanism of drug resistance. Worldwide genome project enabled the whole genome sequence of host resistant against tuberculosis as well as the whole genome sequence of M. tuberculosis H37Rv. DNA technology has also provided a great impact on the development of novel vaccine against TB. In this symposium, we have invited leading researchers in the field of the frontier study of Mycobacterium research in order to provide general overview of the cutting edge of frontier research. Molecular mechanism of drug resistance of M. tuberculosis has been clarified. On the other hand, molecular mechanism of host-defence (insusceptibility of host) against M. tuberculosis has not yet elucidated. Dr. Taro Shirakawa (Kyoto University) reviewed the susceptibility genes of host in TB infection and presented candidate genes associated with multi-drug resistant tuberculosis. Dr. Naoto Keicho (International Medical Center of Japan) tried to identify host genetic factors involved in susceptibility to pulmonary Mycobacterium avium complex (MAC) infection by candidate gene approach and genome-wide approach. In Japan, Dr. Masaji Okada (National Hospital Organization Kinki-Chuo Chest Medical Center) has been engaged actively in the development of new tuberculosis vaccines (HVJ-liposome/Hsp65 DNA + IL-12 DNA vaccine and recombinant 72f BCG vaccine). He showed basic strategy for construction of new candidate vaccines and also showed significant efficacy on the protection of tuberculosis infection using cynomolgus monkeys, which are very similar to human tuberculosis. Dr. Hatsumi Taniguchi (University of Occupational and Environmental Health) presented that M. tuberculosis mIHF and the neighbor genes went into a dormacy-like state of M. smegmatis in J774 macrophage cells. This study might provide a weapon for elucidating the mechanism of dormacy

EDITORIAL: Selected papers from the 10th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2010) Selected papers from the 10th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2010)

NASA Astrophysics Data System (ADS)

Reynaerts, Dominiek; Vullers, Ruud

2011-10-01

collaboration with the staff of IOP Publishing. PowerMEMS 2010 contents Harvesting energy from airflow with a michromachined piezoelectric harvester inside a Helmholtz resonator S P Matova, R Elfrink, R J M Vullers and R van Schaijk Analysis and characterization of triangular electrode structures for electrostatic energy harvestingDaniel Hoffmann, Bernd Folkmer and Yiannos Manoli A smart and self-sufficient frequency tunable vibration energy harvesterC Eichhorn, R Tchagsim, N Wilhelm and P Woias Power output enhancement of a vibration-driven electret generator for wireless sensor applicationsTatsuakira Masaki, Kenji Sakurai, Toru Yokoyama, Masayo Ikuta, Hiroshi Sameshima, Masashi Doi, Tomonori Seki and Masatoshi Oba Harvesting traffic-induced vibrations for structural health monitoring of bridgesT V Galchev, J McCullagh, R L Peterson and K Najafi Dispenser-printed planar thick-film thermoelectric energy generatorsA Chen, D Madan, P K Wright and J W Evans Silicon nanowire arrays as thermoelectric material for a power microgeneratorD Dávila, A Tarancón, M Fernández-Regúlez, C Calaza, M Salleras, A San Paulo and L Fonseca A micro thermal switch with a stiffness-enhanced thermal isolation structureTakashiro Tsukamoto, Masayoshi Esashi and Shuji Tanaka A dielectric liquid contact thermal switch with electrowetting actuationA R McLanahan, C D Richards and R F Richards A self-regulating valve for single-phase liquid cooling of microelectronicsRadu Donose, Michaël De Volder, Jan Peirs and Dominiek Reynaerts A MEMS-enabled 3D zinc-air microbattery with improved discharge characteristics based on a multilayer metallic substructureA Armutlulu, Y Fang, S H Kim, C H Ji, S A Bidstrup Allen and M G Allen Design, fabrication and testing of an air-breathing micro direct methanol fuel cell with compound anode flow fieldLuwen Wang, Yufeng Zhang, Youran Zhao, Zijiang An, Zhiping Zhou and Xiaowei Liu A shadow-mask evaporated pyroMEMS igniterD A de Koninck, D Briand and N F de Rooij Aerodynamic

Kawasaki disease: A brief history.

PubMed

Burns, J C; Kushner, H I; Bastian, J F; Shike, H; Shimizu, C; Matsubara, T; Turner, C L

2000-08-01

simultaneous recognition of this disease around the world in the 1960s and 1970s. There are several possible explanations. KD may have been a new disease that emerged in Japan and emanated to the Western World through Hawaii, where the disease is prevalent among Asian children. Alternatively, KD and IPN may be part of the spectrum of the same disease and clinically mild KD masqueraded as other diseases, such as scarlet fever in the preantibiotic era. Case reports of IPN from Western Europe extend back to at least the 19th century, but, thus far, cases of IPN have not been discovered in Japan before World War II. Perhaps the factors responsible for KD were introduced into Japan after the World War II and then reemerged in a more virulent form that subsequently spread through the industrialized Western world. It is also possible that improvements in health care and, in particular, the use of antibiotics to treat infections caused by organisms including toxin-producing bacteria reduced the burden of rash/fever illness and allowed KD to be recognized as a distinct clinical entity. Itsuzo Shigematsu, Hiroshi Yanagawa, and colleagues have conducted 14 nationwide surveys in Japan. These have indicated that: 1) KD occurred initially in nationwide epidemics but now occurs in regional outbreaks; 2) there are approximately 5,000 to 6,000 new cases each year; 3) current estimates of incidence rates are 120 to 150 cases per 100,000 children <5 years old; 4) KD is 1.5 times more common in males and 85% of cases occur in children <5 years old; and 5) the recurrence rate is low (4%). In 1978, David Morens at the Centers for Disease Control and Prevention published a case definition based on Kawasaki's original criteria. The Centers for Disease Control and Prevention developed a computerized database in 1984, and a passive reporting system currently exists in 22 states. Regional investigations and national surveys suggest an annual incidence of 4 to 15 cases per 100 000 children <5 years o

Regional variation of carbonaceous aerosols from space and simulations

NASA Astrophysics Data System (ADS)

Mukai, Sonoyo; Sano, Itaru; Nakata, Makiko; Kokhanovsky, Alexander

2017-04-01

effect on carbonaceous aerosols. And then the selected data observed by ADEOS-2/GLI and POLDER in 2003 are treated by using Vector form Method of Successive Order of Scattering (VMSOS) for radiative transfer simulations in the semi-infinite atmosphere [2]. Finally the obtained optical properties of the carbonaceous aerosols are investigated in comparison with the numerical model simulations of SPRINTARS. In spite of the limited case studies, it has been pointed out that NUV-channel data are effective for retrieval of the carbonaceous aerosol properties. Therefore we have to treat with this issue for not only detection of biomass burning plume but also retrieval itself. If that happens, synthetic analysis based on multi-channel and/or polarization measurements become practical, and the proposed procedure and results are available for a feasibility study of coming space missions. [1] Sano, I., Y. Okada, M. Mukai and S. Mukai, "Retrieval algorithm based on combined use of POLDER and GLI data for biomass aerosols," J. RSSJ, vol. 29, no. 1, pp. 54-59, doi:10.11440/rssj.29.54, 2009. [2] Mukai, S., M. Nakata, M. Yasumoto, I. Sano and A. Kokhanovsky, "A study of aerosol pollution episode due to agriculture biomass burning in the east-central China using satellite data," Front. Environ. Sci., vol. 3:57, doi:　10.3389/fenvs.2015.00057, 2015.

A Trial for Earthquake Prediction by Precise Monitoring of Deep Ground Water Temperature

NASA Astrophysics Data System (ADS)

Nasuhara, Y.; Otsuki, K.; Yamauchi, T.

