1,456 research outputs found
Origins of hydrocarbons in the Sagara oil field, central Japan
No full textWe collected free-gas and in situ fluid samples up to a depth of 200.6 m from the Sagara oil field, central Japan (34°44′N, 138°15′E), during the Sagara Drilling Program (SDP) and measured the concentrations and stable carbon isotopic compositions of CH4 and C2H6 in the samples. A combination of the CH4/C2H6 ratios with the carbon isotope ratios of methane indicates that the hydrocarbon gases are predominantly of thermogenic origin at all depths. The isotope signature of hydrocarbon gases of δ13CCH4 < δ13CC2H6 suggests that these gases in the Sagara oil field are not generated by polymerization, but by the decomposition of organic materials
Letter from K. Sagara to Marue and Toshiko Horita
No full textA handwritten letter from K. Sagara on behalf of Poston Cooperative Enterprises, Inc. regarding the "certificate of indebtedness" for Marue and Toshiko Horita.The Horita Family Papers (1940-2010, undated) collection contains documents from the Horita family, a Japanese American family from the Los Angeles area. The collection focuses on married couple Chitoshi "Harry" Horita (1896-1990) and Marue Nakashima Horita (1901-1982) and their extended family and includes records of the family's incarceration at the Poston (Colorado River) incarceration camp, research into the family's history, photographs, and correspondence
Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine induce the tyrosyl phosphorylation of 45 kDa protein in parallel with its stimulation of superoxide generation in human neutrophils
No full textHuman peripheral blood polymorphonuclear leukocytes were preincubated with lanthionine, S-(2-aminoethyl)-L-cysteine, and some of their derivatives found in normal human urine and bovine brain, Among these compounds, lanthionine ketimine and to a lesser extent S-(2-aminoethyl)-L-cysteine ketimine enhanced the N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation. These ketimines induced tyrosyl phosphorylation of 45 kDa protein of cells. The tyrosyl phosphorylation was markedly increased with time, and the phosphorylation process was dependent on the concentration of both ketimines. However, lanthionine, 1,4-thiomorpholine-3,5-dicarboxylic acid, S-(2- aminoethyl)-L-cysteine and 1,4-thiomorpholine-3-carboxylic acid were without effect both on superoxide generation and on tyrosyl phosphorylation of 45 kDa protein, Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine also enhanced superoxide generation induced by opsonized zymosan but not the one induced by arachidonic acid and phorbol 12-myristate 13-acetate. Ketimine-primed superoxide generation and tyrosyl phoshorylation of 45 kDa protein were inhibited by genistein, an inhibitor of protein tyrosine kinase, but not by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C
NF-κB and TNF-α: A positive autocrine loop in human lung mast cells?
No full textThe generation of cytokines, particularly TNF-α, by mast cells is crucial for the initiation of the allergic response. A key transcription factor involved in the synthesis of TNF-α is NF-κB. Using a mAb specific for the activated form of NF-κB, immunocytochemistry, confocal microscopy, and gel shift assays have been used in conjunction to localize this transcription factor to human lung mast cells and to study its activation. Activation of mast cells with stem cell factor (10 ng/ml) and anti-IgE (1 μg/ml) induced maximal activation of NF-κB at 4 and 2 h, respectively. In contrast, with TNF-α (5 ng/ml) maximal activation occurred within 15 min. Parallel falls in IκB were demonstrated. Confocal microscopy demonstrated the localization of the activated form of NF-κB to the nuclei of activated mast cells. NF-κB activation was verified using a gel shift assay. A supershift assay showed mast cell NF-κB to be composed primarily of p50 with smaller amounts of p65. No interaction with Abs for Rel-A, c-Rel, Rel-B, and p52 was seen. Immunocytochemistry and ELISAs showed TNF-α to be stored within mast cells and released into the extracellular environment following activation. The possible participation of TNF-α generated by mast cells in NF-κB activation by anti-IgE was investigated using a blocking Ab for TNF-α. The blocking Ab reduced NF-κB activation by anti-IgE by >50%, suggesting that the release of preformed mast cell-associated TNF-α acts as a positive autocrine feedback signal to augment NF-κB activation and production of further cytokine, including GM-CSF and IL-8.The mast cell has long been considered a pivotal effector cell in allergic disease by virtue of its capacity to respond rapidly to provoking stimuli and its ability to release a wide range of preformed and newly generated proinflammatory mediators. The generation by mast cells of cytokines likely to be crucial for the initiation and maintenance of the allergic responses is now well established (reviewed in Ref. 1). One of the major mast cell-derived cytokines is TNF-α, a pleotropic cytokine encoded on chromosome 6, which exists in its biologically active form as a homotrimer of a 17-kDa subunit cleaved proteolytically from its 26-kDa cell surface-associated form (2, 3). It has a broad range of biological activities associated with inflammatory diseases, many of which are pertinent to allergy (reviewed in Ref. 4). Preformed immunoreactive TNF-α has been observed within the granules of mast cells from human skin (5) and lung (6), suggesting its rapid availability following mast cell activation. That this preformed TNF-α may be biologically relevant has been shown by its release within 2 min of allergen challenge in parallel with tryptase in patients