Zhou, Jingling; Feng, Gaoqian; Beeson, James; Hogarth, P Mark; Rogerson, Stephen J; Yan, Yan; Jaworowski, Anthony
2015-07-07
With more than 600,000 deaths from malaria, mainly of children under five years old and caused by infection with Plasmodium falciparum, comes an urgent need for an effective anti-malaria vaccine. Limited details on the mechanisms of protective immunity are a barrier to vaccine development. Antibodies play an important role in immunity to malaria and monocytes are key effectors in antibody-mediated protection by phagocytosing antibody-opsonised infected erythrocytes (IE). Eliciting antibodies that enhance phagocytosis of IE is therefore an important potential component of an effective vaccine, requiring robust assays to determine the ability of elicited antibodies to stimulate this in vivo. The mechanisms by which monocytes ingest IE and the nature of the monocytes which do so are unknown. Purified trophozoite-stage P. falciparum IE were stained with ethidium bromide, opsonised with anti-erythrocyte antibodies and incubated with fresh whole blood. Phagocytosis of IE and TNF production by individual monocyte subsets was measured by flow cytometry. Ingestion of IE was confirmed by imaging flow cytometry. CD14(hi)CD16+ monocytes phagocytosed antibody-opsonised IE and produced TNF more efficiently than CD14(hi)CD16- and CD14(lo)CD16+ monocytes. Blocking experiments showed that Fcγ receptor IIIa (CD16) but not Fcγ receptor IIa (CD32a) or Fcγ receptor I (CD64) was necessary for phagocytosis. CD14(hi)CD16+ monocytes ingested antibody-opsonised IE when peripheral blood mononuclear cells were reconstituted with autologous serum but not heat-inactivated autologous serum. Antibody-opsonised IE were rapidly opsonised with complement component C3 in serum (t1/2 = 2-3 minutes) and phagocytosis of antibody-opsonised IE was inhibited in a dose-dependent manner by an inhibitor of C3 activation, compstatin. Compared to other monocyte subsets, CD14(hi)CD16+ monocytes expressed the highest levels of complement receptor 4 (CD11c) and activated complement receptor 3 (CD11b) subunits. We show a special role for CD14(hi)CD16+ monocytes in phagocytosing opsonised P. falciparum IE and production of TNF. While ingestion was mediated by Fcγ receptor IIIa, this receptor was not sufficient to allow phagocytosis; despite opsonisation with antibody, phagocytosis of IE also required complement opsonisation. Assays which measure the ability of vaccines to elicit a protective antibody response to P. falciparum should consider their ability to promote phagocytosis and fix complement.
McGregor, S J; Brock, J H; Briggs, J D; Junor, B J
1987-01-01
IgG, C3 and transferrin in peritoneal dialysis effluent of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were 1%-2% of those in serum. In contrast, the values in normal peritoneal fluid were not significantly different from those in serum. The three proteins correlated with each other in peritoneal dialysis effluent, but were independent of the amount in the corresponding patients' sera. There was also an overall inverse correlation between total protein in peritoneal dialysis effluent and time on CAPD during the first 6 months of treatment but not thereafter, which suggests that changes in membrane permeability occur during the early months. In peritoneal dialysis effluent, but not in normal peritoneal fluid, there was a correlation between opsonising capacity and IgG or C3 concentrations. An inverse correlation between opsonic activity of peritoneal dialysis effluent and frequency of peritonitis was also found. Peritoneal dialysis effluent permitted significantly faster multiplication of Staphylococcus epidermidis than sera or normal peritoneal fluid, and the growth rate correlated inversely with the transferrin levels in peritoneal dialysis effluent. Overall IgG, C3 and transferrin in peritoneal dialysis effluent are inadequate for optimal opsonising and bacteriostatic activity, and the peritoneal cavities of CAPD patients are therefore immunocompromised sites.
Ataíde, Ricardo; Hasang, Wina; Wilson, Danny W; Beeson, James G; Mwapasa, Victor; Molyneux, Malcolm E; Meshnick, Steven R; Rogerson, Stephen J
2010-05-25
Pregnant women residing in malaria endemic areas are highly susceptible to Plasmodium falciparum malaria, particularly during their first pregnancy, resulting in low birth weight babies and maternal anaemia. This susceptibility is associated with placental sequestration of parasitised red blood cells expressing pregnancy-specific variant surface antigens. Acquisition of antibodies against these variant surface antigens may protect women and their offspring. Functions of such antibodies may include prevention of placental sequestration or opsonisation of parasitised cells for phagocytic clearance. Here we report the development and optimisation of a new high-throughput flow cytometry-based phagocytosis assay using undifferentiated Thp-1 cells to quantitate the amount of opsonizing antibody in patient sera, and apply this assay to measure the impact of HIV on the levels of antibodies to a pregnancy malaria-associated parasite line in a cohort of Malawian primigravid women. The assay showed high reproducibility, with inter-experimental correlation of r(2) = 0.99. In primigravid women, concurrent malaria infection was associated with significantly increased antibodies, whereas HIV decreased the ability to acquire opsonising antibodies (Mann-Whitney ranksum: p = 0.013). This decrease was correlated with HIV-induced immunosuppression, with women with less than 350 x 10(6) CD4+ T- cells/L having less opsonising antibodies (coef: -11.95,P = 0.002). Levels of antibodies were not associated with protection from low birth weight or anaemia. This flow cytometry-based phagocytosis assay proved to be efficient and accurate for the measurement of Fc-receptor mediated phagocytosis-inducing antibodies in large cohorts. HIV was found to affect mainly the acquisition of antibodies to pregnancy-specific malaria in primigravidae. Further studies of the relationship between opsonising antibodies to malaria in pregnancy and HIV are indicated.
Antibody- and TRIM21-dependent intracellular restriction of Salmonella enterica.
Rakebrandt, Nikolas; Lentes, Sabine; Neumann, Heinz; James, Leo C; Neumann-Staubitz, Petra
2014-11-01
TRIM21 ('tripartite motif-containing protein 21', Ro52) is a ubiquitously expressed cytosolic Fc receptor, which has a potent role in protective immunity against nonenveloped viruses. TRIM21 mediates intracellular neutralisation of antibody-coated viruses, a process called ADIN (antibody-dependent intracellular neutralisation). Our results reveal a similar mechanism to fight bacterial infections. TRIM21 is recruited to the intracellular pathogen Salmonella enterica in epithelial cells early in infection. TRIM21 does not bind directly to S. enterica, but to antibodies opsonising it. Most importantly, bacterial restriction is dependent on TRIM21 as well as on the opsonisation state of the bacteria. Finally, Salmonella and TRIM21 colocalise with the autophagosomal marker LC3, and intracellular defence is enhanced in starved cells suggesting an involvement of the autophagocytic pathway. Our data extend the protective role of TRIM21 from viruses to bacteria and thereby strengthening the general role of ADIN in cellular immunity. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
2012-01-01
Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses. PMID:22934974
Ruchaud-Sparagano, Marie-Hélène; Mills, Ross; Scott, Jonathan; Simpson, A John
2014-10-01
Monophosphoryl lipid A (MPLA) is a lipopolysaccharides (LPS) derivative associated with neutrophil-dependent anti-inflammatory outcomes in animal models of sepsis. Little is known about the effect of MPLA on neutrophil function. This study sought to test the hypothesis that MPLA would reduce release of cytotoxic mediators from neutrophils without impairing bacterial clearance. Neutrophils were isolated from whole blood of healthy volunteers. The effects of MPLA and LPS on autologous serum-opsonised Pseudomonas aeruginosa killing by neutrophils and phagocytosis of autologous serum-opsonised zymosan were examined. Neutrophil oxidative burst, chemotaxis, enzyme and cytokine release as well as Toll-like receptor 4 (TLR4) expression were assessed following exposure to LPS or MPLA. LPS, but not MPLA, induced significant release of superoxide and myeloperoxidase from neutrophils. However, MPLA did not impair neutrophil capacity to ingest microbial particles and kill P. aeruginosa efficiently. MPLA was directly chemotactic for neutrophils, involving TLR4, p38 mitogen-activated protein kinase and tyrosine and alkaline phosphatases. LPS, but not MPLA, impaired N-formyl-methionyl-leucyl phenylalanine-directed migration of neutrophils, increased surface expression of TLR4, increased interleukin-8 release and strongly activated the myeloid differentiation primary response 88 pathway. Phosphoinositide 3-kinase inhibition significantly augmented IL-8 release from MPLA-treated neutrophils. The addition of MPLA to LPS-preincubated neutrophils led to a significant reduction in LPS-mediated superoxide release and TLR4 surface expression. Collectively, these findings suggest that MPLA directs efficient chemotaxis and bacterial killing in human neutrophils without inducing extracellular release of cytotoxic mediators and suggest that MPLA warrants further attention as a potential therapeutic in human sepsis.
Goh, Yun Shan; Armour, Kathryn L; Clark, Michael R; Grant, Andrew J; Mastroeni, Pietro
2016-01-01
Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte-like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease. PMID:27366588
Heath, Candice; Gillen, Christine M; Chrysanthopoulos, Panagiotis; Walker, Mark J; Barnes, Andrew C
2016-09-25
Streptococcus iniae causes septicaemia and meningitis in marine and freshwater fish wherever they are farmed in warm-temperate and tropical regions. Although serotype specific, vaccination with bacterins (killed bacterial cultures) is largely successful and vaccine failure occurs only occasionally through emergence of new capsular serotypes. Previously we showed that mutations in vaccine escapes are restricted to a limited repertoire of genes within the 20-gene capsular polysaccharide (cps) operon. cpsG, a putative UDP-galactose 4-epimerase, has three sequence types based on the insertion or deletion of the three amino acids leucine, serine and lysine in the substrate binding site of the protein. To elucidate the role of cpsG in capsular polysaccharide (CPS) biosynthesis and capsular composition, we first prepared isogenic knockout and complemented mutants of cpsG by allelic exchange mutagenesis. Deletion of cpsG resulted in changes to colony morphology and cell buoyant density, and also significantly decreased galactose content relative to glucose in the capsular polysaccharide as determined by GC-MS, consistent with epimerase activity of CpsG. There was also a metabolic penalty of cpsG knockout revealed by slower growth in complex media, and reduced proliferation in whole fish blood. Moreover, whilst antibodies raised in fish against the wild type cross-reacted in whole cell and cps ELISA, they did not cross-opsonise the mutant in a peripheral blood neutrophil opsonisation assay, consistent with reported vaccine escape. We have shown here that mutation in cpsG results in altered CPS composition and this in turn results in poor cross-opsonisation that explains some of the historic vaccination failure on fish farms in Australia. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.
Pondman, Kirsten M; Sobik, Martin; Nayak, Annapurna; Tsolaki, Anthony G; Jäkel, Anne; Flahaut, Emmanuel; Hampel, Silke; Ten Haken, Bennie; Sim, Robert B; Kishore, Uday
2014-08-01
Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. Copyright © 2014 Elsevier Inc. All rights reserved.
Barrio, Maria Belén; Rainard, Pascal; Poutrel, Bernard
2003-01-01
Phagocytosis of bacteria by bovine polymorphonuclear neutrophils (PMN) has long been regarded as essential for host defense against mastitis infection. Complement-mediated opsonisation by complement component 3 (C3) binding is an important component of the innate immune system. We investigated the role of milk complement as an opsonin and its involvement in the phagocytosis and killing of Staphylococcus aureus isolates from cases of bovine mastitis by bovine blood PMN. We show that deposition of milk C3 component occurred on six different isolates of S. aureus and that the alternative pathway was the sole complement pathway operating in milk of uninflamed mammary gland. This deposition was shown to occur at the same location as the capsule, but not on capsular antigen. Milk complement enhanced the chemiluminescence response of PMN induced by S. aureus. Nevertheless, the association of S. aureus to cells and the overall killing of bacteria by bovine PMN were not affected by the presence of milk complement. Therefore, as all milk samples contained antibodies to capsular polysaccharide type 5 and to other surface antigens, it is likely that milk antibodies were responsible for these two phagocytic events. Results of this study suggest that the deposition of milk complement components on the surface of S. aureus does not contribute to the defence of the mammary gland against S. aureus.
Sóñora, Cecilia; Arbildi, Paula; Miraballes-Martínez, Iris; Hernández, Ana
2018-01-01
Phagocytosis is a fundamental process for removal of pathogens and for clearance of apoptotic cells. The objective of this work was the preparation of fluorescent microspheres by a simple method and the evaluation of its applicability in phagocytosis assays by using different human derived cells, differentiated THP-1 cell line and blood monocytes, with flow cytometry measurements for functionality assays. Our results show that microparticles are efficiently internalised in a non-opsonised form and in dose-dependent manner by both cellular types. Concerning mechanism we determined that tTG-β3 integrin signaling could be involved in the uptake of these particles.
Kumar, Abhinav; Bicer, Elif Melis; Morgan, Anna Babin; Pfeffer, Paul E; Monopoli, Marco; Dawson, Kenneth A; Eriksson, Jonny; Edwards, Katarina; Lynham, Steven; Arno, Matthew; Behndig, Annelie F; Blomberg, Anders; Somers, Graham; Hassall, Dave; Dailey, Lea Ann; Forbes, Ben; Mudway, Ian S
2016-05-01
When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semi-quantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. Copyright © 2016. Published by Elsevier Inc.
Ludlow, Louise E.; Hasang, Wina; Umbers, Alexandra J.; Forbes, Emily K.; Ome, Maria; Unger, Holger W.; Mueller, Ivo; Siba, Peter M.; Jaworowski, Anthony; Rogerson, Stephen J.
2014-01-01
Immunopathology of placental malaria is most significant in women in their first pregnancy especially in endemic areas, due to a lack of protective immunity to Plasmodium falciparum, which is acquired in successive pregnancies. In some studies (but not all), grand multigravidae (defined as 5 or more pregnancies, G5–7) are more susceptible to poor birth outcomes associated with malaria compared to earlier gravidities. By comparing peripheral cellular responses in primigravidae (G1), women in their second to fourth pregnancy (G2–4) and grand multigravidae we sought to identify key components of the dysregulated immune response. PBMC were exposed to CS2-infected erythrocytes (IE) opsonised with autologous plasma or unopsonised IE, and cytokine and chemokine secretion was measured. Higher levels of opsonising antibody were present in plasma derived from multigravid compared to primigravid women. Significant differences in the levels of cytokines and chemokines secreted in response to IE were observed. Less IL-10, IL-1β, IL-6 and TNF but more CXCL8, CCL8, IFNγ and CXCL10 were detected in G5–7 compared to G2–4 women. Our study provides fresh insight into the modulation of peripheral blood cell function and effects on the balance between host protection and immunopathology during placental malaria infection. PMID:24465935
Husain, Mainul; Wu, Dongmei; Saber, Anne T.; Decan, Nathalie; Jacobsen, Nicklas R.; Williams, Andrew; Yauk, Carole L.; Wallin, Hakan; Vogel, Ulla; Halappanavar, Sabina
2015-01-01
Abstract An estimated 1% or less of nanoparticles (NPs) deposited in the lungs translocate to systemic circulation and enter other organs; however, this estimation may not be accurate given the low sensitivity of existing in vivo NP detection methods. Moreover, the biological effects of such low levels of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 µg of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. This study characterizes the subtle systemic effects that occur in liver and heart tissues following pulmonary exposure and low levels of translocation of nano-TiO2 from lungs. PMID:25993494
Functional Aspects of Fish Mucosal Lectins-Interaction with Non-Self.
Brinchmann, Monica Fengsrud; Patel, Deepti Manjari; Pinto, Nevil; Iversen, Martin Haugmo
2018-05-09
Mucosal surfaces are of key importance in protecting animals against external threats including pathogens. In the mucosal surfaces, host molecules interact with non-self to prevent infection and disease. Interestingly, both inhibition and stimulation of uptake hinder infection. In this review, the current knowledgebase on teleost mucosal lectins’ ability to interact with non-self is summarised with a focus on agglutination, growth inhibition, opsonisation, cell adhesion, and direct killing activities. Further research on lectins is essential, both to understand the immune system of fishes, since they rely more on the innate immune system than mammals, and also to explore these molecules’ antibiotic and antiparasitic activities against veterinary and human pathogens.
Moriguchi, Keiichi
2018-03-01
When polymorphonuclear leukocytes (PMNs) phagocytose opsonised zymosan particles (OPZ), free radicals and reactive oxygen species (ROS) are formed in the phagosomes. ROS production is mediated by NADPH oxidase (Nox), which transfers electrons in converting oxygen to superoxide (O 2 - ). Nox-generated O 2 - is rapidly converted to other ROS. Free radical-forming secretory vesicles containing the Nox redox center flavocytochrome b558, a membrane protein, and azurophil granules with packaged myeloperoxidase (MPO) have been described. Presuming the probable fusion of these vesicular and granular organelles with phagosomes, the translation process of the enzymes was investigated using energy-filtering and energy-dispersive spectroscopy-scanning transmission electron microscopy. In this work, the primary method for imaging cerium (Ce) ions demonstrated the localisation of H 2 O 2 generated by phagocytosing PMNs. The MPO activity of the same PMNs was continuously monitored using 0.1% 3,3'-diaminobenzidine-tetrahydrochloride (DAB) and 0.01% H 2 O 2 . A detailed view of these vesicular and granular structures was created by overlaying each electron micrograph with pseudocolors: blue for Ce and green for nitrogen (N). © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.
Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders.
Ferluga, Janez; Kouser, Lubna; Murugaiah, Valarmathy; Sim, Robert B; Kishore, Uday
2017-04-01
Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part. These include systemic lupus erythematosus, rheumatoid arthritis, atypical haemolytic uremic syndrome, anti-phospholipid syndrome and age-related macular degeneration. Such diseases are generally complex - multigenic and heterogeneous in their symptoms and predisposition/susceptibility. They usually need to be triggered by vascular trauma, drugs or infection and non-complement genetic factors also play a part. Underlying events seem to include decline in peripheral regulatory T cells, dendritic cell, and B cell tolerance, associated with alterations in lymphoid organ microenvironment. Factor H is an abundant protein, synthesised in many cell types, and its reported binding to many different ligands, even if not of high affinity, may influence a large number of molecular interactions, together with the accepted role of Factor H within the complement system. Factor H is involved in mesenchymal stem cell mediated tolerance and also contributes to self-tolerance by augmenting iC3b production and opsonisation of apoptotic cells for their silent dendritic cell engulfment via complement receptor CR3, which mediates anti-inflammatory-tolerogenic effects in the apoptotic cell context. There may be co-operation with other phagocytic receptors, such as complement C1q receptors, and the Tim glycoprotein family, which specifically bind phosphatidylserine expressed on the apoptotic cell surface. Factor H is able to discriminate between self and nonself surfaces for self-protection and anti-microbe defence. Factor H, particularly as an abundant platelet protein, may also modulate blood coagulation, having an anti-thrombotic role. Here, we review a number of interaction pathways in coagulation and in immunity, together with associated diseases, and indicate where Factor H may be expected to exert an influence, based on reports of the diversity of ligands for Factor H. Copyright © 2017 Elsevier Ltd. All rights reserved.
Duperthuy, Marylise; Schmitt, Paulina; Garzón, Edwin; Caro, Audrey; Rosa, Rafael D.; Le Roux, Frédérique; Lautrédou-Audouy, Nicole; Got, Patrice; Romestand, Bernard; de Lorgeril, Julien; Kieffer-Jaquinod, Sylvie; Bachère, Evelyne; Destoumieux-Garzón, Delphine
2011-01-01
OmpU porins are increasingly recognized as key determinants of pathogenic host Vibrio interactions. Although mechanisms remain incompletely understood, various species, including the human pathogen Vibrio cholera, require OmpU for host colonization and virulence. We have shown previously that OmpU is essential for virulence in the oyster pathogen Vibrio splendidus LGP32. Here, we showed that V. splendidus LGP32 invades the oyster immune cells, the hemocytes, through subversion of host-cell actin cytoskeleton. In this process, OmpU serves as an adhesin/invasin required for β-integrin recognition and host cell invasion. Furthermore, the major protein of oyster plasma, the extracellular superoxide dismutase Cg-EcSOD, is used as an opsonin mediating the OmpU-promoted phagocytosis through its RGD sequence. Finally, the endocytosed bacteria were found to survive intracellularly, evading the host defense by preventing acidic vacuole formation and limiting reactive oxygen species production. We conclude that (i) V. splendidus is a facultative intracellular pathogen that manipulates host defense mechanisms to enter and survive in host immune cells, and (ii) that OmpU is a major determinant of host cell invasion in Vibrio species, used by V. splendidus LGP32 to attach and invade oyster hemocytes through opsonisation by the oyster plasma Cg-EcSOD. PMID:21282662
Phagocytes in cell suspensions of human colon mucosa.
Beeken, W; Northwood, I; Beliveau, C; Gump, D
1987-01-01
Because little is known of the phagocytes of the human colon we enumerated these cells in mucosal suspensions and studied their phagocytic activity. Phagocyte rich suspensions were made by EDTA collagenase dissociation followed by elutriation centrifugation. Phagocytosis was evaluated by measuring cellular radioactivity after incubation of phagocytes with 3H-adenine labelled E coli ON2 and checked microscopically. Dissociation of normal mucosa from colorectal neoplasms yielded means of 1.9 X 10(6) eosinophils, 1.4 X 10(6) macrophages and 2 X 10(5) neutrophils per gram of mucosa. Visually normal mucosa of inflammatory states yielded 2.2 X 10(6) eosinophils, 2.3 X 10(6) macrophages and 7 X 10(5) neutrophils per gram of mucosa. Phagocyte rich suspensions of normal mucosa from tumour patients phagocytosed 21.8% of a pool of opsonised tritiated E coli ON2 and by microscopy 100% of mucosal neutrophils ingested bacteria, 83% of eosinophils were phagocytic, and 53% of macrophages contained bacteria. These results suggest that in the human colonic mucosa, the eosinophil is more abundant than the macrophage and the per cent of those cells exhibiting phagocytosis is intermediate between that of the macrophage and the neutrophil. Thus these three types of cells are actively phagocytic and share the potential for a major role in host defence against invasive enteric bacteria. PMID:3666566
McKenzie, Zofi; Kendall, Michaela; Mackay, Rose-Marie; Whitwell, Harry; Elgy, Christine; Ding, Ping; Mahajan, Sumeet; Morgan, Cliff; Griffiths, Mark; Clark, Howard; Madsen, Jens
2015-01-01
The lung provides the main route for nanomaterial exposure. Surfactant protein A (SP-A) is an important respiratory innate immune molecule with the ability to bind or opsonise pathogens to enhance phagocytic removal from the airways. We hypothesised that SP-A, like surfactant protein D, may interact with inhaled nanoparticulates, and that this interaction will be affected by nanoparticle (NP) surface characteristics. In this study, we characterise the interaction of SP-A with unmodified (U-PS) and amine-modified (A-PS) polystyrene particles of varying size and zeta potential using dynamic light scatter analysis. SP-A associated with both 100 nm U-PS and A-PS in a calcium-independent manner. SP-A induced significant calcium-dependent agglomeration of 100 nm U-PS NPs but resulted in calcium-independent inhibition of A-PS self agglomeration. SP-A enhanced uptake of 100 nm U-PS into macrophage-like RAW264.7 cells in a dose-dependent manner but in contrast inhibited A-PS uptake. Reduced association of A-PS particles in RAW264.7 cells following pre-incubation of SP-A was also observed with coherent anti-Stokes Raman spectroscopy. Consistent with these findings, alveolar macrophages (AMs) from SP-A(-/-) mice were more efficient at uptake of 100 nm A-PS compared with wild type C57Bl/6 macrophages. No difference in uptake was observed with 500 nm U-PS or A-PS particles. Pre-incubation with SP-A resulted in a significant decrease in uptake of 100 nm A-PS in macrophages isolated from both groups of mice. In contrast, increased uptake by AMs of U-PS was observed after pre-incubation with SP-A. Thus we have demonstrated that SP-A promotes uptake of non-toxic U-PS particles but inhibits the clearance of potentially toxic A-PS particles by blocking uptake into macrophages.
Barriers to Liposomal Gene Delivery: from Application Site to the Target.
Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R
2016-01-01
Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.
Risco, Ester; Ghia, Felipe; Vila, Roser; Iglesias, José; Alvarez, Elida; Cañigueral, Salvador
2003-09-01
The immunomodulatory activity of the latex from Croton lechleri (sangre de drago) was determined by in vitro assays. Classical (CP) and alternative (AP) complement pathways activities were determined in human serum. Intracellular generation of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) and monocytes, and phagocytosis of opsonised fluorescent microspheres were measured by flow cytometry. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Activity on proliferation of murine lymphocytes was also investigated. In addition, anti-inflammatory activity was assayed in vivo by carrageenan-induced rat paw oedema test. Some of the activities were compared with those of the isolated alkaloid taspine. Sangre de drago from Croton lechleri showed immunomodulatory activity. It exhibited a potent inhibitory activity on CP and AP of complement system and inhibited the proliferation of activated T-cells. The latex showed free radical scavenging capacity. Depending on the concentration, it showed antioxidant or prooxidant properties, and stimulated or inhibited the phagocytosis. Moreover, the latex has strong anti-inflammatory activity when administered i. p. Taspine cannot be considered the main responsible for these activities, and other constituents, probably proanthocyanidins, should be also involved.
Guentsch, Arndt; Puklo, Magdalena; Preshaw, Philip M.; Glockmann, Eike; Pfister, Wolfgang; Potempa, Jan; Eick, Sigrun
2014-01-01
AIM The aim of this in vitro study was to study phagocytosis and killing of Porphyromonas gingivalis ATCC 33277 and Aggregatibacter actinomycetemcomitans Y4 by peripheral blood PMNs taken from aggressive and chronic periodontitis patients. Also, the release of reactive oxygen species (ROS) and human neutrophil elastase (HNE) upon the interaction of PMNs with bacteria was measured. METHODS Peripheral blood PMNs obtained from 12 chronic periodontitis patients, 6 aggressive periodontitis patients and 12 healthy controls were exposed to Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans following opsonisation of the bacteria using the patient’s own serum. Phagocytosis and killing of the bacteria as well as the extracellular HNE activity were quantified for up to 2 hours. The total amount and the extracellular release of ROS were measured by luminol and isoluminol dependent chemiluminescence. RESULTS PMNs from chronic (62.16 ± 19.39 %) and aggressive periodontitis (43.26 ± 26.63 %) patients phagocytosed more P. gingivalis than the healthy controls (24.43 ± 19.87 %) at 30 mins after exposure to the bacteria (p < 0.05). PMNs from subjects with chronic and aggressive periodontitis released significantly more ROS and demonstrated greater HNE activity in the absence of any stimulus than PMNs from healthy controls (p < 0.05). The total release of ROS increased in chronic periodontitis PMNs and in the control group PMNs after interaction with P. gingivalis. The interaction with A. actinomycetemcomitans resulted in greater total ROS release in chronic periodontitis PMNs and in the control group PMNs than P. gingivalis. CONCLUSION PMNs in aggressive and chronic periodontitis are hyperactive even without any particular stimulus. The extracellular release of ROS and neutrophil elastase by PMNs may not only affect bacterial virulence and/or viability, but also contribute to damage of the surrounding periodontal tissues. PMID:19210340
Chapple, Iain Lc; Matthews, John B; Wright, Helen J; Scott, Ann E; Griffiths, Helen R; Grant, Melissa M
2013-01-01
Periodontitis, a ubiquitous chronic inflammatory disease, is associated with reduced antioxidant defences and neutrophil hyperactivity in terms of reactive oxygen species (ROS) generation. Its phenotype is thus characterized by oxidative stress. We have determined the effect of antioxidant micronutrients ascorbate and α-tocopherol on neutrophil ROS generation. Peripheral neutrophils from periodontally-healthy individuals (n = 20) were challenged with phorbol myristate acetate, IgG-opsonised Staphylococcus aureus, Fusobacterium nucleatum or PBS in the presence and absence of micronutrients (50 µM). Total and extracellular ROS were measured by luminol and isoluminol chemiluminescence respectively. Total and extracellular unstimulated, baseline ROS generation was unaffected by α-tocopherol, but inhibited by ascorbate and a combination of both micronutrients. Fcγ-receptor (Fcγ-R)-stimulated total or extracellular ROS generation was not affected by the presence of individual micronutrients. However, the combination significantly reduced extracellular FcγR-stimulated ROS release. Neither micronutrient inhibited TLR-stimulated total ROS, but the combination caused inhibition. Ascorbate and the micronutrient combination, but not α-tocopherol, inhibited extracellular ROS release by TLR-stimulated cells. Such micronutrient effects in vivo could be beneficial in reducing collateral tissue damage in chronic inflammatory diseases, such as periodontitis, while retaining immune-mediated neutrophil function.
Muzila, Mbaki; Rumpunen, Kimmo; Wright, Helen; Roberts, Helen; Grant, Melissa; Nybom, Hilde; Sehic, Jasna; Ekholm, Anders; Widén, Cecilia
2016-01-01
Harpagophytum, Devil's Claw, is a genus of tuberiferous xerophytic plants native to southern Africa. Some of the taxa are appreciated for their medicinal effects and have been traditionally used to relieve symptoms of inflammation. The objectives of this pilot study were to investigate the antioxidant capacity and the content of total phenols, verbascoside, isoverbascoside, and selected iridoids, as well as to investigate the capacity of various Harpagophytum taxa in suppressing respiratory burst in terms of reactive oxygen species produced by human neutrophils challenged with phorbol myristate acetate (PMA), opsonised Staphylococcus aureus, and Fusobacterium nucleatum. Harpagophytum plants were classified into different taxa according to morphology, and DNA analysis was used to confirm the classification. A putative new variety of H. procumbens showed the highest degree of antioxidative capacity. Using PMA, three Harpagophytum taxa showed anti-inflammatory effects with regard to the PBS control. A putative hybrid between H. procumbens and H. zeyheri in contrast showed proinflammatory effect on the response of neutrophils to F. nucleatum in comparison with treatment with vehicle control. Harpagophytum taxa were biochemically very variable and the response in suppressing respiratory burst differed. Further studies with larger number of subjects are needed to corroborate anti-inflammatory effects of different taxa of Harpagophytum.
Muzila, Mbaki; Wright, Helen; Roberts, Helen; Grant, Melissa; Nybom, Hilde; Sehic, Jasna; Ekholm, Anders
2016-01-01
Harpagophytum, Devil's Claw, is a genus of tuberiferous xerophytic plants native to southern Africa. Some of the taxa are appreciated for their medicinal effects and have been traditionally used to relieve symptoms of inflammation. The objectives of this pilot study were to investigate the antioxidant capacity and the content of total phenols, verbascoside, isoverbascoside, and selected iridoids, as well as to investigate the capacity of various Harpagophytum taxa in suppressing respiratory burst in terms of reactive oxygen species produced by human neutrophils challenged with phorbol myristate acetate (PMA), opsonised Staphylococcus aureus, and Fusobacterium nucleatum. Harpagophytum plants were classified into different taxa according to morphology, and DNA analysis was used to confirm the classification. A putative new variety of H. procumbens showed the highest degree of antioxidative capacity. Using PMA, three Harpagophytum taxa showed anti-inflammatory effects with regard to the PBS control. A putative hybrid between H. procumbens and H. zeyheri in contrast showed proinflammatory effect on the response of neutrophils to F. nucleatum in comparison with treatment with vehicle control. Harpagophytum taxa were biochemically very variable and the response in suppressing respiratory burst differed. Further studies with larger number of subjects are needed to corroborate anti-inflammatory effects of different taxa of Harpagophytum. PMID:27429708
Markiewicz, H; Krumrych, W; Gehrke, M
2013-01-01
The aim of this field study was to assess the impact of a single i.m. injection of lysozyme dimer and flunixin meglumine in combination with intramammary and systemic antibiotic on chemiluminescence of PMN (polymorphonuclear leucocytes) and subpopulations of lymphocyte T in blood of cows with E. coli mastitis. Examinations were performed on 30 dairy cows affected with naturally occurring acute form of E. coli mastitis. Cows were randomly divided into three groups according to the method of treatment. The first group was treated with approved intramammary antibiotic product, the same antibiotic in i.m. injection and one injection of flunixin meglumine on the first day of therapy. Next group was treated with the same antibiotic and additionally one injection of lysozyme dimer on the first day of therapy. The third one was treated only with an antibiotic and served as a control group. Blood samples were taken before treatment and on days 3 and 7. In samples haematology indices were determined, spontaneous and opsonised zymosan stimulated CL and PMA measurements were performed and the subpopulations of T lymphocyte (CD2(+), CD4(+), CD8(+)) were assayed in whole blood. There was no effect of the applied supportive treatment on the value of morphological blood indices. A significant influence of the time of sample collection on the level of CL and dynamics of lymphocytes T subpopulation was demonstrated. A single injection of flunixin meglumine or lysozyme dimer on the day of the beginning of treatment of E. coli mastitis, does not affect the level of neutrophil chemiluminescence and the percentage of T lymphocytes in the blood of mastitic cows in the analysed period of time.
Hofmans, Dorien; Khodaparast, Laleh; Khodaparast, Ladan; Vanstreels, Els; Shahrooei, Mohammad; Van Eldere, Johan; Van Mellaert, Lieve
2018-05-09
The opportunistic pathogen Staphylococcus epidermidis is progressively involved in device-related infections. Since these infections involve biofilm formation, antibiotics are not effective. Conversely, a vaccine can be advantageous to prevent these infections. In view of vaccine development, predicted surface proteins were evaluated on their potential as a vaccine target. Immunoglobulins directed against S. epidermidis surface proteins SesB, M, O, Q and R, were used to firstly affirm their surface location. Further, inhibitory effects of these IgGs on biofilm formation were determined in vitro on polystyrene and polyurethane surfaces and in vivo using a subcutaneous catheter mouse model. We also examined the opsonophagocytic capacity of these IgGs. Surface localization of the five Ses proteins was demonstrated both for planktonic and sessile cells, though to a variable extent. Ses-specific IgGs added to planktonic cells had a variable inhibitory effect on cell adhesion to polystyrene, while only anti-SesO IgGs decreased cell attachment to polyurethane catheters. Although phagocytic killing was only obtained after opsonisation with SesB-specific IgGs, a significant reduction of in vivo formed biofilms was observed after administration of SesB-, SesM- and SesO-specific IgGs. Regardless of their characterization or function, S. epidermidis surface proteins can be adequate targets for vaccine development aiming the prevention of device-related infections caused by invasive S. epidermidis strains. Copyright © 2018 Elsevier Ltd. All rights reserved.
Arora, Geetanjali; Shukla, Jaya; Ghosh, Sourabh; Maulik, Subir Kumar; Malhotra, Arun; Bandopadhyaya, Gurupad
2012-01-01
Background Peptide receptor radionuclide therapy (PRRT), employed for treatment of neuroendocrine tumors (NETs) is based on over-expression of Somatostatin Receptors (SSTRs) on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, 177Lu-DOTATATE loaded PLGA nanoparticles (NPs) were formulated in the present study, as a potential therapeutic model for NETs. Methodology and Findings DOTATATE was labeled with Lutetium-177 (177Lu) (labeling efficiency 98%; Rf∼0.8). Polyethylene Glycol (PEG) coated 177Lu-DOTATATE-PLGA NPs (50∶50 and 75∶25) formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated) and 303.8±67.2 and 494.3±71.8 nm (coated) for PLGA(50∶50) and PLGA(75∶25) respectively. Encapsulation efficiency (EE) and In-vitro release kinetics for uncoated and coated NPs of PLGA (50∶50 & 75∶25) were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated) and 65.385±5.67% & 58.495±5.35% (coated). NPs showed initial burst release between 16.64–21.65% with total 42.83–44.79% over 21days. The release increased with coating to 20.4–23.95% initially and 60.97–69.12% over 21days. In-vivo studies were done in rats injected with 177Lu-DOTATATE and 177Lu-DOTATATE-NP (uncoated and PEG-coated) by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With 177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated 177Lu-DOTATATE-NP. The high liver uptake with uncoated 177Lu-DOTATATE-NP (13.68±3.08% ID/g), reduced to 7.20±2.04%ID/g (p = 0.02) with PEG coating. Conclusion PLGA NPs were easily formulated and modified for desired release properties. PLGA 50∶50 NPs were a more suitable delivery vehicle for 177Lu-DOTATATE than PLGA 75∶25 because of higher EE and slower release rate. Reduced renal retention of 177Lu-DOTATATE and reduced opsonisation strongly advocate the potential of 177Lu-DOTATATE-PLGA-PEG NPs to reduce radiation dose in PRRT. PMID:22442740
Chandrasekaran, Murugesan; Pandurangan, Muthuraman
2016-07-01
The zinc oxide (ZnO) nanoparticle has been widely used in biomedical applications and cancer therapy and has been reported to induce a selective cytotoxic effect on cancer cell proliferation. The present study investigated the cytotoxicity of ZnO nanoparticles against co-cultured C2C12 myoblastoma cancer cells and 3T3-L1 adipocytes. Our results showed that the ZnO nanoparticles could be cytotoxic to C2C12 myoblastoma cancer cells than 3T3-L1 cells. The messenger RNA (mRNA) expressions of p53 and bax were significantly increased 114.3 and 118.2 % in the C2C12 cells, whereas 42.5 and 40 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was reduced 38.2 and 28.5 % in the C2C12 and 3T3-L1 cells, respectively, whereas the mRNA expression of caspase-3 was increased 80.7 and 51.6 % in the C2C12 and 3T3-L1 cells, respectively. The protein expressions of p53, bax, and caspase-3 were significantly increased 40, 81.8, and 80 % in C2C12 cells, whereas 20.3, 28.2, and 37.9 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was significantly reduced 32.2 and 22.7 % in C2C12 and 3T3-L1 cells, respectively. Caspase-3 enzyme activity and reactive oxygen species (ROS) were increased in co-cultured C2C12 cells compared to 3T3-L1 cells. Taking all these data together, it may suggest that ZnO nanoparticles severely induce apoptosis in C2C12 myoblastoma cancer cells than 3T3-L1 cells.
Spiesman, Brian J; Kummel, Herika; Jackson, Randall D
2018-02-01
Long-term soil carbon (C) storage is essential for reducing CO 2 in the atmosphere. Converting unproductive and environmentally sensitive agricultural lands to grasslands for bioenergy production may enhance C storage. However, a better understanding of the interacting effects of grass functional composition (i.e., relative abundance of C 4 and C 3 grass cover) and soil productivity on C storage will help guide sustainable grassland management. Our objective was to examine the relationship between grass functional composition and potential C storage and how it varies with potential soil productivity. We estimated C inputs from above- and belowground net primary productivity (ANPP and BNPP), and heterotrophic respiration (R H ) to calculate net ecosystem production (NEP), a measure of potential soil C storage, in grassland plots of relatively high- and low-productivity soils spanning a gradient in the ratio of C 4 to C 3 grass cover (C 4 :C 3 ). NEP increased with increasing C 4 :C 3 , but only in potentially productive soils. The positive relationship likely stemmed from increased ANPP, rather than BNPP, which was possibly related to efficient resource-use and physiological/anatomical advantages of C 4 plants. R H was negatively correlated with C 4 :C 3 , possibly because of changes in microclimate or plant-microbe interactions. It is possible that in potentially productive soils, C storage can be enhanced by favoring C 4 over C 3 grasses through increased ANPP and BNPP and reduced R H . Results also suggest that potential C storage gains from C 4 productivity would not be undermined by a corresponding increase in R H .
Feng, Gaoqian; Aitken, Elizabeth; Yosaatmadja, Francisca; Kalilani, Linda; Meshnick, Steven R; Jaworowski, Anthony; Simpson, Julie A; Rogerson, Stephen J
2009-01-01
Background In pregnancy associated malaria (PAM), Plasmodium falciparum infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonise IEs for phagocytic clearance, protecting women from anemia and low birth weight Methods and findings Using sera from 141 parasitemic pregnant Malawian women enrolled in a randomized trial of antimalarials and VSA-PAM-expressing CS2 IEs, we quantitated levels of IgG to VSA-PAM by flow cytometry and opsonizing antibodies by measuring uptake of IEs by THP1 promonocytes. After controlling for gravidity and antimalarial treatment, IgG against VSA-PAM was associated with decreased anemia at delivery (OR=0.66, 95% confidence interval [CI] 0.46, 0.93; P=0.018) and weakly associated with decreased parasitological failure (OR=0.78; 95% CI, 0.60, 1.03; P=0.075), especially re-infection (OR=0.73; CI, 0.53,1.01; P=0.057). Opsonizing antibodies to CS2 IE were associated with less maternal anemia. (OR=0.31, 95% CI, 0.13, 0.74; P=0.008) and treatment failure (OR=0.48; 95% CI, 0.25, 0.90; P=0.023), primarily due to recrudescent infection (OR=0.49; 95% CI, 0.21, 1.12; P=0.089). Conclusion Both IgG antibody to VSA-PAM and opsonizing antibody, a functional measure of immunity correlate with parasite clearance and less anemia in pregnancy malaria. PMID:19500037
Role of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the renal 2',3'-cAMP-adenosine pathway.
Jackson, Edwin K; Gillespie, Delbert G; Mi, Zaichuan; Cheng, Dongmei; Bansal, Rashmi; Janesko-Feldman, Keri; Kochanek, Patrick M
2014-07-01
Energy depletion increases the renal production of 2',3'-cAMP (a positional isomer of 3',5'-cAMP that opens mitochondrial permeability transition pores) and 2',3'-cAMP is converted to 2'-AMP and 3'-AMP, which in turn are metabolized to adenosine. Because the enzymes involved in this "2',3'-cAMP-adenosine pathway" are unknown, we examined whether 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) participates in the renal metabolism of 2',3'-cAMP. Western blotting and real-time PCR demonstrated expression of CNPase in rat glomerular mesangial, preglomerular vascular smooth muscle and endothelial, proximal tubular, thick ascending limb and collecting duct cells. Real-time PCR established the expression of CNPase in human glomerular mesangial, proximal tubular and vascular smooth muscle cells; and the level of expression of CNPase was greater than that for phosphodiesterase 4 (major enzyme for the metabolism of 3',5'-cAMP). Overexpression of CNPase in rat preglomerular vascular smooth muscle cells increased the metabolism of exogenous 2',3'-cAMP to 2'-AMP. Infusions of 2',3'-cAMP into isolated CNPase wild-type (+/+) kidneys increased renal venous 2'-AMP, and this response was diminished by 63% in CNPase knockout (-/-) kidneys, whereas the conversion of 3',5'-cAMP to 5'-AMP was similar in CNPase +/+ vs. -/- kidneys. In CNPase +/+ kidneys, energy depletion (metabolic poisons) increased kidney tissue levels of adenosine and its metabolites (inosine, hypoxanthine, xanthine, and uric acid) without accumulation of 2',3'-cAMP. In contrast, in CNPase -/- kidneys, energy depletion increased kidney tissue levels of 2',3'-cAMP and abolished the increase in adenosine and its metabolites. In conclusion, kidneys express CNPase, and renal CNPase mediates in part the renal 2',3'-cAMP-adenosine pathway. Copyright © 2014 the American Physiological Society.
Influence of time, temperature and coagulation on the measurement of C3, C3 split products and C4.
Sinosich, M J; Teisner, B; Brandslund, I; Fisher, M; Grudzinskas, J G
1982-11-26
Quantitative and qualitative immunoelectrophoretic analyses of circulating C3, C3 split products and C4 were performed in matched EDTA plasma and serum obtained from 5 normal subjects and stored for up to 48 h at room temperature (18 degrees C-22 degrees C) and 4 degrees C. Fluctuations in apparent levels of C3 were greater in serum than plasma stored at room temperature, a fall in levels seen by 24 h being followed by a significant increase. By contrast, levels of C3 did not alter if stored at 4 degrees C. C4 levels in both EDTA plasma and serum remained unchanged for 24 h, a slight decrease being seen at 48 h. Levels of C4 remained constant if samples were stored at 4 degrees C. Crossed immunoelectrophoresis revealed a significant progressive decrease in C3 levels and a simultaneous increase in C3c occurring after 4 h in serum and 8 h in EDTA plasma, stored at room temperature. In studies conducted at 4 degrees C, similar but delayed fluctuations were seen. A progressive and significant increase in C3d levels was seen in both plasma and serum samples stored at room temperature, levels rising to 276% (plasma) and 308% (serum) of levels seen at zero time. At 4 degrees C marginal increases in C3d levels only were observed. These results suggest that in vitro degradation of C3 and C4 are readily facilitated by temperature, time and coagulation, and that conditions of collection and storage of samples must be optimized for the accurate definition of activation of the complement cascade.
Role of 2′,3′-cyclic nucleotide 3′-phosphodiesterase in the renal 2′,3′-cAMP-adenosine pathway
Gillespie, Delbert G.; Mi, Zaichuan; Cheng, Dongmei; Bansal, Rashmi; Janesko-Feldman, Keri; Kochanek, Patrick M.
2014-01-01
Energy depletion increases the renal production of 2′,3′-cAMP (a positional isomer of 3′,5′-cAMP that opens mitochondrial permeability transition pores) and 2′,3′-cAMP is converted to 2′-AMP and 3′-AMP, which in turn are metabolized to adenosine. Because the enzymes involved in this “2′,3′-cAMP-adenosine pathway” are unknown, we examined whether 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) participates in the renal metabolism of 2′,3′-cAMP. Western blotting and real-time PCR demonstrated expression of CNPase in rat glomerular mesangial, preglomerular vascular smooth muscle and endothelial, proximal tubular, thick ascending limb and collecting duct cells. Real-time PCR established the expression of CNPase in human glomerular mesangial, proximal tubular and vascular smooth muscle cells; and the level of expression of CNPase was greater than that for phosphodiesterase 4 (major enzyme for the metabolism of 3′,5′-cAMP). Overexpression of CNPase in rat preglomerular vascular smooth muscle cells increased the metabolism of exogenous 2′,3′-cAMP to 2′-AMP. Infusions of 2′,3′-cAMP into isolated CNPase wild-type (+/+) kidneys increased renal venous 2′-AMP, and this response was diminished by 63% in CNPase knockout (−/−) kidneys, whereas the conversion of 3′,5′-cAMP to 5′-AMP was similar in CNPase +/+ vs. −/− kidneys. In CNPase +/+ kidneys, energy depletion (metabolic poisons) increased kidney tissue levels of adenosine and its metabolites (inosine, hypoxanthine, xanthine, and uric acid) without accumulation of 2′,3′-cAMP. In contrast, in CNPase −/− kidneys, energy depletion increased kidney tissue levels of 2′,3′-cAMP and abolished the increase in adenosine and its metabolites. In conclusion, kidneys express CNPase, and renal CNPase mediates in part the renal 2′,3′-cAMP-adenosine pathway. PMID:24808540
cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion.
Myers, N C; Grune, S; Jameson, H L; Sawkat-Anwer, M
1996-03-01
The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on hepatic bile formation was studied in isolated perfused rat livers and rat hepatocytes. Studies in isolated perfused rat livers showed that infusion of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 3 micromol/min or 100 microM) 1) increased bile flow without affecting biliary excretion of simultaneously infused taurocholate, 2) increased biliary concentration and excretion of HCO3(-) but did not affect biliary excretion of glutathione, and 3) increased net perfusate H+ efflux without affecting hepatic O2 uptake. Studies in isolated rat hepatocytes showed that 1) 8-BrcGMP increased intracellular pH in the presence (but not in the absence) of extracellular HCO-3, and effect inhibited by 4,4' -diisothiocyanostilbene-2,2'-disulfonic acid and Na+ replacement, 2) 8-BrcGMP did not affect taurocholate uptake and intracellular [Ca2+], and 3) bile acids, like ursodeoxycholate and cholate, did not increase cellular cGMP. Taken together, these results indicate that cGMP stimulates bile acid-independent bile formation, in part by stimulating biliary HCO3- excretion. cGMP may increase HCO3- excretion by stimulating sinusoidal Na+ - HCO3- cotransport, but not Na+/H+ exchange. cGMP, unlike adenosine 3',5'-cyclic monophosphate, may not regulate hepatic taurocholate transport, and bile acid-induced HCO3- rich choleresis may not be mediated via cGMP.
Lee, Hsin-Yi; Chen, Chi-Kuan; Ho, Chun-Ming; Lee, Szu-Shuo; Chang, Chieh-Yu; Chen, Kuan-Ju; Jou, Yuh-Shan
2018-01-01
Targeting tumor angiogenesis is a common strategy against human hepatocellular carcinoma (HCC). However, identification of molecular targets as biomarker for elevating therapeutic efficacy is critical to prolong HCC patient survival. Here, we showed that EIF3C (eukaryotic translation initiation factor 3 subunit C) is upregulated during HCC tumor progression and associated with poor patient survival. Expression of EIF3C did not alter proliferation and expression of other tumor progressive genes such as HIF1A, TGFβ1 and VEGF, but reduced cell migration in HCC cells. Nevertheless, expression of EIF3C in HCC cells significantly increase secretion of extracellular exosomes confirmed by increased exosomes labelling by PKH26 fluorescent dye, vesicles in exosome size detected by electronic microscopy and nanoparticle tracking analysis, and expression of divergent exosome markers. The EIF3C-increased exosomes were oncogenic to potentiate tumor angiogenesis via tube formation of HUVEC cells and growth of vessels by plugs assays on nude mice. Subcutaneous inoculation of EIF3C-exosomes mixed with Huh7 HCC cells not only promoted growth of vessels but also increased expression of EIF3C in tumors. Conversely, treatment of exosome inhibitor GW4869 reversed aforementioned oncogenic assays. We identified EIF3C activated expression of S100A11 involved in EIF3C-exosome increased tube formation in angiogenesis. Simultaneous high expression of EIF3C and S100A11 in human HCC tumors for RNA level in TCGA and protein level by IHC are associated with poor survival of HCC patients. Collectively, our results demonstrated that EIF3C overexpression is a potential target of angiogenesis for treatment with exosome inhibitor or S100A11 reduction to suppress HCC angiogenesis and tumorigenesis. PMID:29568350
Benya, R V; Fathi, Z; Kusui, T; Pradhan, T; Battey, J F; Jensen, R T
1994-08-01
Stimulation of the gastrin-releasing peptide receptor (GRP-R) in Swiss 3T3 cells resembles that of a number of other recently described G protein-coupled receptors, insofar as both the phospholipase C and adenylyl cyclase signal transduction pathways are activated. GRP-R activation induces numerous alterations in both the cell and the receptor, but because two signal transduction pathways are activated it is difficult to determine the specific contributions of either pathway. We have found that BALB/3T3 fibroblasts transfected with the coding sequence for the GRP-R are pharmacologically indistinguishable from native receptor-expressing cells and activate phospholipase C in a manner similar to that of the native receptor but fail to increase cAMP in response to bombesin; thus, they may be useful cells to explore the role of activation of each pathway in altering cell and receptor function. Swiss 3T3 cells and GRP-R-transfected BALB/3T3 cells expressed identically glycosylated receptors that bound various agonists and antagonists similarly. G protein activation, as determined by evaluation of agonist-induced activation of phospholipase C and by analysis of the effect of guanosine-5'-(beta,gamma-imido)triphosphate on GRP-R binding affinity, was indistinguishable. Agonist stimulation of GRP-R caused similar receptor changes (internalization and down-regulation) and homologous desensitization in both cell types. Bombesin stimulation of Swiss 3T3 cells that had been preincubated with forskolin increased cAMP levels 9-fold, but no bombesin-specific increase in cAMP levels was detected in transfected cells, even though forskolin and cholera toxin increased cAMP levels in these cells. Quiescent Swiss 3T3 cells treated with bombesin rapidly increased c-fos mRNA levels and [3H]thymidine incorporation, whereas both effects were potentiated by forskolin. The specific protein kinase A inhibitor H-89 blocked increases in c-fos levels and [3H]thymidine incorporation induced by low concentrations of bombesin. GRP-R-transfected BALB/3T3 cells increased c-fos mRNA levels and [3H]thymidine incorporation with the addition of serum but not bombesin. These data suggest that bombesin-stimulated increases in cellular levels of cAMP appear not to be an important mediator of GRP-R internalization, down-regulation, or desensitization but do play an important role in bombesin-induced mitogenesis.
NASA Astrophysics Data System (ADS)
Hobbie, Erik A.; Schubert, Brian A.; Craine, Joseph M.; Linder, Ernst; Pringle, Anne
2017-02-01
How climate and rising carbon dioxide concentrations (pCO2) have influenced competition between C3 and C4 plants over the last 50 years is a critical uncertainty in climate change research. Here we used carbon isotope (δ13C) values of the saprotrophic lawn fungus Amanita thiersii to integrate the signal of C3 and C4 carbon in samples collected between 1982 and 2009 from the Midwestern USA. We then calculated 13C fractionation (Δ) to assess the balance between C3 and C4 photosynthesis as influenced by mean annual temperature (MAT), mean annual precipitation over a 30 year period (MAP-30), and pCO2. Sporocarp Δ correlated negatively with MAT (-1.74‰ °C-1, 79% of variance) and positively with MAP (9.52‰ m-1, 15% of variance), reflecting the relative productivity of C3 and C4 grasses in lawns. In addition, Δ values correlated positively with pCO2 (0.072‰ ppm-1, 5% of variance). Reduced photorespiration with rising pCO2 accounted for 20% of this increased Δ, but the remaining 80% is consistent with increased assimilation of C3-derived carbon by Amanita thiersii resulting from increased productivity of C3 grasses with rising pCO2. Between 1982 and 2009, pCO2 rose by 46 ppm and the relative contribution of C3 photosynthesis to Amanita thiersii carbon increased 18.5%. The δ13C value of Amanita thiersii may integrate both lawn maintenance practices and the physiological responses of turf grasses to rising CO2 concentrations.
NASA Astrophysics Data System (ADS)
Yang, Xin-Bo; Xu, Jun; Li, Hong-Jun; Bi, Qun-Yu; Cheng, Yan; Su, Liang-Bi; Tang, Qiang
2010-04-01
Recently, α-Al2O3:C crystal with highly sensitive thermoluminescence (TL) and optically stimulated luminescence (OSL) has been successfully grown by the temperature gradient technique. This paper investigates the heating rate dependence of TL sensitivity, light-induced fading of TL signals and thermal stability of OSL of α-Al2O3:C crystals. As the heating rate increases, the integral TL response decreases and the dosimetric glow peak shifts to higher temperatures in α-Al2O3:C crystals. Light-induced fading of TL increases with the irradiation dose, and TL response decreases as the exposure time increases, especially in the first 15 minutes. With the increasing intensity of the exposure light, the TL fading of α-Al2O3:C crystal increases sharply. The OSL response of as-grown α-Al2O3:C crystal is quite stable below 373 K and decreases sharply for higher temperatures.
Way, Danielle A; Katul, Gabriel G; Manzoni, Stefano; Vico, Giulia
2014-07-01
C4 photosynthesis evolved independently numerous times, probably in response to declining atmospheric CO2 concentrations, but also to high temperatures and aridity, which enhance water losses through transpiration. Here, the environmental factors controlling stomatal behaviour of leaf-level carbon and water exchange were examined across the evolutionary continuum from C3 to C4 photosynthesis at current (400 μmol mol(-1)) and low (280 μmol mol(-1)) atmospheric CO2 conditions. To this aim, a stomatal optimization model was further developed to describe the evolutionary continuum from C3 to C4 species within a unified framework. Data on C3, three categories of C3-C4 intermediates, and C4 Flaveria species were used to parameterize the stomatal model, including parameters for the marginal water use efficiency and the efficiency of the CO2-concentrating mechanism (or C4 pump); these two parameters are interpreted as traits reflecting the stomatal and photosynthetic adjustments during the C3 to C4 transformation. Neither the marginal water use efficiency nor the C4 pump strength changed significantly from C3 to early C3-C4 intermediate stages, but both traits significantly increased between early C3-C4 intermediates and the C4-like intermediates with an operational C4 cycle. At low CO2, net photosynthetic rates showed continuous increases from a C3 state, across the intermediates and towards C4 photosynthesis, but only C4-like intermediates and C4 species (with an operational C4 cycle) had higher water use efficiencies than C3 Flaveria. The results demonstrate that both the marginal water use efficiency and the C4 pump strength increase in C4 Flaveria to improve their photosynthesis and water use efficiency compared with C3 species. These findings emphasize that the advantage of the early intermediate stages is predominantly carbon based, not water related. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Larsen, Mette Krogh; Vogdanou, Stefania; Hellwing, Anne Louise F; Rybicka, Iga; Weisbjerg, Martin Riis
2016-11-01
The composition of grass/clover silage varies depending on time of harvest time. In particular silage from late regrowths is expected to contain lower fibre and higher linolenic acid concentrations compared to spring growth, thereby autumn silage is expected to increase linolenic acid content of milk fat. Rapeseed supplementation is expected to increase milk production and to increase all C18 fatty acids in milk fat. An interaction between rapeseed and silage type is expected, as hydrogenation of unsaturated fatty acids in rapeseed is expected to be less when low fibre silage is fed. Thirty-six Jersey cows were used in a 4 × 4 Latin square design, for 4 periods of 3 weeks and with a 2 × 2 factorial arrangement of treatments: spring grass/clover silage from primary growth or autumn grass/clover silage which was an equal mixture of 3rd regrowth and 4th regrowth, with or without rapeseed supplementation. Dry matter intake and milk production was higher for autumn than for spring silage. Rapeseed supplementation did not affect dry matter intake, but increased milk production. The concentrations of C18 : 1cis9, C18 : 2n6 and β-carotene and C18 : 3n3 in milk were increased whereas the concentrations of C16 : 0, riboflavin and α-tocopherol were decreased with autumn silage. The majority of C18 FAs in milk and α-tocopherol concentration increased with rapeseed whereas C11 : 0 to C16 : 0 FA were reduced. Autumn silage reduced biohydrogenation of C18 : 2n6, whereas rapeseed increased biohydrogenation of C18 : 2n6 and reduced biohydrogenation of C18 : 3n3. Apparent recovery of C18 : 2n6 was reduced with rapeseed. Minor interaction effects of silage type and rapeseed addition were observed for some milk fatty acids. Feeding silage from late regrowth increased linolenic acid concentration in milk fat. Rapeseed inclusion increased milk production, and increased C18 : 0 as well as C18 : 1 fatty acids, but not C18 : 2 and C18 : 3 in milk fat. Interactions between silage type and rapeseed supplementation were minimal.
Hara, Shuichi; Kobayashi, Masamune; Kuriiwa, Fumi; Mukai, Toshiji; Mizukami, Hajime
2012-03-15
Studies have suggested that cAMP signaling pathways may be associated with the production of reactive oxygen species. In this study, we examined how modifications in cAMP signaling affected the production of hydroxyl radicals in rat striatum using microdialysis to measure extracellular 2,3-dihydroxybenzoic acid (2,3-DHBA), which is a hydroxyl radical adduct of salicylate. Up to 50 nmol of the cell-permeative cAMP mimetic 8-bromo-cAMP (8-Br-cAMP) increased 2,3-DHBA in a dose-dependent manner (there was no additional increase in 2,3-DHBA at 100 nmol). Another cAMP mimetic, dibutyryl cAMP (db-cAMP), caused a nonsignificant increase in 2,3-DHBA at 50 nmol and a significant decrease at 100 nmol. Up to 20 nmol of forskolin, which is a direct activator of adenylyl cyclase, increased 2,3-DHBA, similar to the effect of 8-Br-cAMP; however, forskolin resulted in a much greater increase in 2,3-DHBA. A potent inhibitor of protein kinase A (PKA), H89 (500 μM), potentiated the 8-Br-cAMP- and forskolin-induced increases in 2,3-DHBA and antagonized the inhibitory effect of 100 nmol of db-cAMP. Interestingly, the administration of 100 nmol of 8-bromo-cGMP alone or in combination with H89 had no significant effect on 2,3-DHBA levels. Doses of 100 nmol of a preferential PKA activator (6-phenyl-cAMP) or a preferential PKA inhibitor (8-bromoadenosine-3',5'-cyclic monophosphorothionate, Rp-isomer; Rp-8-Br-cAMPS), which also inhibits the cAMP-mediated activation of Epac (the exchange protein directly activated by cAMP), suppressed or enhanced, respectively, the formation of 2,3-DHBA. Up to 100 nmol of 8-(4-chlorophenylthio)-2'-O-methyladenosine-cAMP, which is a selective activator of Epac, dose-dependently stimulated the formation of 2,3-DHBA. These findings suggest that cAMP signaling plays contradictory roles (stimulation and inhibition) in the production of hydroxyl radicals in rat striatum by differential actions of Epac and PKA. These roles might contribute to the production of hydroxyl radicals concomitant with cAMP in carbon monoxide poisoning, because the formation of 2,3-DHBA was potentiated by the PKA inhibitor H89 and suppressed by Rp-8-Br-cAMPS, which inhibits PKA and Epac. Copyright © 2012 Elsevier Inc. All rights reserved.
Coupling Meteorological, Land Surface and Water Temperature Models in the Mississippi River Basin
NASA Astrophysics Data System (ADS)
Tang, C.; Cooter, E. J.
2017-12-01
Water temperature is a significant factor influencing of the stream ecosystem and water management especially under climate change. In this study, we demonstrate a physically based semi-Lagrangian water temperature model (RBM) coupled with the Variable Infiltration Capacity (VIC) hydrology model and Weather Research & Forecasting Model (WRF) in the Mississippi River Basin (MRB). The results of this coupling compare favorably with observed water temperature data at river gages throughout the MRB. Further sensitivity analysis shows that mean water temperatures increase by 1.3°C, 1.5°C, and 1.8°C in northern, central and southern MRB zones, respectively, under a hypothetical uniform air temperature increase of 3°C. If air temperatures increase uniformly by 6°C in this scenario, then water temperatures are projected to increase by 3.3°C, 3.5°C and 4.0°C. Lastly, downscaled air temperatures from a global climate model are used to drive the coupled VIC and RBM model from 2020 to 2099. Average stream temperatures from 2020 to 2099 increase by 1°C to 8°C above 1950 to 2010 average water temperatures, with non-uniform increases along the river. In some portions of the MRB, stream temperatures could increase above survival thresholds for several native fish species, which are critical components of the stream ecosystem. The increased water temperature accelerates harmful algal blooming which results in a larger dead zone in the Gulf of Mexico.
Kang, Seong-Il; Shin, Hye-Sun; Kim, Se-Jae
2015-01-01
Sinensetin is a rare polymethoxylated flavone (PMF) found in certain citrus fruits. In this study, we investigated the effects of sinensetin on lipid metabolism in 3T3-L1 cells. Sinensetin promoted adipogenesis in 3T3-L1 preadipocytes growing in incomplete differentiation medium, which did not contain 3-isobutyl-1-methylxanthine. Sinensetin up-regulated expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and sterol regulatory element-binding protein 1c. It also potentiated expression of C/EBPβ and activation of cAMP-responsive element-binding protein. Sinensetin enhanced activation of protein kinase A and increased intracellular cAMP levels in 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, sinensetin stimulated lipolysis via a cAMP pathway. Taken together, these results suggest that sinensetin enhances adipogenesis and lipolysis by increasing cAMP levels in adipocytes.
Blackhole formula and example relativity
NASA Astrophysics Data System (ADS)
Shin, Philip
Black hole formula 1) Second dimension (x,y) f(x)=y Energy E=m*c2 2) Third dimension (x,y,z) really x=y=z Black hole formula Root(c2)=c=Root(E/m) As mass go the velocity of light, mass become black hole so there are energy as multiply by mass. Example relativity When E=m*c2 1) Root(c2)=c=Root(E/m) 2) 3*c*Root(c2)=3*c*Root(E/m)=3*c2 From 1) to 2) as an example, As velocity is faster, mass increased. It means when velocity is increased, sec(time) is slower, and m(distance) is increased. The number is good to study physics.
Effects of W on microstructure of as-cast 28 wt.%Cr–2.6 wt.%C–(0–10)wt.%W irons
DOE Office of Scientific and Technical Information (OSTI.GOV)
Imurai, S.; Thanachayanont, C.; Pearce, J.T.H.
2015-01-15
Microstructures of as-cast 28 wt.%Cr–2.6 wt.%C irons containing (0–10)wt.%W with the Cr/C ratio about 10 were studied and related to their hardness. The experimental irons were cast into dry sand molds. Microstructural investigation was performed by light microscopy, X-ray diffractometry, scanning electron microscopy, transmission electron microscopy and energy-dispersive X-ray spectrometry. It was found that the irons with 1 to 10 wt.%W addition was hypereutectic containing large primary M{sub 7}C{sub 3}, whereas the reference iron without W addition was hypoeutectic. The matrix in all irons was austenite, partly transformed to martensite during cooling. The volume fractions of primary M{sub 7}C{sub 3}more » and the total carbides increased, but that of eutectic carbides decreased with increasing the W content of the irons. W addition promoted the formation of W-rich M{sub 7}C{sub 3}, M{sub 6}C and M{sub 23}C{sub 6}. At about 4 wt.%W, two eutectic carbides including M{sub 7}C{sub 3} and M{sub 6}C were observed together with primary M{sub 7}C{sub 3}. At 10 wt.%W, multiple carbides including primary M{sub 7}C{sub 3}, fish-bone M{sub 23}C{sub 6}, and M{sub 6}C were observed. M{sub x}C where x = 3 or less has not been found due possibly to the high M/C ratio in the studied irons. W distribution to all carbides has been determined increasing from ca. 0.3 to 0.8 in mass fraction as the W content in the irons was increased. W addition led to an increase in Vickers macro-hardness of the irons up to 671 kgf/(mm){sup 2} (HV30/15) obtained from the iron with 10 wt.%W. The formation of primary M{sub 7}C{sub 3} and aggregates of M{sub 6}C and M{sub 23}C{sub 6} were the main reasons for hardness increase, indicating potentially improved wear performance of the as-cast irons with W addition. - Highlights: • W addition at 1 up to 10 wt.%W to Fe–28Cr–2.6C produced “hypereutectic” structure. • W addition promoted the formation of W-rich M{sub 7}C{sub 3}, M{sub 6}C and M{sub 23}C{sub 6}. • M{sub 23}C{sub 6} has higher Fe/Cr and W/Cr atm% ratios than those in M{sub 7}C{sub 3}. • Si content and high W content over about 11 atm% are characteristics of M{sub 6}C. • Primary M{sub 7}C{sub 3} and aggregates of M{sub 6}C and M{sub 23}C{sub 6} increased the alloy macro-hardness.« less
Johnson, R A; Rhodes, J S; Jeffrey, S L; Garland, T; Mitchell, G S
2003-01-01
Voluntary wheel running in rats increases hippocampal brain-derived neurotrophic factor (BDNF) expression, a neurochemical important for neuronal survival, differentiation, connectivity and synaptic plasticity. Here, we report the effects of wheel running on BDNF and neurotrophin-3 (NT-3) protein levels in normal control mice, and in mice selectively bred (25 generations) for increased voluntary wheel running. We hypothesized that increased voluntary wheel running in selected (S) mice would increase CNS BDNF and NT-3 protein levels more than in control (C) mice. Baseline hippocampal BDNF levels (mice housed without running wheels) were similar in S and C mice. Following seven nights of running, hippocampal BDNF increased significantly more in S versus C mice, and levels were correlated with distance run (considering C and S mice together). Spinal and cerebellar BDNF and hippocampal NT-3 levels were not significantly affected by wheel running in any group, but there was a small, positive correlation between spinal C3-C6 BDNF levels and distance run (considering C and S mice together). This is the first study to demonstrate that mice which choose to run more have greater elevations in hippocampal BDNF, suggesting enhanced potential for exercise-induced hippocampal neuroplasticity.
Interaction of microRNA-21/145 and Smad3 domain-specific phosphorylation in hepatocellular carcinoma
Wang, Ji Yu; Fang, Meng; Boye, Alex; Wu, Chao; Wu, Jia Jun; Ma, Ying; Hou, Shu; Kan, Yue; Yang, Yan
2017-01-01
MicroRNAs 21 and 145 exhibit inverse expression in Hepatocellular carcinoma (HCC), but how they relate to Smad3 C-terminal and Link region phosphorylation (pSmad3C and pSmad3L) downstream of TGF-β/MAPK signaling, remains inconclusive. Our results suggest microRNA-145 targets Smad3 in HepG2 cells. Decreased tumor volume and increased apoptosis were produced in both microRNA-21 antagomir and microRNA-145 agomir groups compared to controls. Inhibition of TβRI and MAPK (ERK, JNK, and p38) activation respectively produced decreased microRNA-21 but increased microRNA-145 expression. Correspondingly, the expression level of pSmad3C obviously increased while pSmad3L decreased in microRNA-145 agomir-group and the expression of pSmad3C/3L were not markedly changed but pERK, pJNK, pp38 decreased in microRNA-21 antagomir-group compared to controls. On the other hand, microRNA-145 and 21 increased respectively in xenografts of HepG2 cells transfected with Smad3 EPSM and 3S-A plasmid, and this correlated with the overexpression of pSmad3C and pSmad3L respectively compared to control. To conclude, microRNA-21 promotes tumor progression in a MAPK-dependent manner while microRNA-145 suppresses it via domain-specific phosphorylation of Smad3 in HCC. Meanwhile, increased pSmad3C/3L lead to the up-regulation of microRNA-145/21 respectively. The interaction between pSmad3C/3L and microRNA-145/21 regulates HCC progression and the switch of pSmad3C/3L may serve as an important target for HCC therapy. PMID:29156696
Weinstein, J A; Taylor, S J; Rosenberg, M; DePeters, E J
2016-08-01
Previously, feeding whey protein gels containing polyunsaturated fatty acids (PUFA) reduced their rumen biohydrogenation and increased their concentration in milk fat of Holstein cows. Our objective was to test the efficacy of whey protein isolate (WPI) gels produced in a steam tunnel as a method to alter the fatty acid (FA) composition of the milk lipids. Four primiparous Lamancha goats in midlactation were fed three diets in a 3 × 4 Latin square design. The WPI gels were added to a basal concentrate mix that contained one of three lipid sources: (i) 100% soya bean oil (S) to create (WPI/S), (ii) a 1:1 (wt/wt) mixture of S and linseed (L) oil to create (WPI/SL), or (iii) 100% L to create (WPI/L). Periods were 22 days with the first 10 days used as an adjustment phase followed by a 12-day experimental phase. During the adjustment phase, all goats received a rumen available source of lipid, yellow grease, to provide a baseline for milk FA composition. During the experimental phase, each goat received its assigned WPI. Milk FA concentration of C18:2 n-6 and C18:3 n-3 reached 9.3 and 1.64 g/100 g FA, respectively, when goats were fed WPI/S. Feeding WPI/SL increased the C18:2 n-6 and C18:3 n-3 concentration to 6.22 and 4.36 g/100 g FA, and WPI/L increased C18:2 n-6 and C18:3 n-3 to 3.96 and 6.13 g/100 g FA respectively. The adjusted transfer efficiency (%) of C18:3 n-3 to milk FA decreased significantly as dietary C18:3 n-3 intake increased. Adjusted transfer efficiency for C18:2 n-6 did not change with increasing intake of C18:2 n-6. The WPI gels were effective at reducing rumen biohydrogenation of PUFA; however, we observed a change in the proportion increase of C18:3 n-3 in milk FA suggesting possible regulation of n-3 FA to the lactating caprine mammary gland. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.
Cropley, Vanessa; Laskaris, Liliana; Zalesky, Andrew; Weickert, Cynthia Shannon; Biase, Maria Di; Chana, Gursharan; Baune, Bernhard; Bousman, Chad; Nelson, Barnaby; McGorry, Patrick D; Everall, Ian; Pantelis, Christos
2018-01-01
Abstract Background The complement system - a key component of the innate immune system, has been proposed to contribute to the pathogenesis of schizophrenia. Recently, complement C4 was associated with increased risk of schizophrenia, and in a mouse model, developmentally-timed synaptic pruning. These observations have led to proposals that abnormal activation of the complement system might contribute to the development of schizophrenia by disrupting synaptic pruning during key developmental periods. However, despite renewed interest in the complement system in schizophrenia it remains unclear whether peripheral complement levels differ in cases compared to controls, change over the course of illness and whether they are associated with current symptomatology and brain cortical thickness. This study aimed to: i) investigate whether peripheral complement protein levels are altered at different stages of illness, and ii) identify patterns among complement protein levels that predict clinical symptoms and grey matter thickness across the cortex. Methods Complement factors C1q, C3 and C4 were quantified in 183 participants [n=83 Healthy Controls (HC), n=10 Ultra-High Risk (UHR) for psychosis, n=40 First Episode Psychosis (FEP), n=50 Chronic schizophrenia] using Multiplex ELISA. Permutation-based t-tests were used to assess between-group differences in complement protein levels at each of the three illness stages, relative to age- and gender-matched healthy controls. Canonical correlation analysis was used to identify patterns of complement protein levels that correlated with clinical symptoms and regional thickness across the cortex. Results C3 and C4 were significantly increased in FEP and UHR patients, whereas only C4 was significantly increased in chronic patients. A molecular pattern of increased C4 and decreased C3 was associated with positive and negative symptom severity in the pooled patient sample. Increased C4 levels alone, or decreased C3 levels alone, did not correlate with symptom severity as strongly as the pattern of increased C4 in combination with decreased C3. Preliminary canonical correlation analyses revealed that, in healthy controls, a molecular pattern characterised by increased C3 and decreased C4 was associated with relatively thinner paracentral, inferior parietal and inferior temporal cortices, but relatively thicker insular, in the left hemisphere. In the pooled patient group, a trend for increased C3 in combination with decreased C1q was associated with relatively thinner left lateral occipital cortex and pars orbitalis but relatively thicker pars opercularis and precuneus. Discussion Our findings indicate that peripheral complement concentration is particularly increased early and preceding psychosis and its imbalance may be associated with symptom severity and variation in regional grey matter thickness across the cortex.
NASA Astrophysics Data System (ADS)
Unruh, Eckehardt; Hansen, Peter-Diedrich
Hemocytes are the primary defence of the Blue Mussel against invading microorganisms and foreign particles. The hemocytes of mussels as part of the immune system of invertebrates has not been studied so far in space. The choice of the phagocytes from invertebrates is justified by the claim to study the universal validity of innate immune responses. The hemocytes of mussels have a lot in common with macrophages of higher organisms. They are able to detect the presence of microorganisms and kill these microorganisms by phagocytosis. The phagocy-tosis related production of ROS will be stimulated with opsonised zymosan. The hemocytes will be stored frozen and reconstituted in-flight for the experiment. The signals of the im-muno cellular responses are translated into luminescence as a rapid optical reporter system. The primary aim of Triplelux B is to investigate under space flight conditions the effect of microgravity on the ability of isolated Blue Mussel hemocytes to perform phagocytosis. As a secondery objectiv, the results expected will allow to conclude whether the observed responses are caused by microgravity and/or radiation (change in permeability, endpoints in genotoxicity: DNA unwinding). The TRIPLELUX-B Experiment contributes to risk assessment concerning immunotoxicity under space flight conditions. The components of the fully automated AEC (Advanced Experimental Containment) will be demonstrated. The AEC of the TRIPLELUX-B experiment will contribute to a real time operational monitoring for immunotoxicity testing for earth. Blue mussels have been used repeatedly for monitoring imunotoxicity and genotoxicity in coastal waters. Based on the AEC an automatet measuring device will allow "real time monitoring" providing observations of immunotoxicity in coastal and inland waters.
Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk.
den Hartog, Gerco; Jacobino, Shamir; Bont, Louis; Cox, Linda; Ulfman, Laurien H; Leusen, Jeanette H W; van Neerven, R J Joost
2014-01-01
Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV. ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.
Barger, N.N.; Ojima, D.S.; Belnap, J.; Shiping, W.; Yanfen, W.; Chen, Z.
2004-01-01
This study reports on changes in plant functional group composition, litter quality, and soil C and N mineralization dynamics from a 9-year sheep grazing study in Inner Mongolia. Addressed are these questions: 1) How does increasing grazing intensity affect plant community composition? 2) How does increasing grazing intensity alter soil C and N mineralization dynamics? 3) Do changes in soil C and N mineralization dynamics relate to changes in plant community composition via inputs of the quality or quantity of litter? Grazing plots were set up near the Inner Mongolia Grassland Ecosystem Research Station (IMGERS) with 5 grazing intensities: 1.3, 2.7, 4.0, 5.3, and 6.7 sheep ha -1??yr-1. Plant cover was lower with increasing grazing intensity, which was primarily due to a dramatic decline in grasses, Carex duriuscula, and Artemisia frigida. Changes in litter mass and percentage organic C resulted in lower total C in the litter layer at 4.0 and 5.3 sheep ha-1??yr-1 compared with 2.7 sheep ha -1??yr-1. Total litter N was lower at 5.3 sheep ha-1??yr-1 compared with 2.7 sheep ha -1??yr-1. Litter C:N ratios, an index of litter quality, were significantly lower at 4.0 sheep ha-1??yr -1 relative to 1.3 and 5.3 sheep ha-1??yr -1. Cumulative C mineralized after 16 days decreased with increasing grazing intensity. In contrast, net N mineralization (NH4+ + NO3-) after a 12-day incubation increased with increasing grazing intensity. Changes in C and N mineralization resulted in a narrowing of CO2-C:net Nminratios with increasing grazing intensity. Grazing explained 31% of the variability in the ratio of CO 2-C:net Nmin. The ratio of CO2-C:net N min was positively correlated with litter mass. Furthermore, there was a positive correlation between litter mass and A. frigida cover. Results suggest that as grazing intensity increases, microbes become more C limited resulting in decreased microbial growth and demand for N.
Cell wall modifications triggered by the down-regulation of Coumarate 3-hydroxylase-1 in maize.
Fornalé, Silvia; Rencoret, Jorge; Garcia-Calvo, Laura; Capellades, Montserrat; Encina, Antonio; Santiago, Rogelio; Rigau, Joan; Gutiérrez, Ana; Del Río, José-Carlos; Caparros-Ruiz, David
2015-07-01
Coumarate 3-hydroxylase (C3H) catalyzes a key step of the synthesis of the two main lignin subunits, guaiacyl (G) and syringyl (S) in dicotyledonous species. As no functional data are available in regards to this enzyme in monocotyledonous species, we generated C3H1 knock-down maize plants. The results obtained indicate that C3H1 participates in lignin biosynthesis as its down-regulation redirects the phenylpropanoid flux: as a result, increased amounts of p-hydroxyphenyl (H) units, lignin-associated ferulates and the flavone tricin were detected in transgenic stems cell walls. Altogether, these changes make stem cell walls more degradable in the most C3H1-repressed plants, despite their unaltered polysaccharide content. The increase in H monomers is moderate compared to C3H deficient Arabidopsis and alfalfa plants. This could be due to the existence of a second maize C3H protein (C3H2) that can compensate the reduced levels of C3H1 in these C3H1-RNAi maize plants. The reduced expression of C3H1 alters the macroscopic phenotype of the plants, whose growth is inhibited proportionally to the extent of C3H1 repression. Finally, the down-regulation of C3H1 also increases the synthesis of flavonoids, leading to the accumulation of anthocyanins in transgenic leaves. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3.
Chen, Shuzhen; Cao, Wei; Yue, Ping; Hao, Chunhai; Khuri, Fadlo R; Sun, Shi-Yong
2011-10-01
Celecoxib is a COX-2 inhibitor that reduces the risk of colon cancer. However, the basis for its cancer chemopreventive activity is not fully understood. In this study, we defined a mechanism of celecoxib action based on degradation of cellular FLICE-inhibitory protein (c-FLIP), a major regulator of the death receptor pathway of apoptosis. c-FLIP protein levels are regulated by ubiquitination and proteasome-mediated degradation. We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition of glycogen synthase kinase-3 (GSK3), itself a candidate therapeutic target of interest in colon cancer. Celecoxib increased the levels of phosphorylated GSK3, including the α and β forms, even in cell lines, where phosphorylated Akt levels were not increased. Phosphoinositide 3-kinase inhibitors abrogated Akt phosphorylation as expected but had no effect on celecoxib-induced GSK3 phosphorylation. In contrast, protein kinase C (PKC) inhibitors abolished celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3 phosphorylation through a mechanism that relied upon PKC and not Akt. GSK3 blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as expected. Our findings reveal a novel mechanism through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3, which celecoxib acts at an upstream level to control independently of Akt.
Bates, Ryan C.; Stith, Bradley J.; Stevens, Karen E.; Adams, Catherine E.
2014-01-01
Decreased expression of CHRNA7, the gene encoding the α7* subtype of nicotinic receptor, may contribute to the cognitive dysfunction observed in schizophrenia by disrupting the inhibitory/excitatory balance in the hippocampus. C3H mice with reduced Chrna7 expression have significant reductions in hippocampal α7* receptor density, deficits in hippocampal auditory gating, increased hippocampal activity as well as significant decreases in hippocampal glutamate decarboxylase-65 (GAD65) and γ-aminobutyric acid-A (GABAA) receptor levels. The current study investigated whether altered Chrna7 expression is associated with changes in the levels of parvalbumin, GAD67 and/or GABAA receptor subunits in hippocampus from male and female C3H Chrna7 wildtype, C3H Chrna7 heterozygous and C3H Chrna7 knockout mice using quantitative western immunoblotting. Reduced Chrna7 expression was associated with significant increases in hippocampal parvalbumin and GAD67 and with complex alterations in GABAA receptor subunits. A decrease in α3 subunit protein was seen in both female C3H Chrna7 Het and KO mice while a decrease in α4 subunit protein was also detected in C3H Chrna7 KO mice with no sex difference. In contrast, an increase in δ subunit protein was observed in C3H Chrna7 Het mice while a decrease in this subunit was observed in C3H Chrna7 KO mice, with δ subunit protein levels being greater in males than in females. Finally, an increase in γ2 subunit protein was found in C3H Chrna7 KO mice with the levels of this subunit again being greater in males than in females. The increases in hippocampal parvalbumin and GAD67 observed in C3H Chrna7 mice are contrary to reports of reductions in these proteins in postmortem hippocampus from schizophrenic individuals. We hypothesize that the disparate results may occur because of the influence of factors other than CHRNA7 that have been found to be abnormal in schizophrenia. PMID:24836856
Puckette, Michael; Clark, Benjamin A; Smith, Justin D; Turecek, Traci; Martel, Erica; Gabbert, Lindsay; Pisano, Melia; Hurtle, William; Pacheco, Juan M; Barrera, José; Neilan, John G; Rasmussen, Max
2017-11-15
The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a Gaussia luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCE The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production. Copyright © 2017 Puckette et al.
Increased Notch3 Activity Mediates pathological Changes in Structure of Cerebral arteries
Baron-Menguy, Celine; Domenga-Denier, Valérie; Ghezali, Lamia; Faraci, Frank; Joutel, Anne
2016-01-01
CADASIL, the most frequent genetic cause of stroke and vascular dementia, is caused by highly stereotyped mutations in the NOTCH3 receptor, which is predominantly expressed in vascular smooth muscle. The well-established TgNotch3R169C mouse model develops characteristic features of the human disease, with deposition of NOTCH3 and other proteins, including TIMP3 (tissue inhibitor of metalloproteinase 3), on brain vessels as well as reduced maximal dilation, and attenuated myogenic tone of cerebral arteries, but without elevated blood pressure. Increased TIMP3 levels were recently shown to be a major determinant of altered myogenic tone. In this study, we investigated the contribution of TIMP3 and Notch3 signaling to the impairment of maximal vasodilator capacity caused by the archetypal R169C mutation. Maximally dilated cerebral arteries in TgNotch3R169C mice exhibited a decrease in lumen diameter over a range of physiological pressures that occurred prior to myogenic tone deficits. This defect was not prevented by genetic reduction of TIMP3 in TgNotch3R169C mice and was not observed in mice overexpressing TIMP3. Knock-in mice with the R169C mutation (Notch3R170C/R170C) exhibited similar reductions in arterial lumen, and both TgNotch3R169C and Notch3R170C/R170C mice showed increased cerebral artery expression of Notch3 target genes. Reduced maximal vasodilation was prevented by conditional reduction of Notch activity in smooth muscle of TgNotch3R169C mice and mimicked by conditional activation of Notch3 in smooth muscle, an effect that was blood pressure-independent. We conclude that increased Notch3 activity mediates reduction in maximal dilator capacity of cerebral arteries in CADASIL and may contribute to reductions in cerebral blood flow. PMID:27821617
Increased Notch3 Activity Mediates Pathological Changes in Structure of Cerebral Arteries.
Baron-Menguy, Celine; Domenga-Denier, Valérie; Ghezali, Lamia; Faraci, Frank M; Joutel, Anne
2017-01-01
CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), the most frequent genetic cause of stroke and vascular dementia, is caused by highly stereotyped mutations in the NOTCH3 receptor, which is predominantly expressed in vascular smooth muscle. The well-established TgNotch3 R169C mouse model develops characteristic features of the human disease, with deposition of NOTCH3 and other proteins, including TIMP3 (tissue inhibitor of metalloproteinase 3), on brain vessels, as well as reduced maximal dilation, and attenuated myogenic tone of cerebral arteries, but without elevated blood pressure. Increased TIMP3 levels were recently shown to be a major determinant of altered myogenic tone. In this study, we investigated the contribution of TIMP3 and Notch3 signaling to the impairment of maximal vasodilator capacity caused by the archetypal R169C mutation. Maximally dilated cerebral arteries in TgNotch3 R169C mice exhibited a decrease in lumen diameter over a range of physiological pressures that occurred before myogenic tone deficits. This defect was not prevented by genetic reduction of TIMP3 in TgNotch3 R169C mice and was not observed in mice overexpressing TIMP3. Knock-in mice with the R169C mutation (Notch3 R170C/R170C ) exhibited similar reductions in arterial lumen, and both TgNotch3 R169C and Notch3 R170C/R170C mice showed increased cerebral artery expression of Notch3 target genes. Reduced maximal vasodilation was prevented by conditional reduction of Notch activity in smooth muscle of TgNotch3 R169C mice and mimicked by conditional activation of Notch3 in smooth muscle, an effect that was blood pressure-independent. We conclude that increased Notch3 activity mediates reduction in maximal dilator capacity of cerebral arteries in CADASIL and may contribute to reductions in cerebral blood flow. © 2016 American Heart Association, Inc.