2006-12-01

ca. 0.0005 deg. C is superposed on the cyclic fluctuation due to the earth tide. Using the earth tide as a reference, the resolution of our observation system is estimated to be higher than 10^-8 strain (0.5kPa). How small earthquakes off Miyagi Pref. can we detect by our observation system? Using a computer simulation code MICAP-G released by Okada (1992) and Naito & Yoshikawa (1999), we calculated the change in crustal strain at our observation site for assumed earthquakes off Miyagi Pref. with various sizes. These simulation results estimated that our system can detect earthquakes larger than about M6. Actually, we detected successfully the preseismic and coseismic temperature signals for the earthquake off Miyagi Pref. on Dec. 2, 2005 (M6.6) which is largest one since our observation started. The temperature began to decrease about 2.5 hours before the main shock, it was minimum (0.003 deg) one hour before the main, and abruptly increased by 0.002 deg. C 10 minutes after the main shock.

Tsunami focusing and leading wave height

NASA Astrophysics Data System (ADS)

Kanoglu, Utku

2016-04-01

and Synolakis, 1994, Proc. R. Soc. A: Math. Phys. Eng. Sci., 445, 99-112) with a finite crest length, which is most common tsunami initial waveform. We fit earthquake initial waveform calculated through Okada (1985, Bull. Seismol. Soc. Am. 75, 1135-1040) to the N-wave form presented by Tadepalli and Synolakis (1994). First, we investigate focusing phenomena as presented by Kanoglu et al. (2013, Proc. R. Soc. A: Math. Phys. Eng. Sci., 469, 20130015) and compare our results with their non-dispersive and dispersive linear analytical solutions. We confirm focusing phenomena, which amplify the wave height in the leading depression side. We then study sequencing of an N-wave profile with a finite crest length. Our preliminary results show that sequencing is more pronounced on the leading depression side. We perform parametric study to understand sequencing in terms of N-wave, hence earthquake, parameters. We then discuss the results both in terms of tsunami focusing and leading wave amplitude. Acknowledgment: The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 603839 (Project ASTARTE - Assessment, Strategy and Risk Reduction for Tsunamis in Europe).

Tsunami hazard assessment along the U. S. East Coast

NASA Astrophysics Data System (ADS)

Tajalli Bakhsh, T.; Grilli, S. T.; Harris, J. C.; Kirby, J. T.; Shi, F.; Tehranirad, B.

2012-12-01

sources are modeled using the standard Okada method. For landslide tsunamis, we first generate tsunami sources using a three-dimensional Navier-Stokes model (THETIS or NHWAVE). These models feature all relevant physical processes, such as frequency dispersion (very important for landslide sources), nonlinear wave effects during shoaling, and dissipation by bottom friction and wave breaking (via a shock-capturing TVD algorithm). In modeling coastal hazard from various sources, we find that tsunamigenic SMFs, which are the nearest tsunami sources and can potentially cause highly focused coastal runup, may control tsunami hazard for many east coast communities north of the Carolinas. In many cases, however, we find that a wide shallow continental shelf may cause significant dissipation of the shorter waves caused by SMFs and hence offer some protection. The accurate modeling of the delicate balance between nonlinear and dissipative processes governing such situations is currently being researched and will be the object of a separate presentation. Additionally, considerable efforts are being devoted to properly parameterizing extreme SMFs, which are also the object of collaborative work with geologists and marine geotechnical experts (reported independently).

dc3dm: Software to efficiently form and apply a 3D DDM operator for a nonuniformly discretized rectangular planar fault

NASA Astrophysics Data System (ADS)

Bradley, A. M.

2013-12-01

My poster will describe dc3dm, a free open source software (FOSS) package that efficiently forms and applies the linear operator relating slip and traction components on a nonuniformly discretized rectangular planar fault in a homogeneous elastic (HE) half space. This linear operator implements what is called the displacement discontinuity method (DDM). The key properties of dc3dm are: 1. The mesh can be nonuniform. 2. Work and memory scale roughly linearly in the number of elements (rather than quadratically). 3. The order of accuracy of my method on a nonuniform mesh is the same as that of the standard method on a uniform mesh. Property 2 is achieved using my FOSS package hmmvp [AGU 2012]. A nonuniform mesh (property 1) is natural for some problems. For example, in a rate-state friction simulation, nucleation length, and so required element size, scales reciprocally with effective normal stress. Property 3 assures that if a nonuniform mesh is more efficient than a uniform mesh (in the sense of accuracy per element) at one level of mesh refinement, it will remain so at all further mesh refinements. I use the routine DC3D of Y. Okada, which calculates the stress tensor at a receiver resulting from a rectangular uniform dislocation source in an HE half space. On a uniform mesh, straightforward application of this Green's function (GF) yields a DDM I refer to as DDMu. On a nonuniform mesh, this same procedure leads to artifacts that degrade the order of accuracy of the DDM. I have developed a method I call IGA that implements the DDM using this GF for a nonuniformly discretized mesh having certain properties. Importantly, IGA's order of accuracy on a nonuniform mesh is the same as DDMu's on a uniform one. Boundary conditions can be periodic in the surface-parallel direction (in both directions if the GF is for a whole space), velocity on any side, and free surface. The mesh must have the following main property: each uniquely sized element must tile each element

Fault geometric complexity and how it may cause temporal slip-rate variation within an interacting fault system

NASA Astrophysics Data System (ADS)

Zielke, Olaf; Arrowsmith, Ramon

2010-05-01

Slip-rates along individual faults may differ as a function of measurement time scale. Short-term slip-rates may be higher than the long term rate and vice versa. For example, vertical slip-rates along the Wasatch Fault, Utah are 1.7+/-0.5 mm/yr since 6ka, <0.6 mm/yr since 130ka, and 0.5-0.7 mm/yr since 10Ma (Friedrich et al., 2003). Following conventional earthquake recurrence models like the characteristic earthquake model, this observation implies that the driving strain accumulation rates may have changed over the respective time scales as well. While potential explanations for such slip-rate variations may be found for example in the reorganization of plate tectonic motion or mantle flow dynamics, causing changes in the crustal velocity field over long spatial wavelengths, no single geophysical explanation exists. Temporal changes in earthquake rate (i.e., event clustering) due to elastic interactions within a complex fault system may present an alternative explanation that requires neither variations in strain accumulation rate or nor changes in fault constitutive behavior for frictional sliding. In the presented study, we explore this scenario and investigate how fault geometric complexity, fault segmentation and fault (segment) interaction affect the seismic behavior and slip-rate along individual faults while keeping tectonic stressing-rate and frictional behavior constant in time. For that, we used FIMozFric--a physics-based numerical earthquake simulator, based on Okada's (1992) formulations for internal displacements and strains due to shear and tensile faults in a half-space. Faults are divided into a large number of equal-sized fault patches which communicate via elastic interaction, allowing implementation of geometrically complex, non-planar faults. Each patch has assigned a static and dynamic friction coefficient. The difference between those values is a function of depth--corresponding to the temperature-dependence of velocity-weakening that is

Precursor to the Matuyama/Brunhes Polarity Transition 0.78 Million Years Ago at Bishop, CA

NASA Astrophysics Data System (ADS)

Kravchinsky, Vadim; Liddicoat, Joseph

2013-04-01

Van Zijl et al.'s 1962 report of a polarity transition in Stormberg lavas was the first of many investigations of the Matuyama/Brunhes polarity transition (MBPT) about 0.78 m.y. ago. Among the earliest of those investigations was a study of bathyal siltstone in the Boso Peninsula in Japan (Niitsuma, 1971; Okada and Niitsuma, 1989). That investigation was preceded by a report that the relative intensity of the palaeomagnetic field as recorded in a marine core is reduced for a longer period of time than is required for the field directions to reverse (Ninkovich et al., 1966), a discovery that was summarized for other reversals in cored marine sediment (Opdyke, 1973). In the U.S., Hillhouse and Cox (1976) documented the field directions and relative intensity during the MBPT using exposed Pleistocene Lake Tecopa sediments in southeastern California. They reported a generally smooth path of the Virtual Geomagnetic Poles (VGPs) as the field changed from reverse to normal that does not coincide with the VGP path for the MBPT in Japan, concluding that the transitional field is predominantly the non-dipole field. At Lake Tecopa, as in the marine record, the reduction in field strength occurred sooner and lasted longer by a factor of at least two the time required for the directions to reverse polarity, which was confirmed by Valet et al. (1988) in a restudy of the Lake Tecopa sediments. The Lake Tecopa study by Hillhouse and Cox (1976) was followed by one of Pleistocene lacustrine sediments exposed beneath the Bishop Tuff (Dalrymple et al., 1965) near Bishop, California (37.4˚ N, 241˚ E) (Liddicoat, 1982, 1993). The data we report are for directional and normalized relative intensity measurements of additional samples from each horizon at the Bishop locality that indicate the time spanned by the reduction in relative intensity for the full transition exceeds by about 20 percent the time during which the palaeomagnetic directions reverse. Although the change in field

Two distinct pathways mediate the formation of intermediate density cells and hyperdense cells from normal density sickle red blood cells.