with allergic rhinitis (7).A key transcription factor involved in the synthesis of TNF-α is NF-κB. NF-κB, which also regulates the transcription of a number of proinflammatory molecules, including GM-CSF, IL-8, IL-2, IL-6, E-selectin, ICAM-1, and VCAM-1, may be of variable composition but is classically presented in a wide range of cells as a heterodimer comprising of p50 and p65, each of which contains the 300-aa NF-κB/rel/dorsal domain (8, 9). In resting cells NF-κB is present in the cytoplasm in an inactive form reversibly bound to proteins of the IκB family (10). On cell stimulation by a range of stimuli including TNF-α, IL-1, IL-2, leukotriene B4, viruses, and free radicals (10), IκB undergoes proteolysis and the nuclear location site of NF-κB becomes revealed. This activation of NF-κB is necessary for its translocation across the nuclear membrane and binding to its target gene promoter regions. In addition to increasing the transcription of cytokines and adhesion proteins, NF-κB also increases the transcription of IκB, thus leading to its own inactivation and subsequent termination of the response.In human lung mast cells, we demonstrate the presence and activation of NF-κB and the generation of TNF-α. We then examined the hypothesis that when mast cells are stimulated immunologically, the release of preformed TNF-α acts as a positive autocrine feedback signal to augment NF-κB activation.</p
Effect of cystathionine and cystathionine metabolites on the phosphorylation of tyrosine residues in human neutrophils
No full textThe effect of cystathionine and cystathionine metabolites found in the urine of patients with cystathioninuria on the phosphorylation of tyrosine residues was studied with human peripheral blood polymorphonuclear leukocytes. Among the cystathionine metabolites, cystathionine ketimine markedly increased phosphorylation of a 45 kDa protein with time and the phosphorylation depended on the concentration of cystathionine ketimine, while cystathionine and the reduced form of cystathionine ketimine (cyclothionine) did not increase the phosphorylation of the 45 kDa protein. The phosphorylation of the 45 kDa protein induced by cystathionine ketimine was inhibited by genistein and herbimycin A, inhibitors of tyrosine kinase, but was not inhibited by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine and staurosporine, inhibitors of protein kinase C. (C) 1996 Academic Press, Inc
සිදත් සඟරාවේ ලිංග භේදය පිළිබඳ විමර්ශනාත්මක අධ්යයනයක්
No full textThe only book currently available to learn Sinhala grammar is Sidath Sagara. This was written in the thirteenth century. Sidath Sagara talks about gender, only two genders as masculine and feminine nouns. Although Sidath Sagara says that there are two genders, according to the Sinhala practice, three genders are implemented. The third gender is the neuter gender. Sinhala gender has been introduced after paying attention to the gender difference in Pali and Sanskrit languages. Understand gender discrimination in Sidath Sagara without knowledge of Pali and Sanskrit languages. This is a problematic situation. Because of this, scholars refuse to explain the gender of the Sidath Sagara. Some people justify sidath Sagara's gender bias. This research was carried out in order to properly investigate Sidath Sagarava's gender examination and arrive at conclusions. why neuter gender is not valid in Sinhala in Sidath Sagarava's gender examination? is kept as the research problem. The main objective of the research was to study gender discrimination in Sidath Sagara. Studying the various ideologies that have been presented regarding gender discrimination, Sidath Sagara's research on gender and reaching balanced conclusions began. Sidath Sagara was kept as the primary source. Various editions of Sidath Sagara, Sinhala grammar books and Journals written in this regard, newspaper articles etc. were the secondary sources by studying the gender difference in Sidath Sagara and grammar tradition of Sinhala, it was kept as the basis of the research that the existing problems regarding gender discrimination in Sidath Sagara will be resolved. the research sample was only for the work of Sidath Sagara and Sinhala grammar tradition. From the data analysis of the research 1. Gender distiction as discrimination in Sidath Sagara is a gender discrimination used for poetry 2. the author of Sidath Sagara explains focusing on the gender distinction in Pali and Sanskrit languages and not focusing on the Sinhala language. 3. it is uncinded the three conclusions that Sidath Sagara's gender distinction is a traditional Sinhala grammatical tradition
Allergen activates peripheral blood eosinophil nuclear factor-kappaB to generate granulocyte macrophage-colony stimulating factor, tumour necrosis factor-alpha and interleukin-8
No full textBackground Allergic inflammation is characterized by the influx and activation of eosinophils. Cytokines generated by both resident and infiltrating cells are responsible for the initiation and maintenance of this pathogenesis. This study focuses on allergen‐induced activation of eosinophil NF‐κB and generation of granulocyte macrophage‐colony stimulating factor (GM‐CSF), TNF‐α, and IL‐8.Methods Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient sedimentation and negative magnetic affinity chromatography. NF‐κB activation by 10 μg/mL house dust mite (HDM) extract was demonstrated immunocytochemically using a monoclonal antibody against the active form of NF‐κB (NF‐κBa). The authenticity of NF‐κB was confirmed by Western blot. Cytokine production was assessed both by immuno‐staining of eosinophils and by assay of cytokines in the cell supernatant.Results Activation