C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients.
Nsaiba, Mohamed Jalloul; Lapointe, Marc; Mabrouk, Hajer; Douki, Wahiba; Gaha, Lotfi; Pérusse, Louis; Bouchard, Claude; Jrad, Besma Bel Hadj; Cianflone, Katherine
2015-05-01
Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.
Strunk, R C; Whitehead, A S; Cole, F S
1985-01-01
The third component of complement (C3) is a plasma glycoprotein with a variety of biologic functions in the initiation and maintenance of host response to infectious agents. While the hepatocyte is the primary source of plasma C3, mononuclear phagocytes contribute to the regulation of tissue availability of C3. Lipopolysaccharide (LPS), a constituent of cell walls of gram-negative bacteria, consists of a polysaccharide moiety (core polysaccharide and O antigen) covalently linked to a lipid portion (lipid A). Using metabolic labeling with [35S]methionine, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis, we examined the effects of LPS on synthesis of C3 by human mononuclear phagocytes as well as synthesis of the second component of complement (C2), factor B, lysozyme, and total protein. LPS increased C3 synthesis 5-30-fold without affecting the kinetics of secretion of C3 or the synthesis of C2, lysozyme, or total protein. Factor B synthesis was consistently increased by LPS. Experiments with lipid A-inactivated LPS (alkaline treated), LPS from a polysaccharide mutant strain, and lipid X (a lipid A precursor) indicated that the lipid A portion is the structural element required for this effect. Northern blot analysis demonstrated at least a fivefold increase in C3 mRNA in LPS-treated monolayers, which suggests that the regulation of the increase in C3 synthesis is pretranslational. C2 mRNA and factor B mRNA were increased approximately twofold. The availability of specific gene products in human mononuclear phagocytes that respond to LPS should permit understanding of the molecular regulation of more complex functions of these cells elicited by LPS in which multiple gene products are coordinately expressed. Images PMID:3900137
CO2 availability influences hydraulic function of C3 and C4 grass leaves
Blackman, Chris J
2018-01-01
Abstract Atmospheric CO2 (ca) has increased since the last glacial period, increasing photosynthetic water use efficiency and improving plant productivity. Evolution of C4 photosynthesis at low ca led to decreased stomatal conductance (gs), which provided an advantage over C3 plants that may be reduced by rising ca. Using controlled environments, we determined how increasing ca affects C4 water use relative to C3 plants. Leaf gas exchange and mass per area (LMA) were measured for four C3 and four C4 annual, crop-related grasses at glacial (200 µmol mol−1), ambient (400 µmol mol−1), and super-ambient (640 µmol mol−1) ca. C4 plants had lower gs, which resulted in a water use efficiency advantage at all ca and was broadly consistent with slower stomatal responses to shade, indicating less pressure on leaf water status. At glacial ca, net CO2 assimilation and LMA were lower for C3 than for C4 leaves, and C3 and C4 grasses decreased leaf hydraulic conductance (Kleaf) similarly, but only C4 leaves decreased osmotic potential at turgor loss. Greater carbon availability in C4 leaves at glacial ca generated a different hydraulic adjustment relative to C3 plants. At current and future ca, C4 grasses have advantages over C3 grasses due to lower gs, lower stomatal sensitivity, and higher absolute water use efficiency. PMID:29538702
Pysanenko, Andriy; Zabka, Jan; Feketeová, Linda; Märk, Tilmann D; Herman, Zdenek
2008-01-01
Collisions of C3Hn+ (n = 2-8) ions and some of their per- deuterated analogs with room temperature carbon (HOPG) surfaces (hydrocarbon-covered) were investigated over the incident energy range 13-45 eV in beam scattering experiments. The mass spectra of product ions were measured and main fragmentation paths of the incident projectile ions, energized in the surface collision, were determined. The extent of fragmentation increased with increasing incident energy. Mass spectra of even-electron ions C3H7+ and C3H5+ showed only fragmentations, mass spectra of radical cations C3H8*+ and C3H6*+ showed both simple fragmentations of the projectile ion and formation of products of its surface chemical reaction (H-atom transfer between the projectile ion and hydrocarbons on the surface). No carbon-chain build-up reaction (formation of C4 hydrocarbons) was detected. The survival probability of the incident ions, S(a), was usually found to be about 1-2% for the radical cation projectile ions C3H8*+, C3H6*+, C3H4*+ and C3H2*+ and several percent up to about 20% for the even-electron projectile ions C3H7+, C3H5+, C3H3+. A plot of S(a) values of C1, C2, C3, some C7 hydrocarbon ions, Ar+ and CO2+ on hydrocarbon-covered carbon surfaces as a function of the ionization energies (IE) of the projectile species showed a drop from about 10% to about 1% and less at IE 8.5-9.5 eV and further decrease with increasing IE. A strong correlation was found between log S(a) and IE, a linear decrease over the entire range of IE investigated (7-16 eV), described by log S(a) = (3.9 +/- 0.5)-(0.39 +/- 0.04) IE.
Gecgel, Umit
2013-06-01
Meatball samples were irradiated using a (60)Co irradiation source (with the dose of 1, 3, 5 and 7 kGy) and stored (1, 2 and 3 weeks at 4°C) to appraise some physicochemical properties and the fatty acid composition. The physicochemical results showed no significant differences in moisture, protein, fat and ash content of meatballs because of irradiation. However, total acidity, peroxide and thiobarbituric acid (TBA) values increased significantly as a result of irradiation doses and storage period. The fatty acid profile in meatball samples changed with irradiation. While saturated fatty acids (C16:0, C17:0, C18:0, and C20:0) increased with irradiation, monounsaturated (C14:1, C15:1, C18:1, and C20:1) and polyunsaturated (C18:2, C18:3, and C22:2) fatty acids decreased with irradiation. Trans fatty acids (C16:1trans, C18:1trans, C18:2trans, C18:3trans) increased with increasing irradiation doses. Meatball samples irradiated at 7 kGy had the highest total trans fatty acid content. This research shows that some physicochemical properties and fatty acid composition of meatballs can be changed by gamma irradiation.
Buono, Michael J.; Krippes, Taylor; Kolkhorst, Fred W.; Williams, Alexander T.; Cabrales, Pedro
2015-01-01
Previous studies have reported that blood viscosity is significantly increased following exercise. However, these studies measured both pre- and post-exercise blood viscosity at 37 °C even though core and blood temperatures would be expected to have increased during the exercise. Consequently, the effect of exercise-induced hyperthermia on mitigating change in blood viscosity may have been missed. The purpose of this study was to isolate the effects of exercise-induced hemoconcentration and hyperthermia, as well as determine their combined effects, on blood viscosity. Nine subjects performed 2 h of moderate-intensity exercise in the heat (37 °C, 40% rH), which resulted in significant increases from pre-exercise values for rectal temperature (37.11 ± 0.35 °C to 38.76 ± 0.13 °C), hemoconcentration (hematocrit = 43.6 ± 3.6% to 45.6 ± 3.5%), and dehydration (Δbody weight = −3.6 ± 0.7%). Exercise-induced hemoconcentration significantly (P < 0.05) increased blood viscosity by 9% (3.97 to 4.30 cP at 300 s−1) while exercise-induced hyperthermia significantly decreased blood viscosity by 7% (3.97 to 3.70 cP at 300 s−1). However, when both factors were considered together, there was no overall change in blood viscosity (3.97 to 4.03 cP at 300 s−1). The effects of exercise-induced hemoconcentration, increased plasma viscosity, and increased red blood cell aggregation, all of which increased blood viscosity, were counterbalanced by increased RBC deformability (e.g., RBC membrane shear elastic modulus and elongation index) caused by the hyperthermia. Thus, blood viscosity remained unchanged following prolonged moderate-intensity exercise in the heat. PMID:26682653
Cunniff, Jennifer; Jones, Glynis; Charles, Michael; Osborne, Colin P
2017-01-01
Limitation of plant productivity by the low partial pressure of atmospheric CO 2 (C a ) experienced during the last glacial period is hypothesized to have been an important constraint on the origins of agriculture. In support of this hypothesis, previous work has shown that glacial C a limits vegetative growth in the wild progenitors of both C 3 and C 4 founder crops. Here, we present data showing that glacial C a also reduces grain yield in both crop types. We grew four wild progenitors of C 3 (einkorn wheat and barley) and C 4 crops (foxtail and broomcorn millets) at glacial and postglacial C a , measuring grain yield and the morphological and physiological components contributing to these yield changes. The C 3 species showed a significant increase in unthreshed grain yield of ~50% with the glacial to postglacial increase in C a , which matched the stimulation of photosynthesis, suggesting that increases in photosynthesis are directly translated into yield at subambient levels of C a . Increased yield was controlled by a higher rate of tillering, leading to a larger number of tillers bearing fertile spikes, and increases in seed number and size. The C 4 species showed smaller, but significant, increases in grain yield of 10-15%, arising from larger seed numbers and sizes. Photosynthesis was enhanced by C a in only one C 4 species and the effect diminished during development, suggesting that an indirect mechanism mediated by plant water relations could also be playing a role in the yield increase. Interestingly, the C 4 species at glacial C a showed some evidence that photosynthetic capacity was upregulated to enhance carbon capture. Development under glacial C a also impacted negatively on the subsequent germination and viability of seeds. These results suggest that the grain production of both C 3 and C 4 crop progenitors was limited by the atmospheric conditions of the last glacial period, with important implications for the origins of agriculture. © 2016 John Wiley & Sons Ltd.
Høgåsen, A K; Abrahamsen, T G
1993-01-01
Activation of the complement system is an important part of host resistance against fungal infections. When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found. However, when C. albicans was administered to freshly isolated monocytes, a consistent stimulation of factor B biosynthesis occurred, while the C3 production was increased in about 50% of the donors. C. albicans also induced the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the cultured cells, apparently in larger amounts in the donors in whom no stimulation of C3 production was found. An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 production. Furthermore, when monocytes were treated with recombinant human GM-CSF either at the same time as or 4 days prior to the addition of C. albicans, the increase in C3 production was suppressed or neutralized, while factor B biosynthesis was unaffected. Taken together, these results indicate that monocytes respond to C. albicans with an increased production of complement factors. This may be an important mechanism both for opsonization of the fungus and for initiation of an inflammatory reaction. At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF. PMID:8478067
Altered performance of forest pests under atmospheres enriched by C02 and O3
Kevin E. Percy; Caroline S. Awmack; Richard L. Lindroth; Mark E. Kubiske; Brian J. Kopper; J. G. Isebrands; Kurt S. Pregitzer; George R. Hendrey; Richard E. Dickson; Donald R. Zak; Elina Oksanen; Jaak Sober; Richard Harrington; David F. Karnosky
2002-01-01
Human activity causes increasing background concentrations of the greenhouse gases C02 and O3. Increased levels of C02 can be found in all terrestrial ecosystems. Damaging O3 concentrations currently occur over 29% of the world's temperate and subpolar forests but are...
Xu, Zhongcheng; Wu, Jimin; Xin, Junzhou; Feng, Yenan; Hu, Guomin; Shen, Jing; Li, Mingzhe; Zhang, Youyi; Xiao, Han; Wang, Li
2018-06-05
In heart failure, the expression of cardiac β 3 -adrenergic receptors (β 3 -ARs) increases. However, the precise role of β 3 -AR signaling within cardiomyocytes remains unclear. Transforming growth factor β1 (TGFβ1) is a crucial cytokine mediating the cardiac remodeling that plays a causal role in the progression of heart failure. Here, we set out to determine the effect of β 3 -AR activation on TGFβ1 expression in rat cardiomyocytes and examine the underlying mechanism. The selective β 3 -AR agonist BRL37344 induced an increase in TGFβ1 expression and the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun in β 3 -AR-overexpressing cardiomyocytes. Those effects of BRL37344 were suppressed by a β 3 -AR antagonist. Moreover, the inhibition of JNK and c-Jun activity by a JNK inhibitor and c-Jun siRNA blocked the increase in TGFβ1 expression upon β 3 -AR activation. A protein kinase G (PKG) inhibitor also attenuated β 3 -AR-agonist-induced TGFβ1 expression and the phosphorylation of JNK and c-Jun. In conclusion, the β 3 -AR activation in cardiomyocytes increases the expression of TGFβ1 via the PKG/JNK/c-Jun pathway. These results help us further understand the role of β 3 -AR signaling in heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.
Joffe, Yael T.; van der Merwe, Lize; Evans, Juliet; Collins, Malcolm; Lambert, Estelle V.; September, Alison; Goedecke, Julia H.
2014-01-01
This study investigated interactions between dietary fat intake and IL-6 polymorphisms on obesity and serum lipids in black and white South African (SA) women. Normal-weight and obese, black and white women underwent measurements of body composition, serum lipids and dietary fat intake, and were genotyped for the IL-6 −174 G>C, IVS3 +281 G>T and IVS4 +869 A>G polymorphisms. In black women the IVS4 +869 G allele was associated with greater adiposity, and with increasing dietary fat intake adiposity increased in the IVS3 +281 GT+GG and IVS4 +869 AA or AG genotypes. In white women, with increasing omega-3 (n-3) intake and decreasing n-6:n-3 ratio, body mass index (BMI) decreased in those with the −174 C allele, IVS3 +281 T allele and IVS4 +869 AG genotype. In the white women, those with the IVS3 +281 T allele had lower triglycerides. Further, with increasing n-3 polyunsaturated fatty acid (PUFA); triglyceride and total cholesterol:high-density lipoprotein cholesterol (T-C:HDL-C) ratio decreased in those with the −174 C allele. In black women, with increasing total fat intake, triglycerides and T-C:HDL-C ratio increased in those with the IVS4 +869 G allele. This study is the first to show that dietary fat intake modulates the relationship between the IL-6 −174 G>C, IVS3 +281 G>T and IVS4 +869 A>G polymorphisms on obesity and serum lipids in black and white SA women. PMID:24962479
Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3
Chen, Shuzhen; Cao, Wei; Yue, Ping; Hao, Chunhai; Khuri, Fadlo R.; Sun, Shi-Yong
2011-01-01
Celecoxib is a COX2 inhibitor that reduces the risk of colon cancer. However, the basis for its cancer chemopreventive activity is not fully understood. In this study, we defined a mechanism of celecoxib action based on degradation of c-FLIP, a major regulator of the death receptor pathway of apoptosis. c-FLIP protein levels are regulated by ubiquitination and proteasome-mediated degradation. We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition of GSK3 kinase, itself a candidate therapeutic target of interest in colon cancer. Celecoxib increased the levels of phosphorylated GSK3 (p-GSK3), including the α and β forms, even in cell lines where p-Akt levels were not increased. PI3K inhibitors abrogated Akt phosphorylation as expected but had no effect on celecoxib-induced GSK3 phosphorylation. In contrast, PKC inhibitors abolished celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3 phosphorylation through a mechanism relied upon PKC but not Akt. GSK3 blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as expected. Our findings reveal a novel mechanism through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3, which celecoxib acts at an upstream level to control independently of Akt. PMID:21868755
Stresses in chemical vapor deposited epitaxial 3C-SiC membranes
NASA Astrophysics Data System (ADS)
Su, C. M.; Fekade, A.; Spencer, M.; Wuttig, Manfred
1995-02-01
The internal stresses in chemical-vapor-deposited 3C-SiC films were studied by a vibrating membrane technique. The differential thermal expansivity of 3C-SiC films was investigated by the change of the internal stress as a function of temperature. It was found that the internal stress of the films is dominated by thermal stresses and its magnitude depends both on doping and the film thickness. While p doping substantially increases the stress, increasing the film thickness reduces the stress of the SiC layer. The thermal expansivity of the SiC layer shows a lower value which is significantly less than of bulk 3C-SiC and tends to approach the expansivity of the Si substrate. It is proposed that the stress dependence of the SiC films on doping and film thickness is the result of the film morphology which is heavily faulted for very thin films and more perfect as the film thickness increases.
Thompson, S N; Borchardt, D B; Wang, L-W
2003-03-01
This study examined the effects of dietary casein and sucrose levels on nutrient intake, and distinguished the effects of carbohydrate and protein consumption on growth, fat content, pyruvate metabolism and blood trehalose level of 5th instar Manduca sexta larvae. Growth increased with increasing casein consumption but was unaffected by carbohydrate intake. Fat content also increased with carbohydrate consumption, but on carbohydrate-free diets fat content increased with increased protein consumption. Blood trehalose level and pyruvate metabolism were examined by nuclear magnetic resonance spectroscopy analysis of blood following administration of (3-(13)C)pyruvate. On diets containing sucrose, blood trehalose increased with increasing carbohydrate intake, and on most diets trehalose was synthesized entirely from dietary sucrose. Pyruvate cycling, indicated by the alanine C2/C3 (13)C enrichment ratio, increased with carbohydrate consumption reflecting increased glycolysis, and pyruvate decarboxylation exceeded carboxylation on all sucrose diets. Larvae that consumed <75 mg/day sucrose were gluconeogenic, based on the [2 (trehalose C6)(Glx C3/C2)]/alanine C2] (13)C enrichment ratio. On carbohydrate-free diets, blood trehalose levels were low and maintained entirely by gluconeogenesis. Blood trehalose level increased with increasing protein intake. Pyruvate cycling was very low, although many insects displayed higher levels of pyruvate decarboxylation than carboxylation. All gluconeogenic larvae displayed alanine (13)C enrichment ratios <0.35 and had blood trehalose levels <50 mM.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tasaka, Akimasa, E-mail: aki-tasaka-load@yahoo.co.jp; Kotaka, Yuki; Oda, Atsushi
2014-09-01
In pure NF{sub 3} plasma, the etching rates of four kinds of single-crystalline SiC wafer etched at NF{sub 3} pressure of 2 Pa were the highest and it decreased with an increase in NF{sub 3} pressure. On the other hand, they increased with an increase in radio frequency (RF) power and were the highest at RF power of 200 W. A smooth surface was obtained on the single-crystalline 4H-SiC after reactive ion etching at NF{sub 3}/Ar gas pressure of 2 Pa and addition of Ar to NF{sub 3} plasma increased the smoothness of SiC surface. Scanning electron microscopy observation revealed that the numbermore » of pillars decreased with an increase in the Ar-concentration in the NF{sub 3}/Ar mixture gas. The roughness factor (R{sub a}) values were decreased from 51.5 nm to 25.5 nm for the As-cut SiC, from 0.25 nm to 0.20 nm for the Epi-SiC, from 5.0 nm to 0.7 nm for the Si-face mirror-polished SiC, and from 0.20 nm to 0.16 nm for the C-face mirror-polished SiC by adding 60% Ar to the NF{sub 3} gas. Both the R{sub a} values of the Epi- and the C-face mirror-polished wafer surfaces etched using the NF{sub 3}/Ar (40:60) plasma were similar to that treated with mirror polishing, so-called the Catalyst-Referred Etching (CARE) method, with which the lowest roughness of surface was obtained among the chemical mirror polishing methods. Etching duration for smoothing the single-crystalline SiC surface using its treatment was one third of that with the CARE method.« less
Shaw, My Le; Kelley, Brian; Camarata, Paul; Sokol, Jason A
2012-01-01
To determine factors associated with increased heat transfer during neurosurgical drilling as a mechanism for optic nerve injury. On a nonembalmed cadaver, the optic canal was exposed through a standard craniotomy and optic nerve sparing exenteration. The temperature was measured with a thermocoupler during each 30-second continuous drill session using 2 types of neurosurgical drills. The location of the probe, drill site, drill power, and irrigation rate were varied. A <1 °C change was measured in the optic canal at all test distances with the Cavitron Ultrasonic Surgical Aspirator and diamond drill. The use of manual irrigation decreased the mean change in temperature (ΔT) in the sphenoid bone from 4.7 °C without irrigation to 1.3 °C with irrigation. Increasing Cavitron Ultrasonic Surgical Aspirator power from 50% to 80% at an irrigation rate of 4 ml/minute more than doubled ΔT in sphenoid bone from 3.2 °C at 50% to 8.1 °C at 80%. Increasing irrigation from 2 to 4 ml/minute decreased mean ΔT by -1.1 °C (3.2 °C at 2 ml/minute versus 2.1 °C at 4 ml/minute) at Cavitron Ultrasonic Surgical Aspirator power of 50%, but at Cavitron Ultrasonic Surgical Aspirator power of 80%, increasing irrigation increased mean ΔT by 3.0 °C (3.7 °C at 2 ml/minute versus 6.8 °C at 4 ml/minute). Care must be taken during neurosurgical procedures to decrease heat transfer during drilling to nearby structures. With increase in drill power, there is a noticeable increase in temperature change from baseline. These temperature changes can be mediated by irrigation, although the effect of increasing irrigation rate to suppress the raise in temperature decreases with increasing drill power.
Lu, Xinyue; Song, Kaimei
2015-01-01
Belonging to the PLIN family, PLIN2 associates with lipid storage droplets (LSDs), but other functions of PLIN2 remain unclear. Here, we suggest that PLIN2 mediates Wnt signaling because PLIN2 small interfering RNA (siRNA) suppresses activation of Wnt/coreceptor pathways. The mediation in the Wnt/Frizzled pathway seems to occur from Dishevelleds to axin/glycogen synthase kinase 3(GSK3)/β-catenin complexes (AGβC) as Wnt decreases Dishevelled/PLIN2 but increases AGβC/PLIN2 associations. Augmenting cellular LSDs that affect PLIN2 associations with these proteins, oleic acid (OA) treatment inhibits Wnt-increased AGβC/PLIN2 associations and β-catenin T-cell factor signaling (β-CTS). Revealing that PLIN2 is a GSK3-associated protein, the study explored PLIN2-mediated effects on GSK3/GSK3 substrates. PLIN2 siRNA reduces inhibitory GSK3 levels and lithium chloride (LiCl)-upregulated β-catenin or CCAAT/enhancer binding protein α (c/EBPα) expression. OA treatment decreases LiCl-increased c/EBPα via PLIN2-c/EBPα dissociation. In addition to PLIN2 overexpression increasing β-CTS, PLIN2 depletion or overexpression drops or adds expression of GSK3 substrates, such as β-catenin, c/EBPα,c-Myc, cyclin D1, and insulin receptor substrate 1, and cell growth/survival. PLIN2 N or C terminus overexpression that is associated with higher levels of the substrates suggests that those substrates bind to specific regions of PLIN2. Mimicking the possible high lipid concentrations in cells in the human body under conditions of hyperlipidemia/obesity, OA-treated cells gain or reduce GSK3 substrate expression in parallel with a decrease (a Wnt-like effect) or increase in GSK3 activity, likely regulated by GSK3/PLIN2/GSK3 substrate associations. PMID:26598603
Wang, He-ling; Zhang, Qiang; Wang, Run-yuan; Gan, Yan-tai; Niu, Jun-yi; Zhang, Kai; Zhao, Fu-nian; Zhao, Hong
2015-01-01
In order to predict effects of climate changing on growth, quality and grain yields of spring wheat, a field experiment was conducted to investigate the effects of air temperature increases (0 °C, 1.0 °C, 2.0° C and 3.0°) and precipitation variations (decrease 20%, unchanging and increase 20%) on grain yields, quality, diseases and insect pests of spring wheat at the Dingxi Arid Meteorology and Ecological Environment Experimental Station of the Institute of Arid Meteorology of China Meteorological Administration (35°35' N ,104°37' E). The results showed that effects of precipitation variations on kernel numbers of spring wheat were not significant when temperature increased by less than 2.0° C , but was significant when temperature increased by 3.0° C. Temperature increase enhanced kernel numbers, while temperature decrease reduced kernel numbers. The negative effect of temperature on thousand-kernel mass of spring wheat increased with increasing air temperature. The sterile spikelet of spring wheat response to air temperature was quadratic under all precipitation regimes. Compared with control ( no temperature increase), the decreases of grain yield of spring wheat when air temperature increased by 1.0°C, 2.0°C and 3.0°C under each of the three precipitation conditions (decrease 20%, no changing and increase 20%) were 12.1%, 24.7% and 42.7%, 8.4%, 15.1% and 21.8%, and 9.0%, 15.5% and 22.2%, respectively. The starch content of spring wheat decreased and the protein content increased with increasing air temperature. The number of aphids increased when air temperature increased by 2.0°C , but decreased when air temperature increased by 3.0°CT. The infection rates of rust disease increased with increasing air temperature.
NASA Technical Reports Server (NTRS)
Koscheyev, Victor S.; Leon, Gloria R.; Trevino, Robert C.
2000-01-01
This study explored the effectiveness of local wrist/palm warming as a potential countermeasure for providing finger comfort during extended duration EVA. Methods: Six subjects (5 males and 1 female) were evaluated in a sagitally divided liquid cooling/warming garment (LCWG) with modified liquid cooling/warming (LCW) gloves in three different experimental conditions. Condition 1: Stage 1- no LCWG; chamber adaptation with LCW glove inlet water temperature 33 C; Stage 2-LCW glove inlet water temperature cooled to 8 C; Stage 3-LCW glove inlet water temperature warmed to 45 C; Condition 2: Stage1-LCWG and LCW glove inlet water temperature 33 C; Stage 2-LCWG inlet temperature cooled to 31 C, LCW gloves, 8 C; Stage 3-LCWG inlet water temperature remains at 31 C, LCW glove inlet water temperature warmed to 45 C; Condition 3: Stage l -LCWG and LCW gloves 33 C; Stage 2-LCWG inlet water temperature cooled to 28 C, LCW gloves, 8 C; Stage 3-LCWG remains at 28 C, LCW glove water temperature warmed to 45 C. Results: Wrist/palm area warming significantly increased finger temperature (Tfing) and blood perfusion in Stage 3 compared to Stage 2. The LCW gloves were most effective in increasing Stage 3 Tfing in Condition 1; and in increasing blood perfusion in Conditions 1 and 2 compared to Condition 3. Ratings of subjective perception of heat in the hand and overall body heat were higher at Stage 3 than Stage 2, with no significant differences across Conditions. Conclusions: Local wrist/palm warming was effective in increasing blood circulation to the distal extremities, suggesting the potential usefulness of this technique for increasing astronaut thermal comfort during EVA while decreasing power requirements. The LCW gloves were effective in heating the highly cooled fingers when the overall body was in a mild heat deficit.
Chronic ethanol increases systemic TLR3 agonist-induced neuroinflammation and neurodegeneration
2012-01-01
Background Increasing evidence links systemic inflammation to neuroinflammation and neurodegeneration. We previously found that systemic endotoxin, a TLR4 agonist or TNFα, increased blood TNFα that entered the brain activating microglia and persistent neuroinflammation. Further, we found that models of ethanol binge drinking sensitized blood and brain proinflammatory responses. We hypothesized that blood cytokines contribute to the magnitude of neuroinflammation and that ethanol primes proinflammatory responses. Here, we investigate the effects of chronic ethanol on neuroinflammation and neurodegeneration triggered by toll-like receptor 3 (TLR3) agonist poly I:C. Methods Polyinosine-polycytidylic acid (poly I:C) was used to induce inflammatory responses when sensitized with D-galactosamine (D-GalN). Male C57BL/6 mice were treated with water or ethanol (5 g/kg/day, i.g., 10 days) or poly I:C (250 μg/kg, i.p.) alone or sequentially 24 hours after ethanol exposure. Cytokines, chemokines, microglial morphology, NADPH oxidase (NOX), reactive oxygen species (ROS), high-mobility group box 1 (HMGB1), TLR3 and cell death markers were examined using real-time PCR, ELISA, immunohistochemistry and hydroethidine histochemistry. Results Poly I:C increased blood and brain TNFα that peaked at three hours. Blood levels returned within one day, whereas brain levels remained elevated for at least three days. Escalating blood and brain proinflammatory responses were found with ethanol, poly I:C, and ethanol-poly I:C treatment. Ethanol pretreatment potentiated poly I:C-induced brain TNFα (345%), IL-1β (331%), IL-6 (255%), and MCP-1(190%). Increased levels of brain cytokines coincided with increased microglial activation, NOX gp91phox, superoxide and markers of neurodegeneration (activated caspase-3 and Fluoro-Jade B). Ethanol potentiation of poly I:C was associated with ethanol-increased expression of TLR3 and endogenous agonist HMGB1 in the brain. Minocycline and naltrexone blocked microglial activation and neurodegeneration. Conclusions Chronic ethanol potentiates poly I:C blood and brain proinflammatory responses. Poly I:C neuroinflammation persists after systemic responses subside. Increases in blood TNFα, IL-1β, IL-6, and MCP-1 parallel brain responses consistent with blood cytokines contributing to the magnitude of neuroinflammation. Ethanol potentiation of TLR3 agonist responses is consistent with priming microglia-monocytes and increased NOX, ROS, HMGB1-TLR3 and markers of neurodegeneration. These studies indicate that TLR3 agonists increase blood cytokines that contribute to neurodegeneration and that ethanol binge drinking potentiates these responses. PMID:22709825
Adverse factors increase preeclampsia-like changes in pregnant mice with abnormal lipid metabolism.
Ding, Xiaoyan; Yang, Zi; Han, Yiwei; Yu, Huan
2014-01-01
Preeclampsia (PE) is a multifactorial pregnancy complication. Maternal underlying condition and adverse factors both influence the pathogenesis of PE. Abnormal lipid metabolism as a maternal underlying disease may participate in the occurrence and development of PE. This study aimed to observe the effects of adverse factors on PE-like symptoms of pregnant mice with genetic abnormal lipid metabolism. Apolipoprotein C-III (ApoC3) transgenic mice with abnormal lipid metabolism were subcutaneously injected with L-arginine methyl ester (L-NAME) or normal saline (NS) daily starting at Day 7 or 16 of pregnancy (ApoC3+L-NA and ApoC3+NS groups), and wild-type (WT) mice served as a control (WT+L-NA and WT+NS groups). All mice were subdivided into early and late subgroups by injection time. The mean arterial pressure (MAP) and urinary protein were measured. Pregnancy outcomes, including fetal weight, placental weight, live birth rate, and fetal absorption rate, were analyzed. Pathologic changes in the placenta were observed by hematoxylin-eosin staining. One-way analysis of variance, t-test, and χ(2) test were used for statistical analysis. MAP significantly increased for ApoC3+NS groups compared with WT+NS groups (P < 0.05), without significant difference in urine protein. Following L-NAME injection, MAP and urinary protein significantly increased for ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), and the increase for ApoC3+L-NA was more obvious. Urinary protein levels in early ApoC3+L-NA and WT+L-NA significantly increased compared with the corresponding late groups (P < 0.05). Fetal absorption rate significantly increased and fetal and placental weights significantly decreased in early ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), without significant difference in late ApoC3+L-NA and WT+L-NA groups. Fetal weight in early ApoC3+L-NA was significantly lower than in early WT+L-NA group (P < 0.05). Morphologic examination of placentas from early ApoC3+L-NA and WT+L-NA groups showed varying degrees of fibrinoid necrosis. ApoC3 transgenic mice with abnormal lipid metabolism showed gestational hypertension. Adverse factors and early effect time could aggravate the PE-like symptoms for ApoC3 transgenic mice.
Trapping-mediated dissociative chemisorption of C3H8 and C3D8 on Ir(110)
NASA Astrophysics Data System (ADS)
Kelly, D.; Weinberg, W. H.
1996-07-01
We have employed molecular beam techniques to investigate the molecular trapping and trapping-mediated dissociative chemisorption of C3H8 and C3D8 on Ir(110) at low beam translational energies, Ei≤5 kcal/mol, and surface temperatures, Ts, from 85 to 1200 K. For Ts=85 K, C3H8 is molecularly adsorbed on Ir(110) with a trapping probability, ξ, equal to 0.94 at Ei=1.6 kcal/mol and ξ=0.86 at Ei=5 kcal/mol. At Ei=1.9 kcal/mol and Ts=85 K, ξ of C3D8 is equal to 0.93. From 150 K to approximately 700 K, the initial probabilities of dissociative chemisorption of propane decrease with increasing Ts. For Ts from 700 to 1200 K, however, the initial probability of dissociative chemisorption maintains the essentially constant value of 0.16. These observations are explained within the context of a kinetic model which includes both C-H (C-D) and C-C bond cleavage. Below 450 K propane chemisorption on Ir(110) arises essentially solely from C-H (C-D) bond cleavage, an unactivated mechanism (with respect to a gas-phase energy zero) for this system, which accounts for the decrease in initial probabilities of chemisorption with increasing Ts. With increasing Ts, however, C-C bond cleavage, the activation energy of which is greater than the desorption energy of physically adsorbed propane, increasingly contributes to the measured probability of dissociative chemisorption. The activation energies, referenced to the bottom of the physically adsorbed molecular well, for C-H and C-C bond cleavage for C3H8 on Ir(110) are found to be Er,CH=5.3±0.3 kcal/mol and Er,CC=9.9±0.6 kcal/mol, respectively. The activation energies for C-D and C-C bond cleavage for C3D8 on Ir(110) are 6.3±0.3 kcal/mol and 10.5±0.6 kcal/mol, respectively. The desorption activation energy of propane from Ir(110) is approximately 9.5 kcal/mol. These activation energies are compared to activation energies determined recently for ethane and propane adsorption on Ir(111), Ru(001), and Pt(110)-(1×2), and ethane activation on Ir(110).
Calcitriol enhances fat synthesis factors and calpain activity in co-cultured cells.
Choi, Hyuck; Myung, Kyuho
2014-08-01
We have conducted an in vitro experiment to determine whether calcitriol can act as a fat synthesizer and/or meat tenderizer when skeletal muscle cells, adipose tissue, and macrophages are co-cultured. When co-cultured, pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression increased, whereas decreased anti-inflammatory cytokine (IL-10 and IL-15) expression decreased in both C2C12 and 3T3-L1 cells. Calcitriol increased reactive oxygen species (ROS) production in the media. While adiponectin gene expression decreased, leptin, resistin, CCAAT-enhancer-binding protein-beta (C/EBP-β), and peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression was significantly (P < 0.047) increased with calcitriol in 3T3-L1 cells co-cultured with two different cell types. Inducible nitric oxide synthase (iNOS) protein levels were also stimulated in the C2C12 and 3T3-L1 cells, but arginase l was attenuated by calcitriol. Cacitriol highly amplified (P = 0.008) µ-calpain gene expression in co-cultured C2C12 cells. The results showed an overall increase in pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines of C2C12 and 3T3-L1 cells with calcitriol in co-culture systems. µ-Calpain protein was also augmented in differentiated C2C12 cells with calcitriol. These findings suggest that calcitriol can be used as not only fat synthesizer, but meat tenderizer, in meat-producing animals. © 2014 International Federation for Cell Biology.
Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblasts
NASA Technical Reports Server (NTRS)
Fitzgerald, J.; Hughes-Fulford, M.
1999-01-01
In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.
Kjelgaard-Petersen, Cecilie; Siebuhr, Anne Sofie; Christiansen, Thorbjørn; Ladel, Christoph; Karsdal, Morten; Bay-Jensen, Anne-Christine
2015-01-01
Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1β also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs. The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model.
Semple, Fiona; MacPherson, Heather; Webb, Sheila; Kilanowski, Fiona; Lettice, Laura; McGlasson, Sarah L; Wheeler, Ann P; Chen, Valerie; Millhauser, Glenn L; Melrose, Lauren; Davidson, Donald J; Dorin, Julia R
2015-12-01
Human β-defensin 3 (hBD3) is a cationic host defence peptide and is part of the innate immune response. HBD3 is present on a highly copy number variable block of six β-defensin genes, and increased copy number is associated with the autoimmune disease psoriasis. It is not known how this increase influences disease development, but psoriasis is a T cell-mediated disease and activation of the innate immune system is required for the initial trigger that leads to the amplification stage. We investigated the effect of hBD3 on the response of primary macrophages to various TLR agonists. HBD3 exacerbated the production of type I Interferon-β in response to the viral ligand mimic polyinosinic:polycytidylic acid (polyI:C) in both human and mouse primary cells, although production of the chemokine CXCL10 was suppressed. Compared to polyI:C alone, mice injected with both hBD3 peptide and polyI:C also showed an enhanced increase in Interferon-β. Mice expressing a transgene encoding hBD3 had elevated basal levels of Interferon-β, and challenge with polyI:C further increased this response. HBD3 peptide increased uptake of polyI:C by macrophages, however the cellular response and localisation of polyI:C in cells treated contemporaneously with hBD3 or cationic liposome differed. Immunohistochemistry showed that hBD3 and polyI:C do not co-localise, but in the presence of hBD3 less polyI:C localises to the early endosome. Using bone marrow derived macrophages from knockout mice we demonstrate that hBD3 suppresses the polyI:C-induced TLR3 response mediated by TICAM1 (TRIF), while exacerbating the cytoplasmic response through MDA5 (IFIH1) and MAVS (IPS1/CARDIF). Thus, hBD3, a highly copy number variable gene in human, influences cellular responses to the viral mimic polyI:C implying that copy number may have a significant phenotypic effect on the response to viral infection and development of autoimmunity in humans.
Semple, Fiona; MacPherson, Heather; Webb, Sheila; Kilanowski, Fiona; Lettice, Laura; McGlasson, Sarah L.; Wheeler, Ann P.; Chen, Valerie; Millhauser, Glenn L.; Melrose, Lauren; Davidson, Donald J.; Dorin, Julia R.
2015-01-01
Human β-defensin 3 (hBD3) is a cationic host defence peptide and is part of the innate immune response. HBD3 is present on a highly copy number variable block of six β-defensin genes, and increased copy number is associated with the autoimmune disease psoriasis. It is not known how this increase influences disease development, but psoriasis is a T cell-mediated disease and activation of the innate immune system is required for the initial trigger that leads to the amplification stage. We investigated the effect of hBD3 on the response of primary macrophages to various TLR agonists. HBD3 exacerbated the production of type I Interferon-β in response to the viral ligand mimic polyinosinic:polycytidylic acid (polyI:C) in both human and mouse primary cells, although production of the chemokine CXCL10 was suppressed. Compared to polyI:C alone, mice injected with both hBD3 peptide and polyI:C also showed an enhanced increase in Interferon-β. Mice expressing a transgene encoding hBD3 had elevated basal levels of Interferon-β, and challenge with polyI:C further increased this response. HBD3 peptide increased uptake of polyI:C by macrophages, however the cellular response and localisation of polyI:C in cells treated contemporaneously with hBD3 or cationic liposome differed. Immunohistochemistry showed that hBD3 and polyI:C do not co-localise, but in the presence of hBD3 less polyI:C localises to the early endosome. Using bone marrow derived macrophages from knockout mice we demonstrate that hBD3 suppresses the polyI:C-induced TLR3 response mediated by TICAM1 (TRIF), while exacerbating the cytoplasmic response through MDA5 (IFIH1) and MAVS (IPS1/CARDIF). Thus, hBD3, a highly copy number variable gene in human, influences cellular responses to the viral mimic polyI:C implying that copy number may have a significant phenotypic effect on the response to viral infection and development of autoimmunity in humans. PMID:26646717
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hampel, Regina, E-mail: regina.hampel@helmholtz-mu
Background: Epidemiological studies have shown associations between air temperature and cardiovascular health outcomes. Metabolic dysregulation might also play a role in the development of cardiovascular disease. Objectives: To investigate short-term temperature effects on metabolites related to cardiovascular disease. Methods: Concentrations of 45 acylcarnitines, 15 amino acids, ketone bodies and total free fatty acids were available in 2869 participants from the CATHeterization GENetics cohort recruited at the Duke University Cardiac Catheterization Clinic (Durham, NC) between 2001 and 2007. Ten metabolites were selected based on quality criteria and cluster analysis. Daily averages of meteorological variables were obtained from the North American Regionalmore » Reanalysis project. Immediate, lagged, and cumulative temperature effects on metabolite concentrations were analyzed using (piecewise) linear regression models. Results: Linear temperature effects were found for glycine, C16-OH:C14:1-DC, and aspartic acid/asparagine. A 5 °C increase in temperature was associated with a 1.8% [95%-confidence interval: 0.3%; 3.3%] increase in glycine (5-day average), a 3.2% [0.1%; 6.3%] increase in C16-OH:C14:1-DC (lag of four days), and a −1.4% [−2.4%; −0.3%] decrease in aspartic acid/asparagine (lag of two days). Non-linear temperature effects were observed for alanine and total ketone bodies with breakpoint of 4 °C and 20 °C, respectively. Both a 5 °C decrease in temperature on colder days (<4 °C)and a 5 °C increase in temperature on warmer days (≥4 °C) were associated with a four day delayed increase in alanine by 6.6% [11.7; 1.8%] and 1.9% [0.3%; 3.4%], respectively. For ketone bodies we found immediate (0-day lag) increases of 4.2% [−0.5%; 9.1%] and 12.3% [0.1%; 26.0%] associated with 5 °C decreases on colder (<20 °C) days and 5 °C increases on warmer days (≥20 °C), respectively. Conclusions: We observed multiple effects of air temperature on metabolites several of which are reported to be involved in cardiovascular disease. Our findings might help to understand the link between air temperature and cardiovascular disease. - Highlights: • Certain metabolites are assumed to be novel biomarkers for cardiovascular disease. • First study investigating associations between air temperature and metabolites. • Short-term effects of temperature on amino acids, ketone bodies and acylcarnitines. • Our findings may help to understand the link between temperature and cardiovascular disease.« less
Reorganization of equivalence classes: effects of preliminary training and meaningful stimuli.
Arntzen, Erik; Nartey, Richard K; Fields, Lanny
2018-05-01
In Condition 1, adults learned the baseline relations for the three equivalence classes A1-B1-C1-D1-E1, A2-B2-C2-D2-E2, and A3-B3-C3-D3-E3. Classes contained abstract shapes in the ABS and four preliminary training groups. Each class in the PIC group contained one picture and four abstract shapes. Before class formation for four other groups, preliminary training involved establishing identity (CC) or arbitrary (CX) relations either with or without a delay. Without preliminary training, classes formed with low and high likelihoods in the ABS and PIC groups, respectively. Preliminary training with no delay produced modest increases in class formation, while preliminary training with delay produced large increases in class formation. Condition 2 replicated Condition 1 but with training of reassigned BC and CD relations that linked C from one class to B and D from another class: B1-C2, B2-C3, B3-C1, C2-D1, C3-D2, and C1-D3. Subsequent tests assessed the emergence of the reorganized classes A1-B1-C2-D1-E1, A2-B2-C3-D2-E2, and A3-B3-C1-D3-E3. All preliminary training procedures increased likelihood of forming the reorganized classes to the level seen in the PIC group. Greater gains were produced by preliminary training with no delays than with delays. Test performances also showed how preliminary training influenced baseline acquisition speed and participant-defined relations. © 2018 Society for the Experimental Analysis of Behavior.
Liao, Zhenhua; Fogel, Guy R.; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang
2015-01-01
Background The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Material/Methods Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Results Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). Conclusions ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion. PMID:26529430
Liao, Zhenhua; Fogel, Guy R; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang
2015-11-03
The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion.
Silva, Kleiton Augusto Santos; Dong, Jiangling; Dong, Yanjun; Dong, Yanlan; Schor, Nestor; Tweardy, David J; Zhang, Liping; Mitch, William E
2015-04-24
Cachexia occurs in patients with advanced cancers. Despite the adverse clinical impact of cancer-induced muscle wasting, pathways causing cachexia are controversial, and clinically reliable therapies are not available. A trigger of muscle protein loss is the Jak/Stat pathway, and indeed, we found that conditioned medium from C26 colon carcinoma (C26) or Lewis lung carcinoma cells activates Stat3 (p-Stat3) in C2C12 myotubes. We identified two proteolytic pathways that are activated in muscle by p-Stat3; one is activation of caspase-3, and the other is p-Stat3 to myostatin, MAFbx/Atrogin-1, and MuRF-1 via CAAT/enhancer-binding protein δ (C/EBPδ). Using sequential deletions of the caspase-3 promoter and CHIP assays, we determined that Stat3 activation increases caspase-3 expression in C2C12 cells. Caspase-3 expression and proteolytic activity were stimulated by p-Stat3 in muscles of tumor-bearing mice. In mice with cachexia caused by Lewis lung carcinoma or C26 tumors, knock-out of p-Stat3 in muscle or with a small chemical inhibitor of p-Stat3 suppressed muscle mass losses, improved protein synthesis and degradation in muscle, and increased body weight and grip strength. Activation of p-Stat3 stimulates a pathway from C/EBPδ to myostatin and expression of MAFbx/Atrogin-1 and increases the ubiquitin-proteasome system. Indeed, C/EBPδ KO decreases the expression of MAFbx/Atrogin-1 and myostatin, while increasing muscle mass and grip strength. In conclusion, cancer stimulates p-Stat3 in muscle, activating protein loss by stimulating caspase-3, myostatin, and the ubiquitin-proteasome system. These results could lead to novel strategies for preventing cancer-induced muscle wasting. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Silva, Kleiton Augusto Santos; Dong, Jiangling; Dong, Yanjun; Dong, Yanlan; Schor, Nestor; Tweardy, David J.; Zhang, Liping; Mitch, William E.
2015-01-01
Cachexia occurs in patients with advanced cancers. Despite the adverse clinical impact of cancer-induced muscle wasting, pathways causing cachexia are controversial, and clinically reliable therapies are not available. A trigger of muscle protein loss is the Jak/Stat pathway, and indeed, we found that conditioned medium from C26 colon carcinoma (C26) or Lewis lung carcinoma cells activates Stat3 (p-Stat3) in C2C12 myotubes. We identified two proteolytic pathways that are activated in muscle by p-Stat3; one is activation of caspase-3, and the other is p-Stat3 to myostatin, MAFbx/Atrogin-1, and MuRF-1 via CAAT/enhancer-binding protein δ (C/EBPδ). Using sequential deletions of the caspase-3 promoter and CHIP assays, we determined that Stat3 activation increases caspase-3 expression in C2C12 cells. Caspase-3 expression and proteolytic activity were stimulated by p-Stat3 in muscles of tumor-bearing mice. In mice with cachexia caused by Lewis lung carcinoma or C26 tumors, knock-out of p-Stat3 in muscle or with a small chemical inhibitor of p-Stat3 suppressed muscle mass losses, improved protein synthesis and degradation in muscle, and increased body weight and grip strength. Activation of p-Stat3 stimulates a pathway from C/EBPδ to myostatin and expression of MAFbx/Atrogin-1 and increases the ubiquitin-proteasome system. Indeed, C/EBPδ KO decreases the expression of MAFbx/Atrogin-1 and myostatin, while increasing muscle mass and grip strength. In conclusion, cancer stimulates p-Stat3 in muscle, activating protein loss by stimulating caspase-3, myostatin, and the ubiquitin-proteasome system. These results could lead to novel strategies for preventing cancer-induced muscle wasting. PMID:25787076
Glasser, S W; Korfhagen, T R; Wert, S E; Bruno, M D; McWilliams, K M; Vorbroker, D K; Whitsett, J A
1991-10-01
Transgenic mice bearing chimeric genes consisting of 5'-sequences derived from the human surfactant protein C (SP-C) gene and the bacterial chloramphenicol acetyltransferase (CAT) gene were generated. Analysis of CAT activity was utilized to demonstrate tissue-specific and developmental expression of chimeric genes containing 3.7 kb of sequences from the human SP-C gene. Lung-specific expression of the 3.7 SP-C-CAT transgene was observed in eight distinct transgenic mouse lines. Expression of the 3.7 SP-C-CAT transgene was first detected in fetal lung on day 11 of gestation and increased dramatically with advancing gestational age, reaching adult levels of activity before birth. In situ hybridization demonstrated that expression of 3.7 SP-C-CAT mRNA was confined to the distal respiratory epithelium. Antisense CAT hybridization was detected in bronchiolar and type II epithelial cells in the adult lung of the 3.7 SP-C-CAT transgenic mice. In situ hybridization of four distinct 3.7 SP-C-CAT transgenic mouse lines demonstrated bronchiolar-alveolar expression of the chimeric CAT gene, although the relative intensity of expression at each site varied within the lines studied. Glucocorticoids increased murine SP-C mRNA in fetal lung organ culture. Likewise, expression of 3.7 SP-C-CAT transgene increased during fetal lung organ or explant culture and was further enhanced by glucocorticoid in vitro. The 5'-regions of human SP-C conferred developmental, lung epithelial, and glucocorticoid-enhanced expression of bacterial CAT in transgenic mice. The increased expression of SP-C accompanying prenatal lung development and exposure to glucocorticoid is mediated, at least in part, at the transcriptional level, being influenced by cis-active elements contained within the 5'-flanking region of the human SP-C gene.
Mozafar, A
1996-02-01
Excessive use of nitrogen fertilizers is known to increase the NO3 and reduce the vitamin C contents in fruits and vegetables. We investigated the concentration of these compounds in spinach leaves when plants were transferred to nitrogen-free media prior to their harvest. It was noted that a pre-harvest transfer of spinach to N-free media reduces the NO3 and increases the vitamin C content of the leaves by a substantial amount in a 2-3 day period. It is suggested that this technique may be suited to produce spinach or other leafy vegetables with low NO3 and high vitamin C contents under commercial hydroponic conditions.
Influence of thyroid hormones and transforming growth factor-β1 on cystatin C concentrations.
Kotajima, N; Yanagawa, Y; Aoki, T; Tsunekawa, K; Morimura, T; Ogiwara, T; Nara, M; Murakami, M
2010-01-01
Serum cystatin C concentrations are reported to increase in the hyperthyroid state. Serum concentrations of cystatin C and transforming growth factor-β1 (TGF-β1) were measured in patients with thyroid dysfunction, and the effects of 3,5,3'-tri-iodothyronine (T(3)) and TGF-β1 on cystatin C production in human hepatoblastoma (Hep G2) cells were studied. Serum concentrations of cystatin C and TGF-β1 were significantly higher in patients with Graves' disease compared with control subjects. Significantly positive correlations were observed between thyroid hormones and cystatin C, thyroid hormones and TGF-β1, and TGF-β1 and cystatin C in patients with thyroid dysfunction. Serum concentrations of cystatin C and TGF-β1 decreased after treatment for hyperthyroidism. Cystatin C mRNA levels and cystatin C secretion were increased by T(3) and TGF-β1 in cultured Hep G2 cells. These results suggest that serum cystatin C concentrations increase in patients with hyperthyroidism. The mechanisms for this may involve elevation of serum TGF-β1 levels and the stimulatory effects of T(3) and TGF-β1 on cystatin C production.
Zhou, Xueli; Fukuda, Noboru; Matsuda, Hiroyuki; Endo, Morito; Wang, Xiaofei; Saito, Kosuke; Ueno, Takahiro; Matsumoto, Taro; Matsumoto, Koichi; Soma, Masayoshi; Kobayashi, Naohiko; Nishiyama, Akira
2013-10-01
We have demonstrated that mesenchymal cells from spontaneously hypertensive rats genetically express complement 3 (C3). Mature tubular epithelial cells can undergo epithelial-to-mesenchymal transition (EMT) that is linked to the pathogenesis of renal fibrosis and injury. In this study, we investigated the contribution of C3 in EMT and in the renal renin-angiotensin (RA) systems associated with hypertension. C3a induced EMT in mouse TCMK-1 epithelial cells, which displayed increased expression of renin and Krüppel-like factor 5 (KLF5) and nuclear localization of liver X receptor α (LXRα). C3 and renin were strongly stained in the degenerated nephrotubulus and colocalized with LXRα and prorenin receptor in unilateral ureteral obstruction (UUO) kidneys from wild-type mice. In C3-deficient mice, hydronephrus and EMT were suppressed, with no expression of renin and C3. After UUO, systolic blood pressure was increased in wild-type but not C3-deficient mice. In wild-type mice, intrarenal angiotensin II (ANG II) levels were markedly higher in UUO kidneys than normal kidneys and decreased with aliskiren. There were no increases in intrarenal ANG II levels after UUO in C3-deficient mice. Thus C3 induces EMT and dedifferentiation of epithelial cells, which produce renin through induction of LXRα. These data indicate for the first time that C3 may be a primary factor to activate the renal RA systems to induce hypertension.
Identification of cytosolic phosphodiesterases in the erythrocyte: A possible role for PDE5
Adderley, Shaquria P.; Thuet, Kelly M.; Sridharan, Meera; Bowles, Elizabeth A.; Stephenson, Alan H.; Ellsworth, Mary L.; Sprague, Randy S.
2011-01-01
Summary Background Within erythrocytes (RBCs), cAMP levels are regulated by phosphodiesterases (PDEs). Increases in cAMP and ATP release associated with activation of β-adrenergic receptors (βARs) and prostacyclin receptors (IPRs) are regulated by PDEs 2, 4 and PDE 3, respectively. Here we establish the presence of cytosolic PDEs in RBCs and determine a role for PDE5 in regulating levels of cGMP. Material/Methods Purified cytosolic proteins were obtained from isolated human RBCs and western analysis was performed using antibodies against PDEs 3A, 4 and 5. Rabbit RBCs were incubated with dbcGMP, a cGMP analog, to determine the effect of cGMP on cAMP levels. To determine if cGMP affects receptor-mediated increases in cAMP, rabbit RBCs were incubated with dbcGMP prior to addition of isoproterenol (ISO), a βAR receptor agonist. To demonstrate that endogenous cGMP produces the same effect, rabbit and human RBCs were incubated with SpNONOate (SpNO), a nitric oxide donor, and YC1, a direct activator of soluble guanylyl cyclase (sGC), in the absence and presence of a selective PDE5 inhibitor, zaprinast (ZAP). Results Western analysis identified PDEs 3A, 4D and 5A. dbcGMP produced a concentration dependent increase in cAMP and ISO-induced increases in cAMP were potentiated by dbcGMP. In addition, incubation with YC1 and SpNO in the presence of ZAP potentiated βAR-induced increases in cAMP. Conclusions PDEs 2, 3A and 5 are present in the cytosol of human RBCs. PDE5 activity in RBCs regulates cGMP levels. Increases in intracellular cGMP augment cAMP levels. These studies suggest a novel role for PDE5 in erythrocytes. PMID:21525805
NASA Astrophysics Data System (ADS)
Pu, Yuping; Guo, Baogang; Zhou, Jiansong; Zhang, Shitang; Zhou, Huidi; Chen, Jianmin
2008-12-01
TiC, TiN, and SiC reinforced Ti 3Al intermetallic matrix composite (IMC) coatings were in situ synthesized on a pure Ti substrate by laser cladding. It was found that the surface hardness and the wear resistance of the Ti 3Al coating were improved by the formation of these Ti 3Al IMC coatings. The surface hardness and the wear resistance of the TiC/Ti 3Al IMC coatings increased with the increasing volume fraction of TiC powder. Under the same dry sliding test conditions, the wear resistance of TiC, TiN, and SiC reinforced Ti 3Al IMC coatings with 40 vol.% reinforced powder was in the following order: TiN/Ti 3Al IMC coating > TiC/Ti 3Al IMC coating > SiC/Ti 3Al IMC coating. It should be noted that both the TiC/Ti 3Al IMC coating with 40 vol.% TiC powder and the TiN/Ti 3Al coating with 40 vol.% TiN powder showed excellent wear resistance under 5 N normal load.
Synthesis of transparent BaTiO3 nanoparticle/polymer composite film using DC field
NASA Astrophysics Data System (ADS)
Kondo, Yusuke; Okumura, Yasuko; Oi, Chifumi; Sakamoto, Wataru; Yogo, Toshinobu
2008-10-01
Transparent BaTiO3 nanoparticle/polymer composite films were synthesized from titanium-organic film and barium ion in aqueous solution under direct current (DC) field. Titanium-organic precursor was synthesized from titanium isopropoxide, acetylacetone and methacrylate derivative. The UV treatment was effective to increase the anti-solubility of the titanium-organic film during DC processing. BaTiO3 nanoparticles were crystallized in the precursor films on stainless substrates without high temperature process, as low as 40°C. The crystallite size of BaTiO3 increased with increasing reaction temperature from 40 to 50 °C at 3.0 V/cm. BaTiO3 nanoparticles also grew in size with increasing reaction time from 15 min to 45 min at 3.0 V/cm and 50 °C. Transparent BaTiO3 nanoparticle/polymer films were synthesized on stainless substrates at 3.0 V/cm and 50°C for 45 min.
Lin, Jiefu; Wang, Tingting; Li, Yalan; Wang, Mengxia; Li, Haobo; Irwin, Michael G; Xia, Zhengyuan
2016-01-01
The effect of sevoflurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four weeks starting at five weeks after streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3 which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC but not N-Acetylcysteine significantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic rats displayed reduction of cardiac p-STAT3, adiponectin deficiency, and increase of FoxO1 and CD36 expression, which may be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36.
Ren, Jin; Gillespie, Delbert G.
2011-01-01
Rat vascular smooth muscle cells (VSMCs) from renal microvessels metabolize 2′,3′-cAMP to 2′-AMP and 3′-AMP, and these AMPs are converted to adenosine that inhibits microvascular VSMC proliferation via A2B receptors. The goal of this study was to test whether this mechanism also exists in VSMCs from conduit arteries and whether it is similarly expressed in human vs. rat VSMCs. Incubation of rat and human aortic VSMCs with 2′,3′-cAMP concentration-dependently increased levels of 2′-AMP and 3′-AMP in the medium, with a similar absolute increase in 2′-AMP vs. 3′-AMP. In contrast, in human coronary VSMCs, 2′,3′-cAMP increased 2′-AMP levels yet had little effect on 3′-AMP levels. In all cell types, 2′,3′-cAMP increased levels of adenosine, but not 5′-AMP, and 2′,3′-AMP inhibited cell proliferation. Antagonism of A2B receptors (MRS-1754), but not A1 (1,3-dipropyl-8-cyclopentylxanthine), A2A (SCH-58261), or A3 (VUF-5574) receptors, attenuated the antiproliferative effects of 2′,3′-cAMP. In all cell types, 2′-AMP, 3′-AMP, and 5′-AMP increased adenosine levels, and inhibition of ecto-5′-nucleotidase blocked this effect of 5′-AMP but not that of 2′-AMP nor 3′-AMP. Also, 2′-AMP, 3′-AMP, and 5′-AMP, like 2′,3′-cAMP, exerted antiproliferative effects that were abolished by antagonism of A2B receptors with MRS-1754. In conclusion, VSMCs from conduit arteries metabolize 2′,3′-cAMP to AMPs, which are metabolized to adenosine. In rat and human aortic VSMCs, both 2′-AMP and 3′-AMP are involved in this process, whereas, in human coronary VSMCs, 2′,3′-cAMP is mainly converted to 2′-AMP. Because adenosine inhibits VSMC proliferation via A2B receptors, local vascular production of 2′,3′-cAMP may protect conduit arteries from atherosclerosis. PMID:21622827
DOE Office of Scientific and Technical Information (OSTI.GOV)
Plucknett, K.P.; Becher, P.F.; Waters, S.B.
TiC/Ni{sub 3}Al composites were prepared using a simple melt-infiltration process, performed at either 1300 or 1400 C, with the Ni{sub 3}Al content varied over the range of 8--25 vol%. Densities >96% of theoretical were obtained for all composites. Four-point flexure strengths at 22 C increased as the Ni{sub 3}Al content increased (i.e., {approximately}1,100 MPa at 20 vol% Ni{sub 3}Al), with the highest strengths being observed for composites processed at 1300 C, because of reduced TiC grain size. Strengths at elevated temperatures increased with test temperature, up to {approximately}1,000 C. As with the yielding behavior of the Ni{sub 3}Al alloy used,more » a maximum in composite strength ({approximately}1,350 MPa) versus temperature was observed; this occurred at 950 C, which is {approximately}300 C above the yield maximum for the alloy. Extensive plastic strain was achieved in the composites even at high loading rates at 1,135 C, and the yield stress was dependent on the applied loading rate.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hong, Gia-Ming; Present address: The University of Chicago, Section of Hematology/Oncology, 900 E. 57th Street, Room 7134, Chicago, IL 60637; Bain, Lisa J., E-mail: lbain@clemson.edu
2012-05-01
Arsenic is a toxicant commonly found in water systems and chronic exposure can result in adverse developmental effects including increased neonatal death, stillbirths, and miscarriages, low birth weight, and altered locomotor activity. Previous studies indicate that 20 nM sodium arsenite exposure to C2C12 mouse myocyte cells delayed myoblast differentiation due to reduced myogenin expression, the transcription factor that differentiates myoblasts into myotubes. In this study, several mechanisms by which arsenic could alter myogenin expression were examined. Exposing differentiating C2C12 cells to 20 nM arsenic increased H3K9 dimethylation (H3K9me2) and H3K9 trimethylation (H3K9me3) by 3-fold near the transcription start site ofmore » myogenin, which is indicative of increased repressive marks, and reduced H3K9 acetylation (H3K9Ac) by 0.5-fold, indicative of reduced permissive marks. Protein expression of Glp or Ehmt1, a H3-K9 methyltransferase, was also increased by 1.6-fold in arsenic-exposed cells. In addition to the altered histone remodeling status on the myogenin promoter, protein and mRNA levels of Igf-1, a myogenic growth factor, were significantly repressed by arsenic exposure. Moreover, a 2-fold induction of Ezh2 expression, and an increased recruitment of Ezh2 (3.3-fold) and Dnmt3a (∼ 2-fold) to the myogenin promoter at the transcription start site (− 40 to + 42), were detected in the arsenic-treated cells. Together, we conclude that the repressed myogenin expression in arsenic-exposed C2C12 cells was likely due to a combination of reduced expression of Igf-1, enhanced nuclear expression and promoter recruitment of Ezh2, and altered histone remodeling status on myogenin promoter (− 40 to + 42). -- Highlights: ► Igf-1 expression is decreased in C2C12 cells after 20 nM arsenite exposure. ► Arsenic exposure alters histone remodeling on the myogenin promoter. ► Glp expression, a H3–K9 methyltransferase, was increased in arsenic-exposed cells. ► Ezh2 and Dnmt3a localization to the myogenin promoter is induced by arsenic.« less
Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun
2017-02-14
Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 μg/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.
Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun
2017-01-01
Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit. PMID:27713142
Ziebell, Angela; Gjersing, Erica; Hinchee, Maud; ...
2016-01-20
Lignin reduction through breeding and genetic modification has the potential to reduce costs in biomass processing in pulp and paper, forage, and lignocellulosic ethanol industries. Here, we present detailed characterization of the extractability and lignin structure of Eucalyptus urophylla x Eucalyptus grandis RNAi downregulated in p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H) or cinnamate-4-hydroxylase (C4H). Both the C3'H and C4H downregulated lines were found to have significantly higher extractability when exposed to NaOH base extraction, indicating altered cell wall construction. The molecular weight of isolated lignin was measured and lignin structure was determined by HSQC NMR-based lignin subunit analysis for control and themore » C3'H and C4H downregulated lines. The slight reductions in average molecular weights of the lignin isolated from the transgenic lines (C3'H = 7000, C4H = 6500, control = 7300) does not appear to explain the difference in extractability. The HSQC NMR-based lignin subunit analysis showed increases in H lignin content for the C3'H but only slight differences in the lignin subunit structure of the C3'H and C4H downregulated lines when compared to the control. The greatest difference between the C3'H and C4H downregulated lines is the total lignin content; therefore, it appears that overall lowered lignin content contributes greatly to reduced recalcitrance and increased extractability of cell wall biopolymers. Furthermore, studies will be conducted to determine how the reduction in lignin content creates a less rigid cell wall that is more prone to extraction and sugar release.« less
Amorphization of nanocrystalline 3C-SiC irradiated with Si+ ions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, Weilin; Wang, H.; Zhang, Yanwen
2010-01-01
Irradiation induced amorphization in nanocrystalline and single crystal 3C-SiC has been studied using 1 MeV Si+ ions under identical irradiation conditions at room temperature and 400 K. The disordering behavior has been characterized using in-situ ion channeling and ex-situ x-ray diffraction methods. The results show that, compared to single crystal 3C-SiC, full amorphization of small 3C-SiC grains (~3.8 nm in size) at room temperature occurs at a slightly lower dose. Grain size decreases with increasing dose until a fully amorphized state is attained. The amorphization dose increases at 400 K relative to room temperature. However, at 400 K, the dosemore » for amorphization for 2.0 nm grains is about a factor of 4 and 8 smaller than for 3.0 nm grains and bulk single crystal 3C-SiC, respectively. The behavior is attributed to the dominance of defect-stimulated interfacial amorphization.« less
Pang, Rui-Ping; Xie, Man-Xiu; Yang, Jie; Shen, Kai-Feng; Chen, Xi; Su, Ying-Xue; Yang, Chao; Tao, Jing; Liang, Si-Jia; Zhou, Jia-Guo; Zhu, He-Quan; Wei, Xu-Hong; Li, Yong-Yong; Qin, Zhi-Hai; Liu, Xian-Guo
2016-11-01
ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, while overexpression of ClC-3 reversed the hypersensitivity to mechanical stimuli after peripheral nerve injury. In addition, genetic deletion of ClC-3 enhances mouse mechanical sensitivity but did not affect thermal and cold threshold. Restoration of ClC-3 expression in ClC-3 deficient mice reversed the mechanical sensitivity. Mechanistically, loss of ClC-3 enhanced mechanical sensitivity through increasing the excitability of DRG neurons. These data indicate that ClC-3 is an endogenous inhibitor of neuropathic pain development. Downregulation of ClC-3 by peripheral nerve injury is critical for mechanical hypersensitivity. Our findings suggest that ClC-3 is a novel therapeutic target for treating neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.
Yang, Ji Seon; Perveen, Shazia; Ha, Tae Joung; Kim, Seong Yun; Yoon, Shin Hee
2015-05-05
Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. However, effects of C3G on glutamate-induced [Zn(2+)]i increase and neuronal cell death remain unknown. We studied the effects of C3G on glutamate-induced [Zn(2+)]i increase and cell death in cultured rat hippocampal neurons from embryonic day 17 maternal Sprague-Dawley rats using digital imaging methods for Zn(2+), Ca(2+), reactive oxygen species (ROS), mitochondrial membrane potential and a MTT assay for cell survival. Treatment with glutamate (100 µM) for 7 min induces reproducible [Zn(2+)]i increase at 35 min interval in cultured rat hippocampal neurons. The intracellular Zn(2+)-chelator TPEN markedly blocked glutamate-induced [Zn(2+)]i increase, but the extracellular Zn(2+) chelator CaEDTA did not affect glutamate-induced [Zn(2+)]i increase. C3G inhibited the glutamate-induced [Zn(2+)]i response in a concentration-dependent manner (IC50 of 14.1 ± 1.1 µg/ml). C3G also significantly inhibited glutamate-induced [Ca(2+)]i increase. Two antioxidants such as Trolox and DTT significantly inhibited the glutamate-induced [Zn(2+)]i response, but they did not affect the [Ca(2+)]i responses. C3G blocked glutamate-induced formation of ROS. Trolox and DTT also inhibited the formation of ROS. C3G significantly inhibited glutamate-induced mitochondrial depolarization. However, TPEN, Trolox and DTT did not affect the mitochondrial depolarization. C3G, Trolox and DTT attenuated glutamate-induced neuronal cell death in cultured rat hippocampal neurons, respectively. Taken together, all these results suggest that cyanidin-3-glucoside inhibits glutamate-induced [Zn(2+)]i increase through a release of Zn(2+) from intracellular sources in cultured rat hippocampal neurons by inhibiting Ca(2+)-induced mitochondrial depolarization and formation of ROS, which is involved in neuroprotection against glutamate-induced cell death. Copyright © 2015 Elsevier B.V. All rights reserved.
Characterization of aluminum oxide doped with carbon and magnesium for radiation detection
NASA Astrophysics Data System (ADS)
Rodriguez, Matthew Gorman
Scope and Method of Study. A general characterization of the dosimetric properties of Al2O3:C,Mg. This included the thermoluminescence (TL) optically stimulated luminescence (OSL), radioluminescence (RL) and scintillation characteristics of Al2O3:C,Mg compared to Al2O3:C. Findings and Conclusions. The presence of aggregate defects as well as an increased F+-center concentration leads to the behavior of Al2O3:C,Mg being far more complex than Al2O3:C. The main TL peak is shifted to a lower temperature and narrower when compared to the main TL peak of Al 2O3:C. The OSL curves of Al2O3:C,Mg decay faster than Al2O3:C. Al2O3:C,Mg shows smaller dependence on the RL sensitivity as a function of dose, thus reducing the dynamic behavior of the RL signal associated with Al2O 3:C. Al2O3:C,Mg also has fast luminescence centers with lifetimes <100 ns. Finally, Annealing Al2O 3:C,Mg to 900°C would appear to increase the number of F+ and F recombination centers while destroying the aggregate defects present in the material.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shangguan, Junnan; Olarte, Mariefel V.; Chin, Ya-Huei
Catalytic pathways for acetic acid (CH3COOH) and hydrogen (H2) reactions on dispersed Ru clusters in the aqueous medium and the associated kinetic requirements for C-O and C-C bond cleavages and hydrogen insertion are established from rate and isotopic assessments. CH3COOH reacts with H2 in steps that either retain its carbon backbone and lead to ethanol, ethyl acetate, and ethane (47-95 %, 1-23 %, and 2-17 % carbon selectivities, respectively) or break its C-C bond and form methane (1-43 % carbon selectivities) at moderate temperatures (413-523 K) and H2 pressures (10-60 bar, 298 K). Initial CH3COOH activation is the kinetically relevantmore » step, during which CH3C(O)-OH bond cleaves on a metal site pair at Ru cluster surfaces nearly saturated with adsorbed hydroxyl (OH*) and acetate (CH3COO*) intermediates, forming an adsorbed acetyl (CH3CO*) and hydroxyl (OH*) species. Acetic acid turnover rates increase proportionally with both H2 (10-60 bar) and CH3COOH concentrations at low CH3COOH concentrations (<0.83 M), but decrease from first to zero order as the CH3COOH concentration and the CH3COO* coverages increase and the vacant Ru sites concomitantly decrease. Beyond the initial CH3C(O)-OH bond activation, sequential H-insertions on the surface acetyl species (CH3CO*) lead to C2 products and their derivative (ethanol, ethane, and ethyl acetate) and the competitive C-C bond cleavage of CH3CO* causes the eventual methane formation. The instantaneous carbon selectivities towards C2 species (ethanol, ethane, and ethyl acetate) increase linearly with the concentration of proton-type Hδ+ (derived from carboxylic acid dissociation) and chemisorbed H*. The selectivities towards C2 products decrease with increasing temperature, because of higher observed barriers for C-C bond cleavage than H-insertion. This study offers an interpretation of mechanism and energetics and provides kinetic evidence of carboxylic acid assisted proton-type hydrogen (Hδ+) shuffling during H-insertion steps in the aqueous phase, unlike those in the vapor phase, during the hydrogenation of acetic acid on Ru clusters.« less
Kwak, Jun Yup; Park, Soojin; Seok, Jin Kyung; Liu, Kwang-Hyeon; Boo, Yong Chool
2015-09-01
L-Ascorbic acid (AA) and p-coumaric acid (p-CA) are naturally occurring antioxidants that are known to enhance collagen synthesis and inhibit melanin synthesis, respectively. The purpose of this study was to examine hybrid compounds between AA and p-CA as multifunctional cosmeceutical agents. Ascorbyl 3-p-coumarate (A-3-p-C), ascorbyl 2-p-coumarate (A-2-p-C), and their parent compounds were tested for their effects on cellular melanin synthesis and collagen synthesis. At 100 μM, A-3-p-C and A-2-p-C decreased melanin content of human dermal melanocytes stimulated by L-tyrosine, by 65 and 59%, respectively, compared to 11% inhibition of AA and 70% inhibition of p-CA. A-3-p-C and A-2-p-C were less effective than p-CA but more effective than AA at inhibiting tyrosinase activity. A-3-p-C and A-2-p-C were more effective than p-CA at inhibiting the autoxidation of L-3,4-dihydroxyphenylalanine. At 100-300 μM, A-3-p-C and A-2-p-C augmented collagen release from human dermal fibroblasts by 120-144% and 125-191%, respectively, compared to 126-133% increase of AA and 120-146% increase of p-CA. They increased procollagen type I C-peptide release (A-3-p-C, and A-2-p-C) like AA, and decreased matrix metalloproteinase 1 level (A-2-p-C) like p-CA, implicating that they might regulate collagen metabolism by multiple mechanisms. This study suggests that A-3-p-C and A-2-p-C could be used as multifunctional cosmeceutical agents for the attenuation of certain aspects of skin aging.
LIU, LI; CAI, SIYI; QIU, GUIXING; LIN, JIN
2016-01-01
ClC-3 is a volume-sensitive chloride channel that is responsible for cell volume adjustment and regulatory cell volume decrease (RVD). In order to evaluate the effects of fluid shear stress (FSS) stimulation on the osteoblast ClC-3 chloride channel, MC3T3-E1 cells were stimulated by FSS in the experimental group. Fluorescence quantitative polymerase chain reaction was used to detect changes in ClC-3 mRNA expression, the chloride ion fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) was used to detect the chloride channel activity, and whole-cell patch clamping was used to monitor the changes in the volume-sensitive chloride current activated by a hypotonic environment following mechanical stimulation. The results show that the expression of the osteoblast chloride channel ClC-3 was significantly higher in the FSS group compared with the control group. MQAE fluorescence intensity was significantly reduced in the FSS group compared to the control group, suggesting that mechanical stimulation increased chloride channel activity and increased the efflux of intracellular chloride ions. Image analysis of osteoblast volume changes showed that osteoblast RVD was enhanced by mechanical stimulation. Whole-cell patch clamping showed that the osteoblast volume-sensitive chloride current was larger in the stimulated group compared to the control group, suggesting that elevated ClC-3 chloride channel expression results in an increased volume-sensitive chloride current. In conclusion, FSS stimulation enhances the RVD of osteoblast cell by increasing the expression of the ClC-3 and enhancing the chloride channel activity. PMID:27073622
Baicalin prevents Candida albicans infections via increasing its apoptosis rate
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Shulong; Fu, Yingyuan, E-mail: yingyuanfu@126.com; Wu, Xiuzhen
2014-08-15
Highlights: • Baicalin increases the ratio of the G0/G1 stages and C. albicans apoptosis. • Baicalin decreases the proliferation index of C. albicans. • Baicalin inhibits the biosynthesis of DNA, RNA and protein in C. albicans. • Baicalin depresses Succinate Dehydrogenase and Ca{sup 2+}–Mg{sup 2+} ATPase in C. albicans. • Baicalin increases the endocytic free Ca{sup 2+} concentration in C. albicans. - Abstract: Background: These experiments were employed to explore the mechanisms underlying baicalin action on Candida albicans. Methodology and principal findings: We detected the baicalin inhibition effects on three isotope-labeled precursors of {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucinemore » incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca{sup 2+}–Mg{sup 2+} ATPase, cytosolic Ca{sup 2+} concentration, the cell cycle and apoptosis, as well as the ultrastructure of C.albicans were also tested. We found that baicalin inhibited {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucine incorporation into C.albicans (P < 0.005). The activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase of C.albicans in baicalin groups were lower than those in control group (P < 0.05). Ca{sup 2+} concentrations of C. albicans in baicalin groups were much higher than those in control group (P < 0.05). The ratio of C.albicans at the G0/G1 stage increased in baicalin groups in dose dependent manner (P < 0.01). There were a significant differences in the apoptosis rate of C.albicans between baicalin and control groups (P < 0.01). After 12–48 h incubation with baicalin (1 mg/ml), C. albicans shown to be markedly damaged under transmission electron micrographs. Innovation and significance: Baicalin can increase the apoptosis rate of C. albicans. These effects of Baicalin may involved in its inhibiting the activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase, increasing cytosolic Ca{sup 2+} content and damaging the ultrastructure of C. albicans.« less
Webb, William M; Sanchez, Richard G; Perez, Gabriella; Butler, Anderson A; Hauser, Rebecca M; Rich, Megan C; O'Bierne, Aidan L; Jarome, Timothy J; Lubin, Farah D
2017-07-01
Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription changes during memory consolidation. However, it is unknown how these epigenetic modifications coordinate control of gene expression following reactivation of a previously consolidated memory. Here, we found that retrieval of a recent contextual fear conditioned memory increased global levels of H3 lysine 4-trimethylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) in area CA1 of the dorsal hippocampus. Further experiments revealed increased levels of H3K4me3 and DNA 5hmC within a CpG-enriched coding region of the Npas4, but not c-fos, gene. Intriguingly, retrieval of a 30-day old memory increased H3K4me3 and DNA 5hmC levels at a CpG-enriched coding region of c-fos, but not Npas4, in the anterior cingulate cortex, suggesting that while these two epigenetic mechanisms co-occur following the retrieval of a recent or remote memory, their gene targets differ depending on the brain region. Additionally, we found that in vivo siRNA-mediated knockdown of the H3K4me3 methyltransferase Mll1 in CA1 abolished retrieval-induced increases in DNA 5hmC levels at the Npas4 gene, suggesting that H3K4me3 couples to DNA 5hmC mechanisms. Consistent with this, loss of Mll1 prevented retrieval-induced increases in Npas4 mRNA levels in CA1 and impaired fear memory. Collectively, these findings suggest an important link between histone methylation and DNA hydroxymethylation mechanisms in the epigenetic control of de novo gene transcription triggered by memory retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.
CovR Regulates Streptococcus mutans Susceptibility To Complement Immunity and Survival in Blood
Alves, Lívia A.; Nomura, Ryota; Mariano, Flávia S.; Harth-Chu, Erika N.; Stipp, Rafael N.; Nakano, Kazuhiko
2016-01-01
Streptococcus mutans, a major pathogen of dental caries, may promote systemic infections after accessing the bloodstream from oral niches. In this study, we investigate pathways of complement immunity against S. mutans and show that the orphan regulator CovR (CovRSm) modulates susceptibility to complement opsonization and survival in blood. S. mutans blood isolates showed reduced susceptibility to C3b deposition compared to oral isolates. Reduced expression of covRSm in blood strains was associated with increased transcription of CovRSm-repressed genes required for S. mutans interactions with glucans (gbpC, gbpB, and epsC), sucrose-derived exopolysaccharides (EPS). Consistently, blood strains showed an increased capacity to bind glucan in vitro. Deletion of covRSm in strain UA159 (UAcov) impaired C3b deposition and binding to serum IgG and C-reactive protein (CRP) as well as phagocytosis through C3b/iC3b receptors and killing by neutrophils. Opposite effects were observed in mutants of gbpC, epsC, or gtfBCD (required for glucan synthesis). C3b deposition on UA159 was abolished in C1q-depleted serum, implying that the classical pathway is essential for complement activation on S. mutans. Growth in sucrose-containing medium impaired the binding of C3b and IgG to UA159, UAcov, and blood isolates but had absent or reduced effects on C3b deposition in gtfBCD, gbpC, and epsC mutants. UAcov further showed increased ex vivo survival in human blood in an EPS-dependent way. Consistently, reduced survival was observed for the gbpC and epsC mutants. Finally, UAcov showed an increased ability to cause bacteremia in a rat model. These results reveal that CovRSm modulates systemic virulence by regulating functions affecting S. mutans susceptibility to complement opsonization. PMID:27572331
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martinson, E.A.; Goldstein, D.; Brown, J.H.
We examined the relationship between phosphatidylcholine (PC) hydrolysis, phosphoinositide hydrolysis, and diacylglycerol (DAG) formation in response to muscarinic acetylcholine receptor (mAChR) stimulation in 1321N1 astrocytoma cells. Carbachol increases the release of (3H)choline and (3H)phosphorylcholine ((3H)Pchol) from cells containing (3H)choline-labeled PC. The production of Pchol is rapid and transient, while choline production continues for at least 30 min. mAChR-stimulated release of Pchol is reduced in cells that have been depleted of intracellular Ca2+ stores by ionomycin pretreatment, whereas choline release is unaffected by this pretreatment. Phorbol 12-myristate 13-acetate (PMA) increases the release of choline, but not Pchol, from 1321N1 cells, andmore » down-regulation of protein kinase C blocks the ability of carbachol to stimulate choline production. Taken together, these results suggest that Ca2+ mobilization is involved in mAChR-mediated hydrolysis of PC by a phospholipase C, whereas protein kinase C activation is required for mAChR-stimulated hydrolysis of PC by a phospholipase D. Both carbachol and PMA rapidly increase the formation of (3H)phosphatidic acid ((3H)PA) in cells containing (3H)myristate-labeled PC. (3H)Diacylglycerol ((3H)DAG) levels increase more slowly, suggesting that the predominant pathway for PC hydrolysis is via phospholipase D. When cells are labeled with (3H)myristate and (14C)arachidonate such that there is a much greater 3H/14C ratio in PC compared with the phosphoinositides, the 3H/14C ratio in DAG and PA increases with PMA treatment but decreases in response to carbachol.« less
Elhag, Amro S; Da, Chang; Chen, Yunshen; Mukherjee, Nayan; Noguera, Jose A; Alzobaidi, Shehab; Reddy, Prathima P; AlSumaiti, Ali M; Hirasaki, George J; Biswal, Sibani L; Nguyen, Quoc P; Johnston, Keith P
2018-07-15
The viscosity and stability of CO 2 /water foams at elevated temperature can be increased significantly with highly viscoelastic aqueous lamellae. The slow thinning of these viscoelastic lamellae leads to greater foam stability upon slowing down Ostwald ripening and coalescence. In the aqueous phase, the viscoelasticity may be increased by increasing the surfactant tail length to form more entangled micelles even at high temperatures and salinity. Systematic measurements of the steady state shear viscosity of aqueous solutions of the diamine surfactant (C 16-18 N(CH 3 )C 3 N(CH 3 ) 2 ) were conducted at varying surfactant concentrations and salinity to determine the parameters for formation of entangled wormlike micelles. The apparent viscosity and stability of CO 2 /water foams were compared for systems with viscoelastic entangled micellar aqueous phases relative to those with much less viscous spherical micelles. We demonstrated for the first time stable CO 2 /water foams at temperatures up to 120 °C and CO 2 volumetric fractions up to 0.98 with a single diamine surfactant, C 16-18 N(CH 3 )C 3 N(CH 3 ) 2 . The foam stability was increased by increasing the packing parameter of the surfactant with a long tail and methyl substitution on the amine to form entangled viscoelastic wormlike micelles in the aqueous phase. The foam was more viscous and stable compared to foams with spherical micelles in the aqueous lamellae as seen with C 12-14 N(EO) 2 and C 16-18 N(EO)C 3 N(EO) 2 . Copyright © 2018. Published by Elsevier Inc.
Morley, Simon A; Hirse, Timo; Thorne, Michael A S; Pörtner, Hans O; Peck, Lloyd S
2012-05-01
To further investigate the previously reported limited acclimation capacities of Antarctic marine stenotherms, the Antarctic mud clam, Laternula elliptica (King and Broderip, 1830-1831), was incubated at 3.0°C for 89days. The thermal windows of a suite of biochemical and physiological metrics that characterise tissue aerobic status, were then measured in response to acute temperature elevation (2-2.5°C increase per week). To test if acclimation had occurred at the higher temperature, results were compared with published data, from the preceding year, for L. elliptica which had been incubated at ambient temperature (0.0°C) and then subjected to the same acute temperature treatments. Incubation to 3.0°C led to a temperature induced increase of tissue aerobic status (reduced intracellular cCO(2) with increased O(2) consumption, PLA (phospho-L-arginine) and ATP). At the highest acute temperature (7.5°C) the increase in anaerobic pathways (summed acetate/succinate and propionate) was less after 3.0°C than 0.0°C incubation. No other metric shifted its reaction norm in response to acute temperature elevation and so whole animal acclimation had not occurred, even after 3months at 3.0°C. Combined with the constant mortality throughout the 3.0°C incubation period, these data suggest that the recorded physiological changes were either the early stages of acclimation or, more likely, time limited resistance mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.
Germination shifts of C3 and C4 species under simulated global warming scenario.
Zhang, Hongxiang; Yu, Qiang; Huang, Yingxin; Zheng, Wei; Tian, Yu; Song, Yantao; Li, Guangdi; Zhou, Daowei
2014-01-01
Research efforts around the world have been increasingly devoted to investigating changes in C3 and C4 species' abundance or distribution with global warming, as they provide important insight into carbon fluxes and linked biogeochemical cycles. However, changes in the early life stage (e.g. germination) of C3 and C4 species in response to global warming, particularly with respect to asymmetric warming, have received less attention. We investigated germination percentage and rate of C3 and C4 species under asymmetric (+3/+6°C at day/night) and symmetric warming (+5/+5°C at day/night), simulated by alternating temperatures. A thermal time model was used to calculate germination base temperature and thermal time constant. Two additional alternating temperature regimes were used to test temperature metrics effect. The germination percentage and rate increased continuously for C4 species, but increased and then decreased with temperature for C3 species under both symmetric and asymmetric warming. Compared to asymmetric warming, symmetric warming significantly overestimated the speed of germination percentage change with temperature for C4 species. Among the temperature metrics (minimum, maximum, diurnal temperature range and average temperature), maximum temperature was most correlated with germination of C4 species. Our results indicate that global warming may favour germination of C4 species, at least for the C4 species studied in this work. The divergent effects of asymmetric and symmetric warming on plant germination also deserve more attention in future studies.
Martín-Granado, Víctor; Ortiz-Rivero, Sara; Carmona, Rita; Gutiérrez-Herrero, Sara; Barrera, Mario; San-Segundo, Laura; Sequera, Celia; Perdiguero, Pedro; Lozano, Francisco; Martín-Herrero, Francisco; González-Porras, José Ramón; Muñoz-Chápuli, Ramón; Porras, Almudena; Guerrero, Carmen
2017-12-19
Previous observations indicated that C3G (RAPGEF1) promotes α-granule release, evidenced by the increase in P-selectin exposure on the platelet surface following its activation. The goal of the present study is to further characterize the potential function of C3G as a modulator of the platelet releasate and its implication in the regulation of angiogenesis. Proteomic analysis revealed a decreased secretion of anti-angiogenic factors from activated transgenic C3G and C3G∆Cat platelets. Accordingly, the secretome from both transgenic platelets had an overall pro-angiogenic effect as evidenced by an in vitro capillary-tube formation assay with HUVECs (human umbilical vein endothelial cells) and by two in vivo models of heterotopic tumor growth. In addition, transgenic C3G expression in platelets greatly increased mouse melanoma cells metastasis. Moreover, immunofluorescence microscopy showed that the pro-angiogenic factors VEGF and bFGF were partially retained into α-granules in thrombin- and ADP-activated mouse platelets from both, C3G and C3GΔCat transgenic mice. The observed interaction between C3G and Vesicle-associated membrane protein (Vamp)-7 could explain these results. Concomitantly, increased platelet spreading in both transgenic platelets upon thrombin activation supports this novel function of C3G in α-granule exocytosis. Collectively, our data point out to the co-existence of Rap1GEF-dependent and independent mechanisms mediating C3G effects on platelet secretion, which regulates pathological angiogenesis in tumors and other contexts. The results herein support an important role for platelet C3G in angiogenesis and metastasis.