PubMed

Schwartz, R S; Musto, S; Fabry, M E; Nagel, R L

1998-12-15

did inhibitors of the K:Cl cotransporter, okadaic acid, and [(dihydroindenyl) oxy]alkanoic acid (DIOA). Conversely, inhibitors of K(Ca2+), charybdotoxin and clotrimazole, inhibited HD cell formation. The combined use of K(Ca2+) and K:Cl inhibitors nearly eliminated dense cell (ID + HD cell) formation. In summary, dense cells formed by O-D cycling for 22 hours at pH 7.4 cycling are predominately the ID type, whereas dense cells formed by O-D cycling for 22 hours at pH 6.8 are both the ID and HD type, with the latter low in HbF, suggesting that HD cell formation has a greater dependency on HbS polymerization. A combination of K:Cl cotransport and the K(Ca2+) activities account for the majority of dense cells formed, and these pathways can be driven independently. We propose a model in which reversible sickling-induced K+ loss by K:Cl primarily generates ID cells and K+ loss by the K(Ca2+) channel primarily generates HD cells. These results imply that both pathways must be inhibited to completely prevent dense SS cell formation and have potential therapeutic implications.

PREFACE AND CONFERENCE INFORMATION: Eighth International Conference on Laser Ablation

NASA Astrophysics Data System (ADS)

Hess, Wayne P.; Herman, Peter R.; Bäuerle, Dieter; Koinuma, Hideomi

2007-04-01

enjoy the collection of papers in this proceeding. Also, please join us for COLA 2007, to be held in the Canary Islands, Spain (http://www.io.csic.es/cola07/index.php). Conference on Laser Ablation (COLA'05) September 11-16, 2005 Banff, Canada Supported by University of Toronto, Canada (UT) Pacific Northwest National Laboratory (PNNL) Sponsors Sponsorship from the following companies is gratefully acknowledged and appreciated AMBP Tech Corporation GSI Lumonics Amplitude Systèmes IMRA America, Inc. Andor Technologies Journal of Physics D: Applied Physics North Canadian Institute for Photonic Innovations LUMERA LASER GmbH Clark-MXR, Inc. Pascal Coherent, Lamdbda Physik, TuiLaser PVD Products, Inc. Continuum Staib Instruments, Inc. Cyber Laser Inc. Surface GAM LASER, Inc. International Steering Committee C. Afonso (Spain)W. Husinsky (Austria) D. Bäuerle (Austria)W. Kautek (Germany) I.W. Boyd (UK) H. Koinuma (Japan) E.B. Campbell (Sweden) H.U. Krebs (Germany) J.T. Dickinson (USA) D.H. Lowndes (USA) M. Dinescu (Romania) J.G. Lunney (Ireland) J.J. Dubowski (Canada) W. Marine (France) E. Fogarassy (France) K. Murakami (Japan) C. Fotakis (Greece) T. Okada (Japan) D. Geohegan (USA) R.E. Russo (USA) M. Gower (UK) J. Schou (Denmark) R.H. Haglund Jr. (USA) M. Stuke (Germany) R.R. Herman (Canada) K. Sugioka (Japan) W.P. Hess (USA) F. Traeger (Germany) J.S Horwitz (USA) A. Yabe (Japan) Local Organizing Committee Nikki Avery Pacific Northwest National Laboratory Ken Beck Pacific Northwest National Laboratory Jan J. Dubowski University of Alberta Robert Fedosejevs Université de Sherbrooke Alan Joly Pacific Northwest National Laboratory Michel Meunier École Polytechnique de Montréal Suwas Nikumb National Research Council Canada Ying Tsui University of Alberta Conference photograph.

PREFACE: International Conference on Computing in High Energy and Nuclear Physics (CHEP 2012)

NASA Astrophysics Data System (ADS)

Ernst, Michael; Düllmann, Dirk; Rind, Ofer; Wong, Tony

2012-12-01

Wisconsin-Madison, United States Günter Duckeck, Ludwig Maximilian University of Munich, Germany Richard Dubois, SLAC, United States Michael Ernst, BNL, United States Ian Fisk, Fermilab, United States Gonzalo Merino, PIC, Spain John Gordon, STFC-RAL, United Kingdom Volker Gülzow, DESY, Germany Frederic Hemmer, CERN, Switzerland Viatcheslav Ilyin, Moscow State University, Russia Nobuhiko Katayama, KEK, Japan Alexei Klimentov, BNL, United States Simon C. Lin, Academia Sinica, Taiwan Milos Lokajícek, FZU Prague, Czech Republic David Malon, ANL, United States Pere Mato Vila, CERN, Switzerland Mauro Morandin, INFN CNAF, Italy Harvey Newman, Caltech, United States Farid Ould-Saada, University of Oslo, Norway Ruth Pordes, Fermilab, United States Hiroshi Sakamoto, University of Tokyo, Japan Alberto Santoro, UERJ, Brazil Jim Shank, Boston University, United States Dongchul Son, Kyungpook National University, South Korea Reda Tafirout, TRIUMF, Canada Stephen Wolbers, Fermilab, United States Frank Wuerthwein, UCSD, United States

Magnetic Fields Sculpt Narrow Jets From Dying Star

NASA Astrophysics Data System (ADS)

2006-03-01

of hydrogen atoms in their cores. As they near the end of their lives they begin to blow off their outer atmospheres and eventually collapse down to a white dwarf star about the size of Earth. Intense ultraviolet radiation from the white dwarf causes the gas thrown off earlier to glow, producing a planetary nebula. Astronomers believe that W43A is in the transition phase that will produce a planetary nebula. That transition phase, they say, is probably only a few decades old, so W43A offers the astronomers a rare opportunity to watch the process. While the stars that produce planetary nebulae are spherical, most of the nebulae themselves are not. Instead, they show complex shapes, many elongated. The earlier discovery of jets in W43A showed one mechanism that could produce the elongated shapes. The latest observations will help scientists understand the mechanisms producing the jets. The water molecules the scientists observed are in regions nearly 100 billion miles from the old star, where they are amplifying, or strengthening, radio waves at a frequency of 22 GHz. Such regions are called masers, because they amplify microwave radiation the same way a laser amplifies light radiation. The earlier observations showed that the jets are coming out from the star in a corkscrew shape, indicating that whatever is squirting them out is slowly rotating. Vlemmings and Diamond worked with Hiroshi Imai of Kagoshima University in Japan. The astronomers reported their work in the March 2 issue of the scientific journal Nature. The VLBA is a system of ten radio-telescope antennas, each with a dish 25 meters (82 feet) in diameter and weighing 240 tons. From Mauna Kea on the Big Island of Hawaii to St. Croix in the U.S. Virgin Islands, the VLBA spans more than 5,000 miles, providing astronomers with the sharpest vision of any telescope on Earth or in space. Dedicated in 1993, the VLBA has an ability to see fine detail equivalent to being able to stand in New York and read a

PREFACE: The fifth International Conference on Inertial Fusion Sciences and Applications (IFSA2007)