of peripheral blood eosinophils from atopic, but not non‐atopic, donors induced activation of NF‐κB, which peaked at 4 h and was accompanied by a decline in IκB‐α. The activation of authentic NF‐κB was confirmed in gel shift assays. Supershift assays showed p65 to be the major subunit of eosinophil NF‐κB. Immunofluorescent confocal microscopy demonstrated localization of NF‐κBa to the nucleus. Following activation, cytokine immunoreactivity was seen in a fraction of the eosinophils and cytokines were released into the supernatant. The NF‐κB inhibitors, calpain inhibitor 1 (10 μm), pentoxifylline (0.5 mm), pyrrolidine dithiocarbamate (PDTC, 10 μm) or gliotoxin (1 pg/mL) reduced the generation of GM‐CSF, TNF‐α and IL‐8 in parallel with their inhibition of NF‐κB.Conclusions HDM allergen activates human eosinophil NF‐κB leading to the production of the cytokines GM‐CSF, TNF‐α and IL‐8. We speculate that a role for eosinophil NF‐κB‐dependent cytokines is to act as an autocrine loop augmenting the survival of eosinophils in vivo.</p
Scapinin, the Protein Phosphatase 1 Binding Protein, Enhances Cell Spreading and Motility by Interacting with the Actin Cytoskeleton
No full textCopyright (c) 2009 Sagara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Scapinin, also named phactr3, is an actin and protein phosphatase 1 (PP1) binding protein, which is expressed in the adult brain and some tumor cells. At present, the role(s) of scapinin in the brain and tumors are poorly understood. We show that the RPEL-repeat domain of scapinin, which is responsible for its direct interaction with actin, inhibits actin polymerization in vitro. Next, we established a Hela cell line, where scapinin expression was induced by tetracycline. In these cells, expression of scapinin stimulated cell spreading and motility. Scapinin was colocalized with actin at the edge of spreading cells. To explore the roles of the RPEL-repeat and PP1-binding domains, we expressed wild-type and mutant scapinins as fusion proteins with green fluorescence protein (GFP) in Cos7 cells. Expression of GFP-scapinin (wild type) also stimulated cell spreading, but mutation in the RPEL-repeat domain abolished both the actin binding and the cell spreading activity. PP1-binding deficient mutants strongly induced cell retraction. Long and branched cytoplasmic processes were developed during the cell retraction. These results suggest that scapinin enhances cell spreading and motility through direct interaction with actin and that PP1 plays a regulatory role in scapinin-induced morphological changes.Articleapplication/pdfPLOS ONE. 4(1):e4247 (2009)journal articl
Dispersible formulation of artemether/lumefantrine: specifically developed for infants and young children.
No full textInfants and children under five years of age are the most vulnerable to malaria with over 1,700 deaths per day from malaria in this group. However, until recently, there were no WHO-endorsed paediatric anti-malarial formulations available. Artemisinin-based combination therapy is the current standard of care for patients with uncomplicated falciparum malaria in Africa. Artemether/lumefantrine (AL) meets WHO pre-qualification criteria for efficacy, safety and quality. Coartem, a fixed dose combination of artemether and lumefantrine, has consistently achieved cure rates of >95% in clinical trials. However, AL tablets are inconvenient for caregivers to administer as they need to be crushed and mixed with water or food for infants and young children. Further, in common with other anti-malarials, they have a bitter taste, which may result in children spitting the medicine out and not receiving the full therapeutic dose. There was a clear unmet medical need for a formulation of AL specifically designed for children. Ahead of a call from WHO for child-friendly medicines, Novartis, working in partnership with Medicines for Malaria Venture (MMV), started the development of a new formulation of AL for infants and young children: Coartem Dispersible. The excellent efficacy, safety and tolerability already demonstrated by AL tablets were confirmed with dispersible AL in a large trial comparing the crushed tablets with dispersible tablets in 899 African children with falciparum malaria. In the evaluable population, 28-day PCR-corrected cure rates of >96% were achieved. Further, its sweet taste means that it is palatable for children, and the dispersible formulation makes it easier for caregivers to administer than bitter crushed tablets. Easing administration may foster compliance, hence improving therapeutic outcomes in infants and young children and helping to preserve the efficacy of ACT
NPAT expression is regulated by E2F and is essential for cell cycle progression
No full textNPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G1/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G1/S-phase boundary in growth-stimulated cells and that the NPAT promoter responds to activation by E2F proteins. We demonstrate that endogenous E2F proteins interact with the promoter of the NPAT gene in vivo and that induced expression of E2F1 stimulates NPAT mRNA expression, supporting the idea that the expression of NPAT is regulated by E2F. Consistently, we find that the E2F sites in the NPAT promoter are required for its activation during the G1/S-phase transition. Moreover, we show that the expression of NPAT accelerates S-phase entry in cells released from quiescence. The inhibition of NPAT expression by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription, our findings indicate that NPAT links E2F to the activation of S-phase-specific histone gene transcription
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