The Brain In Vivo Expresses the 2′,3′-cAMP-Adenosine Pathway
Verrier, Jonathan D.; Jackson, Travis C.; Bansal, Rashmi; Kochanek, Patrick M.; Puccio, Ava M.; Okonkwo, David O.; Jackson, Edwin K.
2012-01-01
Although multiple biochemical pathways produce adenosine, studies suggest that the 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP/3′-AMP → adenosine) contributes to adenosine production in some cells/tissues/organs. To determine whether the 2′,3′-cAMP-adenosine pathway exists in vivo in the brain, we delivered to the brain (gray matter and white matter separately) via the inflow perfusate of a microdialysis probe either 2′,3′-cAMP, 3′,5′-cAMP, 2′-AMP, 3′-AMP, or 5′-AMP and measured the recovered metabolites in the microdialysis outflow perfusate with mass spectrometry. In both gray and white matter, 2′,3′-cAMP increased 2′-AMP, 3′-AMP and adenosine, and 3′,5′-cAMP increased 5′-AMP and adenosine. In both brain regions, 2′-AMP, 3-AMP and 5′-AMP were converted to adenosine. Microdialysis experiments in 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) wild-type mice demonstrated that traumatic brain injury (TBI; controlled cortical impact model) activated the brain 2,3′-cAMP-adenosine pathway; similar experiments in CNPase knockout mice indicated that CNPase was involved in the metabolism of endogenous 2′,3′-cAMP to 2′-AMP and to adenosine. In CSF from TBI patients, 2′,3′-cAMP was significantly increased in the initial 12 hours after injury and strongly correlated with CSF levels of 2′-AMP, 3′-AMP, adenosine and inosine. We conclude that in vivo, 2′,3′-cAMP is converted to 2′-AMP/3′-AMP, and these AMPs are metabolized to adenosine. This pathway exists endogenously in both mice and humans. PMID:22360621
Moriyama, Kengo; Negami, Masako; Takahashi, Eiko
2014-11-01
Recent data have suggested a relationship between the high-density lipoprotein (HDL) subclass ratio and metabolic syndrome (MetS). However, limited information is available regarding the relationships between the HDL subclass ratio and insulin resistance, associated adipocytokine levels, and MetS components. The associations of the high-density lipoprotein 2 cholesterol (HDL2-C) to high-density lipoprotein 3 cholesterol (HDL3-C) ratio with the homeostasis model assessment of insulin resistance (HOMA-IR) index, high-molecular-weight adiponectin (HMW-Ad) levels, and MetS components were examined. The study included 1155 Japanese subjects who met our inclusion criteria and underwent an annual health examination that included an HDL subclass analysis. The HDL2-C/HDL3-C ratio and the HMW-Ad level gradually decreased as the number of MetS components increased. In contrast, HOMA-IR gradually increased as the number of MetS components increased. The HDL2-C/HDL3-C ratio correlated inversely with HOMA-IR and positively with the HMW-Ad level. A strong positive correlation was observed between the HDL2-C/HDL3-C ratio and the HDL-C level. The HDL2-C/HDL3-C ratio exhibited moderate negative correlations with the body mass index, waist circumference, and triglyceride level. Weak negative correlations were observed for the HDL2-C/HDL3-C ratio with the systolic and diastolic blood pressure and fasting plasma glucose levels. Our data indicated that the HDL2-C/HDL3-C ratio was associated with insulin resistance, the HMW-Ad level, and MetS components, and it was useful for evaluating MetS in Japanese individuals. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Li, Jieting; Liu, Yujiao; Ren, Xiuyun; Chang, Le; Yue, Zijie; Shi, Xuexue
2014-09-01
To establish chronic periodontitis model in SD rats, and to investigate the effect of oral intervention on atherosclerosis. Fifty male SD rats were randomly divided into three groups, group A (normal control), group B (atherosclerosis,As) and group C (chronic periodontitis, CP). Group C was further divided into group C1 (natural process), group C2 (simple mechanical treatment), group C3 (systemic antibiotics), group C4-1 (teeth extraction) and group C4-2 (teeth extraction+systemic antibiotics), each group consisted of 7 rats. Every group received oral intervention. Serum interleukin (IL)- 6 levels were detected in five different time points (1, 3, 5, 7, 9 weeks after a successful modeling) by enzyme linked immunosorbent assay. All animals were killed after 24 weeks. Matrix metalloproteinase (MMP)- 2, 9 in the proximal aorta was detected by immuno histochemistry. The levels of serum IL-6 in groups B and C1 increased gradually with time and became significantly higher than that in group A (P < 0.01). Levels of serum IL-6 were increased gradually in each intervention group (C2, C3, C4-1, C4-2) and reached its peak at 5 weeks after modeling [C2:(62.3 ± 14.3) ng/L, C3:(58.2 ± 8.7) ng/L, C4-1:(127.0 ± 29.9) ng/L, C4-2:(120.6 ± 23.1) ng/L]. Compared with group B, group C4- 1 and C4- 2 increased most significantly (P < 0.01). Levels of serum IL- 6 decreased gradually. Eventually, group C2 [(28.6 ± 8.1) ng/L], C3 [(40.8 ± 15.1) ng/L] and C4-2 [(32.7 ± 11.1) ng/L] were significantly lower than group B (P < 0.05), and in group C2 IL- 6 was the lowest. Although levels of serum of IL-6 significantly decreased in group C4-1 [(72.8 ± 16.4) ng/L], but remained the highest. Immunohistochemistry showed that MMP-2, 9 were expressed in group B, C1 and C4-1, and significantly higher than in group A (183.0 ± 2.0, 181.3 ± 2.0), the gray value differences were statistically significant (P < 0.01). Group C4-1 (123.1 ± 2.9, 121.0 ± 3.2) was the strongest, group B (126.4 ± 2.0, 124.8 ± 2.8) and C1 (140.0 ± 2.2, 139.7 ± 3.2) were decreased (P < 0.01). While group C2(169.3 ± 3.4, 169.7 ± 2.3), C3 (149.0 ± 1.7, 145.1 ± 2.5) and C4-2 (157.7 ± 1.2, 155.8 ± 2.7) were significantly lower than group C1 (P < 0.01), and group C2 was close to normal. Periodontitis could increase the risk of atherosclerosis in rats with chronic periodontitis. Periodontal mechanical treatment and teeth extraction may increase the risk of As in the short time. However, the risk would gradually reduce in a long time.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pang, W. K.; Low, I. M.; O'Connor, B. H.
2010-01-05
Titanium silicon carbide (Ti{sub 3}SiC{sub 2}) possesses a unique combination of properties of both metals and ceramics, for it is thermally shock resistant, thermally and electrically conductive, damage tolerant, lightweight, highly oxidation resistant, elastically stiff, and mechanically machinable. In this paper, the effect of high vacuum annealing on the phase stability and phase transitions of Ti{sub 3}SiC{sub 2}/TiC/TiSi{sub 2} composites at up to 1550 deg. C was studied using in-situ neutron diffraction. The role of TiC and TiSi{sub 2} on the thermal stability of Ti{sub 3}SiC{sub 2} during vacuum annealing is discussed. TiC reacts with TiSi{sub 2} between 1400-1450 deg.more » C to form Ti{sub 3}SiC{sub 2}. Above 1400 deg. C, decomposition of Ti{sub 3}SiC{sub 2} into TiC commenced and the rate increased with increased temperature and dwell time. Furthermore, the activation energy for the formation and decomposition of Ti{sub 3}SiC{sub 2} was determined.« less
Oxidative stress in hepatitis C infected end-stage renal disease subjects
Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Filiz F; Aslan, Mehmet; Koylu, Ahmet O; Selek, Sahbettin; Erel, Ozcan
2006-01-01
Background Both uremia and hepatitis C infection is associated with increased oxidative stress. In the present study, we aimed to find out whether hepatitis C infection has any impact on oxidative stress in hemodialysis subjects. Methods Sixteen hepatitis C (+) hemodialysis subjects, 24 hepatitis C negative hemodialysis subjects and 24 healthy subjects were included. Total antioxidant capacity, total peroxide level and oxidative stress index were determined in all subjects. Results Total antioxidant capacity was significantly higher in controls than hemodialysis subjects with or without hepatitis C infection (all p < 0.05/3), while total peroxide level and oxidative stress index were significantly lower (all p < 0.05/3). Hepatitis C (-) hemodialysis subjects had higher total antioxidant capacity compared to hepatitis C (+) hemodialysis subjects (all p < 0.05/3). Total peroxide level and oxidative stress index was comparable between hemodialysis subjects with or without hepatitis C infection (p > 0.05/3). Conclusion Oxidative stress is increased in both hepatitis C (+) and hepatitis C (-) hemodialysis subjects. However, hepatitis C infection seems to not cause any additional increase in oxidative stress in hemodialysis subjects and it may be partly due to protective effect of dialysis treatment on hepatitis C infection. PMID:16842626
Oxidative stress in hepatitis C infected end-stage renal disease subjects.
Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Filiz F; Aslan, Mehmet; Koylu, Ahmet O; Selek, Sahbettin; Erel, Ozcan
2006-07-14
Both uremia and hepatitis C infection is associated with increased oxidative stress. In the present study, we aimed to find out whether hepatitis C infection has any impact on oxidative stress in hemodialysis subjects. Sixteen hepatitis C (+) hemodialysis subjects, 24 hepatitis C negative hemodialysis subjects and 24 healthy subjects were included. Total antioxidant capacity, total peroxide level and oxidative stress index were determined in all subjects. Total antioxidant capacity was significantly higher in controls than hemodialysis subjects with or without hepatitis C infection (all p < 0.05/3), while total peroxide level and oxidative stress index were significantly lower (all p < 0.05/3). Hepatitis C (-) hemodialysis subjects had higher total antioxidant capacity compared to hepatitis C (+) hemodialysis subjects (all p < 0.05/3). Total peroxide level and oxidative stress index was comparable between hemodialysis subjects with or without hepatitis C infection (p > 0.05/3). Oxidative stress is increased in both hepatitis C (+) and hepatitis C (-) hemodialysis subjects. However, hepatitis C infection seems to not cause any additional increase in oxidative stress in hemodialysis subjects and it may be partly due to protective effect of dialysis treatment on hepatitis C infection.
GA binding protein augments autophagy via transcriptional activation of BECN1-PIK3C3 complex genes
Zhu, Wan; Swaminathan, Gayathri; Plowey, Edward D
2014-01-01
Macroautophagy is a vesicular catabolic trafficking pathway that is thought to protect cells from diverse stressors and to promote longevity. Recent studies have revealed that transcription factors play important roles in the regulation of autophagy. In this study, we have identified GA binding protein (GABP) as a transcriptional regulator of the combinatorial expression of BECN1-PIK3C3 complex genes involved in autophagosome initiation. We performed bioinformatics analyses that demonstrated highly conserved putative GABP sites in genes that encode BECN1/Beclin 1, several BECN1 interacting proteins, and downstream autophagy proteins including the ATG12–ATG5-ATG16L1 complex. We demonstrate that GABP binds to the promoter regions of BECN1-PIK3C3 complex genes and activates their transcriptional activities. Knockdown of GABP reduced BECN1-PIK3C3 complex transcripts, BECN1-PIK3C3 complex protein levels and autophagy in cultured cells. Conversely, overexpression of GABP increased autophagy. Nutrient starvation increased GABP-dependent transcriptional activity of BECN1-PIK3C3 complex gene promoters and increased the recruitment of GABP to the BECN1 promoter. Our data reveal a novel function of GABP in the regulation of autophagy via transcriptional activation of the BECN1-PIK3C3 complex. PMID:25046113
Kjelgaard-Petersen, Cecilie; Siebuhr, Anne Sofie; Christiansen, Thorbjørn; Ladel, Christoph; Karsdal, Morten; Bay-Jensen, Anne-Christine
2015-01-01
Abstract Objective: Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. Methods: Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. Results: TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1β also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs. Conclusion: The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model. PMID:26863055
Lee, Jae Young; Kim, Ejin; Lee, Woo-Seop; Chae, Yeora; Kim, Ho
2018-01-01
The Paris Agreement aims to limit the global temperature increase to below 2 °C above pre-industrial levels and to pursue efforts to limit the increase to even below 1.5 °C. Now, it should be asked what benefits are in pursuing these two targets. In this study, we assessed the temperature–mortality relationship using a distributed lag non-linear model in seven major cities of South Korea. Then, we projected future temperature-attributable mortality under different Representative Concentration Pathway (RCP) and Shared Socioeconomic Pathway (SSP) scenarios for those cities. Mortality was projected to increase by 1.53 under the RCP 4.5 (temperature increase by 2.83 °C) and 3.3 under the RCP 8.5 (temperature increase by 5.10 °C) until the 2090s, as compared to baseline (1991–2015) mortality. However, future mortality is expected to increase by less than 1.13 and 1.26 if the 1.5 °C and 2 °C increase targets are met, respectively, under the RCP 4.5. Achieving the more ambitious target of 1.5 °C will reduce mortality by 12%, when compared to the 2 °C target. When we estimated future mortality due to both temperature and population changes, the future mortality was found to be increased by 2.07 and 3.85 for the 1.5 °C and 2 °C temperature increases, respectively, under the RCP 4.5. These increases can be attributed to a growing proportion of elderly population, who is more vulnerable to high temperatures. Meeting the target of 1.5 °C will be particularly beneficial for rapidly aging societies, including South Korea. PMID:29690535
Lee, Jae Young; Kim, Ejin; Lee, Woo-Seop; Chae, Yeora; Kim, Ho
2018-04-21
The Paris Agreement aims to limit the global temperature increase to below 2 °C above pre-industrial levels and to pursue efforts to limit the increase to even below 1.5 °C. Now, it should be asked what benefits are in pursuing these two targets. In this study, we assessed the temperature⁻mortality relationship using a distributed lag non-linear model in seven major cities of South Korea. Then, we projected future temperature-attributable mortality under different Representative Concentration Pathway (RCP) and Shared Socioeconomic Pathway (SSP) scenarios for those cities. Mortality was projected to increase by 1.53 under the RCP 4.5 (temperature increase by 2.83 °C) and 3.3 under the RCP 8.5 (temperature increase by 5.10 °C) until the 2090s, as compared to baseline (1991⁻2015) mortality. However, future mortality is expected to increase by less than 1.13 and 1.26 if the 1.5 °C and 2 °C increase targets are met, respectively, under the RCP 4.5. Achieving the more ambitious target of 1.5 °C will reduce mortality by 12%, when compared to the 2 °C target. When we estimated future mortality due to both temperature and population changes, the future mortality was found to be increased by 2.07 and 3.85 for the 1.5 °C and 2 °C temperature increases, respectively, under the RCP 4.5. These increases can be attributed to a growing proportion of elderly population, who is more vulnerable to high temperatures. Meeting the target of 1.5 °C will be particularly beneficial for rapidly aging societies, including South Korea.
Takayama, Mariko; Matsukura, Chiaki; Ariizumi, Tohru; Ezura, Hiroshi
2017-01-01
The C-terminal extension region of SlGAD3 is likely involved in autoinhibition, and removing this domain increases GABA levels in tomato fruits. γ-Aminobutyric acid (GABA) is a ubiquitous non-protein amino acid with several health-promoting benefits. In many plants including tomato, GABA is synthesized via decarboxylation of glutamate in a reaction catalyzed by glutamate decarboxylase (GAD), which generally contains a C-terminal autoinhibitory domain. We previously generated transgenic tomato plants in which tomato GAD3 (SlGAD3) was expressed using the 35S promoter/NOS terminator expression cassette (35S-SlGAD3-NOS), yielding a four- to fivefold increase in GABA levels in red-ripe fruits compared to the control. In this study, to further increase GABA accumulation in tomato fruits, we expressed SlGAD3 with (SlGAD3 OX ) or without (SlGAD3ΔC OX ) a putative autoinhibitory domain in tomato using the fruit ripening-specific E8 promoter and the Arabidopsis heat shock protein 18.2 (HSP) terminator. Although the GABA levels in SlGAD3 OX fruits were equivalent to those in 35S-SlGAD3-NOS fruits, GABA levels in SlGAD3ΔC OX fruits increased by 11- to 18-fold compared to control plants, indicating that removing the autoinhibitory domain increases GABA biosynthesis activity. Furthermore, the increased GABA levels were accompanied by a drastic reduction in glutamate and aspartate levels, indicating that enhanced GABA biosynthesis affects amino acid metabolism in ripe-fruits. Moreover, SlGAD3ΔC OX fruits exhibited an orange-ripe phenotype, which was associated with reduced levels of both carotenoid and mRNA transcripts of ethylene-responsive carotenogenic genes, suggesting that over activation of GAD influences ethylene sensitivity. Our strategy utilizing the E8 promoter and HSP terminator expression cassette, together with SlGAD3 C-terminal deletion, would facilitate the production of tomato fruits with increased GABA levels.
You, Yilin; Yuan, Xiaoxue; Liu, Xiaomeng; Liang, Chen; Meng, Minghui; Huang, Yuanyuan; Han, Xue; Guo, Jielong; Guo, Yu; Ren, Chenglong; Zhang, Qianwen; Sun, Xiangyu; Ma, Tingting; Liu, Guojie; Jin, Wanzhu; Huang, Weidong; Zhan, Jicheng
2017-11-01
Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue (BAT) formation and function increases energy expenditure and may protect against obesity. Cyanidin-3-glucoside (C3G) is an anthocyanin compound that occurs naturally in many fruits and vegetables. In this study, we investigated the effect and mechanism of C3G on the prevention of obesity. Db/db mice received C3G dissolved in drinking water for 16 wk; drinking water served as the vehicle treatment. The total body weight, energy intake, metabolic rate, and physical activity were measured. The lipid droplets, gene expression and protein expression were evaluated by histochemical staining, real-time PCR, and western blots. We found that C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown-like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function. Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Macrophysical climate models and Holocene hunter-gatherer subsistence shifts in Central Texas, USA
NASA Astrophysics Data System (ADS)
Mauldin, R. P.; Munoz, C.
2013-12-01
We use stable carbon isotopic values from bone collagen, as well as carbon values from carbonate extracted from bone apatite from 69 prehistoric human skeletal samples to investigate past resource use and climate relationships over the Middle and Late Holocene in Central Texas. Bone samples come from seven archaeological sites and samples date from 6,900 BP to the close of the prehistoric sequence at about 350 BP. Carbon isotopes from these samples suggest four broad dietary trends. From 6,900 through about 3,800 BP, carbon isotopes suggest a gradual increase in the consumption of resources that ultimately use a C3 photosynthetic pathway. A decline in δ13C in both collagen and carbonate values follows, suggesting a decrease in C3 resource use through roughly 2,900 BP. A variable, but once again increasing pattern on C3 resource use by prehistoric hunter-gatherers is indicated in bone isotopes through about 1,000 BP. After that date, a decrease in C3 resource dependence, with hints at greater subsistence diversity, is suggested through the close of the sequence at 350 BP. To assess the impact of climate shifts on this isotopic pattern, we developed a series of macrophysical climate models (MCM) for several locations in Central Texas focusing on fall, winter, and early spring precipitation. This fall-spring rainfall should closely determine C3 production. If subsistence shifts are responding to climate-induced changes in resource availability, then the measured hunter-gatherer carbon isotope trends summarized above should pattern with C3 production as monitored by the modeled fall-spring precipitation values. For the Middle Holocene portion of the sequence, the precipitation models suggest increasing C3 production, consistent with increasing C3 dependence shown in the isotopic data. A decline in C3 production between 3,900 and 3,000 BP in the models is also consistent with the isotopic decline at that point. After 3,000 BP, however, the coupling between fall-spring rainfall pattern and the bone isotope patterns begin to break down. Precipitation models suggest an essentially flat or slightly increasing pattern of production, while the isotopic data show a rapid C3 increase, and then a decline. This divergence is especially the case late in the sequence, with isotopic patterns showing rapid decreases in C3 resource use that are not consistent with the macrophysical climate models. If the precipitation models are accurate, the Late Holocene pattern of resource use reflects additional elements (e.g., regional population density changes, mobility shifts, social alliances) that require investigation. Standardized values. Data point colors reflect distinct climate trends.
NASA Technical Reports Server (NTRS)
Hoobler, Ray J.; Leone, Stephen R.
1997-01-01
Rate coefficients for the reactions of C2H + HCN yields products and C2H + CH3CN yields products have been measured over the temperature range 262-360 K. These experiments represent an ongoing effort to accurately measure reaction rate coefficients of the ethynyl radical, C2H, relevant to planetary atmospheres such as those of Jupiter and Saturn and its satellite Titan. Laser photolysis of C2H2 is used to produce C2H, and transient infrared laser absorption is employed to measure the decay of C2H to obtain the subsequent reaction rates in a transverse flow cell. Rate constants for the reaction C2H + HCN yields products are found to increase significantly with increasing temperature and are measured to be (3.9-6.2) x 10(exp 13) cm(exp 3) molecules(exp -1) s(exp -1) over the temperature range of 297-360 K. The rate constants for the reaction C2H + CH3CN yields products are also found to increase substantially with increasing temperature and are measured to be (1.0-2.1) x 10(exp -12) cm(exp 3) molecules(exp -1) s(exp -1) over the temperature range of 262-360 K. For the reaction C2H + HCN yields products, ab initio calculations of transition state structures are used to infer that the major products form via an addition/elimination pathway. The measured rate constants for the reaction of C2H + HCN yields products are significantly smaller than values currently employed in photochemical models of Titan, which will affect the HC3N distribution.
The Effect of an Amino Acid Infusion on Central Thermoregulatory Control in Humans
Nakajima, Yasufumi; Takamata, Akira; Matsukawa, Takashi; Sessler, Daniel I.; Kitamura, Yoshihiro; Ueno, Hiroshi; Tanaka, Yoshifumi; Mizobe, Toshiki
2005-01-01
Background Administration of protein or amino acids enhances thermogenesis, presumably by stimulating oxidative metabolism. However, hyperthermia results even when thermoregulatory responses are intact, suggesting that amino acids also alter central thermoregulatory control. We thus tested the hypothesis that amino acid infusion increases the thermoregulatory setpoint. Methods Nine male volunteers each participated on four study days in randomized order: 1) intravenous amino acids infused at 4 kJ·kg−1·hr−1 for 2.5 h combined with skin-surface warming; 2) amino acid infusion combined with cutaneous cooling; 3) a saline infusion combined with skin-surface warming; and, 4) saline infusion combined with cutaneous cooling. Results Amino acid infusion increased resting core temperature by 0.3 ± 0.1°C (mean ± SD) and oxygen consumption by 18 ± 12%. Furthermore, amino acid infusion increased the calculated core temperature threshold (triggering core temperature at a designated mean-skin temperature of 34°C) for active cutaneous vasodilation by 0.3 ± 0.3°C, for sweating by 0.2 ± 0.2°C, for thermoregulatory vasoconstriction by 0.3 ± 0.3°C, and for thermogenesis by 0.4 ± 0.5°C. Amino acid infusion did not alter the incremental response intensity (i.e., gain) of thermoregulatory defenses. Conclusions Amino acid infusion increased the metabolic rate and resting core temperature. However, amino acids also produced a synchronous increase in all major autonomic thermoregulatory defense thresholds; the increase in core temperature was identical to the setpoint increase — even in a cold environment with amble potential to dissipate heat. In subjects with intact thermoregulatory defenses, amino acid-induced hyperthermia appears to result from an elevated setpoint increase rather than increased metabolic rate per se. PMID:15108979
Fertilization Increases Below-Ground Carbon Sequestration of Loblolly Pine Plantations
K.H. Johnsen; J.R. Butnor; C. Maier; R. Oren; R. Pangle; L. Samuelson; J. Seiler; S.E. McKeand; H.L. Allen
2001-01-01
The extent of fertilization of southern pine forests is increasing rapidly; industrial fertilization increased from 16,200 ha per year in 1988, to 344,250 ha in 1998. Fertilization increases stand productivity and can increase carbon (C) sequestration by: 1) increasing above-ground standing C; 2) increasing C stored in forest products; and 3) increasing below-ground...
Appleton, Allison A.; Jackson, Brian P.; Marsit, Carmen J.
2017-01-01
ABSTRACT Epigenetic alterations related to prenatal neurotoxic metals exposure may be key in understanding the origins of cognitive and neurobehavioral problems in children. Placental glucocorticoid receptor (NR3C1) methylation has been linked to neurobehavioral risk in early life, but has not been examined in response to neurotoxic metals exposure despite parallel lines of research showing metals exposure and NR3C1 methylation each contribute to a similar set of neurobehavioral phenotypes. Thus, we conducted a study of prenatal neurotoxic metals exposure and placental NR3C1 methylation in a cohort of healthy term singleton pregnancies from Rhode Island, USA (n = 222). Concentrations of arsenic (As; median 0.02 ug/g), cadmium (Cd; median 0.03 μg/g), lead (Pb; median 0.40 μg/g), manganese (Mn; median 0.56 μg/g), mercury (Hg; median 0.02 μg/g), and zinc (Zn; 145.18 μg/g) measured in infant toenails were categorized as tertiles. Multivariable linear regression models tested the independent associations for each metal with NR3C1 methylation, as well as the cumulative risk of exposure to multiple metals simultaneously. Compared to the lowest exposure tertiles, higher levels of As, Cd, Pb, Mn, and Hg were each associated with increased placental NR3C1 methylation (all P<0.02). Coefficients for these associations corresponded with a 0.71–1.41 percent increase in NR3C1 methylation per tertile increase in metals concentrations. For Zn, the lowest exposure tertile compared with the highest tertile was associated with 1.26 percent increase in NR3C1 methylation (P=0.01). Higher cumulative metal risk scores were marginally associated with greater NR3C1 methylation. Taken together, these results indicate that prenatal exposure to neurotoxic metals may affect the offspring's NR3C1 activity, which may help explain cognitive and neurodevelopmental risk later in life. PMID:28548590
Appleton, Allison A; Jackson, Brian P; Karagas, Margaret; Marsit, Carmen J
2017-08-01
Epigenetic alterations related to prenatal neurotoxic metals exposure may be key in understanding the origins of cognitive and neurobehavioral problems in children. Placental glucocorticoid receptor (NR3C1) methylation has been linked to neurobehavioral risk in early life, but has not been examined in response to neurotoxic metals exposure despite parallel lines of research showing metals exposure and NR3C1 methylation each contribute to a similar set of neurobehavioral phenotypes. Thus, we conducted a study of prenatal neurotoxic metals exposure and placental NR3C1 methylation in a cohort of healthy term singleton pregnancies from Rhode Island, USA (n = 222). Concentrations of arsenic (As; median 0.02 ug/g), cadmium (Cd; median 0.03 μg/g), lead (Pb; median 0.40 μg/g), manganese (Mn; median 0.56 μg/g), mercury (Hg; median 0.02 μg/g), and zinc (Zn; 145.18 μg/g) measured in infant toenails were categorized as tertiles. Multivariable linear regression models tested the independent associations for each metal with NR3C1 methylation, as well as the cumulative risk of exposure to multiple metals simultaneously. Compared to the lowest exposure tertiles, higher levels of As, Cd, Pb, Mn, and Hg were each associated with increased placental NR3C1 methylation (all P<0.02). Coefficients for these associations corresponded with a 0.71-1.41 percent increase in NR3C1 methylation per tertile increase in metals concentrations. For Zn, the lowest exposure tertile compared with the highest tertile was associated with 1.26 percent increase in NR3C1 methylation (P=0.01). Higher cumulative metal risk scores were marginally associated with greater NR3C1 methylation. Taken together, these results indicate that prenatal exposure to neurotoxic metals may affect the offspring's NR3C1 activity, which may help explain cognitive and neurodevelopmental risk later in life.
Mesophyll Chloroplast Investment in C3, C4 and C2 Species of the Genus Flaveria.
Stata, Matt; Sage, Tammy L; Hoffmann, Natalie; Covshoff, Sarah; Ka-Shu Wong, Gane; Sage, Rowan F
2016-05-01
The mesophyll (M) cells of C4 plants contain fewer chloroplasts than observed in related C3 plants; however, it is uncertain where along the evolutionary transition from C3 to C4 that the reduction in M chloroplast number occurs. Using 18 species in the genus Flaveria, which contains C3, C4 and a range of C3-C4 intermediate species, we examined changes in chloroplast number and size per M cell, and positioning of chloroplasts relative to the M cell periphery. Chloroplast number and coverage of the M cell periphery declined in proportion to increasing strength of C4 metabolism in Flaveria, while chloroplast size increased with increasing C4 cycle strength. These changes increase cytosolic exposure to the cell periphery which could enhance diffusion of inorganic carbon to phosphenolpyruvate carboxylase (PEPC), a cytosolic enzyme. Analysis of the transcriptome from juvenile leaves of nine Flaveria species showed that the transcript abundance of four genes involved in plastid biogenesis-FtsZ1, FtsZ2, DRP5B and PARC6-was negatively correlated with variation in C4 cycle strength and positively correlated with M chloroplast number per planar cell area. Chloroplast size was negatively correlated with abundance of FtsZ1, FtsZ2 and PARC6 transcripts. These results indicate that natural selection targeted the proteins of the contractile ring assembly to effect the reduction in chloroplast numbers in the M cells of C4 Flaveria species. If so, efforts to engineer the C4 pathway into C3 plants might evaluate whether inducing transcriptome changes similar to those observed in Flaveria could reduce M chloroplast numbers, and thus introduce a trait that appears essential for efficient C4 function. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
N fertilization reduces the losses of old soil organic carbon
NASA Astrophysics Data System (ADS)
Zang, H.; Blagodatskaya, E.; Wang, J.; Kuzyakov, Y.; Xu, X.
2016-12-01
Agricultural soils have experiencing large anthropogenic nitrogen (N) inputs, which directly and indirectly affect soil organic matter (SOM) stocks and CO2 emissions. However, current understanding of how these additional N inputs affect SOM pools of various ages and turnover remains incomplete. The δ13C values of SOM after wheat (C3) - maize (C4) vegetation change enable to calculate the contribution of C4-derived rhizodeposited C (rhizo-C) and C3-derived old SOM pools. Soil (Ap from Haplic Luvisol) sampled from maize rhizosphere was incubated over 56 days after increasing N fertilization (4 levels up to 300 kg N ha-1). N fertilization decreased soil CO2 emissions by 27-42% as compared to unfertilized control. This decrease was mainly caused by the retardation of old C mineralization. The relative availability of rhizo-C (released by maize roots within 4 weeks) for microorganisms was about 10 times higher than of old C (older than 4 weeks). Microbial biomass and dissolved organic C were unaffected by increasing N. N fertilization, however, increased relative contribution of rhizo-C to microbial biomass for 2 - 5 times and to CO2 for about 2 times. This clearly reflects acceleration of microbial biomass turnover by N addition. The decomposition rate of rhizo-C was 3.7 times higher than of old C, and it increased additionally by the factor of 6.5 under high N fertilization. Our study is the first estimated the turnover and incorporation of very recent rhizo-C (within 4 weeks). Compared with several-years old C4, the turnover of rhizo-C was about 2 times faster. Concluding, the contribution of rhizo-C to CO2 and microbial biomass was highly responsive to N fertilization. N fertilization facilitates C sequestration in agricultural soils by decreasing old SOM decomposition mainly through increase the turnover and C use efficiency of rhizo-C. Keywords: CO2 partitioning; C3-C4 vegetation; microbial biomass; SOM decomposition; Nutrient availability
Immunotoxicity and genotoxicity testing for in-flight experiments under microgravity
NASA Astrophysics Data System (ADS)
Hansen, Peter-Diedrich; Hansen, Peter-Diedrich; Unruh, Eckehardt
Life Sciences as Related to Space (F) Influence of Spaceflight Environment on Biological Systems (F44) Immunotoxicity and genotoxicity testing for In-flight experiments under microgravity Sensing approaches for ecosystem and human health Author: Peter D. Hansen Technische Universit¨t Berlin, Faculty VI - Planen, Bauen, Umwelt, a Institute for Ecological Research and Technology, Department for Ecotoxicology, Berlin, Germany Peter-diedrich.hansen@tu-berlin.de Eckehardt Unruh Technische Universit¨t Berlin, Faculty VI - Planen, Bauen, Umwelt, Institute a for Ecological Research and Technology, Department for Ecotoxicology, Berlin, Germany An immune response by mussel hemocytes is the selective reaction to particles which are identified as foreign by its immune system shown by phagocytosis. Phagocytotic activity is based on the chemotaxis and adhesion, ingestion and phagosome formation. The attachment at the surface of the hemocytes and consequently the uptake of the particles or bacteria can be directly quantified in the format of a fluorescent assay. Another relevant endpoint of phagocytosis is oxidative burst measured by luminescence. Phagocytosis-related production of ROS will be stimulated with opsonised zymosan. The hemocytes will be stored frozen at -80oC and reconstituted in-flight for the experiment. The assay system of the TRIPLELUX-B Experiment has been performed with a well-defined quantification and evaluation of the immune function phagocytosis. The indicator cells are the hemocytes of blue mussels (Mytilus edulis). The signals of the immuno cellular responses are translated into luminescence as a rapid optical reporter system. The results expected will determine whether the observed responses are caused by microgravity and/or radiation (change in permeability, endpoints in genotoxicity: DNA unwinding). The samples for genotoxicity will be processed after returning to earth. The immune system of invertebrates has not been studied so far in space. The choice of phagocytes from invertebrates is justified to study the universal validity of innate immune responses. The TRIPLELUX-B Experiment contributes to risk assessment concerning immunotoxicity under space flight conditions. The components of the phagocytosis test system for the BIOLAB are now established and the technical realization of the TRIPLELUX- B Experiment is in final progess. The components of the fully automated AEC (Advanced Experimental Containment) will be demonstrated in the poster. There will be two AECs for reference measurements at 1xg and 0xg. The AEC of the TRIPLELUX-B experiment will contribute to a real time operational monitoring for immunotoxicity testing on earth. The AEC will allow "real time monitoring" providing automated observations of immunotoxicity in coastal and inland waters.
Etherton, Mark; Földy, Csaba; Sharma, Manu; Tabuchi, Katsuhiko; Liu, Xinran; Shamloo, Mehrdad; Malenka, Robert C; Südhof, Thomas C
2011-08-16
Multiple independent mutations in neuroligin genes were identified in patients with familial autism, including the R451C substitution in neuroligin-3 (NL3). Previous studies showed that NL3(R451C) knock-in mice exhibited modestly impaired social behaviors, enhanced water maze learning abilities, and increased synaptic inhibition in the somatosensory cortex, and they suggested that the behavioral changes in these mice may be caused by a general shift of synaptic transmission to inhibition. Here, we confirm that NL3(R451C) mutant mice behaviorally exhibit social interaction deficits and electrophysiologically display increased synaptic inhibition in the somatosensory cortex. Unexpectedly, however, we find that the NL3(R451C) mutation produced a strikingly different phenotype in the hippocampus. Specifically, in the hippocampal CA1 region, the NL3(R451C) mutation caused an ∼1.5-fold increase in AMPA receptor-mediated excitatory synaptic transmission, dramatically altered the kinetics of NMDA receptor-mediated synaptic responses, induced an approximately twofold up-regulation of NMDA receptors containing NR2B subunits, and enhanced long-term potentiation almost twofold. NL3 KO mice did not exhibit any of these changes. Quantitative light microscopy and EM revealed that the NL3(R451C) mutation increased dendritic branching and altered the structure of synapses in the stratum radiatum of the hippocampus. Thus, in NL3(R451C) mutant mice, a single point mutation in a synaptic cell adhesion molecule causes context-dependent changes in synaptic transmission; these changes are consistent with the broad impact of this mutation on murine and human behaviors, suggesting that NL3 controls excitatory and inhibitory synapse properties in a region- and circuit-specific manner.
Sun, Jianxia; Xu, Wei; Zhu, Cuijuan; Hu, Yunfeng; Jiang, Xinwei; Ou, Shiyi; Su, Zhijian; Huang, Yadong; Jiao, Rui; Bai, Weibin
2016-01-01
1,3-Dichloro-2-propanol (1,3-DCP) is a food processing contaminant and has been shown to perturb male reproductive function. Cyanidin-3-O-glucoside (C3G), an anthocyanin antioxidant, is reported to have protective effects on many organs. However, it remains unclear whether C3G protects against chemical-induced reproductive toxicity. The present study was therefore to investigate the intervention of C3G on 1,3-DCP-induced reproductive toxicity in R2C Leydig cells. Results demonstrated that C3G inhibited the 1,3-DCP-induced cytotoxicity and cell shape damage with the effective doses being ranging from 10 to 40 μmol/L. In addition, 1,3-DCP (2 mmol/L) exposure significantly increased the ROS level and mitochondrial membrane potential damage ratio, leading to a decrease in progesterone production, while C3G intervention reduced the ROS level, and increased the progesterone production after 24 h treatment. Most importantly, C3G intervention could up-regulate the cyclic adenosine monophosphate (cAMP) level and protein expression of steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase. It was concluded that C3G is effective in reducing 1,3-DCP-induced reproductive toxicity via activating steroidogenic enzymes and cAMP level. PMID:27867356
Sun, Jianxia; Xu, Wei; Zhu, Cuijuan; Hu, Yunfeng; Jiang, Xinwei; Ou, Shiyi; Su, Zhijian; Huang, Yadong; Jiao, Rui; Bai, Weibin
2016-01-01
1,3-Dichloro-2-propanol (1,3-DCP) is a food processing contaminant and has been shown to perturb male reproductive function. Cyanidin-3- O -glucoside (C3G), an anthocyanin antioxidant, is reported to have protective effects on many organs. However, it remains unclear whether C3G protects against chemical-induced reproductive toxicity. The present study was therefore to investigate the intervention of C3G on 1,3-DCP-induced reproductive toxicity in R2C Leydig cells. Results demonstrated that C3G inhibited the 1,3-DCP-induced cytotoxicity and cell shape damage with the effective doses being ranging from 10 to 40 μmol/L. In addition, 1,3-DCP (2 mmol/L) exposure significantly increased the ROS level and mitochondrial membrane potential damage ratio, leading to a decrease in progesterone production, while C3G intervention reduced the ROS level, and increased the progesterone production after 24 h treatment. Most importantly, C3G intervention could up-regulate the cyclic adenosine monophosphate (cAMP) level and protein expression of steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase. It was concluded that C3G is effective in reducing 1,3-DCP-induced reproductive toxicity via activating steroidogenic enzymes and cAMP level.
Speed, Haley E; Masiulis, Irene; Gibson, Jay R; Powell, Craig M
2015-01-01
A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I) imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs) onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs) from parvalbumin-positive (PV) or somatostatin-positive (SOM) interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at interneurons other than PV or SOM.
Speed, Haley E.; Masiulis, Irene; Gibson, Jay R.; Powell, Craig M.
2015-01-01
A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I) imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs) onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs) from parvalbumin-positive (PV) or somatostatin-positive (SOM) interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at interneurons other than PV or SOM. PMID:26469287
Dudas, Bertalan; Rose, Michael; Cornelli, Umberto; Hanin, Israel
2005-02-01
Glycosaminoglycans (GAGs) play a pivotal role in the pathogenesis of Alzheimer's disease (AD). Although, as we have shown earlier, a low molecular weight GAG, C3, protects against ethylcholine aziridinium (AF64A)-induced cholinergic damage, and against A(beta)-induced tau-2-immunoreactivity (IR), the mechanism of the neuroprotective effect of GAGs is not yet known. Several clues exist. Previous studies in rats revealed that continuous NGF infusion (icv) after AF64A injection increases septal ChAT and AChE activities. Moreover, C3 increases axonal outgrowth in the rat hippocampus, raising the possibility of a NGF-receptor mediated neuroprotection. Furthermore, it has been reported that NGF expression is increased in the septum following AF64A administration. To study the question regarding the mechanism of neuroprotective action of GAGs, AF64A, a selective cholinotoxin, was administered stereotaxically, bilaterally, into the lateral ventricles of Fischer albino male rats (1 nmol/2 microl/side). In order to establish the effect of C3 on the expression of the NGF receptor-IR elements, C3 was administered orally (25 mg/kg, once a day), by gavage, 7 days before, and 7 days after the AF64A injection. NGF receptor immunohistochemistry revealed that AF64A induced the appearance of NGF-receptor-IR axonal varicosities in the rat medial septum. These varicose fibers were attenuated by 14 days' administration of C3. The possible explanation of our data may be that C3 increases NGF synthesis in the lateral septum. The increased level of NGF could suppress the increased, AF64A-induced NGF receptor expression in the medial septal nucleus. These results further accentuate our earlier observations that C3 may have potential as a therapeutic agent in AD and other neurodegenerative disorders.
NASA Astrophysics Data System (ADS)
Zhu, Hong-Bin; Shen, Jie; Gao, Feng; Yu, Yueguang; Li, Changhai
2017-01-01
This work is aimed at developing a new type of Cr7C3-(Ni,Cr)3(Al,Cr) coating for parts used in heavy-duty diesel engines. The feedstock, in which the stripe-shaped Cr7C3 was in situ formed, was firstly prepared by vacuum melting and gas atomization and then subjected by high-velocity oxy-fuel spraying to form the coatings. The carbon content, microstructure and phase constitution of the powders, as well as the sprayed coatings, were analyzed by chemical analysis, SEM and XRD. The hardness and sliding wear performance of the sprayed coatings were also tested and compared to a commercial Cr3C2-NiCr coating used on piston rings. The results showed that the content of carbon in feedstock was almost the same as designed, and that the volume content of in situ formed Cr7C3 was increased with carbon and chromium added. The major phases of the powders and sprayed coatings are Cr7C3 and Cr-alloyed Ni3Al. Only a small amount of carbon lost during the spraying process. As Cr7C3 content increased in the coatings, the microhardness at room temperature was firstly increased to about 1000Hv0.3. The microhardness of the coatings stayed almost constant, while the testing temperature was raised up to 700 °C for 0.5 h, which illustrates the potential application of the investigated coatings under high temperature conditions. The coatings containing 70 and 77 vol.% Cr7C3 showed the most promising wear resistance, lower friction coefficient and better tribological compatibility to gray cast iron counterpart than other tested Cr7C3-(Ni,Cr)3(Al,Cr) coatings and the reference Cr3C2-NiCr coating.
Xu, Fei; Matsumoto, Kazuhiko; Hagiwara, Rika
2012-08-23
The effects of the HF composition, n, in 1-dodecyl-3-methylimidazolium fluorohydrogenate salts (C(12)MIm(FH)(n)F, n = 1.0-2.3) on their physicochemical and structural properties have been investigated using infrared spectroscopy, thermal analysis, polarized optical microscopy, X-ray diffraction, and anisotropic ionic conductivity measurements. The phase diagram of C(12)MIm(FH)(n)F (n vs transition temperature) suggests that C(12)MIm(FH)(n)F is a mixed crystal system that has a boundary around n = 1.9. For all compositions, a liquid crystalline mesophase with a smectic A interdigitated bilayer structure is observed. The temperature range of the mesophase decreases with increasing n value (from 61.8 °C for C(12)MIm(FH)(1.0)F to 37.0 °C for C(12)MIm(FH)(2.3)F). The layer spacing of the smectic structure decreases with increasing n value or increasing temperature. Two structural types with different layer spacings are observed in the crystalline phase (type I, 1.0 ≤ n ≤ 1.9, and type II, 1.9 ≤ n ≤ 2.3). Ionic conductivities parallel and perpendicular to the smectic layers (σ(||) and σ([perpendicular])) increase with increasing n value, whereas the anisotropy of the ionic conductivities (σ(||)/σ([perpendicular])) is independent of the n value, since the thickness of the insulating sheet formed by the dodecyl group remains nearly unchanged.
Wertin, Timothy M.; Reed, Sasha C.; Belnap, Jayne
2015-01-01
Dryland ecosystems represent >40 % of the terrestrial landscape and support over two billion people; consequently, it is vital to understand how drylands will respond to climatic change. However, while arid and semiarid ecosystems commonly experience extremely hot and dry conditions, our understanding of how further temperature increases or altered precipitation will affect dryland plant communities remains poor. To address this question, we assessed plant physiology and growth at a long-term (7-year) climate experiment on the Colorado Plateau, USA, where the community is a mix of shallow-rooted C3 and C4 grasses and deep-rooted C4 shrubs. The experiment maintained elevated-temperature treatments (+2 or +4 °C) in combination with altered summer monsoonal precipitation (+small frequent precipitation events or +large infrequent events). Increased temperature negatively affected photosynthesis and growth of the C3 and C4 grasses, but effects varied in their timing: +4 °C treatments negatively affected the C3 grass early in the growing season of both years, while the negative effects of temperature on the C4 grass were seen in the +2 and +4 °C treatments, but only during the late growing season of the drier year. Increased summer precipitation did not affect photosynthesis or biomass for any species, either in the year the precipitation was applied or the following year. Although previous research suggests dryland plants, and C4 grasses in particular, may respond positively to elevated temperature, our findings from a cool desert show marked declines in C3 and C4 photosynthesis and growth, with temperature effects dependent on the degree of warming and growing-season precipitation.
NASA Astrophysics Data System (ADS)
Usacheva, T. R.; Lan, Pham Thi; Sharnin, V. A.
2014-06-01
The effect of a water-dimethylsulfoxide (DMSO) solvent on the formation of a molecular complex of 18-crown-6 (18C6) with triglycine (diglycylglycine, 3Gly) is studied via calorimetric titration. It is found that switching from water to an H2O-DMSO mixture with DMSO mole fraction of 0.30 is accompanied by a monotonic increase in the stability of [3Gly18C6] complex, from log K ∘ = 1.10 to log K ∘ = 2.44, and an increase in the exothermicity of the reaction of its formation, from -5.9 to -16.9 kJ/mol. It is shown that the [3Gly18C6] complex exhibits enthalpy stabilization with negative values of enthalpy and entropy over the investigated range of H2O-DMSO solvents. Analysis of the reagents' solvation characteristics reveals that the increase in the reaction's exothermicity of transfer is due to differences in the solvation of [3Gly18C6] and 18C6 with a small solvation contribution from 3Gly. It is concluded that the change in the Gibbs energy of the reaction 3Glysolv + 18C6solv ↔ [3Gly18C6]solv is due to differences in the change in the solvation state of the complex and the peptide (Δtr G ∘([3Gly18C6])-Δtr G ∘(3Gly)).
Macrophyte Community Response to Nitrogen Loading and ...
Empirical determination of nutrient loading thresholds that negatively impact seagrass communities have been elusive due to the multitude of factors involved. Using a mesocosm system that simulated Pacific Northwest estuaries, we evaluated macrophyte metrics across gradients of NO3 loading (0, 1.5, 3 and 6x ambient) and temperature (10 and 20 °C). Macroalgal growth, biomass, and C:N responded positively to increased NO3 load and floating algal mats developed at 20 ºC. Zostera japonica metrics, including C:N, responded more to temperature than to NO3 loading. Z. marina biomass exhibited a negative temperature effect and in some cases a negative NO3 effect, while growth rate increased with temperature. Shoot survival decreased at 20 ºC but was not influenced by NO3 loading. Wasting disease index exhibited a significant temperature by NO3 interaction consistent with increased disease susceptibility. Community shifts observed were consistent with the nutrient loading hypothesis at 20 ºC, but there was no evidence of other eutrophication symptoms due to the short residence time. The Nutrient Pollution Index tracked the NO3 gradient at 10 ºC but exhibited no response at 20 ºC. We suggest that systems characterized by cool temperatures, high NO3 loads, and short residence time may be resilient to many symptoms of eutrophication. Estuarine systems characterized by cool temperatures, high nutrient loads and rapid flushing may be resilient to some symptoms
Aquilante, Christina L; Kosmiski, Lisa A; Bourne, David W A; Bushman, Lane R; Daily, Elizabeth B; Hammond, Kyle P; Hopley, Charles W; Kadam, Rajendra S; Kanack, Alexander T; Kompella, Uday B; Le, Merry; Predhomme, Julie A; Rower, Joseph E; Sidhom, Maha S
2013-01-01
AIM The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug–drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). METHODS In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. RESULTS Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P < 0.001) and there was interindividual variability in the magnitude of this interaction (range, 1.8- to 12.1-fold). When pioglitazone was administered alone, the mean AUC(0,∞) was 29.7% lower (P= 0.01) in CYP2C8*3 carriers compared with CYP2C8*1 homozygotes. The relative change in pioglitazone plasma exposure following gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P= 0.02). CONCLUSION CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil–pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug–drug interactions. PMID:22625877
Aquilante, Christina L; Kosmiski, Lisa A; Bourne, David W A; Bushman, Lane R; Daily, Elizabeth B; Hammond, Kyle P; Hopley, Charles W; Kadam, Rajendra S; Kanack, Alexander T; Kompella, Uday B; Le, Merry; Predhomme, Julie A; Rower, Joseph E; Sidhom, Maha S
2013-01-01
The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P < 0.001) and there was interindividual variability in the magnitude of this interaction (range, 1.8- to 12.1-fold). When pioglitazone was administered alone, the mean AUC(0,∞) was 29.7% lower (P = 0.01) in CYP2C8*3 carriers compared with CYP2C8*1 homozygotes. The relative change in pioglitazone plasma exposure following gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P = 0.02). CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
AshokKumar, Manickaraj; Subhashini, Navaneethan Gnana Veera; SaiBabu, Ramineni; Ramesh, Arabandi; Cherian, Kotturathu Mammen; Emmanuel, Cyril
2010-01-01
Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction-restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.
Veltmeijer, Matthijs T W; Veeneman, Dineke; Bongers, Coen C C W; Netea, Mihai G; van der Meer, Jos W; Eijsvogels, Thijs M H; Hopman, Maria T E
2017-05-01
Exercise increases core body temperature (T C ) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 (IL-6) may also contribute to the rise in T C by increasing the hypothalamic temperature set point. This study investigated whether the exercise-induced increase in T C is partly caused by an altered hypothalamic temperature set point. Fifteen healthy, active men age 36 ± 14 y were recruited. Subjects performed submaximal treadmill exercise in 3 randomized test conditions: (1) 400 mg ibuprofen and 1000 mg acetaminophen (IBU/APAP), (2) 1000 mg acetaminophen (APAP), and (3) a control condition (CTRL). Acetaminophen and ibuprofen were used to block the effect of IL-6 at a central and peripheral level, respectively. T C , skin temperature, and heart rate were measured continuously during the submaximal exercise tests. Baseline values of T C , skin temperature, and heart rate did not differ across conditions. Serum IL-6 concentrations increased in all 3 conditions. A significantly lower peak T C was observed in IBU/APAP (38.8°C ± 0.4°C) vs CTRL (39.2°C ± 0.5°C, P = .02) but not in APAP (38.9°C ± 0.4°C) vs CTRL. Similarly, a lower ΔT C was observed in IBU/APAP (1.7°C ± 0.3°C) vs CTRL (2.0°C ± 0.5°C, P < .02) but not in APAP (1.7°C ± 0.5°C) vs CTRL. No differences were observed in skin temperature and heart-rate responses across conditions. The combined administration of acetaminophen and ibuprofen resulted in an attenuated increase in T C during exercise compared with a CTRL. This observation suggests that a prostaglandin-E2-induced elevated hypothalamic temperature set point may contribute to the exercise-induced rise in T C .
Carbon Nanostructure of Kraft Lignin Thermally Treated at 500 to 1000 °C.
Zhang, Xuefeng; Yan, Qiangu; Leng, Weiqi; Li, Jinghao; Zhang, Jilei; Cai, Zhiyong; Hassan, El Barbary
2017-08-21
Kraft lignin (KL) was thermally treated at 500 to 1000 °C in an inert atmosphere. Carbon nanostructure parameters of thermally treated KL in terms of amorphous carbon fraction, aromaticity, and carbon nanocrystallites lateral size ( L a ), thickness ( L c ), and interlayer space ( d 002 ) were analyzed quantitatively using X-ray diffraction, Raman spectroscopy, and high-resolution transmission electron microscopy. Experimental results indicated that increasing temperature reduced amorphous carbon but increased aromaticity in thermally treated KL materials. The L c value of thermally treated KL materials averaged 0.85 nm and did not change with temperature. The d 002 value decreased from 3.56 Å at 500 °C to 3.49 Å at 1000 °C. The L a value increased from 0.7 to 1.4 nm as temperature increased from 500 to 1000 °C. A nanostructure model was proposed to describe thermally treated KL under 1000 °C. The thermal stability of heat treated KL increased with temperature rising from 500 to 800 °C.
Yan, Li-Hong; Chen, Xue-Jun; Su, Rong-Guo; Han, Xiu-Rong; Zhang, Chuan-Song; Shi, Xiao-Yong
2013-01-01
The distribution and estuarine behavior of fluorescent components of chromophoric dissolved organic matter in the seawater of outer Yangtze Estuary were determined by fluorescence excitation emission matrix spectra combined with parallel factor analysis. Six individual fluorescent components were identified by PARAFAC models, including three terrestrial humic-like components C1 [330 nm/390(430) nm], C2 (390 nm/480 nm), C3 (360 nm/440 nm), marine biological production component C5 (300 nm/400 nm) and protein-like components C4 (290 nm/350 nm) and C6 (275 nm/300 nm). The results indicated that C1, C2, and C3 showed a conservative mixing behavior in the whole estuarine region, especially in high-salinity region. And the fluorescence intensity proportion of C1 and C3 decreased with increase of salinity and fluorescence intensity proportion of C2 kept constant with increase of salinity in the whole estuarine region. While C4 showed conservative mixing behavior in low-salinity region and non-conservative mixing behavior in high-salinity region, and fluorescence intensity proportion of C4 increased with increase of salinity. However, C5 and C6 showed a non-conservative mixing behavior and fluorescence intensity proportion increased with increase of salinity in high-salinity region. Significantly spatial difference was recorded for CDOM absorption coefficient in the coastal region and in the open water areas with the highest value in coastal region and the lowest value in the open water areas. The scope of absorption coefficient and absorption slope was higher in coastal region than that in the open water areas. Significantly positive correlations were found between CDOM absorption coefficient and the fluorescence intensities of C1, C2, C3, and C4, but no significant correlation was found between C5 and C6, suggesting that the river inputs contributed to the coastal areas, while CDOM in the open water areas was affected by terrestrial inputs and phytoplankton degradation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
San, Long K.; Spisak, Sarah N.; Dubceac, Cristina
Two series of aromatic compounds with perfluoroalkyl (RF) groups of increasing length, 1,3,5,7-naphthalene(RF)4 and 1,3,5,7,9-corannulene(RF)5, have been prepared and their electronic properties studied by low-temperature PES (i.e., gas-phase electron affinity (EA) measurements). These and many related compounds were also studied by DFT calculations. The data demonstrate unambiguously that the electron-withdrawing ability of RF substituents increases significantly and uniformly from CF3 to C2F5 to n-C3F7 to n-C4F9.
DOE Office of Scientific and Technical Information (OSTI.GOV)
San, Long K.; Spisak, Sarah N.; Dubceac, Cristina
2018-01-26
Two series of aromatic compounds with perfluoroalkyl (RF) groups of increasing length, 1,3,5,7-naphthalene(RF)4 and 1,3,5,7,9-corannulene(RF)5, have been prepared and their electronic properties studied by low-temperature PES (i.e., gas-phase electron affinity (EA) measurements). These and many related compounds were also studied by DFT calculations. The data demonstrate unambiguously that the electron-withdrawing ability of RF substituents increases significantly and uniformly from CF3 to C2F5 to n-C3F7 to n-C4F9.
NASA Astrophysics Data System (ADS)
Mai Oanh, Le Thi; Hang, Lam Thi; Lai, Ngoc Diep; Phuong, Nguyen Thi; Thang, Dao Viet; Hung, Nguyen Manh; Danh Bich, Do; Minh, Nguyen Van
2018-03-01
The influences of annealing temperature on structure, morphology, vibration, optical properties and photocatalytic ability of g-C3N4 nanosheets synthesized from urea in Ar atmosphere were investigated in detail by using x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET), Fourier transform infrared spectroscopy (FTIR), UV-vis absorption, and photoluminescence (PL). It was found that the preparation temperature had a great effect on structure and physical properties of g-C3N4. As the processing temperature increased from 450 °C to 650 °C, the interlayer stacking distance of g-C3N4 decreased from 3.281 Å to 3.217 Å and the lattice parameter a decreased from 5.010 Å to 4.934 Å. This indicated a denser packing fashion of g-C3N4 at high annealing temperature. Moreover, the FTIR spectra and SEM images revealed a large fraction of small polymer segments containing only a few heptazine units as annealing temperature increased. BET result indicated an increasing specific surface area as preparation temperature increased. UV-vis absorption spectra showed a decrease of the band gap energy with increasing calcination temperature which agrees well with the measured PL spectra. It was demonstrated that samples annealed at 550 °C exhibited the strongest photocatalytic activity. A decomposition of 80% and 100% of rhodamine B was obtained within respectively 1 h and 2 h under Xenon lamp irradiation. Photocatalytic result could be adequately explained based on evidences of specific surface area, average pore volume and pore size, and recombination rate of photoinduced electron-hole pairs.
Behera, B; Das, Puspendu K
2018-05-10
Blue-shifting H-bonded (C-D···O) complexes between CDCl 3 and CH 3 HCO, (CH 3 ) 2 CO, and C 2 H 5 (CH 3 )CO, and red-shifting H-bonded (C-D···S) complexes between CDCl 3 with (CH 3 ) 2 S and (C 2 H 5 ) 2 S have been identified by Fourier transform infrared spectroscopy in the gas phase at room temperature. With increasing partial pressure of the components, a new band appears in the C-D stretching region of the vibrational spectra. The intensity of this band decreases with an increase in temperature at constant pressure, which provides the basis for identification of the H-bonded bands in the spectrum. The C-D stretching frequency of CDCl 3 is blue-shifted by +7.1, +4, and +3.2 cm -1 upon complexation with CH 3 HCO, (CH 3 ) 2 CO, and C 2 H 5 (CH 3 )CO, respectively, and red-shifted by -14 and -19.2 cm -1 upon complexation with (CH 3 ) 2 S and (C 2 H 5 ) 2 S, respectively. By using quantum chemical calculations at the MP2/6-311++G** level, we predict the geometry, electronic structural parameters, binding energy, and spectral shift of H-bonded complexes between CDCl 3 and two series of compounds named RCOR' (H 2 CO, CH 3 HCO, (CH 3 ) 2 CO, and C 2 H 5 (CH 3 )CO) and RSR' (H 2 S, CH 3 HS, (CH 3 ) 2 S, and (C 2 H 5 ) 2 S) series. The calculated and observed spectral shifts follow the same trends. With an increase in basicity of the H-bond acceptor, the C-D bond length increases, force constant decreases, and the frequency shifts to the red from the blue. The potential energy scans of the above complexes are done, which show that electrostatic attraction between electropositive D and electron-rich O/S causes bond elongation and red shift, and the electronic and nuclear repulsions lead to bond contraction and blue shifts. The dominance of the two opposing forces at the equilibrium geometry of the complex determines the nature of the shift, which changes both in magnitude and in direction with the basicity of the hydrogen-bond acceptor.
Tuning the oxidative power of free iron-sulfur clusters.
Lang, Sandra M; Zhou, Shaodong; Schwarz, Helmut
2017-03-15
The gas-phase reactions between a series of di-iron sulfur clusters Fe 2 S x + (x = 1-3) and the small alkenes C 2 H 4 , C 3 H 6 , and C 4 H 8 have been investigated by means of Fourier-transform ion-cyclotron resonance mass spectrometry. For all studied alkenes, the reaction efficiency is found to increase in the order Fe 2 S + < Fe 2 S 2 + < Fe 2 S 3 + . In particular, Fe 2 S + and Fe 2 S 2 + only form simple association products, whereas the sulfur-rich Fe 2 S 3 + is able to dehydrogenate propene and 2-butene via desulfurization of the cluster and formation of H 2 S. This indicates an increased propensity to induce oxidation reactions, i.e. oxidative power, of Fe 2 S 3 + that is attributed to an increased formal oxidation state of the iron atoms. Furthermore, the ability of Fe 2 S 3 + to activate and dissociate the C-H bonds of the alkenes is observed to increase with increasing size of the alkene and thus correlates with the alkene ionization energy.
Area 3a Neuron Response to Skin Nociceptor Afferent Drive
Favorov, Oleg V.; Li, Yongbiao; Quibrera, Miguel; Tommerdahl, Mark
2009-01-01
Area 3a neurons are identified that respond weakly or not at all to skin contact with a 25–38 °C probe, but vigorously to skin contact with the probe at ≥49 °C. Maximal rate of spike firing associated with 1- to 7-s contact at ≥49 °C occurs 1-2 s after probe removal from the skin. The activity evoked by 5-s contact with the probe at 51 °C remains above-background for ∼20 s after probe retraction. After 1-s contact at 55–56 °C activity remains above-background for ∼4 s. Magnitude of spike firing associated with 5-s contact increases linearly as probe temperature is increased from 49–51 °C. Intradermal capsaicin injection elicits a larger (∼2.5×) and longer-lasting (100×) increase in area 3a neuron firing rate than 5-s contact at 51 °C. Area 3a neurons exhibit enhanced or novel responsivity to 25–38 °C contact for a prolonged time after intradermal injection of capsaicin or α, β methylene adenosine triphosphate. Their 1) delayed and persisting increase in spike firing in response to contact at ≥49 °C, 2) vigorous and prolonged response to intradermal capsaicin, and 3) enhanced and frequently novel response to 25–38 °C contact following intradermal algogen injection or noxious skin heating suggest that the area 3a neurons identified in this study contribute to second pain and mechanical hyperalgesia/allodynia. PMID:18534992
Zhao, Jie; Wang, Jing; Wu, Jingxia
2014-09-01
To investigate the roles of cytochrome c (Cyt-c), caspase-9, and caspase-3 in pentavalent vanadium-induced neuronal apoptosis and to provide a basis for mechanism research. Neurons from rats aged 1-3 days were cultured and treated with vanadium pentoxide (V2O5) at 5, 10, or 20 mmol/L. Neuronal apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL). The protein levels of Cyt-c, caspase-9, and caspase-3 were determined by Western blot. Apoptosis bodies were detected in the nuclei of neurons by TUNEL. The number of neurons with apoptosis bodies increased with increasing dose of V2O5 The apoptosis index (AI) was significantly higher in the 10 and 20 mm/L exposure groups than in the control group (P < 0.05 or P < 0.01). Western blot showed that the protein expression levels of Cyt-c and caspase-3 significantly increased in the 5 mmol/L exposure group as compared with the control group (P < 0.05). In the 10 and 20 mmol/L exposure groups, the protein expression of Cyt-c, caspase-9, and caspase-3 all increased as compared with the control group (P < 0.01). Neuronal AI was positively correlated with Cyt-c, caspase-9, and caspase-3 (r = 0.954, P < 0.01; r = 0.938, P < 0.01; r = 0.943, P < 0.01). Pentavalent vanadium may induce neuronal apoptosis. The protein expression of Cyt-c, caspase-9, and caspase-3 may play an important role in neuronal apoptosis induced by pentavalent vanadium.
Lu, Y; Li, M; Shen, Y
1998-03-01
To determine the effects of epinephrine (EPI) and adrenergic antagonists on adenosine 3', 5'-monophosphate (cAMP) level of bovine trabecular cells (BTC) in vitro. (3)H-cAMP was used in protein binding assay for measuring the intracellular level of cAMP. (1) 10(-5) mol/L EPI induced a fold increase of cAMP in cultured BTC in vitro; (2) Timilol and ICI 118, 551 blocked efficiently the effect of EPI at a lower concentration (10(-6) mol/L). (3) Bisoprolol did not efficiently block the effect of EPI unless at high concentrations (>or= 10(-5) mol/L). The effects of EPI increasing outflow facility may be associated with its increase of cAMP in trabecular cells; BTC contains beta-adrenergic receptors, and beta(2)-adrenergic receptors are dominant.
Photosynthetic pathway diversity in a seasonal pool community
Keeley, Jon E.
1999-01-01
1. Photosynthetic pathway diversity was evaluated for the dominant species in a seasonally aquatic community in the south-western USA using 14C pulse-chase techniques.2. Under submerged conditions, only about half of the species were clearly C3, three of the 15 dominants were CAM, one species was C4 and three were potentially assimilating carbon with both C3 and C4 fixation.3. During the brief terrestrial stage in the life history of these amphibious plants, both the CAM and the C3 + C4 species switched to C3, whereas the C4 species did not switch.4. Numerous variations were apparent; for example, the C4 species, while exhibiting a biochemical pathway indistinguishable from terrestrial C4 plants, lacked Kranz anatomy in the aquatic foliage. Also, despite well-developed CAM in several species, others exhibited low-level diel changes in acidity, apparently not indicative of CAM.5. Species with C4 or CAM CO2 concentrating mechanisms lacked the capacity for bicarbonate uptake, an alternative CO2 concentrating mechanism found in certain C3 species in this community.6. Rubisco/PEPC in aquatic foliage was higher in C3 species than in C4, CAM or putative C3 + C4species. In the terrestrial phase, as expected, the switch from CAM or C3 + C4 to strictly C3assimilation was associated with a substantial increase in Rubisco/PEPC. Quite unexpected, however, was the substantial increase in this ratio in terrestrial C3 foliage. It is hypothesized that submerged C3 plants utilize PEPC for recycling of respiratory CO2 and/or C4 phototrophism under field conditions of limited CO2 and O2 saturation, and this is lost in the terrestrial foliage.
Increased activity of the complement system in the liver of patients with alcoholic hepatitis.
Shen, Hong; French, Barbara A; Liu, Hui; Tillman, Brittany C; French, Samuel W
2014-12-01
Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH. Copyright © 2014 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Liu, Hongfei; Yang, Ren Bin; Yang, Weifeng; Jin, Yunjiang; Lee, Coryl J. J.
2018-05-01
Ultrathin MoO3 layers have been grown on Si substrates at 120 °C by atomic layer deposition (ALD) using molybdenum hexacarbonyl [Mo(CO)6] and ozone (O3) as the Mo- and O-source precursors, respectively. The ultrathin films were further annealed in air at Tann = 550-750 °C for 15 min. Scanning-electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy have been employed to evaluate the morphological and elemental properties as well as their evolutions upon annealing of the thin films. They revealed an interfacial SiOx layer in between the MoO3 layer and the Si substrate; this SiOx layer converted into SiO2 during the annealing; and the equivalent thickness of the MoO3 (SiO2) layer decreased (increased) with the increase in Tann. Particles with diameters smaller than 50 nm emerged at Tann = 550 °C and their sizes (density) were reduced (increased) by increasing Tann to 650 °C. A further increase of Tann to 750 °C resulted in telephone-cord-like MoO3 structures, initiated from isolated particles on the surface. These observations have been discussed and interpreted based on temperature-dependent atomic interdiffusions, surface evaporations, and/or melting of MoO3, which shed new light on ALD MoO3 towards its electronic applications.
Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle
Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Sleeman, Mark W.; Kulkarni, Rohit N.; Musi, Nicolas; Hirshman, Michael F.; Goodyear, Laurie J.
2013-01-01
Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle. PMID:23695665
Decomposition Mechanism of C5F10O: An Environmentally Friendly Insulation Medium.
Zhang, Xiaoxing; Li, Yi; Xiao, Song; Tang, Ju; Tian, Shuangshuang; Deng, Zaitao
2017-09-05
SF 6 , the most widely used electrical-equipment-insulation gas, has serious greenhouse effects. C 5 F 10 O has attracted much attention as an alternative gas in recent two years, but the environmental impact of its decomposition products is unclear. In this work, the decomposition characteristics of C 5 F 10 O were studied based on gas chromatography-mass spectrometry and density functional theory. We found that the amount of decomposition products of C 5 F 10 O, namely, CF 4 , C 2 F 6 , C 3 F 6 , C 3 F 8 , C 4 F 10 , and C 6 F 14 , increased with increased number of discharges. Under a high-energy electric field, the C-C bond of C 5 F 10 O between carbonyl carbon and α-carbon atoms was most likely to break and generate CF 3 CO•, C 3 F 7 • or C 3 F 7 CO•, CF 3 • free radicals. CF 3 •, and C 3 F 7 • free radicals produced by the breakage more easily recombined to form small molecular products. By analyzing the ionization parameters, toxicity, and environmental effects of C 5 F 10 O and its decomposition products, we found that C 5 F 10 O gas mixtures exhibit great decomposition and environmental characteristics with low toxicity, with great potential to replace SF 6 .
Stoyanov, Evgenii S
2017-04-20
Chloronium cations in their salts (C n H 2n+1 ) 2 Cl + {CHB 11 Cl 11 - }, with n = 1 to 3 and exceptionally stable carborane anions, are stable at ambient and elevated temperatures. The temperature at which they decompose to carbocations with HCl elimination (below 150 °C) decreases with the increasing n from 1 to 3 because of increasing ionicity of C-Cl bonds in the C-Cl + -C bridge. At room temperature, the salts of cations with n ≥ 4 [starting from t-Bu 2 Cl + or (cyclo-C 5 H 11 ) 2 Cl + ] are unstable and decompose. With decreasing chloronium ion stability, their ability to interact with chloroalkanes to form oligomeric cations increases. It was shown indirectly that unstable salt of fluoronium ions (CH 3 ) 2 F + (CHB 11 F 11 - ) must exist at low temperatures. The proposed (CH 3 ) 2 F + cation is much more reactive than the corresponding chloronium, showing at room temperature chemical properties expected of (CH 3 ) 2 Cl + at elevated temperatures.
Liang, Hua; Xu, Jing; Xu, Fen; Liu, Hongxia; Yuan, Ding; Yuan, Shuhua; Cai, Mengyin; Yan, Jinhua; Weng, Jianping
2015-09-01
Patatin-like phospholipase domain containing 3 (PNPLA3) is a non-secreted protein primarily expressed in liver and adipose tissue. Recently, numerous genetic studies have shown that PNPLA3 is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD). However, the mechanism involved in transcriptional regulation of the PNPLA3 gene remains unknown. We performed a detailed analysis of the human PNPLA3 gene promoter and identified two novel cis-acting elements (SRE and NFY binding motifs) located at -97/-88 and -26/-22 bp, respectively. Overexpression of SREBP-1c in HepG2 cells significantly increased PNPLA3 promoter activity. Mutation of either of the putative SRE or NFY binding motifs blocked the transactivation effects of SREBP-1c on the promoter. Overexpression of SREBP-1c and NFY together increased PNPLA3 promoter activity twice as much as that of SREBP-1c or NFY expression alone. This result suggests that SREBP-1c and NFY synergistically transactivate the human PNPLA3 gene. The ability of SREBP-1c and NFY to bind these cis-elements was confirmed using gel shift analysis. Putative SRE and NFY motifs also mediated synergistic insulin-induced transactivation of the PNPLA3 promoter in HepG2 cells. Additionally, the ability of SREBP-1c to bind to the PNPLA3 promoter was increased by insulin in a dose-dependent manner. Moreover, the treatment of HepG2 cells with the PI3K inhibitor LY294002 led to reduced insulin promoter-activating ability accompanied by a decrease in PNPLA3 and SREBP-1c protein expression. These results demonstrate that SREBP-1c is a direct activator of the human PNPLA3 gene and insulin transactivates the PNPLA3 gene via the PI3K-SREBP-1c/NFY pathway in HepG2 cells. © 2015 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Li, Yefei; Sun, Liang; Xing, Jiandong; Ma, Shengqiang; Zheng, Qiaoling; Liu, Yangzhen
2017-12-01
First-principles calculations based on density functional theory (DFT) were used to investigate the mechanical properties, elastic anisotropy, electronic structure, optical properties and thermodynamic properties of a new quaternary MAX phase (W2/3Ti1/3)3AlC2 and its counterpart W3AlC2 under hydrostatic pressure. The results indicate that the volumetric shrinkage of (W2/3Ti1/3)3AlC2 is faster than that of axial shrinkage under hydrostatic pressure. The stress-strain method and Voigt-Reuss-Hill approximation were used to calculate elastic constants and moduli, respectively. These compounds are mechanically stable under hydrostatic pressure. Moreover, the moduli of (W2/3Ti1/3)3AlC2 and W3AlC2 increase with an increase in pressure. The anisotropic indexes and surface constructions of bulk and Young’s moduli were used to illustrate the mechanical anisotropy under hydrostatic pressure. Electronic structure and optical property of (W2/3Ti1/3)3AlC2 and W3AlC2 have also been discussed. The results of Debye temperature reveal that the covalent bonds among atoms in (W2/3Ti1/3)3AlC2 may be stronger than that of W3AlC2. The heat capacity, Cp-Cv, and thermal expansion coefficient of (W2/3Ti1/3)3AlC2 and W3AlC2 were discussed in the ranges of 0-30 GPa and 0-2000 K using quasi-harmonic Debye model considering the phonon effects.
Wijerathna, Thilini Madushanka; Gawarammana, Indika Bandara; Dissanayaka, Dhammika Menike; Palanagasinghe, Chathura; Shihana, Fathima; Dassanayaka, Gihani; Shahmy, Seyed; Endre, Zoltan Huba; Mohamed, Fahim; Buckley, Nicholas Alan
2017-11-01
Acute kidney injury (AKI) is common following deliberate self-poisoning with a combination washing powder containing oxalic acid (H 2 C 2 O 4 ) and potassium permanganate (KMnO 4 ). Early and rapid increases in serum creatinine (sCr) follow severe poisoning. We investigated the relationship of these increases with direct nephrotoxicity in an ongoing multicenter prospective cohort study in Sri Lanka exploring AKI following poisoning. Multiple measures of change in kidney function were evaluated in 48 consenting patients who had serial sCr and serum cystatin C (sCysC) data available. Thirty-eight (38/48, 79%) patients developed AKI (AKIN criteria). Twenty-eight (58%) had AKIN stage 2 or 3. Initial increases in urine creatinine (uCr) excretion were followed by a substantial loss of renal function. The AKIN stage 2 and 3 (AKIN2/3) group had very rapid rises in sCr (a median of 118% at 24 h and by 400% at 72 h post ingestion). We excluded the possibility that the rapid rise resulted from the assay used or muscle damage. In contrast, the average sCysC increase was 65% by 72 h. In most AKI, sCysC increases to the same extent but more rapidly than sCr, as sCysC has a shorter half-life. This suggests either a reduction in Cystatin C production or, conversely, that the rapid early rise of sCr results from increased production of creatine and creatinine to meet energy demands following severe oxidative stress mediated by H 2 C 2 O 4 and KMnO 4 . Increased early creatinine excretion supports the latter explanation, since creatinine excretion usually decreases transiently in AKIN2/3 from other causes.
Yamazaki, Takao; Desai, Amit; Goldwater, Ronald; Han, David; Howieson, Corrie; Akhtar, Shahzad; Kowalski, Donna; Lademacher, Christopher; Pearlman, Helene; Rammelsberg, Diane; Townsend, Robert
2017-01-01
This report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23). Compared with each drug alone, coadministration with isavuconazole changed the area under the concentration-time curves (AUC ∞ ) and maximum concentrations (C max ) as follows: bupropion, AUC ∞ reduced 42%, C max reduced 31%; repaglinide, AUC ∞ reduced 8%, C max reduced 14%; caffeine, AUC ∞ increased 4%, C max reduced 1%; dextromethorphan, AUC ∞ increased 18%, C max increased 17%; R-methadone, AUC ∞ reduced 10%, C max increased 3%; S-methadone, AUC ∞ reduced 35%, C max increased 1%. In all studies, there were no deaths, 1 serious adverse event (dextromethorphan study; perioral numbness, numbness of right arm and leg), and adverse events leading to study discontinuation were rare. Thus, isavuconazole is a mild inducer of CYP2B6 but does not appear to affect CYP1A2-, CYP2C8-, or CYP2D6-mediated metabolism. © 2016 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.
Lin, Rong-Jyh; Wu, Bin-Nan; Lo, Yi-Ching; An, Li-Mei; Dai, Zen-Kong; Lin, Young-Tso; Tang, Chao-Shun; Chen, Ing-Jun
2006-02-01
KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) was investigated in guinea pig tracheal smooth muscle. Intratracheal instillation of tumor necrosis factor (TNF)-alpha (0.01 mg/kg/300 microl) induced bronchoconstriction, increases of lung resistance, and decreases of dynamic lung compliance. Instillation of KMUP-3 (0.5-2.0 mg/kg) reversed this situation. In isolated trachea precontracted with carbachol, KMUP-3 (10-100 microM)-caused relaxations were attenuated by epithelium removal and by pretreatments with an inhibitor of K(+) channel, tetraethylammonium (10 mm); K(ATP) channel, glibenclamide (1 microM); voltage-dependent K(+) channel, 4-aminopyridine (100 microM); Ca(2+)-dependent K(+) channel, charybdotoxin (0.1 microM) or apamin (1 microM); soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1one (ODQ, 1 microM); nitric-oxide (NO) synthase, N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM); and adenylate cyclase, SQ 22536 [9-(terahydro-2-furanyl)-9H-purin-6-amine] (100 microM). KMUP-3 (0.01-100 microM) induced increases of cGMP and cAMP in primary culture of tracheal smooth muscle cells (TSMCs). The increase in cGMP by KMUP-3 was reduced by ODQ and L-NAME; the increase in cAMP was reduced by SQ 22536. Western blot analysis indicated that KMUP-3 (1 microM) induced expression of protein kinase A (PKA)(ri) and protein kinase G (PKG)(1alpha 1beta) in TSMCs.SQ 22536 inhibited KMUP-3-induced expression of (PKA)(ri). On the contrary, ODQ inhibited KMUP-3-induced expression of PKG(1alpha 1beta) In epithelium-intact trachea, KMUP-3 increased the NO release. Activation of sGC, NO release, and inhibition of phosphodiesterases in TSMCs by KMUP-3 may result in increases of intracellular cGMP and cAMP, which subsequently activate PKG and PKA, efflux of K(+) ion, and associated reduction in Ca(2+) influx in vitro, indicating the action mechanism to protect against TNF-alpha-induced airway dysfunction in vivo.
Nociceptor Response - A Review of Literature
2015-02-20
receptor potential vanilloid, type 4 (TRPV4) receptors respond to temperatures above 27 °C; TRPV3, TRPV1 , and TRPV2 respond to temperature increases...respond to temperatures above 27 °C; TRPV3, TRPV1 , and TRPV2 respond to temperature increases above 31 °C, 43 °C, and 52 °C, respectively (Kandel et al...2013). TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron, 77(4), 667-679. 15
Brown, Richard P; Au, Timothy
2009-06-01
Little is known about the impact of increased metabolism on body temperatures of small ectotherms. We found that postprandial metabolic rates of 5 g Anolis carolinensis lizards were elevated by factorial increases of 2.3+/-1.0 (mean+/-S.E.) at 26 degrees C and 3.8+/-2.1 at 30 degrees C over their fasting rates. Cloacal body temperatures exceeded environmental temperatures by a small amount in fasted individuals (26 degrees C: 0.3+/-0.02 degrees C, 30 degrees C: 0.3+/-0.02 degrees C), and by a significantly larger amount in fed individuals (26 degrees C: 1.0+/-0.06 degrees C, 30 degrees C: 0.8+/-0.08 degrees C). We conclude that an increased metabolic rate due to specific dynamic action leads to a small but significant elevation of body temperature in this species. Comparisons with thermal increments reported for a large (750 g) varanid lizard suggest that body size has only a minor influence on body-air temperature differentials of ectotherms. This is consistent with theoretical predictions. Finally, endogenous heat production could help elevate body temperatures in the wild and therefore play a minor role in thermoregulation.
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.
Removal of H2O2 and generation of superoxide radical: Role of cytochrome c and NADH
Velayutham, Murugesan; Hemann, Craig; Zweier, Jay L.
2011-01-01
In cells, mitochondria, endoplasmic reticulum, and peroxisomes are the major sources of reactive oxygen species (ROS) under physiological and pathophysiological conditions. Cytochrome c (cyt c) is known to participate in mitochondrial electron transport and has antioxidant and peroxidase activities. Under oxidative or nitrative stress, the peroxidase activity of Fe3+cyt c is increased. The level of NADH is also increased under pathophysiological conditions such as ischemia and diabetes and a concurrent increase in hydrogen peroxide (H2O2) production occurs. Studies were performed to understand the related mechanisms of radical generation and NADH oxidation by Fe3+cyt c in the presence of H2O2. Electron paramagnetic resonance (EPR) spin trapping studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were performed with NADH, Fe3+cyt c, and H2O2 in the presence of methyl-β-cyclodextrin. An EPR spectrum corresponding to the superoxide radical adduct of DMPO encapsulated in methyl-β-cyclodextrin was obtained. This EPR signal was quenched by the addition of the superoxide scavenging enzyme Cu,Zn-superoxide dismutase (SOD1). The amount of superoxide radical adduct formed from the oxidation of NADH by the peroxidase activity of Fe3+cyt c increased with NADH and H2O2 concentration. From these results, we propose a mechanism in which the peroxidase activity of Fe3+cyt c oxidizes NADH to NAD•, which in turn donates an electron to O2 resulting in superoxide radical formation. A UV-visible spectroscopic study shows that Fe3+cyt c is reduced in the presence of both NADH and H2O2. Our results suggest that Fe3+cyt c could have a novel role in the deleterious effects of ischemia/reperfusion and diabetes due to increased production of superoxide radical. In addition, Fe3+cyt c may play a key role in the mitochondrial “ROS-induced ROS-release (RIRR)” signaling and in mitochondrial and cellular injury/death. The increased oxidation of NADH and generation of superoxide radical by this mechanism may have implications for the regulation of apoptotic cell death, endothelial dysfunction, and neurological diseases. We also propose an alternative electron transfer pathway, which may protect mitochondria and mitochondrial proteins from oxidative damage. PMID:21545835
Evidence of shift in C4 species range in central Argentina during the late Holocene
Silva, L.C.R.; Giorgis, M.A.; Anand, M.; Enrico, L.; Perez-Harguindeguy, N.; Falczuk, V.; Tieszen, L.L.; Cabido, M.
2011-01-01
AimMillennial-scale biogeographic changes are well understood in many parts of the world, but little is known about long-term vegetation dynamics in subtropical regions. Here we investigate shifts in C3/C4 plant abundance occurred in central Argentina during the past few millenniaMethodsWe determined present day soil organic matter δ13C signatures of grasslands, shrublands and woodlands, containing different mixtures of C3 and C4 plants. We measured past changes in the relative cover of C3/C4 plants by comparing δ13C values in soil profiles with present day δ13C signatures. We analyzed 14C activity in soil depths that showed major changes in vegetation.ResultsPresent day relative cover of C3/C4 plants determines whole ecosystem δ13C signatures integrated as litter and superficial soil organic matter (R2 = 0.78; p < 0.01). Deeper soils show a consistent shift in δ13C, indicating a continuous replacement of C4 by C3 plants since 3,870 (±210) YBP. During this period, the relative abundance of C3 plants increased 32% (average across sites) with significant changes being observed in all studied ecosystems.ConclusionsOur results show that C4 species were more abundant in the past, but C3 species became dominant during the late Holocene. We identified increases in the relative C3/C4 cover in grasslands, shrublands and woodlands, suggesting a physiological basis for changes in vegetation. The replacement of C4 by C3 plants coincided with changes in climate towards colder and wetter conditions and could represent a climatically driven shift in the C4 species optimum range.
NASA Technical Reports Server (NTRS)
Sliney, Harold E.; Deadmore, Daniel L.
1989-01-01
The friction and wear of oxide-ceramics sliding against the nickel base alloy IN-718 at 25 to 800 C were measured. The oxide materials tested were mullite (3Al2O3.2SiO2); lithium aluminum silicate (LiAlSi(x)O(y)); polycrystalline monolithic alpha alumina (alpha-Al2O3); single crystal alpha-Al2O3 (sapphire); zirconia (ZrO2); and silicon carbide (SiC) whisker-reinforced Al2O3 composites. At 25 C the mullite and zirconia had the lowest friction and the polycrystalline monolithic alumina had the lowest wear. At 800 C the Al2O3-8 vol/percent SiC whisker composite had the lowest friction and the Al2O3-25 vol/percent SiC composite had the lowest wear. The friction of the Al2O3-SiC whisker composites increased with increased whisker content while the wear decreased. In general, the wear-resistance of the ceramics improve with their hardness.
High temperature compounds for turbine vanes
NASA Technical Reports Server (NTRS)
Rhodes, W. H.; Cannon, R. M., Jr.
1972-01-01
Fabrication and microstructure control studies were conducted on SiC, Si3N4, and composites based on these compounds. Charpy mode impact testing to 2400 F established that beta-spodumene, lithium aluminum silicate, coated Si3N4, Si3N4 derived from alpha-Si3N4 powder, and SiC containing 5-25 v/o chopped C fibers had the most promising strengths. Several other composite systems had excellent microstructures and could prove interesting materials in the future. Stress-rupture testing on Si3N4 established that increasing 2000 F - 100 hour strengths were obtained for increasing grain size to at least 5 micrometers, increasing density and possibly increasing phase purity. These parameters became less important at 2400 F where it is thought a grain boundary phase controls strength.