NASA Astrophysics Data System (ADS)

Azechi, Hiroshi; Hammel, Bruce; Gauthier, Jean-Claude

2008-06-01

subject are gathered. The IFSA International Organizing Committee and Scientific Advisory Board appreciate the efforts of inertial fusion researchers worldwide in making IFSA 2007 an extremely successful conference. The proceedings were published with the support of Dr Y Sakawa, Dr H Homma, Ms S Karasuyama, Ms M Odagiri, and Ms I Kobatake. Kunioki Mima Co-chair Hiroshi Azechi Technical Program Committee Co-chair John Lindl Co-chair Bruce Hammel Technical Program Committee Co-chair Christine Labaune Co-chair Jean-Claude Gauthier Technical Program Committee Co-chair

Vlasov simulations of electron hole dynamics in inhomogeneous magnetic field

NASA Astrophysics Data System (ADS)

Kuzichev, Ilya; Vasko, Ivan; Agapitov, Oleksiy; Mozer, Forrest; Artemyev, Anton

2017-04-01

particular, our simulations suggest that slow EHs (which generation is usually attributed to the Buneman instability) can arise due to slowing down of fast EH generated by electron-beam instability. The estimate of the potential drop along EHs allow to estimate the parallel potential drop provided by EHs in a particular plasma system. 1. Matsumoto, H., H. Kojima, T. Miyatake, Y. Omura, M. Okada, I. Nagano, and M. Tsutsui, Electrotastic Solitary Waves (ESW) in the magnetotail: BEN wave forms observed by GEOTAIL, Geophys. Res. Lett., 21, 2915-2918, doi:10.1029/94GL01284, 1994. 2. Norgren, C., M. Andŕe, A. Vaivads, and Y. V. Khotyaintsev, Slow electron phase space holes: Magnetotail observations, Geophys. Res. Lett., 42, 1654-1661, doi:10.1002/2015GL063218, 2015. 3. Malaspina, D. M., J. R. Wygant, R. E. Ergun, G. D. Reeves, R. M. Skoug, and B. A. Larsen, Electric field structures and waves at plasma boundaries in the inner magnetosphere, Journal of Geophysical Research (Space Physics), 120, 4246-4263, doi:10.1002/2015JA021137, 2015. 4. Franz, J. R., P. M. Kintner, J. S. Pickett, and L.-J. Chen, Properties of small-amplitude electron phase-space holes observed by Polar, Journal of Geophysical Research (Space Physics), 110, A09212, doi:10.1029/2005JA011095, 2005. 5. Cattell, C., C. Neiman, J. Dombeck, J. Crumley, J. Wygant, C. A. Kletzing, W. K. Peterson, F. S. Mozer, and M. André (2003), Large amplitude solitary waves in and near the Earth's magnetosphere, magnetopause and bow shock: Polar and Cluster observations, Nonlinear Processes Geophys., 10, 13-26. 6. Mandrake, L., P. L. Pritchett, and F. V. Coroniti, Electron beam generated solitary structures in a nonuniform plasma system, Geophys. Res. Lett., 27, 2869-2872, doi:10.1029/2000GL003785, 2000. The work of I.K. was supported by Russian Foundation for Basic Research 16-32-00721 mol_a. The work of I.V., O.A. and F.M. was supported by JHU/APL contract 922613 (RBSPEFW).

PREFACE: International Conference on Computing in High Energy and Nuclear Physics (CHEP 2010)

NASA Astrophysics Data System (ADS)

Lin, Simon C.; Shen, Stella; Neufeld, Niko; Gutsche, Oliver; Cattaneo, Marco; Fisk, Ian; Panzer-Steindel, Bernd; Di Meglio, Alberto; Lokajicek, Milos

2011-12-01

& Genoa University/INFN, Switzerland Lothar Bauerdick, Fermilab, USA Ian Bird, CERN, Switzerland Amber Boehnlein, US Department of Energy, USA Kors Bos, CERN, Switzerland Federico Carminati, CERN, Switzerland Philippe Charpentier, CERN, Switzerland Gang Chen, Institute of High Energy Physics, China Peter Clarke, University of Edinburgh, UK Michael Ernst, Brookhaven National Laboratory, USA David Foster, CERN, Switzerland Merino Gonzalo, CIEMAT, Spain John Gordon, STFC-RAL, UK Volker Guelzow, Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany John Harvey, CERN, Switzerland Frederic Hemmer, CERN, Switzerland Hafeez Hoorani, NCP, Pakistan Viatcheslav Ilyin, Moscow State University, Russia Matthias Kasemann, DESY, Germany Nobuhiko Katayama, KEK, Japan Milos Lokajícek, FZU Prague, Czech Republic David Malon, ANL, USA Pere Mato Vila, CERN, Switzerland Mirco Mazzucato, INFN CNAF, Italy Richard Mount, SLAC, USA Harvey Newman, Caltech, USA Mitsuaki Nozaki, KEK, Japan Farid Ould-Saada, University of Oslo, Norway Ruth Pordes, Fermilab, USA Hiroshi Sakamoto, The University of Tokyo, Japan Alberto Santoro, UERJ, Brazil Jim Shank, Boston University, USA Alan Silverman, CERN, Switzerland Randy Sobie , University of Victoria, Canada Dongchul Son, Kyungpook National University, South Korea Reda Tafirout , TRIUMF, Canada Victoria White, Fermilab, USA Guy Wormser, LAL, France Frank Wuerthwein, UCSD, USA Charles Young, SLAC, USA

Structure, function, and evolution of bacterial ATP-binding cassette systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davidson, A.L.; Dassa, E.; Orelle, C.

2010-07-27

The ATP-binding cassette (ABC) systems constitute one of the largest superfamilies of paralogous sequences. All ABC systems share a highly conserved ATP-hydrolyzing domain or protein (the ABC; also referred to as a nucleotide-binding domain [NBD]) that is unequivocally characterized by three short sequence motifs (Fig. 1): these are the Walker A and Walker B motifs, indicative of the presence of a nucleotide-binding site, and the signature motif, unique to ABC proteins, located upstream of the Walker B motif (426). Other motifs diagnostic of ABC proteins are also indicated in Fig. 1. The biological significance of these motifs is discussed inmore » Structure, Function, and Dynamics of the ABC. ABC systems are widespread among living organisms and have been detected in all genera of the three kingdoms of life, with remarkable conservation in the primary sequence of the cassette and in the organization of the constitutive domains or subunits (203, 420). ABC systems couple the energy of ATP hydrolysis to an impressively large variety of essential biological phenomena, comprising not only transmembrane (TM) transport, for which they are best known, but also several non-transport-related processes, such as translation elongation (62) and DNA repair (174). Although ABC systems deserve much attention because they are involved in severe human inherited diseases (107), they were first discovered and characterized in detail in prokaryotes, as early as the 1970s (13, 148, 238, 468). The most extensively analyzed systems were the high-affinity histidine and maltose uptake systems of Salmonella enterica serovar Typhimurium and Escherichia coli. Over 2 decades ago, after the completion of the nucleotide sequences encoding these transporters in the respective laboratories of Giovanna Ames and Maurice Hofnung, Hiroshi Nikaido and colleagues noticed that the two systems displayed a global similarity in the nature of their components and, moreover, that the primary sequences of

Titan Casts Revealing Shadow

NASA Astrophysics Data System (ADS)