Halverstadt, Amy; Phares, Dana A; Roth, Stephen; Ferrell, Robert E; Goldberg, Andrew P; Hagberg, James M
2005-05-15
High-density lipoprotein cholesterol (HDL-C) and its subfractions are modifiable with exercise training and these responses are heritable. The interleukin-6 (IL6)-174G/C polymorphism may be associated with HDL-C levels. We hypothesized that the IL6-174G/C polymorphism would be associated with plasma HDL-C response to exercise training. Sixty-five 50- to 75-year-olds on a standardized diet were studied before and after 24 weeks of aerobic exercise training. Significant differences existed among genotype groups for change with exercise training in HDL-C, HDL3-C, integrated HDL4,5NMR-C, and HDLsize. The CC genotype group increased HDL-C more than the GG (7.0 +/- 1.3 v. 1.0 +/- 1.1 mg/dL, p = 0.001) and GC groups (3.3 +/- 0.9 mg/dL, p = 0.02); for HDL3-C, the CC group increased more than the GG (6.1 +/- 1.0 v. 0.9 +/- 0.9, mg/dL p < 0.001) and GC groups (2.5 +/- 0.7 mg/dL, p = 0.006). Integrated HDL4,5NMR-C increased more in the CC than GG group (6.5 +/- 1.6 mg/dL v. 1.0 +/- 1.3 mg/dL, p = 0.01), as did HDLsize compared to the GG (CC: 0.3 +/- 0.1 v. GG: 0.1 +/- 0.1 nm, p = 0.02) and GC (0.0 +/- 0.0 nm, p = 0.007) groups. IL6 genotype is associated with HDL-C response to exercise training.
CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction
DOE Office of Scientific and Technical Information (OSTI.GOV)
Oue, Erika; Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Global Center of Excellence
Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cellmore » lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.« less
Liu, Yantao; Ren, Wei; Shi, Peng; Liu, Dan; Zhang, Yijun; Liu, Ming; Jing, Weixuan; Tian, Bian; Jiang, Zhuangde
2018-01-01
An In2O3/ITO thin film thermocouple was prepared via screen printing. Glass additives were added to improve the sintering process and to increase the density of the In2O3/ITO films. The surface and cross-sectional images indicate that both the grain size and densification of the ITO and In2O3 films increased with the increase in annealing time. The thermoelectric voltage of the In2O3/ITO thermocouple was 53.5 mV at 1270 °C at the hot junction. The average Seebeck coefficient of the thermocouple was calculated as 44.5 μV/°C. The drift rate of the In2O3/ITO thermocouple was 5.44 °C/h at a measuring time of 10 h at 1270 °C. PMID:29570680
NASA Technical Reports Server (NTRS)
Winchester, S. K.; Selvamurugan, N.; D'Alonzo, R. C.; Partridge, N. C.
2000-01-01
Collagenase-3 mRNA is initially detectable when osteoblasts cease proliferation, increasing during differentiation and mineralization. We showed that this developmental expression is due to an increase in collagenase-3 gene transcription. Mutation of either the activator protein-1 or the runt domain binding site decreased collagenase-3 promoter activity, demonstrating that these sites are responsible for collagenase-3 gene transcription. The activator protein-1 and runt domain binding sites bind members of the activator protein-1 and core-binding factor family of transcription factors, respectively. We identified core-binding factor a1 binding to the runt domain binding site and JunD in addition to a Fos-related antigen binding to the activator protein-1 site. Overexpression of both c-Fos and c-Jun in osteoblasts or core-binding factor a1 increased collagenase-3 promoter activity. Furthermore, overexpression of c-Fos, c-Jun, and core-binding factor a1 synergistically increased collagenase-3 promoter activity. Mutation of either the activator protein-1 or the runt domain binding site resulted in the inability of c-Fos and c-Jun or core-binding factor a1 to increase collagenase-3 promoter activity, suggesting that there is cooperative interaction between the sites and the proteins. Overexpression of Fra-2 and JunD repressed core-binding factor a1-induced collagenase-3 promoter activity. Our results suggest that members of the activator protein-1 and core-binding factor families, binding to the activator protein-1 and runt domain binding sites are responsible for the developmental regulation of collagenase-3 gene expression in osteoblasts.
Zhu, Wei; Jia, Qianju; Wang, Yun; Zhang, Yuhua; Xia, Min
2012-01-15
Enhanced oxidative stress due to high glucose contributes to pathological changes in diabetes-related liver complications. Reducing oxidative stress may alleviate these pathogenic processes. Anthocyanin, a natural antioxidant, has been reported to reduce intracellular reactive oxygen species (ROS) levels but the mechanism of this reduction is not fully understood. The glutathione (GSH) antioxidant system is critical for counteracting oxidative stress-induced intracellular injury. In this study, we evaluated the mechanism of the anthocyanin-mediated regulation of GSH synthesis and reduction in intracellular ROS levels. We observed that treatment of human HepG2 cells with the anthocyanin C3G significantly reduced ROS levels induced by high glucose. C3G incubation increased glutamate-cysteine ligase expression, which in turn mediated the reduction in ROS levels. However, the upregulation of glutamate-cysteine ligase catalytic subunit (Gclc) expression by C3G occurred independent of the Nrf1/2 transcription factors. Notably, the cAMP-response element binding protein (CREB) was identified as the target transcription factor involved in the C3G-mediated upregulation of Gclc expression. C3G increased phosphorylation of CREB through protein kinase A (PKA) activation, which induced a CREB-mediated upregulation of Gclc transcription. In vivo, treatment with C3G increased the GSH synthesis in the liver of diabetic db/db mice through PKA-CREB-dependent induction of Gclc expression. Finally, oxidative stress determined by lipid peroxidation, neutrophil infiltration, and hepatic steatosis was attenuated in C3G-treated db/db mice. Our results demonstrate that the anthocyanin C3G has an effect of activating GSH synthesis through a novel antioxidant defense mechanism against excessive ROS production, contributing to the prevention of hyperglycemia-induced hepatic oxidative damage. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.
Olivieri, Oliviero; Martinelli, Nicola; Sandri, Marco; Bassi, Antonella; Guarini, Patrizia; Trabetti, Elisabetta; Pizzolo, Francesca; Girelli, Domenico; Friso, Simonetta; Pignatti, Pier Franco; Corrocher, Roberto
2005-02-01
Apolipoprotein C-III (apo C-III) is a marker of cardiovascular disease risk associated with triglyceride (TG)-rich lipoproteins. The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apo C-III concentrations. Long-chain n-3 polyunsaturated fatty acids (PUFAs) contained in fish have well-known apo C-III-lowering properties. We investigated the possibility of an interactive effect between the APOC3 gene variant and erythrocyte n-3 PUFAs, suitable markers of dietary intake of fatty acids, on apo C-III concentrations in a population of 848 heart disease patients who had coronary angiography. In the population as a whole, apo C-III concentrations were significantly inversely correlated with total erythrocyte PUFAs, but the correlation was not significant when only -455CC homozygous individuals were taken into account. In the total population and in subgroups with the -455TT and -455CT genotypes, the relative proportions of individuals presenting with increased apo C-III (i.e., above the 75th percentile value calculated on the entire population after exclusion of individuals taking lipids-lowering medications) decreased progressively as the n-3 PUFA and docosahexaenoic acid concentrations increased. The opposite situation was observed in the homozygous -455CC subgroup, in whom increasing erythrocyte n-3 PUFA and docosahexaenoic acid concentrations were associated with higher proportions of individuals with high apo C-III. A formal interactive effect between genotype and n-3 PUFAs was confirmed even after adjustment for possible confounding variables [age, sex, body mass index, smoking, coronary artery disease (CAD)/CAD-free status, or use of lipid-lowering medications] by logistic models. Patients homozygous for the -455C APOC3 variant are poorly responsive to the apo C-III-lowering effects of n-3 PUFAs.
Mechanisms underlying aberrant expression of miR-29c in uterine leiomyoma.
Chuang, Tsai-Der; Khorram, Omid
2016-01-01
To determine the expression of miR-29c and its target genes in leiomyoma and the role of NF-κB, specific protein 1 (SP1), and DNA methylation in its regulation. Experimental study. Academic research laboratory. Women undergoing hysterectomy for leiomyoma. Over- and underexpression of miR-29c; blockade of transcription factors. MiR-29c and its target gene levels in leiomyoma and the effects of blockade of transcription factors on miR-29c expression. Leiomyoma as compared with myometrium expressed significantly lower levels of miR-29c, with an inverse relationship with expression of its targets, COL3A1 and DNMT3A. Gain of function of miR-29c inhibited the expression of COL3A1 and DNMT3A at protein and mRNA levels, secreted COL3A1, and rate of cell proliferation. Loss of function of miR-29c had the opposite effect. E2, P, and their combination inhibited miR-29c in leiomyoma smooth muscle cells (LSMC). Phosphorylated NF-κB (p65) and SP1 protein expression were significantly increased in leiomyoma. SiRNA knockdown of SP1 and DNMT3A or their specific inhibitors significantly increased the expression of miR-29c, accompanied by the inhibition of cellular and secreted COL3A1 in siRNA-treated cells. Knockdown of p65 also induced miR-29c expression but had no effect on COL3A1 expression. MiR-29c expression is suppressed in leiomyoma, resulting in an increase in expression of its targets COL3A1 and DNMT3A. The suppression of miR-29c in LSMC is primarily mediated by SP1, NF-κB signaling, and epigenetic modification. Collectively, these results indicate a significant role for miR-29c in leiomyoma pathogenesis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
In Vivo Cardiovascular Pharmacology of 2′,3′-cAMP, 2′-AMP, and 3′-AMP in the Rat
Mi, Zaichuan
2013-01-01
The naturally occurring purine 2′,3′-cAMP is metabolized in vitro to 2′-AMP and 3′-AMP, which are subsequently metabolized to adenosine. Whether in vivo 2′,3′-cAMP, 2′-AMP, or 3′-AMP are rapidly converted to adenosine and exert rapid effects via adenosine receptors is unknown. To address this question, we compared the cardiovascular and renal effects of 2′,3′-cAMP, 2′-AMP, 3′-AMP, 3′,5′-cAMP, 5′-AMP, and adenosine in vivo in the rat. Purines were infused intravenously while monitoring mean arterial blood pressure (MABP), heart rate (HR), cardiac output, and renal and mesenteric blood flows. Total peripheral (TPR), renal vascular (RVR), and mesenteric vascular (MVR) resistances were calculated. Urine was collected for determination of urine excretion rate [urine volume (UV)]. When sufficient urine was available, the sodium excretion rate (Na+ER) and glomerular filtration rate (GFR) were determined. 2′,3′-cAMP, 2′-AMP, and 3′-AMP dose-dependently and profoundly reduced MABP, HR, TPR, and MVR with efficacy and potency similar to adenosine and 5′-AMP. These effects of 2′,3′-cAMP, 2′-AMP, and 3′-AMP were attenuated by blockade of adenosine receptors with 1,3-dipropyl-8-(p-sulfophenyl)xanthine. 2′,3′-cAMP, 2′-AMP, 3′-AMP, adenosine, and 5′-AMP variably affected RVR, but profoundly (nearly 100%) decreased UV at higher doses. GFR and Na+ER could be measured at the lower doses and were suppressed by 2′,3′-cAMP, 2′-AMP, and 3′-AMP, but not by adenosine or 5′-AMP. 2′,3′-cAMP increased urinary excretion rates of 2′-AMP, 3′-AMP, and adenosine. 3′,5′-cAMP exerted no adverse hemodynamic effects yet increased urinary adenosine as efficiently as 2′,3′-cAMP. Conclusions: In vivo 2′,3′-cAMP is rapidly converted to adenosine. Because both cAMPs increase adenosine in the urinary compartment, these agents may provide unique therapeutic opportunities. PMID:23759508
NASA Astrophysics Data System (ADS)
Tabata, Akimori; Komura, Yusuke; Hoshide, Yoshiki; Narita, Tomoki; Kondo, Akihiro
2008-01-01
Silicon carbide (SiC) thin films were prepared by hot-wire chemical vapor deposition from SiH4/CH4/H2 gases, and the influence of substrate temperature, Ts (104 < Ts < 434 °C), on the properties of the SiC thin films was investigated. X-ray diffraction patterns and Raman scattering spectra revealed that nanocrystalline cubic SiC (nc-3C-SiC) films grew at Ts above 187 °C, while completely amorphous films grew at Ts = 104 °C. Fourier transform infrared absorption spectra revealed that the crystallinity of the nc-3C-SiC was improved with increasing Ts up to 282 °C and remained almost unchanged with a further increase in Ts from 282 to 434 °C. The spin density was reduced monotonically with increasing Ts.
Ozone and haze pollution weakens net primary productivity in China
NASA Astrophysics Data System (ADS)
Yue, Xu; Unger, Nadine; Harper, Kandice; Xia, Xiangao; Liao, Hong; Zhu, Tong; Xiao, Jingfeng; Feng, Zhaozhong; Li, Jing
2017-05-01
Atmospheric pollutants have both beneficial and detrimental effects on carbon uptake by land ecosystems. Surface ozone (O3) damages leaf photosynthesis by oxidizing plant cells, while aerosols promote carbon uptake by increasing diffuse radiation and exert additional influences through concomitant perturbations to meteorology and hydrology. China is currently the world's largest emitter of both carbon dioxide and short-lived air pollutants. The land ecosystems of China are estimated to provide a carbon sink, but it remains unclear whether air pollution acts to inhibit or promote carbon uptake. Here, we employ Earth system modeling and multiple measurement datasets to assess the separate and combined effects of anthropogenic O3 and aerosol pollution on net primary productivity (NPP) in China. In the present day, O3 reduces annual NPP by 0.6 Pg C (14 %) with a range from 0.4 Pg C (low O3 sensitivity) to 0.8 Pg C (high O3 sensitivity). In contrast, aerosol direct effects increase NPP by 0.2 Pg C (5 %) through the combination of diffuse radiation fertilization, reduced canopy temperatures, and reduced evaporation leading to higher soil moisture. Consequently, the net effects of O3 and aerosols decrease NPP by 0.4 Pg C (9 %) with a range from 0.2 Pg C (low O3 sensitivity) to 0.6 Pg C (high O3 sensitivity). However, precipitation inhibition from combined aerosol direct and indirect effects reduces annual NPP by 0.2 Pg C (4 %), leading to a net air pollution suppression of 0.8 Pg C (16 %) with a range from 0.6 Pg C (low O3 sensitivity) to 1.0 Pg C (high O3 sensitivity). Our results reveal strong dampening effects of air pollution on the land carbon uptake in China today. Following the current legislation emission scenario, this suppression will be further increased by the year 2030, mainly due to a continuing increase in surface O3. However, the maximum technically feasible reduction scenario could drastically relieve the current level of NPP damage by 70 % in 2030, offering protection of this critical ecosystem service and the mitigation of long-term global warming.
Nag, Okhil Kumar; Nayak, Rati Ranjan; Lim, Chang Su; Kim, In Hong; Kyhm, Kwangseuk; Cho, Bong Rae; Woo, Han Young
2010-07-29
Two-photon absorption properties of 1,4-bis{4'-[N,N-bis(6''-trimethylammoniumhexyl)amino]styryl}benzene tetrabromide (C1) and its inclusion complexes (ICs) with cyclodextrins (CDs) have been studied. Upon complexation with CDs, the absorption spectra of C1 showed a slight red shift, whereas the emission spectra showed a blue shift with concomitant increase in the fluorescence quantum efficiency. A Stern-Volmer study using K(3)Fe(CN)(6) as a quencher revealed significant reduction in the photoinduced charge transfer quenching, in accord with the IC formation. Comparison of the spectroscopic results reveals that C1 forms increasingly more stable ICs in the order C1/beta-CD < C1/gamma-CD < C1/(3gamma:beta)-CD (gamma-CD/beta-CD 3:1, mole ratio). Moreover, the two-photon action cross section of C1 increased from 200 GM for C1 to 400 GM for C1/beta-CD, 460 GM for C1/gamma-CD, and 650 GM for C1/(3gamma:beta)-CD, respectively. Furthermore, the two-photon microscopy images of HeLa cells stained with C1 emitted strong two-photon excited fluorescence in the plasma membrane. These results provide a useful guideline for the development of efficient two-photon materials for bioimaging applications.
Oxygen vacancy induced room temperature ferromagnetism in (In1-xNix)2O3 thin films
NASA Astrophysics Data System (ADS)
Chakraborty, Deepannita; Kaleemulla, S.; Kuppan, M.; Rao, N. Madhusudhana; Krishnamoorthi, C.; Omkaram, I.; Reddy, D. Sreekantha; Rao, G. Venugopal
2018-05-01
Nickel doped indium oxide thin films (In1-xNix)2O3 at x = 0.00, 0.03, 0.05 and 0.07 were deposited onto glass substrates by electron beam evaporation technique. The deposited thin films were subjected to annealing in air at 250 °C, 350 °C and 450 °C for 2 h using high temperature furnace. A set of films were vacuum annealed at 450 °C to study the role of oxygen on magnetic properties of the (In1-xNix)2O3 thin films. The thin films were subjected to different characterization techniques to study their structural, chemical, surface, optical and magnetic properties. All the synthesized air annealed and vacuum annealed films exhibit body centered cubic structure without any secondary phases. No significant change in the diffraction peak position, either to lower or higher diffraction angles has been observed. The band gap of the films decreased from 3.73 eV to 3.63 eV with increase of annealing temperature from 250 °C to 450 °C, in the presence of air. From a slight decrease in strength of magnetization to a complete disappearance of hysteresis loop has been observed in pure In2O3 thin films with increasing the annealing temperature from 250 °C to 450 °C, in the presence of air. The (In1-xNix)2O3 thin films annealed under vacuum follow a trend of enhancement in the strength of magnetization to increase in temperature from 250 °C to 450 °C. The hysteresis loop does not disappear at 450 °C in (In1-xNix)2O3 thin films, as observed in the case of pure In2O3 thin films.
Sebban, Claude; Tesolin-Decros, Brigitte; Ciprian-Ollivier, Jorge; Perret, Laurent; Spedding, Michael
2002-01-01
1. The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 - 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 - 3 mg kg(-1) s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1 - 3 Hz with decreases in power at higher frequencies (9 - 30 Hz). At high doses (3 mg kg(-1) s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 - 0.1 mg kg(-1) i.p.) caused similar effects but with lesser changes in power. 2. In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 - 10 mg kg(-1) i.p.). The atypical antipsychotic clozapine (0.2 mg kg(-1) s.c.) synchronized the EEG (peak 8 Hz). The 5-HT(2A)-antagonist, M100907, specifically increased EEG power at 2 - 3 Hz at low doses (10 and 50 microg kg(-1) s.c.), whereas at higher doses (0.1 mg kg(-1) s.c.) the profile resembled that of clozapine. 3. Clozapine (0.2 mg kg(-1) s.c. ), GYKI 53655 (5 mg kg(-1) i.p.), prazosin (0.05 and 0.1 mg kg(-1) i.p.), and M100907 (0.01 and 0.05 mg kg(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg(-1) s.c.), but not the increase in power at 1 - 3 Hz in prefrontal cortex.
Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering
Yang, Yunzhi Peter
2015-01-01
Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies. PMID:26407291
Development of mRuby2-Transfected C3H10T1/2 Fibroblasts for Musculoskeletal Tissue Engineering.
Ker, Dai Fei Elmer; Sharma, Rashmi; Wang, Evelyna Tsi Hsin; Yang, Yunzhi Peter
2015-01-01
Mouse C3H10T1/2 fibroblasts are multipotent, mesenchymal stem cell (MSC)-like progenitor cells that are widely used in musculoskeletal research. In this study, we have established a clonal population of C3H10T1/2 cells stably-transfected with mRuby2, an orange-red fluorescence reporter gene. Flow cytometry analysis and fluorescence imaging confirmed successful transfection of these cells. Cell counting studies showed that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells proliferated at similar rates. Adipogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Oil Red O and showed increased expression of adipogenic genes including adiponectin and lipoprotein lipase. Chondrogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for Alcian Blue and showed increased expression of chondrogenic genes including aggrecan. Osteogenic differentiation experiments demonstrated that untransfected C3H10T1/2 cells and mRuby2-transfected C3H10T1/2 cells stained positive for alkaline phosphatase (ALP) as well as Alizarin Red and showed increased expression of osteogenic genes including alp, ocn and osf-1. When seeded on calcium phosphate-based ceramic scaffolds, mRuby2-transfected C3H10T1/2 cells maintained even fluorescence labeling and osteogenic differentiation. In summary, mRuby2-transfected C3H10T1/2 cells exhibit mRuby2 fluorescence and showed little-to-no difference in terms of cell proliferation and differentiation as untransfected C3H10T1/2 cells. These cells will be available from American Type Culture Collection (ATCC; CRL-3268™) and may be a valuable tool for preclinical studies.
Schnatz, Peter F; Jiang, Xuezhi; Vila-Wright, Sharon; Aragaki, Aaron K; Nudy, Matthew; O'Sullivan, David M; Jackson, Rebecca; LeBlanc, Erin; Robinson, Jennifer G; Shikany, James M; Womack, Catherine R; Martin, Lisa W; Neuhouser, Marian L; Vitolins, Mara Z; Song, Yiqing; Kritchevsky, Stephen; Manson, JoAnn E
2014-08-01
The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. The parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women's Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. There was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46-mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). Supplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.
Beland, Frederick A; Mellick, Paul W; Olson, Greg R; Mendoza, Maria C B; Marques, M Matilde; Doerge, Daniel R
2013-01-01
Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F(1) mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F(1) mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F(1) mice. Male B6C3F(1) mice also had a significantly increased incidence of forestomach tumors, while female B6C3F(1) mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide. Published by Elsevier Ltd.
Yuan, Bingbing; Sun, Haixiang; Wang, Tao; Xu, Yanyan; Li, Peng; Kong, Ying; Niu, Q. Jason
2016-01-01
Nanopore containing graphene nanosheets were synthesized by graphene oxide and a reducing agent using a facile hydrothermal treatment in sodium hydroxide media. The as-prepared nanoporous graphene was incorporated into ethyl cellulose (EC) to prepare the mixed matrix membranes (MMMs) for C3H6/C3H8 separation. Transmission electron microscopy (TEM) photograph and X-ray photoelectron spectroscopy (XPS) analysis of nanoporous graphene nanosheets indicated that the structure of nano-pore was irregular and the oxygen-containing groups in the surface were limited. More importantly, the as-prepared MMMs presented better separation performance than that of pristine EC membrane due to simultaneous enhancement of C3H6 permeability and ideal selectivity. The ideal selectivity of the MMMs with 1.125 wt‰ nanoporous graphene content for C3H6/C3H8 increased from 3.45 to 10.42 and the permeability of C3H6 increased from 57.9 Barrer to 89.95 Barrer as compared with the pristine membrane. The presumed facilitated mechanism was that the high specific surface area of nanoporous graphene in polymer matrix increased the length of the tortuous pathway formed by nanopores for the gas diffusion as compared with the pristine graphene nanosheets, and generated a rigidified interface between the EC chains and fillers, thus enhanced the diffusivity selectivity. Therefore, it is expected that nanoporous graphene would be effective material for the C3H6/C3H8 separation. PMID:27352851
Nizami, Syed Moazzam; Yiping, Zhang; Liqing, Sha; Zhao, Wei; Zhang, Xiang
2014-01-01
Extension of the rotation length in forest management has been highlighted in Article 3.4 of the Kyoto Protocol to help the countries in their commitments for reduction in greenhouse gas emissions. CO2FIX Model Ver.3.2 was used to examine the dynamics of carbon stocks (C stocks) in a rubber plantation in South Western China with the changing rotation lengths. To estimate the efficiency of increasing the rotation length as an Article 3.4 activity, study predicted that the rubber production and C stocks of the ecosystem increased with the increasing rotation (25, 30, 35, 40 and 45 years). While comparing the pace of growth both in economical (rubber production) and ecological (C stocks) terms in each rotation, 40 years rotation length showed maximum production and C stocks. After elongation of 40 year rotation to four consecutive cycles, it was concluded that the total C stocks of the ecosystem were 186.65 Mg ha(-1). The longer rotation lengths showed comparatively increased C stocks in below ground C stock after consecutive four rotations. The pace of C input (Mg C ha(-1) yr(-1)) and rubber production indicated that 40 years rotation is best suited for rubber plantation. The study has developed carbon mitigation based on four rotation scenarios. The possible stimulated increase in C stocks of the entire ecosystem after consecutive long rotations indicated that the emphasis must be paid on deciding the rotation of rubber plantation in SW China for reporting under article 3.4 of the Kyoto Protocol.
Nizami, Syed Moazzam; Yiping, Zhang; Liqing, Sha; Zhao, Wei; Zhang, Xiang
2014-01-01
Extension of the rotation length in forest management has been highlighted in Article 3.4 of the Kyoto Protocol to help the countries in their commitments for reduction in greenhouse gas emissions. CO2FIX Model Ver.3.2 was used to examine the dynamics of carbon stocks (C stocks) in a rubber plantation in South Western China with the changing rotation lengths. To estimate the efficiency of increasing the rotation length as an Article 3.4 activity, study predicted that the rubber production and C stocks of the ecosystem increased with the increasing rotation (25, 30, 35, 40 and 45 years). While comparing the pace of growth both in economical (rubber production) and ecological (C stocks) terms in each rotation, 40 years rotation length showed maximum production and C stocks. After elongation of 40 year rotation to four consecutive cycles, it was concluded that the total C stocks of the ecosystem were 186.65 Mg ha-1. The longer rotation lengths showed comparatively increased C stocks in below ground C stock after consecutive four rotations. The pace of C input (Mg C ha-1yr-1) and rubber production indicated that 40years rotation is best suited for rubber plantation. The study has developed carbon mitigation based on four rotation scenarios. The possible stimulated increase in C stocks of the entire ecosystem after consecutive long rotations indicated that the emphasis must be paid on deciding the rotation of rubber plantation in SW China for reporting under article 3.4 of the Kyoto Protocol. PMID:25536041
Hwang, Cho Rong; Lee, Sang Hoon; Jang, Gwi Yeong; Hwang, In Guk; Kim, Hyun Young; Woo, Koan Sik; Lee, Junsoo; Jeong, Heon Sang
2014-01-01
Background This study evaluated changes in ginsenoside compositions and antioxidant activities in hydroponic-cultured ginseng roots (HGR) and leaves (HGL) with heating temperature. Methods Heat treatment was performed at temperatures of 90°C, 110°C, 130°C, and 150°C for 2 hours. Results The ginsenoside content varied significantly with heating temperature. The levels of ginsenosides Rg1 and Re in HGR decreased with increasing heating temperature. Ginsenosides F2, F4, Rk3, Rh4, Rg3 (S form), Rg3 (R form), Rk1, and Rg5, which were absent in the raw ginseng, were formed after heat treatment. The levels of ginsenosides Rg1, Re, Rf, and Rb1 in HGL decreased with increasing heating temperature. Conversely, ginsenosides Rk3, Rh4, Rg3 (R form), Rk1, and Rg5 increased with increasing heating temperature. In addition, ginsenoside contents of heated HGL were slightly higher than those of HGR. The highest extraction yield was 14.39% at 130°C, whereas the lowest value was 10.30% at 150°C. After heating, polyphenol contents of HGR and HGL increased from 0.43 mg gallic acid equivalent/g (mg GAE eq/g) and 0.74 mg GAE eq/g to 6.16 mg GAE eq/g and 2.86 mg GAE eq/g, respectively. Conclusion Antioxidant activities of HGR and HGL, measured by 1,1-diphenyl-2-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging ability, increased with increasing heating temperature. These results may aid in improving the biological activity and quality of ginseng subjected to heat treatments. PMID:25378992
Das, Sudhir Kumar; Sarkar, Moloy
2012-08-06
Steady-state and time-resolved fluorescence behavior of coumarin 153 (C153) is investigated in a series of 1-ethyl-3-methylimidazolium alkylsulfate ([C(2)mim][C(n)OSO(3)]) ionic liquids differing only in the length of the linear alkyl chain (n = 4, 6, and 8) in the anion. The aim of the present study is to understand the role of alkyl chain length in solute rotation and solvation dynamics of C153 in these ionic liquids. The blueshift observed in the steady-state absorption and emission maxima of C153 on going from the C(4)OSO(3) to the C(8)OSO(3) system indicates increasing nonpolar character of the microenvironment of the solute with increasing length of the alkyl side chain of the anion of the ionic liquids. The average solvation time is also found to increase on changing the substituent from butyl to octyl, and this is attributed to the increase in the bulk viscosity of the ILs. A steady blueshift of the time-zero maximum of the fluorescence spectrum with increasing alkyl chain length also indicates that the probe molecule experiences a less polar environment in the early part of the dynamics. Rotational dynamics of C153 are also analyzed by using the Stokes-Einstein-Debye (SED), Gierer-Wirtz (GW), and Dote-Kivelson-Schwartz (DKS) theories. Analyses of the results seem to suggest decoupling of the rotational motion of the probe from solvent viscosity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Cuddy, John S; Hailes, Walter S; Ruby, Brent C
2014-07-01
The purpose of this study was to determine the impact of the core to skin temperature gradient during incremental running to volitional fatigue across varying environmental conditions. A secondary aim was to determine if a "critical" core temperature would dictate volitional fatigue during running in the heat. 60 participants (n=49 male, n=11 female; 24±5 yrs, 177±11 cm, 75±13 kg) completed the study. Participants were uniformly stratified into a specific exercise temperature group (18 °C, 26 °C, 34 °C, or 42 °C) based on a 3-mile run performance. Participants were equipped with core and chest skin temperature sensors and a heart rate monitor, entered an environmental chamber (18 °C, 26 °C, 34 °C, or 42 °C), and rested in the seated position for 10 min before performing a walk/run to volitional exhaustion. Initial treadmill speed was 3.2 km h(-1) with a 0% grade. Every 3 min, starting with speed, speed and grade increased in an alternating pattern (speed increased by 0.805 km h(-1), grade increased by 0.5%). Time to volitional fatigue was longer for the 18 °C and 26 °C group compared to the 42 °C group, (58.1±9.3 and 62.6±6.5 min vs. 51.3±8.3 min, respectively, p<0.05). At the half-way point and finish, the core to skin gradient for the 18 °C and 26 °C groups was larger compared to 42 °C group (halfway: 2.6±0.7 and 2.0±0.6 vs. 1.3±0.5 for the 18 °C, 26 °C and 42 °C groups, respectively; finish: 3.3±0.7 and 3.5±1.1 vs. 2.1±0.9 for the 26 °C, 34 °C, and 42 °C groups, respectively, p<0.05). Sweat rate was lower in the 18 °C group compared to the 26 °C, 34 °C, and 42 °C groups, 3.6±1.3 vs. 7.2±3.0, 7.1±2.0, and 7.6±1.7 g m(-2) min(-1), respectively, p<0.05. There were no group differences in core temperature and heart rate response during the exercise trials. The current data demonstrate a 13% and 22% longer run time to exhaustion for the 18 °C and 26 °C group, respectively, compared to the 42 °C group despite no differences in beginning and ending core temperatures or baseline 3-mile run time. This capacity difference appears to result from a magnified core to skin gradient via an environmental temperature advantageous to convective heat loss, and in part from an increased sweat rate. Copyright © 2014 Elsevier Ltd. All rights reserved.
Mechanism of cyanoacetylene photochemistry at 185 and 254 nm
NASA Technical Reports Server (NTRS)
Clarke, D. W.; Ferris, J. P.
1996-01-01
The role of cyanoacetylene (HC3N) in the atmospheric photochemistry of Titan and its relevance to polymer formation are discussed. Investigation of the relative light absorption of HC3N, acetylene (C2H2), and diacetylene (C4H2) revealed that HC3N is an important absorber of UV light in the 205- to 225-nanometer wavelength region in Titan's polar regions. Laboratory studies established that photolysis of C2H2 initiates the polymerization of HC3N even though the HC3N is not absorbing the UV light. Quantum yield measurements establish that HC3N is 2-5 times as reactive as C2H2 for polymer formation. Photolysis of HC3N with 185-nanometer light in the presence of N2, H2, Ar, or CF4 results in a decrease in the yield of 1,3,5-tricyanobenzene (1,3,5-tcb), while photolysis in the presence of CH4, C2H6, or n-C4H10 results in an increase in 1,3,5-tcb. The rate of loss of HC3N is increased by all gases except H2, where it is unchanged. It was not possible to detect 1,3,5-tcb as a photoproduct when the partial pressure of HC3N was decreased to 1 torr. Photolysis of HC3N with 254-nanometer light in the presence of H2 or N2 results in the formation of 1,2,4-tcb, while photolysis in the presence of CH4, C2H6, or n-C4H10 results in the formation of increasing amounts of 1,3,5-tcb. Mechanisms for the formation of polymers are presented.
Lee, Seung Hee; Jeong, Eojin; Paik, Sun-Sook; Jeon, Ji Hyun; Jung, Sung Won; Kim, Hyun-Bok; Kim, Muyan; Chun, Myung-Hoon; Kim, In-Beom
2014-01-01
To investigate the effect of cyanidin-3-O-glucoside (C3G) on a rat retinal degeneration (RD) model. Experimental RD was induced in rats by the intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg. C3G extracted from mulberry (Morus alba L.) fruit (50 mg/kg) was orally administered, daily for 1, 2 and 4 weeks after MNU injection. The effects of C3G administration on MNU-induced RD retinas were histologically and functionally assessed by hematoxylin and eosin staining and electroretinography (ERG), respectively. The degree of retinal injury in C3G-administered RD rats was evaluated by immunohistochemistry with an antibody against glial fibrillary acidic protein (GFAP). The preferential protective effect of C3G on scotopic vision was examined by western blot analysis. Marked loss of photoreceptors in the outer nuclear layer (ONL) was observed in RD rats at 2 and 4 weeks after MNU injection, while the ONL in the MNU-induced RD rats given C3G was relatively well preserved. Immunohistochemistry with anti-GFAP showed that retinal injury was also reduced in the retinas of the rats given C3G. Functional assessment by using ERG recordings showed that scotopic ERG responses were significantly increased in RD rats given C3G for 4 weeks (p < 0.01) compared with that of untreated RD rats. In the RD rats given short-term C3G (for 1 and 2 weeks), the increase in ERG responses was not significant. In addition, western blot analysis showed that rhodopsin level in the C3G-administered RD retinas significantly increased compared to that in the non-administered RD retinas (p < 0.05), whereas red/green opsin level did not show any significant difference. Long-term administration of C3G extracted from mulberry fruit could structurally reduce photoreceptor damage and functionally improve scotopic visual functions in the RD rat model induced by MNU.
Finding the genes to build C4 rice.
Wang, Peng; Vlad, Daniela; Langdale, Jane A
2016-06-01
Rice, a C3 crop, is a staple food for more than half of the world's population, with most consumers living in developing countries. Engineering C4 photosynthetic traits into rice is increasingly suggested as a way to meet the 50% yield increase that is predicted to be needed by 2050. Advances in genome-wide deep-sequencing, gene discovery and genome editing platforms have brought the possibility of engineering a C3 to C4 conversion closer than ever before. Because C4 plants have evolved independently multiple times from C3 origins, it is probably that key genes and gene regulatory networks that regulate C4 were recruited from C3 ancestors. In the past five years there have been over 20 comparative transcriptomic studies published that aimed to identify these recruited C4 genes and regulatory mechanisms. Here we present an overview of what we have learned so far and preview the efforts still needed to provide a practical blueprint for building C4 rice. Copyright © 2016 Elsevier Ltd. All rights reserved.
Aono, Masami; Miyazaki, Hisashi; Takekiyo, Takahiro; Tsuzuki, Seiji; Abe, Hiroshi
2018-02-21
We investigated the optical absorption and photoconductivity of iodine-excess ionic liquids (ILs) based on 1-alkyl-3-methyl imidazolium iodide ([C n mim][I]; n = 3, 4, and 6). The iodide concentration m was 2 ≦ m ≦ 8, which was determined by the molar fraction [C n mim] + : [I m ] - = 1 : m. By adding iodine, an absorption edge shifted from 282 nm in the UV region to around 600 nm in the visible-light region. The optical bandgaps E o decreased gradually from 2.3 eV to 1.9 eV with increasing m from 2 to 8. The alkyl-side chain lengths of the cations have little effect on the E o . This experimental result was confirmed by ab initio molecular orbital calculations. The effects were reflected in the photoconductivity of the ILs, as expected. [C 4 mim][I m ] exhibited greater photo-induced electron generation compared with [C 3 mim][I m ] and [C 6 mim][I m ]. The photoconductivity in both [C 3 mim][I m ] and [C 6 mim][I m ] increased slightly with increasing m. The trend of photoconductivity in [C 4 mim][I m ] exhibited an N-shaped form. The highest photoconductivity 1.6 was observed in [C 4 mim][I 8 ].
Reversing Anoikis Resistance in Triple-Negative Breast Cancer
2014-10-01
determine if restoration of miR-200c and inhibition of miR-222 can enhance TNBC differentiation in 3D culture . We found addition of miR-200c and miR-222...inhibition make TNBC colonies in culture in 3D in matrigel smaller, rounder and increase Dicer protein. Additionally, restoration of miR-200c decreases... culture , we have found that addition of miR- 200c and miR-222 inhibition make TNBC colonies in 3D culture in matrigel smaller, rounder and increase Dicer
Cooper, Jason P.; Kang, Min H.; Erdreich-Epstein, Anat
2012-01-01
Inhibition of integrins αvβ3/αvβ5 by the cyclic function-blocking peptide, RGDfV (Arg-Gly-Asp-Phe-Val) can induce apoptosis in both normal cells and tumor cells. We show that RGDfV induced apoptosis in ECV-304 carcinoma cells, increased activity and mRNA expression of acid sphingomyelinase (ASM), and increased ceramides C16, C18∶0, C24∶0 and C24∶1 while decreasing the corresponding sphingomyelins. siRNA to ASM decreased RGDfV-induced apoptosis as measured by TUNEL, PARP cleavage, mitochondrial depolarization, and caspase-3 and caspase-8 activities, as well as by annexinV in a 3D collagen model. These findings indicate a causal role for ASM in RGDfV-induced apoptosis in ECV-304. We have shown that c-Abl, a non-receptor tyrosine kinase, also mediates RGDfV-induced apoptosis. However, c-Abl, has not been previously linked to ASM in any system. Here we show that STI-571 (imatinib, inhibitor of c-Abl) inhibited RGDfV-induced ASM activity. Furthermore, STI-571 and c-Abl-siRNA both inhibited RGDfV-induced increase in ASM mRNA, but ASM-siRNA did not affect c-Abl phosphorylation or expression, supporting that c-Abl regulates the RGDfV-induced increase in ASM expression. These studies implicate ASM as a mediator of apoptosis induced by inhibition of integrins αvβ3/αvβ5, and for the first time place c-Abl as an upstream regulator of ASM expression and activity. PMID:22879933
NASA Astrophysics Data System (ADS)
Tang, Jianjun; Xu, Liming; Chen, Xin; Hu, Shuijin
2009-03-01
Atmospheric CO 2 enrichment may impact arbuscular mycorrhizae (AM) development and function, which could have subsequent effects on host plant species interactions by differentially affecting plant nutrient acquisition. However, direct evidence illustrating this scenario is limited. We examined how elevated CO 2 affects plant growth and whether mycorrhizae mediate interactions between C 4 barnyard grass ( Echinochloa crusgalli (L.) Beauv.) and C 3 upland rice ( Oryza sativa L.) in a low nutrient soil. The monocultures and combinations with or without mycorrhizal inoculation were grown at ambient (400 ± 20 μmol mol -1) and elevated CO 2 (700 ± 20 μmol mol -1) levels. The 15N isotope tracer was introduced to quantify the mycorrhizally mediated N acquisition of plants. Elevated CO 2 stimulated the growth of C 3 upland rice but not that of C 4 barnyard grass under monoculture. Elevated CO 2 also increased mycorrhizal colonization of C 4 barnyard grass but did not affect mycorrhizal colonization of C 3 upland rice. Mycorrhizal inoculation increased the shoot biomass ratio of C 4 barnyard grass to C 3 upland rice under both CO 2 concentrations but had a greater impact under the elevated than ambient CO 2 level. Mycorrhizae decreased relative interaction index (RII) of C 3 plants under both ambient and elevated CO 2, but mycorrhizae increased RII of C 4 plants only under elevated CO 2. Elevated CO 2 and mycorrhizal inoculation enhanced 15N and total N and P uptake of C 4 barnyard grass in mixture but had no effects on N and P acquisition of C 3 upland rice, thus altering the distribution of N and P between the species in mixture. These results implied that CO 2 stimulation of mycorrhizae and their nutrient acquisition may impact competitive interaction of C 4 barnyard grass and C 3 upland rice under future CO 2 scenarios.
Opii, Wycliffe O; Sultana, Rukhsana; Abdul, Hafiz Mohmmad; Ansari, Mubeen Ahmad; Nath, Avindra; Butterfield, D Allan
2007-03-01
Human immunodeficiency virus dementia (HIVD) is the most common form of dementia occurring among young adults. In HIVD, neuronal cell loss occurs in the absence of neuronal infection. With the advent of highly active anti-retroviral therapy (HAART), the incidence of HIVD has drastically reduced, though prevalence of milder forms of HIVD continues to rise. Though these agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. Here we examine the possible role of NRTIs, in particular 2',3'-dideoxycytidine (ddC), in the neuropathology of HIVD. Synaptosomes and isolated mitochondria treated and incubated for 6 h with CSF-achievable concentrations of ddC, i.e., 6-11 ng/ml, were found to show a significant increase in oxidative stress with 40 nM ddC as measured by protein carbonyls and 3-nitrotyrosine (3NT), effects that were not observed in the more tolerable NRTI, 3TC. Protection against protein oxidation induced by ddC was observed when brain mitochondria were isolated from gerbils 1 h after injection i.p. with the brain accessible antioxidant and glutathione mimetic, tricyclodecan-9-yl-xanthogenate (D609). In addition, there is a significant reduction in the levels of anti-apoptotic protein Bcl-2 and a significant increase in cytochrome c release and also a significant increase in the expression of pro-apoptotic protein caspase-3 after mitochondria were treated with 40 nM ddC. The results reported here show that ddC at 40 nM can induce oxidative stress, cause the release of cytochrome c, and in addition, reduce the levels of anti-apoptotic proteins, increase the levels of pro-apoptotic proteins, thereby increasing the possibility for induction of apoptosis. These findings are consistent with the notion of a possible role of the NRTIs, and in particular, ddC, in the mechanisms involved in HIVD.
NASA Astrophysics Data System (ADS)
Hsieh, Chih-Chun; Liu, Yi-Chia; Wang, Jia-Siang; Wu, Weite
2014-07-01
The aim of this study is to discuss the effect of microstructural development with different Ti contents in Fe-based hardfacing alloys. A series of Fe-Cr-C-Si-Mn-xTi alloy fillers was deposited on SS400 low carbon steel substrate using oscillating gas tungsten arc welding. The microstructure in the Fe-based hardfacing alloy without Ti content addition included: the primary γ, eutectic γ+(Fe,Cr)3C, eutectic γ+(Fe,Cr)2C and martensite. With increasing Ti contents, the microstructures showed the primary TiC carbide, γ phase and eutectic γ+(Fe,Cr,Ti)3C. The amount and size of TiC carbide in the hardfacing layers increased as the Ti content increased. However, the eutectic γ+(Fe,Cr,Ti)3C content decreased as the Ti content increased. According to the results of the hardness test, the lowest hardness value (HRC 54.93) was found with 0% wt% Ti and the highest hardness (HRC 60.29) was observed with 4.87 wt% Ti.
Increase in Ca2+ current by sustained cAMP levels enhances proliferation rate in GH3 cells.
Rodrigues, Andréia Laura; Brescia, Marcella; Koschinski, Andreas; Moreira, Thaís Helena; Cameron, Ryan T; Baillie, George; Beirão, Paulo S L; Zaccolo, Manuela; Cruz, Jader S
2018-01-01
Ca 2+ and cAMP are important intracellular modulators. In order to generate intracellular signals with various amplitudes, as well as different temporal and spatial properties, a tightly and precise control of these modulators in intracellular compartments is necessary. The aim of this study was to evaluate the effects of elevated and sustained cAMP levels on voltage-dependent Ca 2+ currents and proliferation in pituitary tumor GH3 cells. Effect of long-term exposure to forskolin and dibutyryl-cyclic AMP (dbcAMP) on Ca 2+ current density and cell proliferation rate were determined by using the whole-cell patch-clamp technique and real time cell monitoring system. The cAMP levels were assayed, after exposing transfected GH3 cells with the EPAC-1 cAMP sensor to forskolin and dbcAMP, by FRET analysis. Sustained forskolin treatment (24 and 48h) induced a significant increase in total Ca 2+ current density in GH3 cells. Accordingly, dibutyryl-cAMP incubation (dbcAMP) also elicited increase in Ca 2+ current density. However, the maximum effect of dbcAMP occurred only after 72h incubation, whereas forskolin showed maximal effect at 48h. FRET-experiments confirmed that the time-course to elevate intracellular cAMP was distinct between forskolin and dbcAMP. Mibefradil inhibited the fast inactivating current component selectively, indicating the recruitment of T-type Ca 2+ channels. A significant increase on cell proliferation rate, which could be related to the elevated and sustained intracellular levels of cAMP was observed. We conclude that maintaining high levels of intracellular cAMP will cause an increase in Ca 2+ current density and this phenomenon impacts proliferation rate in GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.
Study of P3HT/ PCBM morphology using Raman spectroscopy
NASA Astrophysics Data System (ADS)
Kumar, Sunil; Kumar, Manoj; Rathi, Sonika; Yadav, Anjali; Upadhyaya, Aditi; Gupta, Saral K.; Singh, Amarjeet
2018-05-01
In the present work we have deposited PEDOT: PSS (poly3,4-ethylene dioxythiophene -poly (styrenesulfonate)) then Pristine P3HT (Poly-3 hexylthiophene-2,5-diyl), PCBM (6,6- PhenylC61 butyric acid methyl ester) and its blend composite (P3HT:PCBM) thin films on ITO substrate via spin coating technique. Pristine P3HT, pristine PCBM and blend thin film samples were annealed at different temperatures (50°C, 80°C and 110°C) for 1 hr. Raman spectra was measured for each thin film samples as prepared (at room temperature or 25°C) and annealed at different temperatures (50°C, 80°C, 110°C). Then we calculated area under Raman peaks which is representation of Raman Intensity and observed that area under Raman peak varies with annealing temperatures. The increase in peak intensity appears due to increased crystallinity in annealed thin films. The mixing of PCBM hinders the crystallization of P3HT in blend. Mixed amorphous phase plays major role in charge transportation in electronic devices.
Bochkov, Yury A; Watters, Kelly; Ashraf, Shamaila; Griggs, Theodor F; Devries, Mark K; Jackson, Daniel J; Palmenberg, Ann C; Gern, James E
2015-04-28
Members of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared with other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We report here that expression of human cadherin-related family member 3 (CDHR3) enables the cells normally unsusceptible to RV-C infection to support both virus binding and replication. A coding single nucleotide polymorphism (rs6967330, C529Y) was previously linked to greater cell-surface expression of CDHR3 protein, and an increased risk of wheezing illnesses and hospitalizations for childhood asthma. Compared with wild-type CDHR3, cells transfected with the CDHR3-Y529 variant had about 10-fold increases in RV-C binding and progeny yields. We developed a transduced HeLa cell line (HeLa-E8) stably expressing CDHR3-Y529 that supports RV-C propagation in vitro. Modeling of CDHR3 structure identified potential binding sites that could impact the virus surface in regions that are highly conserved among all RV-C types. Our findings identify that the asthma susceptibility gene product CDHR3 mediates RV-C entry into host cells, and suggest that rs6967330 mutation could be a risk factor for RV-C wheezing illnesses.
Choi, Kyung Ha; Lee, Hyun Ah; Park, Mi Hwa; Han, Ji-Sook
2017-09-01
In this study, the effect of cyanidin-3-rutinoside (C3R) on glucose uptake by 3T3-L1 adipocytes was studied. C3R significantly increased glucose uptake, which was associated with enhanced plasma membrane glucose transporter type 4 (PM-GLUT4) expression in 3T3-L1 adipocytes. The potentiating effect of C3R on glucose uptake and PM-GLUT4 expression was related to enhanced phosphorylation of insulin receptor substrate 1 (IRS-1) and Akt, as well as augmented activation of phosphatidylinositol-3-kinase (PI3K) in the insulin signaling pathway. C3R induced glucose uptake was inhibited only by the PI3K inhibitor, but not by an AMPK inhibitor in 3T3-L1 adipocytes. Therefore, C3R likely up-regulates glucose uptake and PM-GLUT4 expression in 3T3-L1 adipocytes by activating the PI3K/Akt pathways. Copyright © 2017 Elsevier B.V. All rights reserved.
van Haaften, W T; Mortensen, J H; Karsdal, M A; Bay-Jensen, A C; Dijkstra, G; Olinga, P
2017-07-01
Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro-C3, Pro-C5, Pro-C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L. C3M and Pro-C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6±5 vs 25.8±2.2 [P=.004] and 27.2±2.3 [P=.018] nmol/L C3M, 1262.7±259.4 vs 902.9±109.9 [P=.005] and 953.0±106.4 [P=.015] nmol/L Pro-C5). C1M (71.2±26.1 vs 46.2±6.2 nmol/L [P<.001]), C3M (31.6±3.9 vs 26.1±1.6 nmol/L [P=.002] and Pro-C5 levels (1171.7±171.5 vs 909.6±80.4 nmol/L [P=.002]) were higher in patients with active inflammation vs without active inflammation. Pro-C3/C3M-ratios were best to differentiate between penetrating vs nonstricturing/nonpenetrating and stricturing disease with area under the curves of 0.815±0.109 (P<.001) and 0.746±0.114 (P=.002) respectively. Serological biomarkers show that penetrating Crohn's disease is characterised by increased matrix metalloproteinase-9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro-C3/C3M ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease. © 2017 The Authors. Alimentary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
Francisco, A; Alves, S P; Portugal, P V; Pires, V M R; Dentinho, M T; Alfaia, C M; Jerónimo, E; Prates, J A M; Santos-Silva, J; Bessa, R J B
2016-12-01
The effects of feeding Cistus ladanifer (Cistus) and a blend of soybean and linseed oil (1 : 2 vol/vol) on fatty acid (FA) composition of lamb meat lipids and messenger RNA (mRNA) expression of desaturase enzymes was assessed. In total, 54 male lambs were randomly assigned to 18 pens and to nine diets, resulting from the combination of three inclusion levels of Cistus (50 v. 100 v. 200 g/kg of dry matter (DM)) and three inclusion levels of oil (0 v. 40 v. 80 g/kg of DM). The forage-to-concentrate ratio of the diets was 1 : 1. Longissimus muscle lipids were extracted, fractionated into neutral (NL) and polar lipid (PL) and FA methyl esters obtained and analyzed by GLC. The expression of genes encoding Δ5, Δ6 and Δ9 desaturases (fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2) and stearoyl CoA desaturase (SCD)) was determined. Intramuscular fat, NL and PL contents were not affected by oil or Cistus. Oil supplementation reduced (P<0.05) 16:0, c9-16:1, 17:0, c9-17:1 and c9-18:1 FA and increased (P<0.05) 18:2n-6, 18:3n-3 and the majority of biohydrogenation intermediates in NL. Cistus alone had few effects on FA of NL but interacted with oil (P<0.05) by increasing t10-18:1,t10,t12-18:2,t10,c12-18:2 and t7,c9-18:2. The t10-/t11-18:1 ratio increased with both Cistus and oil levels. The c9, t11-18:2 did not increase (P<0.05) with both oil and Cistus dietary inclusion. Oil reduced c9-16:1, 17:0, c9-17:1,c9-18:1, 20:4n-6, 22:4n-6 and 20:3n-9 proportions in PL, and increased 18:2n-6, 18:3n-3, 20:3n-3 and of most of the biohydrogenation intermediates. The Cistus had only minor effects on FA composition of PL. Cistus resulted in a reduction (P<0.05) of 20:5n-3 and 22:6n-3 in the meat PL. The expression level of SCD mRNA increased (P=0.015) with Cistus level, although a linear relationship with condensed tannins intake (P=0.11) could not be established. FADS1 mRNA expressed levels increased linearly (P=0.019) with condensed tannins intake. In summary, the inclusion of Cistus and oil in 1 : 1 forage-to-concentrate ratio diets resulted in a large increase in t10-18:1 and no increase in c9,t11-18:2 or n-3 long chain poor in polyunsaturated fatty acids in lamb meat.
Lee, Dong-Ha; Kwon, Hyuk-Woo; Kim, Hyun-Hong; Lim, Deok Hwi; Nam, Gi Suk; Shin, Jung-Hae; Kim, Yun-Yi; Kim, Jong-Lae; Lee, Jong-Jin; Kwon, Ho-Kyun; Park, Hwa-Jin
2015-01-01
In this study, we investigated the effect of cordycepin-enriched (CE)-WIB801C from Cordyceps militaris on ADP (20 µM)-stimulated platelet aggregation. CE-WIB801C dose-dependently inhibited ADP-induced platelet aggregation, and its IC50 value was 18.5 μg/mL. CE-WIB801C decreased TXA2 production, but did not inhibit the activities of COX-1 and thromboxane synthase (TXAS) in ADP-activated platelets, which suggests that the inhibition of TXA2 production by CE-WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. CE-WIB801C inhibited ATP release and [Ca(2+)]i mobilization, and increased cAMP level and IP3RI (Ser(1756)) phosphorylation in ADP-activated platelets. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased CE-WIB801C-inhibited [Ca(2+)]i mobilization, and strongly inhibited CE-WIB801C-increased IP3RI (Ser(1756)) phosphorylation. CE-WIB801C elevated the phosphorylation of VASP (Ser(157)), an A-kinase substrate, but inhibited fibrinogen binding to αIIb/β3. These results suggest that CE-WIB801C-elevated cAMP involved in IP3RI (Ser(1756)) phosphorylation to inhibit [Ca(2+)]i mobilization and, VASP (Ser(157)) phosphorylation to inhibit αIIb/β3 activation. Therefore, in this study, we demonstrate that CE-WIB801C may have a preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.
Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas
2016-06-15
Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.
Liu, Wei; Xu, Jingcheng; Liu, Jia; Cao, Haihua; Huang, Xiang-Feng; Li, Guangming
2015-01-01
Thermal drying was used to reduce sludge moisture content before co-combustion in cement kilns. The characteristics of ammonia (NH3) emission during thermal drying of lime sludge (LS) were investigated in a laboratory-scale tubular dry furnace under different temperature and time conditions. As the temperature increased, the NH3 concentration increased in the temperature range 100-130°C, decreased in the temperature range 130-220°C and increased rapidly at >220°C. Emission of NH3 also increased as the lime dosage increased and stabilized at lime dosages>5%. In the first 60 min of drying experiments, 55% of the NH3 was released. NH3 accounted for about 67-72% of the change in total nitrogen caused by the release of nitrogen-containing volatile compounds (VCs) from the sludge. X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy revealed that the main forms of nitrogen in sludge were amides and amines. The addition of lime (CaO) could cause conversion of N-H, N-O or C-N containing compounds to NH3 during the drying process.
2016-05-01
distribution is unlimited. PA Clearance #16274 2 Overall Process DISTRIBUTION A. Approved for public release; distribution unlimited. 3 Sulfur in Fuels...Mercaptans (Thiols) The presence of sulfur in fuels leads to many detrimental effects: • Coking on rocket engine injector plates • Deposit formation in... Sulfur Compounds by GC-SCD ( Sulfur Speciation) Concentration (ppm) C2 Thiophenes 0.3 C3-C4 Thiophenes 1.4 C5 Thiophenes 3.7 C6 Thiophenes 3.5 C7
Crop responses to elevated CO2 and interactions with H2O, N, and temperature.
Kimball, Bruce A
2016-06-01
About twenty-seven years ago, free-air CO2 enrichment (FACE) technology was developed that enabled the air above open-field plots to be enriched with CO2 for entire growing seasons. Since then, FACE experiments have been conducted on cotton, wheat, ryegrass, clover, potato, grape, rice, barley, sugar beet, soybean, cassava, rape, mustard, coffee (C3 crops), and sorghum and maize (C4 crops). Elevated CO2 (550ppm from an ambient concentration of about 353ppm in 1990) decreased evapotranspiration about 10% on average and increased canopy temperatures about 0.7°C. Biomass and yield were increased by FACE in all C3 species, but not in C4 species except when water was limiting. Yields of C3 grain crops were increased on average about 19%. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Jordan, C. E.; Griffin, R. J.; Lim, Y. B.; Ziemann, P. J.; Atkinson, R.; Arey, J.
2005-12-01
Recent laboratory studies show that δ-hydroxycarbonyls formed in the atmosphere via OH-initiated reactions with alkanes can cyclize then dehydrate to form substituted dihydrofurans. These dihydrofurans are highly reactive, with lifetimes in the atmosphere of 1.3 h (OH), 24 s (NO3), and 7 min (O3). The ability of the δ-hydroxycarbonyls to cyclize and dehydrate has been shown to increase with increasing carbon number. Recent laboratory results show that the secondary organic aerosol (SOA) yields from alkanes also increase with carbon number reaching ~53% for C15. The reaction mechanism proposed based on the chamber results is the basis of the modeling study presented here. We have incorporated this proposed mechanism into the Caltech Atmospheric Chemistry Mechanism (CACM). For computational reasons, similar compounds are lumped together and represented by a single suitable compound. In the present case, alkanes are lumped into 3 groups: short chains (≤C6), medium chains (C7 - C12), and long chains (≥C13). SOA yields obtained in chamber studies increase dramatically from 0.5% for C8 to 25% for C12. The most dramatic increase is observed from C11 (8%) to C13 (~50%). This is attributed to the low volatility of first generation products contributing to the SOA from longer chain alkanes. Here we have studied OH reactions with the substituted dihydrofurans for medium (represented by C10) and long (represented by C16) chain alkanes using CACM along with the aerosol partitioning module MPMPO (Model to Predict the Multi-phase Partitioning of Organics). We will present the results of this modeling study, characterizing the influence of substituted dihydrofurans on the SOA forming potential of alkanes.
Bucher, John R
2007-01-01
Sodium dichromate dihydrate is one of a number of inorganic compounds containing hexavalent chromium (CR VI) found in drinking water supplies as a contaminant resulting from various industrial processes including electroplating operations, leather tanning, and textile manufacturing. Because of the lack of adequate experimental data on the toxicity and carcinogenicity of hexavalent chromium ingested orally, and because hexavalent chromium has been found in human drinking water supplies, the California Congressional delegation and the California Environmental Protection Agency nominated hexavalent chromium to the NTP for study. In study 1, male and female F344/N rats and B6C3F1 mice were exposed to sodium dichromate dihydrate (greater than 99% pure) in drinking water for 3 months. In study 2, sodium dichromate dihydrate was administered in drinking water to male B6C3F1, BALB/c, and am3-C57BL/6 mice for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. In study 1, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were given drinking water containing 0, 62.5, 125, 250, 500, or 1,000 mg sodium dichromate dihydrate/L for 3 months (equivalent to average daily doses of approximately 5, 10, 17, 32, or 60 mg sodium dichromate dihydrate/kg body weight to rats and 9, 15, 26, 45, or 80 mg/kg to mice). On a molecular weight basis, these doses are equivalent to approximately 1.7, 3.5, 5.9, 11.2, and 20.9 mg hexavalent chromium/kg body weight per day to rats and 3.1, 5.2, 9.1, 15.7, and 27.9 mg/kg per day to mice. Additional groups of 10 rats per sex were exposed to the same concentrations of sodium dichromate dihydrate for 4 weeks. All rats and mice survived to the end of the study. Reduced body weights occurred in 500 and 1,000 mg/L male rats, 1,000 mg/L female rats, and in male and female mice exposed to 125 mg/L or greater. Water consumption by male and female rats exposed to 250 mg/L or greater and male and female mice exposed to 125 mg/L or greater was generally less than that by the control groups, and decreases in urine volume and increases in urine specific gravity in rats were related to reduced water consumption. Exposure to sodium dichromate dihydrate caused a microcytic hypochromic anemia in rats and mice, but the severity was less in mice. Serum cholesterol and triglyceride concentrations were decreased in rats. Increased bile acid concentrations in exposed groups of rats may have been due to altered hepatic function. The incidences of histiocytic cellular infiltration were generally significantly increased in the duodenum of rats and mice, the liver of female rats, and the mesenteric lymph node of mice exposed to 125 mg/L or greater. Significantly increased nonneoplastic lesions (focal ulceration, regenerative epithelial hyperplasia, and squamous epithelial metaplasia) occurred in the glandular stomach of male and female rats exposed to 1,000 mg/L. Incidences of epithelial hyperplasia of the duodenum were significantly increased in all exposed groups of mice. In study 2, sodium dichromate dihydrate was administered in drinking water to groups of 10 male B6C3F1, 10 male BALB/c, and five male am3-C57BL/6 mice for 3 months at exposure concentrations of 0, 62.5, 125, or 250 mg/L (equivalent to average daily doses of approximately 8, 15, or 25 mg/kg sodium dichromate dihydrate or 2.8, 5.2, or 8.7 mg/kg chromium to B6C3F1, BALB/c, and am3-C57BL/6 mice). All mice in study 2 survived until study termination. Mean body weights of 125 and 250 mg/L B6C3F1 and BALB/c mice and all exposed groups of am3-C57BL/6 mice were less than those of the control groups. Mice exposed to 250 mg/L consumed less water than the control groups. Exposure concentration-related decreases in mean red cell volumes and mean red cell hemoglobin values were observed in all three mouse strains. Erythrocyte counts were increased in exposed B6C3F1 and BALB/c mice but not in am3-C57BL/6 mice. Changes in organ weights were generally consistent with reduced body weights in exposed groups in all mouse strains. No biologically significant differences in reproductive parameters were observed in any strain. Histiocytic cellular infiltration and epithelial hyperplasia of the duodenum occurred in most mice exposed to 125 or 250 mg/L, and the incidences of these lesions were increased in the 62.5 mg/L group compared to controls. Secretory depletion was present in the pancreas of most mice exposed to 125 or 250 mg/L. The incidences of glycogen depletion of the liver were significantly increased in male B6C3F1 mice exposed to 125 or 250 mg/L and in all exposed groups of male am3-C57BL/6 mice. The incidence of histiocytic cellular infiltration in the mesenteric lymph node was significantly increased in the 250 mg/L group of male am3-C57BL/6 mice. Sodium dichromate dihydrate was mutagenic in S. typhimurium strains TA100 and TA98 and in E. coli strain WP2 uvrA pKM101 with and without induced rat liver S9 enzymes. The results of four micronucleus tests conducted in the three strains of mice from studies 1 and 2 were mixed. In study 1, no significant increases were seen in micronucleated normochromatic erythrocytes in peripheral blood samples from male or female B6C3F1 mice; there was a decrease in the percentage of polychromatic erythrocytes among total erythrocytes (an indication of bone marrow toxicity), but the changes were small and not well correlated with exposure concentrations. In study 2, a significant exposure concentration-related increase (P<0.001) in micronucleated normochromatic erythrocytes was seen in am3-C57BL/6 male mice. An equivocal increase in micronucleated erythrocytes was noted in male B6C3F1 mice, based on a small increase in micronucleated normochromatic erythrocytes that did not reach statistical significance. No increase in micronucleated normochromatic erythrocytes was observed in male BALB/c mice. No significant effect of sodium dichromate dihydrate exposure on the percentage of polychromatic erythrocytes was observed in any of the three micronucleus tests conducted in study 2. In summary, administration of sodium dichromate dihydrate in the drinking water to F344/N rats and B6C3F1 mice resulted in focal ulceration, hyperplasia, and metaplasia in the glandular stomach at the limiting ridge in rats in the 1,000 mg/L group and evidence of increased histiocytic infiltration in the liver (female), duodenum of the small intestine, and/or pancreatic lymph nodes at concentrations as low as 62.5 mg/L, the lowest concentration studied. In addition, a microcytic, hypochromic anemia occurred at all exposure concentrations and was considered evidence of a toxic response resulting from absorption of Cr VI following oral ingestion in rats. A similar, but less severe, anemia was evident in mice receiving drinking water containing sodium dichromate dihydrate; histiocytic infiltration was noted in the duodenum of all three strains studied (B6C3F1, BALB/c, and am3-C57BL/6) at all concentrations employed, in the mesenteric lymph nodes at 125 mg/L or greater in the B6C3F1 strain, and at 250 mg/L in the am3-C57BL/6 strain. There was no consistent evidence of hepatocyte injury in mice in any of the strains tested. Variations in glycogen content were considered more likely related to diminished food intake than to the toxicity of sodium dichromate dihydrate. Synonyms: Chromic acid; dichromic acid; disodium salt, dihydrate; disodium dichromate dihydrate; chromium VI.
Structure and properties of sintered MM-Fe-B magnets
NASA Astrophysics Data System (ADS)
Shang, R. X.; Xiong, J. F.; Li, R.; Zuo, W. L.; Zhang, J.; Zhao, T. Y.; Chen, R. J.; Sun, J. R.; Shen, B. G.
2017-05-01
MM14Fe79.9B6.1 magnets were prepared by conventional sintering method. The Curie temperature of the sintered MM2Fe14B magnet was about 210 °C. When the sintering temperature increased from 1010 °C to 1030 °C, the density of the magnet increased from 6.85 g/cm3 to 7.52 g/cm3. After the first stage tempering at 900 °C, the (BH)max and Hcj had a slight increase. The maximum value of (BH)max = 7.6 MGOe and Hcj = 1080 Oe was obtained when sintered at 1010 °C and tempering at 900 °C, respectively. The grain size grew very large when the sintering temperature increased to 1050 °C, and the magnetic properties deteriorated rapidly. La reduced by ˜ 7.5 at. % in grains, which is almost equal to the increased percentage of Nd. That is mainly because La-Fe-B is very difficult to form the 2: 14: 1 phase.
DiMarco, Diana M; Missimer, Amanda; Murillo, Ana Gabriela; Lemos, Bruno S; Malysheva, Olga V; Caudill, Marie A; Blesso, Christopher N; Fernandez, Maria Luz
2017-03-01
Eggs are a source of cholesterol and choline and may impact plasma lipids and trimethylamine-N-oxide (TMAO) concentrations, which are biomarkers for cardiovascular disease (CVD) risk. Therefore, the effects of increasing egg intake (0, 1, 2, and 3 eggs/day) on these and other CVD risk biomarkers were evaluated in a young, healthy population. Thirty-eight subjects [19 men/19 women, 24.1 ± 2.2 years, body mass index (BMI) 24.3 ± 2.5 kg/m 2 ] participated in this 14-week crossover intervention. Participants underwent a 2-week washout with no egg consumption, followed by intake of 1, 2, and 3 eggs/day for 4 weeks each. Anthropometric data, blood pressure (BP), dietary records, and plasma biomarkers (lipids, glucose, choline, and TMAO) were measured during each intervention phase. BMI, waist circumference, systolic BP, plasma glucose, and plasma triacylglycerol did not change throughout the intervention. Diastolic BP decreased with egg intake (P < 0.05). Compared to 0 eggs/day, intake of 1 egg/day increased HDL cholesterol (HDL-c) (P < 0.05), and decreased LDL cholesterol (LDL-c) (P < 0.05) and the LDL-c/HDL-c ratio (P < 0.01). With intake of 2-3 eggs/day, these changes were maintained. Plasma choline increased dose-dependently with egg intake (P < 0.0001) while fasting plasma TMAO was unchanged. These results indicate that in a healthy population, consuming up to 3 eggs/day results in an overall beneficial effect on biomarkers associated with CVD risk, as documented by increased HDL-c, a reduced LDL-c/HDL-c ratio, and increased plasma choline in combination with no change in plasma LDL-c or TMAO concentrations.
United States Air Force Summer Research Program -- 1993. Volume 2. Armstrong Laboratory
1993-12-01
increase of both left and right hearts as ... Ahl = (h2 - h,) + (h., - h3) (h 2 - h) = cATLH + vAPH (h, - h3) = cAT • + vAP, next applying the 1st law to...CATR T Cs *-hC3 ,C, v P,- jA -HV + vAPc 3 + AG)T a=-HV+ AG)T.P -tuAPc2,c, + cATLH + cATRH + cAT , Since AG)T.P Wrev and Wact = HV - CATC, assuming Q2...Ah3 - vAP, - ,AN, -- HV + cAT , + vAP, + AG)TI mis (- HV +cAT3 + vAPý G), C;=iMs (- HV+ AG +vAP,,),,) PULMONARY CIRCULATION: Shown below is the schematic
A Regulation of Tropical Climate by Radiative Cooling as Simulated in a Cumulus Ensemble Model
NASA Technical Reports Server (NTRS)
Sui, Chung-Hsiung; Lau, K.-M.; Li, X.; Chou, M.-D.; Einaudi, Franco (Technical Monitor)
2000-01-01
Responses of tropical atmosphere to low-boundary forcing are investigated in a 2-D cumulus ensemble model (CEM) with an imposed warm-pool and cold-pool SST contrast (deltaSST). The domain-mean vertical motion is constrained to produce heat sink and moisture source as in the observed tropical climate. In a series of experiments, the warm pool SST is specified at different values while the cold pool SST is specified at 26 C. The strength of the circulation increases with increasing deltaSST until deltaSST reaches 3.5 C, and remains unchanged as deltaSST exceeds 3.5 C. The regulation of tropical convection by zonal SST gradient is constrained by the radiative cooling over the cold pool. For deltaSST less than 3.5 C, an enhanced subsidence warming is balanced by a reduced condensation heating over the cold pool. For deltaSST greater than 3.5 C, the subsidence regime expands over the entire cold pool where no condensation heating exist so that a further enhanced subsidence warming can no longer be sustained. The above regulation mechanism is also evident in the change of energy at the top of the atmosphere (TOA) that is dominated by cloud and water vapor greenhouse effect (c (sub LW)) and G (sub clear). The change in shortwave radiation at TOA is largely cancelled between the warm pool and cold pool, likely due to the same imposed vertical motion in our experiments. For deltaSST less than 3.5 C, an increase of deltaSST is associated with a large increase in c (sub Lw) due to increased total clouds in response to enhanced SST-induced circulation. For deltaSST greater than 3.5 C, clouds over the warm pool decrease with increasing SST, and the change in c (sub LW) is much smaller. In both dSST regimes, the change in CLW is larger than the change in G(sub clear) which is slightly negative. However, in the case of uniform warming (deltaSST=0), DeltaG(sub clear), is positive, approximately 5 W per square meters per degree change of SST.
The bioeroding sponge Cliona orientalis will not tolerate future projected ocean warming.
Ramsby, Blake D; Hoogenboom, Mia O; Smith, Hillary A; Whalan, Steve; Webster, Nicole S
2018-05-29
Coral reefs face many stressors associated with global climate change, including increasing sea surface temperature and ocean acidification. Excavating sponges, such as Cliona spp., are expected to break down reef substrata more quickly as seawater becomes more acidic. However, increased bioerosion requires that Cliona spp. maintain physiological performance and health under continuing ocean warming. In this study, we exposed C. orientalis to temperature increments increasing from 23 to 32 °C. At 32 °C, or 3 °C above the maximum monthly mean (MMM) temperature, sponges bleached and the photosynthetic capacity of Symbiodinium was compromised, consistent with sympatric corals. Cliona orientalis demonstrated little capacity to recover from thermal stress, remaining bleached with reduced Symbiodinium density and energy reserves after one month at reduced temperature. In comparison, C. orientalis was not observed to bleach during the 2017 coral bleaching event on the Great Barrier Reef, when temperatures did not reach the 32 °C threshold. While C. orientalis can withstand current temperature extremes (<3 °C above MMM) under laboratory and natural conditions, this species would not survive ocean temperatures projected for 2100 without acclimatisation or adaptation (≥3 °C above MMM). Hence, as ocean temperatures increase above local thermal thresholds, C. orientalis will have a negligible impact on reef erosion.
NASA Astrophysics Data System (ADS)
Zhao, Changchun; Zhou, Yefei; Xing, Xiaolei; Liu, Sha; Ren, Xuejun; Yang, Qingxiang
2018-05-01
The wear resistance of Fe-based composite coating is significantly related with the character of carbides and matrix, which could be strongly affected by C content in it. In this work, the Fe-based composite coatings with different C contents were prepared. The microstructure and phase structure of the coatings were analyzed by scanning electron microscope (SEM) equipped with an energy-dispersive spectroscopy (EDS) and X-ray diffractometer (XRD). The hardness and wear resistance of the coatings were determined. Then the hardness and brittleness of carbon poor niobium carbides were calculated by first principles calculation. The results show that, the phase structures of the coatings are mainly composed of NbC, γ phase (retained austenite) and α phase (martensite). With the increase of C content, the retained austenite appears and C content of martensite is increased. The hardness of the coatings are increased from HRC 22 to HRC 59. The distribution and morphology of NbC are changed with the increase of C content. The NbC precipitated in reticular grain boundary can be observed when C content is 0.4 wt.% C (C-1). NbC turn into granular and small rod morphology when C content increases to 0.8 wt.% C (C-2). The cracks and defects cannot been found on the surface of the coating when C content is 1.2 wt.% C(C-3), whose hardness is HRC 58 and wear loss is 0.27 g/N cm2 in 8 h. The flaky M7C3 carbide precipitates on the coating when C content is 1.4 wt.% C(C-4), which weaken the wear resistance of the matrix. Compared with the hardfacing coatings with different C contents, the C-3 coating processes higher hardness and wear resistance.
Thermoelectric properties of Ca0.8Dy0.2MnO3 synthesized by solution combustion process
NASA Astrophysics Data System (ADS)
Park, Kyeongsoon; Lee, Ga Won
2011-10-01
High-quality Ca0.8Dy0.2MnO3 nano-powders were synthesized by the solution combustion process. The size of the synthesized Ca0.8Dy0.2MnO3 powders was approximately 23 nm. The green pellets were sintered at 1150-1300°C at a step size of 50°C. Sintered Ca0.8Dy0.2MnO3 bodies crystallized in the perovskite structure with an orthorhombic symmetry. The sintering temperature did not affect the Seebeck coefficient, but significantly affected the electrical conductivity. The electrical conductivity of Ca0.8Dy0.2MnO3 increased with increasing temperature, indicating a semiconducting behavior. The absolute value of the Seebeck coefficient gradually increased with an increase in temperature. The highest power factor (3.7 × 10-5 Wm-1 K-2 at 800°C) was obtained for Ca0.8Dy0.2MnO3 sintered at 1,250°C. In this study, we investigated the microstructure and thermoelectric properties of Ca0.8Dy0.2MnO3, depending on sintering temperature.
Thermoelectric properties of Ca0.8Dy0.2MnO3 synthesized by solution combustion process
2011-01-01
High-quality Ca0.8Dy0.2MnO3 nano-powders were synthesized by the solution combustion process. The size of the synthesized Ca0.8Dy0.2MnO3 powders was approximately 23 nm. The green pellets were sintered at 1150-1300°C at a step size of 50°C. Sintered Ca0.8Dy0.2MnO3 bodies crystallized in the perovskite structure with an orthorhombic symmetry. The sintering temperature did not affect the Seebeck coefficient, but significantly affected the electrical conductivity. The electrical conductivity of Ca0.8Dy0.2MnO3 increased with increasing temperature, indicating a semiconducting behavior. The absolute value of the Seebeck coefficient gradually increased with an increase in temperature. The highest power factor (3.7 × 10-5 Wm-1 K-2 at 800°C) was obtained for Ca0.8Dy0.2MnO3 sintered at 1,250°C. In this study, we investigated the microstructure and thermoelectric properties of Ca0.8Dy0.2MnO3, depending on sintering temperature. PMID:21974984
Thermoelectric properties of Ca0.8Dy0.2MnO3 synthesized by solution combustion process.
Park, Kyeongsoon; Lee, Ga Won
2011-10-05
High-quality Ca0.8Dy0.2MnO3 nano-powders were synthesized by the solution combustion process. The size of the synthesized Ca0.8Dy0.2MnO3 powders was approximately 23 nm. The green pellets were sintered at 1150-1300°C at a step size of 50°C. Sintered Ca0.8Dy0.2MnO3 bodies crystallized in the perovskite structure with an orthorhombic symmetry. The sintering temperature did not affect the Seebeck coefficient, but significantly affected the electrical conductivity. The electrical conductivity of Ca0.8Dy0.2MnO3 increased with increasing temperature, indicating a semiconducting behavior. The absolute value of the Seebeck coefficient gradually increased with an increase in temperature. The highest power factor (3.7 × 10-5 Wm-1 K-2 at 800°C) was obtained for Ca0.8Dy0.2MnO3 sintered at 1,250°C. In this study, we investigated the microstructure and thermoelectric properties of Ca0.8Dy0.2MnO3, depending on sintering temperature.
Huang, Yun-Ying; Huang, Xiong-Qin; Zhao, Li-Yan; Sun, Fang-Yun; Chen, Wen-Liang; Du, Jie-Yi; Yuan, Feng; Li, Jie; Huang, Xue-Lian; Liu, Jie; Lv, Xiao-Fei; Guan, Yong-Yuan; Chen, Jian-Wen; Wang, Guan-Lei
2014-11-01
Palmitate, a common saturated free fatty acid (FFA), has been demonstrated to induce preadipocyte apoptosis in the absence of adipogenic stimuli, suggesting that preadipocytes may be prone to apoptosis under adipogenic insufficient conditions, like type 2 diabetes mellitus (T2DM). ClC-3, encoding Cl(-) channel or Cl(-)/H(+) antiporter, is critical for cell fate choices of proliferation versus apoptosis under diseased conditions. However, it is unknown whether ClC-3 is related with preadipocyte apoptosis induced by palmitate or T2DM. Palmitate, but not oleate, induced apoptosis and increase in ClC-3 protein expression and endoplasmic reticulum (ER) stress in 3T3-L1 preadipocyte. ClC-3 specific siRNA attenuated palmitate-induced apoptosis and increased protein levels of Grp78, ATF4, CHOP and phosphorylation of JNK1/2, whereas had no effects on increased phospho-PERK and phospho-eIF2α protein expression. Moreover, the enhanced apoptosis was shown in preadipocytes from high-sucrose/fat, low-dose STZ induced T2DM mouse model with hyperglycemia, hyperlipidemia (elevated serum TG and FFA levels) and insulin resistance. ClC-3 knockout significantly attenuated preadipocyte apoptosis and the above metabolic disorders in T2DM mice. These data demonstrated that ClC-3 deficiency prevent preadipocytes against palmitate-induced apoptosis via suppressing ER stress, and also suggested that ClC-3 may play a role in regulating cellular apoptosis and disorders of glucose and lipid metabolism during T2DM.
Ma, Hongwei; Butler, Michael R.; Thapa, Arjun; Belcher, Josh; Yang, Fan; Baehr, Wolfgang; Biel, Martin; Michalakis, Stylianos; Ding, Xi-Qin
2015-01-01
Photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in phototransduction. Mutations in the cone CNG channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophies. We have shown endoplasmic reticulum (ER) stress-associated apoptotic cone death and increased phosphorylation of the ER Ca2+ channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in CNG channel-deficient mice. We also presented a remarkable elevation of cGMP and an increased activity of the cGMP-dependent protein kinase (protein kinase G, PKG) in CNG channel deficiency. This work investigated whether cGMP/PKG signaling regulates ER stress and IP3R1 phosphorylation in CNG channel-deficient cones. Treatment with PKG inhibitor and deletion of guanylate cyclase-1 (GC1), the enzyme producing cGMP in cones, were used to suppress cGMP/PKG signaling in cone-dominant Cnga3−/−/Nrl−/− mice. We found that treatment with PKG inhibitor or deletion of GC1 effectively reduced apoptotic cone death, increased expression levels of cone proteins, and decreased activation of Müller glial cells. Furthermore, we observed significantly increased phosphorylation of IP3R1 and reduced ER stress. Our findings demonstrate a role of cGMP/PKG signaling in ER stress and ER Ca2+ channel regulation and provide insights into the mechanism of cone degeneration in CNG channel deficiency. PMID:26124274
Nanoindentation investigation of heavy ion irradiated Ti 3(Si,Al)C 2
NASA Astrophysics Data System (ADS)
Liu, X. M.; Le Flem, M.; Béchade, J. L.; Monnet, I.
2010-06-01
Because of good damage tolerance, thermal stability and interesting mechanical properties, Ti 3SiC 2, belonging to M n+1AX n phases, has been considered as a potential candidate material for applications in the future Gas Fast nuclear Reactors (GFR) such as components of fuel cladding working between 500 °C and 800 °C. However, the outstanding mechanical properties of Ti 3SiC 2 related to a layered microstructure could be impacted by irradiation. In this work, high energy Kr and Xe ion irradiated Ti 3Si 0.95Al 0.05C 2 and Ti 3Si 0.90Al 0.10C 2 samples, provided by IMR Shenyang, Chinese Academy of Science, were characterized by nanoindentation technique. After irradiation at room temperature, an increase in hardness with irradiation dose was highlighted. Nevertheless, some damage tolerance remained because of preservation of the typical MAX layered structure. Irradiations at 300 °C and 500 °C lead to less significant increase suggesting irradiation defect annealing. A complete recovery of the properties at 800 °C seems to be obtained.
da Silva, Josefa B; Ramos, Tatiane M V; de Franco, Marcelo; Paiva, Delhi; Ho, Paulo Lee; Martins, Elizabeth A L; Pereira, Martha M
2009-08-01
The role of innate immune responses in protection against leptospirosis remains unclear. We examined the expression of the chemokines CCL2/JE (MCP-1), CCL3/MIP-1 alpha (MIP-1 alpha) and CXCL1/KC (IL-8) regarding resistance and susceptibility to leptospirosis in experimental mice models BALB/c and C3H/HeJ, respectively. A virulent strain of Leptospira interrogans serovar Copenhageni was used in this study. Twenty-five animals of each mouse strain of C3H/HeJ and BALB/c, were infected intraperitoneally with 10(6) cells. Five un-infected animals of each strain were kept as control. Mortality of C3H/HeJ mouse was observed while BALB/c mice were asymptomatic. The presence of leptospire DNA in tissues of infected animals was demonstrated by PCR. Chemokines were measured in serum, spleen, liver, kidney and lung of both strains of animals using immunoenzymatic assay (ELISA). Elevations in the levels of chemokines MCP-1 and IL-8 occurred in all organs and sera of C3H/HeJ and BALB/c infected mice. The levels of MIP-1 alpha were lower when compared to MCP-1 and IL-8 in all analyzed organs, with a slight increase in liver and kidney. Our results indicate that the expression of inflammatory mediators can vary greatly, depending on the tissue and mouse strains. It is possible that the resistance to Leptospira can be partially correlated to the increase of MIP-1 alpha observed in BALB/c mice, while an increasing and a sustained expression of MCP-1 and IL-8 in the lungs of C3H/HeJ mice can be correlated to the severity and progression of leptospirosis.
NASA Astrophysics Data System (ADS)
Yang, Mao-Sheng; Liu, Xiu-Bo; Fan, Ji-Wei; He, Xiang-Ming; Shi, Shi-Hong; Fu, Ge-Yan; Wang, Ming-Di; Chen, Shu-Fa
2012-02-01
The high temperature self-lubricating wear-resistant NiCr/Cr3C2-30%WS2 coating and wear-resistant NiCr/Cr3C2 coating were fabricated on 0Cr18Ni9 austenitic stainless steel by laser cladding. Phase constitutions and microstructures were investigated, and the tribological properties were evaluated using a ball-on-disc wear tester under dry sliding condition at room-temperature (17 °C), 300 °C and 600 °C, respectively. Results indicated that the laser clad NiCr/Cr3C2 coating consisted of Cr7C3 primary phase and γ-(Fe,Ni)/Cr7C3 eutectic colony, while the coating added with WS2 was mainly composed of Cr7C3 and (Cr,W)C carbides, with the lubricating WS2 and CrS sulfides as the minor phases. The wear tests showed that the friction coefficients of two coatings both decrease with the increasing temperature, while the both wear rates increase. The friction coefficient of laser clad NiCr/Cr3C2-30%WS2 is lower than the coating without WS2 whatever at room-temperature, 300 °C, 600 °C, but its wear rate is only lower at 300 °C. It is considered that the laser clad NiCr/Cr3C2-30%WS2 composite coating has good combination of anti-wear and friction-reducing capabilities at room-temperature up to 300 °C.
Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang
2015-01-01
Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835
Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang
2015-12-23
BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion.
Buono, Michael J; Krippes, Taylor; Kolkhorst, Fred W; Williams, Alexander T; Cabrales, Pedro
2016-02-01
What is the central question of this study? The purpose of the present study was to determine the effects of exercise-induced haemoconcentration and hyperthermia on blood viscosity. What is the main finding and its importance? Exercise-induced haemoconcentration, increased plasma viscosity and increased blood aggregation, all of which increased blood viscosity, were counterbalanced by increased red blood cell (RBC) deformability (e.g. RBC membrane shear elastic modulus and elongation index) caused by the hyperthermia. Thus, blood viscosity remained unchanged following prolonged moderate-intensity exercise in the heat. Previous studies have reported that blood viscosity is significantly increased following exercise. However, these studies measured both pre- and postexercise blood viscosity at 37 °C even though core and blood temperatures would be expected to have increased during the exercise. Consequently, the effect of exercise-induced hyperthermia on mitigating change in blood viscosity may have been missed. The purpose of this study was to isolate the effects of exercise-induced haemoconcentration and hyperthermia and to determine their combined effects on blood viscosity. Nine subjects performed 2 h of moderate-intensity exercise in the heat (37 °C, 40% relative humidity), which resulted in significant increases from pre-exercise values for rectal temperature (from 37.11 ± 0.35 to 38.76 ± 0.13 °C), haemoconcentration (haematocrit increased from 43.6 ± 3.6 to 45.6 ± 3.5%) and dehydration (change in body weight = -3.6 ± 0.7%). Exercise-induced haemoconcentration significantly (P < 0.05) increased blood viscosity by 9% (from 3.97 to 4.33 cP at 300 s(-1)), whereas exercise-induced hyperthermia significantly decreased blood viscosity by 7% (from 3.97 to 3.69 cP at 300 s(-1)). When both factors were considered together, there was no overall change in blood viscosity (from 3.97 to 4.03 cP at 300 s(-1)). The effects of exercise-induced haemoconcentration, increased plasma viscosity and increased red blood cell aggregation, all of which increased blood viscosity, were counterbalanced by increased red blood cell deformability (e.g. red blood cell membrane shear elastic modulus and elongation index) caused by the hyperthermia. Thus, blood viscosity remained unchanged following prolonged moderate-intensity exercise in the heat. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.
Chen, Taiyu; Zhu, Xin-Guang; Lin, Yongjun
2014-09-01
Engineering C4 photosynthetic metabolism into C3 crops is regarded as a major strategy to increase crop productivity, and clarification of the evolutionary processes of C4 photosynthesis can help the better use of this strategy. Here, Eleocharis baldwinii, a species in which C4 photosynthesis can be induced from a C3-C4 state under either environmental or ABA treatments, was used to identify the major transcriptional modifications during the process from C3-C4 to C4. The transcriptomic comparison suggested that in addition to the major differences in C4 core pathway, the pathways of glycolysis, citrate acid metabolism and protein synthesis were dramatically modified during the inducement of C4 photosynthetic states. Transcripts of many transporters, including not only metabolite transporters but also ion transporters, were dramatically increased in C4 photosynthetic state. Many candidate regulatory genes with unidentified functions were differentially expressed in C3-C4 and C4 photosynthetic states. Finally, it was indicated that ABA, auxin signaling and DNA methylation play critical roles in the regulation of C4 photosynthesis. In summary, by studying the different photosynthetic states of the same species, this work provides the major transcriptional differences between C3-C4 and C4 photosynthesis, and many of the transcriptional differences are potentially related to C4 development and therefore are the potential targets for reverse genetics studies.
Formation of MgO-B{sub 4}C composite via a thermite-based combustion reaction
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, L.L.; Munir, Z.A.; Holt, J.B.
1995-03-01
The combustion synthesis of MgO-B{sub 4}C composites was investigated by coupling a highly exothermic Mg-B{sub 2}O{sub 3} thermite reaction with a weakly exothermic B{sub 4}C formation reaction. Unlike the case of using Al as the reducing agent, the interaction between Mg and B{sub 2}O{sub 3} depends on the surrounding inert gas pressure due to the high vapor pressure of Mg. The interaction changes from one involving predominantly gaseous Mg and liquid B{sub 2}O{sub 3} to one involving liquid Mg and liquid B{sub 2}O{sub 3} as the pressure increases. At low inert gas pressure, the initiation temperature is found to bemore » just below the melting point of Mg (650 C). As the inert gas pressure increases, the vaporization loss of reactants is reduced, and this in turn increases the combustion temperature, which promotes greater grain growth of the product phases, MgO and B{sub 4}C. The particle size of B{sub 4}C increased from about 0.2 to 5 {mu}m as the pressure changed from 1 to 30 atm.« less
Liu, Hao; Smedskjaer, Morten M; Tao, Haizheng; Jensen, Lars R; Zhao, Xiujian; Yue, Yuanzheng
2016-04-28
It has been reported that the configurational heat capacity (C(p,conf)) first increases and then becomes saturated with increasing B2O3/SiO2 ratio in borate-silicate mixed glasses. Through Raman spectroscopy measurements, we have, in this work, found an implication for the intermediate range order (IRO) structural connection to the composition dependence of the C(p,conf) of borate-silicate mixed glasses. In the silica-rich compositions, the C(p,conf) rapidly increases with increasing B2O3 content. This is attributed to the increase of the content of the B-O-Si network units ([B2Si2O8](2-)) and 6-membered borate rings with 1 or 2 B(4). In the boron-rich compositions, the C(p,conf) is almost constant, independent of the increase in the B2O3/SiO2 ratio. This is likely attributed to the counteraction between the decrease of the fraction of two types of metaborate groups and the increase of the fraction of other borate superstructural units (particularly 6-membered borate rings). The overall results suggest that the glasses containing more types of superstructural units have a larger C(p,conf).
Ruiz-Narváez, Edward A; Yang, Yadong; Nakanishi, Yukiko; Kirchdorfer, Jill; Campos, Hannia
2005-12-01
Genetic variation in the APOC3 and APOA5 genes has been associated with plasma triglyceride concentrations and may affect the risk of myocardial infarction (MI). To assess whether APOC3/A5 haplotypes are associated with risk of MI, we examined three single-nucleotide polymorphisms (SNPs) in APOC3 (3238C>G, -455T>C, and -482C>T) and six SNPs in the APOA5 gene (-1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C) in incident cases (n = 1,703) of a first nonfatal MI matched for gender, age, and area of residence with population-based controls (n = 1,703). Conditional logistic regression models, adjusted for potential environmental confounders, were used for analysis. The common APOC3*222 haplotype was more frequent in cases than in controls (17.4% and 13.7%, respectively, P < 0.001) and was associated with increased risk of MI [odds ratio (OR) = 1.27; 95% confidence interval (95% CI), 1.09, 1.48] compared with APOC3*111 wild-type haplotype. This association was independent of the APOA5 SNPs. Although the APOC3 3238G, APOA5 -1131C, APOA5 c.-3G, and APOA5 c.1259C alleles were associated with higher triglyceride plasma concentrations, these effects could not explain the associations with MI in this population. In summary, this study supports the hypothesis that haplotypes in the APOC3 gene but not in the APOA5 gene increase susceptibility to MI.
Sun, Y; Zhou, R B; Chen, D M
2015-12-28
The aim of this study was to investigate correlations between apolipoprotein A-V (APOA5) -1131T>C and apolipoprotein C-III (APOC3) -455T>C polymorphisms and coronary heart disease (CHD). PubMed, Ovid, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched using combinations of keywords relating to these polymorphisms and CHD. Studies retrieved from database searches were screened using our stringent inclusion and exclusion criteria, and Comprehensive Meta-Analysis Version 2.0 software was used for statistical analyses. In total, 115 studies were initially retrieved and after further selection, 11 were included in the meta-analysis. These 11 articles comprised 4840 patients with CHD in the case group and 4913 healthy participants in the control group. Meta-analysis revealed that APOA5 -1131T>C and APOC3 -455T>C polymorphisms increased CHD risk. In addition, subgroup analysis by ethnicity showed that while the -1131T>C polymorphism elevated the risk of CHD in the Caucasian population under both allelic and dominant models, this increased risk was observed only under a dominant model in the Asian population. The results of our meta-analysis point to a strong link between both APOA5 -1131T>C and APOC3 -455T>C polymorphisms and an increased risk of CHD. Thus, these polymorphisms constitute important predictive indicators of CHD susceptibility.
Sugihara, T; Kobori, A; Imaeda, H; Tsujikawa, T; Amagase, K; Takeuchi, K; Fujiyama, Y; Andoh, A
2010-01-01
Recent studies have demonstrated that the complement system participates in the regulation of T cell functions. To address the local biosynthesis of complement components in inflammatory bowel disease (IBD) mucosa, we investigated C3 and interleukin (IL)-17 mRNA expression in mucosal samples obtained from patients with IBD. The molecular mechanisms underlying C3 induction were investigated in human colonic subepithelial myofibroblasts (SEMFs). IL-17 and C3 mRNA expressions in the IBD mucosa were evaluated by real-time polymerase chain reaction. The C3 levels in the supernatant were determined by enzyme-linked immunosorbent assay. IL-17 and C3 mRNA expressions were elevated significantly in the active lesions from ulcerative colitis (UC) and Crohn's disease (CD) patients. There was a significant positive correlation between IL-17 and C3 mRNA expression in the IBD mucosa. IL-17 stimulated a dose- and time-dependent increase in C3 mRNA expression and C3 secretion in colonic SEMFs. The C3 molecules secreted by colonic SEMFs were a 115-kDa α-chain linked to a 70-kDa β-chain by disulphide bonds, which was identical to serum C3. The IL-17-induced C3 mRNA expression was blocked by p42/44 mitogen-activated protein kinase (MAPK) inhibitors (PD98059 and U0216) and a p38 MAPK inhibitor (SB203580). Furthermore, IL-17-induced C3 mRNA expression was inhibited by an adenovirus containing a stable mutant form of IκBα. C3 and IL-17 mRNA expressions are enhanced, with a strong correlation, in the inflamed mucosa of IBD patients. Part of these clinical findings was considered to be mediated by the colonic SEMF response to IL-17. PMID:20089077
Al-Khayal, Khayal; Alafeefy, Ahmed; Vaali-Mohammed, Mansoor-Ali; Mahmood, Amer; Zubaidi, Ahmed; Al-Obeed, Omar; Khan, Zahid; Abdulla, Maha; Ahmad, Rehan
2017-01-03
Colorectal cancer (CRC) is the 3 rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.
Change in Sedentary Time, Physical Activity, Bodyweight, and HbA1c in High-Risk Adults.
McCarthy, Matthew; Edwardson, Charlotte L; Davies, Melanie J; Henson, Joseph; Gray, Laura; Khunti, Kamlesh; Yates, Thomas
2017-06-01
In recent years, there has been a migration toward the use of glycated hemoglobin (HbA1c) in determining glycemic control. This study aimed to quantify the associations between changes in body weight, sedentary time, and moderate to vigorous physical activity (MVPA) time with HbA1c levels for a 3-yr period among adults at high risk of type 2 diabetes. This study reports baseline and 3-yr follow-up data from the Walking Away from Type 2 Diabetes study. ActiGraph GT3X accelerometers captured sedentary time and MVPA. Linear regression examined the independent associations of changes in sedentary time, MVPA, and body weight with HbA1c between baseline and 3-yr follow-up. The sample composed of 489 participants (mean age = 64.2 ± 7.3 yr, body mass index = 31.7 ± 5.1, 63.4% male) with valid baseline and follow-up accelerometer, body weight, and HbA1c data. After adjustment for known confounders, an increase in MVPA time (per 30 min·d) was associated with a decrease in HbA1c percentage (β = -0.11 [-0.18 to -0.05], P = 0.001), and an increase in body weight (per 6 kg) was associated with an increase in HbA1c percentage (β = 0.08 [0.04-0.12], P < 0.001). The presence of dysglycemia at baseline (HbA1c ≥ 6.0%) strengthened these associations (P < 0.001 for interactions). Change in sedentary time was not significantly associated with change in HbA1c after adjustment for change in MVPA time. Increases in MVPA and body weight were associated with a reduction and increase in HbA1c, respectively, particularly in those with dysglycemia. Quantifying the effect that health behavior changes have on HbA1c can be used to inform prevention programs.
Sun, Wei; Li, Lian; Li, Li-jia; Yang, Qing-qing; Zhang, Zhi-rong; Huang, Yuan
2017-01-01
Active tumor-targeting approaches using specific ligands have drawn considerable attention over the years. However, a single ligand often fails to simultaneously target the cancer cell surface and subcellular organelles, which limits the maximum therapeutic efficacy of delivered drugs. We describe a polymeric delivery system modified with the G3-C12 peptide for sequential dual targeting. In this study, galectin-3-targeted G3-C12 peptide was conjugated onto the N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer for the delivery of D(KLAKLAK)2 (KLA) peptide. G3-C12-HPMA-KLA exhibited increased receptor-mediated internalization into galectin-3-overexpressing PC-3 cells. Furthermore, G3-C12 peptide also directed HPMA-KLA conjugates to mitochondria. This occurred because the apoptosis signal triggered the accumulation of galectin-3 in mitochondria, and the G3-C12 peptide that specifically bound to galectin-3 was trafficked along with its receptor intracellularly. As a result, G3-C12-HPMA-KLA disrupted the mitochondrial membrane, increased the generation of reactive oxygen species (ROS) and induced cytochrome c release, which ultimately resulted in enhanced cytotoxicity. An in vivo study revealed that the G3-C12 peptide significantly enhanced the tumor accumulation of the KLA conjugate. In addition, G3-C12-HPMA-KLA exhibited the best therapeutic efficacy and greatly improved the animal survival rate. Our work demonstrates that G3-C12 is a promising ligand with dual-targeting functionality. PMID:28065935
Whitney, Spencer M; Sharwood, Robert E; Orr, Douglas; White, Sarah J; Alonso, Hernan; Galmés, Jeroni
2011-08-30
Improving global yields of important agricultural crops is a complex challenge. Enhancing yield and resource use by engineering improvements to photosynthetic carbon assimilation is one potential solution. During the last 40 million years C(4) photosynthesis has evolved multiple times, enabling plants to evade the catalytic inadequacies of the CO(2)-fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco). Compared with their C(3) ancestors, C(4) plants combine a faster rubisco with a biochemical CO(2)-concentrating mechanism, enabling more efficient use of water and nitrogen and enhanced yield. Here we show the versatility of plastome manipulation in tobacco for identifying sequences in C(4)-rubisco that can be transplanted into C(3)-rubisco to improve carboxylation rate (V(C)). Using transplastomic tobacco lines expressing native and mutated rubisco large subunits (L-subunits) from Flaveria pringlei (C(3)), Flaveria floridana (C(3)-C(4)), and Flaveria bidentis (C(4)), we reveal that Met-309-Ile substitutions in the L-subunit act as a catalytic switch between C(4) ((309)Ile; faster V(C), lower CO(2) affinity) and C(3) ((309)Met; slower V(C), higher CO(2) affinity) catalysis. Application of this transplastomic system permits further identification of other structural solutions selected by nature that can increase rubisco V(C) in C(3) crops. Coengineering a catalytically faster C(3) rubisco and a CO(2)-concentrating mechanism within C(3) crop species could enhance their efficiency in resource use and yield.
Preparation and Properties of (YCa)(TiMn)O3−δ Ceramics Interconnect of Solid Oxide Fuel Cells
Liou, Yi-Cheng; Tsai, Wen-Chou; Yen, Hao-Hsuan; Chang, Yung-Chia
2015-01-01
(YCa)(TiMn)O3–δ ceramics prepared using a reaction-sintering process were investigated. Without any calcination involved, the mixture of raw materials was pressed and sintered directly. Y2Ti2O7 instead of YTiO3 formed when a mixture of Y2O3 and TiO2 with Y/Ti ratio 1/1 were sintered in air. Y2Ti2O7, YTiO2.085 and some unknown phases were detected in Y0.6Ca0.4Ti0.6Mn0.4O3–δ. Monophasic Y0.6Ca0.4Ti0.4Mn0.6O3–δ ceramics were obtained after 1400–1500 °C sintering. Dense Y0.6Ca0.4Ti0.4Mn0.6O3–δ with a density 4.69 g/cm3 was observed after 1500 °C/4 h sintering. Log σ for Y0.6Ca0.4Ti0.6Mn0.4O3–δ increased from –3.73 Scm–1 at 350 °C to –2.14 Scm–1 at 700 °C. Log σ for Y0.6Ca0.4Ti0.4Mn0.6O3–δ increased from –2.1 Scm–1 at 350 °C to –1.36 Scm–1 at 700 °C. Increasing Mn content decreased activation energy Ea and increased electrical conductivity. Reaction-sintering process is proved to be a simple and effective method to obtain (YCa)(TiMn)O3–δ ceramics for interconnects in solid oxide fuel cells. PMID:28793436
Cho, Jungeun; Park, Minkyu; Choi, Doil; Lee, Seung Koo
2012-01-30
Garlic greening occurs when garlic cloves are stored at low temperature, increasing 1-propenyl cysteine sulfoxide, which is induced by γ-glutamyl transpeptidase (GGT) activity. Although the metabolism of the γ-glutamyl peptide is important for the biosynthesis of green pigments in crushed garlic cloves, garlic GGT is poorly characterised. For the analysis of GGT at the gene level, the garlic GGT sequence was partially cloned using an onion GGT sequence. The relationship between garlic greening and related gene expressions, depending on storage condition, was investigated using reverse transcription polymerase chain reaction for garlic GGT and alliinase. Three storage conditions were set: A, storage at a constant temperature of 20 °C; B, storage at 20 °C for 3 months and then transfer to 0 °C for an additional 3 months; C, storage at 0 °C for 3 months and then transfer to 20 °C for an additional 3 months. GGT expression increased under storage condition B and decreased under storage condition C. However, alliinase expression was not affected by storage condition. Greening in crushed garlic cloves increases with increasing GGT expression at low temperature, while alliinase expression is not affected. Copyright © 2011 Society of Chemical Industry.
Vila Petroff, M; Vittone, L; Mundiña, C; Chiappe de Cingolani, G; Alicia, M
1992-01-01
In intact ventricular strips from toad heart, we studied the relaxant or positive lusitropic effect of different interventions known to increase intracellular cAMP levels. Isoproterenol increased developed tension (DT), maximal rate of contraction (+T), and maximal velocity of relaxation (-T). From 10(-8) to 10(-4)M isoproterenol, -T increased proportionally more than +T being the ratio +T/-T significantly decreased. A single dose of isoproterenol (3 x 10(-8)M) increased cAMP levels from 0.174 +/- 0.022 to 0.329 +/- 0.039 pmoles/mg ww (P < 0.05), increased contractility by 69 +/- 13% and decreased +T/-T by 18.5 +/- 4.55%. Administration of 10(-3)M of dibutyryl cyclic AMP (dcAMP) significantly increased DT and +T and decreased the ratio +T/-T. Similar effects were obtained with milrinone, a specific cAMP phosphodiesterase inhibitor. Papaverine, a non selective phosphodiesterase inhibitor, failed to increase +T but significantly increased -T. In chemically skinned ventricular trabeculae, calcium sensitivity of the myofibrils was significantly increased by 10(-5)M of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX). 10(-3)M dcAMP failed to affect calcium sensitivity of chemically skinned ventricular trabeculae when given alone, but produced a decrease in calcium sensitivity of the myofibrils in the presence of 10(-5)M of either IBMX or papaverine. The results would indicate that the relaxant effect of isoproterenol is mediated in toad ventricle by an increase in intracellular cAMP levels. They furthermore suggest that a decrease in myofilament sensitivity to calcium may be a mechanism by which cAMP produces its relaxant effect.
Han, Kyung Ah; Woo, Doyeon; Kim, Seungjoon; Choii, Gayoung; Jeon, Sangmin; Won, Seoung Youn; Kim, Ho Min; Heo, Won Do; Um, Ji Won; Ko, Jaewon
2016-04-27
Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10-25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semiquantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 μW) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 μW) further triggered the activation of phospholipase C-γ1 and CREB independently of PTPσ. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTPσ complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes. In this study, we present several lines of experimental evidences to support the conclusion that neurotrophin-3 (NT-3) modulates the synaptic adhesion pathway involving neurotrophin receptor tyrosine kinase C (TrkC) and presynaptic protein tyrosine phosphatase σ (PTPσ) in a bidirectional manner at excitatory synapses. NT-3 acts in concentration-independent manner to facilitate TrkC-mediated presynaptic differentiation, whereas it acts in a concentration-dependent manner to exert differential effects on TrkC-mediated organization of postsynaptic development. We further investigated TrkC extracellular ligand binding, intracellular signaling pathways, and kinase activity in NT-3-induced synapse development. Last, we found that interneuronal differences in TrkC levels regulate the synapse number. Overall, these results suggest that NT-3 functions as a positive modulator of synaptogenesis involving TrkC and PTPσ. Copyright © 2016 the authors 0270-6474/16/364817-16$15.00/0.
Can the tricyanomethanide anion improve CO2 absorption by acetate-based ionic liquids?
Lepre, L F; Szala-Bilnik, J; Pison, L; Traïkia, M; Pádua, A A H; Ando, R A; Costa Gomes, M F
2017-05-17
Carbon dioxide absorption by mixtures of two ionic liquids with a common cation-1-butyl-3-methylimidazolium acetate, [C 4 C 1 Im][OAc], and 1-butyl-3-methylimidazolium tricyanomethanide, [C 4 C 1 Im][C(CN) 3 ]-was determined experimentally at pressures below atmospheric pressure as a function of temperature between 303 K and 343 K, and at 303 K as a function of pressure up to 10 bar. It is observed that the absorption of carbon dioxide decreases with increasing tricyanomethanide anion concentration and with increasing temperature, showing a maximum of 0.4 mole fraction of carbon dioxide in pure [C 4 C 1 Im][OAc] at 303 K. At this temperature, the CO 2 absorption in the mixtures [C 4 C 1 Im][OAc] (1-x) [C(CN) 3 ] x is approximately the mole-fraction average of that in the pure ionic liquids. By applying an appropriate thermodynamic treatment, after identification of the species in solution, it was possible to calculate both the equilibrium constant, K eq , and Henry's law constant, K H , in the different mixtures studied thus obtaining an insight into the relative contribution of chemical and physical absorption of the gas. It is shown that chemical sorption proceeds through a 1 : 2 stoichiometry between CO 2 and acetate-based ionic liquid. The presence of the C(CN) 3 - anion does not significantly affect the chemical reaction of the gas with the solvent (K eq = 75 ± 2 at 303 K) but leads to lower Henry's law constants (from K H = 77.8 ± 0.6 bar to K H = 49.5 ± 0.5 bar at 303 K), thus pointing towards larger physical absorption of the gas. The tricyanomethanide anion considerably improves the mass transfer by increasing the fluidity of the absorbent as proven by the larger diffusivities of all the ions when the concentration of the C(CN) 3 - anion increases in the mixtures.
White, K.P.; Langley, J.A.; Cahoon, D.R.; Megonigal, J.P.
2012-01-01
Plants alter biomass allocation to optimize resource capture. Plant strategy for resource capture may have important implications in intertidal marshes, where soil nitrogen (N) levels and atmospheric carbon dioxide (CO2) are changing. We conducted a factorial manipulation of atmospheric CO2 (ambient and ambient + 340 ppm) and soil N (ambient and ambient + 25 g m-2 year-1) in an intertidal marsh composed of common North Atlantic C3 and C4 species. Estimation of C3 stem turnover was used to adjust aboveground C3 productivity, and fine root productivity was partitioned into C3-C4 functional groups by isotopic analysis. The results suggest that the plants follow resource capture theory. The C3 species increased aboveground productivity under the added N and elevated CO2 treatment (P 2 alone. C3 fine root production decreased with added N (P 2 (P = 0.0481). The C4 species increased growth under high N availability both above- and belowground, but that stimulation was diminished under elevated CO2. The results suggest that the marsh vegetation allocates biomass according to resource capture at the individual plant level rather than for optimal ecosystem viability in regards to biomass influence over the processes that maintain soil surface elevation in equilibrium with sea level.
The effect of oral and intraurethral trimetazidine use on urethral healing
Ayyildiz, Ali; Ayyildiz, Sema Nur; Benli, Erdal; Erdem, Havva; Cirrik, Selma; Noyan, Tevfik; Germiyanoglu, R. Cankon; Çirakoglu, Abdullah
2016-01-01
Objective(s): We aimed to study the effect of trimetazidine (TMZ) on urethral wound repair. Materials and Methods: A total of 52 male rats were used; 8 groups were formed: 1-week and 3-week control (C1, C3), sham (S1, S3), oral (OT1, OT3), and intraurethral TMZ (IUT1, IUT3) groups. Serum and urine total antioxidant capacity (TAC), total oxidant capacity (TOC), and 8-hydroxy-deoxy-guanosine (8-OHdG) were studied. Hematoxyline-Eosin was used for the histopathological study. In addition, tumor necrosis factor alpha (TNF- α), interleukin 1α, and β levels were compared across groups by an immunohistochemical method. Results: There were significant differences between C3 and IUT3, OT3 and IUT3 with respect to serum TAC in 3-week groups (P=0.013; P =0.001). Serum TOC levels were significantly different between C3 and IUT3; S3 and OT3; and OT3 and IUT3 groups (P =0.024; P =0.019; P =0.000, respectively). Serum 8-OHdG levels were significantly different between C3 and OT3 groups (P=0.033). In the immunohistochemical examination, C1 and OT1; C1 and IUT1; and S1, S3, OT1, OT3, IUT1 groups were significantly different with respect to IL-1β staining (P=0.007; P =0.000; P=0.009), while there was a significant difference between C3 and S3 with respect to IL-1β (P =0.000). Conclusion: TMZ increased urinary total oxidant level; while increasing serum TAC levels in the long-term. It also reduced serum TAC levels in urethral use and caused an increase in serum TOC levels with minimal effects on DNA injury and repair. No effect was detected on IL1 α and TNF, but partially reduced the effect on IL-1 β levels. PMID:27803779
Libik-Konieczny, Marta; Surówka, Ewa; Kuźniak, Elżbieta; Nosek, Michał; Miszalski, Zbigniew
2011-07-01
Mesembryathemum crystallinum plants performing C(3) or CAM (crassulacean acid metabolism) appear to be highly resistant to Botrytis cinerea as well as to Pseudomonas syringae. Fungal hyphae growth was restricted to 48h post-inoculation (hpi) in both metabolic types and morphology of hyphae differed between those growing in C(3) and CAM plants. Growth of bacteria was inhibited significantly 24 hpi in both C(3) and CAM plants. B. cinerea and P. syringae infection led to an increase in the concentration of H(2)O(2) in C(3) plants 3 hpi, while a decrease in H(2)O(2) content was observed in CAM performing plants. The concentration of H(2)O(2) returned to the control level 24 and 48 hpi. Changes in H(2)O(2) content corresponded with the activity of guaiacol peroxidase (POD), mostly 3 hpi. We noted that its activity decreased significantly in C(3) plants and increased in CAM plants in response to inoculation with both pathogens. On the contrary, changes in the activity of CAT did not correlate with H(2)O(2) level. It increased significantly after interaction of C(3) plants with B. cinerea or P. syringae, but in CAM performing plants, the activity of this enzyme was unchanged. Inoculation with B. cinerea or P. syringae led to an increase in the total SOD activity in C(3) plants while CAM plants did not exhibit changes in the total SOD activity after interaction with both pathogens. In conclusion, the pathogen-induced changes in H(2)O(2) content and in SOD, POD and CAT activities in M. crystallinum leaves, were related to the photosynthetic metabolism type of the stressed plants rather than to the lifestyle of the invading pathogen. Copyright © 2011 Elsevier GmbH. All rights reserved.
High temperature XRD of Cu2GeSe3
NASA Astrophysics Data System (ADS)
Premkumar D., S.; Chetty, Raju; Malar, P.; Mallik, Ramesh Chandra
2015-06-01
The Cu2GeSe3 is prepared by solid state synthesis method. The high temperature XRD has been done at different temperature from 30 °C to 450 °C. The reitveld refinement confirms Cu2GeSe3 phase and orthorhombic crystal structure. The lattice constants are increasing with increase in the temperature and their rate of increase with respect to temperature are used for finding the thermal expansion coefficient. The calculation of the linear and volume coefficient of thermal expansion is done from 30 °C to 400 °C. Decrease in the values of linear expansion coefficients with temperature are observed along a and c axis. Since thermal expansion coefficient is the consequence of the distortion of atoms in the lattice; this can be further used to find the minimum lattice thermal conductivity at given temperature.
Yee, Wee L
2016-02-01
Western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), is a quarantine pest of sweet cherry (Prunus avium (L.) L.) that is managed using insecticides, including spinosad, an organic compound that can be applied in low spray volumes. Identifying factors that can increase the efficacy of spinosad can be useful for improving fly control. Here, the major objective was to determine if temperature mediates kill and oviposition of R. indifferens in the presence of low spinosad coverage in the laboratory. Experiments were conducted by placing flies in cages with cherries and with a Petri dish containing 3-12 small spots of dry spinosad at 18.3, 23.9, and 29.4°C. Effects of spinosad rates were also determined. More flies were killed at 23.9 and 29.4°C than at 18.3°C by 1-7 d post exposure. More flies were killed at 29.4 than 23.9°C by 1 d post exposure. However, flies laid more eggs at these temperatures than at 18.3°C. Higher spinosad rates increased kill and decreased oviposition, but even within the highest rate, oviposition was greater at 29.4 than 18.3°C. More flies walked over 5-min observation periods at 29.4 and 23.9°C than 18.3°C, suggesting higher temperatures up to 29.4°C increase kill by increasing fly contact with spinosad as well as increase oviposition rate. Results suggest that spinosad rates in sprays used against R. indifferens should be greater at higher than lower ambient temperatures. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by a US Government employee and is in the public domain in the US.
Melton, Elaina M.; Cerny, Ronald L.; DiRusso, Concetta C.; Black, Paul N.
2014-01-01
In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4, for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4hr. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The trafficking of exogenous C16:0 and C22:6 into PA was significant where there was 6.9- and 5.3-fold increased incorporation, respectively, over the control; C18:3 and C20:4 also trended to increase in the PA pool while there were no changes for C18:1 and C18:2. The trafficking of C18:3 into PC and PI trended higher and approached significance. In the case of C20:4, expression of FATP2 resulted in increases in all four classes of phospholipid, indicating little selectivity. In the case of C22:6, there were significant increases of this exogenous fatty acids being trafficking into PC and PI. Collectively, these data support the conclusion that FATP2 has a dual function in the pathways linking the transport and activation of exogenous fatty acids. We discuss the differential roles of FATP2 and its role in both fatty acid transport and fatty acid activation in the context of lipid homeostasis. PMID:24113382
Melton, Elaina M; Cerny, Ronald L; DiRusso, Concetta C; Black, Paul N
2013-11-01
In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4, for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4h. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The trafficking of exogenous C16:0 and C22:6 into PA was significant where there was 6.9- and 5.3-fold increased incorporation, respectively, over the control; C18:3 and C20:4 also trended to increase in the PA pool while there were no changes for C18:1 and C18:2. The trafficking of C18:3 into PC and PI trended higher and approached significance. In the case of C20:4, expression of FATP2 resulted in increases in all four classes of phospholipid, indicating little selectivity. In the case of C22:6, there were significant increases of this exogenous fatty acids being trafficking into PC and PI. Collectively, these data support the conclusion that FATP2 has a dual function in the pathways linking the transport and activation of exogenous fatty acids. We discuss the differential roles of FATP2 and its role in both fatty acid transport and fatty acid activation in the context of lipid homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Kan; Jesse, Stephen; Wang, Shanfeng
2012-01-01
The thermal properties, morphological development, crystallization behavior, and miscibility of semicrystalline PCL and its 25, 50, and 75 wt% blends with amorphous PPF in spin-coated thin films crystallized at various crystallization temperatures (T{sub c}) from 25 to 52 C are investigated. The surface roughness of PPF/PCL ({phi}{sub PCL} = 75%) films increases with increasing T{sub c} and consequently the adsorption of serum proteins is also increased. No significant variance is found in surface hydrophilicity or in mouse MC3T3-E1 cell attachment, spreading, and proliferation on PPF/PCL ({phi}{sub PCL} = 75%) films crystallized isothermally at 25, 37, and 45 C, because ofmore » low ridge height, nonuniformity in structures, and PPF surface segregation« less
Sari Erkan, Hanife; Onkal Engin, Guleda
2018-02-22
This study investigated the effect of carbon to nitrogen (C/N) ratio of influent wastewater on performance and activated sludge properties at a sludge retention time of 5 d in a submerged membrane bioreactor. The chemical oxygen demand and ammonia-Nitrogen (NH 3 -N) removal efficiencies were found to be over 96.3% and 86.9% in the sMBRs having different C/N ratios. It was found that total extracellular polymeric substances and total soluble microbial products increased with an increase in C/N ratio. It was also observed that critical flux, relative hydrophobicity and zeta potential values decreased, and capillary suction time, particle size and viscosity of sludge increased as the C/N ratio increased.
Clausen, Per Axel; Liu, Zhe; Kofoed-Sørensen, Vivi; Little, John; Wolkoff, Peder
2012-01-17
Emissions of di-(2-ethylhexyl) phthalate (DEHP) from one type of polyvinylchloride (PVC) flooring with approximately 13% (w/w) DEHP as plasticizer were measured in the Field and Laboratory Emission Cell (FLEC). The gas-phase concentrations of DEHP versus time were measured at air flow rate of 450 mL·min(-1) and five different temperatures: 23 °C, 35 °C, 47 °C, 55 °C, and 61 °C. The experiments were terminated two weeks to three months after steady-state was reached and the interior surface of the FLECs was rinsed with methanol to determine the surface concentration of DEHP. The most important findings are (1) DEHP steady-state concentrations increased greatly with increasing temperature (0.9 ± 0.1 μg·m(-3), 10 ± 1 μg·m(-3), 38 ± 1 μg·m(-3), 91 ± 4 μg·m(-3), and 198 ± 5 μg·m(-3), respectively), (2) adsorption to the chamber walls decreased greatly with increasing temperature (measured partition coefficient between FLEC air and interior surface are: 640 ± 146 m, 97 ± 20 m, 21 ± 5 m, 11 ± 2 m, and 2 ± 1 m, respectively), (3) gas-phase DEHP concentration in equilibrium with the vinyl flooring surface is close to the vapor pressure of pure DEHP, and (4) with an increase of temperature in a home from 23 to 35 °C, the amount of DEHP in the gas- and particle-phase combined is predicted to increase almost 10-fold. The amount in the gas-phase increases by a factor of 24 with a corresponding decrease in the amount on the airborne particles.
Dai, Libing; Liu, Zhihe; Liang, Weiguo; Yao, Yicun; Xu, Jiakel; Ye, Dongping; Zou, Longqiang; Shen, Yan
2015-04-01
To explore the effect of Vitamin C (Vit C) on the apoptosis of human nucleus pulposus (NP) cells induced by tumor necrosis factor a (TNF-alpha) and serum deprivation. The NP cells were isolated from patients undergoing spine corrective operation by collagenase trypsin. The experiment was divided into 3 groups: Vit C group (group A), TNF-alpha group (group B), and serum deprivation group (group C). Group A was reassigned to Al subgroup (basic medium), A2 subgroup (100 pg/mL Vit C), and A3 subgroup (200 pg/mL Vit C). Group B was reassigned to B0 subgroup (control group), Bi subgroup (100 ng/mL TNF-alpha), B2 subgroup (100 microg/mL Vit C+100 ng/mL TNF-alpha), and B3 subgroup (200 microg/mL Vit C+100 ng/mL TNF-alpha). Group C was reassigned to C0 subgroup (Control group), C1 subgroup (2% FBS), C2 subgroup (2% FBS+100 microg/mL Vit C), and C3 subgroup (2% FBS+200 microg/mL Vit C). After application of 100 pg/mL or 200 microg/mL Vit C for 24 hours, NP cells were stimulated by TNF-alpha and serum deprivation, then the apoptosis rate of NP cells was detected by a flow cytometry, and the gene expressions of the extracellular matrix of NP cells (collagen type I, collagen type II, aggrecan, and Sox9) and apoptosis related genes (p53, FAS, and Caspase 3) were detected by real-time fluoroscent quantitative PCR. Results Group A: Vit C could significantly reduce the apoptosis rate and gene expressions of p53, FAS, and Caspase 3 of NP cells in A2 and A3 subgroups when compared with Al subgroup (P<0.05), but there was no significant difference between A2 subgroup and A3 subgroup (P>0.05); Vit C could promote the expressions of the extracellular matrix (collagen type I, collagen type II, aggrecan, and Sox9) of NP cells in a concentration dependent manner (P<0.05). Group B: TNF-alpha significantly increased the apoptosis rate and the gene expressions of p53, FAS, and Caspase 3 in B1 subgroup when compared with B0 subgroup (P<0.05); however, Vit C significantly increased the apoptosis rate and the gene expressions in B2 subgroup, and significantly decreased them in B3 subgroup when compared with B1 subgroup (P<0.05). Group C: 2% FBS significantly increased the apoptosis rate of NP cells and significantly reduced the gene expressions of p53, FAS, and Caspase 3 in C1 subgroup when compared with C0 subgroup (P<0.05); Vit C could significantly reduce the apoptosis rate and gene expressions of p53, FAS, and Caspase 3 in C3 subgroup, but it could significantly increase them in C2 subgroup when compared with C1 subgroup (P<0.05). Vit C can promote the synthesis and secretion of extracellular matrix of NP cells. 200 microg/mL Vit C may delay the apoptosis induced by TNF-alpha and serum deprivation, indicating the potential therapeutic effect of Vit C on intervertebral disc degeneration.
Lane, Thirusha; Pinney, Jennifer H; Gilbertson, Janet A; Hutt, David F; Rowczenio, Dorota M; Mahmood, Shameem; Sachchithanantham, Sajitha; Fontana, Marianna; Youngstein, Taryn; Quarta, Candida C; Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N; Lachmann, Helen J
2017-09-01
Systemic AA amyloidosis is a serious complication of chronic inflammation; however, there are relatively few published data on its incidence. We investigated the changing epidemiology of AA amyloidosis over a 25-year period at a single national referral centre. We conducted a retrospective study of all patients diagnosed with AA amyloidosis who had attended the centre between 1990 and 2014 inclusive. Six hundred and twenty-five patients were studied in three cohorts: C1: 1990-1997; C2: 1998-2006; C3: 2007-2014. Mean age at presentation increased from 46 in C1 to 56 in C3 (p < .0001). The proportion of South Asian patients increased from 4% in C1 to 17% in C3 (p = .0006). Comparison of underlying diseases between C1 and C3 revealed a reduction in patients with juvenile idiopathic arthritis from 25% to 2% (p < .0001), but an increase in patients with chronic infection due to intravenous recreational drug use from 1% to 13% (p < .0001), and uncharacterized inflammatory disorders from 10% to 27% (p <.0001). More patients were in end-stage renal failure at presentation in C3 (29%) than C1 (15%) (p = .0028). Median age at death was later in C3 (62 years) than C1 (54 years) (p = .0012). These data suggest both falling incidence and better outcome in AA amyloidosis over a quarter of a century, reflecting advances in therapeutics and overall management of complex chronic disease in an ageing population. AA amyloidosis of uncertain aetiology presents an emerging major problem. Newer techniques such as next-generation sequencing may aid diagnosis and effective treatment, thereby improving overall survival.
NASA Astrophysics Data System (ADS)
Xu, Jian; Wang, Guanxi; Fan, Jiajie; Liu, Baoshun; Cao, Shaowen; Yu, Jiaguo
2015-01-01
Dye-sensitized solar cells (DSSCs) were fabricated by using g-C3N4 modified TiO2 nanosheets (CTS) as photoanode materials in this research. A thin layer of g-C3N4 was coated on the surface of TiO2 nanosheets by simply heating the mixture of TiO2 nanosheets and urea, which led to the formation of TiO2@g-C3N4 nanosheet heterostructure. The experimental results showed that the photoelectric conversion efficiency of DSSCs was obviously improved after modified by g-C3N4. The measurements of I-V characteristic indicated that the introduction of g-C3N4 could increase both the open circuit voltage and short-circuit photocurrent density. Along with the analysis of electrochemical impedance spectroscopy, it is considered that the thin layer of g-C3N4 can act as the blocking layer for electron backward recombination with electrolyte, which can be used as the functional material to increase the DSSC performance.
Raccuglia, Margherita; Lloyd, Alex; Filingeri, Davide; Faulkner, Steve H; Hodder, Simon; Havenith, George
2016-02-01
Passive muscle heating has been shown to reduce the drop in post-warm-up muscle temperature (Tm) by about 25% over 30 min, with concomitant sprint/power performance improvements. We sought to determine the role of leg blood flow in this cooling and whether optimising the heating procedure would further benefit post-warm-up T m maintenance. Ten male cyclists completed 15-min sprint-based warm-up followed by 30 min recovery. Vastus lateralis Tm (Tmvl) was measured at deep-, mid- and superficial-depths before and after the warm-up, and after the recovery period (POST-REC). During the recovery period, participants wore water-perfused trousers heated to 43 °C (WPT43) with either whole leg heating (WHOLE) or upper leg heating (UPPER), which was compared to heating with electrically heated trousers at 40 °C (ELEC40) and a non-heated control (CON). The blood flow cooling effect on Tmvl was studied comparing one leg with (BF) and without (NBF) blood flow. Warm-up exercise significantly increased Tmvl by ~3 °C at all depths. After the recovery period, BF Tmvl was lower (~0.3 °C) than NBF Tmvl at all measured depths, with no difference between WHOLE versus UPPER. WPT43 reduced the post-warm-up drop in deep-Tmvl (-0.12 °C ± 0.3 °C) compared to ELEC40 (-1.08 ± 0.4 °C) and CON (-1.3 ± 0.3 °C), whereas mid- and superficial-Tmvl even increased by 0.15 ± 0.3 and 1.1 ± 1.1 °C, respectively. Thigh blood flow contributes to the post-warm-up Tmvl decline. Optimising the external heating procedure and increasing heating temperature of only 3 °C successfully maintained and even increased T mvl, demonstrating that heating temperature is the major determinant of post-warm-up Tmvl cooling in this application.
Piezoresistive effect in p-type 3C-SiC at high temperatures characterized using Joule heating
Phan, Hoang-Phuong; Dinh, Toan; Kozeki, Takahiro; Qamar, Afzaal; Namazu, Takahiro; Dimitrijev, Sima; Nguyen, Nam-Trung; Dao, Dzung Viet
2016-01-01
Cubic silicon carbide is a promising material for Micro Electro Mechanical Systems (MEMS) applications in harsh environ-ments and bioapplications thanks to its large band gap, chemical inertness, excellent corrosion tolerance and capability of growth on a Si substrate. This paper reports the piezoresistive effect of p-type single crystalline 3C-SiC characterized at high temperatures, using an in situ measurement method. The experimental results show that the highly doped p-type 3C-SiC possesses a relatively stable gauge factor of approximately 25 to 28 at temperatures varying from 300 K to 573 K. The in situ method proposed in this study also demonstrated that, the combination of the piezoresistive and thermoresistive effects can increase the gauge factor of p-type 3C-SiC to approximately 20% at 573 K. The increase in gauge factor based on the combination of these phenomena could enhance the sensitivity of SiC based MEMS mechanical sensors. PMID:27349378
Piezoresistive effect in p-type 3C-SiC at high temperatures characterized using Joule heating
NASA Astrophysics Data System (ADS)
Phan, Hoang-Phuong; Dinh, Toan; Kozeki, Takahiro; Qamar, Afzaal; Namazu, Takahiro; Dimitrijev, Sima; Nguyen, Nam-Trung; Dao, Dzung Viet
2016-06-01
Cubic silicon carbide is a promising material for Micro Electro Mechanical Systems (MEMS) applications in harsh environ-ments and bioapplications thanks to its large band gap, chemical inertness, excellent corrosion tolerance and capability of growth on a Si substrate. This paper reports the piezoresistive effect of p-type single crystalline 3C-SiC characterized at high temperatures, using an in situ measurement method. The experimental results show that the highly doped p-type 3C-SiC possesses a relatively stable gauge factor of approximately 25 to 28 at temperatures varying from 300 K to 573 K. The in situ method proposed in this study also demonstrated that, the combination of the piezoresistive and thermoresistive effects can increase the gauge factor of p-type 3C-SiC to approximately 20% at 573 K. The increase in gauge factor based on the combination of these phenomena could enhance the sensitivity of SiC based MEMS mechanical sensors.
Scheffler, Tracy L; Park, Sungkwon; Roach, Peter J; Gerrard, David E
2016-06-01
Chronic activation of AMP-activated protein kinase (AMPK) increases glycogen content in skeletal muscle. Previously, we demonstrated that a mutation in the ryanodine receptor (RyR1(R615C)) blunts AMPK phosphorylation in longissimus muscle of pigs with a gain of function mutation in the AMPKγ3 subunit (AMPKγ3(R200Q)); this may decrease the glycogen storage capacity of AMPKγ3(R200Q) + RyR1(R615C) muscle. Therefore, our aim in this study was to utilize our pig model to understand how AMPKγ3(R200Q) and AMPK activation contribute to glycogen storage and metabolism in muscle. We selected and bred pigs in order to generate offspring with naturally occurring AMPKγ3(R200Q), RyR1(R615C), and AMPKγ3(R200Q) + RyR1(R615C) mutations, and also retained wild-type littermates (control). We assessed glycogen content and parameters of glycogen metabolism in longissimus muscle. Regardless of RyR1(R615C), AMPKγ3(R200Q) increased the glycogen content by approximately 70%. Activity of glycogen synthase (GS) without the allosteric activator glucose 6-phosphate (G6P) was decreased in AMPKγ3(R200Q) relative to all other genotypes, whereas both AMPKγ3(R200Q) and AMPKγ3(R200Q) + RyR1(R615C) muscle exhibited increased GS activity with G6P. Increased activity of GS with G6P was not associated with increased abundance of GS or hexokinase 2. However, AMPKγ3(R200Q) enhanced UDP-glucose pyrophosphorylase 2 (UGP2) expression approximately threefold. Although UGP2 is not generally considered a rate-limiting enzyme for glycogen synthesis, our model suggests that UGP2 plays an important role in increasing flux to glycogen synthase. Moreover, we have shown that the capacity for glycogen storage is more closely related to the AMPKγ3(R200Q) mutation than activity. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Yu, Jiaguo; Wang, Ke; Xiao, Wei; Cheng, Bei
2014-06-21
Photocatalytic reduction of CO2 into renewable hydrocarbon fuels is an alternative way to develop reproducible energy, which is also a promising way to solve the problem of the greenhouse effect. In this work, graphitic carbon nitride (g-C3N4) was synthesized by directly heating thiourea at 550 °C and then a certain amount of Pt was deposited on it to form g-C3N4-Pt nanocomposites used as catalysts for photocatalytic reduction of CO2 under simulated solar irradiation. The main products of photocatalysis were CH4, CH3OH and HCHO. The deposited Pt acted as an effective cocatalyst, which not only influenced the selectivity of the product generation, but also affected the activity of the reaction. The yield of CH4 first increased upon increasing the amount of Pt deposited on the g-C3N4 from 0 to 1 wt%, then decreased at 2 wt% Pt loading. The production rates of CH3OH and HCHO also increased with the content of Pt increasing from 0 to 0.75 wt% and the maximum yield was observed at 0.75 wt%. The Pt nanoparticles (NPs) could facilitate the transfer and enrichment of photogenerated electrons from g-C3N4 to its surface for photocatalytic reduction of CO2. At the same time, Pt was also used a catalyst to promote the oxidation of products. The transient photocurrent response further confirmed the proposed photocatalytic reduction mechanism of CO2. This work indicates that the deposition of Pt is a good strategy to improve the photoactivity and selectivity of g-C3N4 for CO2 reduction.
NASA Astrophysics Data System (ADS)
El Khakani, My A.; Gat, E.; Beaudoin, Yves; Chaker, Mohamed; Monteil, C.; Guay, Daniel; Letourneau, G.; Pepin, Henri
1995-04-01
Laser ablation deposition technique was used to deposit silicon carbide thin films on both Si(100) and quartz substrates. The deposition was accomplished by ablating SiC sintered ceramic targets, using a KrF (248 nm) excimer laser. At a laser intensity of about 1 X 109 W/cm2, substrate temperatures in the (25-700) degree(s)C range were investigated. When the deposition temperature is varied from 27 to 650 degree(s)C, (i) the density of a-SiC films increases from 2.6 to 3.0 g cm-3, while their mean roughness value (for a film thickness of about 1 micrometers ) slightly changes from 0.44 to 0.5 nm; (ii) the optical transmission of a-SiC films is significantly improved (the absorption coefficient at 632.8 nm wavelength was reduced by a factor of about 5); and (iii) their Si-C bond density, as determined by FTIR spectroscopy, increases from (13.1 +/- 1.3) to (23.4 +/- 2.4) 1022 bond cm-3. The increased number of Si-C bonds is correlated to the increase of the optical transmission. Over all the investigated deposition temperature range, the a-SiC films were found to be under high compressive stress around a mean value of about 1.26 GPa. The control of the stress of a-SiC films was achieved by means of post- thermal annealings and the annealed a-SiC films were successfully used to fabricate x-ray membranes.
Wertin, Timothy M; Reed, Sasha C; Belnap, Jayne
2015-04-01
Dryland ecosystems represent >40% of the terrestrial landscape and support over two billion people; consequently, it is vital to understand how drylands will respond to climatic change. However, while arid and semiarid ecosystems commonly experience extremely hot and dry conditions, our understanding of how further temperature increases or altered precipitation will affect dryland plant communities remains poor. To address this question, we assessed plant physiology and growth at a long-term (7-year) climate experiment on the Colorado Plateau, USA, where the community is a mix of shallow-rooted C3 and C4 grasses and deep-rooted C4 shrubs. The experiment maintained elevated-temperature treatments (+2 or +4 °C) in combination with altered summer monsoonal precipitation (+small frequent precipitation events or +large infrequent events). Increased temperature negatively affected photosynthesis and growth of the C3 and C4 grasses, but effects varied in their timing: +4 °C treatments negatively affected the C3 grass early in the growing season of both years, while the negative effects of temperature on the C4 grass were seen in the +2 and +4 °C treatments, but only during the late growing season of the drier year. Increased summer precipitation did not affect photosynthesis or biomass for any species, either in the year the precipitation was applied or the following year. Although previous research suggests dryland plants, and C4 grasses in particular, may respond positively to elevated temperature, our findings from a cool desert show marked declines in C3 and C4 photosynthesis and growth, with temperature effects dependent on the degree of warming and growing-season precipitation.
NASA Astrophysics Data System (ADS)
Al-Jawad, Selma M. H.; Elttayf, Abdulhussain K.; Saber, Amel S.
Pure nanocrystalline SnO2 films were grown on a clean glass substrate by using sol-gel dip coating and chemical bath deposition (CBD) techniques for gas sensor applications. The films were annealed in air at 300∘C, 400∘C, and 500∘C for 60min. The deposited films with a thickness of approximately 300 ± 20 nm were analyzed through X-ray diffraction, scanning electron microscopy (SEM), atomic force microscopy (AFM), and optical absorption spectroscopy. Results revealed that the films produced by dip coating exhibited a tetragonal rutile structure and those produced by CBD showed a tetragonal rutile and orthorhombic structure. The crystalline sizes of the films produced by dip coating annealed at 300∘C, 400∘C, and 500∘C were 8, 14, and 22.34 nm and those for CBD films at these temperatures were 10, 15, and 22 nm, respectively. AFM and SEM results indicated that the average grain size increased as annealing temperature increased. The transmittance and absorbance spectra were then recorded at wavelengths ranging from 300nm to 1000nm. The films produced by both the methods yielded high transmission at visible regions. The optical band gap energy of dip-coated films also increased as annealing temperature increased. In particular, their optical band gap energies were 3.5, 3.75, and 3.87eV at 300∘C, 400∘C, and 500∘C, respectively. By comparison, the energy band gap of CBD-prepared films decreased as annealing temperature increased, and their corresponding band gaps were 3.95, 3.85, and 3.8eV at the specified annealing temperatures. The films were further investigated in terms of their sensing abilities for carbon monoxide (CO) gas at 50 ppm by measuring their sensitivity to this gas at different times and temperatures. Our results demonstrated that dip-coated and CBD-prepared films were highly sensitive to CO at 200∘C and 250∘C, respectively.
Lee, Luke J.; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark
2013-01-01
Elevated levels of intracellular Ca2+ ([Ca2+]i) inhibit Na+/H+ exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca2+]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca2+ signaling proteins necessary for regulation of NHE3 activity. [Ca2+]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca2+]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y416 phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca2+]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca2+]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca2+]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3. PMID:23703528
Zachos, Nicholas C; Lee, Luke J; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark
2013-08-01
Elevated levels of intracellular Ca(2+) ([Ca(2+)]i) inhibit Na(+)/H(+) exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca(2+)]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca(2+) signaling proteins necessary for regulation of NHE3 activity. [Ca(2+)]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca(2+)]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y(416) phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca(2+)]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca(2+)]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca(2+)]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3.
Effect of Al and Y2O3 on Mechanical Properties in Mechanically Alloyed Nanograin Ni-Based Alloys.
Kim, Chung Seok; Kim, Il-Ho
2015-08-01
The effects of aluminum and Y2O3 on the mechanical properties in nano grain Ni-based alloys have been investigated. The test specimens are prepared by mechanical alloying at an Ar atmosphere. The addition of Y2O3 and Al may cause an increase in the tensile strength at room temperature, 400 °C and 600 °C. However, it was confirmed that the increase of tensile strength at room temperature and 400 °C was predominantly caused by addition of Y2O3, while that at 600 °C was mainly due to addition of Al. These results can be attributed to the dispersion strengthening of Y2O3, preventing the formation of Cr2O3 and the change of fracture mode at 600 °C by the addition of Al.
Shivran, Hari Singh; Kumar, S; Kumar, Dinesh; Singh, R V
2005-04-01
The biological denitrification processes possess many advantages in comparison to other denitrification processes. The present study was undertaken to observe the effect of quantity of carbon on biological denitrification with Pseudomonas stutzeri at different C/N ratios. The results obtained in the present investigations show that the pH and alkalinity of the effluent increased with increase in C/N ratio due to alkalinity generated during denitrification. The COD of the influent was increased with increase in C/N ratio. The effluent COD was nil under pseudo-steady state condition up to the C/N ratio of 2.5. Above this C/N ratio, the organics started entering in the treated water. The maximum feasible economic reduction of NO(3-)N from 51.6 mg/l to 1.2 mg/l occurred at C/N ratio of 2.5 and the obtained concentration of NO(3-)N was found to be lower than the tolerance limit (10 mg/l) prescribed by the WHO. The present work provides a feasible approach for a more efficient NO(3-)N removal process.
Temperature Dependence of Attenuation of Coplanar Waveguide on 4H High Resistivity SIC Through 540C
NASA Technical Reports Server (NTRS)
Ponchak, G. E.; Schwartz, Z.; Alterovitz, S. A.; Downey, A. N.; Freeman, J. C.
2003-01-01
For the first time, the temperature and frequency dependence of the attenuation of a Coplanar Waveguide (CPW) on 4H, High Resistivity Sic substrate is reported. The low frequency attenuation increases by 2 dB/cm at 500 C and the high frequency attenuation increases by 3.3 dB/cm at 500 C compared to room temperature.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ruan, Linwei; Xu, Gengsheng; Gu, Lina
2015-06-15
Highlights: • Systematically research on Li-doped g-C{sub 3}N{sub 4} monolayer sheets by first-principles calculation. • Optimal dopant concentration for optical absorption is 7.12%. • Thermodynamics stability of the doped substrate g-C{sub 3}N{sub 4} decreased with Li dopant concentration increasing. • The values of work function Φ decreased monotonously with the increasing of Li dopant concentration. - Abstract: The geometric, electronic, optical properties, thermodynamic stability, and work function of Li-doped g-C{sub 3}N{sub 4} monolayer were investigated by the first-principles calculation. It was found that the Li atoms were preferentially substituted the open-hollow sites of g-C{sub 3}N{sub 4}. Interestingly, the “odd” numbermore » of Li doped g-C{sub 3}N{sub 4} showed metallic properties, while the “even” number of Li atoms widened the band gap of g-C{sub 3}N{sub 4}. The HOMO and LUMO distributions reveal that the active sites located at edge N and C atoms for both pristine and the Li-doped g-C{sub 3}N{sub 4}. In addition, thermodynamic analysis showed that the doped Li atoms reduced the thermodynamic stability of g-C{sub 3}N{sub 4} monolayer sheets.« less
Secondary organic aerosol formation from propylene irradiations in a chamber study
NASA Astrophysics Data System (ADS)
Ge, Shuangshuang; Xu, Yongfu; Jia, Long
2017-05-01
Some studies have shown that low-molecular-weight VOCs such as ethylene and acetylene can form SOA. However, so far propylene (C3H6) has not been studied. The current work systematically investigates irradiations of propylene in the presence of NOx (x = 1, 2) in a self-made indoor chamber. Only a small amount of secondary organic aerosols (SOA) was formed under 5% and 80% RH conditions without sodium chloride (NaCl) seed particles or in the presence of solid NaCl. When NaCl was in the form of droplets, liquid water content (LWC) increased from 34.5 to 169.8 μg m-3 under different initial NaCl concentrations, and correspondingly the amount of SOA linearly increased from 5.9 to 29.8 μg m-3 (SOA = 0.0164 × LWC+1.137, R2 = 0.97) at the C3H6/NOx ratio of 32.2-44.9 (ppbC/ppb). The initial C3H6/NOx concentration ratio considerably impacted the formation of SOA, in which the amount of SOA increased from 12.1 to 47.9 μg m-3 exponentially as the ratio decreased from 46.5 to 6.3 with an important point of the ratio value of 11. At the ratio of less than 11 in the regime under the control of C3H6, SOA concentrations decreased considerably with increasing ratio, whereas at the ratio value of larger than 11 in the NOx controlled regime, SOA slightly decreased with increasing ratio. From combination of the analysis of different functional groups of particles by IR spectra and ESI-Exactive-Orbitrap mass spectrometer, the constituents of SOA were identified to be hydroperoxides (e.g. HOCH2CCl(CH3)OOH), esters (e.g. CH2ClC(O)OCHClCHO), organic nitrates (e.g. HO2CH(CH2Cl)C(O)OCCl(CH2Cl)C(O)OCHClCH2ONO2), etc. Furthermore, a liquid-phase mechanism of SOA formation has been proposed in this study.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xiang, Zhonghua; Qiao, Ling; Zhou, Yan
Research highlights: {yields} A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. {yields} HCV-3a NS5A increases mature SREBP-1c protein level. {yields} HCV-3a NS5A activates SREBP-1c transcription. {yields} Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. {yields} Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that themore » nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.« less
Gagaoua, Mohammed; Picard, Brigitte; Monteils, Valérie
2018-06-01
This study investigated the effects of animal, carcass and muscle characteristics on initial color traits of steaks from 887 Charolais cattle. First, the fixed factors of year of birth, experiment and sex had strong impacts on color traits. From the covariates, increased age lead to intense color (low h*, -1.55 units) and darker and vivid meat (high a*, b* and C*: +4.56, +3.41 and +5.61, respectively). Increases in fatness score and carcass fat weight were associated with increases in a*, b* and C* (redness; +2.90 to +4.06 for a*; yellowness; +2.60 to +3.76 for b*; and vividness, +3.87 to +5.49 for C*) and a darker colored lean (L*; -1.56 to -3.23). As pH24h increased, a* (less red) and C* (less vivid) decreased (-3.06), whereas hue angle increased (+2.69) leading to poorer color. The selection of animals for high degree of muscularity or slaughter weight resulted in lighter and darker meat, respectively. The studied covariates could be used as indicators of Charolais beef color traits. Copyright © 2018 Elsevier Ltd. All rights reserved.
Quispe, Renato; Manalac, Raoul J; Faridi, Kamil F; Blaha, Michael J; Toth, Peter P; Kulkarni, Krishnaji R; Nasir, Khurram; Virani, Salim S; Banach, Maciej; Blumenthal, Roger S; Martin, Seth S; Jones, Steven R
2015-09-01
High levels of the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio are associated with obesity, metabolic syndrome, and insulin resistance. We evaluated variability in the remaining lipid profile, especially remnant lipoprotein particle cholesterol (RLP-C) and its components (very low-density lipoprotein cholesterol subfraction 3 and intermediate-density lipoprotein cholesterol), with variability in the TG/HDL-C ratio in a very large study cohort representative of the general U.S. We examined data from 1,350,908 US individuals who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL) from 2009 to 2011. Demographic information other than age and sex was not available. Changes to the remaining lipid profile across percentiles of the TG/HDL-C ratio were quantified, as well as by three TG/HDL-C cut-off points previously proposed in the literature: 2.5 (male) and 2 (female), 3.75 (male) and 3 (female), and 3.5 (male and female). The mean age of our study population was 58.7 years, and 48% were men. The median TG/HDL-C ratio was 2.2. Across increasing TG/HDL-C ratios, we found steadily increasing levels of RLP-C, non-HDL-C and LDL density. Among the lipid parameters studied, RLP-C and LDL density had the highest relative increase when comparing individuals with elevated TG/HDL-C levels to those with lower TG/HDL-C levels using established cut-off points. Approximately 47% of TG/HDL-C ratio variance was attributable to RLP-C. In the present analysis, a higher TG/HDL-C ratio was associated with an increasingly atherogenic lipid phenotype, characterized by higher RLP-C along with higher non-HDL-C and LDL density. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Fei, Mingming; Lin, Ruizhi; Deng, Yuming; Xian, Hongxi; Bian, Renji; Zhang, Xiaole; Cheng, Jigui; Xu, Chenxi; Cai, Dongyu
2018-01-19
This report demonstrated the first study on the use of a new 2D nanomaterial (Mxene) for enhancing membrane performance of intermediate temperature (>100 °C) polymer electrolyte membrane fuel cells (ITPEMFCs). In this study, a typical Ti 3 C 2 T x -MXene was synthesized and incorporated into polybenzimidazole (PBI)-based membranes by using a solution blending method. The composite membrane with 3 wt% Ti 3 C 2 T x -MXene showed the proton conductivity more than 2 times higher than that of pristine PBI membrane at the temperature range of 100 °C-170 °C, and led to substantial increase in maximum power density of fuel cells by ∼30% tested at 150 °C. The addition of Ti 3 C 2 T x -MXene also improved the mechanical properties and thermal stability of PBI membranes. At 3 wt% Ti 3 C 2 T x -MXene, the elongation at break of phosphoric acid doped PBI remained unaffected at 150 °C, and the tensile strength and Young's modulus was increased by ∼150% and ∼160%, respectively. This study pointed out promising application of MXene in ITPEMFCs.
Replacing precious metals with carbide catalysts for hydrogenation reactions
Ruijun, Hou; Chen, Jingguang G.; Chang, Kuan; ...
2015-03-03
Molybdenum carbide (Mo₂C and Ni/Mo₂C) catalysts were compared with Pd/SiO₂ for the hydrogenation of several diene molecules, 1,3- butadiene, 1,3- and 1,4-cyclohexadiene (CHD). Compared to Pd/SiO₂, Mo₂C showed similar hydrogenation rate for 1,3-butadiene and 1,3-CHD and even higher rate for 1,4-CHD, but with significant deactivation rate for 1,3-CHD hydrogenation. However, the hydrogenation activity of Mo₂C could be completely regenerated by H₂ treatment at 723 K for the three molecules. The Ni modified Mo₂C catalysts retained similar activity for 1,3-butadiene hydrogenation with significantly enhanced selectivity for 1-butene production. The 1-butene selectivity increased with increasing Ni loading below 15%. Among the Nimore » modified Mo₂C catalysts, 8.6%Ni/Mo₂C showed the highest selectivity to 1-butene, which was even higher selectivity than that over Pd/SiO₂. Compared to Pd/SiO₂, both Mo₂C and Ni/Mo₂C showed combined advantages in hydrogenation activity and catalyst cost reduction, demonstrating the potential to use less expensive carbide catalysts to replace precious metals for hydrogenation reactions.« less
NASA Astrophysics Data System (ADS)
Fei, Mingming; Lin, Ruizhi; Deng, Yuming; Xian, Hongxi; Bian, Renji; Zhang, Xiaole; Cheng, Jigui; Xu, Chenxi; Cai, Dongyu
2018-01-01
This report demonstrated the first study on the use of a new 2D nanomaterial (Mxene) for enhancing membrane performance of intermediate temperature (>100 °C) polymer electrolyte membrane fuel cells (ITPEMFCs). In this study, a typical Ti3C2T x -MXene was synthesized and incorporated into polybenzimidazole (PBI)-based membranes by using a solution blending method. The composite membrane with 3 wt% Ti3C2T x -MXene showed the proton conductivity more than 2 times higher than that of pristine PBI membrane at the temperature range of 100 °C-170 °C, and led to substantial increase in maximum power density of fuel cells by ˜30% tested at 150 °C. The addition of Ti3C2T x -MXene also improved the mechanical properties and thermal stability of PBI membranes. At 3 wt% Ti3C2T x -MXene, the elongation at break of phosphoric acid doped PBI remained unaffected at 150 °C, and the tensile strength and Young’s modulus was increased by ˜150% and ˜160%, respectively. This study pointed out promising application of MXene in ITPEMFCs.
Ma, Yiming; Fu, Shaoting; Lu, Lin; Wang, Xiaohui
2017-07-15
To detect the effects of androgen receptor (AR) on cyclic mechanical stretch-modulated proliferation of C2C12 myoblasts and its pathways: roles of IGF-1, PI3K and MAPK. C2C12 were randomly divided into five groups: un-stretched control, six or 8 h of fifteen percent stretch, and six or 8 h of twenty percent stretch. Cyclic mechanical stretch of C2C12 were completed using a computer-controlled FlexCell Strain Unit. Cell proliferation and IGF-1 concentration in medium were detected by CCK8 and ELISA, respectively. Expressions of AR and IGF-1R, and expressions and activities of PI3K, p38 and ERK1/2 in stretched C2C12 cells were determined by Western blot. ①The proliferation of C2C12 cells, IGF-1 concentration in medium, expressions of AR and IGF-1R, and activities of PI3K, p38 and ERK1/2 were increased by 6 h of fifteen percent stretch, while decreased by twenty percent stretch for six or 8 h ②The fifteen percent stretch-increased proliferation of C2C12 cells was reversed by AR inhibitor, Flutamide. ③The increases of AR expression, activities of PI3K, p38 and ERK1/2 resulted from fifteen percent stretch were attenuated by IGF-1 neutralizing antibody, while twenty percent stretch-induced decreases of the above indicators were enhanced by recombinant IGF-1. ④Specific inhibitors of p38, ERK1/2 and PI3K all decreased the expression of AR in fifteen percent and twenty percent of stretched C2C12 cells. Cyclic mechanical stretch modulated the proliferation of C2C12 cells, which may be attributed to the alterations of AR via IGF-1-PI3K/Akt and IGF-1-MAPK (p38, ERK1/2) pathways in C2C12 cells. Copyright © 2017 Elsevier B.V. All rights reserved.
Ruan, Cheng-Jiang; Shao, Hong-Bo; Teixeira da Silva, Jaime A
2012-03-01
Global warming is one of the most serious challenges facing us today. It may be linked to the increase in atmospheric CO2 and other greenhouse gases (GHGs), leading to a rise in sea level, notable shifts in ecosystems, and in the frequency and intensity of wild fires. There is a strong interest in stabilizing the atmospheric concentration of CO2 and other GHGs by decreasing carbon emission and/or increasing carbon sequestration. Biotic sequestration is an important and effective strategy to mitigate the effects of rising atmospheric CO2 concentrations by increasing carbon sequestration and storage capacity of ecosystems using plant photosynthesis and by decreasing carbon emission using biofuel rather than fossil fuel. Improvement of photosynthetic carbon assimilation, using transgenic engineering, potentially provides a set of available and effective tools for enhancing plant carbon sequestration. In this review, firstly different biological methods of CO2 assimilation in C3, C4 and CAM plants are introduced and three types of C4 pathways which have high photosynthetic performance and have evolved as CO2 pumps are briefly summarized. Then (i) the improvement of photosynthetic carbon assimilation of C3 plants by transgenic engineering using non-C4 genes, and (ii) the overexpression of individual or multiple C4 cycle photosynthetic genes (PEPC, PPDK, PCK, NADP-ME and NADP-MDH) in transgenic C3 plants (e.g. tobacco, potato, rice and Arabidopsis) are highlighted. Some transgenic C3 plants (e.g. tobacco, rice and Arabidopsis) overexpressing the FBP/SBPase, ictB and cytochrome c6 genes showed positive effects on photosynthetic efficiency and growth characteristics. However, over the last 28 years, efforts to overexpress individual, double or multiple C4 enzymes in C3 plants like tobacco, potato, rice, and Arabidopsis have produced mixed results that do not confirm or eliminate the possibility of improving photosynthesis of C3 plants by this approach. Finally, a prospect is provided on the challenges of enhancing carbon assimilation of C3 plants using transgenic engineering in the face of global warming, and the trends of the most promising approaches to improving the photosynthetic performance of C3 plants.
Yajima, Toshitaka; Murofushi, Yoshiteru; Zhou, Hanbing; Park, Stanley; Housman, Jonathan; Zhong, Zhao-Hua; Nakamura, Michinari; Machida, Mitsuyo; Hwang, Kyung-Kuk; Gu, Yusu; Dalton, Nancy D.; Yajima, Tomoko; Yasukawa, Hideo; Peterson, Kirk L; Knowlton, Kirk U.
2011-01-01
Background Suppressor of cytokine signaling-3 (SOCS3) is a key negative-feedback regulator of gp130 receptor that provides crucial signaling for cardiac hypertrophy and survival; however, an in vivo role of SOCS3 regulation on cardiac gp130 signaling remains obscure. Methods and Results We generated cardiac-specific SOCS3 knockout (SOCS3 cKO) mice. These mice showed increased activation of gp130 downstream signaling targets (STAT3, ERK1/2, AKT and p38) from 15 weeks of age and developed cardiac dysfunction from around 25 weeks of age with signs of heart failure. Surprisingly, SOCS3 cKO failing hearts had minimal histological abnormalities with intact myofibril ultrastructure. In addition, Ca2+ transients were significantly increased in SOCS3 cKO failing hearts compared to wild-type (WT) hearts. We also found that Ser23/24 residues of troponin I were hypophosphorylated in SOCS3 cKO hearts before the manifestation of cardiac dysfunction. These data suggested the presence of abnormalities in myofilament Ca2+ sensitivity in SOCS3 cKO mice. In addition to the contractile dysfunction, we found various ventricular arrhythmias in SOCS3 cKO non-failing hearts accompanied by a sarcoplasmic reticulum Ca2+ overload. To determine the contribution of gp130 signaling to the cardiac phenotype that occurs with SOCS3 deficiency, we generated cardiac-specific gp130 and SOCS3 double knockout mice. Double KO mice lived significantly longer and had different histological abnormalities when compared to SOCS3 cKO mice; thus, demonstrating the importance of gp130 signaling in the SOCS3 cKO cardiac phenotype. Conclusions Our results demonstrate an important role of SOCS3 regulation on cardiac gp130 signaling in the pathogenesis of contractile dysfunction and ventricular arrhythmias. PMID:22082679
Zou, Xian-Guo; Huang, Yu-Hua; Xu, Tong-Cheng; Fan, Ya-Wei; Li, Jing
2018-01-01
This study aims to investigate the effect of Chinese diet pattern of fat content (30% or 36.06%), n-6/n-3 polyunsaturated fatty acid (PUFA) ratio (5 : 1 or 9 : 1), and cholesterol content (0.04 or 0.057 g/kg total diet) on lipid profile using a rat model. Results showed that rats' body weights (BWs) were controlled by the simultaneous intakes of cholesterol level of 0.04 g/kg total diet and n-6/n-3 ratio of 5 : 1. In addition, under high-fat diet, increased cholesterol feeding led to increased total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels and decreased triacylglycerols (TG) in rats' plasma. However, high density lipoprotein cholesterol (HDL-C) level and the ratios of HDL-C/LDL-C and HDL-C/TC in rats' plasma increased in response to simultaneous intakes of low n-6/n-3 ratio (5 : 1) and cholesterol (0.04 g/kg total diet) even under high-fat diet. Moreover, as the n-6/n-3 PUFA ratio in the diet decreased, the proportion of n-3 PUFAs increased in plasma, liver, and muscle and resulted in the decrease of n-6/n-3 PUFA ratio. PMID:29744358
NASA Astrophysics Data System (ADS)
Kumagami, Manabu; Ogami, Yasuhiro; Tamaki, Yuichi; Kobayashi, Hideaki
Numerical analysis of CH4/O2/H2O laminar premixed flame under various conditions of pressure, equivalence ratio and steam concentration was performed using GRI-Mech 3.0 and the mechanism proposed by Davis and Law, which consists of C1 to C6 hydrocarbons in addition to GRI-Mech 3.0. The pressure dependence of laminar burning velocity and flame structure under fuel-rich conditions was focused on. Effects of the formation of higher hydrocarbons under fuel-rich conditions were also clarified using the mechanism proposed by Davis and Law. Results showed that for extremely fuel-rich conditions, laminar burning velocity increases as pressure increases for both mechanisms. The increase of laminar burning velocity is caused by the shift of the oxidation pathway of CH3 radical from the C2 Route to the C1 Route. The formation of C3-C6 hydrocarbons has only a small effect on laminar burning velocity. Under fuel-rich conditions, super-adiabatic flame temperature (SAFT) occurs and its pressure dependency was clarified.
Effects of gaseous ammonia on intracellular pH values in leaves of C 3- and C 4-plants
NASA Astrophysics Data System (ADS)
Yin, Zu-Hua; Kaiser, Werner; Heber, Ulrich; Raven, John A.
Responses of cytosolic and vacuolar pH to different concentrations (1.3-5.4 μmol NH 3 mol -1 gas or 0.940-3.825 mg NH 3 m -3 gas) of gaseous NH 3 were studied in experiments of 3 h duration by recording changes in fluorescence of pyranine and esculin in leaves of C 3 and C 4 plants. After a lag phase of 0.5-4 min, the uptake of NH 3 at 50-200 nmol m -2 leaf area s -1 increased pyranine fluorescence, indicating cytosolic alkalinization in leaves of Pelargonium zonale L. (C 3) and Amaranthus caudatus L. (C 4). A smaller increase in esculin fluorescence induced by NH 3 indicated some vacuolar alkalization in a Spinacia oleracea L. leaf. Photosynthesis and transpiration remained unchanged during exposure of illuminated leaves to NH 3 for up to 30 min (the maximum tested). CO 2 concentrations influenced the extent of cytosolic alkalinization. 500 μmol CO 2 mol -1 gas suppressed the NH 3-induced cytosolic alkalinization relative to that found in 16 μmol CO 2 mol -1 gas. The suppressing effect of CO 2 on NH 3-induced alkalization was larger in illuminated leaves of the C 4Amaranthus than the C 3Pelargonium. These results indicate that the alkaline pH shift caused by solution and protonation of NH 3 in aqueous leaf compartments is affected by assimilation of NH 3.
Walther, Stefanie; Pluteanu, Florentina; Renz, Susanne; Nikonova, Yulia; Maxwell, Joshua T; Yang, Li-Zhen; Schmidt, Kurt; Edwards, Joshua N; Wakula, Paulina; Groschner, Klaus; Maier, Lars S; Spiess, Joachim; Blatter, Lothar A; Pieske, Burkert; Kockskämper, Jens
2014-09-01
Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca(2+)-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. Copyright © 2014 the American Physiological Society.
Liu, Hong; Cheng, Tie-Ming; Zhang, Hong-Mei; Li, Run-Tao
2003-11-01
Based on the structure characteristics of the lead compounds, 1, 1' octanedioyl-4, 4'-dimethyl-4, 4'-dibenzyl dipiperazinium dibromide (2) and 3, 8-disubstituted-3, 8-diazabicyclo [3.2.1]octanes (DBO), di-(3, 8-diazabicyclo [3.2.1]octane) diquaternary ammonium salts 3 a-c were designed and synthesized through a highly practical procedure. Target compounds 3 a-c and the hydrochloride salts of their precursors 10 a-c were evaluated for their in vivo analgesic and sedative activities. Interestingly, the introduction of an endoethylenic bridge in the piperazine of lead compound 2 causes loss of the analgesic activity and increases the toxicity dramatically. This result shows that the flexible conformation of piperazine in compound 2 is favorable for interaction with the receptor, and the quaternization of compounds 10 a-c is the main reason for the toxicity increase.
Errors in calculated oncotic pressure of dog plasma.
Gabel, J C; Scott, R L; Adair, T H; Drake, R E; Traber, D L
1980-12-01
Several equations to calculate plasma oncotic pressure (pi) from the total protein concentration (C) have been previously described. These equations were derived empirically from samples with a wide range of C obtained by diluting or concentrating normal plasma samples. To test these equations over a range of naturally occurring C, we measured C and pi of plasma samples from 40 dogs. C ranged from 5.3 to 8.7 g/dl and averaged 6.5 +/- 0.1 (mean +/- SE) and pi averaged 17.9 +/- 0.3 mmHg. The regression equation was pi = 78.14 + 1.67 C (r = 0.74). pi increased with C much less than predicted with the commonly used equations. The albumin-to-globulin concentration ratios (A/G), determined in 27 of the dogs, decreased with increasing C (A/G = 1.56-0.128 C, r = 0.62). The lower A/G at the higher C's could cause the lower than predicted increase in pi with C, because the equations were developed from data in which A/G was constant.
Phase formation and UV luminescence of Gd3+ doped perovskite-type YScO3
NASA Astrophysics Data System (ADS)
Shimizu, Yuhei; Ueda, Kazushige
2016-10-01
Synthesis of pure and Gd3+doped perovskite-type YScO3 was attempted by a polymerized complex (PC) method and solid state reaction (SSR) method. Crystalline phases and UV luminescence of samples were examined with varying heating temperatures. The perovskite-type single phase was not simply formed in the SSR method, as reported in some literatures, and two cubic C-type phases of starting oxide materials remained forming slightly mixed solid solutions. UV luminescence of Gd3+ doped samples increased with an increase in heating temperatures and volume of the perovskite-type phase. In contrast, a non-crystalline precursor was crystallized to a single C-type phase at 800 °C in the PC method forming a completely mixed solid solution. Then, the phase of perovskite-type YScO3 formed at 1200 °C and its single phase was obtained at 1400 °C. It was revealed that high homogeneousness of cations was essential to generate the single perovskite-phase of YScO3. Because Gd3+ ions were also dissolved into the single C-type phase in Gd3+ doped samples, intense UV luminescence was observed above 800 °C in both C-type phase and perovskite-type phase.
Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Breloer, Minka
2014-01-01
Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3+ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3+ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6 mice. PMID:24516385
Blankenhaus, Birte; Reitz, Martina; Brenz, Yannick; Eschbach, Marie-Luise; Hartmann, Wiebke; Haben, Irma; Sparwasser, Tim; Huehn, Jochen; Kühl, Anja; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Breloer, Minka
2014-02-01
Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection. Here we report a different impact of Foxp3⁺ regulatory T cells (Treg) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice. Infection with Strongyloides ratti induced Treg expansion with similar kinetics and phenotype in both strains. Strikingly, Treg depletion reduced parasite burden selectively in BALB/c but not in C57BL/6 mice. Treg function was apparent in both strains as Treg depletion increased nematode-specific humoral and cellular Th2 response in BALB/c and C57BL/6 mice to the same extent. Improved resistance in Treg-depleted BALB/c mice was accompanied by increased production of IL-9 and accelerated degranulation of mast cells. In contrast, IL-9 production was not significantly elevated and kinetics of mast cell degranulation were unaffected by Treg depletion in C57BL/6 mice. By in vivo neutralization, we demonstrate that increased IL-9 production during the first days of infection caused accelerated mast cell degranulation and rapid expulsion of S. ratti adults from the small intestine of Treg-depleted BALB/c mice. In genetically mast cell-deficient (Cpa3-Cre) BALB/c mice, Treg depletion still resulted in increased IL-9 production but resistance to S. ratti infection was lost, suggesting that IL-9-driven mast cell activation mediated accelerated expulsion of S. ratti in Treg-depleted BALB/c mice. This IL-9-driven mast cell degranulation is a central mechanism of S. ratti expulsion in both, BALB/c and C57BL/6 mice, because IL-9 injection reduced and IL-9 neutralization increased parasite burden in the presence of Treg in both strains. Therefore our results suggest that Foxp3⁺ Treg suppress sufficient IL-9 production for subsequent mast cell degranulation during S. ratti infection in a non-redundant manner in BALB/c mice, whereas additional regulatory pathways are functional in Treg-depleted C57BL/6 mice.
Nkukwana, T T; Muchenje, V; Masika, P J; Hoffman, L C; Dzama, K; Descalzo, A M
2014-01-01
Effects of diets supplemented with or without Moringa oleifera leaf meal (MOLM) on fatty acid (FA) composition and oxidative stability of broiler breast meat during refrigerated storage was determined. Dietary treatments (T) were as follows: T1, positive control, 668g/ton Salinomycin and 500g/ton Albac; T2, T3 and T4 contained graded levels of MOLM at 1%, 3% and 5% of dry matter (DM) intake, respectively; and T5, a negative control (0% additives). Oxidative stability was evaluated by thiobarbituric acid reactive substances (TBARS) on day (D) 1-8 of storage at 4°C; and FA analysis was done on samples obtained on D1 and D8. Significant effects on TBARS were noted on day (D) 1, 3, 4 and 7; increased with increasing storage time, and with increase in MOLM supplementation. Highest (P<0.05) C18:0 and C15:0 levels were noted on D1 in T2; C20:0 in T4 on D8; C20:2, C20:3n6 and C22:6n3 in T2; C18:3n6 and P/S ratio in T4 on D1; and n-3 in T3. Thus, despite the high SFA content, additive supplementation of M. oleifera leaf meal up to 5% of the bird's DMI improved the FA profile and reduced lipid oxidation in broiler breast meat. Copyright © 2013 Elsevier Ltd. All rights reserved.
Solvent effects on infrared spectra of progesterone in CHCl 3/ cyclo-C 6H 12 binary solvent systems
NASA Astrophysics Data System (ADS)
Liu, Qing; Wang, Xiao-yan; Zhang, Hui
2007-01-01
The infrared spectroscopy studies of the C 3 and C 20 carbonyl stretching vibrations ( υ(C dbnd O)) of progesterone in CHCl 3/ cyclo-C 6H 12 binary solvent systems were undertaken to investigate the solute-solvent interactions. With the mole fraction of CHC1 3 in the binary solvent mixtures increase, three types of C 3 and C 20 carbonyl stretching vibration band of progesterone are observed, respectively. The assignments of υ(C dbnd O) of progesterone are discussed in detail. In the CHCl 3-rich binary solvent systems or pure CHCl 3 solvent, two kinds of solute-solvent hydrogen bonding interactions coexist for C 20 C dbnd O. Comparisons are drawn for the solvent sensitivities of υ(C dbnd O) for acetophenone and 5α-androstan-3,17-dione, respectively.
Li, Jun; Zhou, Yin-yan; Kou, Yu; Yu, Xin-fen; Zheng, Zhi-bei; Yang, Xu-hui; Wang, Hao-qiu
2015-11-01
In the post-pandemic period 2010-2015, seasonal influenza A(H3N2) virus predominated in Hangzhou, southeast of China, with an increased activity and semi-annual seasons. This study utilized HA virus gene segment sequences to analyze the divergence date and vaccine strain match of human influenza A(H3N2) virus from systematic influenza surveillance in Hangzhou. Virological and serological analyses of 124 representative A(H3N2) viruses from prospective studies of systematic surveillance samples were conducted to quantify the genetic and antigenic characteristics and their vaccine strain match. Bayesian phylogenetic inference showed that two separate subgroups 3C.3 and 3C.2 probably diverged from group 3C in early 2012 and then evolved into groups 3C.3a and 3C.2a, respectively, in the 2014/15 influenza season. Furthermore, high amino acid substitution rates of the HA1 subunit were found in A(H3N2) group 3C.2a variants, indicating that increased antigenic drift of A(H3N2) group 3C.2a virus is associated with a vaccine mismatch to the 2015/16 vaccine reference strain Switzerland/9715293/2013 (group 3C.3a). A portion of the group 3C.2a isolates are not covered by the current A(H3N2) vaccine strain. These findings offer insights into the emergence of group 3C.2a variants with epidemic potential in the imminent influenza seasons. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Choi, Ju Yeon; Park, Seonghee, E-mail: sp@ewha.ac.kr
The intermediate conductance calcium-activated potassium channel (KCa3.1) mediates proliferation of many cell types including fibroblasts, and is a molecular target for intervention in various cell proliferative diseases. Our previous study showed that reduction of KCa3.1 channel expression by lyso-globotriaosylceramide (lyso-Gb3) inhibits differentiation into myofibroblasts and collagen synthesis, which might lead to development of ascending thoracic aortic aneurysm secondary to Fabry disease. However, how lyso-Gb3 downregulates KCa3.1 channel expression is unknown. Therefore, we aimed to investigate the underlying mechanisms of lyso-Gb3-mediated KCa3.1 channel downregulation, focusing on the cAMP signaling pathway. We found that lyso-Gb3 increased the intracellular cAMP concentration by upregulationmore » of adenylyl cyclase 6 and inhibited ERK 1/2 phosphorylation through the protein kinase A (PKA) pathway, leading to the inhibition of KCa3.1 channel synthesis, not the exchange protein directly activated by cAMP (Epac) pathway. Moreover, lyso-Gb3 suppressed expression of class II phosphatidylinositol 3-kinase C2β (PI3KC2β) by PKA activation, which reduces the production of phosphatidylinositol 3-phosphate [PI(3)P], and the reduced membrane surface expression of KCa3.1 channel was recovered by increasing the intracellular levels of PI(3)P. Consequently, our findings that lyso-Gb3 inhibited both KCa3.1 channel synthesis and surface expression by increasing intracellular cAMP, and controlled surface expression through changes in PI3KC2β-mediated PI(3)P production, suggest that modulation of PKA and PI3KC2β activity to control of KCa3.1 channel expression can be an alternative important target to attenuate ascending thoracic aortic aneurysms in Fabry disease. - Highlights: • Lyso-Gb3 causes elevation of intracellular cAMP. • Lyso-Gb3 inhibits the ERK 1/2 phosphorylation through PKA, thereby reducing KCa3.1 channel synthesis. • Lyso-Gb3 reduces PI3KC2β-mediated intracellular PI(3)P production. • Lyso-Gb3 reduces both surface and total expression of the KCa3.1 channel. • Increasing intracellular levels of PI(3)P only recovers the reduced surface expression.« less
Zhang, Yan; Guo, Jingjing; Li, Lanlan; Liu, Xuewei; Yao, Xiaojun; Liu, Huanxiang
2016-10-01
The interactions of complement receptor 2 (CR2) and the degradation fragment C3d of complement component C3 play important links between the innate and adaptive immune systems. Due to the importance of C3d-CR2 interaction in the design of vaccines and inhibitors, a number of studies have been performed to investigate C3d-CR2 interaction. Many studies have indicated C3d-CR2 interactions are ionic strength-dependent. To investigate the molecular mechanism of C3d-CR2 interaction and the origin of effects of ionic strength, molecular dynamics simulations for C3d-CR2 complex together with the energetic and structural analysis were performed. Our results revealed the increased interactions between charged protein and ions weaken C3d-CR2 association, as ionic strengths increase. Moreover, ion strengths have similar effects on antigen-binding site and CR2 binding site. Meanwhile, Ala17 and Gln20 will transform between the activated and non-activated states mediated by His133 and Glu135 at different ion strengths. Our results reveal the origins of the effects of ionic strengths on C3d-CR2 interactions are due to the changes of water, ion occupancies and distributions. This study uncovers the origin of the effect of ionic strength on C3d-CR2 interaction and deepens the understanding of the molecular mechanism of their interaction, which is valuable for the design of vaccines and small molecule inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.