2004-05-01

A rare celestial event was captured by NASA's Chandra X-ray Observatory as Titan -- Saturn's largest moon and the only moon in the Solar System with a thick atmosphere -- crossed in front of the X-ray bright Crab Nebula. The X-ray shadow cast by Titan allowed astronomers to make the first X-ray measurement of the extent of its atmosphere. On January 5, 2003, Titan transited the Crab Nebula, the remnant of a supernova explosion that was observed to occur in the year 1054. Although Saturn and Titan pass within a few degrees of the Crab Nebula every 30 years, they rarely pass directly in front of it. "This may have been the first transit of the Crab Nebula by Titan since the birth of the Crab Nebula," said Koji Mori of Pennsylvania State University in University Park, and lead author on an Astrophysical Journal paper describing these results. "The next similar conjunction will take place in the year 2267, so this was truly a once in a lifetime event." Animation of Titan's Shadow on Crab Nebula Animation of Titan's Shadow on Crab Nebula Chandra's observation revealed that the diameter of the X-ray shadow cast by Titan was larger than the diameter of its solid surface. The difference in diameters gives a measurement of about 550 miles (880 kilometers) for the height of the X-ray absorbing region of Titan's atmosphere. The extent of the upper atmosphere is consistent with, or slightly (10-15%) larger, than that implied by Voyager I observations made at radio, infrared, and ultraviolet wavelengths in 1980. "Saturn was about 5% closer to the Sun in 2003, so increased solar heating of Titan may account for some of this atmospheric expansion," said Hiroshi Tsunemi of Osaka University in Japan, one of the coauthors on the paper. The X-ray brightness and extent of the Crab Nebula made it possible to study the tiny X-ray shadow cast by Titan during its transit. By using Chandra to precisely track Titan's position, astronomers were able to measure a shadow one arcsecond in

Shallow Moho with aseismic upper crust and deep Moho with seismic lower crust beneath the Japanese Islands obtained by seismic tomography using data from dense seismic network

NASA Astrophysics Data System (ADS)

Matsubara, Makoto; Obara, Kazushige

2015-04-01

. The Moho discontinuity deepens over 35 km in the collision zone like as Kanto Mountains, the volcanic underplating zone as the Tohoku backbone range, and non-tension region like as Chugoku Mountains. These regions associated with deep Moho are characterized by the crustal seismicity within the depth range from 20 to 30 km. The iso-depth contour of 35 km beneath the southwestern Japan is consistent with that derived from the receiver function method (Shiomi et al. 2006). There are nonvolcanic tremors and short-time slow slip events (SSE) beneath the southwestern Japan (eg. Obara, 2002). Matsubara et al. (2009) consider that the tremors and SSEs occur along the contact zone of Moho discontinuity beneath the Eurasian plate and the subducting Philippine Sea plate beneath southwestern Japan. Our Moho model is consistent with this since they exist along the southern edge of the Moho discontinuity of the continental Eurasian plate. Reference: Hirata, N., Sakai, S., Nakagawa, S., Ishikawa, M., Sato, H., Kasahara, K., Kimura, H. and Honda, R. (2012) A new tomographic image on the Philippine Sea Slab beneath Tokyo - Implication to seismic hazard in the Tokyo metropolitan region, EOS, Transactions, AGU, T11C-06. Kita, S., T. Okada, A. Hasegawa, J. Nakajima, and T. Matsuzawa (2010) Anomalous deepening of a seismic belt in the upper-plane of the double seismic zone in the Pacific slab beneath the Hokkaido corner: Possible evidence for thermal shielding caused by subducted forearc crust materials, Earth Planet. Science Lett., 290, 415-426. Matsubara, M. and K. Obara (2011) The 2011 Off the Pacific Coast of Tohoku earthquake related to a strong velocity gradient with the Pacific plate, Earth Planets Space, 63, 663-667. Matsubara, M., K. Obara, and K. Kasahara (2009) High-Vp/Vs zone accompanying non-volcanic tremors and slow-slip events beneath southwestern Japan, Tectonophysics, 472, 6-17, doi:10.1016/j.tecto.2008.06.013. Obara, K. (2002) Nonvolcanic deep tremor associated with

Preface

NASA Astrophysics Data System (ADS)

Gauthier, Jean-Claude; Hammel, Bruce; Azechi, Hiroshi; Labaune, Christine

2006-06-01

and the Teller lectures. The keynotes give an overview of progress in inertial fusion in North America, Europe and Asia. The Teller lectures show the contributions of this year's two winners: Joe Kilkenny of General Atomics and Max Tabak of LLNL. The remainder of the Proceedings is divided into three parts. Part A covers the physics of inertial fusion; Part B covers facilities, lasers, particle beams, Z-pinches, target fabrication and reactor design; Part C covers fundamental high-energy density science and other applications of inertial fusion VI technology such as plasma diagnostics, atomic physics and X-ray sources, laboratory astrophysics and laser particle acceleration. The readers should be aware that for some of the papers, only a short version is presented in this book: the extended version will be published in a topical issue of the European Physical Journal. The IFSA International Organizing Committee and Scientific Advisory Board appreciate the efforts of inertial fusion researchers worldwide in making IFSA 2005 an extremely successful conference. Jean-Claude Gauthier, technical committee co-chair Bruce Hammel, technical committee co-chair Hiroshi Azechi, technical committee co-chair Christine Labaune, proceedings co-editor

EDITORIAL: Focus on Carbon Nanotubes

NASA Astrophysics Data System (ADS)

2003-09-01

planes to stable loops caused by annealing M Endo, B J Lee, Y A Kim, Y J Kim, H Muramatsu, T Yanagisawa, T Hayashi, M Terrones and M S Dresselhaus Energetics and electronic structure of C70-peapods and one-dimensional chains of C70 Susumu Okada, Minoru Otani and Atsushi Oshiyama Theoretical characterization of several models of nanoporous carbon F Valencia, A H Romero, E Hernández, M Terrones and H Terrones First-principles molecular dynamics study of the stretching frequencies of hydrogen molecules in carbon nanotubes Gabriel Canto, Pablo Ordejón, Cheng Hansong, Alan C Cooper and Guido P Pez The geometry and the radial breathing mode of carbon nanotubes: beyond the ideal behaviour Jeno Kürti, Viktor Zólyomi, Miklos Kertesz and Sun Guangyu Curved nanostructured materials Humberto Terrones and Mauricio Terrones A one-dimensional Ising model for C70 molecular ordering in C70-peapods Yutaka Maniwa, Hiromichi Kataura, Kazuyuki Matsuda and Yutaka Okabe Nanoengineering of carbon nanotubes for nanotools Yoshikazu Nakayama and Seiji Akita Narrow diameter double-wall carbon nanotubes: synthesis, electron microscopy and inelastic light scattering R R Bacsa, E Flahaut, Ch Laurent, A Peigney, S Aloni, P Puech and W S Bacsa Sensitivity of single multiwalled carbon nanotubes to the environment M Krüger, I Widmer, T Nussbaumer, M Buitelaar and C Schönenberger Characterizing carbon nanotube samples with resonance Raman scattering A Jorio, M A Pimenta, A G Souza Filho, R Saito, G Dresselhaus and M S Dresselhaus FTIR-luminescence mapping of dispersed single-walled carbon nanotubes Sergei Lebedkin, Katharina Arnold, Frank Hennrich, Ralph Krupke, Burkhard Renker and Manfred M Kappes Structural properties of Haeckelite nanotubes Ph Lambin and L P Biró Structural changes in single-walled carbon nanotubes under non-hydrostatic pressures: x-ray and Raman studies Sukanta Karmakar, Surinder M Sharma, P V Teredesai, D V S Muthu, A Govindaraj, S K Sikka and A K Sood Novel properties of 0

Water Fountains in the Sky: Streaming Water Jets from Aging Star Provide Clues to Planetary-Nebula Formation

NASA Astrophysics Data System (ADS)