Photocatalytic decomposition of N2O over TiO2/g-C3N4 photocatalysts heterojunction
NASA Astrophysics Data System (ADS)
Kočí, K.; Reli, M.; Troppová, I.; Šihor, M.; Kupková, J.; Kustrowski, P.; Praus, P.
2017-02-01
TiO2/g-C3N4 photocatalysts with the various TiO2/g-C3N4 weight ratios from 1:2 to 1:6 were fabricated by mechanical mixing in water suspension followed by calcination. Pure TiO2 was prepared by thermal hydrolysis and pure g-C3N4 was prepared from commercial melamine by thermal annealing at 620 °C. All the nanocomposites were characterized by X-ray powder diffraction, UV-vis diffuse reflectance spectroscopy, Raman spectroscopy, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, photoelectrochemical measurements and nitrogen physisorption. The prepared mixtures along with pure TiO2 and g-C3N4 were tested for the photocatalytic decomposition of nitrous oxide under UVC (λ = 254 nm), UVA (λ = 365 nm) and Vis (λ > 400 nm) irradiation. The TiO2/g-C3N4 nanocomposites showed moderate improvement compared to pure g-C3N4 but pure TiO2 proved to be a better photocatalyst under UVC irradiation. However, under UVA irradiation conditions, the photocatalytic activity of TiO2/g-C3N4 (1:2) nanocomposite exhibited an increase compared to pure TiO2. Nevertheless, further increase of g-C3N4 amount leads/led to a decrease in reactivity. These results are suggesting the nanocomposite with the optimal weight ratio of TiO2 and g-C3N4 have shifted absorption edge energy towards longer wavelengths and decreased the recombination rate of charge carriers compared to pure g-C3N4. This is probably due to the generation of heterojunction on the TiO2/g-C3N4 interface.
Somatostatin Signaling in Neuronal Cilia Is Criticalfor Object Recognition Memory
Einstein, Emily B.; Patterson, Carlyn A.; Hon, Beverly J.; Regan, Kathleen A.; Reddi, Jyoti; Melnikoff, David E.; Mateer, Marcus J.; Schulz, Stefan; Johnson, Brian N.
2010-01-01
Most neurons possess a single, nonmotile cilium that projects out from the cell surface. These microtubule-based organelles are important in brain development and neurogenesis; however, their function in mature neurons is unknown. Cilia express a complement of proteins distinct from other neuronal compartments, one of which is the somatostatin receptor subtype SST3. We show here that SST3 is critical for object recognition memory in mice. sst3 knock-out mice are severely impaired in discriminating novel objects, whereas they retain normal memory for object location. Further, systemic injection of an SST3 antagonist (ACQ090) disrupts recall of familiar objects in wild-type mice. To examine mechanisms of SST3, we tested synaptic plasticity in CA1 hippocampus. Electrically evoked long-term potentiation (LTP) was normal in sst3 knock-out mice, while adenylyl cyclase/cAMP-mediated LTP was impaired. The SST3 antagonist also disrupted cAMP-mediated LTP. Basal cAMP levels in hippocampal lysate were reduced in sst3 knock-out mice compared with wild-type mice, while the forskolin-induced increase in cAMP levels was normal. The SST3 antagonist inhibited forskolin-stimulated cAMP increases, whereas the SST3 agonist L-796,778 increased basal cAMP levels in hippocampal slices but not hippocampal lysate. Our results show that somatostatin signaling in neuronal cilia is critical for recognition memory and suggest that the cAMP pathway is a conserved signaling motif in cilia. Neuronal cilia therefore represent a novel nonsynaptic compartment crucial for signaling involved in a specific form of synaptic plasticity and in novelty detection. PMID:20335466
Kostova, I.J.; Hower, J.C.; Mastalerz, Maria; Vassilev, S.V.
2011-01-01
Mercury capture by fly ash C was investigated at five lignite- and subbituminous-coal-burning Bulgarian power plants (Republika, Bobov Dol, Maritza East 2, Maritza East 3, and Sliven). Although the C content of the ashes is low, never exceeding 1.6%, the Hg capture on a unit C basis demonstrates that the low-rank-coal-derived fly ash carbons are more efficient in capturing Hg than fly ash carbons from bituminous-fired power plants. While some low-C and low-Hg fly ashes do not reveal any trends of Hg versus C, the 2nd and, in particular, the 3rd electrostatic precipitator (ESP) rows at the Republika power plant do have sufficient fly ash C range and experience flue gas sufficiently cool to capture measurable amounts of Hg. The Republika 3rd ESP row exhibits an increase in Hg with increasing C, as observed in other power plants, for example, in Kentucky power plants burning Appalachian-sourced bituminous coals. Mercury/C decreases with an increase in fly ash C, suggesting that some of the C is isolated from the flue gas stream and does not contribute to Hg capture. Mercury capture increases with an increase in Brunauer-Emmett-Teller (BET) surface area and micropore surface area. The differences in Hg capture between the Bulgarian plants burning low-rank coal and high volatile bituminous-fed Kentucky power plants suggests that the variations in C forms resulting from the combustion of the different ranks also influence the efficiency of Hg capture. ?? 2010 Elsevier Ltd.
Gajewska-Woźniak, Olga; Skup, Małgorzata; Kasicki, Stefan; Ziemlińska, Ewelina; Czarkowska-Bauch, Julita
2013-01-01
The importance of neurotrophin 3 (NT-3) for motor control prompted us to ask the question whether direct electrical stimulation of low-threshold muscle afferents, strengthening the proprioceptive signaling, could effectively increase the endogenous pool of this neurotrophin and its receptor TrkC in the Hoffmann-reflex (H-reflex) circuitry. The effects were compared with those of brain-derived neurotrophic factor (BDNF) and its TrkB receptor. Continuous bursts of stimuli were delivered unilaterally for seven days, 80 min daily, by means of a cuff-electrode implanted over the tibial nerve in awake rats. The H-reflex was recorded in the soleus muscle to control the strength of stimulation. Stimulation aimed at activation of Ia fibers produced a strong increase of NT-3 protein, measured with ELISA, in the lumbar L3-6 segments of the spinal cord and in the soleus muscle. This stimulation exerted much weaker effect on BDNF protein level which slightly increased only in L3-6 segments of the spinal cord. Increased protein level of NT-3 and BDNF corresponded to the changes of NT-3 mRNA and BDNF mRNA expression in L3-6 segments but not in the soleus muscle. We disclosed tissue-specificity of TrkC mRNA and TrkB mRNA responses. In the spinal cord TrkC and TrkB transcripts tended to decrease, whereas in the soleus muscle TrkB mRNA decreased and TrkC mRNA expression strongly increased, suggesting that stimulation of Ia fibers leads to sensitization of the soleus muscle to NT-3 signaling. The possibility of increasing NT-3/TrkC signaling in the neuromuscular system, with minor effects on BDNF/TrkB signaling, by means of low-threshold electrical stimulation of peripheral nerves, which in humans might be applied in non-invasive way, offers an attractive therapeutic tool. PMID:23776573
Gajewska-Woźniak, Olga; Skup, Małgorzata; Kasicki, Stefan; Ziemlińska, Ewelina; Czarkowska-Bauch, Julita
2013-01-01
The importance of neurotrophin 3 (NT-3) for motor control prompted us to ask the question whether direct electrical stimulation of low-threshold muscle afferents, strengthening the proprioceptive signaling, could effectively increase the endogenous pool of this neurotrophin and its receptor TrkC in the Hoffmann-reflex (H-reflex) circuitry. The effects were compared with those of brain-derived neurotrophic factor (BDNF) and its TrkB receptor. Continuous bursts of stimuli were delivered unilaterally for seven days, 80 min daily, by means of a cuff-electrode implanted over the tibial nerve in awake rats. The H-reflex was recorded in the soleus muscle to control the strength of stimulation. Stimulation aimed at activation of Ia fibers produced a strong increase of NT-3 protein, measured with ELISA, in the lumbar L3-6 segments of the spinal cord and in the soleus muscle. This stimulation exerted much weaker effect on BDNF protein level which slightly increased only in L3-6 segments of the spinal cord. Increased protein level of NT-3 and BDNF corresponded to the changes of NT-3 mRNA and BDNF mRNA expression in L3-6 segments but not in the soleus muscle. We disclosed tissue-specificity of TrkC mRNA and TrkB mRNA responses. In the spinal cord TrkC and TrkB transcripts tended to decrease, whereas in the soleus muscle TrkB mRNA decreased and TrkC mRNA expression strongly increased, suggesting that stimulation of Ia fibers leads to sensitization of the soleus muscle to NT-3 signaling. The possibility of increasing NT-3/TrkC signaling in the neuromuscular system, with minor effects on BDNF/TrkB signaling, by means of low-threshold electrical stimulation of peripheral nerves, which in humans might be applied in non-invasive way, offers an attractive therapeutic tool.
Brunson, Jessi; Pyke, David A.; Perakis, Steven S.
2010-01-01
Restoration of sagebrush-steppe plant communities dominated by the invasive ruderals Bromus tectorum (cheatgrass) and Taeniatherum caput-medusae (medusahead) can be facilitated by adding carbon (C) to the soil, stimulating microbes to immobilize nitrogen (N) and limit inorganic N availability. Our objectives were to determine responses in (1) cheatgrass and medusahead biomass and seed production; (2) soil microbial biomass C and N; and (3) inorganic soil N to a range of C doses and to calculate the lowest dose that yielded a significant response. In November 2005, we applid 12 C doses ranging from 0 to 2,400 kg C/ha as sucrose to plots sown with cheatgrass and medusahead at two sites in the northern Great Basin. Other ruderal plants established in our plots, and this entire ruderal community was negatively affected by C addition. End-of-year biomass of the ruderal community decreased approximately by approximately 6% at each site for an increase in C dose of 100 kg C/ha. For the same increase in C, microbial biomass C increased by 2–4 mg/kg in November 2005 and March 2006, but not in July 2006. There was little, if any, microbial soil N uptake, as microbial biomass N increased by 0.3 mg/kg at only one site at the earliest date, in November 2005. Soil nitrate (NO3−) measured via resin capsules placed in situ for the study duration decreased at both sites with increasing C. Although we found no threshold dose of C, for a significant reduction in ruderal biomass, we calculated lowest significant doses of 240–640 kg C/ha.
Synthesis and Characterization of MAX Ceramics (MAXCERs)
NASA Astrophysics Data System (ADS)
Nelson, Johnny Carl
This research has focused on the design and development of novel multifunctional MAX reinforced ceramics (MAXCERs). These MAXCERs were manufactured with 1-50 vol% ratios of ceramics to MAX phases. Chapter II reports on the synthesis and tribological behavior of Ti3SiC2 matrix composites by incorporating (1 and 6 vol%) Al2O3, (1 and 5 vol%) BN, and (1 and 5 vol%) B4C ceramic particulate additives in the matrix. All the composites were fabricated by pressureless sintering by using 1 wt% Ni as a sintering agent at 1550 °C for 2 hours. SEM and XRD studies showed that Al2O3 is relatively inert in the Ti3SiC 2 matrix whereas BN and B4C reacted significantly with the Ti3 SiC2 matrix to form TiB2. Detailed tribological studies showed that Ti3SiC2-1wt%Ni (baseline) samples showed dual type tribological behavior where the friction coefficient (micro) was low ( 0.2) during stage 1, thereafter micro increased sharply and transitioned into stage 2 ( 0.8). The addition of Al2O3 as an additive had little effect on the tribological behavior, but the addition of B4C and BN was able to enhance the tribological behavior by increasing the transition distance (TD). Chapter III reports on the synthesis and tribological behavior of TiB2 matrix composites by incorporating (10, 30, and 50 vol%) Ti3SiC2 ceramic particulate additives in the matrix. The fabrication parameters were similar to the Ti3SiC2 samples from Chapter II. There was minimal reaction between the TiB2 and the Ti3SiC2. Detailed tribological studies showed that TiB2 (baseline) and TiB2-10%Ti 3SiC2 samples showed an average micro of 0.29 and 0.28, respectively. TiB2-30%Ti3SiC2 and TiB 2-50%Ti3SiC2 showed dual-type tribological behavior where micro was low ( 0.25) during stage 1, thereafter micro increased gradually and transitioned into stage 2 ( 0.6). Low wear rates were seen for all samples.
Palner, Mikael; Shen, Bin; Jeon, Jongho; Lin, Jianguo; Chin, Frederick T; Rao, Jianghong
2015-09-01
Early detection of tumor response to therapy is crucial to the timely identification of the most efficacious treatments. We recently developed a novel apoptosis imaging tracer, (18)F-C-SNAT (C-SNAT is caspase-sensitive nanoaggregation tracer), that undergoes an intramolecular cyclization reaction after cleavage by caspase-3/7, a biomarker of apoptosis. This caspase-3/7-dependent reaction leads to an enhanced accumulation and retention of (18)F activity in apoptotic tumors. This study aimed to fully examine in vivo pharmacokinetics of the tracer through PET imaging and kinetic modeling in a preclinical mouse model of tumor response to systemic anticancer chemotherapy. Tumor-bearing nude mice were treated 3 times with intravenous injections of doxorubicin before undergoing a 120-min dynamic (18)F-C-SNAT PET/CT scan. Time-activity curves were extracted from the tumor and selected organs. A 2-tissue-compartment model was fitted to the time-activity curves from tumor and muscle, using the left ventricle of the heart as input function, and the pharmacokinetic rate constants were calculated. Both tumor uptake (percentage injected dose per gram) and the tumor-to-muscle activity ratio were significantly higher in the treated mice than untreated mice. Pharmacokinetic rate constants calculated by the 2-tissue-compartment model showed a significant increase in delivery and accumulation of the tracer after the systemic chemotherapeutic treatment. Delivery of (18)F-C-SNAT to the tumor tissue, quantified as K1, increased from 0.31 g⋅(mL⋅min)(-1) in untreated mice to 1.03 g⋅(mL⋅min)(-1) in treated mice, a measurement closely related to changes in blood flow. Accumulation of (18)F-C-SNAT, quantified as k3, increased from 0.03 to 0.12 min(-1), proving a higher retention of (18)F-C-SNAT in treated tumors independent from changes in blood flow. An increase in delivery was also found in the muscular tissue of treated mice without increasing accumulation. (18)F-C-SNAT has significantly increased tumor uptake and significantly increased tumor-to-muscle ratio in a preclinical mouse model of tumor therapy. Furthermore, our kinetic modeling of (18)F-C-SNAT shows that chemotherapeutic treatment increased accumulation (k3) in the treated tumors, independent of increased delivery (K1). © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Whitney, Spencer M.; Sharwood, Robert E.; Orr, Douglas; White, Sarah J.; Alonso, Hernan; Galmés, Jeroni
2011-01-01
Improving global yields of important agricultural crops is a complex challenge. Enhancing yield and resource use by engineering improvements to photosynthetic carbon assimilation is one potential solution. During the last 40 million years C4 photosynthesis has evolved multiple times, enabling plants to evade the catalytic inadequacies of the CO2-fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco). Compared with their C3 ancestors, C4 plants combine a faster rubisco with a biochemical CO2-concentrating mechanism, enabling more efficient use of water and nitrogen and enhanced yield. Here we show the versatility of plastome manipulation in tobacco for identifying sequences in C4-rubisco that can be transplanted into C3-rubisco to improve carboxylation rate (VC). Using transplastomic tobacco lines expressing native and mutated rubisco large subunits (L-subunits) from Flaveria pringlei (C3), Flaveria floridana (C3-C4), and Flaveria bidentis (C4), we reveal that Met-309-Ile substitutions in the L-subunit act as a catalytic switch between C4 (309Ile; faster VC, lower CO2 affinity) and C3 (309Met; slower VC, higher CO2 affinity) catalysis. Application of this transplastomic system permits further identification of other structural solutions selected by nature that can increase rubisco VC in C3 crops. Coengineering a catalytically faster C3 rubisco and a CO2-concentrating mechanism within C3 crop species could enhance their efficiency in resource use and yield. PMID:21849620
Neuronal-glial interactions in rats fed a ketogenic diet.
Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula
2006-01-01
Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative metabolism of glucose as well as the increased astrocytic metabolism, may reflect adaptation of the brain to ketone bodies as major source of fuel.
High temperature XRD of Cu{sub 2}GeSe{sub 3}
DOE Office of Scientific and Technical Information (OSTI.GOV)
Premkumar, D. S.; Malar, P.; Chetty, Raju
2015-06-24
The Cu{sub 2}GeSe{sub 3} is prepared by solid state synthesis method. The high temperature XRD has been done at different temperature from 30 °C to 450 °C. The reitveld refinement confirms Cu{sub 2}GeSe{sub 3} phase and orthorhombic crystal structure. The lattice constants are increasing with increase in the temperature and their rate of increase with respect to temperature are used for finding the thermal expansion coefficient. The calculation of the linear and volume coefficient of thermal expansion is done from 30 °C to 400 °C. Decrease in the values of linear expansion coefficients with temperature are observed along a andmore » c axis. Since thermal expansion coefficient is the consequence of the distortion of atoms in the lattice; this can be further used to find the minimum lattice thermal conductivity at given temperature.« less
Liu, Li-Ming; Li, Yin; Du, Guo-Cheng; Chen, Jian
2003-11-01
A large amount of alpha-ketoglutarate (alpha-KG) (6.8 g/L) was accumulated in flask culture when CaCO3 was used as a buffering agent in the production of pyruvate by multi-vitamin auxotrophic yeast Torulopsis glabrata CCTCC M202019. In a 5 L jar-fermentor, less alpha-KG (1.3 g/L) was produced when NaOH was used to adjust the pH, while more alpha-KG (11.5 g/L) detected when CaCO3 was used as the buffer. In the latter case, the molar carbon ratio of pyruvate to alpha-KG (C(PYR)/ CalphaKG) was similar to that obtained in flask culture, suggesting the accumulation of alpha-ketoglutarate was related to the addition of CaCO3. Furthermore, it was found that: (1) delaying the addition time of CaCO3 decreased the a-ketoglutarate formation but increased C(PYR)/ C(alphaKG); and (2) under vitamin limitation conditions increasing the concentration of CaCO3 led to an increased a-KG accumulation at the expenses of pyruvate. To study which ions in CaCO3 was responsible for the accumulation of alpha-KG, the effects of different pH buffers on the a-KG accumulation were studied. The level of alpha-KG was found to correlate with the levels of both Ca2+ and CO3(2-), with Ca2+ played a dominant role and CO3(2-) played a minor role. To find out which pathway was responsible for the accumulation of alpha-KG, the effects of biotin and thiamine on alpha-KG accumulation was investigated. The increase in biotin concentration led to an increase in alpha-KG accumulation and a decrease in C(PYR)/ C(alpha-KG), while the levels of alpha-KG and C(PYR)/C(alphaKG) were not affected by thiamine concentration. The activity of pyruvate carboxylase was increased as much as 40% when the medium was supplemented with Ca2+ . On the other hand, the activity of the pyruvate dehydrogenase complex was unaffected by the presence of Ca2+. To conclude, the higher level of a-KG was caused by higher activity of pyruvate carboxylase stimulated by Ca2+, with CO3(2-) served as the substrate of the reaction.
Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.
Stokowska, Anna; Atkins, Alison L; Morán, Javier; Pekny, Tulen; Bulmer, Linda; Pascoe, Michaela C; Barnum, Scott R; Wetsel, Rick A; Nilsson, Jonas A; Dragunow, Mike; Pekna, Marcela
2017-02-01
Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Patton, W F; Alexander, J S; Dodge, A B; Patton, R J; Hechtman, H B; Shepro, D
1991-07-01
Cell-cell apposition in bovine pulmonary endothelial cell monolayers was modulated by inducing transient increases in intracellular adenosine 3':5'-cyclic monophosphate (cAMP) and 1,4,5-inositol triphosphate (IP3). This was accomplished by mercury-arc flash photolysis of o-nitrobenzyl derivatives of the second messengers (caged compounds). Second messenger release by the mercury-arc lamp was determined by radioimmunoassay of cAMP to have a t1/2 of approximately 8 min. Each second messenger induced the phosphorylation of a distinct subset of cytoskeletal proteins; however, both IP3 and cAMP increased vimentin phosphorylation. Actin isoform patterns were not altered by the second messengers. Intracellular pulses of IP3 in pulmonary endothelial cells caused disruption of endothelial monolayer integrity as determined by phase-contrast microscopy and by visualization of actin stress fibers with rhodamine-phalloidin. Intracellular pulses of cAMP increased cell-cell contact, cell surface area, and apposition. IP3 appeared to have its greatest effect on the actin peripheral band. In silicone rubber contractility assays this agent caused contraction of pulmonary microvascular endothelial cells as visualized by an increase in wrinkles beneath the cells. On the other hand, cAMP appeared to effect both the peripheral band and centralized actin domains. Caged cAMP caused relaxation of endothelial cells as visualized by a disappearance of wrinkles beneath the cells.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee
Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver ofmore » SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.« less
Wooster, David G; Maruvada, Ravi; Blom, Anna M; Prasadarao, Nemani V
2006-01-01
Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood–brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA+E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA–E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA+E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum. PMID:16556262
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eichenbaum-Voline, Sophie; Olivier, Michael; Jones, Emma L.
2002-09-15
Combined hyperlipidemia (CHL) is a common disorder of lipidmetabolism that leads to an increased risk of cardiovascular disease. Thelipid profile of CHL is characterised by high levels of atherogeniclipoproteins and low levels of high-density-lipoprotein-cholesterol.Apolipoprotein (APO) A5 is a newly discovered gene involved in lipidmetabolism located within 30kbp of the APOA1/C3/A4 gene cluster. Previousstudies have indicated that sequence variants in this cluster areassociated with increased plasma lipid levels. To establish whethervariation at the APOA5 gene contributes to the transmission of CHL, weperformed linkage and linkage disequilibrium (LD) tests on a large cohortof families (n=128) with familial CHL (FCHL). The linkage datamore » producedevidence for linkage of the APOA1/C3/A4/A5 genomic interval to FCHL (NPL= 1.7, P = 0.042). The LD studies substantiated these data. Twoindependent rare alleles, APOA5c.56G and APOC3c.386G of this gene clusterwere over-transmitted in FCHL (P = 0.004 and 0.007, respectively), andthis was associated with a reduced transmission of the most commonAPOA1/C3/A4/A5 haplotype (frequency 0.4425) to affected subjects (P =0.013). The APOA5c.56G allele was associated with increased plasmatriglyceride levels in FCHL probands, whereas the second, andindependent, APOC3c.386G allele was associated with increased plasmatriglyceride levels in FCHL pedigree founders. Thus, this allele (or anallele in LD) may mark a quantitative trait associated with FCHL, as wellas representing a disease susceptibility locus for the condition. Thisstudy establishes that sequence variation in the APOA1/C3/A4/A5 genecluster contributes to the transmission of FCHL in a substantialproportion of affected families, and that these sequence variants mayalso contribute to the lipid abnormalities of the metabolic syndrome,which is present in up to 40 percent of persons with cardiovasculardisease.« less
NASA Technical Reports Server (NTRS)
Ossandon, J. G.; Thompson, J. R.; Sun, Yang Ren; Christen, D. K.; Chakoumakos, B. C.
1995-01-01
Magnetization studies of polycrystalline Bi(1.8)Pb(0.3)Sr2Ca2Cu3O10 superconductor, prior to and after neutron irradiation, showed an increase in J(sub c) due to irradiation damage. Analysis of the equilibrium magnetization revealed significant increases in other more fundamental properties. In particular, the London penetration depth increased by approximately 15 percent following irradiation with 8 x 10(exp 16) neutrons/sq cm. Corresponding changes were observed in the upper critical magnetic field H(sub c2). However, the most fundamental thermodynamic property, the superconductive condensation energy F(sub c), was unaffected by the moderate level of neutron-induced damage.
Evaluation of the Nutritional and Storage Quality of Meatballs Formulated with Bee Pollen.
Turhan, Sadettin; Yazici, Fehmi; Saricaoglu, Furkan Turker; Mortas, Mustafa; Genccelep, Huseyin
2014-01-01
In this study, the nutritional and storage quality of meatballs formulated with different levels (0, 1.5, 3.0, 4.5 and 6.0%) of bee pollen were investigated during storage at 41℃ for 9 d. Protein content of meatballs increased, while moisture content decreased with increased pollen. The addition of pollen improved cooking loss but decreased the redness (Hunter a value) and sensory scores. Textural parameters (hardness, springsness, gumminess, and chewiness) were affected by pollen addition and the hardness and gumminess values of meatballs decreased as the pollen content increased. While C18:0 content of meatballs slightly decreased with pollen addition, C18:2n-6c, C18:3n-3, C20:5n-3, and PUFA contents increased. The PUFA/saturated fatty acids (P/S) ratio increased from 0.05 in the control to 0.09 in meatballs with 6.0% pollen. The n-6/n-3 ratio decreased from 11.84 in the control to 3.65 in the meatballs with 6.0% pollen. The addition of pollen retarded the lipid oxidation and inhibited the bacterial growth in meatballs. The pH, redness, TBA value and total aerobic mesophilic bacteria, coliform bacteria and S. aureus counts values changed significantly during storage. The results suggest that bee pollen could be added to enhance the nutritional and storage quality of meatballs with minimal changes in composition and/or sensory properties.
Evaluation of the Nutritional and Storage Quality of Meatballs Formulated with Bee Pollen
2014-01-01
In this study, the nutritional and storage quality of meatballs formulated with different levels (0, 1.5, 3.0, 4.5 and 6.0%) of bee pollen were investigated during storage at 41℃ for 9 d. Protein content of meatballs increased, while moisture content decreased with increased pollen. The addition of pollen improved cooking loss but decreased the redness (Hunter a value) and sensory scores. Textural parameters (hardness, springsness, gumminess, and chewiness) were affected by pollen addition and the hardness and gumminess values of meatballs decreased as the pollen content increased. While C18:0 content of meatballs slightly decreased with pollen addition, C18:2n-6c, C18:3n-3, C20:5n-3, and PUFA contents increased. The PUFA/saturated fatty acids (P/S) ratio increased from 0.05 in the control to 0.09 in meatballs with 6.0% pollen. The n-6/n-3 ratio decreased from 11.84 in the control to 3.65 in the meatballs with 6.0% pollen. The addition of pollen retarded the lipid oxidation and inhibited the bacterial growth in meatballs. The pH, redness, TBA value and total aerobic mesophilic bacteria, coliform bacteria and S. aureus counts values changed significantly during storage. The results suggest that bee pollen could be added to enhance the nutritional and storage quality of meatballs with minimal changes in composition and/or sensory properties. PMID:26761280
Aydin, R; Cook, M E
2004-12-01
Conjugated linoleic acid (CLA) increased the ratio of saturated fatty acids to monounsaturated fatty acids in yolk and caused embryo mortality. Our preliminary studies showed that CLA had less of an effect on hatchability of quail than chickens. Hence, the objective was to determine the effects of dietary CLA on quail egg fatty acid content and hatchability. Eight male-female Japanese quail pairs per group were randomly assigned to diets containing 0 (canola oil; CO), 0.25, 0.5, 1, 2, or 3% CLA for 8 wk. Eggs were collected, held at 15 degrees C for 24 h, and then incubated. Three eggs from each group were collected for fatty acid analysis on the 45th day. At the end of the 8 wk, all quail were euthanized. Liver samples from female quail were obtained for fatty acid analysis. Diet containing 3, 2, or 1% CLA caused 100% embryo mortality after 6, 10, or 12 d of feeding, whereas overall hatchabilities in groups 0, 0.25, and 0.5 were 84, 86, and 64%, respectively. As the dietary CLA increased, egg and hepatic CLA increased, C16:0 increased and C16:1(n-7) and C18:1(n-9) decreased, whereas C18:0 remained unchanged. Diets containing 1, 2, or 3% CLA decreased the C20:4(n-6) levels in yolk (significantly) and liver (inconsistently) lipids. Yolk CLA levels from 0, 0.25, 0.5, 1, 2, and 3% CLA were 0.31, 0.90, 1.48, 2.44, 5.88, and 11.2%, respectively. The ratios of C16:0/C16:1(n-7) in yolks from groups fed 0, 0.25, 0.5, 1, 2, or 3% CLA were 8.2, 16.3, 20.4, 24.6, 26.1, and 28.6, respectively. The ratios of C18:0/C18:1(n-9) in yolks from hens fed 0, 0.25, 0.5, 1, 2, or 3% CLA were 0.28, 0.40, 0.48, 0.49, 0.69, and 0.83, respectively. Quail fed 0.25% CLA had increased egg size, whereas quail fed 2 or 3% had reduced egg size compared with those fed CO. Liver sizes (%) in all of the groups were increased, except for the group fed 0.25% CLA. These data suggest that CLA may affect hatchability possibly by changing the fatty acid composition of the yolk.
LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends.
Bueno, Murilo T D; Reyes, Daniel; Llano, Manuel
2017-09-15
Processing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intriguingly, impaired HIV-1 integration in LEDGF/p75-deficient cells does not result in a correspondent increase in viral cDNA circles. We postulate that increased degradation of unintegrated linear viral cDNA in cells lacking the lens epithelium-derived growth factor (LEDGF/p75) account for this inconsistency. To evaluate this hypothesis, we characterized the nucleotide sequence spanning 2-LTR junctions isolated from LEDGF/p75-deficient and control cells. LEDGF/p75 deficiency resulted in a significant increase in the frequency of 2-LTRs harboring large deletions. Of note, these deletions were dependent on the 3' processing activity of integrase and were not originated by aberrant reverse transcription. Our findings suggest a novel role of LEDGF/p75 in protecting the unintegrated 3' processed linear HIV-1 cDNA from exonucleolytic degradation.
Malaria transmission potential could be reduced with current and future climate change.
Murdock, C C; Sternberg, E D; Thomas, M B
2016-06-21
Several studies suggest the potential for climate change to increase malaria incidence in cooler, marginal transmission environments. However, the effect of increasing temperature in warmer regions where conditions currently support endemic transmission has received less attention. We investigate how increases in temperature from optimal conditions (27 °C to 30 °C and 33 °C) interact with realistic diurnal temperature ranges (DTR: ± 0 °C, 3 °C, and 4.5 °C) to affect the ability of key vector species from Africa and Asia (Anopheles gambiae and An. stephensi) to transmit the human malaria parasite, Plasmodium falciparum. The effects of increasing temperature and DTR on parasite prevalence, parasite intensity, and mosquito mortality decreased overall vectorial capacity for both mosquito species. Increases of 3 °C from 27 °C reduced vectorial capacity by 51-89% depending on species and DTR, with increases in DTR alone potentially halving transmission. At 33 °C, transmission potential was further reduced for An. stephensi and blocked completely in An. gambiae. These results suggest that small shifts in temperature could play a substantial role in malaria transmission dynamics, yet few empirical or modeling studies consider such effects. They further suggest that rather than increase risk, current and future warming could reduce transmission potential in existing high transmission settings.
Ren, Weihong; Liu, Yan; Wang, Xuerui; Piao, Chunmei; Ma, Youcai; Qiu, Shulan; Jia, Lixin; Chen, Boya; Wang, Yuan; Jiang, Wenjian; Zheng, Shuai; Liu, Chang; Dai, Nan; Lan, Feng; Zhang, Hongjia; Song, Wen-Chao; Du, Jie
2018-03-01
Thoracic aortic dissection (TAD), once ruptured, is devastating to patients, and no effective pharmaceutical therapy is available. Anaphylatoxins released by complement activation are involved in a variety of diseases. However, the role of the complement system in TAD is unknown. We found that plasma levels of C3a, C4a, and C5a were significantly increased in patients with TAD. Elevated circulating C3a levels were also detected in the developmental process of mouse TAD, which was induced by β-aminopropionitrile monofumarate (BAPN) treatment, with enhanced expression of C1q and properdin in mouse dissected aortas. These findings indicated activation of classical and alternative complement pathways. Further, expression of C3aR was obviously increased in smooth muscle cells of human and mouse dissected aortas, and knockout of C3aR notably inhibited BAPN-induced formation and rupture of TAD in mice. C3aR antagonist administered pre- and post-BAPN treatment attenuated the development of TAD. We found that C3aR knockout decreased matrix metalloproteinase 2 (MMP2) expression in BAPN-treated mice. Additionally, recombinant C3a stimulation enhanced MMP2 expression and activation in smooth muscle cells that were subjected to mechanical stretch. Finally, we generated MMP2-knockdown mice by in vivo MMP2 short hairpin RNA delivery using recombinant adeno-associated virus and found that MMP2 deficiency significantly reduced the formation of TAD. Therefore, our study suggests that the C3a - C3aR axis contributes to the development of TAD via regulation of MMP2 expression. Targeting the C3a-C3aR axis may represent a strategy for inhibiting the formation of TAD. Copyright © 2018 by The American Association of Immunologists, Inc.
Cottrell, M B; Jackson, C W; McDonald, T P
1991-07-01
Several previous studies have shown that hypoxia increases erythropoiesis and decreases thrombocytopoiesis in mice. It has been postulated that the thrombocytopenia is caused by stem cell competition between the erythrocytic and megakaryocytic cell lines. In the present work, we compared the effects of severe hypoxia (5.5-6.0% O2) in both male and female C3H and BALB/c mice by measuring their abilities to produce red blood cells and platelets. All mice had significant increases in packed cell volumes and marked decreases in platelet production after hypoxia; however, there were significant differences in the degree of stimulation in the two mouse strains. After 14 days of hypoxia, the percentage of 35S incorporation into platelets, total circulating platelet counts and total circulating platelet masses were lower in C3H mice than in BALB/c mice, but platelet sizes were larger. Also, hypoxia caused greater changes in male mice than in female mice, with male C3H mice showing the greatest increase in packed cell volumes and the lowest platelet counts of all mice tested. The least responses were observed in female BALB/c mice. BALB/c mice had higher P50 (right-shifted O2 dissociation curves) and lower erythrocyte 2,3-diphosphoglycerate values than C3H mice, indicating a lower hemoglobin O2 affinity for BALB/c mice. The results indicate that the effects of hypoxia are not direct upon platelet production, but that the thrombocytopenia is a result of stimulation of erythropoiesis. These data support the stem cell competition hypothesis and illustrate that the degree of the inverse relationship between red blood cells and platelet production of hypoxic mice is dependent, to a large degree, upon the sex and strain of mice that are used.
Bi, Nan; Yan, Sheng-kai; Li, Guo-ping; Yin, Zhi-nong; Chen, Bao-sheng
2004-11-01
The disorder of triglyceride (TG) metabolism leading to hypertriglyceridemia is an independent risk factor for coronary artery disease (CAD). Variants in the newly identified apolipoprotein APOA5 gene were found to be strongly associated with elevated TG levels in different racial groups. In this study, we investigated the phenotypic effects of two polymorphisms (APOA5-1131T>C and APOC3-482C>T) on susceptibility to CAD in 312 Chinese CAD patients diagnosed by angiography. The frequency of the APOA5-1131C allele in these patients was significantly higher than that of the control group (39.9 vs. 33.3%, P=0.02). Compared with the wild type TT, CC homozygotes had a significantly increased CAD risk (OR=1.93 and OR=1.80 using unadjusted and adjusted logistic regression models, respectively). This association still existed after adjustment for the APOC3-482 variant. The APOA5-1131C allele also showed a correlation with increasing plasma TG levels (P<0.001). These data suggest that the APOA5-1131T>C polymorphism might contribute to an increased risk of CAD among Chinese as a result of its effect on TG metabolism; this effect was found to be independent of the APOC3-482C>T variant.
Joko, Masahiro; Osuka, Koji; Usuda, Nobuteru; Atsuzawa, Kimie; Aoyama, Masahiro; Takayasu, Masakazu
2013-08-09
Transforming growth factor-β (TGF-β) is an anti-inflammatory cytokine and is expressed in the injured spinal cord. TGF-β signals through receptors to activate Smad proteins, which translocate into the nucleus. In the present study, we investigated the chronological alterations and cellular locations of the TGF-β/Smad signaling pathway following spinal cord injury (SCI) in mice. ELISA analysis showed that the concentration of interleukin-6 (IL-6) in injured spinal cords significantly increases immediately after SCI, while the concentration of TGF-β gradually increased after SCI, peaked at 2 days, and then gradually decreased. Immunohistochemical studies revealed that Smad3 was mainly expressed in neurons of the spinal cord. Phosphorylated Smad3 at the C-terminus (p-Smad3C) was stained within the motor neurons in the anterior horn, while phosphorylated Smad3 at the linker regions (p-Smad3L) was expressed in astrocytes within gray matter. These findings suggest that SCI induces gradual increases in TGF-β and induces different activation of p-Smad3C and p-Smad3L. Phosphorylated Smad3C might be involved in neuronal degeneration after SCI, and p-Smad3L may play a role in glial scar formation by astrocytes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Akopyan, T. K.; Padalko, A. G.; Belov, N. A.; Shurkin, P. K.
2016-07-01
The phase-transition temperatures of a high-strength cast AM5 aluminum alloy are determined at atmospheric pressure and an excess pressure of 100 MPa using differential barothermic analysis (DBA) and classical differential thermal analysis (DTA). An excess pressure of 100 MPa is shown to increase the critical temperatures of the alloy by 12-17°C (including an increase in the solidus temperature by 12°C), which makes it possible to increase the hot isostatic pressing (HIP) temperature above the temperature of heating for quenching. The following three barothermal treatment schedules at p = 100 MPa and τ = 3 h, which have different isothermal holding temperatures, are chosen to study the influence of HIP on the structure and the properties of alloy AM5 castings: HIP1 ( t 1 = 505 ± 2°C), HIP2 ( t 2 = 520 ± 2°C), and HIP3 ( t 3 = 540 ± 2°C). High-temperature HIP treatment is found to increase the casting density and improve the morphology of secondary phases additionally, which ensures an increase in the plasticity of the alloy. In particular, the plasticity of the alloy after heat treatment according to schedule HIP3 + T6 (T6 means artificial aging to achieve the maximum strength) increases by a factor of ˜1.5.
Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.
Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P
2016-10-01
The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog. © 2016 Society for Reproduction and Fertility.
Marjot, Jack; Kaier, Thomas E; Martin, Eva D; Reji, Shiney S; Copeland, O'Neal; Iqbal, Mohammed; Goodson, Bob; Hamren, Sarah; Harding, Sian E; Marber, Michael S
2017-05-01
Myocardial infarction is diagnosed when biomarkers of cardiac necrosis exceed the 99th centile, although guidelines advocate even lower concentrations for early rule-out. We examined how many myocytes and how much myocardium these concentrations represent. We also examined if dietary troponin can confound the rule-out algorithm. Individual rat cardiac myocytes, rat myocardium, ovine myocardium, or human myocardium were spiked into 400-μL aliquots of human serum. Blood was drawn from a volunteer after ingestion of ovine myocardium. High-sensitivity assays were used to measure cardiac troponin T (cTnT; Roche, Elecsys), cTnI (Abbott, Architect), and cardiac myosin-binding protein C (cMyC; EMD Millipore, Erenna ® ). The cMyC assay could only detect the human protein. For each rat cardiac myocyte added to 400 μL of human serum, cTnT and cTnI increased by 19.0 ng/L (95% CI, 16.8-21.2) and 18.9 ng/L (95% CI, 14.7-23.1), respectively. Under identical conditions cTnT, cTnI, and cMyC increased by 3.9 ng/L (95% CI, 3.6-4.3), 4.3 ng/L (95% CI, 3.8-4.7), and 41.0 ng/L (95% CI, 38.0-44.0) per μg of human myocardium. There was no detectable change in cTnI or cTnT concentration after ingestion of sufficient ovine myocardium to increase cTnT and cTnI to approximately 1 × 10 8 times their lower limits of quantification. Based on pragmatic assumptions regarding cTn and cMyC release efficiency, circulating species, and volume of distribution, 99th centile concentrations may be exceeded by necrosis of 40 mg of myocardium. This volume is much too small to detect by noninvasive imaging. © 2017 American Association for Clinical Chemistry.
Jang, Min-Kyung; Kim, Ji-Hyun; Jung, Myeong Ho
2017-01-01
Previous studies have shown that tri- or di-methylation of histone H3 at lysine 9 (H3K9me3/me2) on the promoter of the peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) contribute to the repression of PPARγ and C/EBPα and inhibition of adipogenesis in 3T3-L1 preadipocytes. The balance of histone methylation is regulated by histone methyltransferases and demethylases. However, it is poorly understood which demethylases are responsible for removing H3K9me3/me2 on the promoter of PPARγ and C/EBPα. JMJD2B is a H3K9me3/me2 demethylase that was previously shown to activate adipogenesis by promoting mitotic clonal expansion. Nevertheless, it remains unclear whether JMJD2B plays a role in the regulation of adipogenesis by removing H3K9me3/me2 on the promoter of PPARγ and C/EBPα and subsequently activating PPARγ and C/EBPα expression. Here, we showed that JMJD2B decreased H3K9me3/me2 on the promoter of PPARγ and C/EBPα, which in turn stimulated the expression of PPARγ and C/EBPα. JMJD2B knockdown using siRNA in 3T3-L1 preadipocytes repressed the expression of PPARγ and C/EBPα, resulting in inhibition of adipogenesis. This was accompanied by increased enrichment of H3K9me3/me2 on the promoter of PPARγ and C/EBPα. In contrast, overexpression of JMJD2B increased the expression of PPARγ and C/EBPα, which was accompanied by decreased enrichment of H3K9me3/me2 on the promoter and activated adipogenesis. Together, these results indicate that JMJD2B regulates PPARγ and C/EBPα during adipogenesis. PMID:28060835
Rat liver mitochondrial dysfunction by addition of copper(II) or iron(III) ions.
Saporito-Magriñá, Christian; Musacco-Sebio, Rosario; Acosta, Juan M; Bajicoff, Sofía; Paredes-Fleitas, Paola; Boveris, Alberto; Repetto, Marisa G
2017-01-01
Increased copper (Cu) and iron (Fe) levels in liver and brain are associated to oxidative stress and damage with increased phospholipid oxidation process. The aim of this work was to assess the toxic effects of Cu 2+ and Fe 3+ addition to rat liver mitochondria by determining mitochondrial respiration in states 3 (active respiration) and 4 (resting respiration), and phospholipid peroxidation. Both, Cu 2+ and Fe 3+ produced decreases in O 2 consumption in a concentration-dependent manner in active state 3: both ions by 42% with malate-glutamate as complex I substrate (concentration for half maximal response (C 50 ) 60μM Cu 2+ and 1.25mM Fe 3+ ), and with succinate as complex II substrate: 64-69% with C 50 of 50μM Cu 2+ and with C 50 of 1.25mM of Fe 3+ . Respiratory control decreased with Cu 2+ (C 50 50μM) and Fe 3+ (C 50 1.25-1-75mM) with both substrates. Cu 2+ produced a 2-fold increase and Fe 3+ a 5-fold increase of thiobarbituric acid-reactive substances (TBARS) content from 25μM Cu 2+ (C 50 40μM) and from 100μM Fe 3+ (C 50 1.75mM). Supplementations with Cu 2+ and Fe 3+ ions induce mitochondrial dysfunction with phospholipid peroxidation in rat liver mitochondria. Although is proved that a Fenton/Haber Weiss mechanism of oxidative damage occurs in metal-ion induced mitochondrial toxicity, slightly different responses to the metal ions suggest some differences in the mechanism of intracellular toxicity. The decreased rates of mitochondrial respiration and the alteration of mitochondrial function by phospholipid and protein oxidations lead to mitochondrial dysfunction, cellular dyshomeostasis and cell death. Copyright © 2016 Elsevier Inc. All rights reserved.
Priego, Neibla; Arechederra, María; Sequera, Celia; Bragado, Paloma; Vázquez-Carballo, Ana; Gutiérrez-Uzquiza, Álvaro; Martín-Granado, Víctor; Ventura, Juan José; Kazanietz, Marcelo G.; Guerrero, Carmen; Porras, Almudena
2016-01-01
C3G, a Guanine nucleotide Exchange Factor (GEF) for Rap1 and R-Ras, has been shown to play important roles in development and cancer. Previous studies determined that C3G regulates cell death through down-regulation of p38α MAPK activity. Here, we found that C3G knock-down in MEFs and HCT116 cells promotes migration and invasion through Rap1-mediated p38α hyper-activation. These effects of C3G were inhibited by Rap1 knock-down or inactivation. The enhanced migration observed in C3G depleted HCT116 cells was associated with reduction in E-cadherin expression, internalization of ZO-1, actin cytoskeleton reorganization and decreased adhesion. We also found that matrix metalloproteases MMP2 and MMP9 are involved in the pro-invasive effect of C3G down-regulation. Additionally, our studies revealed that both C3G and p38α collaborate to promote growth of HCT116 cells in vitro and in vivo, possibly by enhancing cell survival. In fact, knocking-down C3G or p38α individually or together promoted cell death in vitro, although only the double C3G-p38α silencing was able to increase cell death within tumors. Notably, we found that the pro-tumorigenic function of C3G does not depend on p38α or Rap1 activation. Altogether, our studies uncover novel mechanisms by which C3G controls key aspects of tumorigenesis. PMID:27286263
Park, Joo-Hung; Lee, Jeong-Min; Lee, Eun-Jin; Hwang, Won-Bhin; Kim, Da-Jeong
2018-04-30
Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of α-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent. I3C increased the expression of Muc2 and lysozyme, lineage-specific genes for goblet cells and Paneth cells, respectively, but inhibits the expression of IAP, a marker gene for enterocytes. In the intestines of mice treated with I3C, the number of goblet cells was reduced, but the number of Paneth cells and the depth and length of crypts and villi were not changed. I3C increased the level of active nonphosphorylated β-catenin, but suppressed the Notch signal. As a result, expression of Hes1, a Notch target gene and a transcriptional repressor that plays a key role in enterocyte differentiation, was reduced, whereas expression of Math1, involved in the differentiation of secretory lineages, was increased. These results provide direct evidence for the role of AhR in the regulation of the development of intestinal stem cells and indicate that such regulation is likely mediated by regulation of Wnt and Notch signals.
NASA Technical Reports Server (NTRS)
Smedley, J. E.; Leone, S. R.
1983-01-01
Wavelength-specific relative quantum yields of metastable I from pulsed laser photodissociation of i-C3F7I and n-C3F7I in the range 265-336 nm are determined by measuring the time-resolved infrared emission from the atomic I(P-2(1/2) P-2(3/2) transition. It is shown that although this yield appears to be unity from 265 to 298 nm, it decreases dramatically at longer wavelengths. Values are also reported for the enhancement of emission from metastable I due to exciplex formation at several temperatures. The exciplex formation emission increases linearly with parent gas pressure, but decreases with increasing temperature. Absorption spectra of i- and n-C3F7I between 303 and 497 K are presented, and the effect of temperature on the quantum yields at selected wavelengths greater than 300 nm, where increasing the temperature enhances the absorption considerably, are given. The results are discussed in regard to the development of solar-pumped iodine lasers.
Significant increase of Curie temperature in nano-scale BaTiO{sub 3}
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Yueliang; Liao, Zhenyu; Fang, Fang
2014-11-03
The low Curie temperature (T{sub c} = 130 °C) of bulk BaTiO{sub 3} greatly limits its applications. In this work, the phase structures of BaTiO{sub 3} nanoparticles with sizes ranging from 2.5 nm to 10 nm were studied at various temperatures by using aberration-corrected transmission electron microscopy (TEM) equipped with an in-situ heating holder. The results implied that each BaTiO{sub 3} nanoparticle was composed of different phases, and the ferroelectric ones were observed in the shells due to the complicated surface structure. The ferroelectric phases in BaTiO{sub 3} nanoparticles remained at 600 °C, suggesting a significant increase of T{sub c}. Based on the in-situ TEM resultsmore » and the data reported by others, temperature-size phase diagrams for BaTiO{sub 3} particles and ceramics were proposed, showing that the phase transition became diffused and the T{sub c} obviously increased with decreasing size. The present work sheds light on the design and fabrication of advanced devices for high temperature applications.« less
Kawamata, Seiji; Matsuzaki, Koichi; Murata, Miki; Seki, Toshihito; Matsuoka, Katsuyoshi; Iwao, Yasushi; Hibi, Toshifumi; Okazaki, Kazuichi
2011-03-01
Both chronic inflammation and somatic mutations likely contribute to the pathogenesis of ulcerative colitis (UC)-associated dysplasia and cancer. On the other hand, both tumor suppression and oncogenesis can result from transforming growth factor (TGF)-β signaling. TGF-β type I receptor (TβRI) and Ras-associated kinases differentially phosphorylate a mediator, Smad3, to become C-terminally phosphorylated Smad3 (pSmad3C), linker phosphorylated Smad3 (pSmad3L), and both C-terminally and linker phosphorylated Smad3 (pSmad3L/C). The pSmad3C/p21(WAF1) pathway transmits a cytostatic TGF-β signal, while pSmad3L and pSmad3L/C promote cell proliferation by upregulating c-Myc oncoprotein. The purpose of this study was to clarify the alteration of Smad3 signaling during UC-associated carcinogenesis. By immunostaining and immunofluorescence, we compared pSmad3C-, pSmad3L-, and pSmad3L/C-mediated signaling in colorectal specimens representing colitis, dysplasia, or cancer from eight UC patients with signaling in normal colonic crypts. We also investigated p53 expression and mutations of p53 and K-ras genes. We further sought functional meaning of the phosphorylated Smad3-mediated signaling in vitro. As enterocytes in normal crypts migrated upward toward the lumen, cytostatic pSmad3C/p21(WAF1) tended to increase, while pSmad3L/c-Myc shown by progenitor cells gradually decreased. Colitis specimens showed prominence of pSmad3L/C/c-Myc, mediated by TGF-β and tumor necrosis factor (TNF)-α, in all enterocyte nuclei throughout entire crypts. In proportion with increases in frequency of p53 and K-ras mutations during progression from dysplasia to cancer, the oncogenic pSmad3L/c-Myc pathway came to be dominant with suppression of the pSmad3C/p21(WAF1) pathway. Oncogenic Smad3 signaling, altered by chronic inflammation and eventually somatic mutations, promotes UC-associated neoplastic progression by upregulating growth-related protein. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
Effect of Initiators on Thermal Changes in Soft Tissues Using a Diode Laser.
Romanos, Georgios E; Sacks, Danielle; Montanaro, Nicholas; Delgado-Ruiz, Rafael; Calvo-Guirado, Jose Luis; Javed, Fawad
2018-06-15
The aim was to determine the effect of various initiators on the thermal changes that occur during incisions performed in soft tissues using a diode laser. There are no studies that have assessed the effect of various initiators on the thermal changes that occur during incisions performed in soft tissues using a diode laser. Thermal changes were observed during standardized incisions in chicken breast (without skin) via thermoelements over a 10-sec irradiation period. Incisions were created using a 975 nm diode laser with a 320 μ fiber tip diameter. Incisions (10 in each group) were performed with and without an initiator (control group). Red/blue articulating paper, cork, and SureStep ® were used as initiators. The tissue was irradiated in a continuous wave mode at 3 and 6 W in room temperature (21°C). At 3 and 6 W without any initiator, the mean temperature increased by 5.7°C versus 12.4°C, respectively. Cork initiator at 3 and 6 W resulted in temperature increase by 4.88°C versus 6.21°C, respectively. Incisions made using the blue/red articulating paper-initiated tip resulted in temperature increase by 2.9/5.8°C versus 8.2/7.6°C at 3 and 6 W power settings, respectively. Initiation with SureStep resulted in temperature increase by 2.3°C and at 6 W by 4.1°C. No significant differences were recorded between the different groups, but higher temperatures were associated with higher power settings. The power settings of the diode laser and type of initiator used, both effect the degree to which the temperature of the soft tissue increases during incisions and have to be considered for the safety in soft tissue applications.
Yousufzai, S Y; Chen, A L; Abdel-Latif, A A
1988-12-01
Comparative studies on the effects of prostaglandins (PGs) on 1,2-diacylglycerol, measured as phosphatidic acid (PA), and inositol trisphosphate (IP3) production, cyclic AMP (cAMP) formation, myosin light chain (MLC) phosphorylation and contraction in the iris sphincter smooth muscle of rabbit, bovine and other mammalian species were undertaken and functional and biochemical relationships between the IP3-Ca++ and cAMP second messenger systems were demonstrated. The findings obtained from these studies can be summarized as follows: 1) all PGs investigated, including PGE2, PGF2 alpha, PGF2 alpha-ester, PGE1 and PGA2 increased IP3 accumulation and PA formation, and the extent of stimulation was dependent on the animal species. Thus, PGF2 alpha-ester (1 microM), the most potent of the PGs, increased IP3 accumulation in rabbit and bovine sphincters by 33 and 58%, respectively, and increased PA formation by 67 and 56%, respectively. The PG increased IP3 accumulation in both rabbit and bovine sphincters very rapidly (T1/2 values about 26 sec) and in a dose-dependent manner. 2) The PG had no effect on MLC phosphorylation in the rabbit sphincter, but it increased that of the bovine by 36%. 3) The PG increased cAMP formation by 75% in the rabbit sphincter but it had no effect on that of the bovine. 4) The PG induced a maximal contractile response in the bovine sphincter but it had no effect on that of the rabbit. 5) In the bovine, PGA2 induced IP3 accumulation and contraction, without an effect on cAMP formation; however, in the rabbit, cat and dog it increased cAMP formation and had no effect on IP3 accumulation and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Kimme-Smith, C; Rothschild, P A; Bassett, L W; Gold, R H; Moler, C
1989-01-01
Six different combinations of film-processor temperature (33.3 degrees C, 35 degrees C), development time (22 sec, 44 sec), and chemistry (Du Pont medium contrast developer [MCD] and Kodak rapid process [RP] developer) were each evaluated by separate analyses with Hurter and Driffield curves, test images of plastic step wedges, noise variance analysis, and phantom images; each combination also was evaluated clinically. Du Pont MCD chemistry produced greater contrast than did Kodak RP chemistry. A change in temperature from 33.3 degrees C (92 degrees F) to 35 degrees C (95 degrees F) had the least effect on dose and image contrast. Temperatures of 36.7 degrees C (98 degrees F) and 38.3 degrees C (101 degrees F) also were tested with extended processing. The speed increased for 36.7 degrees C but decreased at 38.3 degrees C. Base plus fog increased, but contrast decreased for these higher temperatures. Increasing development time had the greatest effect on decreasing the dose required for equivalent film darkening when imaging BR12 breast equivalent test objects; ion chamber measurements showed a 32% reduction in dose when the development time was increased from 22 to 44 sec. Although noise variance doubled in images processed with the extended development time, diagnostic capability was not compromised. Extending the processing time for mammographic films was an effective method of dose reduction, whereas varying the processing temperature and chemicals had less effect on contrast and dose.
Patterns of Care for Locally Advanced Pancreatic Adenocarcinoma Using the National Cancer Database.
Amini, Arya; Jones, Bernard L; Stumpf, Priscilla; Leong, Stephen; Lieu, Christopher H; Weekes, Colin; Davis, S Lindsey; Messersmith, Wells A; Purcell, William T; Ghosh, Debashis; Schefter, Tracey; Goodman, Karyn A
2017-08-01
The role of radiotherapy (RT) in locally advanced pancreatic cancer (LAPC) is uncertain. This study examines patterns of care and survival outcomes of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT). The National Cancer Database was queried for nonmetastatic LAPC patients who received chemotherapy alone or C + RT. Of the 13,695 patients included, 5306 underwent chemotherapy alone and 4971, C + RT. Use of C + RT declined from 2003 to 2011 (73%-53%), whereas chemotherapy alone increased. Of those receiving RT, rates of intensity-modulated radiotherapy (IMRT) increased (27%-72%), whereas 3-dimensional (3D) RT decreased (73%-28%). Unadjusted 1-year overall survival (OS) was longer for versus chemotherapy (45.6% vs 38.7%), as was 2-year OS (12.9% vs 11.9%) (hazard ratio, 0.88; 0.85-0.91; P < 0.001). Under multivariate analysis, C + RT was associated with improved OS (hazard ratio, 0.84; 0.81-0.87; P < 0.001). On subgroup analysis comparing C + IMRT, C + 3D RT, and chemotherapy alone, 1-year OS was 49.1%, 45.1%, and 38.7%, and 2-year OS was 13.1%, 11.6%, and 11.9% accordingly. Utilization of RT in LAPC is decreasing, whereas chemotherapy alone is increasing. Of patients undergoing RT, rates of IMRT are increasing. Whereas C + IMRT appeared to be associated with improved OS compared with chemotherapy alone, 3D RT was not.
Zhang, Yu; Tang, Yibo; Shen, Hongxing
2017-12-01
In order to reduce the incidence of adjacent segment disease (ASD), the current study was designed to establish Chinese finite element models of normal 3rd~7th cervical vertebrae (C3-C7) and anterior cervical corpectomy and fusion (ACCF) with internal fixation , and analyze the influence of screw sagittal angle (SSA) on stress on endplate of adjacent cervical segments. Mimics 8.1 and Abaqus/CAE 6.10 softwares were adopted to establish finite element models. For C4 superior endplate and C6 inferior endplate, their anterior areas had the maximum stress in anteflexion position, and their posterior areas had the maximum stress in posterior extension position. As SSA increased, the stress reduced. With an increase of 10° in SSA, the stress on anterior areas of C4 superior endplate and C6 inferior endplate reduced by 12.67% and 7.99% in anteflexion position, respectively. With an increase of 10° in SSA, the stress on posterior areas of C4 superior endplate and C6 inferior endplate reduced by 9.68% and 10.22% in posterior extension position, respectively. The current study established Chinese finite element models of normal C3-C7 and ACCF with internal fixation , and demonstrated that as SSA increased, the stress on endplate of adjacent cervical segments decreased. In clinical surgery, increased SSA is able to play important role in protecting the adjacent cervical segments and reducing the incidence of ASD.
Ibeagha-Awemu, Eveline M; Li, Ran; Ammah, Adolf A; Dudemaine, Pier-Luc; Bissonnette, Nathalie; Benchaar, Chaouki; Zhao, Xin
2016-02-09
Nutritional strategies can decrease saturated fatty acids (SFAs) and increase health beneficial fatty acids (FAs) in bovine milk. The pathways/genes involved in these processes are not properly defined. Next-generation RNA-sequencing was used to investigate the bovine mammary gland transcriptome following supplemental feeding with 5% linseed oil (LSO) or 5% safflower oil (SFO). Holstein cows in mid-lactation were fed a control diet for 28 days (control period) followed by supplementation with 5% LSO (12 cows) or 5% SFO (12 cows) for 28 days (treatment period). Milk and mammary gland biopsies were sampled on days-14 (control period), +7 and +28 (treatment period). Milk was used to measure fat(FP)/protein(PP) percentages and individual FAs while RNA was subjected to sequencing. Milk FP was decreased by 30.38% (LSO) or 32.42% (SFO) while PP was unaffected (LSO) or increased (SFO). Several beneficial FAs were increased by LSO (C18:1n11t, CLA:10t12c, CLA:9c11t, C20:3n3, C20:5n3, C22:5n3) and SFO (C18:1n11t, CLA:10t12c, C20:1c11, C20:2, C20:3n3) while several SFAs (C4:0, C6:0, C8:0, C14:0, C16:0, C17:0, C24:0) were decreased by both treatments (P < 0.05). 1006 (460 up- and 546 down-regulated) and 199 (127 up- and 72 down-regulated) genes were significantly differentially regulated (DE) by LSO and SFO, respectively. Top regulated genes (≥ 2 fold change) by both treatments (FBP2, UCP2, TIEG2, ANGPTL4, ALDH1L2) are potential candidate genes for milk fat traits. Involvement of SCP2, PDK4, NQO1, F2RL1, DBI, CPT1A, CNTFR, CALB1, ACADVL, SPTLC3, PIK3CG, PIGZ, ADORA2B, TRIB3, HPGD, IGFBP2 and TXN in FA/lipid metabolism in dairy cows is being reported for the first time. Functional analysis indicated similar and different top enriched functions for DE genes. DE genes were predicted to significantly decrease synthesis of FA/lipid by both treatments and FA metabolism by LSO. Top canonical pathways associated with DE genes of both treatments might be involved in lipid/cholesterol metabolism. This study shows that rich α-linolenic acid LSO has a greater impact on mammary gland transcriptome by affecting more genes, pathways and processes as compared to SFO, rich in linoleic acid. Our study suggest that decrease in milk SFAs was due to down-regulation of genes in the FA/lipid synthesis and lipid metabolism pathways while increase in PUFAs was due to increased availability of ruminal biohydrogenation metabolites that were up taken and incorporated into milk or used as substrate for the synthesis of PUFAs.
NASA Astrophysics Data System (ADS)
Rafi-ud-din; Shafqat, Q. A.; Shahzad, M.; Ahmad, Ejaz; Asghar, Z.; Rafiq, Nouman; Qureshi, A. H.; Syed, Waqar adil; asim Pasha, Riffat
2016-12-01
Sodium benzoate (SB) is used for the first time to inhibit the corrosion of Al6061-B4C composites in H3BO3 and NaCl solutions. Al6061100-x -x wt% B4C (x = 0, 5, and 10) composites are manufactured by a powder metallurgy route. The corrosion inhibition efficiency of SB is investigated as a function of the volume fractions of B4C particles by using potentiodynamic polarization and electrochemical impedance techniques. Without the use of an inhibitor, an increase of the B4C particles in the composite decreases the corrosion resistance of Al6061-B4C composites. It is found that SB is an efficient corrosion inhibitor for Al6061-B4C composites in both investigated solutions. The corrosion inhibition efficiency of SB increases with an increase in B4C content. Since SB is an adsorption type inhibitor, it is envisaged that an extremely thin layer of molecules adsorbs onto the surface and suppresses the oxidation and reduction. It is found that the inhibitor effect of SB is more pronounced in a H3BO3 environment than in NaCl solution. Further, the mechanism of corrosion inhibition by SB is illustrated by using optical and scanning electron microscopy of corroded samples. It is found that the adsorption of benzoate ions on the Al surface and its bonding with Al3+ ions forms a hydrophobic layer on top of the exposed Al surface, which enhances the protection against dissolved boride ions.
Ruan, D; Lin, Y C; Chen, W; Wang, S; Xia, W G; Fouad, A M; Zheng, C T
2015-12-01
The study was designed to evaluate the effects of different dietary levels of rice bran (RB) in laying duck diets on performance, egg quality, oxidation status, egg yolk fatty acid composition, and hepatic expression of fatty acid metabolism-related genes. Longyan females (1080) with similar BW at 19 wk of age were randomly assigned to 6 dietary treatments, each consisting of 6 replicates of 30 birds. The basal diet (I) was a typical corn-soybean ration while the experimental diets (II to VI) substituted RB for corn and wheat bran and a small reduction of soybean meal. The level of substitution in diets (II to VI) was 6%, 12%, 18%, 24%, and 30%, respectively. The experiment lasted for 12 wks. Average egg weight and daily egg mass decreased linearly as the level of RB inclusion increased (P<0.001) and feed conversion ratio linearly increased (P<0.001). The proportions of C14:0 and C18:0 and total saturated fatty acids (SFA) in egg yolk linearly decreased with increasing RB, and many of the key polyunsaturated fatty acids (PUFA), like C18:2 n-6 and C18:3 n-3, linearly increased (P<0.001), but not those of C20:5 n-3 and C22:6 n-3. There were linear decreases (P<0.001) in hepatic abundance of FAS and SREBP1 transcripts, with a substantial reduction to about 30% those of ducks fed the control diet; there were no treatment effects on productive performance, eggshell thickness, strength, Haugh unit, antioxidation status, and egg yolk cholesterol or triglyceride content (P>0.05). In conclusion, the current study suggests that ducks from 19 to 31 wk could be fed diets with up to about 18% RB without effect on the number of eggs produced, egg quality, and oxidative status. Increasing amounts of RB linearly increased egg yolk concentrations of key fatty acids like C18:2 n-6 and C18:3 n-3 and decreased the hepatic abundance of FAS and SREBP-1 transcripts. © 2015 Poultry Science Association Inc.
Xu, Jianhua; Morris, Lynsie; Thapa, Arjun; Ma, Hongwei; Michalakis, Stylianos; Biel, Martin; Baehr, Wolfgang; Peshenko, Igor V; Dizhoor, Alexander M; Ding, Xi-Qin
2013-09-11
Photoreceptor cyclic nucleotide-gated (CNG) channels regulate Ca(2+) influx in rod and cone photoreceptors. cGMP, the native ligand of the photoreceptor CNG channels, has been associated with cytotoxicity when its levels rise above normal due to defects in photoreceptor phosphodiesterase (PDE6) or regulation of retinal guanylyl cyclase (retGC). We found a massive accumulation of cGMP in CNGA3-deficient retina and investigated whether cGMP accumulation plays a role in cone degeneration in CNG channel deficiency. The time course study showed that the retinal cGMP level in Cnga3(-/-);Nrl(-/-) mice with CNGA3 deficiency on a cone-dominant background was sharply increased at postnatal day 8 (P8), peaked around P10-P15, remained high through P30-P60, and returned to near control level at P90. This elevation pattern correlated with photoreceptor apoptotic death, which peaked around P15-P20. In Cnga3(-/-);Gucy2e(-/-) mice lacking retGC1, cone density and expression levels of cone-specific proteins were significantly increased compared with Cnga3(-/-), consistent with a role of cGMP accumulation as the major contributor to cone death caused by CNG channel deficiency. The activity and expression levels of cGMP-dependent protein kinase G (PKG) were significantly increased in Cnga3(-/-);Nrl(-/-) retina compared with Nrl(-/-), suggesting an involvement of PKG regulation in cell death. Our results indicate that cGMP accumulation in photoreceptors can itself exert cytotoxic effect in cones, independently of CNG channel activity and Ca(2+) influx.
Ding, K H; Latimer, A J; Abdel-Latif, A A
1999-01-01
We investigated the effects of endothelins (ETs) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ET-3 increased cGMP formation in a concentration-dependent manner (EC50 = 98nM), which was 2.5 times higher than that of ET-1. The ET(B)receptor agonists sarafotoxin-S6c and IRL 1620 also increased cGMP production, mimicking the effects of the ETs. The ET(B) receptor antagonist BQ 788, but not the ET(A) receptor antagonist BQ610, dose-dependently blocked ET-3-stimulated cGMP formation (IC50=10nM). The phorbol ester, Phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylyl cyclase in smooth muscle, dose-dependently inhibited ET-3-stimulated cGMP accumulation (IC50=66nM). LY83583 and ODQ, inhibitors of soluble guanylyl cyclases, as well as inhibitors of the nitric oxide cascade and of intracellular Ca2+ elevation had no appreciable effect on ET-3-induced cGMP production. ET-3 markedly inhibited carbachol-induced intracellular Ca2+ mobilization. We conclude that ET-3 increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ET(B) receptor subtype and subsequent stimulation of the membrane-bound guanylyl cyclase. Elevation of cGMP by ET and the subsequent inhibition of muscarinic stimulation of intracellular Ca2+ mobilization by the cyclic nucleotide could serve to modulate the contractile effects of Ca2+-mobilizing agonists in the iris sphincter smooth muscle.
Potential carbon emissions dominated by carbon dioxide from thawed permafrost soils
Schadel, Christina; Bader, Martin K. F.; Schuur, Edward; ...
2016-01-01
Increasing temperatures in northern high latitudes are causing permafrost to thaw, making large amounts of previously frozen organic matter vulnerable to microbial decomposition. Permafrost thaw also creates a fragmented landscape of drier and wetter soil conditions that determine the amount and form (carbon dioxide (CO2), or methane (CH4)) of carbon (C) released to the atmosphere. The rate and form of C release control the magnitude of the permafrost C feedback, so their relative contribution with a warming climate remains unclear. We quantified the effect of increasing temperature and changes from aerobic to anaerobic soil conditions using 25 soil incubation studiesmore » from the permafrost zone. Here we show, using two separate meta-analyses, that a 10 C increase in incubation temperature increased C release by a factor of 2.0 (95% confidence interval (CI), 1.8 to 2.2). Under aerobic incubation conditions, soils released 3.4 (95% CI, 2.2 to 5.2) times more C than under anaerobic conditions. Even when accounting for the higher heat trapping capacity of CH4, soils released 2.3 (95% CI, 1.5 to 3.4) times more C under aerobic conditions. These results imply that permafrost ecosystems thawing under aerobic conditions and releasing CO2 will strengthen the permafrost C feedback more than waterlogged systemsreleasingCO2 andCH4 for a given amount of C.« less
Potential carbon emissions dominated by carbon dioxide from thawed permafrost soils
Schädel, Christina; Bader, Martin K.-F.; Schuur, Edward A.G.; Biasi, Christina; Bracho, Rosvel; Čapek, Petr; De Baets, Sarah; Diáková, Kateřina; Ernakovich, Jessica; Estop-Aragones, Cristian; Graham, David E.; Hartley, Iain P.; Iversen, Colleen M.; Kane, Evan S.; Knoblauch, Christian; Lupascu, Massimo; Martikainen, Pertti J.; Natali, Susan M.; Norby, Richard J.; O'Donnell, Jonathan A.; Roy Chowdhury, Taniya; Šantrůčková, Hana; Shaver, Gaius; Sloan, Victoria L.; Treat, Claire C.; Turetsky, Merritt R.; Waldrop, Mark P.; Wickland, Kimberly P.
2016-01-01
Increasing temperatures in northern high latitudes are causing permafrost to thaw, making large amounts of previously frozen organic matter vulnerable to microbial decomposition. Permafrost thaw also creates a fragmented landscape of drier and wetter soil conditions that determine the amount and form (carbon dioxide (CO2), or methane (CH4)) of carbon (C) released to the atmosphere. The rate and form of C release control the magnitude of the permafrost C feedback, so their relative contribution with a warming climate remains unclear. We quantified the effect of increasing temperature and changes from aerobic to anaerobic soil conditions using 25 soil incubation studies from the permafrost zone. Here we show, using two separate meta-analyses, that a 10 °C increase in incubation temperature increased C release by a factor of 2.0 (95% confidence interval (CI), 1.8 to 2.2). Under aerobic incubation conditions, soils released 3.4 (95% CI, 2.2 to 5.2) times more C than under anaerobic conditions. Even when accounting for the higher heat trapping capacity of CH4, soils released 2.3 (95% CI, 1.5 to 3.4) times more C under aerobic conditions. These results imply that permafrost ecosystems thawing under aerobic conditions and releasing CO2 will strengthen the permafrost C feedback more than waterlogged systems releasing CO2 and CH4 for a given amount of C.
Faucitano, L; Chouinard, P Y; Fortin, J; Mandell, I B; Lafrenière, C; Girard, C L; Berthiaume, R
2008-07-01
Five beef cattle management regimens were evaluated for their effect on meat quality, fatty acid composition, and overall palatability of the longis-simus dorsi (LD) muscle in Angus cross steers. A 98-d growing phase was conducted using grass silage with or without supplementation of growth promotants (Revalor G and Rumensin) or soybean meal. Dietary treatments in the finishing phase were developed with or without supplementation of growth promotants based on exclusive feeding of forages with no grain supplementation, or the feeding of grain:forage (70:30) diets. Growth promotants increased (P < 0.01) shear force and tended (P = 0.06) to increase toughness of the LD muscle due to limited postmortem proteolytic activity (lower myofibrillar fragmentation index value; P = 0.02). Grain feeding increased DM and intramuscular fat content (P = 0.03 and P = 0.05, respectively) in the LD but decreased the sensory panel tenderness score (P = 0.01). Growth promotants increased (P = 0.05) the proportion of C18:0, C20:0, trans isomers of C18:1, and cis-9, trans-11 C18:2. Exclusive feeding of forages increased the proportion of cis-9, cis-12, cis-15 C18:3 as well as several other isomers of the n-3 family and decreased in the ratio of n-6 to n-3 fatty acids in the LD muscle as compared with supplementing grain (P < 0.05). In addition, the forage-based diet increased (P < 0.01) the concentration in the intramuscular fat of several intermediates (cis-9, trans-11, cis-15 C18:3; trans-11, cis-15 C18:2; trans-11 C18:1) of ruminal biohydrogenation. Forage feeding also increased the proportion of cis-9, trans-11 C18:2 (P < 0.01) and decreased the concentration of trans-10 C18:1 in the LD muscle (P = 0.03). It is concluded that quality demands of health-conscious consumers can be met through a forage-finishing and growth promotants-free beef production system.
Kim, Yundeok; Eom, Ju-In; Jeung, Hoi-Kyung; Jang, Ji Eun; Kim, Jin Seok; Cheong, June-Won; Kim, Young Sam; Min, Yoo Hong
2015-07-01
We investigated the effects of the autophagy inhibitor hydroxychloroquine (HCQ) on cell death of cytosine arabinoside (Ara-C)-resistant human acute myeloid leukemia (AML) cells. Ara-C-sensitive (U937, AML-2) and Ara-C-resistant (U937/AR, AML-2/AR) human AML cell lines were used to evaluate HCQ-regulated cytotoxicity, autophagy, and apoptosis as well as effects on cell death-related signaling pathways. We found that HCQ-induced dose- and time-dependent cell death in Ara-C-resistant cells compared to Ara-C-sensitive cell lines. The extent of cell death and features of HCQ-induced autophagic markers including increase in microtubule-associated protein light chain 3 (LC3) I conversion to LC3-II, beclin-1, ATG5, as well as green fluorescent protein-LC3 positive puncta and autophagosome were remarkably greater in U937/AR cells. Also, p62/SQSTM1 was increased in response to HCQ. p62/SQSTM1 protein interacts with both LC3-II and ubiquitin protein and is degraded in autophagosomes. Therefore, a reduction of p62/SQSTM1 indicates increased autophagic degradation, whereas an increase of p62/SQSTM1 by HCQ indicates inhibited autophagic degradation. Knock down of p62/SQSTM1 using siRNA were prevented the HCQ-induced LC3-II protein level as well as significantly reduced the HCQ-induced cell death in U937/AR cells. Also, apoptotic cell death and caspase activation in U937/AR cells were increased by HCQ, provided evidence that HCQ-induced autophagy blockade. Taken together, our data show that HCQ-induced apoptotic cell death in Ara-C-resistant AML cells through autophagy regulation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Cytokine expression in patients with bladder pain syndrome/interstitial cystitis ESSIC type 3C.
Logadottir, Yr; Delbro, Dick; Fall, Magnus; Gjertsson, Inger; Jirholt, Pernilla; Lindholm, Catharina; Peeker, Ralph
2014-11-01
Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls. Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-α, TGF-β and IFN-γ was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count. IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-α, TGF-β and IFN-γ mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C. Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Changes of flavonoid content and antioxidant capacity in blueberries after UV-C illumination
USDA-ARS?s Scientific Manuscript database
The levels of flavonoids in blueberries were found to increase after illumination with UV-C. Phytochemicals affected included resveratrol, myricetin 3-arabinoside, quercetin 3-galactoside, quercetin derivative, kaempferol derivative, delphinidin-3-galactoside, cyaniding 3-galactoside, delphinidin 3-...
He, Jie; Austin, Paul T; Lee, Sing Kong
2010-09-01
Effects of elevated root zone (RZ) CO(2) and air temperature on photosynthesis, productivity, nitrate (NO(3)(-)), and total reduced nitrogen (N) content in aeroponically grown lettuce plants were studied. Three weeks after transplanting, four different RZ [CO(2)] concentrations [ambient (360 ppm) and elevated concentrations of 2000, 10,000, and 50,000 ppm] were imposed on plants grown at two air temperature regimes of 28 degrees C/22 degrees C (day/night) and 36 degrees C/30 degrees C. Photosynthetic CO(2) assimilation (A) and stomatal conductance (g(s)) increased with increasing photosynthetically active radiation (PAR). When grown at 28 degrees C/22 degrees C, all plants accumulated more biomass than at 36 degrees C/30 degrees C. When measured under a PAR >or=600 micromol m(-2) s(-1), elevated RZ [CO(2)] resulted in significantly higher A, lower g(s), and higher midday leaf relative water content in all plants. Under elevated RZ [CO(2)], the increase of biomass was greater in roots than in shoots, causing a lower shoot/root ratio. The percentage increase in growth under elevated RZ [CO(2)] was greater at 36 degrees C/30 degrees C although the total biomass was higher at 28 degrees C/22 degrees C. NO(3)(-) and total reduced N concentrations of shoot and root were significantly higher in all plants under elevated RZ [CO(2)] than under ambient RZ [CO(2)] of 360 ppm at both temperature regimes. At each RZ [CO(2)], NO(3)(-) and total reduced N concentration of shoots were greater at 28 degrees C/22 degrees C than at 36 degrees C/30 degrees C. At all RZ [CO(2)], roots of plants at 36 degrees C/30 degrees C had significantly higher NO(3)(-) and total reduced N concentrations than at 28 degrees C/22 degrees C. Since increased RZ [CO(2)] caused partial stomatal closure, maximal A and maximal g(s) were negatively correlated, with a unique relationship for each air temperature. However, across all RZ [CO(2)] and temperature treatments, there was a close correlation between maximal A and total shoot reduced N concentration of plants under different RZ [CO(2)], indicating that increased A under elevated RZ [CO(2)] could partially be due to the higher shoot total reduced N.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, Qing -He; Du, An; Yang, Ze -Jin
The structural inheritance and difference between Ti 2AlC, Ti 3AlC 2 and Ti 5Al 2C 3 under pressure from first principles are studied. The results indicate that the lattice parameter a are almost the same within Ti 2AlC, Ti 3AlC 2 and Ti 5Al 2C 3, and the value of c in Ti 5Al 2C 3 is the sum of Ti 2AlC and Ti 3AlC 2 which is revealed by the covalently bonded chain in the electron density difference: Al–Ti–C–Ti–Al for Ti 2AlC, Al–Ti 2–C–Ti 1–C–Ti 2–Al for Ti 3AlC 2 and Al–Ti 3–C 2–Ti 3–Al–Ti 2–C 1–Ti 1–C 1–Timore » 2–Al for Ti 5Al 2C 3. The calculated axial compressibilities, volumetric shrinkage, elastic constant c 11, c 33/c 11 ratio, bulk modulus, shear modulus, and Young’s modulus of Ti 5Al 2C 3 are within the range of the end members (Ti 2AlC and Ti 3AlC 2) in a wide pressure range of 0–100 GPa. Only Ti 2AlC is isotropic crystal at about 50 GPa within the Ti–Al–C compounds. All of the Ti 3 d density of states curves of the three compounds move from lower energy to higher energy level with pressure increasing. The similarities of respective bond length, bond overlap population (Ti–C, Ti–Al and Ti–Ti), atom Mulliken charges under pressure as well as the electron density difference for the three compounds are discovered. Among the Ti–Al–C ternary compounds, Ti–Ti bond behaves least compressibility, whereas the Ti–Al bond is softer than that of Ti–C bonds, which can also been confirmed by the density of states and electron density difference. Bond overlap populations of Ti–Ti, Ti–C and Ti–Al indicate that the ionicity interaction becomes more and more stronger in the three structures as the pressure increasing. Lastly, Mulliken charges of Ti 1, Ti 2, Ti 3, C and Al are 0.65, 0.42, 0.39, –0.73, –0.04 at 0 GPa, respectively, which are consistent with the Pauling scale.« less
Gao, Qing -He; Du, An; Yang, Ze -Jin
2017-02-08
The structural inheritance and difference between Ti 2AlC, Ti 3AlC 2 and Ti 5Al 2C 3 under pressure from first principles are studied. The results indicate that the lattice parameter a are almost the same within Ti 2AlC, Ti 3AlC 2 and Ti 5Al 2C 3, and the value of c in Ti 5Al 2C 3 is the sum of Ti 2AlC and Ti 3AlC 2 which is revealed by the covalently bonded chain in the electron density difference: Al–Ti–C–Ti–Al for Ti 2AlC, Al–Ti 2–C–Ti 1–C–Ti 2–Al for Ti 3AlC 2 and Al–Ti 3–C 2–Ti 3–Al–Ti 2–C 1–Ti 1–C 1–Timore » 2–Al for Ti 5Al 2C 3. The calculated axial compressibilities, volumetric shrinkage, elastic constant c 11, c 33/c 11 ratio, bulk modulus, shear modulus, and Young’s modulus of Ti 5Al 2C 3 are within the range of the end members (Ti 2AlC and Ti 3AlC 2) in a wide pressure range of 0–100 GPa. Only Ti 2AlC is isotropic crystal at about 50 GPa within the Ti–Al–C compounds. All of the Ti 3 d density of states curves of the three compounds move from lower energy to higher energy level with pressure increasing. The similarities of respective bond length, bond overlap population (Ti–C, Ti–Al and Ti–Ti), atom Mulliken charges under pressure as well as the electron density difference for the three compounds are discovered. Among the Ti–Al–C ternary compounds, Ti–Ti bond behaves least compressibility, whereas the Ti–Al bond is softer than that of Ti–C bonds, which can also been confirmed by the density of states and electron density difference. Bond overlap populations of Ti–Ti, Ti–C and Ti–Al indicate that the ionicity interaction becomes more and more stronger in the three structures as the pressure increasing. Lastly, Mulliken charges of Ti 1, Ti 2, Ti 3, C and Al are 0.65, 0.42, 0.39, –0.73, –0.04 at 0 GPa, respectively, which are consistent with the Pauling scale.« less
Schwann Cells Metabolize Extracellular 2′,3′-cAMP to 2′-AMP
Verrier, Jonathan D.; Kochanek, Patrick M.
2015-01-01
The 3′,5′-cAMP–adenosine pathway (3′,5′-cAMP→5′-AMP→adenosine) and the 2′,3′-cAMP–adenosine pathway (2′,3′-cAMP→2′-AMP/3′-AMP→adenosine) are active in the brain. Oligodendrocytes participate in the brain 2′,3′-cAMP–adenosine pathway via their robust expression of 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase; converts 2′,3′-cAMP to 2′-AMP). Because Schwann cells also express CNPase, it is conceivable that the 2′,3′-cAMP–adenosine pathway exists in the peripheral nervous system. To test this and to compare the 2′,3′-cAMP–adenosine pathway to the 3′,5′-cAMP–adenosine pathway in Schwann cells, we examined the metabolism of 2′,3′-cAMP, 2′-AMP, 3′-AMP, 3′,5′-cAMP, and 5′-AMP in primary rat Schwann cells in culture. Addition of 2′,3′-cAMP (3, 10, and 30 µM) to Schwann cells increased levels of 2′-AMP in the medium from 0.006 ± 0.002 to 21 ± 2, 70 ± 3, and 187 ± 10 nM/µg protein, respectively; in contrast, Schwann cells had little ability to convert 2′,3′-cAMP to 3′-AMP or 3′,5′-cAMP to either 3′-AMP or 5′-AMP. Although Schwann cells slightly converted 2′,3′-cAMP and 2′-AMP to adenosine, they did so at very modest rates (e.g., 5- and 3-fold, respectively, more slowly compared with our previously reported studies in oligodendrocytes). Using transected myelinated rat sciatic nerves in culture medium, we observed a time-related increase in endogenous intracellular 2′,3′-cAMP and extracellular 2′-AMP. These findings indicate that Schwann cells do not have a robust 3′,5′-cAMP–adenosine pathway but do have a 2′,3′-cAMP–adenosine pathway; however, because the pathway mostly involves 2′-AMP formation rather than 3′-AMP, and because the conversion of 2′-AMP to adenosine is slow, metabolism of 2′,3′-cAMP mostly results in the accumulation of 2′-AMP. Accumulation of 2′-AMP in peripheral nerves postinjury could have pathophysiological consequences. PMID:25998049
DOE Office of Scientific and Technical Information (OSTI.GOV)
Konishi, Hiroaki, E-mail: hiroaki.konishi.yj@hitachi.com; Gunji, Akira; Feng, Xiaoliang
2017-05-15
To evaluate the effect of transition metal composition on the electrochemical properties of Li-rich layer-structured cathode materials, Li{sub 1.2}Ni{sub x}Mn{sub 0.8−x}O{sub 2} (x=0.2, 0.25, 0.3, and 0.4) were synthesized, and their electrochemical properties were investigated. As nickel content x increased in Li{sub 1.2}Ni{sub x}Mn{sub 0.8−x}O{sub 2} (x=0.2, 0.25, 0.3, and 0.4), charge-discharge capacities at a low C-rate (0.05 C) decreased. The results obtained by dQ/dV curves indicate that, as the nickel content increased, the discharge capacity below 3.6 V greatly decreased, but that above 3.6 V increased. As the C-rate of the discharge process increased, the discharge reaction of Li{submore » 1.2}Ni{sub x}Mn{sub 0.8−x}O{sub 2} (x=0.2) below 3.6 V greatly decreased. In contrast, that above 3.6 V slightly decreased. This indicates that the discharge reaction above 3.6 V exhibits higher rate performance than that below 3.6 V. For the high-nickel-content cathodes, the ratio of the discharge capacity above 3.6 V to the total discharge capacity was high. Therefore, they exhibited high rate performance. - Graphical abstract: Figure shows the discharge curves of Li{sub 1.2}Ni{sub x}Mn{sub 0.8−x}O{sub 2} (x=0.2 and 0.3) within potential range of 2.5−4.6 V (vs. Li/Li{sup +}) at 0.05 and 3 C. At low C-rate (0.05 C), the discharge capacity of high-nickel-content cathode (Li{sub 1.2}Ni{sub 0.3}Mn{sub 0.5}O{sub 2}) was less than that of low-nickel-content cathode (Li{sub 1.2}Ni{sub 0.2}Mn{sub 0.6}O{sub 2}); however, the discharge potential and capacity of Li{sub 1.2}Ni{sub 0.3}Mn{sub 0.5}O{sub 2} was higher than those of Li{sub 1.2}Ni{sub 0.2}Mn{sub 0.6}O{sub 2} at high C-rate (3 C). This means that the increase in Ni/Mn ratio was effective in improving rate-performance.« less
Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection
Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.