2002-06-01

Astronomers using the National Science Foundation's Very Long Baseline Array (VLBA) radio telescope have found that an aging star is spewing narrow, rotating streams of water molecules into space, like a jerking garden hose that has escaped its owner's grasp. The discovery may help resolve a longstanding mystery about how the stunningly beautiful objects called planetary nebulae are formed. Artist's Conception of W43A. Artist's conception of W43A, with the aging star surrounded by a disk of material and a precessing, twisted jet of molecules streaming away from it in two directions. Credit: Kirk Woellert/National Science Foundation. The astronomers used the VLBA, operated by the National Radio Astronomy Observatory, to study a star called W43A. W43A is about 8,500 light-years from Earth in the direction of the constellation Aquila, the eagle. This star has come to the end of its normal lifetime and, astronomers believe, is about to start forming a planetary nebula, a shell of brightly glowing gas lit by the hot ember into which the star will collapse. "A prime mystery about planetary nebulae is that many are not spherical even though the star from which they are ejected is a sphere," said Phillip Diamond, director of the MERLIN radio observatory at Jodrell Bank in England, and one of the researchers using the VLBA. "The spinning jets of water molecules we found coming from this star may be one mechanism for producing the structures seen in many planetary nebulae," he added. The research team, led by Hiroshi Imai of Japan's National Astronomical Observatory (now at the Joint Institute for VLBI in Europe, based in the Netherlands), also includes Kumiko Obara of the Mizusawa Astrogeodynamics Observatory and Kagoshima University; Toshihiro Omodaka, also of Kagoshima University; and Tetsuo Sasao of the Japanese National Astronomical Observatory. The scientists reported their findings in the June 20 issue of the scientific journal Nature. As stars similar to our Sun

Message from the Editor

NASA Astrophysics Data System (ADS)

Stambaugh, Ronald D.

2014-01-01

thank the following outgoing Board Members whose term of service was reached at the end of 2012: Keith Burrell, Atsushi Fukuyama, Guenter Janeschitz, Myeun Kwon, Alberto Loarte, Derek Stork, Tony Taylor and Kazuo Toi. We welcome the new Board Members who have joined the Board from the start of 2013: Pietro Barabaschi, Riccardo Betti, Rich Callis, Wonho Choi, Yasuaki Kishimoto, Joaquin Sánchez, Paul Thomas, Mickey Wade, Howard Wilson, Hiroshi Yamada and Steve Zinkle. We look forward to working with the Board to maintain the high standing of Nuclear Fusion . The Nuclear Fusion office and IOP Publishing Just as the journal depends on the authors, referees, and Board of Editors, so its success is also due to the tireless and largely unsung efforts of the IAEA Nuclear Fusion office in Vienna and IOP Publishing in Bristol. I would like to express my personal thanks to the team for the support that they have given to me, the authors and the referees. Season's greetings I would like to wish our readers, authors, referees, Board of Editors, and Vienna and Bristol office staff season's greetings and thank them for their contributions to Nuclear Fusion in 2013. References [1] Whyte D.G. et al 2010 I-mode: an H-mode energy confinement regime with L-mode particle transport in Alcator C-Mod Nucl. Fusion 50 105005 [2] Bosch H.-S. et al 2013 Technical challenges in the construction of the steady-state stellarator Wendelstein 7-X Nucl. Fusion 53 126001 [3] Chapman I.T. et al 2013 Power requirements for electron cyclotron current drive and ion cyclotron resonance heating for sawtooth control in ITER Nucl. Fusion 53 066001 [4] Knaster J. et al 2013 IFMIF: overview of the validation activities Nucl. Fusion 53 116001

PREFACE: Exploring surfaces and buried interfaces of functional materials by advanced x-ray and neutron techniques Exploring surfaces and buried interfaces of functional materials by advanced x-ray and neutron techniques

NASA Astrophysics Data System (ADS)

Sakurai, Kenji

2010-12-01

measurement. Advances in such technologies are bringing with them new opportunities in surface and buried interface science. In the not too distant future, we will publish a special issue or a book detailing such progress. Exploring surfaces and buried interfaces of functional materials by advanced x-ray and neutron techniques contents Lateral uniformity in chemical composition along a buried reaction front in polymers using off-specular reflectivity Kristopher A Lavery, Vivek M Prabhu, Sushil Satija and Wen-li Wu Orientation dependence of Pd growth on Au electrode surfaces M Takahasi, K Tamura, J Mizuki, T Kondo and K Uosaki A grazing incidence small-angle x-ray scattering analysis on capped Ge nanodots in layer structures Hiroshi Okuda, Masayuki Kato, Keiji Kuno, Shojiro Ochiai, Noritaka Usami, Kazuo Nakajima and Osami Sakata High resolution grazing-incidence in-plane x-ray diffraction for measuring the strain of a Si thin layer Kazuhiko Omote X-ray analysis of mesoporous silica thin films templated by Brij58 surfactant S Fall, M Kulij and A Gibaud Review of the applications of x-ray refraction and the x-ray waveguide phenomenon to estimation of film structures Kouichi Hayashi Epitaxial growth of largely mismatched crystals on H-terminated Si(111) surfaces Hidehito Asaoka Novel TiO2/ZnO multilayer mirrors at 'water-window' wavelengths fabricated by atomic layer epitaxy H Kumagai, Y Tanaka, M Murata, Y Masuda and T Shinagawa Depth-selective structural analysis of thin films using total-external-reflection x-ray diffraction Tomoaki Kawamura and Hiroo Omi Structures of Yb nanoparticle thin films grown by deposition in He and N2 gas atmospheres: AFM and x-ray reflectivity studies Martin Jerab and Kenji Sakurai Ga and As composition profiles in InP/GaInAs/InP heterostructures—x-ray CTR scattering and cross-sectional STM measurements Yoshikazu Takeda, Masao Tabuchi and Arao Nakamura Polarized neutron reflectivity study of a thermally treated MnIr/CoFe exchange bias system Naoki

Strong Coupling Gauge Theories in LHC ERA

NASA Astrophysics Data System (ADS)

Fukaya, H.; Harada, M.; Tanabashi, M.; Yamawaki, K.

2011-01-01

AdS/QCD, light-front holography, and the nonperturbative running coupling / Stanley J. Brodsky, Guy de Teramond and Alexandre Deur -- New results on non-abelian vortices - Further insights into monopole, vortex and confinement / K. Konishi -- Study on exotic hadrons at B-factories / Toru Iijima -- Cold compressed baryonic matter with hidden local symmetry and holography / Mannque Rho -- Aspects of baryons in holographic QCD / T. Sakai -- Nuclear force from string theory / K. Hashimoto -- Integrating out holographic QCD back to hidden local symmetry / Masayasu Harada, Shinya Matsuzaki and Koichi Yamawaki -- Holographic heavy quarks and the giant Polyakov loop / Gianluca Grignani, Joanna Karczmarek and Gordon W. Semenoff -- Effect of vector-axial-vector mixing to dilepton spectrum in hot and/or dense matter / Masayasu Harada and Chihiro Sasaki -- Infrared behavior of ghost and gluon propagators compatible with color confinement in Yang-Mills theory with the Gribov horizon / Kei-Ichi Kondo -- Chiral symmetry breaking on the lattice / Hidenori Fukaya [for JLQCD and TWQCD collaborations] -- Gauge-Higgs unification: Stable Higgs bosons as cold dark matter / Yutaka Hosotani -- The limits of custodial symmetry / R. Sekhar Chivukula ... [et al.] -- Higgs searches at the tevatron / Kazuhiro Yamamoto [for the CDF and D[symbol] collaborations] -- The top triangle moose / R. S. Chivukula ... [et al.] -- Conformal phase transition in QCD like theories and beyond / V. A. Miransky -- Gauge-Higgs unification at LHC / Nobuhito Maru and Nobuchika Okada -- W[symbol]W[symbol] scattering in Higgsless models: Identifying better effective theories / Alexander S. Belyaev ... [et al.] -- Holographic estimate of Muon g - 2 / Deog Ki Hong -- Gauge-Higgs dark matter / T. Yamashita -- Topological and curvature effects in a multi-fermion interaction model / T. Inagaki and M. Hayashi -- A model of soft mass generation / J. Hosek -- TeV physics and conformality / Thomas Appelquist -- Conformal

EDITORIAL: Focus on Carbon Nanotubes

NASA Astrophysics Data System (ADS)

2003-09-01

, P Umek, K Hernadi, P Marcoux, B Lukic, Cs Mikó, M Milas, R Gaál and L Forró Transitional behaviour in the transformation from active end planes to stable loops caused by annealing M Endo, B J Lee, Y A Kim, Y J Kim, H Muramatsu, T Yanagisawa, T Hayashi, M Terrones and M S Dresselhaus Energetics and electronic structure of C70-peapods and one-dimensional chains of C70 Susumu Okada, Minoru Otani and Atsushi Oshiyama Theoretical characterization of several models of nanoporous carbon F Valencia, A H Romero, E Hernández, M Terrones and H Terrones First-principles molecular dynamics study of the stretching frequencies of hydrogen molecules in carbon nanotubes Gabriel Canto, Pablo Ordejón, Cheng Hansong, Alan C Cooper and Guido P Pez The geometry and the radial breathing mode of carbon nanotubes: beyond the ideal behaviour Jeno Kürti, Viktor Zólyomi, Miklos Kertesz and Sun Guangyu Curved nanostructured materials Humberto Terrones and Mauricio Terrones A one-dimensional Ising model for C70 molecular ordering in C70-peapods Yutaka Maniwa, Hiromichi Kataura, Kazuyuki Matsuda and Yutaka Okabe Nanoengineering of carbon nanotubes for nanotools Yoshikazu Nakayama and Seiji Akita Narrow diameter double-wall carbon nanotubes: synthesis, electron microscopy and inelastic light scattering R R Bacsa, E Flahaut, Ch Laurent, A Peigney, S Aloni, P Puech and W S Bacsa Sensitivity of single multiwalled carbon nanotubes to the environment M Krüger, I Widmer, T Nussbaumer, M Buitelaar and C Schönenberger Characterizing carbon nanotube samples with resonance Raman scattering A Jorio, M A Pimenta, A G Souza

Cluster finds giant gas vortices at the edge of Earth's magnetic bubble

NASA Astrophysics Data System (ADS)

2004-08-01

the solar wind. The solar wind itself is launched from the Sun and carries the Sun’s magnetic field throughout the Solar System. Sometimes this magnetic field is aligned with Earth’s and sometimes it points in the opposite direction. When the two fields point in opposite directions, scientists understand how ‘doors’ in Earth’s field can open. This phenomenon, called ‘magnetic reconnection’, allows the solar wind to flow in and collect in the reservoir known as the boundary layer. On the contrary, when the fields are aligned they should present an impenetrable barrier to the flow. However, spacecraft measurements of the boundary layer, dating back to 1987, present a puzzle because they clearly show that the boundary layer is fuller when the fields are aligned than when they are not. So how is the solar wind getting in? Thanks to the data from the four formation-flying spacecraft of ESA’s Cluster mission, scientists have made a breakthrough. On 20 November 2001, the Cluster flotilla was heading around from behind Earth and had just arrived at the dusk side of the planet, where the solar wind slides past Earth’s magnetosphere. There it began to encounter gigantic vortices of gas at the magnetopause, the outer ‘edge’ of the magnetosphere. “These vortices were really huge structures, about six Earth radii across,” says Hiroshi Hasegawa, Dartmouth College, New Hampshire who has been analysing the data with help from an international team of colleagues. Their results place the size of the vortices at almost 40 000 kilometres each, and this is the first time such structures have been detected. These vortices are known as products of Kelvin-Helmholtz instabilities (KHI). They can occur when two adjacent flows are travelling with different speeds, so one is slipping past the other. Good examples of such instabilities are the waves whipped up by the wind slipping across the surface of the ocean. Although KHI-waves had been observed before, this is the

EDITORIAL: Message from the Editor Message from the Editor

NASA Astrophysics Data System (ADS)

Thomas, Paul

2010-02-01

award was Steven A. Sabbagh et al for the paper entitled 'Resistive wall stabilized operation in rotating high beta NSTX plasmas' (Nucl. Fusion 46 635-644). Reviews Last year I announced a revival of Nuclear Fusion Reviews, following a decision by the Board of Editors. 'A review of zonal flow experiments', by Akihide Fujisawa was the first fruit of this. In 2010, we are expecting to publish further review articles, the first of which is entitled 'Gyrokinetic simulations of turbulent transport' by Xavier Garbet, Yasuhiro Idomura, Laurent Villard and Tomo-Hiko Watanabe. Letters At the 2009 Board of Editors Meeting in Atlanta, the current letters procedure was summarized and it was noted that the peer review time for Letters is quite variable. Some are accepted within a month of submission, others take longer. Since the purpose of Letters is to provide a route for rapid communication, this is quite an important matter. It was agreed that the Board of Editors would play a more active role in the Letter approval process. If a reviewer asks for a second revision the Editor or a Board of Editors member will be queried as to whether the submission should still be treated as a Letter rather than a regular Paper. The Board of Editors The following Board of Editors members reached the end of their term in 2009: Amanda Hubbard, Yaroslav Kolesnichenko, Kunioki Mima, Boris Sharkov and Michael Ulrickson. On behalf of the Nuclear Fusion Office and the Chairman of the Board of Editors, Mitsuru Kikuchi, I would like to thank them for their efforts in support of the journal. At the same time, we welcomed: Hiroshi Azechi, Xuru Duan, Richard Hawryluk, Sergey Konovalov, Bruce Lipschultz, Peter Norreys, Francesco Romanelli, Tony Taylor and Hartmut Zohm. I am sure that such an illustrious group does not need any introduction to the readers of Nuclear Fusion and I am confident that the new members can only further the success of the journal. It is with great sadness that I have to note the

25 years of pulsed laser deposition

NASA Astrophysics Data System (ADS)

Lorenz, Michael; Ramachandra Rao, M. S.

2014-01-01

-of-experiment schemes to shorten the optimization effort for new materials is presented at the end of this methodical section. Further, the issue contains original papers on other prominent PLD activities, such as dielectric SrTiO3 films, magnetic and spintronic La1-x Srx MnO3, and multiferroic BiFeO3. The role of cationic and anionic point defects and their control during PLD is discussed based on the examples of the simple perovskite SrMoO3 and the double perovskite Sr2CrWO6. The final paper in this thin-film-related section provides a good account of in situ high-temperature surface smoothing of Ba2TiSi2O8 fresnoite films and growth from glassy fresnoite targets with 100% theoretical density. The flexibility of the PLD technique has resulted in several schemes to grow nanostructures, which is unique in the nature of PLD. Okada's group succeeded in controlling the growth density of ZnO nanowires by varying the thickness of the ZnO buffer layer, and nanowalls could be patterned by interference phenomenon using laser irradiation. PLD-based methods are further used to grow metal nanoparticle plasmonic films with packing densities up to 1011 particles cm-2, and ZnO nanowires from screw dislocation driven two-dimensional hexagonal stacking on diamond substrates. Overall, this special issue provides an up-to-date overview on the current status, potential and the extraordinary success and development of PLD from a simple laboratory growth method to a viable industrial technique for fabrication of advanced oxide thin films. We thank all the authors and reviewers for their contributions to this special issue. We would like to place on record our gratitude for the timely help extended by the editorial team, Dr Olivia Roche, Dean Williams and Colin Adcock. References [1] Dijkkamp D, Venkatesan T, Wu X D, Shaheen S A, Jisrawi N, Min-Lee Y-H, McLean W L and Croft M 1987 Preparation of YBaCu oxide superconductor thin films using pulsed laser evaporation from high T c bulk material Appl. Phys. Lett

The evidences of progressive pressurization of volcanic conduit as driving forces of unrest phenomena analyzed via modelling of multiplatform geodetic measurements: Fernandina (GALAPAGOS) and Maunaloa (HAWAII) case studies

NASA Astrophysics Data System (ADS)

Pepe, Susi; Castaldo, Raffaele; Casu, Francesco; D'Auria, Luca; De Luca, Claudio; De Novellis, Vincenzo; Solaro, Giuseppe; Tizzani, Pietro