2016-01-01
The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374
Zhu, JianXiao; Hu, XueYang; Yao, Hui; Liu, GuoHua; Ji, ChenJun; Fang, JingYun
2015-11-01
Numerous efforts have been made to characterize forest carbon (C) cycles and stocks in various ecosystems. However, long-term observation on each component of the forest C cycle is still lacking. We measured C stocks and fluxes in three permanent temperate forest plots (birch, oak and pine forest) during 2011–2014, and calculated the changes of the components of the C cycle related to the measurements during 1992–1994 at Mt. Dongling, Beijing, China. Forest net primary production in birch, oak, and pine plots was 5.32, 4.53, and 6.73 Mg C ha-1 a-1, respectively. Corresponding net ecosystem production was 0.12, 0.43, and 3.53 Mg C ha-1 a-1. The C stocks and fluxes in 2011–2014 were significantly larger than those in 1992–1994 in which the biomass C densities in birch, oak, and pine plots increased from 50.0, 37.7, and 54.0 Mg C ha-1 in 1994 to 101.5, 77.3, and 110.9 Mg C ha-1 in 2014; soil organic C densities increased from 207.0, 239.1, and 231.7 Mg C ha-1 to 214.8, 241.7, and 238.4 Mg C ha-1; and soil heterotrophic respiration increased from 2.78, 3.49, and 1.81 Mg C ha-1 a-1 to 5.20, 4.10, and 3.20 Mg C ha-1 a-1. These results suggest that the mountainous temperate forest ecosystems in Beijing have served as a carbon sink in the last two decades. These observations of C stocks and fluxes provided field-based data for a long-term study of C cycling in temperate forest ecosystems.
Methane Cycling in a Warming Wetland
NASA Astrophysics Data System (ADS)
Noyce, G. L.; Megonigal, P.; Rich, R.; Kirwan, M. L.; Herbert, E. R.
2017-12-01
Coastal wetlands are global hotspots of carbon (C) storage, but the future of these systems is uncertain. In June 2016, we initiated an in-situ, active, whole-ecosystem warming experiment in the Smithsonian's Global Change Research Wetland to quantify how warming and elevated CO2 affect the stability of coastal wetland soil C pools and contemporary rates of C sequestration. Transects are located in two plant communities, dominated by C3 sedges or C4 grasses. The experiment has a gradient design with air and soil warming treatments ranging from ambient to +5.1 °C and heated plots consistently maintain their target temperature year-round. In April 2017, an elevated CO2 treatment was crossed with temperature in the C3community. Ongoing measurements include soil elevation, C fluxes, porewater chemistry and redox potential, and above- and below-ground growth and biomass. In both years, warming increased methane (CH4) emissions (measured at 3-4 week intervals) from spring through fall at the C3 site, but had little effect on emissions from the C4 site. Winter (Dec-Mar) emissions showed no treatment effect. Stable isotope analysis of dissolved CH4 and DIC also indicated that warming had differing effects on CH4 pathways in the two vegetation communities. To better understand temperature effects on rates of CH4 production and oxidation, 1 m soil cores were collected from control areas of the marsh in summer 2017 and incubated at temperatures ranging from 4 °C to 35 °C. Warming increased CH4 production and oxidation rates in surface samples and oxidation rates in the rooting zone samples from both sites, but temperature responses in deep (1 m) soil samples were minimal. In the surface and rooting zone samples, production rates were also consistently higher in C3 soils compared to C4 soils, but, contrary to our expectations, the temperature response was stronger in the C4 soils. However, oxidation in C3 rooting zone samples did have a strong temperature response. The ratio of CO2:CH4 decreased with increasing temperature in surface samples from both sites, indicating that anaerobic respiration in surface soil may become increasingly methanogenic with warming. In contrast, the rooting zone and deep soil samples showed the opposite trend, again suggesting that the soil profile will not respond consistently to warming.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tomioka, Shigemasa, E-mail: tomioka@dent.tokushima-u.ac.jp; Kaneko, Miyuki; Satomura, Kazuhito
2009-10-09
We investigated the effects of ketamine on the type 3 facilitative glucose transporter (GLUT3), which plays a major role in glucose transport across the plasma membrane of neurons. Human-cloned GLUT3 was expressed in Xenopus oocytes by injection of GLUT3 mRNA. GLUT3-mediated glucose uptake was examined by measuring oocyte radioactivity following incubation with 2-deoxy-D-[1,2-{sup 3}H]glucose. While ketamine and S(+)-ketamine significantly increased GLUT3-mediated glucose uptake, this effect was biphasic such that higher concentrations of ketamine inhibited glucose uptake. Ketamine (10 {mu}M) significantly increased V{sub max} but not K{sub m} of GLUT3 for 2-deoxy-D-glucose. Although staurosporine (a protein kinase C inhibitor) increased glucosemore » uptake, no additive or synergistic interactions were observed between staurosporine and racemic ketamine or S(+)-ketamine. Treatment with ketamine or S(+)-ketamine partially prevented GLUT3 inhibition by the protein kinase C activator phorbol-12-myrisate-13-acetate. Our results indicate that ketamine increases GLUT3 activity at clinically relevant doses through a mechanism involving PKC inhibition.« less
Oxidation Resistance of Materials Based on Ti3AlC2 Nanolaminate at 600 °C in Air
NASA Astrophysics Data System (ADS)
Ivasyshyn, Andrij; Ostash, Orest; Prikhna, Tatiana; Podhurska, Viktoriya; Basyuk, Tatiana
2016-08-01
The oxidation behavior of Ti3AlC2-based materials had been investigated at 600 °C in static air for 1000 h. It was shown that the intense increase of weight gain per unit surface area for sintered material with porosity of 22 % attributed to oxidation of the outer surface of the specimen and surfaces of pores in the bulk material. The oxidation kinetics of the hot-pressed Ti3AlC2-based material with 1 % porosity remarkably increased for the first 15 h and then slowly decreased. The weight gain per unit surface area for this material was 1.0 mg/cm2 after exposition for 1000 h. The intense initial oxidation of Ti3AlC2-based materials can be eliminated by pre-oxidation treatment at 1200 °C in air for 2 h. As a result, the weight gain per unit surface area for the pre-oxidized material did not exceed 0.11 mg/cm2 after 1000 h of exposition at 600 °C in air. It was demonstrated that the oxidation resistance of Ti3AlC2-based materials can be significantly improved by niobium addition.
Ozeki, K; Hoshino, T; Aoki, H; Masuzawa, T
2013-01-01
The adsorption behavior of albumin (BSA) and lysozyme (LSZ) on rod-shaped and plate-shaped hydroxyapatite (HA) was investigated to evaluate the influence of crystal orientation and morphology on the selective protein adsorption of HA. The rod-shaped HA was prepared by hydrothermal treatment from β-tricalcium phosphate (β-TCP) in H3PO4 solution (pH 2.0 and 4.0 for HA-pH 2.0 and HA-pH 4.0). The plate-shaped HA was synthesized by hydrolysis of CaHPO4-2H2O (DCPD) in NaOH solution at 40°C and 80°C (HA-40°C and HA-80°C). The synthesized HA was characterized using scanning electron microscopy (SEM) and X-ray diffractometry (XRD). HA-pH 2.0 and HA-pH 4.0 produced rod-shaped crystals that were highly oriented to the a-face plane, whereas HA-40°C and HA-80°C showed a plate-like shape and a c-face preferred orientation. The peak intensity ratio I(300)/I(002) (a/c intensity ratio) from the XRD patterns increased in the following order: HA-80°C, HA-40°C, HA-pH 2.0 and HA-pH 4.0. It also increased as the Ca/P ratio decreased. The amount of adsorbed BSA increased in the following order: HA-pH 4.0, HA-pH 2.0, HA-40°C and HA-80°C. The amount of adsorbed LSZ on HA increased in the following order--HA-pH 2.0, HA-pH 4.0, HA-40°C and HA-80°C--with a corresponding decrease in the a/c intensity ratio. The BSA/LSA adsorption ratio increased with the a/c intensity ratio in the range of 3.3-8.9, and the BSA and LSZ were selectively adsorbed on HA, depending on the crystal shape.
Xin-Bo, Xiong; Xin-Ye, Ni; Ya-Yun, Li; Cen-Cen, Chu; Ji-Zhao, Zou; Xie-Rong, Zeng
2016-08-05
A novel strategy for the preparation of Si-doped hydroxyapatite (Si-HA) coatings on H2O2-treated carbon/carbon composites (C/C) was developed. HA coating was prepared on C/C through chemical liquid vaporization deposition (CLVD)/hydrothermal treatment. HA coating was immersed in an H2SiO3 solution at an autoclave at 413 K for transformation into Si-HA coating. The effects of H2SiO3 mass contents on the phase, morphology, and composition of the Si-HA coatings were studied through SEM, EDS,XRD, and FTIR. Their bonding performance to C/C was measured through a scratch test. Under the optimal content condition, the in vitro skull osteoblast response behaviors of the Si-HA coating were evaluated. Results showed that SiO3(2-) could enter into the HA lattice and occupy the PO4(3-) sites. Doped SiO3(2-) significantly improved the bonding performance of the HA coating to C/C in comparison with the untreated HA. The adhesive strength of the coatings initially increased and then decreased with increasing H2SiO3 content. Meanwhile, the cohesive strength of the Si-HA coatings was almost nearly identical. The Si-HA coating achieved at a content of 90% H2SiO3 exhibited the best bonding performance, and its osteoblast compatibility in vitro was superior to that of the untreated HA coating on C/C through CLVD/hydrothermal treatment.
A First-Principles Study on the Vibrational and Electronic Properties of Zr-C MXenes
NASA Astrophysics Data System (ADS)
Wang, Chang-Ying; Guo, Yong-Liang; Zhao, Yuan-Yuan; Zeng, Guang-Li; Zhang, Wei; Ren, Cui-Lan; Han, Han; Huai, Ping
2018-03-01
Within the framework of density functional theory calculations, the structural, vibrational, and electronic properties of Zr n C n - 1 (n = 2, 3, and 4) and their functionalized MXenes have been investigated. We find that the most stable configurations for Zr-C MXene are the ones that the terminal groups F, O, and OH locate on the common hollow site of the superficial Zr layer and its adjacent C layer. F and OH-terminated Zr 3 C 2 and Zr 4 C 3 have small imaginary acoustic phonon branches around Γ point while the others have no negative phonon modes. The pristine MXenes (Zr 2 C, Zr 3 C 2 and Zr 4 C 3 ) are all metallic with large DOS contributed by the Zr atom at the Fermi energy. When functionalized by F, O and OH, new hybridization states appear and the DOS at the Fermi level are reduced. Moreover, we find that their metallic characteristic increases with an increase in n. For (Zr n C n - 1 )O 2, Zr 2 CO 2 is a semiconductor, Zr 3C2O2 is a semimetal, and Zr 4 C 3O2 becomes a metal. Supported by the National Natural Science Foundation of China under Grant Nos. 11605273, 21571185, U1404111, 11504089, 21501189, 21676291, the Shanghai Municipal Science and Technology Commission 16ZR1443100, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA02040104)
Disease-associated mutations in CNGB3 promote cytotoxicity in photoreceptor-derived cells
Liu, Chunming; Sherpa, Tshering
2013-01-01
Purpose To determine if achromatopsia associated F525N and T383fsX mutations in the CNGB3 subunit of cone photoreceptor cyclic nucleotide-gated (CNG) channels increases susceptibility to cell death in photoreceptor-derived cells. Methods Photoreceptor-derived 661W cells were transfected with cDNA encoding wild-type (WT) CNGA3 subunits plus WT or mutant CNGB3 subunits, and incubated with the membrane-permeable CNG channel activators 8-(4-chlorophenylthio) guanosine 3′,5′-cyclic monophosphate (CPT-cGMP) or CPT-adenosine 3′,5′-cyclic monophosphate (CPT-cAMP). Cell viability under these conditions was determined by measuring lactate dehydrogenase release. Channel ligand sensitivity was calibrated by patch-clamp recording after expression of WT or mutant channels in Xenopus oocytes. Results Coexpression of CNGA3 with CNGB3 subunits containing F525N or T383fsX mutations produced channels exhibiting increased apparent affinity for CPT-cGMP compared to WT channels. Consistent with these effects, cytotoxicity in the presence of 0.1 μM CPT-cGMP was enhanced relative to WT channels, and the increase in cell death was more pronounced for the mutation with the largest gain-of-function effect on channel gating, F525N. Increased susceptibility to cell death was prevented by application of the CNG channel blocker L-cis-diltiazem. Increased cytotoxicity was also found to be dependent on the presence of extracellular calcium. Conclusions These results indicate a connection between disease-associated mutations in cone CNG channel subunits, altered CNG channel-activation properties, and photoreceptor cytotoxicity. The rescue of cell viability via CNG channel block or removal of extracellular calcium suggests that cytotoxicity in this model depends on calcium entry through hyperactive CNG channels. PMID:23805033
Carmen Chifiriuc, M; Mihaiescu, D; Ilinca, E; Marutescu, L; Mihaescu, G; Mihai Grumezescu, A
2012-12-01
The aim of this study was to investigate the effect of different hybrid inorganic-organic micro- and nanomaterials (Fe(3)O(4)/PEG(600), Fe(3)O(4)/C(12), ZSM-5) on the antibacterial activity of different cephalosporins against Gram-positive and Gram-negative bacterial strains. The synergic effect of the studied materials was demonstrated by the increase in the growth inhibition zones diameter. All tested hybrid micro- and nanomaterials increased the activity of cefotaxime against Staphylococcus aureus. ZSM-5 increased the activity of cefotaxime and ceftriaxone and Fe(3)O(4)/C(12) that of ceftriaxone against Pseudomonas aeruginosa and S. aureus. The anti-Pseudomonas, anti-Klebsiella pneumoniae and anti-Bacillus subtilis activity of cefoperazone was increased by Fe(3)O(4)/C(12) nanoparticles, while the ZSM-5 improved its anti-Escherichia coli, K. pneumoniae, S. aureus and B. subtilis activity, whereas Fe(3)O(4)/PEG(600) against K. pneumoniae. The anti-K. pneumoniae activity of cefepime was increased by all tested nanoparticles, whereas its anti-B. subtilis and anti-E. coli activity was improved by Fe(3)O(4)/C(12) and Fe(3)O(4)/PEG(600) nanoparticles. In conclusion, both magnetic Fe(3)O(4) nanoparticles, charged outside as extra-shell with the antibiotic as well as ZSM-5 microparticles carrying the antibiotic inside the pores, significantly and specifically improved cephalosporin efficacy. A probable explanation for the increase in the antibiotic efficiency is the better penetration through the cellular wall of the antibiotic charged nanoparticles.
Abdelmageed, Mai M; El-Naga, Reem N; El-Demerdash, Ebtehal; Elmazar, Mohamed M
2016-09-09
Sorafenib is the only chemotherapeutic agent currently approved for unresectable hepatocellular carcinoma (HCC). However, poor response rates have been widely reported. Indole-3-carbinol (I3C) is a potential chemopreventive phytochemical. The present study aimed to explore the potential chemomodulatory effects of I3C on sorafenib in HCC cells as well as the possible underlying mechanisms. I3C exhibited a greater cytotoxicity in HepG2 cells compared to Huh-7 cells (p < 0.0001). Moreover, the co-treatment of HepG2 cells with I3C and sorafenib was more effective (p = 0.002). Accordingly, subsequent mechanistic studies were carried on HepG2 cells. The results show that the ability of I3C to enhance sorafenib cytotoxicity in HCC cells could be partially attributed to increasing the apoptotic activity and decreasing the angiogenic potentials. The combination had a negative effect on epithelial-mesenchymal transition (EMT). Increased NOX-1 expression was also observed which may indicate the involvement of NOX-1 in I3C chemomodulatory effects. Additionally, the combination induced cell cycle arrest at the G0/G1 phase. In conclusion, these findings provide evidence that I3C enhances sorafenib anti-cancer activity in HCC cells.
Abdelmageed, Mai M.; El-Naga, Reem N.; El-Demerdash, Ebtehal; Elmazar, Mohamed M.
2016-01-01
Sorafenib is the only chemotherapeutic agent currently approved for unresectable hepatocellular carcinoma (HCC). However, poor response rates have been widely reported. Indole-3-carbinol (I3C) is a potential chemopreventive phytochemical. The present study aimed to explore the potential chemomodulatory effects of I3C on sorafenib in HCC cells as well as the possible underlying mechanisms. I3C exhibited a greater cytotoxicity in HepG2 cells compared to Huh-7 cells (p < 0.0001). Moreover, the co-treatment of HepG2 cells with I3C and sorafenib was more effective (p = 0.002). Accordingly, subsequent mechanistic studies were carried on HepG2 cells. The results show that the ability of I3C to enhance sorafenib cytotoxicity in HCC cells could be partially attributed to increasing the apoptotic activity and decreasing the angiogenic potentials. The combination had a negative effect on epithelial-mesenchymal transition (EMT). Increased NOX-1 expression was also observed which may indicate the involvement of NOX-1 in I3C chemomodulatory effects. Additionally, the combination induced cell cycle arrest at the G0/G1 phase. In conclusion, these findings provide evidence that I3C enhances sorafenib anti-cancer activity in HCC cells. PMID:27612096
Stability of methane in reduced C-O-H fluid at 6.3 GPa and 1300-1400°C
NASA Astrophysics Data System (ADS)
Sokol, A. G.; Tomilenko, A. A.; Bul'bak, T. A.; Palyanova, G. A.; Palyanov, Yu. N.; Sobolev, N. V.
2017-06-01
The composition of a reduced C-O-H fluid was studied by the method of chromatography-mass spectrometry under the conditions of 6.3 GPa, 1300-1400°C, and fO2 typical of the base of the subcratonic lithosphere. Fluids containing water (4.4-96.3 rel. %), methane (37.6-0.06 rel. %), and variable concentrations of ethane, propane, and butane were obtained in experiments. With increasing fO2, the proportion of the CH4/C2H6 peak areas on chromatograms first increases and then decreases, whereas the CH4/C3H8 and CH4/C4H10 ratios continually decrease. The new data show that ethane and heavier HCs may be more stable to oxidation, than previously thought. Therefore, when reduced fluids pass the "redox-front," carbon is not completely released from the fluid and may be involved in diamond formation.
Enhanced Polyubiquitination of Shank3 and NMDA receptor in a mouse model of Autism
Bangash, M Ali; Park, Joo Min; Melnikova, Tatiana; Wang, Dehua; Jeon, Soo Kyeong; Lee, Deidre; Syeda, Sbaa; Kim, Juno; Kouser, Mehreen; Schwartz, Joshua; Cui, Yiyuan; Zhao, Xia; Speed, Haley E.; Kee, Sara E.; Tu, Jian Cheng; Hu, Jia-Hua; Petralia, Ronald S.; Linden, David J.; Powell, Craig M.; Savonenko, Alena; Xiao, Bo; Worley, Paul F.
2011-01-01
Summary We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C-terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the WT gene product and results in >90 % reduction of Shank3 at synapses. This “gain of function” phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of post-synaptic density proteins, spine morphology and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. PMID:21565394
Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.
Bangash, M Ali; Park, Joo Min; Melnikova, Tatiana; Wang, Dehua; Jeon, Soo Kyeong; Lee, Deidre; Syeda, Sbaa; Kim, Juno; Kouser, Mehreen; Schwartz, Joshua; Cui, Yiyuan; Zhao, Xia; Speed, Haley E; Kee, Sara E; Tu, Jian Cheng; Hu, Jia-Hua; Petralia, Ronald S; Linden, David J; Powell, Craig M; Savonenko, Alena; Xiao, Bo; Worley, Paul F
2011-05-27
We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. Copyright © 2011 Elsevier Inc. All rights reserved.
Improvement of photosynthesis in rice (Oryza sativa L.) by inserting the C4 pathway.
Karki, Shanta; Rizal, Govinda; Quick, William Paul
2013-10-28
To boost food production for a rapidly growing global population, crop yields must significantly increase. One of the avenues being recently explored is the improvement of photosynthetic capacity by installing the C4 photosynthetic pathway into C3 crops like rice to drastically increase their yield. Crops with an enhanced photosynthetic mechanism would better utilize the solar radiation that can be translated into yield. This subsequently will help in producing more grain yield, reduce water loss and increase nitrogen use efficiency especially in hot and dry environments. This review provides a summary of the factors that need to be modified in rice so that the C4 pathway can be introduced successfully. It also discusses the differences between the C3 and C4 photosynthetic pathways in terms of anatomy, biochemistry and genetics.
High Resolution 13C MRI With Hyperpolarized Urea: In Vivo T2 Mapping and 15N Labeling Effects
Reed, Galen D.; von Morze, Cornelius; Bok, Robert; Koelsch, Bertram L.; Van Criekinge, Mark; Smith, Kenneth J.; Shang, Hong; Larson, Peder E. Z.; Kurhanewicz, John; Vigneron, Daniel B.
2014-01-01
13C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [13C] urea and [13C, 15N2] urea injected intravenously in rats. 15N labeling gave large T2 increases both in solution and in vivo due to the elimination of a strong scalar relaxation pathway. The T2 increase was pronounced in the kidney, with [13C, 15N2] urea giving T2 values of 6.3±1.3 s in the cortex and medulla, and 11±2 s in the renal pelvis. The measured T2 in the aorta was 1.3±0.3 s. [13C] urea showed shortened T2 values in the kidney of 0.23±0.03 s compared to 0.28±0.03 s measured in the aorta. The enhanced T2 of [13C, 15N2] urea was utilized to generate large signal enhancement by SSFP acquisitions with flip angles approaching the fully refocused regime. Projection images at 0.94 mm in-plane resolution were acquired with both urea isotopes, with [13C, 15N2] urea giving a greater than four-fold increase in signal-to-noise ratio [13C] over urea. PMID:24235273
Harsant, Jeffrey; Pavlovic, Lazar; Chiu, Greta; Sultmanis, Stefanie; Sage, Tammy L.
2013-01-01
The effect of high temperatures on harvest index (HI) and morphological components that contribute to HI was investigated in two lines (Bd21 and Bd21-3) of Brachypodium distachyon, a C3 grass recognized as a tractable plant, to address critical issues associated with enhancing cereal crop yields in the presence of global climate change. The results demonstrated that temperatures ≥32 °C eliminated HI. Reductions in yield at 32 °C were due primarily to declines in pollen viability, retention of pollen in anthers, and pollen germination, while abortion of microspores by the uninucleate stage that was correlated with abnormal tapetal development resulted in yield failure at 36 °C. Increasing temperatures from 24 to 32 °C resulted in reductions in tiller numbers but had no impact on axillary branch numbers per tiller. Grain developed at 24 and 28 °C primarily in tiller spikes, although spikes on axillary branches also formed grain. Grain quantity decreased in tiller spikes but increased in axillary branch spikes as temperatures rose from 24 to 28 °C. Differential patterns of axillary branching and floret development within spikelets between Bd21 and Bd21-3 resulted in higher grain yield in axillary branches of Bd21-3 at 28 °C. The response of male reproductive development and tiller branching patterns in B. distachyon to increasing temperatures mirrors that in other cereal crops, providing support for the use of this C3 grass in assessing the molecular control of HI in the presence of global warming. PMID:23771979
Phase Transitions of Triflate-Based Ionic Liquids under High Pressure.
Faria, Luiz F O; Ribeiro, Mauro C C
2015-11-05
Raman spectroscopy has been used to study phase transitions of ionic liquids based on the triflate anion, [TfO](-), as a function of pressure or temperature. Raman spectra of ionic liquids containing the cations 1-butyl-3-methylimidazolium, [C4C1Im](+), 1-octyl-3-methylimidazolium, [C8C1Im](+), 1-butyl-2,3-dimethylimidazolium, [C4C1C1Im](+), and 1-butyl-1-methylpyrrolidinium, [C4C1Pyr](+), were compared. Vibrational frequencies and binding energy of ionic pairs were calculated by quantum chemistry methods. The ionic liquids [C4C1Im][TfO] and [C4C1Pyr][TfO] crystallize at 1.0 GPa when the pressure is increased in steps of ∼ 0.2 GPa from the atmospheric pressure, whereas [C8C1Im][TfO] and [C4C1C1Im][TfO] do not crystallize up to 2.3 GPa of applied pressure. The low-frequency range of the Raman spectrum of [C4C1Im][TfO] indicates that the system undergoes glass transition, rather than crystallization, when the pressure applied on the liquid has been increased above 2.0 GPa in a single step. Strong hysteresis of spectral features (frequency shift and bandwidth) of the high-pressure crystalline phase when the pressure was released stepwise back to the atmospheric pressure has been found .
Saturable Absorption in 2D Ti3 C2 MXene Thin Films for Passive Photonic Diodes.
Dong, Yongchang; Chertopalov, Sergii; Maleski, Kathleen; Anasori, Babak; Hu, Longyu; Bhattacharya, Sriparna; Rao, Apparao M; Gogotsi, Yury; Mochalin, Vadym N; Podila, Ramakrishna
2018-03-01
MXenes comprise a new class of 2D transition metal carbides, nitrides, and carbonitrides that exhibit unique light-matter interactions. Recently, 2D Ti 3 CNT x (T x represents functional groups such as OH and F) was found to exhibit nonlinear saturable absorption (SA) or increased transmittance at higher light fluences, which is useful for mode locking in fiber-based femtosecond lasers. However, the fundamental origin and thickness dependence of SA behavior in MXenes remain to be understood. 2D Ti 3 C 2 T x thin films of different thicknesses are fabricated using an interfacial film formation technique to systematically study their nonlinear optical properties. Using the open aperture Z-scan method, it is found that the SA behavior in Ti 3 C 2 T x MXene arises from plasmon-induced increase in the ground state absorption at photon energies above the threshold for free carrier oscillations. The saturation fluence and modulation depth of Ti 3 C 2 T x MXene is observed to be dependent on the film thickness. Unlike other 2D materials, Ti 3 C 2 T x is found to show higher threshold for light-induced damage with up to 50% increase in nonlinear transmittance. Lastly, building on the SA behavior of Ti 3 C 2 T x MXenes, a Ti 3 C 2 T x MXene-based photonic diode that breaks time-reversal symmetry to achieve nonreciprocal transmission of nanosecond laser pulses is demonstrated. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cross, E.R.; Hyams, K.C.
1996-07-01
The distribution of Phlebotomus papatasi in Southwest Asia is thought to be highly dependent on temperature and relative humidity. A discriminant analysis model based on weather data and reported vector surveys was developed to predict the seasonal and geographic distribution of P. papatasi in this region. To simulate global warming, temperature values for 115 weather stations were increased by 1 {degrees}C, 3{degrees}C, and 5{degrees}C, and the outcome variable coded as unknown in the model. Probability of occurrence values were then predicted for each location with a weather station. Stations with positive probability of occurrence values for May, June, July, andmore » August were considered locations where two or more life cycles of P. papatasi could occur and which could support endemic transmission of leishmaniasis and sandfly fever. Among 115 weather stations, 71 (62%) would be considered endemic with current temperature conditions; 14 (12%) additional station could become endemic with an increase of 1 {degrees}C; 17 (15%) more than a 3{degrees}C increase; and 12 (10%) more (all but one station) with a t{degrees}C increase. In addition to increased geographic distribution, seasonality of disease transmission could be extended throughout 12 months of the year in 7 (6%) locations with at least a 3{degrees}C rise in temperature and in 29 (25%) locations with a 5{degrees}C rise. 15 refs., 4 figs.« less
Effect of change in ambient temperature on core temperature during the daytime.
Kakitsuba, Naoshi; White, Matthew D
2014-07-01
In this study, the hypothesis is tested that continuous increases in ambient temperature (Ta) during daytime would give elevated core and skin temperatures, and consequently better thermal sensation and comfort. Rectal temperature (Tre), skin temperatures and regional dry heat losses at 7 sites were continuously measured for 10 Japanese male subjects in three thermal conditions: cond. 1, stepwise increases in Ta from 26 °C at 9 h00 to 30 °C at 18 h00; cond. 2, steady Ta at 28 °C from 9 h00 to 18 h00 and cond. 3, stepwise decreases in Ta from 30 °C at 9 h00 to 26 °C at 18 h00. Oxygen consumption was measured and thermal sensation and comfort votes were monitored at 15 min intervals. Body weight loss was measured at 1 h intervals. While Tre increased continuously in the morning period in any condition, it increased to a significantly greater (p<0.05) 36.9±0.3 °C at 18 h00 in cond. 1 relative to 36.7±0.28 °C in Cond. 2 and 36.5±0.37 °C in cond. 3. Better thermal comfort was observed in the afternoon and the evening in Cond.1 as compared with the other 2 conditions. Thus, a progressive and appropriate increase in Ta may induce optimal cycle in core temperature during daytime, particularly for a resting person.
Endothelin-1 Inhibits the Epithelial Na+ Channel through βPix/14-3-3/Nedd4-2
Pavlov, Tengis S.; Chahdi, Ahmed; Ilatovskaya, Daria V.; Levchenko, Vladislav; Vandewalle, Alain; Pochynyuk, Oleh
2010-01-01
Epithelial Na+ channels (ENaCs) mediate sodium reabsorption in the cortical collecting duct (CCD), but the regulatory pathways that modulate the activity of these channels are incompletely understood. Here, we observed that endothelin-1 (ET-1) attenuates ENaC activity acutely by reducing the channel's open probability and chronically by decreasing the number of channels in the plasma membrane. To investigate whether β1Pix, a signaling protein activated by ET-1, mediates ENaC activity, we reconstituted ENaC in CHO cells with or without coexpressed β1Pix and found that β1Pix negatively regulates ENaC. Knockdown of βPix in native principal cells abolished the ET-1-induced decrease in ENaC channel number. Furthermore, we found that βPix does not decrease ENaC activity through its guanine nucleotide exchange factor (GEF) activity for Rac1 and Cdc42. Instead, coexpression of β1Pix mutant constructs revealed that β1Pix affects ENaC activity through binding 14-3-3 proteins. Coimmunoprecipitation experiments supported a physical interaction between β1Pix and 14-3-3β in cultured principal cells. Coexpression of 14-3-3β increased ENaC activity in CHO cells, but concomitant expression of β1Pix attenuated this increase. Recruitment of 14-3-3β by β1Pix impaired the interaction of 14-3-3β with the ubiquitin ligase Nedd4-2, thereby promoting ubiquitination and degradation of ENaC. Taken together, these results suggest that the inhibitory effects of chronic ET-1 on ENaC result from βPix interacting with the 14-3-3/Nedd4-2 pathway. PMID:20338996
Tate, Jennifer J; Georis, Isabelle; Rai, Rajendra; Vierendeels, Fabienne; Dubois, Evelyne; Cooper, Terrance G
2015-05-29
The TorC1 protein kinase complex is a central component in a eukaryotic cell's response to varying nitrogen availability, with kinase activity being stimulated in nitrogen excess by increased intracellular leucine. This leucine-dependent TorC1 activation requires functional Gtr1/2 and Ego1/3 complexes. Rapamycin inhibition of TorC1 elicits nuclear localization of Gln3, a GATA-family transcription activator responsible for the expression of genes encoding proteins required to transport and degrade poor nitrogen sources, e.g., proline. In nitrogen-replete conditions, Gln3 is cytoplasmic and Gln3-mediated transcription minimal, whereas in nitrogen limiting or starvation conditions, or after rapamycin treatment, Gln3 is nuclear and transcription greatly increased. Increasing evidence supports the idea that TorC1 activation may not be as central to nitrogen-responsive intracellular Gln3 localization as envisioned previously. To test this idea directly, we determined whether Gtr1/2- and Ego1/3-dependent TorC1 activation also was required for cytoplasmic Gln3 sequestration and repressed GATA factor-mediated transcription by abolishing the Gtr-Ego complex proteins. We show that Gln3 is sequestered in the cytoplasm of gtr1Δ, gtr2Δ, ego1Δ, and ego3Δ strains either long term in logarithmically glutamine-grown cells or short term after refeeding glutamine to nitrogen-limited or -starved cells; GATA factor-dependent transcription also was minimal. However, in all but a gtr1Δ, nuclear Gln3 localization in response to nitrogen limitation or starvation was adversely affected. Our data demonstrate: (i) Gtr-Ego-dependent TorC1 activation is not required for cytoplasmic Gln3 sequestration in nitrogen-rich conditions; (ii) a novel Gtr-Ego-TorC1 activation-independent mechanism sequesters Gln3 in the cytoplasm; (iii) Gtr and Ego complex proteins participate in nuclear Gln3-Myc(13) localization, heretofore unrecognized functions for these proteins; and (iv) the importance of searching for new mechanisms associated with TorC1 activation and/or the regulation of Gln3 localization/function in response to changes in the cells' nitrogen environment. Copyright © 2015 Tate et al.
Tate, Jennifer J.; Georis, Isabelle; Rai, Rajendra; Vierendeels, Fabienne; Dubois, Evelyne; Cooper, Terrance G.
2015-01-01
The TorC1 protein kinase complex is a central component in a eukaryotic cell’s response to varying nitrogen availability, with kinase activity being stimulated in nitrogen excess by increased intracellular leucine. This leucine-dependent TorC1 activation requires functional Gtr1/2 and Ego1/3 complexes. Rapamycin inhibition of TorC1 elicits nuclear localization of Gln3, a GATA-family transcription activator responsible for the expression of genes encoding proteins required to transport and degrade poor nitrogen sources, e.g., proline. In nitrogen-replete conditions, Gln3 is cytoplasmic and Gln3-mediated transcription minimal, whereas in nitrogen limiting or starvation conditions, or after rapamycin treatment, Gln3 is nuclear and transcription greatly increased. Increasing evidence supports the idea that TorC1 activation may not be as central to nitrogen-responsive intracellular Gln3 localization as envisioned previously. To test this idea directly, we determined whether Gtr1/2- and Ego1/3-dependent TorC1 activation also was required for cytoplasmic Gln3 sequestration and repressed GATA factor-mediated transcription by abolishing the Gtr-Ego complex proteins. We show that Gln3 is sequestered in the cytoplasm of gtr1Δ, gtr2Δ, ego1Δ, and ego3Δ strains either long term in logarithmically glutamine-grown cells or short term after refeeding glutamine to nitrogen-limited or -starved cells; GATA factor−dependent transcription also was minimal. However, in all but a gtr1Δ, nuclear Gln3 localization in response to nitrogen limitation or starvation was adversely affected. Our data demonstrate: (i) Gtr-Ego-dependent TorC1 activation is not required for cytoplasmic Gln3 sequestration in nitrogen-rich conditions; (ii) a novel Gtr-Ego-TorC1 activation-independent mechanism sequesters Gln3 in the cytoplasm; (iii) Gtr and Ego complex proteins participate in nuclear Gln3-Myc13 localization, heretofore unrecognized functions for these proteins; and (iv) the importance of searching for new mechanisms associated with TorC1 activation and/or the regulation of Gln3 localization/function in response to changes in the cells’ nitrogen environment. PMID:26024867
Biró, E; van den Goor, J M; de Mol, B A; Schaap, M C; Ko, L-Y; Sturk, A; Hack, C E; Nieuwland, R
2011-01-01
To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and whether microparticles in pericardial blood contribute to systemic complement activation upon retransfusion. Pericardial blood of 13 patients was retransfused in 9 and discarded in 4 cases. Microparticles were isolated from systemic blood collected before anesthesia (T1) and at the end of CPB (T2), and from pericardial blood. The microparticles were analyzed by flow cytometry for bound complement components C1q, C4 and C3, and bound complement activator molecules C-reactive protein (CRP), serum amyloid P-component (SAP), immunoglobulin (Ig)M and IgG. Fluid-phase complement activation products (C4b/c, C3b/c) and activator molecules were determined by ELISA. Compared with systemic T1 blood, pericardial blood contained increased C4b/c and C3b/c, and increased levels of microparticles with bound complement components. In systemic T1 samples, microparticle-bound CRP, whereas in pericardial blood, microparticle-bound SAP and IgM were associated with complement activation. At the end of CPB, increased C3b/c (but not C4b/c) was present in systemic T2 blood compared with T1, while concentrations of microparticles binding complement components and of those binding complement activator molecules were similar. Concentrations of fluid-phase complement activation products and microparticles were similar in patients whether or not retransfused with pericardial blood. In pericardial blood of patients undergoing cardiac surgery with CPB, microparticles contribute to activation of the complement system via bound SAP and IgM. Retransfusion of pericardial blood, however, does not contribute to systemic complement activation.
TSA increases C/EBP‑α expression by increasing its lysine acetylation in hepatic stellate cells.
Tao, Li-Li; Ding, Di; Yin, Wei-Hua; Peng, Ji-Ying; Hou, Chen-Jian; Liu, Xiu-Ping; Chen, Yao-Li
2017-11-01
CCAAT enhancer binding protein‑α (C/EBP‑α) is a transcription factor expressed only in certain tissues, including the liver. It has been previously demonstrated that C/EBP‑α may induce apoptosis in hepatic stellate cells (HSCs), raising the question of whether acetylation of C/EBP‑α is associated with HSCs, and the potential associated mechanism. A total of three histone deacetylase inhibitors (HDACIs), including trichostatin A (TSA), suberoylanilide hydroxamic acid and nicotinamide, were selected to determine whether acetylation affects C/EBP‑α expression. A Cell Counting Kit‑8 assay was used to determine the rate of proliferation inhibition following treatment with varying doses of the three HDACIs in HSC‑T6 and BRL‑3A cells. Western blot analysis was used to examine Caspase‑3, ‑8, ‑9, and ‑12 levels in HSC‑T6 cells treated with adenoviral‑C/EBP‑α and/or TSA. Following treatment with TSA, a combination of reverse transcription‑quantitative polymerase chain reaction and western blot analyses was used to determine the inherent C/EBP‑α mRNA and protein levels in HSC‑T6 cells at 0, 1, 2, 4, 8, 12, 24, 36 and 48 h. Nuclear and cytoplasmic proteins were extracted to examine C/EBP‑α distribution. Co‑immunoprecipitation analysis was used to examine the lysine acetylation of C/EBP‑α. It was observed that TSA inhibited the proliferation of HSC‑T6 cells to a greater extent compared with BRL‑3A cells, following treatment with the three HDACIs. TSA induced apoptosis in HSC‑T6 cells and enhanced the expression of C/EBP‑α. Following treatment of HSC‑T6 cells with TSA, inherent C/EBP‑α expression increased in a time‑dependent manner, and its lysine acetylation simultaneously increased. Therefore, the results of the present study suggested that TSA may increase C/EBP‑α expression by increasing its lysine acetylation in HSCs.
Effect of elevated temperature on soil hydrothermal regimes and growth of wheat crop.
Pramanik, P; Chakrabarti, Bidisha; Bhatia, Arti; Singh, S D; Maity, A; Aggarwal, P; Krishnan, P
2018-03-14
An attempt has been made to study the effect of elevated temperature on soil hydrothermal regimes and winter wheat growth under simulated warming in temperature gradient tunnel (TGT). Results showed that bulk density (BDs) of 0, 0.9, and 2.5 °C were significantly different whereas BDs of 2.8 and 3.5 °C were not significantly different. Water filled pore space (WFPS) was maximum at 3.5 °C temperature rise and varied between 43.80 and 98.55%. Soil surface temperature (ST) at different dates of sowing increased with rise in sensor temperature and highest ST was observed at S5 sensors (3.5 °C temperature rise). Temperature and its difference were high for the top soil, and were stable for the deep soil. Photosynthesis rate (μmol CO 2 m -2 s -1 ) of wheat was lower at higher temperature in different growth stages of wheat. In wheat, stomatal conductance declined from 0.67 to 0.44 mol m -2 s -1 with temperature rise. Stomatal conductance decreased with increase in soil temperature and gravimetric soil moisture content (SWC). In TGT, 0 °C temperature rise showed highest root weight density (RWD) (5.95 mg cm -3 ); whereas, 2.8 and 3.5 °C showed lowest RWD (4.90 mg cm -3 ). Harvest index was maximum (0.37) with 0 °C temperature rise, and it decreased with increase in temperature, which indicated that both grain and shoot biomass decreased with increase in temperature. Intensive studies are needed to quantify the soil hydrothermal regimes inside TGT along with the crop growth parameters.
Rao, Wenwei; Wang, Yun; Han, Juan; Wang, Lei; Chen, Tong; Liu, Yan; Ni, Liang
2015-06-25
The cloud point of thermosensitive triblock polymer L61, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO), was determined in the presence of various electrolytes (K2HPO4, (NH4)3C6H5O7, and K3C6H5O7). The cloud point of L61 was lowered by the addition of electrolytes, and the cloud point of L61 decreased linearly with increasing electrolyte concentration. The efficacy of electrolytes on reducing cloud point followed the order: K3C6H5O7 > (NH4)3C6H5O7 > K2HPO4. With the increase in salt concentration, aqueous two-phase systems exhibited a phase inversion. In addition, increasing the temperature reduced the concentration of salt needed that could promote phase inversion. The phase diagrams and liquid-liquid equilibrium data of the L61-K2HPO4/(NH4)3C6H5O7/K3C6H5O7 aqueous two-phase systems (before the phase inversion but also after phase inversion) were determined at T = (25, 30, and 35) °C. Phase diagrams of aqueous two-phase systems were fitted to a four-parameter empirical nonlinear expression. Moreover, the slopes of the tie-lines and the area of two-phase region in the diagram have a tendency to rise with increasing temperature. The capacity of different salts to induce aqueous two-phase system formation was the same order as the ability of salts to reduce the cloud point.
Constraints on core-mantle boundary topography from models of thermal and thermochemical convection
NASA Astrophysics Data System (ADS)
Deschamps, Frédéric; Rogister, Yves; Tackley, Paul J.
2018-01-01
Mantle flow induces dynamic topography at the core-mantle boundary (CMB), with distribution and amplitude that depend on details of the flow. To assess whether observations of CMB topography can give constraints on deep mantle structure, we determine CMB dynamic topography associated with different models of mantle convection, including thermochemical and purely thermal models. We investigate the influence of key controlling parameters, specifically the thermal viscosity ratio (ΔηT) and, for thermochemical models, the density contrast (ΔρC) and viscosity ratio (ΔηC) between primordial and regular materials. In purely thermal models, plume clusters induce positive topography with an amplitude that decreases with increasing ΔηT. In thermochemical models with moderate density contrasts, around 100-200 kg m-3, reservoirs of dense material induce depressions in CMB topography, surrounded by a ridge of positive topography. The average depression depth and ridge height increase with increasing ΔρC and ΔηC, but decrease with increasing ΔηT. We find that for purely thermal models or thermochemical models with ΔρC ˜ 90 kg m-3 and less, the long-wavelength (spherical harmonic degrees up to l = 4) dynamic topography and shear wave velocity anomalies predicted by thermochemical distributions anticorrelate. By contrast, for models with ΔρC ≥ 100 kg m-3 and ΔηC > 1, long-wavelength dynamic topography and shear wave velocity anomalies correlate well. This potentially provides a test to infer the nature, that is, either purely or mostly thermal (ΔρC ≤ 100 kg m-3 m-3) or strongly thermochemical (ΔρC ≥ 100 kg m-3), of the low shear wave velocity provinces observed by global tomographic images. The presence of post-perovskite, provided that its viscosity is similar to that of bridgmanite, does not alter these conclusions.
MAGIC detection of increased activity from FSRQ 3C 279 at very-high-energy gamma rays
NASA Astrophysics Data System (ADS)
Mirzoyan, Razmik
2018-04-01
The MAGIC telescopes observed an increase in the very-high-energy (VHE; > 100 GeV) gamma-ray flux from FSRQ 3C 279 at radio coordinates R.A.=194.04652737 deg and Dec= -5.78931242 deg, J2000.0 (Fey et al. 2004, AJ, 127, 3587).
Gao, Jian-mei; Li, Ran; Zhang, Lei; Jia, Li-long; Ying, Xi-xiang; Dou, De-qiang; Li, Jian-chun; Li, Hai-bo
2013-07-09
Cuscuta chinensis (C. chinensis) is a well-known traditional Chinese herb that has been used to treat heart disease, diabetes, liver injury, cancer, and aging. Murine osteoblastic MC3T3-E1 cells were treated with various concentrations of C. chinensis water extraction at different time intervals. The antioxidant effect of C. chinensis on MC3T3-E1 cells was evaluated using MTT and TUNEL assays. The effect of C. chinensis on cell cycle was analyzed by flow cytometry with propidium iodide. Lipid peroxidation was measured by the HPLC method. The cellular redox status was determined from the reduced glutathione to oxidized glutathione ratio (GSH/GSSG) and the enzymes involved in glutathione metabolism, including glutathione reductase (GR), Glutathione S-transferase (GST), and Glucose-6-phosphate dehydrogenase (G6PD). The changes in relative mitochondrial transmembrane potential (ΔΨm) in the MC3T3-E1 cells were analyzed with rhodamine 123 staining. Western blot analysis was used to evaluate the levels of cytochrome c (cyto c), Bax, Bcl-2, caspase 3, Sirt3, and IDH2 expressions. The C. chinensis water extraction protects tertiary butyl hydroperoxide (TBHP)-treated MC3T3-E1 cells from death in a dose-dependent manner. C. chinensis treatment significantly inhibited the reactive oxygen species (ROS) generation, malondialdehyde (MDA) production, and increased the activity of superoxide dismutase (SOD), GR, GST, and G6PD. The release of cyto c from mitochondria was reduced by C. chinensis, which increased the expression of antiapoptotic IDH2, Sirt3, and Bcl-2 and decreased the expression of Bax, cyto c, and caspase 3. C. chinensis modulated the oxidative stress-induced apoptosis in MC3T3-E1 cells, probably due to its antioxidant activity and functioning via mitochondria-dependent pathways. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Vigeolas, Helene; Hühn, Daniela; Geigenberger, Peter
2011-01-01
Nonsymbiotic hemoglobins are ubiquitously expressed in plants and divided into two different classes based on gene expression pattern and oxygen-binding properties. Most of the published research has been on the function of class 1 hemoglobins. To investigate the role of class 2 hemoglobins, transgenic Arabidopsis (Arabidopsis thaliana) plants were generated overexpressing Arabidopsis hemoglobin-2 (AHb2) under the control of a seed-specific promoter. Overexpression of AHb2 led to a 40% increase in the total fatty acid content of developing and mature seeds in three subsequent generations. This was mainly due to an increase in the polyunsaturated C18:2 (ω-6) linoleic and C18:3 (ω-3) α-linolenic acids. Moreover, AHb2 overexpression led to an increase in the C18:2/C18:1 and C18:3/C18:2 ratios as well as in the C18:3 content in mol % of total fatty acids and in the unsaturation/saturation index of total seed lipids. The increase in fatty acid content was mainly due to a stimulation of the rate of triacylglycerol synthesis, which was attributable to a 3-fold higher energy state and a 2-fold higher sucrose content of the seeds. Under low external oxygen, AHb2 overexpression maintained an up to 5-fold higher energy state and prevented fermentation. This is consistent with AHb2 overexpression results in improved oxygen availability within developing seeds. In contrast to this, overexpression of class 1 hemoglobin did not lead to any significant increase in the metabolic performance of the seeds. These results provide evidence for a specific function of class 2 hemoglobin in seed oil production and in promoting the accumulation of polyunsaturated fatty acids by facilitating oxygen supply in developing seeds. PMID:21205621
High temperature compounds for turbine vanes. [of SiC, Si3N4, and Si composites
NASA Technical Reports Server (NTRS)
Rhodes, W. H.; Cannon, R. M., Jr.
1974-01-01
Fabrication and microstructure control studies were conducted on SiC, Si3N and composites based on Si3N. Charpy mode impact testing to 2400 F established that Si3N4/Mo composites have excellent potential. Attempts to fabricate composites of Si3N4 with superalloys, both by hot pressing and infiltration were largely unsuccessful in comparison to using Mo, Re, and Ta which are less reactive. Modest improvements in impact strength were realized for monolithic Si3N4; however, SiC strengths increased by a factor of six and now equal values achieved for Si3N4. Correlations of impact strength with material properties are discussed. Reduced MgO densification aid additions to Si3N4 were found to decrease densification kinetics, increase final porosity, decrease room temperature bend strength, increase high temperature bend strength, and decrease bend stress rupture properties. The decrease in bend strength at high temperature for fine grain size SiC suggested that a slightly larger grain size material with a nearly constant strength-temperature relation may prove desirable in the creep and stress rupture mode.
Goodrum, K J
1987-01-01
Complement levels and complement activation are key determinants in streptococcus-induced inflammatory responses. Activation of macrophage functions, such as complement synthesis, by group B streptococci (GBS) was examined as a possible component of GBS-induced chronic inflammation. Using an enzyme-linked immunosorbent assay, secreted C3 from mouse macrophagelike cell lines (PU5-1.8 and J774A.1) was monitored after cultivation with GBS. Whole, heat-killed GBS (1 to 10 CFU per macrophage) of both type Ia and III strains induced 25 to 300% increases in secreted C3 in both cell lines after a 24-h cultivation. GBS-treated cell lines exhibited increases in secreted lysozyme (10%) and in cellular protein (25 to 50%). Inhibition of macrophage phagocytosis by cytochalasin B inhibited GBS stimulation of C3. Purified cell walls of GBS type III strain 603-79 (1 to 10 micrograms/ml) also enhanced C3 synthesis. Local enhancement of macrophage C3 production by ingested streptococci or by persistent cell wall antigens may serve to promote chronic inflammatory responses. PMID:3552987
Zakharova, Liudmila; Nural-Guvener, Hikmet; Feehery, Lorraine; Popovic-Sljukic, Snjezana
2015-01-01
Cardiac c-Kit+ cells have a modest cardiogenic potential that could limit their efficacy in heart disease treatment. The present study was designed to augment the cardiogenic potential of cardiac c-Kit+ cells through class I histone deacetylase (HDAC) inhibition and evaluate their therapeutic potency in the chronic heart failure (CHF) animal model. Myocardial infarction (MI) was created by coronary artery occlusion in rats. c-Kit+ cells were treated with mocetinostat (MOCE), a specific class I HDAC inhibitor. At 3 weeks after MI, CHF animals were retrogradely infused with untreated (control) or MOCE-treated c-Kit+ cells (MOCE/c-Kit+ cells) and evaluated at 3 weeks after cell infusion. We found that class I HDAC inhibition in c-Kit+ cells elevated the level of acetylated histone H3 (AcH3) and increased AcH3 levels in the promoter regions of pluripotent and cardiac-specific genes. Epigenetic changes were accompanied by increased expression of cardiac-specific markers. Transplantation of CHF rats with either control or MOCE/c-Kit+ cells resulted in an improvement in cardiac function, retardation of CHF remodeling made evident by increased vascularization and scar size, and cardiomyocyte hypertrophy reduction. Compared with CHF infused with control cells, infusion of MOCE/c-Kit+ cells resulted in a further reduction in left ventricle end-diastolic pressure and total collagen and an increase in interleukin-6 expression. The low engraftment of infused cells suggests that paracrine effects might account for the beneficial effects of c-Kit+ cells in CHF. In conclusion, selective inhibition of class I HDACs induced expression of cardiac markers in c-Kit+ cells and partially augmented the efficacy of these cells for CHF repair. Significance The study has shown that selective class 1 histone deacetylase inhibition is sufficient to redirect c-Kit+ cells toward a cardiac fate. Epigenetically modified c-Kit+ cells improved contractile function and retarded remodeling of the congestive heart failure heart. This study provides new insights into the efficacy of cardiac c-Kit+ cells in the ischemic heart failure model. PMID:26240433
NASA Astrophysics Data System (ADS)
Song, Haili; Li, Chao; Nguyen Van, Chien; Dong, Wenxia; Qi, Ruijuan; Zhang, Yuanyuan; Huang, Rong; Chu, Ying-Hao; Duan, Chun-Gang
2018-02-01
A series of self-assembled WO3-BiVO4 nanostructured thin films were grown on the (001) yttria-stabilized zirconia (YSZ) substrate at the substrate temperatures of 400 °C, 500 °C, 550 °C, 600 °C, 650 °C and 700 °C by a pulsed laser deposition method. The microstructures including crystalline phases, epitaxial relationships, surface morphologies and interface structures were investigated by a combination of x-ray diffraction, scanning electron microscopy and high-resolution transmission electron microscopy. The sample grown at 400 °C was amorphous due to the low driving forces for nucleation and diffusion. For the samples made at 500 °C, 550 °C and 600 °C, the monoclinic BiVO4 matrix epitaxially grew on YSZ, forming the matrix, where the WO3 nanopillars were embedded in with a specific orientation relationship among BiVO4, WO3 and YSZ. However, in thin films deposited at 650 °C and 700 °C, the WO3 grains randomly grew on the YSZ substrate, which dominated the microstructures of the resultant thin films. Quantitative analyses of the microstructures revealed that the lateral grain sizes of BiVO4 and WO3 increased and the volume fraction of BiVO4 in the thin films decreased with the increase of the deposition temperature. A three-regime growth mechanism of the WO3-BiVO4 composite thin film was proposed based on the growth dynamics determined by the competition between BiVO4 and WO3.
Garaiova, Iveta; Guschina, Irina A; Plummer, Sue F; Tang, James; Wang, Duolao; Plummer, Nigel T
2007-01-01
Background The health benefits of increased intakes of omega-3 fatty acids are well established but palatability often presents a problem. The process of emulsification is used in the food industry to provide a wider spectrum of use, often with the result of increased consumption. Moreover, as emulsification is an important step in the digestion and absorption of fats, the pre-emulsification process may enhance digestion and absorption. In this study the levels of plasma fatty acid and triacylglycerol (TAG) following the ingestion of either an oil mixture or an emulsified oil mixture have been compared. Methods In this randomised cross-over study, 13 volunteers received the oil mixture and 11 received the oil emulsion as part of an otherwise fat free meal. Blood samples were collected at 0, 1.5, 3, 4.5, 6, 7.5 and 9 hours after ingestion of oil, separated and stored at -20°C. Plasma triacylglycerols were assessed spectrophotometrically and fatty acids were determined by gas chromatography. Following a washout period of twenty days the procedure was repeated with the assignments reversed. Results The postprandial plasma TAG and the C18:3 (n-6), C18:3(n-3), C20:5(n-3) and C22:6 (n-3) polyunsaturated fatty acid (PUFA) levels for the emulsified oil group were increased significantly (P = 0.0182; P = 0.0493; P = 0.0137; P < 0.0001; P = 0.0355 respectively) compared with the non-emulsified oil group. The C16:0 and C18:0 saturated fatty acids, the C18:1 (n-9) monounsaturated fatty acid and the C18:2 PUFA were not significantly different for the oil and emulsified oil groups. Conclusion Pre-emulsification of an oil mixture prior to ingestion increases the absorption of longer chain more highly unsaturated fatty acids (especially eicosapentaenoic acid and docosahexaenoic acid) but does not affect absorption of shorter chain less saturated fatty acids, suggesting that pre-emulsification of fish oils may be a useful means of boosting absorption of these beneficial fatty acids. Trial registration: Current Controlled Trials ISRCTN43202606 PMID:17254329
NASA Astrophysics Data System (ADS)
Marion, G. M.; Millero, F. J.; Feistel, R.
2009-07-01
At the present time, little is known about how broad salinity and temperature ranges are for seawater thermodynamic models that are functions of absolute salinity (SA), temperature (T) and pressure (P). Such models rely on fixed compositional ratios of the major components (e.g., Na/Cl, Mg/Cl, Ca/Cl, SO4/Cl, etc.). As seawater evaporates or freezes, solid phases [e.g., CaCO3(s) or CaSO42H2O(s)] will eventually precipitate. This will change the compositional ratios, and these salinity models will no longer be applicable. A future complicating factor is the lowering of seawater pH as the atmospheric partial pressures of CO2 increase. A geochemical model (FREZCHEM) was used to quantify the SA-T boundaries at P=0.1 MPa and the range of these boundaries for future atmospheric CO2 increases. An omega supersaturation model for CaCO3 minerals based on pseudo-homogeneous nucleation was extended from 25-40°C to 3°C. CaCO3 minerals were the boundary defining minerals (first to precipitate) between 3°C (at SA=104 g kg-) and 40°C (at SA=66 g kg-). At 2.82°C, calcite(CaCO3) transitioned to ikaite(CaCO36H2O) as the dominant boundary defining mineral for colder temperatures, which culminated in a low temperature boundary of -4.93°C. Increasing atmospheric CO2 from 385 μatm (390 MPa) (in Year 2008) to 550 μatm (557 MPa) (in Year 2100) would increase the SA and t boundaries as much as 11 g kg-1 and 0.66°C, respectively. The model-calculated calcite-ikaite transition temperature of 2.82°C is in excellent agreement with ikaite formation in natural environments that occurs at temperatures of 3°C or lower. Furthermore, these results provide a quantitative theoretical explanation (FREZCHEM model calculation) for why ikaite is the solid phase CaCO3 mineral that precipitates during seawater freezing.
Salinity/temperature ranges for application of seawater SA-T-P models
NASA Astrophysics Data System (ADS)
Marion, G. M.; Millero, F. J.; Feistel, R.
2009-01-01
At the present time, little is known about how broad salinity and temperature ranges are for seawater thermodynamic models that are functions of absolute salinity (SA), temperature (T) and pressure (P). Such models rely on fixed compositional ratios of the major components (e.g. Na/Cl, Mg/Cl, Ca/Cl, SO4/Cl, etc.). As seawater evaporates or freezes, solid phases (e.g. CaCO3(s) or CaSO42H2O(s)) will eventually precipitate. This will change the compositional ratios, and these salinity models will no longer be applicable. A future complicating factor is the lowering of seawater pH as the atmospheric concentrations of CO2 increase. A geochemical model (FREZCHEM) was used to quantify the SA-T boundaries at P=0.1 MPa and the range of these boundaries for future atmospheric CO2 increases. An omega supersaturation model for CaCO3 minerals based on homogeneous nucleation was extended from 25-40°C to 3°C. CaCO3 minerals were the boundary defining minerals (first to precipitate) between 3°C (at SA=104 g kg-1 and 40°C (at SA=66 g kg-1. At 2.82°C, calcite(CaCO3) transitioned to ikaite(CaCO36H2O) as the dominant boundary defining mineral for colder temperatures, which culminated in a low temperature boundary of -4.93°C. Increasing atmospheric CO2 from 385 μatm (in Year 2008) to 550 μatm (in Year 2100) would increase the SA and t boundaries as much as 11 g kg-1 and 0.66°C, respectively. The model-calculated calcite-ikaite transition temperature of 2.82°C is in excellent agreement with ikaite formation in natural environments that occurs at temperatures of 3°C or lower. Furthermore, these results provide a quantitative theoretical explanation (FREZCHEM model calculations) for why ikaite is the solid phase CaCO3 mineral that precipitates during seawater freezing.
Engineering epitaxial γ-Al2O3 gate dielectric films on 4H-SiC
NASA Astrophysics Data System (ADS)
Tanner, Carey M.; Toney, Michael F.; Lu, Jun; Blom, Hans-Olof; Sawkar-Mathur, Monica; Tafesse, Melat A.; Chang, Jane P.
2007-11-01
The formation of epitaxial γ-Al2O3 thin films on 4H-SiC was found to be strongly dependent on the film thickness. An abrupt interface was observed in films up to 200 Å thick with an epitaxial relationship of γ-Al2O3(111)‖4H-SiC(0001) and γ-Al2O3(44¯0)‖4H-SiC(112¯0). The in-plane alignment between the film and the substrate is nearly complete for γ-Al2O3 films up to 115 Å thick, but quickly diminishes in thicker films. The films are found to be slightly strained laterally in tension; the strain increases with thickness and then decreases in films thicker than 200 Å, indicating strain relaxation which is accompanied by increased misorientation. By controlling the structure of ultrathin Al2O3 films, metal-oxide-semiconductor capacitors with Al2O3 gate dielectrics on 4H-SiC were found to have a very low leakage current density, suggesting suitability of Al2O3 for SiC device integration.
Kubásek, Jiří; Urban, Otmar; Šantrůček, Jiří
2013-12-01
Plants in the field are commonly exposed to fluctuating light intensity, caused by variable cloud cover, self-shading of leaves in the canopy and/or leaf movement due to turbulence. In contrast to C3 plant species, only little is known about the effects of dynamic light (DL) on photosynthesis and growth in C4 plants. Two C4 and two C3 monocot and eudicot species were grown under steady light or DL conditions with equal sum of daily incident photon flux. We measured leaf gas exchange, plant growth and dry matter carbon isotope discrimination to infer CO2 bundle sheath leakiness in C4 plants. The growth of all species was reduced by DL, despite only small changes in steady-state gas exchange characteristics, and this effect was more pronounced in C4 than C3 species due to lower assimilation at light transitions. This was partially attributed to increased bundle sheath leakiness in C4 plants under the simulated lightfleck conditions. We hypothesize that DL leads to imbalances in the coordination of C4 and C3 cycles and increasing leakiness, thereby decreasing the quantum efficiency of photosynthesis. In addition to their other constraints, the inability of C4 plants to efficiently utilize fluctuating light likely contributes to their absence in such environments as forest understoreys. © 2013 Scandinavian Plant Physiology Society.
Han, Noori; Park, Sun-Young; Kim, Sun-Young; Yoo, Mi-Young; Paik, Hyun-Dong; Lim, Sang-Dong
2016-11-01
This study sought to investigate the change of naturally occurring benzoic acid (BA) during skim milk fermentation by 4 kinds of commercial cheese starters used in domestic cheese. The culture was incubated at 3-h intervals for 24h at 30, 35, and 40°C. The BA content during fermentation by Streptococcus thermophilus STB-01 was detected after 12h at all temperatures, sharply increasing at 30°C. In Lactobacillus paracasei LC431, BA was detected after 9h at all temperatures, sharply increasing until 18h and decreasing after 18h at 30 and 35°C. In the case of R707 (consisting of Lactococcus lactis ssp. lactis and Lactococcus lactis ssp. cremoris), BA increased from 6h to 15h and decreased after 15h at 40°C. The BA during STB-01 and CHN-11 (1:1; mixture of S. thermophilus, Lc. lactis ssp. lactis, Lc. lactis ssp. cremoris, Lc. lactis ssp. diacetylactis, Leuconostoc mesenteroides ssp. cremoris) fermentation was detected after 3h at 35 and 40°C, sharply increasing up to 12h and decreasing after 15h at 35°C, and after 6h, increasing up to 9h at 30°C. After 3h, it steadily decreased at 40°C. The highest amount of BA was found during the fermentation by R707 at 30°C; 15h with 12.46mg/kg. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Involvement of Polyamines in the Chilling Tolerance of Cucumber Cultivars
Shen, Wenyun; Nada, Kazuyoshi; Tachibana, Shoji
2000-01-01
The possible involvement of polyamines (PAs) in the chilling tolerance of cucumber (Cucumis sativus L. cv Jinchun No. 3 and cv Suyo) was investigated. Plants with the first expanded leaves were exposed to 3°C or 15°C in the dark for 24 h (chilling), and then transferred to 28°C/22°C under a 12-h photoperiod for another 24 h (rewarming). Chilling-tolerant cv Jinchun No. 3 showed a marked increase of free spermidine (Spd) in leaves, once during chilling and again during rewarming. Putrescine increased significantly during rewarming, but the increase of spermine was slight. Any of these PAs did not increase in chilling-sensitive cv Suyo during either period. PA-biosynthetic enzyme activities appear to mediate these differences between cultivars. Pretreatment of Spd to cv Suyo prevented chill-induced increases in the contents of hydrogen peroxide in leaves and activities of NADPH oxidases and NADPH-dependent superoxide generation in microsomes and alleviated chilling injury. Pretreatment of methylglyoxal-bis-(guanylhydrazone), a PA biosynthesis inhibitor, to chilled cv Jinchun No. 3 prevented Spd increase and enhanced microsomal NADPH oxidase activity and chilling injury. The results suggest that Spd plays important roles in chilling tolerance of cucumber, probably through prevention of chill-induced activation of NADPH oxidases in microsomes. PMID:10982456
NASA Astrophysics Data System (ADS)
Hessien, M. M.; Mostafa, Nasser Y.; Abd-Elkader, Omar H.
2016-01-01
Citric, oxalic and tartaric acids were used for synthesis of NiFe2O4 using polymeric complex precursor route. The dry precursor gels were calcined at various temperatures (400-1100 °C) for 2 h. All carboxylic acids produce iron-deficient NiFe2O4 with considerable amount of α-Fe2O3 at 400 °C. Increase in the annealing temperature caused reaction of α-Fe2O3 with iron-deficient ferrite phase. The amount of initially formed α-Fe2O3 is directly correlated with stability constant and inversely correlated with the decomposition temperature of Fe(III) carboxylate precursors. In case of tartaric acid precursor, single phase of the ferrite was obtained at 450 °C. However, in case of oxalic acid and citric acid precursors, single phase ferrite was obtained at 550 °C and 700 °C, respectively. The lattice parameters were increased with increasing annealing temperature and with decreasing the amount of α-Fe2O3. Maximum saturation magnetization (55 emu/g) was achieved using tartaric acid precursor annealed at 1100 °C.
Manganiello, Vincent; Vaughan, Martha
1972-01-01
The effect of dexamethasone on adenosine 3′,5′-monophosphate (cAMP) phosphodiesterase activity in cultured HTC hepatoma cells was investigated. Homogenates of these cells contain phosphodiesterase activity with two apparent Michaelis constants for cAMP (2-5 μm and 50 μm). At all substrate concentrations tested, phosphodiesterase activity was decreased 25-40% in cells incubated for 36 hr or more with 1 μm dexamethasone. Acid phosphatase activity in the same cells was not decreased. α-Methyl testosterone, 1 μm, was without effect on phosphodiesterase activity. Incubation for 10 min with epinephrine plus theophylline increased the cAMP content of the HTC cells 3- to 6-fold. In cells incubated for 72 hr with dexamethasone, the basal concentration of cAMP was slightly increased and the increment produced by epinephrine plus theophylline was markedly increased. We believe that in many cells the so-called permissive effects of steroid hormones on cAMP mediated processes may be due to an effect of these hormones on cAMP phosphodiesterase activity similar to that observed in HTC cells incubated with dexamethasone. PMID:4341439
Olson, Michelle L; Jayaraman, Arul; Kao, Katy C
2018-04-15
Candida is a member of the normal human microbiota and often resides on mucosal surfaces such as the oral cavity or the gastrointestinal tract. In addition to their commensality, Candida species can opportunistically become pathogenic if the host microbiota is disrupted or if the host immune system becomes compromised. An important factor for Candida pathogenesis is its ability to form biofilm communities. The two most medically important species- Candida albicans and Candida glabrata -are often coisolated from infection sites, suggesting the importance of Candida coculture biofilms. In this work, we report that biofilm formation of the coculture population depends on the relative ratio of starting cell concentrations of C. albicans and C. glabrata When using a starting ratio of C. albicans to C. glabrata of 1:3, ∼6.5- and ∼2.5-fold increases in biofilm biomass were observed relative to those of a C. albicans monoculture and a C. albicans / C. glabrata ratio of 1:1, respectively. Confocal microscopy analysis revealed the heterogeneity and complex structures composed of long C. albicans hyphae and C. glabrata cell clusters in the coculture biofilms, and reverse transcription-quantitative PCR (qRT-PCR) studies showed increases in the relative expression of the HWP1 and ALS3 adhesion genes in the C. albicans / C. glabrata 1:3 biofilm compared to that in the C. albicans monoculture biofilm. Additionally, only the 1:3 C. albicans / C. glabrata biofilm demonstrated an increased resistance to the antifungal drug caspofungin. Overall, the results suggest that interspecific interactions between these two fungal pathogens increase biofilm formation and virulence-related gene expression in a coculture composition-dependent manner. IMPORTANCE Candida albicans and Candida glabrata are often coisolated during infection, and the occurrence of coisolation increases with increasing inflammation, suggesting possible synergistic interactions between the two Candida species in pathogenesis. During the course of an infection, the prevalence of each Candida species may change over time due to differences in metabolism and in the resistance of each species to antifungal therapies. Therefore, it is necessary to understand the dynamics between C. albicans and C. glabrata in coculture to develop better therapeutic strategies against Candida infections. Existing in vitro work has focused on understanding how an equal-part culture of C. albicans and C. glabrata impacts biofilm formation and pathogenesis. What is not understood, and what is investigated in this work, is how the composition of Candida species in coculture impacts overall biofilm formation, virulence gene expression, and the therapeutic treatment of biofilms. Copyright © 2018 American Society for Microbiology.
The ClC-3 chloride channel and osmoregulation in the European sea bass, Dicentrarchus labrax.
Bossus, Maryline; Charmantier, Guy; Blondeau-Bidet, Eva; Valletta, Bianca; Boulo, Viviane; Lorin-Nebel, Catherine
2013-07-01
Dicentrarchus labrax migrates between sea (SW), brackish and fresh water (FW) where chloride concentrations and requirements for chloride handling change: in FW, fish absorb chloride and restrict renal losses; in SW, they excrete chloride. In this study, the expression and localization of ClC-3 and Na(+)/K(+)-ATPase (NKA) were studied in fish adapted to SW, or exposed to FW from 10 min to 30 days. In gills, NKA-α1 subunit expression transiently increased from 10 min and reached a stabilized intermediate expression level after 24 h in FW. ClC-3 co-localized with NKA in the basolateral membrane of mitochondria-rich cells (MRCs) at all conditions. The intensity of MRC ClC-3 immunostaining was significantly higher (by 50 %) 1 h after the transfer to FW, whereas the branchial ClC-3 protein expression was 30 % higher 7 days after the transfer as compared to SW. This is consistent with the increased number of immunopositive MRCs (immunostained for NKA and ClC-3). However, the ClC-3 mRNA expression was significantly lower in FW gills. In the kidney, after FW transfer, a transient decrease in NKA-α1 subunit expression was followed by significantly higher stable levels from 24 h. The low ClC-3 protein expression detected at both salinities was not observed by immunocytochemistry in the SW kidney; ClC-3 was localized in the basal membrane of the collecting ducts and tubules 7 and 30 days after transfer to FW. Renal ClC-3 mRNA expression, however, seemed higher in SW than in FW. The potential role of this chloride channel ClC-3 in osmoregulatory and osmosensing mechanisms is discussed.
Regulation of Phosphodiesterase 3 in the Pulmonary Arteries During the Perinatal Period in Sheep
Chen, Bernadette; Lakshminrusimha, Satyan; Czech, Lyubov; Groh, Beezly S.; Gugino, Sylvia F.; Russell, James A.; Farrow, Kathryn N.; Steinhorn, Robin H.
2009-01-01
The role of cAMP in the pulmonary vasculature during the transition from intrauterine to extrauterine life is poorly understood. We hypothesized that cAMP levels are regulated by alterations in phosphodiesterase 3 (PDE3), which hydrolyzes cAMP. PDE3 protein expression and hydrolytic activity were increased in resistance pulmonary arteries (PA) from spontaneously breathing one-day-old (1dSB) lambs relative to equivalent-gestation fetuses. This was accompanied by a decrease in steady-state cAMP. Ventilation with 21% O2 and 100% O2 for 24h disrupted the normal transition, whereas ventilation with 100% O2+inhaled NO (iNO) for 24h restored both PDE3 activity and cAMP to 1dSB levels. Consistent with these findings, relaxation to milrinone, a PDE3 inhibitor, was greater in PA isolated from 1dSB and 100% O2+iNO lambs, relative to fetal, 21% O2, and 100% O2 lambs. In conclusion, PDE3 expression and activity in PA dramatically increase after birth, with a concomitant decrease in steady-state cAMP. Ventilation with either 21% O2 or 100% O2 blunts this PDE3 increase, whereas iNO restores PDE3 activity to levels equivalent to 1dSB lambs. The vasodilatory effects of milrinone were most pronounced in vessels from lambs with the highest PDE3 activity, i.e. 1dSB and 100% O2+iNO lambs. Thus, milrinone may be most beneficial when used in conjunction with iNO. PMID:19707176
Tailoring the properties of acetate-based ionic liquids using the tricyanomethanide anion.
Lepre, L F; Szala-Bilnik, J; Padua, A A H; Traïkia, M; Ando, R A; Costa Gomes, M F
2016-08-17
The equilibrium and transport properties of mixtures of two ionic liquids - [C4C1Im][OAc] and [C4C1Im][C(CN)3] - were determined and interpreted at the molecular level using vibration spectroscopy, NMR and molecular dynamics simulation. The non-ideality of the mixtures [C4C1Im][OAc](1-x)[C(CN)3]x was characterized by V(E) = +0.28 cm(3) mol(-1) (293 K, x = 0.65) and H(E) = -2.2 kJ mol(-1) for x = 0.5. These values could be explained by a rearrangement of the hydrogen-bond network of the mixture that favours the interaction of the acetate anion with the imidazolium cation at position C2. The dynamic properties of the mixture are also dramatically influenced by the composition with a decrease of the viscosity and an increase of self-diffusion coefficients of the ions when the amount of tricyanomethanide anion increases in the mixture.
Stewart, M; Verkerk, G A; Stafford, K J; Schaefer, A L; Webster, J R
2010-08-01
The role of the autonomic nervous system (ANS) in mediating eye temperature responses during painful procedures was examined in thirty 4-mo-old bull calves randomly assigned to 4 treatments: 1) sham handling control (C; n=8), 2) surgical castration (SC; n=6), 3) local anesthesia with sham handling (LAC; n=8), and 4) local anesthesia with surgical castration (LASC; n=8). Maximum eye temperature ( degrees C), measured by infrared thermography, heart rate (HR), and heart rate variability (HRV) were recorded continuously from 25 min before to 20 min after castration. The HRV was analyzed by examining segments of 512 interbeat intervals before and after treatments and comparing the root mean square of successive differences (RMSSD), high and low frequency (HF and LF, respectively) power, and the ratio of LF and HF powers (LF:HF). Jugular blood samples were analyzed for norepinephrine and epinephrine in C and SC treatments and for cortisol during all treatments. There was an immediate increase in HR following castration in SC (+15.3+/-2.8 beats/min) and LASC (+6.3+/-2.4 beats/min) calves. Eye temperature increased during the 20-min observation period in SC and LASC calves (+0.47+/-0.05 degrees C and +0.28+/-0.05 degrees C, respectively), and there was a small increase in C calves (+0.10+/-0.05 degrees C). Following castration in SC calves, there was an increase in RMSSD (+25.8+/-6.4) and HF power (+11.0+/-6.5) and LF:HF decreased (-2.1+/-0.7). Following castration in LASC, there was an increase in RMSSD (+18.1+/-4.9) and a decrease in LF power (-10.2+/-5.0). Cortisol increased above baseline within 15 min following treatment in both castrated groups, but was greater for SC calves (+18.4+/-2.3 ng/mL) than for LASC calves (+11.1+/-1.9 ng/mL). After castration, norepinephrine increased 3-fold and epinephrine increased by half in SC calves but not in C calves. There were no changes in HR, HRV, or cortisol responses to C or LAC treatments. Local anesthetic reduced, but did not eliminate, responses to surgical castration. The synchronized increase in catecholamine and HR responses immediately following SC treatment suggests the initial response was mediated by the sympathetic branch of the ANS. The subsequent changes in RMSSD, HF power, and LF:HF ratio indicated this was followed by an increase in parasympathetic activity. The use of HR, HRV, and infrared thermography measurements together provide a noninvasive means to assess ANS responses as indicators of acute pain in cattle. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Saito, Takeshi; Abe, Daigo; Sekiya, Keizo
2007-06-01
Nobiletin is a polymethoxylated flavone found in certain citrus fruits. Here we demonstrate that nobiletin enhance differentiation of 3T3-L1 preadipocytes. Nobiletin dose-dependently increased accumulation of lipid droplets in adipocytes. Quantitative RT-PCR analyses indicated that nobiletin increased the expression of genes critical for acquisition of the adipocyte phenotype. Some of them were known peroxisome proliferator activated receptor {gamma} (PPAR{gamma}) targets and PPAR{gamma} itself, however, nobiletin did not exhibit PPAR{gamma} ligand activity. We observed the expression of CCAAT/enhancer binding protein {beta} (C/EBP{beta}), a transcription factor for PPAR{gamma}, was increased by nobiletin. The activation of cAMP-responsive element binding protein (CREB) and extracellular signal-regulatedmore » kinase (ERK), which play important roles in C/EBP{beta} expression were also potentiated by nobiletin. Furthermore, nobiletin stimulated lipolysis in differentiated adipocytes, which is known to be stimulated by cAMP pathway. These results suggested that nobiletin enhanced both differentiation and lipolysis of adipocyte through activation of signaling cascades mediated by cAMP/CREB.« less
CO2 conversion in non-thermal plasma and plasma/g-C3N4 catalyst hybrid processes
NASA Astrophysics Data System (ADS)
Lu, Na; Sun, Danfeng; Zhang, Chuke; Jiang, Nan; Shang, Kefeng; Bao, Xiaoding; Li, Jie; Wu, Yan
2018-03-01
Carbon dioxide conversion at atmosphere pressure and low temperature has been studied in a cylindrical dielectric barrier discharge (DBD) reactor. Pure CO2 feed flows to the discharge zone and typical filamentary discharges were obtained in each half-cycle of the applied voltage. The gas temperature increased with discharge time and discharge power, which was found to affect the CO2 decomposition deeply. As the DBD reactor was cooled to ambient temperature, both the conversion of CO2 and the CO yield were enhanced. Especially the energy efficiencies changed slightly with the increase of discharge power and were much higher in cooling condition comparing to those without cooling. At a discharge power of 40 W, the energy efficiency under cooling condition was approximately six times more than that without cooling. Gas flow rate was observed to affect CO2 conversion and 0.1 L min-1 was obtained as optimum gas flow rate under cooling condition. In addition, the CO2 conversion rate in plasma/g-C3N4 catalyst hybrid system was twice times as that in plasma-alone system. In case of cooling, the existence of g-C3N4 catalyst contributed to a 47% increase of CO2 conversion compared to the sole plasma process. The maximum energy-efficiency with g-C3N4 was 0.26 mmol kJ-1 at 20 W, which increased by 157% compared to that without g-C3N4. The synergistic effect of DBD plasma with g-C3N4 on pure CO2 conversion was verified.
Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis.
Matsuzaki, K
2006-06-01
Transforming growth factor-beta (TGF-beta) signaling occurring during human colorectal carcinogenesis involves a shift in TGF-beta function, reducing the cytokine's antiproliferative effect, while increasing actions that promote invasion and metastasis. TGF-beta signaling involves phosphorylation of Smad3 at serine residues 208 and 213 in the linker region and serine residues 423 and 425 in the C-terminal region. Exogenous TGF-beta activates not only TGF-beta type I receptor (TbetaRI) but also c-Jun N-terminal kinase (JNK), changing unphosphorylated Smad3 to its phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker phosphorylated Smad3 (pSmad3L). Either pSmad3C or pSmad3L oligomerizes with Smad4, and translocates into nuclei. While the TbetaRI/pSmad3C pathway inhibits growth of normal epithelial cells in vivo, JNK/pSmad3L-mediated signaling promotes tumor cell invasion and extracellular matrix synthesis by activated mesenchymal cells. Furthermore, hepatocyte growth factor signaling interacts with TGF-beta to activate the JNK/pSmad3L pathway, accelerating nuclear transport of cytoplasmic pSmad3L. This reduces accessibility of unphosphorylated Smad3 to membrane-anchored TbetaRI, preventing Smad3C phosphorylation, pSmad3C-mediated transcription, and antiproliferative effects of TGF-beta on epithelial cells. As neoplasia progresses from normal colorectal epithelium through adenoma to invasive adenocarcinoma with distant metastasis, nuclear pSmad3L gradually increases while pSmad3C decreases. The shift from TbetaRI/pSmad3C-mediated to JNK/pSmad3L-mediated signaling is a major mechanism orchestrating a complex transition of TGF-beta signaling during sporadic human colorectal carcinogenesis. This review summarizes the recent understanding of Smad3 phosphoisoform-mediated signaling, particularly 'cross-talk' between Smad3 and JNK pathways that cooperatively promote oncogenic activities. Understanding of these actions should help to develop more effective therapy against human colorectal cancer, involving inhibition of JNK/pSmad3L pathway.
Mammary lipid metabolism and milk fatty acid secretion in alpine goats fed vegetable lipids.
Bernard, L; Rouel, J; Leroux, C; Ferlay, A; Faulconnier, Y; Legrand, P; Chilliard, Y
2005-04-01
Fourteen Alpine goats at midlactation were fed a diet of hay and concentrate (55:45), without (control) or with formaldehyde-treated linseed (FLS) or oleic sunflower oil (OSO) at 11.2 or 3.5% of dry matter intake, respectively, in a 3 x 3 Latin Square design with three 3-wk periods. Milk yield was lower in goats fed FLS than control or OSO (2.13 vs. 2.32 kg/d). Milk fat content was higher with FLS or OSO than control (40.8 vs. 33.8 g/kg). Formaldehyde-treated linseed and OSO caused a significant decrease (23 and 18%, respectively) of C10 to C17 fatty acids secretion compared with control. The secretion of cis-9 C18:1 and cis-9, trans-11 C18:2 were increased 1.44- and 1.54-fold for FLS and 1.78- and 1.36-fold for OSO, compared with control. The C18:3 (n-3) secretion was increased 2.61-fold with FLS compared with control. Milk cis-9 C14:1/C14:0, cis-9 C16:1/C16:0, and cis-9 C18:1/C18:0 ratios decreased with the supplemented diets compared with control. Mammary stearoyl-CoA desaturase mRNA and activity were decreased by the lipid supplements, whereas no significant change was observed for acetyl-CoA carboxylase and fatty acid synthase. The activities of glucose-6-phosphate dehydrogenase, malic enzyme, and glycerol-3-phosphate dehydrogenase were not affected by the lipid supplements. Mammary lipoprotein lipase mRNA increased with OSO, whereas lipoprotein lipase activity tended to decrease with FLS compared with control. Milk lipoprotein lipase activity sharply decreased with lipid supplement (by 59 and 71%, for FLS and OSO, respectively). The changes in milk fatty acid profile due to FLS and OSO supplements were partly related to changes in the levels of mammary enzyme activities or mRNA.
c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3
Sutherland, Kate D; Vaillant, François; Alexander, Warren S; Wintermantel, Tim M; Forrest, Natasha C; Holroyd, Sheridan L; McManus, Edward J; Schutz, Gunther; Watson, Christine J; Chodosh, Lewis A; Lindeman, Geoffrey J; Visvader, Jane E
2006-01-01
Suppressor of cytokine signalling (SOCS) proteins are critical attenuators of cytokine-mediated signalling in diverse tissues. To determine the importance of Socs3 in mammary development, we generated mice in which Socs3 was deleted in mammary epithelial cells. No overt phenotype was evident during pregnancy and lactation, indicating that Socs3 is not a key physiological regulator of prolactin signalling. However, Socs3-deficient mammary glands exhibited a profound increase in epithelial apoptosis and tissue remodelling, resulting in precocious involution. This phenotype was accompanied by augmented Stat3 activation and a marked increase in the level of c-myc. Moreover, induction of c-myc before weaning using an inducible transgenic model recapitulated the Socs3 phenotype, and elevated expression of likely c-myc target genes, E2F-1, Bax and p53, was observed. Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution. PMID:17139252
Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin
2017-05-01
Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.
Cyanidin-3-O-glucoside ameliorates diabetic nephropathy through regulation of glutathione pool.
Qin, Yan; Zhai, Qianqian; Li, Yan; Cao, Meng; Xu, Yun; Zhao, Kelei; Wang, Tao
2018-07-01
Diabetic nephropathy (DN) is a common complication of diabetes and the major cause of chronic kidney disease. Cyanidin 3-glucoside (C3G) is the most widespread anthocyanin in nature. In the present study, we aimed to investigate the possible effects of C3G on DN in db/db mice. We found that body weights and high levels of fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin A1c, and systolic blood pressure in diabetic mice were significantly reduced by C3G. C3G also reduced the ratio of kidney to body weight and the levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR), ameliorated the pathological changes of kidneys, reduced the surface area of Bowman's capsule, glomerular tuft, Bowman's space, and decreased renal expression of collagen IV, fibronectin, transforming growth factor β 1 (TGFβ1), matrix metalloprotein 9 (MMP9) and α-smooth muscle actin (α-SMA) in db/db mice. The Lee's index, perirenal white adipose tissue weight, and high levels of blood and renal triglyceride and cholesterol were decreased by C3G. Moreover, C3G reduced systemic levels and renal expression of tumor necrosis factor ɑ (TNFɑ), IL-1ɑ, and monocyte chemotactic protein-1 (MCP-1), indicating the inhibition of inflammation. Furthermore, C3G increased glutathione (GSH) level and decreased GSSG level in kidneys of diabetic mice. The renal mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) was increased by C3G in diabetic mice. Buthionine sulphoximine (BSO), an inhibitor of GSH synthesis, inhibited the effects of C3G on glucose metabolic dysfunction and DN. The data demonstrates that enhancement of GSH pool is involved in the renal-protective effects of C3G. Overall, C3G could be a promising therapeutic option for attenuation of diabetes and DN. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Melton, Elaina M.; Center for Cardiovascular Sciences, Albany Medical College, Albany, NY; Cerny, Ronald L.