2017-04-01

-12940. Okada, Y. Surface deformation due to shear and tensile faults in a half-space. Bull. Seism. Soc. Am. 75, 1135-1154 (1985). Sansosti, E., Berardino, P., Bonano, M., Calò, F., Castaldo, R., Casu, F., Manunta, M., Manzo, M., Pepe, A., Pepe, S., Solaro, G., Tizzani, P., Zeni, G., Lanari, R. (2014). How second generation SAR systems are impacting the analysis of ground deformation. International Journal of Applied Earth Observation and Geoinformation, 28, doi:10.1016/j.jag.2013.10.007. Tizzani, P., Battaglia, M., Zeni, G., Atzori, S., Berardino, P., Lanari, R. (2009). Uplift and magma intrusion at Long Valley caldera from InSAR and gravity measurements, Geology, January 2009 37; no.1; p. 63-66; doi:10.1130/G25318A.1 Tizzani, P., Battaglia, M., Castaldo, R., Pepe, A., Zeni, G., Lanari, R. (2015). Magma and fluid migration at Yellowstone Caldera in the last three decades inferred from InSAR, leveling, and gravity measurements. J. Geophys. Res. Solid Earth, 120, 2627-2647. doi: 10.1002/2014JB011502. Yang, X. M., Davis, P. M., and Dieterich, J. H. (1988), Deformation from inflation of a dipping finite prolate spheroid in an elastic half-space as a model for volcanic stressing. Journal of Geophysical Research: Solid Earth (1978-2012), 93(B5), 4249-4257.

3rd International Conference on Turbulent Mixing and Beyond

NASA Astrophysics Data System (ADS)

Abarzhi, Snezhana I.; Gauthier, Serge; Keane, Christopher J.; Niemela, Joseph J.

2013-07-01

the accepted contributions have been reviewed by the international team of 27 members of the Scientific Committee, with every contribution considered by four to eleven experts. In the majority of cases, the opinions of referees with diverse backgrounds and expertise converged. In 2011, the award 'Turbulent Mixing and Beyond for Youth' was issued to Gregory P Bewley (Max Plank Institute for Dynamics and Self-Organization, Germany) and Robert Zimmermann (Ecole Normale Superieure de Lyon, France) in recognition of their contributions to TMB-related scientific problems. The Best Poster Award was issued by Physica Scripta to Michael Winkler (University of Potsdam, Germany) in recognition of their poster presentation at TMB-2011. 5. Organization and acknowledgments The Third International Conference on Turbulent Mixing and Beyond was organized by the following members of the Organizing Committee: • Snezhana I Abarzhi (Chairperson, University of Chicago, USA) • Malcolm J Andrews (Los Alamos National Laboratory, USA) • Hiroshi Azechi (Institute for Laser Engineering, Osaka, Japan) • Vladimir E Fortov (Institute for High Energy Density, Russia) • Boris Galperin (Organizer of the Special Course, University of South Florida, USA) • Serge Gauthier (Commissariat à l'Energie Atomique, France) • Christopher J Keane (Lawrence Livermore National Laboratory, USA) • Joseph J Niemela (Local Organizer, International Centre for Theoretical Physics, Italy) • Katepalli R Sreenivasan (New York University, USA) The conference and course were sponsored by several agencies and institutions in the USA, Europe, Russia and Japan. The Organizing Committee of the TMB-2011 gratefully acknowledges support of the: • National Science Foundation (NSF), USA. Programmes: Plasma Physics; Physics Education and Interdisciplinary Research; Astronomy and Astrophysics; Applied Mathematics; Particulate and Multiphase Processes; Combustion, Fire and Plasma Systems • European Office of

X-ray Fluorescence Observations of the Moon by SMART-1/D-CIXS

NASA Astrophysics Data System (ADS)

Grande, Manuel; Swinyard, B.; Joy, K. H.; Kellett, Barry J.; Crawford, Ian A.; Howe, Chris J.

2008-09-01

times as abundant in the Crisium basalts than in the adjacent highlands, the Ca abundance is only some 20% less. Essentially the same trend is obtained by comparing the Fe and Ca Lunar Prospector data [3], which imply a factor of 2 difference in Fe, but less than a 10% difference in Ca, between these two footprints. Figure 2 shows a comparison of a spectrum obtained close to the Apollo 12 site, with a modelled spectrum, derived from averaged Apollo 12 soil compositions [6]. The match between data (black line) and model (grey) is reasonable, with the exception of the low energy continuum, where the model clearly needs refinement. We have extended our observations to comparison of Lunar near and farside, and by careful analysis enabled new elemental lines to be observed (Swinyard et al 2008)[8]. Conclusions: The instrument demonstrates the capability of this method to perform X-ray fluorescence measurements of the Moon. A number of rock forming elements have been successfully detected from the Moon during solar flare events, and we have made the first unambiguous remote detection of Calcium from the lunar surface. For more detail see Grande et al 2007 [7].All of this has been achieved during solar minimum and proves that the technique will be highly suitable for the upcoming Chandrayaan- 1 mission [9]), when the mission will take place during the rising phase of the solar cycle, and for which it forms part of the core payload. Acknowledgements We acknowledge the contributions of the entire DCIXS team (M. Grande, J. Huovelin, B. Kellett, R Browning, C. Howe, B. Swinyard, C. H. Perry, S. Dunkin, N. Waltham, B. Kent, D. Parker, I. Crawford, K. Joy, J. Guest, S. Russell, M. Grady, A. Christou, H. Alleyne, D. Hughes, C. D. Murray, S. Maurice C. L. Duston , O. Gasnaut, N. Bhandari, R. Lundin, S. Barabash, D Lawrence, V. Fernandes, I. Casanova, M. Kato, T. Okada, P. Clark, B. Foing, D. Heather, M. Wieczorek). We acknowledge the SMART-1 teams from ESA/ESTEC project, industrial

PREFACE Turbulent Mixing and Beyond

NASA Astrophysics Data System (ADS)

Abarzhi, Snezhana I.; Gauthier, Serge; Niemela, Joseph J.

2010-12-01

confined plasmas, magneto-convection, magneto-rotational instability, dynamo; Canonical plasmas: coupled plasmas, anomalous resistance, ionosphere; Physics of atmosphere: environmental fluid dynamics, weather forecasting, turbulent flows in stratified media and atmosphere, non-Boussinesq convection; Geophysics and Earth science: mantle-lithosphere tectonics, oceanography, turbulent convection under rotation, planetary interiors; Combustion: dynamics of flames and fires, deflagration-to-detonation transition, blast waves and explosions, flows with chemical reactions, flows in jet engines; Mathematical aspects of non-equilibrium dynamics: vortex dynamics, singularities, discontinuities, asymptotic dynamics, weak solutions, well- and ill-posedness, continuous transports out of thermodynamic equilibrium; Stochastic processes and probabilistic description: long-tail distributions and anomalous diffusion, data assimilation and processing methodologies, error estimate and uncertainty quantification, statistically unsteady processes; Advanced numerical simulations: continuous DNS/LES/RANS, molecular dynamics, Monte-Carlo, predictive modeling, validation and verification of numerical models; Experimental diagnostics: model experiments in high energy density and low energy density regimes, plasma diagnostics, fluid flow visualizations and control, opto-fluidics, novel optical methods, holography, advanced technologies. TMB-2009 was organized by the following members of the Organizing Committee: Snezhana I Abarzhi (chairperson, Chicago, USA) Malcolm J Andrews (Los Alamos National Laboratory, USA) Sergei I Anisimov (Landau Institute for Theoretical Physics, Russia) Hiroshi Azechi (Institute of Laser Engineering, Osaka, Japan) Serge Gauthier (Commissariat à l'Energie Atomique, France) Christopher J Keane (Lawrence Livermore National Laboratory, USA) Robert Rosner (Argonne National Laboratory, USA) Katepalli R Sreenivasan (International Centre for Theoretical Physics, Italy) Alexander