Highlights: •Roles of FATP2 in fatty acid transport/activation contribute to lipid homeostasis. •Use of 13C- and D-labeled fatty acids provide novel insights into FATP2 function. •FATP2-dependent trafficking of FA into phospholipids results in distinctive profiles. •FATP2 functions in the transport and activation pathways for exogenous fatty acids. -- Abstract: In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4,more » for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4 h. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The trafficking of exogenous C16:0 and C22:6 into PA was significant where there was 6.9- and 5.3-fold increased incorporation, respectively, over the control; C18:3 and C20:4 also trended to increase in the PA pool while there were no changes for C18:1 and C18:2. The trafficking of C18:3 into PC and PI trended higher and approached significance. In the case of C20:4, expression of FATP2 resulted in increases in all four classes of phospholipid, indicating little selectivity. In the case of C22:6, there were significant increases of this exogenous fatty acids being trafficking into PC and PI. Collectively, these data support the conclusion that FATP2 has a dual function in the pathways linking the transport and activation of exogenous fatty acids. We discuss the differential roles of FATP2 and its role in both fatty acid transport and fatty acid activation in the context of lipid homeostasis.« less
Liu, Bochuan; Qiao, Meng; Wang, Yanbin; Wang, Lijuan; Gong, Yan; Guo, Tao; Zhao, Xu
2017-12-01
The enhancement of g-C 3 N 4 photocatalytic degradation of bisphenol A (BPA) via persulfate (PS) addition was investigated under visible light irradiation. The effects of various parameters on the BPA degradation were investigated, such as catalysts dosage, PS concentrations, initial pH value and BPA concentration. The results showed that g-C 3 N 4 nanosheets exhibited superior photocatalytic activity toward BPA degradation as compared with bulk g-C 3 N 4 . The addition of PS can further improve the g-C 3 N 4 photocatalytic performance for BPA degradation. With 5 mM PS, the degradation rate of BPA was increased from 72.5% to 100% at 90 min, and the corresponding first-order kinetic constants were increased from 0.0028 to 0.0140 min -1 . The removal efficiency of BPA increased with the decrease of solution pH value. The active radicals in the reaction system were tested by electron spin resonance (ESR) and radicals quenching experiments. Instead of persulfate radicals' oxidation, it was proposed that the main active radicals for BPA degradation were superoxide radicals and the photogenerated holes. Copyright © 2017. Published by Elsevier Ltd.
Seong, Gong Je; Park, Channy; Kim, Chan Yoon; Hong, Young Jae; So, Hong-Seob; Kim, Sang-Duck; Park, Raekil
2005-10-01
To investigate whether mitochondrial dysfunction and mitogen-activated protein kinase family proteins are implicated in apoptotic signaling of human Tenon's capsule fibroblasts (HTCFs) by mitomycin-C. Apoptosis was determined by Hoechst nuclei staining, agarose gel electrophoresis, and flow cytometry in HTCFs treated with 0.4 mg/mL mitomycin-C for 5 minutes. Enzymatic digestion of florigenic biosubstrate assessed the catalytic activity of caspase proteases, including caspase-3, caspase-8, and caspase-9. Phosphotransferase activity of c-Jun N-terminal kinase (JNK) 1 was measured by in vitro immune complex kinase assay using c-Jun(1-79) protein as a substrate. Mitochondrial membrane potential transition (MPT) was measured by flow cytometric analysis of JC-1 staining. Mitomycin-C (0.4 mg/mL) induced the apoptosis of HTCFs, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G(0)/G(1) fraction of cell cycle increase. The catalytic activity of caspase-3 and caspase-9 was significantly increased and was accompanied by cytosolic release of cytochrome c and MPT in response to mitomycin-C. Treatment with mitomycin-C resulted in the increased expression of Fas, FasL, Bad, and phosphorylated p53 and a decreased level of phosphorylated AKT. Treatment with mitomycin-C also increased the phosphotransferase activity and tyrosine phosphorylation of JNK1, whose inhibitor significantly suppressed the cytotoxicity of mitomycin-C. Mitomycin-C induced the apoptosis of HTCFs through the activation of intrinsic and extrinsic caspase cascades with mitochondrial dysfunction. It also activated Fas-mediated apoptotic signaling of fibroblasts. Furthermore, the activation of JNK1 played a major role in the cytotoxicity of mitomycin-C.
The 2′,3′-cAMP-adenosine pathway
2011-01-01
Our recent studies employing HPLC-tandem mass spectrometry to analyze venous perfusate from isolated, perfused kidneys demonstrate that intact kidneys produce and release into the extracellular compartment 2′,3′-cAMP, a positional isomer of the second messenger 3′,5′-cAMP. To our knowledge, this represents the first detection of 2′,3′-cAMP in any cell/tissue/organ/organism. Nuclear magnetic resonance experiments with isolated RNases and experiments in isolated, perfused kidneys suggest that 2′,3′-cAMP likely arises from RNase-mediated transphosphorylation of mRNA. Both in vitro and in vivo kidney experiments demonstrate that extracellular 2′,3′-cAMP is efficiently metabolized to 2′-AMP and 3′-AMP, both of which can be further metabolized to adenosine. This sequence of reactions is called the 2′,3′-cAMP-adenosine pathway (2′,3′-cAMP → 2′-AMP/3′-AMP → adenosine). Experiments in rat and mouse kidneys show that metabolic poisons increase extracellular levels of 2′,3′-cAMP, 2′-AMP, 3′-AMP, and adenosine; however, little is known regarding the pharmacology of 2′,3′-cAMP, 2′-AMP, and 3′-AMP. What is known is that 2′,3′-cAMP facilitates activation of mitochondrial permeability transition pores, a process that can lead to apoptosis and necrosis, and inhibits proliferation of vascular smooth muscle cells and glomerular mesangial cells. In summary, there is mounting evidence that at least some types of cellular injury, by triggering mRNA degradation, engage the 2′,3′-cAMP-adenosine pathway, and therefore this pathway should be added to the list of biochemical pathways that produce adenosine. Although speculative, it is possible that the 2′,3′-cAMP-adenosine pathway may protect against some forms of acute organ injury, for example acute kidney injury, by both removing an intracellular toxin (2′,3′-cAMP) and increasing an extracellular renoprotectant (adenosine). PMID:21937608
Kul, Esra; Aladağ, Lütfü İhsan; Yesildal, Ruhi
2016-11-01
Poly(methyl methacrylate) (PMMA) is widely used in prosthodontics as a denture base material. However, it has several disadvantages, including low strength and low thermal conductivity. The purpose of this in vitro study was to evaluate thermal conductivity and flexural strength after adding powdered Ag, TiO 2 , ZrO 2 , Al 2 O 3 , SiC, SiC-nano, Si 3 N 4 , and HA-nano in ratios of 10 wt% to PMMA. A total of 144 specimens were fabricated and divided into 18 groups. Specimens were left in water for 30 days. Thermal conductivity values were measured using a heat flowmeter, flexural strength was measured with a 3-point bend test, and specimens were investigated with environmental scanning electron microscopy. One-way ANOVA was used to compare means followed by using Duncan multiple range test (α=.05). The thermal conductivity value of PMMA increased significantly after the addition of Si 3 N 4 , SiC, Al 2 O 3 , SiC-nano, TiO 2 , ZrO 2 , HA-nano, and Ag. Progressive increases in thermal conductivity were observed in Si 3 N 4 , SiC, and Al 2 O 3 fillers. Flexural strength values of the control group were not significantly different from those of the SiC, Al 2 O 3 , or Ag group (P>.05). In the other groups, flexural strength values decreased significantly (P<.05). On the basis of electron microscopy, we observed that Si 3 N 4 , SiC, and Al 2 O 3 powders had higher thermal conductivity values that are dissipated more homogeneously in PMMA. Although the addition of 10 wt% SiC, Al 2 O 3, and Ag powder to PMMA significantly increased thermal conductivity, the flexural strength values of PMMA were not significantly changed. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mufti, Nandang, E-mail: nandangmufti@gmail.com; Atma, T., E-mail: nandangmufti@gmail.com; Fuad, A., E-mail: nandangmufti@gmail.com
The aim of this research is to synthesize nanoparticles of black pigment of Magnetite (Fe{sub 3}O{sub 4}), red pigment of hematite (α-Fe{sub 2}O{sub 3}), and yellow pigment of ghoetite (α-FeOOH) from the iron sand. The black pigment of Fe{sub 3}O{sub 4} and the yellow pigment α-FeOOH nanoparticles were synthesized by coprecipitation method with variation of pH. Whereas, the red pigment Fe{sub 2}O{sub 3} was synthesized by sintering Fe{sub 3}O{sub 4} nanoparticles at temperature between 400 °C and 700 7°C for 1 hour. All the pigments has been characterized using X-ray diffraction and SEM. The XRD results shown that the particlemore » size of the black pigmen Fe{sub 3}O{sub 4}, red pigment Fe{sub 3}O{sub 4} and yellow pigment α-FeOOH are around 12, 32, and 30 nm respectively. The particle size of Fe{sub 2}O{sub 3} nanoparticles increase by increasing sintering temperature from 32 nm at 400 °C to 39 nm at 700 °C. For yellow pigment of α-FeOOH, the particle size increase by increasing pH from 30,54 nm at pH 4 to 48,60 nm at pH 7. The SEM results shown that the morphologies of black, yellow and red pigments are aglomarated.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nilsson, A.; Landin, B.; Jensen, E.
1987-06-01
(/sup 3/H)Arachidonic (20:4) and (/sup 14/C)linoleic acid (18:2) were fed to thoracic duct-cannulated rats in test meals of either tracers alone, cream, Intralipid, pure arachidonic acid, or pure linoleic acid. Less (/sup 3/H)20:4 than (/sup 14/C)18:2 was recovered in chyle during the first 5 h. After cream feeding, the proportion of radioactivity found in phospholipids was high and increased during the first 3 h. After the meal 61 +/- 6% of the /sup 3/H and 57 +/- 10% of the /sup 14/C was in phosphatidylcholine, and 11 +/- 3% of the /sup 3/H and 3.0 +/- 4% of the /supmore » 14/C was in phosphatidylethanolamine. Changing the fat vehicle to Intralipid or pure 18:2 decreased the proportion of label in the phospholipds and increased the /sup 3/H and /sup 14/C radioactivity in the triacylglycerol fraction, the distribution of /sup 14/C radioactivity in the triacylglycerol fraction, the distribution of /sup 14/C being influenced more than that of /sup 3/H. After feeding the tracers in 200 ..mu..l of pure 20:4, >90% of both isotopes was in triacylglycerol. During fasting, triacylglycerol transported 56% (0.7 ..mu..mol/h), phosphatidylethanolamine transported 10% (0.1 ..mu..mol/h) of the 20:4 mass. After cream or Intralipid feeding, the output of 20:4-containing phosphatidylcholine and phosphatidylethanolamine increased 2.1- to 2.8-fold, whereas the transport of 20:4 with triacylglycerol remained constant. Phospholipids thus became the predominant transport form for 20:4. After feeding 200 ..mu..l of 20:4, the intestine produced, however, 20:4-rich triacylglycerols that transported 80% of the chyle 20:4.« less
Adeyemi, Kazeem Dauda; Sazili, Awis Qurni; Ebrahimi, Mahdi; Samsudin, Anjas Asmara; Alimon, Abd Rasak; Karim, Roselina; Karsani, Saiful Anuar; Sabow, Azad Behnan
2016-09-01
The study examined the effects of blend of 80% canola oil and 20% palm oil (BCPO) on nutrient intake and digestibility, growth performance, rumen fermentation and fatty acids (FA) in goats. Twenty-four Boer bucks were randomly assigned to diets containing 0, 4 and 8% BCPO on a dry matter basis, fed for 100 days and slaughtered. Diet did not affect feed efficiency, growth performance, intake and digestibility of all nutrients except ether extract. Intakes and digestibilities of ether extract, unsaturated fatty acids (FA) and total FA were higher (P < 0.05) while digestibility of C18:0 was lower (P < 0.05) in oil-fed goats than the control goats. Total volatile FA, acetate, butyrate, acetate/propionate ratio and methane decreased (P < 0.05) with increasing BCPO but propionate, NH3 -N and rumen pH did not differ between diets. Ruminal concentration of C18:0, n-3 FA and total FA increased (P < 0.05) while C12:0, C14:0, C15:0 and n-6 FA decreased with increasing BCPO. Analysis of the FA composition of Triceps brachii muscle showed that concentrations of C16:0, C14:0 and C18:2n-6 were lower (P < 0.05) while C18:1n-9, C18:3n-3 and C20:5n-3 were higher in oil-fed goats compared with control goats. Dietary BCPO altered muscle lipids without having detrimental effects on nutrient intake and digestibility and growth performance in goats. © 2015 Japanese Society of Animal Science.
Luo, Miyang; Lim, Wei Yen; Tan, Chuen Seng; Ning, Yilin; Chia, Kee Seng; van Dam, Rob M; Tang, Wern Ee; Tan, Ngiap Chuan; Chen, Richard; Tai, E Shyong; Venkataraman, Kavita
2017-11-01
This study examined longitudinal trends in HbA1c in a multi-ethnic Asian cohort of diabetes patients, and the associations of these trends with future risk of acute myocardial infarction (AMI), stroke, end stage renal failure (ESRD) and all-cause mortality. 6079 participants with type 2 diabetes mellitus in Singapore were included. HbA1c measurements for the five years previous to recruitment were used to identify patterns of HbA1c trends. Outcomes were recorded through linkage with the National Disease Registry. The median follow-up for longitudinal trends in HbA1c was 4.1years and for outcomes was between 7.0 and 8.3years. HbA1c patterns were identified using latent class growth modeling, and associations with outcomes were analyzed using Cox proportional hazards models. Four distinct HbA1c patterns were observed; "low-stable" (72·2%), "moderate-stable" (22·0%), "moderate-increase" (2·9%), and "high-decrease" (2·8%). The risk of comorbidities and death was significantly higher in moderate-increase and high-decrease groups compared to the low-stable group; the hazard ratios for stroke, ESRD, and death for moderate increase group were 3.22 (95%CI 1.27-8.15), 4.76 (95%CI 1.92-11.83), and 1.88 (95%CI 1.15-3.07), respectively, and for high-decrease group were 2.16 (95%CI 1.02-4.57), 3.05 (95%CI 1.54-6.07), and 2.79 (95%CI 1.97-3.95), respectively. Individuals in the moderate-increase group were significantly younger, with longer diabetes duration, and greater proportions of Malays and Indians. Deteriorating HbA1c pattern and extremely high initial HbA1c are associated with increased risk of long-term comorbidities and death. Therapeutic interventions to alter longitudinal HbA1c trends may be helpful in reducing this risk. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Genet, Hélène; He, Yujie; Lyu, Zhou; McGuire, A David; Zhuang, Qianlai; Clein, Joy; D'Amore, David; Bennett, Alec; Breen, Amy; Biles, Frances; Euskirchen, Eugénie S; Johnson, Kristofer; Kurkowski, Tom; Kushch Schroder, Svetlana; Pastick, Neal; Rupp, T Scott; Wylie, Bruce; Zhang, Yujin; Zhou, Xiaoping; Zhu, Zhiliang
2018-01-01
It is important to understand how upland ecosystems of Alaska, which are estimated to occupy 84% of the state (i.e., 1,237,774 km 2 ), are influencing and will influence state-wide carbon (C) dynamics in the face of ongoing climate change. We coupled fire disturbance and biogeochemical models to assess the relative effects of changing atmospheric carbon dioxide (CO 2 ), climate, logging and fire regimes on the historical and future C balance of upland ecosystems for the four main Landscape Conservation Cooperatives (LCCs) of Alaska. At the end of the historical period (1950-2009) of our analysis, we estimate that upland ecosystems of Alaska store ~50 Pg C (with ~90% of the C in soils), and gained 3.26 Tg C/yr. Three of the LCCs had gains in total ecosystem C storage, while the Northwest Boreal LCC lost C (-6.01 Tg C/yr) because of increases in fire activity. Carbon exports from logging affected only the North Pacific LCC and represented less than 1% of the state's net primary production (NPP). The analysis for the future time period (2010-2099) consisted of six simulations driven by climate outputs from two climate models for three emission scenarios. Across the climate scenarios, total ecosystem C storage increased between 19.5 and 66.3 Tg C/yr, which represents 3.4% to 11.7% increase in Alaska upland's storage. We conducted additional simulations to attribute these responses to environmental changes. This analysis showed that atmospheric CO 2 fertilization was the main driver of ecosystem C balance. By comparing future simulations with constant and with increasing atmospheric CO 2 , we estimated that the sensitivity of NPP was 4.8% per 100 ppmv, but NPP becomes less sensitive to CO 2 increase throughout the 21st century. Overall, our analyses suggest that the decreasing CO 2 sensitivity of NPP and the increasing sensitivity of heterotrophic respiration to air temperature, in addition to the increase in C loss from wildfires weakens the C sink from upland ecosystems of Alaska and will ultimately lead to a source of CO 2 to the atmosphere beyond 2100. Therefore, we conclude that the increasing regional C sink we estimate for the 21st century will most likely be transitional. © 2017 by the Ecological Society of America.
Genet, Hélène; He, Yujie; Lyu, Zhou; McGuire, A. David; Zhuang, Qianlai; Clein, Joy S.; D'Amore, David; Bennett, Alec; Breen, Amy; Biles, Frances; Euskirchen, Eugénie S.; Johnson, Kristofer; Kurkowski, Tom; Schroder, Svetlana (Kushch); Pastick, Neal J.; Rupp, T. Scott; Wylie, Bruce K.; Zhang, Yujin; Zhou, Xiaoping; Zhu, Zhiliang
2018-01-01
It is important to understand how upland ecosystems of Alaska, which are estimated to occupy 84% of the state (i.e., 1,237,774 km2), are influencing and will influence state‐wide carbon (C) dynamics in the face of ongoing climate change. We coupled fire disturbance and biogeochemical models to assess the relative effects of changing atmospheric carbon dioxide (CO2), climate, logging and fire regimes on the historical and future C balance of upland ecosystems for the four main Landscape Conservation Cooperatives (LCCs) of Alaska. At the end of the historical period (1950–2009) of our analysis, we estimate that upland ecosystems of Alaska store ~50 Pg C (with ~90% of the C in soils), and gained 3.26 Tg C/yr. Three of the LCCs had gains in total ecosystem C storage, while the Northwest Boreal LCC lost C (−6.01 Tg C/yr) because of increases in fire activity. Carbon exports from logging affected only the North Pacific LCC and represented less than 1% of the state's net primary production (NPP). The analysis for the future time period (2010–2099) consisted of six simulations driven by climate outputs from two climate models for three emission scenarios. Across the climate scenarios, total ecosystem C storage increased between 19.5 and 66.3 Tg C/yr, which represents 3.4% to 11.7% increase in Alaska upland's storage. We conducted additional simulations to attribute these responses to environmental changes. This analysis showed that atmospheric CO2 fertilization was the main driver of ecosystem C balance. By comparing future simulations with constant and with increasing atmospheric CO2, we estimated that the sensitivity of NPP was 4.8% per 100 ppmv, but NPP becomes less sensitive to CO2increase throughout the 21st century. Overall, our analyses suggest that the decreasing CO2 sensitivity of NPP and the increasing sensitivity of heterotrophic respiration to air temperature, in addition to the increase in C loss from wildfires weakens the C sink from upland ecosystems of Alaska and will ultimately lead to a source of CO2 to the atmosphere beyond 2100. Therefore, we conclude that the increasing regional C sink we estimate for the 21st century will most likely be transitional.
Metal release from simulated fixed orthodontic appliances.
Hwang, C J; Shin, J S; Cha, J Y
2001-10-01
Most orthodontic appliances and archwires are stainless steel or nickel-titanium (NiTi) alloys that can release metal ions, with saliva as the medium. To measure metal released from the fixed orthodontic appliances currently in use, we fabricated simulated fixed orthodontic appliances that corresponded to half of the maxillary arch and soaked them in 50 mL of artificial saliva (pH 6.75 +/- 0.15, 37 degrees C) for 3 months. We used brackets, tubes, and bands made by Tomy (Tokyo, Japan). Four groups were established according to the appliance manufacturer and the type of metal in the .016 x .022-in archwires. Groups A and B were stainless steel archwires from Ormco (Glendora, Calif) and Dentaurum (Ispringen, Germany), respectively, and groups C and D were both NiTi archwires with Ormco's copper NiTi and Tomy's Bioforce sentalloy, respectively. Stainless steel archwires were heat treated in an electric furnace at 500 degrees C for 1 minute and quenched in water. We measured the amount of metal released from each group by immersion time. Our conclusions were as follows: (1) there was no increase in the amount of chromium released after 4 weeks in group A, 2 weeks in group B, 3 weeks in group C, and 8 weeks in group D; (2) there was no increase in the amount of nickel released after 2 weeks in group A, 3 days in group B, 7 days in group C, and 3 weeks in group D; and (3) there was no increase in the amount of iron released after 2 weeks in group A, 3 days in group B, and 1 day in groups C and D. In our 3-month-long investigation, we saw a decrease in metal released as immersion time increased.
NASA Astrophysics Data System (ADS)
Wu, Haitang; Chen, Mingwei; Wei, Xi; Ge, Min; Zhang, Weigang
2010-12-01
Boron nitride thin films were deposited on silicon carbide fibers by chemical vapor deposition at atmospheric pressure from the single source precursor B-trichloroborazine (Cl 3B 3N 3H 3, TCB). The film growth and structure, as a function of deposition temperature, hydrogen gas flow rate, and deposition time, were discussed. The deposition rate reaches a maximum at 1000 °C, then decreases with the increasing of temperature, and the apparent activation energy of the reaction is 127 kJ/mol. Above 1000 °C, gas-phase nucleation determines the deposition process. The deposited BN films were characterized by Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The effect of BN interphase on the mechanical properties of the unidirectional SiC fiber-reinforced SiC matrix (SiC/SiC) composites was also investigated. The results show that the flexural strength of SiC/SiC composites with and without coating is 276 MPa and 70 MPa, respectively, which indicates that BN interphase coating deposited from B-trichloroborazine precursor can effectively adjust the fiber/matrix interface, thus causing a dramatic increase in the mechanical properties of the composites.
Modulation of chloride secretion in the rat ileum by intracellular bicarbonate.
Dagher, P C; Chawla, H; Michael, J; Egnor, R W; Charney, A N
1997-05-01
Increasing intracellular bicarbonate concentration ([HCO3-]i) inhibits calcium-mediated Cl- secretion in rat distal colon and T84 cells. We investigated the effect of [HCO3-]i on Cl- secretion in rat ileum. Segments of intact ileum from Sprague-Dawley rats were studied in Ussing chambers and villus and crypt intracellular pH and [HCO3-]i were determined using BCECF. A range of crypt and villus [HCO3-]i from 0 to 31 mM was obtained by varying Ringer's composition. Basal serosal-to-mucosal Cl- flux (JsmCl) averaged 8.5 +/- 0.2 mu eq.h-1.cm-2 and was unaffected by changing [HCO3-]i or serosal bumetanide. Carbachol increased JsmCl by 3.9 +/- 0.5 mu eq.h-1.cm-2 at [HCO3-]i = 0 mM but only by 1.0 +/- 0.3 mu eq.h-1.cm-2 at high crypt and villus [HCO3-]i. Dibutyryl-cAMP increased JsmCl by 2.5 +/- 0.2 mu eq.h-1.cm-2 at all [HCO3-]i. Carbachol and db-cAMP showed mutual antagonism at low [HCO3-]i and near-additivity at high [HCO3-]i. We conclude that like rat colon and T84 cells, calcium-mediated but not cAMP-mediated Cl- secretion in the ileum is inhibited by increasing [HCO3-]i. Mutual antagonism between carbachol and db-cAMP at low [HCO3-]i was present in ileum and distal colon but not in T84 cells.
Hirano, Kazumi; Sasaki, Norihiko; Ichimiya, Tomomi; Miura, Taichi; Van Kuppevelt, Toin H; Nishihara, Shoko
2012-01-01
Maintenance of self-renewal and pluripotency in mouse embryonic stem cells (mESCs) is regulated by the balance between several extrinsic signaling pathways. Recently, we demonstrated that heparan sulfate (HS) chains play important roles in the maintenance and differentiation of mESCs by regulating extrinsic signaling. Sulfated HS structures are modified by various sulfotransferases during development. However, the significance of specific HS structures during development remains unclear. Here, we show that 3-O-sulfated HS structures synthesized by HS 3-O-sulfotransferases (3OSTs) and recognized by the antibody HS4C3 increase during differentiation of mESCs. Furthermore, expression of Fas on the cell surface of the differentiated cells also increased. Overexpression of the HS4C3-binding epitope in mESCs induced apoptosis and spontaneous differentiation even in the presence of LIF and serum. These data showed that the HS4C3-binding epitope was required for differentiation of mESCs. Up-regulation of the HS4C3-binding epitope resulted in the recruitment of Fas from the cytoplasm to lipid rafts on the cell surface followed by activation of Fas signaling. Indeed, the HS4C3-binding epitope interacted with a region that included the heparin-binding domain (KLRRRVH) of Fas. Reduced self-renewal capability in cells overexpressing 3OST resulted from the degradation of Nanog by activated caspase-3, which is downstream of Fas signaling, and was rescued by the inhibition of Fas signaling. We also found that knockdown of 3OST and inhibition of Fas signaling reduced the potential for differentiation into the three germ layers during embryoid body formation. This is the first demonstration that activation of Fas signaling is mediated by an increase in the HS4C3-binding epitope and indicates a novel signaling pathway for differentiation in mESCs.
Hirano, Kazumi; Sasaki, Norihiko; Ichimiya, Tomomi; Miura, Taichi; Van Kuppevelt, Toin H.; Nishihara, Shoko
2012-01-01
Maintenance of self-renewal and pluripotency in mouse embryonic stem cells (mESCs) is regulated by the balance between several extrinsic signaling pathways. Recently, we demonstrated that heparan sulfate (HS) chains play important roles in the maintenance and differentiation of mESCs by regulating extrinsic signaling. Sulfated HS structures are modified by various sulfotransferases during development. However, the significance of specific HS structures during development remains unclear. Here, we show that 3-O-sulfated HS structures synthesized by HS 3-O-sulfotransferases (3OSTs) and recognized by the antibody HS4C3 increase during differentiation of mESCs. Furthermore, expression of Fas on the cell surface of the differentiated cells also increased. Overexpression of the HS4C3-binding epitope in mESCs induced apoptosis and spontaneous differentiation even in the presence of LIF and serum. These data showed that the HS4C3-binding epitope was required for differentiation of mESCs. Up-regulation of the HS4C3-binding epitope resulted in the recruitment of Fas from the cytoplasm to lipid rafts on the cell surface followed by activation of Fas signaling. Indeed, the HS4C3-binding epitope interacted with a region that included the heparin-binding domain (KLRRRVH) of Fas. Reduced self-renewal capability in cells overexpressing 3OST resulted from the degradation of Nanog by activated caspase-3, which is downstream of Fas signaling, and was rescued by the inhibition of Fas signaling. We also found that knockdown of 3OST and inhibition of Fas signaling reduced the potential for differentiation into the three germ layers during embryoid body formation. This is the first demonstration that activation of Fas signaling is mediated by an increase in the HS4C3-binding epitope and indicates a novel signaling pathway for differentiation in mESCs. PMID:22916262
Performance of a Thermoelectric Device with Integrated Heat Exchangers
NASA Astrophysics Data System (ADS)
Barry, Matthew M.; Agbim, Kenechi A.; Chyu, Minking K.
2015-06-01
Thermoelectric devices (TEDs) convert heat directly into electrical energy, making them well suited for waste heat recovery applications. An integrated thermoelectric device (iTED) is a restructured TED that allows more heat to enter the p-n junctions, thus producing a greater power output . An iTED has heat exchangers incorporated into the hot-side interconnectors with flow channels directing the working fluid through the heat exchangers. The iTED was constructed of p- and n-type bismuth-telluride semiconductors and copper interconnectors and rectangular heat exchangers. The performance of the iTED in terms of , produced voltage and current , heat input and conversion efficiency for various flow rates (), inlet temperatures (C) ) and load resistances () with a constant cold-side temperature ( = 0C) was conducted experimentally. An increase in had a greater effect on the performance than did an increase in . A 3-fold increase in resulted in a 3.2-, 3.1-, 9.7-, 3.5- and 2.8-fold increase in and respectively. For a constant of 50C, a 3-fold increase in from 3300 to 9920 resulted in 1.6-, 1.6-, 2.6-, 1.5- and 1.9-fold increases in , , , and respectively.
West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E
2010-11-01
Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.
Solubility of SC2O3 in NA3ALF6-K3ALF6-ALF3 Melts
NASA Astrophysics Data System (ADS)
Tian, Zhongliang; Hu, Xun; Lai, Yanqing; Yang, Shu; Ye, Shaolong; Li, Jie
The electrolyte with high solubility for Sc2O3 is very important to realize the preparation of Al-Sc master alloy by the molten salt electrolysis. The solubility of Sc2O3 in K3AlF6-Na3AlF6-AlF3 melts is determined with an isothermal saturation method. The effects of KR (ratio of K3AlF6 to K3AlF6+Na3AlF6), the concentration of Al2O3 and the temperature on the solubility of Sc2O3 are also investigated. The results indicate that the solubility of Sc2O3 in K3AlF6-Na3AlF6-AlF3 melts increases and then decreases with KR increasing. The solubility of Sc2O3 is 8.698 wt.% in (K3AlF6-Na3AlF6)(KR25%)-18 wt.%AlF3 melts at 940°C. The effect of temperature on the solubility is little, and the values are 8.575 wt.% and 8.762 wt.% respectively when the temperatures are 930°C and 960°C. The solubility decreases from 8.809 wt.% to 7.058 wt.% as the concentration of Al2O3 increases from 1.5 wt.% to 5.0 wt.% at 950°C.
Xiao, Jianbo; Ni, Xiaoling; Kai, Guoyin; Chen, Xiaoqing
2015-01-01
The dietary polyphenols as aldose reductases inhibitors (ARIs) have attracted great interest among researchers. The aim of this review is to give an overview of the research reports on the structure-activity relationship of dietary polyphenols inhibiting aldose reductases (AR). The molecular structures influence the inhibition of the following: (1) The methylation and methoxylation of the hydroxyl group at C3, C3', and C4' of flavonoids decreased or little affected the inhibitory potency. However, the methylation and methoxylation of the hydroxyl group at C5, C6, and C8 significantly enhanced the inhibition. Moreover, the methylation and methoxylation of C7-OH influence the inhibitory activity depending on the substitutes on rings A and B of flavonoids. (2) The glycosylation on 3-OH of flavonoids significantly increased or little affected the inhibition. However, the glycosylation on 7-OH and 4'-OH of flavonoids significantly decreased the inhibition. (3) The hydroxylation on A-ring of flavones and isoflavones, especially at positions 5 and 7, significantly improved the inhibition and the hydroxylation on C3' and C4' of B-ring of flavonoids remarkably enhanced the inhibition; however, the hydroxylation on the ring C of flavones significantly weakened the inhibition. (4) The hydrogenation of the C2=C3 double bond of flavones reduced the inhibition. (5) The hydrogenation of α=β double bond of stilbenes hardly affected the inhibition and the hydroxylation on C3' of stilbenes decreased the inhibition. Moreover, the methylation of the hydroxyl group of stilbenes obviously reduced the activity. (6) The hydroxylation on C4 of chalcone significantly increased the inhibition and the methylation on C4 of chalcone remarkably weakened the inhibition.
Liméa, L; Alexandre, G; Berthelot, V
2012-02-01
The effects of a concentrate diet on growth, carcass fat, and fatty acid (FA) composition of muscle (supraspinatus), perirenal, and intermuscular adipose tissues of Creole goats (n = 32) were evaluated. Goats were fed a tropical green forage Digitaria decumbens ad libitum with no concentrate (G0) or 1 of 3 levels of concentrate: 140 (G100), 240 (G200), and 340 g•d(-1) (G300), respectively. Goats were slaughtered according to the standard procedure at the commercial BW (22 to 24 kg of BW). Goats fed the concentrate diets (G100, G200, and G300) had greater ADG (P < 0.001), cold carcass weights (P < 0.001), and omental (P < 0.01), perirenal (P < 0.01), and intermuscular (P < 0.01) adipose tissues weights. Dietary intake of C18:0, C18:1n-9, C18:2n-6 increased as concentrate supplementation increased (P < 0.001), whereas C18:3n-3 intake was not affected (P > 0.05). Increased concentrate supplementation did not affect (P > 0.05) the proportion of MUFA in all tissues and had very little effect on SFA in perirenal tissue, but increased the PUFA proportion in muscle (P < 0.05). The major effect of feeding increased concentrate was an increase in n-6 PUFA proportions in all tissues (P < 0.001) and, surprisingly, a decrease in n-3 PUFA (P < 0.001). Focusing on FA, which are supposed to have a beneficial or an adverse effect on human health, feeding increased concentrate did not increase the content of any cholesterol-increasing SFA in meat, but increased the n-6/n-3 ratio above 4 when more than 240 g of concentrate was fed per day.
Han, ShouWei; Ritzenthaler, Jeffrey D; Wingerd, Byron; Roman, Jesse
2005-09-30
The prostaglandin E2 receptor subtype EP4 has been implicated in the growth and progression of human non-small cell lung carcinoma (NSCLC). However, the factors that control its expression have not been entirely elucidated. Our studies show that NSCLC cells express peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) protein and that treatment with a selective PPARbeta/delta agonist (GW501516) increases EP4 mRNA and protein levels. GW501516 induced NSCLC cell proliferation, and this effect was prevented by PPARbeta/delta antisense or EP4 short interfering RNA (siRNA). GW501516 increased the phosphorylation of Akt and decreased PTEN expression. The selective inhibitor of phosphatidylinositol 3-kinase (PI3-K), wortmannin, and PPARbeta/delta antisense, abrogated the effect of GW501516 on EP4 expression, whereas that of the inhibitor of Erk did not. GW501516 also increased EP4 promoter activity through effects on the region between -1555 and -992 bp in the EP4 promoter, and mutation of the CCAAT/enhancer-binding protein (C/EBP) site in this region abrogated the effect of GW501516. GW501516 increased not only the binding activity of C/EBP to the NF-IL6 site in the EP4 promoter, which was prevented by the inhibitor of PI3-K, but also increased C/EBPbeta protein in a dose- and PPARbeta/delta-dependent manner. The effect of GW501516 on EP4 protein was eliminated in the presence of C/EBPbeta siRNA. Finally, we showed that pretreatment of NSCLC with GW501516 further increased NSCLC cell proliferation in response to exogenous dimethyl-prostaglandin E2 (PGE2) that was diminished in the presence of PPARbeta/delta antisense and EP4 siRNA. Taken together, these findings suggest that activation of PPARbeta/delta induces PGE2 receptor subtype EP4 expression through PI3-K signals and increases human lung carcinoma cell proliferation in response to PGE2. The increase in transcription of the EP4 gene by PPARbeta/delta agonist was associated with increased C/EBP binding activity in the NF-IL6 site of EP4 promoter region and C/EBPbeta protein expression that were mediated through both PI3-K/Akt and PPARbeta/delta signaling pathways.
Lillegard, Kathryn E.; Loeks-Johnson, Alex C.; Opacich, Jonathan W.; Peterson, Jenna M.; Bauer, Ashley J.; Elmquist, Barbara J.; Regal, Ronald R.; Gilbert, Jeffrey S.
2014-01-01
Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia–induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14–18. Both the C3aRA and C5aRA attenuated placental ischemia–induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia–induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia–induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia–induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach. PMID:25150279
Hughes, B J; Thomas, J; Lynch, A M; Borghoff, S J; Green, S; Mensing, T; Sarang, S S; LeBaron, M J
2016-11-01
In a National Toxicology Program (NTP) chronic inhalation study with methyl isobutyl ketone (MIBK), increases in hepatocellular adenomas and hepatocellular adenomas and carcinomas (combined) were observed in male and female B6C3F 1 mice at 1800 ppm. A DNA reactive Mode-of-Action (MOA) for this liver tumor response is not supported by the evidence as MIBK and its major metabolites lack genotoxicity in both in vitro and in vivo studies. Constitutive androstane receptor (CAR) nuclear receptor-mediated activation has been hypothesized as the MOA for MIBK-induced mouse liver tumorigenesis. To further investigate the MOA for MIBK-induced murine liver tumors, male and female B6C3F1, C57BL/6, and CAR/PXR Knockout (KO) mice were exposed to either 0 or 1800 ppm MIBK for 6 h/day, 5 days/week for a total of 10 days. On day 1, mice were implanted with osmotic mini-pumps containing 5-Bromo-2-deoxyuridine (BrdU) 1 h following exposure and humanely euthanized 1-3 h following the final exposure. B6C3F 1 and C57BL/6 mice had statistically significant increases in liver weights compared to controls that corresponded with hepatocellular hypertrophy and increased mitotic figures. Hepatocellular proliferation data indicated induction of S-phase DNA synthesis in B6C3F 1 and C57BL/6 mice exposed to 1800 ppm MIBK compared to control, and no increase was observed in MIBK exposed CAR/PXR KO mice. Liver gene expression changes indicated a maximally-induced Cyp2b10 (CAR-associated) transcript and a slight increase in Cyp3a11(PXR-associated) transcript in B6C3F 1 and C57BL/6 mice exposed to 1800 ppm MIBK compared to controls, but not in Cyp1a1 (AhR-associated) or Cyp4a10 (PPAR-α-associated) transcripts. CAR/PXR KO mice exposed to 1800 ppm MIBK showed no evidence of activation of AhR, CAR, PXR or PPAR-α nuclear receptors via their associated transcripts. MIBK induced hepatic effects are consistent with a phenobarbital-like MOA where the initiating events are activation of the CAR and PXR nuclear receptors and resultant hepatocellular proliferation leading to rodent liver tumors. Copyright © 2016 Elsevier Inc. All rights reserved.
Szott, Luisa M.; Horbett, Thomas A.
2010-01-01
The role of complement C3 in mediating adhesion of monocytes to plasma deposited tetraglyme surfaces was studied. Although fibrinogen (Fg) is usually considered the main factor in mediating phagocyte attachment, plasma deposited PEO-like tetraethylene glycol dimethyl ether (tetraglyme) coatings that have ultra-low Fg adsorption (< 10 ng/cm2) from low concentration solutions and low monocyte adhesion in vitro still show high phagocyte adhesion after short implantations and later become encapsulated when tested in vivo. To test whether higher Fg adsorption under in vivo conditions could explain the higher in vivo reactivity, we again measured the resistance of tetraglyme films to Fg adsorption. We found a surprising and previously unreported increased amount of adsorbed Fg on tetraglyme surfaces from higher concentration protein solutions. However, monocyte adhesion to tetraglyme did not markedly increase despite the increased Fg adsorption. We thus suspected proteins other than Fg must be responsible for the increased in vivo reactivity. We found that on tetraglyme pre-adsorbed with C3-depleted serum, monocyte adhesion was greatly reduced as compared to samples adsorbed with normal serum. Addition of exogenous pure C3 to the serum used to pre-adsorb the surfaces restored monocyte adhesion to tetraglyme coatings. While Fg clearly plays an important role in mediating monocyte adhesion to tetraglyme surfaces, the results show an additional role for adsorbed C3 in monocyte adhesion. PMID:20939050
Plasma assisted facile synthesis of vanadium oxide (V3O7) nanostructured thin films
NASA Astrophysics Data System (ADS)
Singh, Megha; Saini, Sujit K.; Kumar, Prabhat; Sharma, Rabindar K.; Reddy, G. B.
2018-05-01
Vanadium oxides nanostructured thin films are synthesized using plasma assisted sublimation process. The effect of temperatures on growth of V2O5 and V3O7 thin films is studied. Scanning electron micrographs shows different morphologies are obtained at different temperatures i.e. at 450 °C nano cubes-like structures are obtained, whereas at 550 °C and 650 °C nanorods are obtained. Sample deposited at 450 °C is entirely composed of V2O5 and sample at higher temperatures are composed of mixed phase of vanadium oxides i.e. V2O5 and V3O7. As temperature increased, so the content of V3O7 in the sample is increased as confirmed by XRD and Raman analyses.
Adam, Aziza A A; van der Mark, Vincent A; Donkers, Joanne M; Wildenberg, Manon E; Oude Elferink, Ronald P J; Chamuleau, Robert A F M; Hoekstra, Ruurdtje
2018-01-01
Practice-changing culturing techniques of hepatocytes are highly required to increase their differentiation. Previously, we found that human liver cell lines HepaRG and C3A acquire higher functionality and increased mitochondrial biogenesis when cultured in the AMC-Bioartificial liver (BAL). Dynamic medium flow (DMF) is one of the major contributors to this stimulatory effect. Recently, we found that DMF-culturing by shaking of HepaRG monolayers resulted in higher mitochondrial biogenesis. Here we further investigated the effect of DMF-culturing on energy metabolism and hepatic functionality of HepaRG and C3A monolayers. HepaRG and C3A DMF-monolayers were incubated with orbital shaking at 60 rpm during the differentiation phase, while control monolayers were maintained statically. Subsequently, energy metabolism and hepatic functionality were compared between static and DMF-cultures. DMF-culturing of HepaRG cells substantially increased hepatic differentiation; transcript levels of hepatic structural genes and hepatic transcription regulators were increased up to 15-fold (Cytochrome P450 3A4) and nuclear translocation of hepatic transcription factor CEBPα was stimulated. Accordingly, hepatic functions were positively affected, including ammonia elimination, urea production, bile acid production, and CYP3A4 activity. DMF-culturing shifted energy metabolism from aerobic glycolysis towards oxidative phosphorylation, as indicated by a decline in lactate production and glucose consumption, and an increase in oxygen consumption. Similarly, DMF-culturing increased mitochondrial energy metabolism and hepatic functionality of C3A cells. In conclusion, simple shaking of monolayer cultures substantially improves mitochondrial energy metabolism and hepatic differentiation of human liver cell lines. This practice-changing culture method may prove to prolong the in-vitro maintenance of primary hepatocytes and increase hepatic differentiation of stem cells.
Structure and Dielectric Properties of (Sr0.2Ca0.488Nd0.208) TiO3-Li3NbO4 Ceramic Composites
NASA Astrophysics Data System (ADS)
Xia, C. C.; Chen, G. H.
2017-12-01
The new ceramic composites of (1-x) Li3NbO4-x (Sr0.2Ca0.488Nd0.208)TiO3 were prepared by the conventional solid state reaction method. The sintering behavior, phase composition, microstructure and microwave dielectric properties of the ceramics were investigated specially. The SEM and XRD results show that (1-x) Li3NbO4-x (Sr0.2Ca0.488Nd0.208) TiO3 (0.35≤x≤0.5) composites were composed of two phase, i.e. perovskite and Li3NbO4. With the increase of x, the ɛr increases from 27.1 to 38.7, Q×f decreases from 55000 GHz to 16770 GHz, and the τ f increases from -49 ppm/°C to 226.7 ppm/°C. The optimized dielectric properties with ɛr∼31.4, Q×f~16770GHz and τf~-8.1ppm/°C could be obtained as x=0.4 sintered at 1100°C for 4h. The as-prepared ceramic is expected to be used in resonators, filters, and other microwave devices.
Initial Events during the Evolution of C4 Photosynthesis in C3 Species of Flaveria1[W][OPEN
Sage, Tammy L.; Busch, Florian A.; Johnson, Daniel C.; Friesen, Patrick C.; Stinson, Corey R.; Stata, Matt; Sultmanis, Stefanie; Rahman, Beshar A.; Rawsthorne, Stephen; Sage, Rowan F.
2013-01-01
The evolution of C4 photosynthesis in many taxa involves the establishment of a two-celled photorespiratory CO2 pump, termed C2 photosynthesis. How C3 species evolved C2 metabolism is critical to understanding the initial phases of C4 plant evolution. To evaluate early events in C4 evolution, we compared leaf anatomy, ultrastructure, and gas-exchange responses of closely related C3 and C2 species of Flaveria, a model genus for C4 evolution. We hypothesized that Flaveria pringlei and Flaveria robusta, two C3 species that are most closely related to the C2 Flaveria species, would show rudimentary characteristics of C2 physiology. Compared with less-related C3 species, bundle sheath (BS) cells of F. pringlei and F. robusta had more mitochondria and chloroplasts, larger mitochondria, and proportionally more of these organelles located along the inner cell periphery. These patterns were similar, although generally less in magnitude, than those observed in the C2 species Flaveria angustifolia and Flaveria sonorensis. In F. pringlei and F. robusta, the CO2 compensation point of photosynthesis was slightly lower than in the less-related C3 species, indicating an increase in photosynthetic efficiency. This could occur because of enhanced refixation of photorespired CO2 by the centripetally positioned organelles in the BS cells. If the phylogenetic positions of F. pringlei and F. robusta reflect ancestral states, these results support a hypothesis that increased numbers of centripetally located organelles initiated a metabolic scavenging of photorespired CO2 within the BS. This could have facilitated the formation of a glycine shuttle between mesophyll and BS cells that characterizes C2 photosynthesis. PMID:24064930
Initial events during the evolution of C4 photosynthesis in C3 species of Flaveria.
Sage, Tammy L; Busch, Florian A; Johnson, Daniel C; Friesen, Patrick C; Stinson, Corey R; Stata, Matt; Sultmanis, Stefanie; Rahman, Beshar A; Rawsthorne, Stephen; Sage, Rowan F
2013-11-01
The evolution of C4 photosynthesis in many taxa involves the establishment of a two-celled photorespiratory CO2 pump, termed C2 photosynthesis. How C3 species evolved C2 metabolism is critical to understanding the initial phases of C4 plant evolution. To evaluate early events in C4 evolution, we compared leaf anatomy, ultrastructure, and gas-exchange responses of closely related C3 and C2 species of Flaveria, a model genus for C4 evolution. We hypothesized that Flaveria pringlei and Flaveria robusta, two C3 species that are most closely related to the C2 Flaveria species, would show rudimentary characteristics of C2 physiology. Compared with less-related C3 species, bundle sheath (BS) cells of F. pringlei and F. robusta had more mitochondria and chloroplasts, larger mitochondria, and proportionally more of these organelles located along the inner cell periphery. These patterns were similar, although generally less in magnitude, than those observed in the C2 species Flaveria angustifolia and Flaveria sonorensis. In F. pringlei and F. robusta, the CO2 compensation point of photosynthesis was slightly lower than in the less-related C3 species, indicating an increase in photosynthetic efficiency. This could occur because of enhanced refixation of photorespired CO2 by the centripetally positioned organelles in the BS cells. If the phylogenetic positions of F. pringlei and F. robusta reflect ancestral states, these results support a hypothesis that increased numbers of centripetally located organelles initiated a metabolic scavenging of photorespired CO2 within the BS. This could have facilitated the formation of a glycine shuttle between mesophyll and BS cells that characterizes C2 photosynthesis.
NASA Astrophysics Data System (ADS)
Badr, A. M.; El-Anssary, E. H.; Elshaikh, H. A.; Afify, H. H.
2017-12-01
In the current study, α-MoO3 nanocrystals were successfully synthesized from ammonium heptamolybdate tetrahydrate using a simple hydrothermal route. The influence of calcination temperature on the structural, optical and electrical properties was systematically investigated for the MoO3 powder products. The XRD results were analyzed for these powders, revealing the formation of a mixed phase (β- and α-MoO3) at calcination temperatures ranging from 350 °C-450 °C, and hence a residual monoclinic phase still exists in the samples at the calcination temperature of 450 °C. Subsequently, the mixed phase was completely converted to a pure single phase of α-MoO3 at a calcination temperature of 500 °C. The optical properties of the MoO3 powders were investigated using the transformed diffuse reflectance technique according to Kubelka-Munk theory. For such a powder product, the results of the optical measurements demonstrated the realization of indirect and direct allowed transitions at the spectral ranges 3.31-3.91 eV and 3.66-4.27 eV, respectively. The indirect- and direct-allowed band-gaps of the MoO3 products were found to increase from 2.69-3.12 eV and from 3.43-3.64 eV, respectively, by increasing the calcination temperature from 350 °C-600 °C. The MoO3 powders calcined at different temperatures were converted into five dense tablets for performing the electrical measurements. These measurements were carried out at different working temperatures using a system operating under high vacuum conditions. The results revealed that the dc-conductivity of such a tablet typically increases by more than five orders of magnitude with an increase in the working temperature from 77-300 K. These results also demonstrated a high dependence of dc-conductivity on the calcination temperature for the MoO3 products. The dc-conductivity as a function of the operating temperature revealed the presence of at least three different electrical conduction mechanisms for the same MoO3 tablet.
Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A; Kwizera, Chantal; Sijbesma, Jurgen W A; Ishiwata, Kiichi; Willemsen, Antoon T M; Elsinga, Philip H; Dierckx, Rudi A J O; van Waarde, Aren
2011-08-01
Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-(11)C-methyl-3-propyl-xanthine ((11)C-MPDX) and PET. This study aims to test whether (11)C-MPDX can be used for quantitative studies of cerebral A(1)R in rodents. (11)C-MPDX was injected (intravenously) into isoflurane-anesthetized male Wistar rats (300 g). A dynamic scan of the central nervous system was obtained, using a small-animal PET camera. A cannula in a femoral artery was used for blood sampling. Three groups of animals were studied: group 1, controls (saline-treated); group 2, animals pretreated with the A(1)R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 mg, intraperitoneally); and group 3, animals pretreated (intraperitoneally) with a 20% solution of ethanol in saline (2 mL) plus the adenosine kinase inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d] pyrimidine dihydrochloride (ABT-702) (1 mg). DPCPX is known to occupy cerebral A(1)R, whereas ethanol and ABT-702 increase extracellular adenosine. In groups 1 and 3, the brain was clearly visualized. High uptake of (11)C-MPDX was noted in striatum, hippocampus, and cerebellum. In group 2, tracer uptake was strongly suppressed and regional differences were abolished. The treatment of group 3 resulted in an unexpected 40%-45% increase of the cerebral uptake of radioactivity as indicated by increases of PET standardized uptake value, distribution volume from Logan plot, nondisplaceable binding potential from 2-tissue-compartment model fit, and standardized uptake value from a biodistribution study performed after the PET scan. The partition coefficient of the tracer (K(1)/k(2) from the model fit) was not altered under the study conditions. (11)C-MPDX shows a regional distribution in rat brain consistent with binding to A(1)R. Tracer binding is blocked by the selective A(1)R antagonist DPCPX. Pretreatment of animals with ethanol and adenosine kinase inhibitor increases (11)C-MPDX uptake. This increase may reflect an increased availability of A(1)R after acute exposure to ethanol.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Zheng; Lü, Tie-Yu; Wang, Hui-Qiong
We have investigated the thermoelectric properties of the 3C, 2H, 4H, and 6H polytypes of the wide-band-gap(n-type) semiconductors SiC, GaN, and ZnO based on first-principles calculations and Boltzmann transport theory. Our results show that the thermoelectric performance increases from 3C to 6H, 4H, and 2H structures with an increase of hexagonality for SiC. However, for GaN and ZnO, their power factors show a very weak dependence on the polytype. Detailed analysis of the thermoelectric properties with respect to temperature and carrier concentration of 4H-SiC, 2H-GaN, and 2H-ZnO shows that the figure of merit of these three compounds increases with temperature,more » indicating the promising potential applications of these thermoelectric materials at high temperature. The significant difference of the polytype-dependent thermoelectric properties among SiC, GaN, and ZnO might be related to the competition between covalency and ionicity in these semiconductors. Our calculations may provide a new way to enhance the thermoelectric properties of wide-band-gap semiconductors through atomic structure design, especially hexagonality design for SiC.« less
Transcriptional regulation of FoxO3 gene by glucocorticoids in murine myotubes
Kuo, Taiyi; Liu, Patty H.; Chen, Tzu-Chieh; Lee, Rebecca A.; New, Jenny; Zhang, Danyun; Lei, Cassandra; Chau, Andy; Tang, Yicheng; Cheung, Edna
2016-01-01
Glucocorticoids and FoxO3 exert similar metabolic effects in skeletal muscle. FoxO3 gene expression was increased by dexamethasone (Dex), a synthetic glucocorticoid, both in vitro and in vivo. In C2C12 myotubes the increased expression is due to, at least in part, the elevated rate of FoxO3 gene transcription. In the mouse FoxO3 gene, we identified three glucocorticoid receptor (GR) binding regions (GBRs): one being upstream of the transcription start site, −17kbGBR; and two in introns, +45kbGBR and +71kbGBR. Together, these three GBRs contain four 15-bp glucocorticoid response elements (GREs). Micrococcal nuclease (MNase) assay revealed that Dex treatment increased the sensitivity to MNase in the GRE of +45kbGBR and +71kbGBR upon 30- and 60-min Dex treatment, respectively. Conversely, Dex treatment did not affect the chromatin structure near the −17kbGBR, in which the GRE is located in the linker region. Dex treatment also increased histone H3 and/or H4 acetylation in genomic regions near all three GBRs. Moreover, using chromatin conformation capture (3C) assay, we showed that Dex treatment increased the interaction between the −17kbGBR and two genomic regions: one located around +500 bp and the other around +73 kb. Finally, the transcriptional coregulator p300 was recruited to all three GBRs upon Dex treatment. The reduction of p300 expression decreased FoxO3 gene expression and Dex-stimulated interaction between distinct genomic regions of FoxO3 gene identified by 3C. Overall, our results demonstrate that glucocorticoids activated FoxO3 gene transcription through multiple GREs by chromatin structural change and DNA looping. PMID:26758684
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Weijiu; Chongqing Municipal Key Laboratory of Institutions of Higher Education for Mould Technology, Chongqing University of Technology, Chongqing 400054; Chai, Linjiang, E-mail: chailinjiang@cqut.edu.cn
2016-04-15
Specimens cut from a rolled tin bronze sheet were annealed at 400–800 °C for 1 h and evolution of their microstructures was then characterized in details by electron channeling contrast imaging and electron backscatter diffraction techniques. Particularly, statistics on special boundaries (SBs) with Σ ≤ 29 and network connectivity of random high angle boundaries (HABs) in the annealed specimens were examined to probe optimization potentials of grain boundary character distribution (GBCD) for this material. Results show that the deformed microstructure in the as-received material begins to be recrystallized when the annealing temperature increase to 500 °C and average grain sizesmore » surge with further increasing temperatures. As a result of the recrystallization, a large number of annealing twins (with Σ3 misorientation) are produced, leading to remarkably increased fractions of SBs (f{sub SBs}). Thanks to preexisting dense low angle boundaries, the majority of SBs in the 500 °C specimen with only partial recrystallization are Σ3{sub ic} (incoherent) boundaries, which effectively disrupt connectivity of random HABs network. Although the f{sub SBs} can be further increased (up to 72.5%) in specimens with full recrystallization (at higher temperatures), the Σ3{sub ic} boundaries would be replaced to some extent by Σ3{sub c} (coherent) boundaries which do not contribute directly to optimizing the GBCD. This work should be able to provide clear suggestions on applying the concept of grain boundary engineering to tin bronze alloys. - Highlights: • The rolled tin bronze begins to be recrystallized as temperature increases to 500 °C. • A lot of SBs are produced after recrystallization and the highest f{sub SBs} is 72.5%. • Partially recrystallized specimen has the optimum GBCD due to more Σ3{sub ic} boundaries. • The Σ3{sub ic} boundaries are replaced by Σ3{sub c} boundaries after full recrystallization.« less
Crosstalk between MLO-Y4 osteocytes and C2C12 muscle cells is mediated by the Wnt/β-catenin pathway.
Huang, Jian; Romero-Suarez, Sandra; Lara, Nuria; Mo, Chenglin; Kaja, Simon; Brotto, Leticia; Dallas, Sarah L; Johnson, Mark L; Jähn, Katharina; Bonewald, Lynda F; Brotto, Marco
2017-10-01
We examined the effects of osteocyte secreted factors on myogenesis and muscle function. MLO-Y4 osteocyte-like cell conditioned media (CM) (10%) increased ex vivo soleus muscle contractile force by ~25%. MLO-Y4 and primary osteocyte CM (1-10%) stimulated myogenic differentiation of C2C12 myoblasts, but 10% osteoblast CMs did not enhance C2C12 cell differentiation. Since WNT3a and WNT1 are secreted by osteocytes, and the expression level of Wnt3a is increased in MLO-Y4 cells by fluid flow shear stress, both were compared, showing WNT3a more potent than WNT1 in inducing myogenesis. Treatment of C2C12 myoblasts with WNT3a at concentrations as low as 0.5ng/mL mirrored the effects of both primary osteocyte and MLO-Y4 CM by inducing nuclear translocation of β-catenin with myogenic differentiation, suggesting that Wnts might be potential factors secreted by osteocytes that signal to muscle cells. Knocking down Wnt3a in MLO-Y4 osteocytes inhibited the effect of CM on C2C12 myogenic differentiation. Sclerostin (100ng/mL) inhibited both the effects of MLO-Y4 CM and WNT3a on C2C12 cell differentiation. RT-PCR array results supported the activation of the Wnt/β-catenin pathway by MLO-Y4 CM and WNT3a. These results were confirmed by qPCR showing up-regulation of myogenic markers and two Wnt/β-catenin downstream genes, Numb and Flh1 . We postulated that MLO-Y4 CM/WNT3a could modulate intracellular calcium homeostasis as the trigger mechanism for the enhanced myogenesis and contractile force. MLO-Y4 CM and WNT3a increased caffeine-induced Ca 2+ release from the sarcoplasmic reticulum (SR) of C2C12 myotubes and the expression of genes directly associated with intracellular Ca 2+ signaling and homeostasis. Together, these data show that in vitro and ex vivo , osteocytes can stimulate myogenesis and enhance muscle contractile function and suggest that Wnts could be mediators of bone to muscle signaling, likely via modulation of intracellular Ca 2+ signaling and the Wnt/β-Catenin pathway.
Microstructure and Oxidation of (La,Sr)CrO3-Added Ti3SiC2 Composites.
Lee, Dong Bok
2015-11-01
Composites of Ti3SiC2-(10, 20, 40)wt% La0.8Sr0.2CrO3 were synthesized by hot pressing powders of Ti3SiC2 and La0.8Sr0.2CrO3. These powders reacted to form stable TiC carbides and LaTiO3, Cr2Ti4O11, La2O3, and SrCrO4 oxides during hot pressing. The composites consisted primarily of a fine TiC-rich matrix phase and coarse Ti3SiC2 dispersoids. The addition of oxidation-immune La0.8Sr0.2CrO3 into Ti3SiC2 increased the oxidation rate because TiC formed during hot pressing. During oxidation of the composites at 800-1000 degrees C for 100 h in air, Ti diffused outward to form an outer rutile-TiO2 layer, and oxygen transported inward to form an inner oxide layer.
Xu, Gui-lian; Zhang, Ke-qin; Guo, Bo; Zhao, Ting-ting; Yang, Fei; Jiang, Man; Wang, Qing-hong; Shang, Yu-hang; Wu, Yu-zhang
2010-10-18
Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer therapies is unclear. In this study, we have engineered a DNA vaccine that expresses extracellular region of murine VEGFR-2 (FLK1(265-2493)) and 3 copies of C3d (C3d3), a component of complement as a molecular adjuvant, designed to increase antitumor immunity. VEGFR-2 has a more restricted expression on endothelial cells and is upregulated once these cells proliferate during angiogenesis in the tumor vasculature. Immunization of mice with vector encoding FLK1(265-2493) alone generated only background levels of anti-VEGFR-2 antibodies and slight inhibitory effect on tumor growth. However, the addition of C3d3 to the vaccine construct significantly augmented the anti-VEGFR-2 humoral immune response and inhibited the tumor growth. The antitumor activity induced by vaccination with vector encoding FLK1(265-2493)-C3d3 fusion protein was also demonstrated via growth inhibition of established tumors following passive transfer of immune serum from vaccinated mice. Our results suggest that vaccination with vector encoding FLK1(265-2493) with C3d3 as a molecular adjuvant induces adaptive humoral activity, which is directed against the murine VEGFR-2 and can significantly inhibit tumor growth, and that administration of C3d as a molecular adjuvant to increase antibodies levels to VEGFR-2 may provide an alternative treatment modality for cancer therapies. Copyright © 2010 Elsevier Ltd. All rights reserved.
Chen, Lin; Hernandez, M. Rosario
2009-01-01
Purpose Investigate the effect of hydrostatic pressure (HP) on 3′, 5′-cyclic adenosine monophosphate (cAMP) levels and downstream signaling in cultures of normal optic nerve head (ONH) astrocytes from Caucasian American (CA) and African American (AA) donors. Methods Intracellular cAMP levels were assayed after exposing ONH astrocytes to HP for varying times. Quantitative RT–PCR was used to determine the expression levels of selected cAMP pathway genes in human ONH astrocytes after HP treatment. Western blots were used to measure changes in the phosphorylation state of cAMP response element binding protein (CREB) in astrocytes subjected to HP, ATP, and phosphodiesterase or kinase inhibitors. Results The basal intracellular cAMP level is similar among AA and CA astrocytes. After exposure to HP for 15 min and 30 min in the presence of a phosphodiesterase inhibitor a further increase of intracellular cAMP was observed in AA astrocytes, but not in CA astrocytes. Consistent with activation of the cAMP-dependent protein kinase pathway, CREB phosphorylation (Ser-133) was increased to a greater extent in AA than in CA astrocytes after 3 h of HP. Exposure to elevated HP for 3–6 h differentially altered the expression levels of selected cAMP pathway genes (ADCY3, ADCY9, PTHLH, PDE7B) in AA compared to CA astrocytes. Treatment with ATP increased more CREB phosphorylation in CA than in AA astrocytes, suggesting differential Ca2+ signaling in these populations. Conclusions Activation of the cAMP-dependent signaling pathway by pressure may be an important contributor to increased susceptibility to elevated intraocular pressure and glaucoma in AA, a population at higher risk for the disease. PMID:19710943
Joondan, Nausheen; Jhaumeer-Laulloo, Sabina; Caumul, Prakashanand
2014-01-01
Cationic amino acid-based surfactants are known to interact with the lipid bilayer of cell membranes resulting in depolarization, lysis and cell death through a disruption of the membrane topology. A range of cationic surfactant analogues derived from L-Phenylalanine (C1-C20) and L-Tyrosine (C8-C14) esters have been synthesized and screened for their antibacterial activity. The esters were more active against gram positive than gram negative bacteria. The activity increased with increasing chain length, exhibiting a cut-off effect at C12 for gram positive and C8/C10 for gram negative bacteria. The cut-off effect for gram negative bacteria was observed at a lower alkyl chain length. The CMC was correlated with the MIC, inferring that micellar activity contribute to the cut-off effect in antibacterial activity. The interaction of the cationic surfactants with the phospholipid vesicles (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) in the presence of 1-anilino-8-naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probes showed that an increase in ionic interaction causes an increase in antibacterial activity. Increase in hydrophobic interaction increases the antibacterial activity only to a certain chain length, attributing to the cut-off effect. Therefore, both electrostatic and hydrophobic interactions, involving the polar and nonpolar moieties are of paramount importance for the bactericidal properties. Copyright © 2014 Elsevier GmbH. All rights reserved.
Energy dependence of radiation interaction parameters of some organic compounds
NASA Astrophysics Data System (ADS)
Singh, Mohinder; Tondon, Akash; Sandhu, B. S.; Singh, Bhajan
2018-04-01
Gamma rays interact with a material through photoelectric absorption, Compton scattering, Rayleigh scattering and Pair production in the intermediate energy range. The probability of occurrence of a particular type of process depends on the energy of incident gamma rays, atomic number of the material, scattering angle and geometrical conditions. Various radiological parameters for organic compounds, namely ethylene glycol (C2H6O2), propylene glycol (C3H8O2), glycerin (C3H8O3), isoamyl alcohol (C5H12O), butanone (C4H8O), acetophenone (C8H8O2), cyclohexanone (C6H10O), furfural (C5H4O2), benzaldehyde (C7H6O), cinnamaldehyde (C9H8O), glutaraldehyde (C5H8O2), aniline (C6H7N), benzyl amine (C6H7N), nitrobenzene (C6H5NO2), ethyl benzene (C8H10), ethyl formate (C3H6O2) and water (H2O) are presented at 81, 122, 356 and 511 keV energies employing NaI(Tl) scintillation detector in narrow-beam transmission geometry. The radiation interaction parameters such as mass attenuation, molar extinction and mass energy absorption coefficients, half value layer, total atomic and effective electronic cross-sections and CT number have been evaluated for these organic compounds. The general trend of values of mass attenuation coefficients, half value layer, molar extinction coefficients, total atomic and effective electronic cross-sections and mass energy absorption coefficients shows a decrease with increase in incident gamma photon energy. The values of CT number are found to increases linearly with increase of effective atomic number (Zeff). The variation in CT number around Zeff ≈ 3.3 shows the peak like structure with respect to water and the correlation between CT number and linear attenuation coefficient is about 0.99. Appropriate equations are fitted to these experimentally determined parameters for the organic compounds at incident photon energy ranging from 81 keV to 511 keV used in the present study. Experimental values are compared with the theoretical data obtained using WinXcom software package, and are found in good agreement.
Teng, Yun; Radde, Brandie N.; Litchfield, Lacey M.; Ivanova, Margarita M.; Prough, Russell A.; Clark, Barbara J.; Doll, Mark A.; Hein, David W.; Klinge, Carolyn M.
2015-01-01
Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3–12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction. PMID:25969534
Chemical glycosylation of cytochrome c improves physical and chemical protein stability.
Delgado, Yamixa; Morales-Cruz, Moraima; Hernández-Román, José; Martínez, Yashira; Griebenow, Kai
2014-08-06
Cytochrome c (Cyt c) is an apoptosis-initiating protein when released into the cytoplasm of eukaryotic cells and therefore a possible cancer drug candidate. Although proteins have been increasingly important as pharmaceutical agents, their chemical and physical instability during production, storage, and delivery remains a problem. Chemical glycosylation has been devised as a method to increase protein stability and thus enhance their long-lasting bioavailability. Three different molecular weight glycans (lactose and two dextrans with 1 kD and 10 kD) were chemically coupled to surface exposed Cyt c lysine (Lys) residues using succinimidyl chemistry via amide bonds. Five neo-glycoconjugates were synthesized, Lac4-Cyt-c, Lac9-Cyt-c, Dex5(10kD)-Cyt-c, Dex8(10kD)-Cyt-c, and Dex3(1kD)-Cyt-c. Subsequently, we investigated glycoconjugate structure, activity, and stability. Circular dichroism (CD) spectra demonstrated that Cyt c glycosylation did not cause significant changes to the secondary structure, while high glycosylation levels caused some minor tertiary structure perturbations. Functionality of the Cyt c glycoconjugates was determined by performing cell-free caspase 3 and caspase 9 induction assays and by measuring the peroxidase-like pseudo enzyme activity. The glycoconjugates showed ≥94% residual enzyme activity and 86 ± 3 to 95 ± 1% relative caspase 3 activation compared to non-modified Cyt c. Caspase 9 activation by the glycoconjugates was with 92 ± 7% to 96 ± 4% within the error the same as the caspase 3 activation. There were no major changes in Cyt c activity upon glycosylation. Incubation of Dex3(1 kD)-Cyt c with mercaptoethanol caused significant loss in the tertiary structure and a drop in caspase 3 and 9 activation to only 24 ± 8% and 26 ± 6%, respectively. This demonstrates that tertiary structure intactness of Cyt c was essential for apoptosis induction. Furthermore, glycosylation protected Cyt c from detrimental effects by some stresses (i.e., elevated temperature and humidity) and from proteolytic degradation. In addition, non-modified Cyt c was more susceptible to denaturation by a water-organic solvent interface than its glycoconjugates, important for the formulation in polymers. The results demonstrate that chemical glycosylation is a potentially valuable method to increase Cyt c stability during formulation and storage and potentially during its application after administration.
Lu, Xingwen; Ning, Xun-An; Chen, Da; Chuang, Kui-Hao; Shih, Kaimin; Wang, Fei
2018-06-01
This study quantitatively determined the extraction of lead from CRT funnel glass and examined the mechanisms of thermally reducing lead in the products of sintering Pb-glass with carbon in the pre-heated furnace. The experimentally derived results indicate that a 90.3 wt% lead extraction efficiency can be achieved with 20 wt% of C addition at 950 °C for 3 min under air. The formation of viscous semi-liquid glass blocked the oxygen supply between the interaction of C and Pb-glass, and was highly effective for the extraction of metallic Pb. A maximum of 87.3% lead recover was obtained with a C to Na 2 CO 3 ratio of 1/3 at 1200 °C. The decrease of C/Na 2 CO 3 ratio enhanced the metallic lead recovery by increasing the glass viscosity for effective sedimentation of metallic lead in the bottom. However, with the further increase of temperature and treatment time, re-vitrification of lead back to silicate-glass matrix was detected in both Pb-glass/C and Pb-glass/C/Na 2 CO 3 systems. The findings indicated that with proper controls, using C as an inexpensive reagent can effectively reduce treatment time and energy, which is crucial to a waste-to-resource technology for economically recovering lead from the waste CRT glass. Copyright © 2018 Elsevier Ltd. All rights reserved.
Li, Chao; D'Agostino, Ralph B; Dabelea, Dana; Liese, Angela D; Mayer-Davis, Elizabeth J; Pate, Russell; Merchant, Anwar T
2018-04-30
Few studies have evaluated the prospective association of eating frequency with HbA1c levels and cardiovascular disease risk markers among youth with diabetes. To examine the 5-year longitudinal association of eating frequency with HbA1c and serum lipid levels among youth with type 1 diabetes (T1D) or type 2 diabetes (T2D). 1,049 youth (≥10 years old) with incident T1D (n=821) or T2D (n=228) who participated in the SEARCH for Diabetes in Youth Study were included. Eating frequency (≤3, 4-5 or 6-10 times/day) measured at baseline and follow-up visits was related to HbA1c and serum lipid levels measured repeatedly over 5 years. Increased eating frequency was associated with larger increases in HbA1c among youth T1D. For example, for youth with T1D who ate ≤ 3 times/day at the outset and ate 6-10 times/day 5 years later, the longitudinal model predicted greater absolute increases in HbA1c (2.77%); whereas for youth with T1D who ate 6-10 times/day at the outset and ate ≤3 times/day 5 years later, the model predicted lesser absolute increases in HbA1c (1.33%). Eating frequency was not associated with changes in serum lipid levels among youth with T1D or T2D. Youth with T1D who increased their eating frequency vs. those who decreased it had larger increases in HbA1c over 5 years. This article is protected by copyright. All rights reserved.
NASA Astrophysics Data System (ADS)
Pandey, Tribhuwan; Polanco, Carlos A.; Lindsay, Lucas; Parker, David S.
2017-06-01
Thermal conductivities of L a3C u3X4 (X =P ,As ,Sb ,Bi ) compounds are examined using first-principles density functional theory and Boltzmann transport methods. We observe a trend of increasing lattice thermal conductivity (κl) with increasing atomic mass, challenging our expectations, as lighter mass systems typically have larger sound speeds and weaker intrinsic scattering. In particular, we find that L a3C u3P4 has the lowest κl, despite having larger sound speed and the most restricted available phase space for phonon-phonon scattering, an important criterion for estimating and comparing κl among like systems. The origin of this unusual behavior lies in the strength of the individual anharmonic phonon scattering matrix elements, which are much larger in L a3C u3P4 than in the heavier L a3C u3B i4 system. Our finding provides insights into the interplay of harmonic and anharmonic properties of complex, low-thermal-conductivity compounds, of potential use for thermoelectric and thermal barrier coating applications.
Yang, W Z; Beauchemin, K A
2009-04-01
A study was conducted to evaluate whether the risk of acidosis in dairy cows can be lowered by increasing the physically effective fiber (peNDF) concentration of the diet, either through increased theoretical chop length of alfalfa silage or higher proportion of forage in the diet. The experiment was designed as a replicated 4 x 4 Latin square using 8 ruminally cannulated lactating dairy cows. Treatments were arranged in a 2 x 2 factorial design; 2 forage particle lengths (FPL) of alfalfa silage (short and long) were combined with low (35:65) and high (60:40) forage:concentrate (F:C) ratios [dry matter (DM) basis]. Dietary peNDF concentration (DM basis) was determined from the sum of the proportion of dietary DM retained either on the 2 sieves (8 and 19 mm) or on the 3 sieves (1.18, 8, and 19 mm) of the Penn State Particle Separator multiplied by the neutral detergent fiber concentration of the diet. The dietary peNDF concentrations were altered by changing the F:C or the FPL, and ranged from 10.7 to 17.5% using 2 sieves, or from 23.1 to 28.2% using 3 sieves. Intake of peNDF was increased by increasing FPL but not by increasing F:C ratio because of the reduction of DM intake at the higher F:C ratio. Chewing activity, including number of chews and chewing time, increased with increasing F:C ratio or FPL. Mean ruminal pH was elevated by 0.4 and 0.2 units with increasing F:C ratio and FPL, respectively. Lowering the F:C ratio decreased the duration that ruminal pH was below 5.8 (1.2 vs. 8 h/d). Increased F:C ratio or FPL reduced ruminal volatile fatty acids concentration from 137 to 122 or from 133 to 126 mM, respectively, whereas acetate:propionate ratio was increased from 2.55 to 3.46 with increasing F:C ratio. Dietary peNDF concentration measured using 2 sieves was correlated to chewing time (r = 0.57) and mean ruminal pH (r = 0.75), whereas dietary peNDF concentration measured using 3 sieves was correlated to mean ruminal pH (r = 0.83) and negatively correlated to the time that pH was below 5.8 (r = -0.78). This study shows that the risk of ruminal acidosis is high for cows fed a low F:C diet. Increasing the proportion of forage in the diet helps prevent ruminal acidosis through increased chewing time, a change in meal patterns, and decreased ruminal acid production. Increasing FPL elevates ruminal pH, but in low forage diets, increased FPL does not alleviate subacute acidosis because the fermentability of the diet is high and changes in chewing activity are marginal.
Kim, In Sik; Kim, Dong-Hee; Yun, Chi-Young; Lee, Ji-Sook
2013-03-01
(S)-(+)-decursin is a biological coumarin compound isolated from Angelica gigas Nakai. (S)-(+)-decursin and its analogue have a variety of pharmacological activities. In the present study, the anti-inflammatory effect of a (S)-(+)-decursin derivative, (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano [3,2-g]-chromen-3-yl-ester (Compound 6, C6), on in vitro and in vivo atopic dermatitis was investigated. C6 suppressed the secretion of IL-6, IL-8, and monocyte chemotactic protein-1 increase by the house dust mite extract in the eosinophilic leukemia cell line and THP-1 cells. C6 inhibited the production of TARC, IL-6, and IL-8 increase by IFN-γ and TNF-α in the human keratinocyte cell line. In the in vivo experiment, NC/Nga mice were sensitized to 2,4-dinitrochlorobenzene, and then C6 or dexamethasone (Dex) were orally and dorsally administered for three weeks. C6 treatment reduced the skin severity score compared with that of the control group. C6 inhibited the thickening of the epidermis and inflammatory cell infiltration into the dermis by evaluating the histological examination. The serum immunoglobulin E (IgE) level decreased in the C6-treated group compared with that of the control group. The inhibitory effect of C6 on IgE concentration was similar to that of Dex. The levels of IL-4, IL-5, IL-13, and eotaxin increased after treatment with concanavalin A in mouse splenocytes. The cytokine levels of the C6-treated group were lower than those of the control group. Taken together, C6 may attenuate atopic dermatitis-like lesions through its anti-inflammatory effect, such as inhibition of IgE and inflammatory cytokines, and it may be valuable as a therapeutic drug for the treatment of atopic dermatitis.
C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tong Tiezhu; Provincial Key Laboratory of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070; Fan Huiying
2006-09-08
Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28{sub 4} were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d{sub 3} DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD{sub 5}) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immunemore » response by inducing IL-4 production. The IL-4 level for sgC-C3d{sub 3} DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response.« less
Sleep Deprivation Decreases [11C]Raclopride’s Binding to Dopamine D2/D3 Receptors in the Human Brain
Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Logan, Jean; Wong, Christopher; Ma, Jim; Pradhan, Kith; Tomasi, Dardo; Thanos, Peter K.; Ferré, Sergi; Jayne, Millard
2009-01-01
Sleep deprivation can markedly impair human performance contributing to accidents and poor productivity. The mechanisms underlying this impairment are not well understood but brain dopamine systems have been implicated. Here we test whether one night of sleep deprivation changes dopamine brain activity. We studied fifteen healthy subjects using positron emission tomography and [11C]raclopride (dopamine D2/3 receptor radioligand) and [11C]cocaine (dopamine transporter radioligand). Subjects were tested twice; after one night of rested sleep and after on night of sleep deprivation. [11C]Raclopride’s specific binding in striatum and thalamus were significantly reduced after sleep deprivation and the magnitude of this reduction correlated with increases in fatigue (tiredness and sleepiness) and with deterioration in cognitive performance (visual attention and working memory). In contrast sleep deprivation did not affect the specific binding of [11C]cocaine in striatum. Since [11C]raclopride competes with endogenous dopamine for binding to D2/D3 receptors, we interpret the decreases in binding to reflect dopamine increases with sleep deprivation. However, we can not rule out the possibility that decreased [11C]raclopride binding reflects decreases in receptor levels or affinity. Sleep deprivation did not affect dopamine transporters (target for most wake-promoting medications) and thus dopamine increases are likely to reflect increases in dopamine cell firing and/or release rather than decreases in dopamine reuptake. Inasmuch as dopamine-enhancing drugs increase wakefulness we postulate that dopamine increases after sleep deprivation is a mechanism by which the brain maintains arousal as the drive to sleep increases but one that is insufficient to counteract behavioral and cognitive impairment. PMID:18716203
Roy, René M.; Paes, Hugo C.; Nanjappa, Som G.; Sorkness, Ron; Gasper, David; Sterkel, Alana; Wüthrich, Marcel; Klein, Bruce S.
2013-01-01
ABSTRACT Levels of the anaphylatoxin C3a are increased in patients with asthma compared with those in nonasthmatics and increase further still during asthma exacerbations. However, the role of C3a during sensitization to allergen is poorly understood. Sensitization to fungal allergens, such as Aspergillus fumigatus, is a strong risk factor for the development of asthma. Exposure to chitin, a structural polysaccharide of the fungal cell wall, induces innate allergic inflammation and may promote sensitization to fungal allergens. Here, we found that coincubation of chitin with serum or intratracheal administration of chitin in mice resulted in the generation of C3a. We established a model of chitin-dependent sensitization to soluble Aspergillus antigens to test the contribution of complement to these events. C3−/− and C3aR−/− mice were protected from chitin-dependent sensitization to Aspergillus and had reduced lung eosinophilia and type 2 cytokines and serum IgE. In contrast, complement-deficient mice were not protected against chitin-induced innate allergic inflammation. In sensitized mice, plasmacytoid dendritic cells from complement-deficient animals acquired a tolerogenic profile associated with enhanced regulatory T cell responses and suppressed Th2 and Th17 responses specific for Aspergillus. Thus, chitin induces the generation of C3a in the lung, and chitin-dependent allergic sensitization to Aspergillus requires C3aR signaling, which suppresses regulatory dendritic cells and T cells and induces allergy-promoting T cells. PMID:23549917
Kawashima, Hidekazu; Kimura, Hiroyuki; Nakaya, Yuta; Tomatsu, Kenji; Arimitsu, Kenji; Nakanishi, Hiroaki; Ozeki, Eiichi; Kuge, Yuji; Saji, Hideo
2015-01-01
A new radiolabeling method using a microreactor was developed for the rapid synthesis of [(11)C]raclopride. A chip bearing a Y-shaped mixing junction with a 200 µm (width)×20 µm (depth)×250 mm (length) flow channel was designed, and the efficiency of O-[11C]methylation was evaluated. Dimethyl sulfoxide solutions containing the O-desmethyl precursor or [11C]CH3I were introduced into separate injection ports by infusion syringes, and the radiochemical yields were measured under various conditions. The decay-corrected radiochemical yield of microreactor-derived [11C]raclopride reached 12% in 20 s at 25 °C, which was observed to increase with increasing temperature. In contrast, batch synthesis at 25 °C produced a yield of 5%: this indicates that this device could effectively achieve O-[11C]methylation in a shorter period of time. The microreactor technique may facilitate simple and efficient routine production of 11C-labeled compounds via O-[11C]methylation with [11C]CH3I.
Pressure Effects on the Magnetic Phase Transition of Mn3SnC1-xNx (x = 0, 0.5)
NASA Astrophysics Data System (ADS)
Hu, Jing-Yu; Wen, Yong-Chun; Yao, Yuan; Wang, Cong; Zhao, Qing; Jin, Chang-Qing; Yu, Ri-Cheng
2012-08-01
The electronic transport properties of Mn3SnC and Mn3SnC0.5N0.5 were measured under pressures up to 1.8 GPa. At ambient pressure, an abrupt increase of resistance occurs around the temperature of magnetic phase transition in both samples. The transition temperature Tc from paramagnetic to ferrimagnetic state decreases linearly at rates of 12.6 and 6.3K/GPa with pressure for Mn3SnC and Mn3SnC0.5N0.5, respectively. This phenomenon could be understood by the Labbe-Jardin tight binding approximation model.
Kempe, Allison; Saville, Alison W; Beaty, Brenda; Dickinson, L Miriam; Gurfinkel, Dennis; Eisert, Sheri; Roth, Heather; Herrero, Diana; Trefren, Lynn; Herlihy, Rachel
2017-04-01
We compared the effectiveness and cost-effectiveness of: 1) centralized reminder/recall (C-R/R) using the Colorado Immunization Information System (CIIS) versus practice-based reminder/recall (PB-R/R) approaches to increase immunization rates; 2) different levels of C-R/R intensity; and 3) C-R/R with versus without the name of the child's provider. We conducted 3 sequential cluster-randomized trials involving children aged 19 to 25 months in 15 Colorado counties in March 2013 (trial 1), October 2013 (trial 2), and May 2014 (trial 3). In C-R/R counties, the intensity of the intervention decreased sequentially in trials 1 through 3, from 3 to 1 recall messages. In PB-R/R counties, practices were offered training using CIIS and financial support. The percentage of children with up-to-date (UTD) vaccinations was compared 6 months after recall. A mixed-effects model assessed the association between C-R/R versus PB-R/R and UTD rates. C-R/R was more effective in trials 1 to 3 (relative risk = 1.11; 95% confidence interval 1.01-1.20; P = .009). Effectiveness did not decrease with decreasing intervention intensity (P = .59). Costs decreased with decreasing intensity in the C-R/R arm, from $18.72 per child brought UTD in trial 1 to $10.11 in trial 3. Costs were higher and more variable in the PB-R/R arm, ranging from $20.63 to $237.81 per child brought UTD. C-R/R was significantly more effective if the child's practice name was included (P < .0001). C-R/R was more effective and cost-effective than PB-R/R for increasing UTD rates in young children and was most effective if messages included the child's provider name. Three reminders were not more effective than one, which may be explained by the increasing accuracy of contact information in CIIS over the course of the trials. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.
A novel TRPM8 agonist relieves dry eye discomfort.
Yang, Jee Myung; Li, Fengxian; Liu, Qin; Rüedi, Marco; Wei, Edward Tak; Lentsman, Michael; Lee, Hyo Seok; Choi, Won; Kim, Seong Jin; Yoon, Kyung Chul
2017-06-26
Physical cooling of the eye surface relieves ocular discomfort, but translating this event to drug treatment of dry eye discomfort not been studied. Here, we synthesized a water-soluble TRPM8 receptor agonist called cryosim-3 (C3, 1-diisopropylphosphorylnonane) which selectively activates TRPM8 (linked to cooling) but not TRPV1 or TRPA1 (linked to nociception) and tested C3 in subjects with mild forms of dry eye disease. A set of 1-dialkylphosphoryalkanes were tested for activation of TRPM8, TRPV1 and TRPA1 receptors in transfected cells. The bioactivity profiles were compared by perioral, topical, and intravenous delivery to anesthetized rats. The selected lead candidate C3 or vehicle (water) was applied with a cotton gauze pad to upper eyelids of patients with dry eye disease (n = 30). Cooling sensation, tear film break-up time (TBUT), basal tear secretion, and corneal staining were evaluated. C3 was then applied four times daily for 2 weeks to patients using a pre-loaded single unit applicator containing 2 mg/mL of C3 in water (n = 20) or water only. TBUT, basal tear secretion, and corneal staining, and three questionnaires surveys of ocular discomfort (VAS scale, OSDI, and CVS symptoms) were analyzed before and at 1 and 2 weeks thereafter. C3 was a selective and potent TRPM8 agonist without TRPV1 or TRPA1 activity. In test animals, the absence of shaking behavior after C3 perioral administration made it the first choice for further study. C3 increased tear secretion in an animal model of dry eye disease and did not irritate when wiped on eyes of volunteers. C3 singly applied (2 mg/ml) produced significant cooling in <5 min, an effecting lasting 46 min with an increase in tear secretion for 60 min. C3 applied for 2 weeks also significantly increased basal tear secretion with questionnaire surveys of ocular discomfort indices clearly showing improvement of symptoms at 1 and 2 weeks. No complaints of irritation or pain were reported by any subject. C3 is a promising candidate for study of TRPM8 function on the eye surface and for relief of dry eye discomfort. ISRCTN24802609 and ISRCTN13359367 . Registered 23 March 2015 and 2 September 2015.
Metabolism of valine and 3-methyl-2-oxobutanoate by the isolated perfused rat kidney.
Miller, R H; Harper, A E
1984-01-01
Metabolism of branched-chain amino and 2-oxo acids was studied in the isolated perfused kidney. Significant amounts of 2-oxo acids were released by perfused kidney with all concentrations of amino acids tested (0.1-1.0 mM each), despite the high activity of branched-chain 2-oxo acid dehydrogenase in kidney. As perfusate valine concentration was increased from 0.2 to 1.0 mM, [1-14C]valine transamination (2-oxo acid oxidized + released) increased roughly linearly; [1-14C]valine oxidation, however, increased exponentially. Increasing perfusate concentration of 3-methyl-2-oxo[1-14C]butanoate from 0 to 1.0 mM resulted in a linear increase in the rate of its oxidation and a rise in perfusate valine concentration; at the same time significant decreases occurred in perfusate isoleucine and leucine concentrations, with corresponding increases in rates of release of their respective 2-oxo acids. Comparison of rates of oxidation of [1-14C]valine and 3-methyl-2-oxo[1-14C]butanoate suggests that 2-oxo acid arising from [1-14C]valine transamination has freer access to the 2-oxo acid dehydrogenase than has the 2-oxo acid from the perfusate. The observations indicate that, when branched-chain amino and 2-oxo acids are present in perfusate at near-physiological concentrations, rates of transamination of the amino and 2-oxo acids by isolated perfused kidney are greater than rates of oxidation. PMID:6508752
Pereira, Clifford T; Herndon, David N; Rocker, Roland; Jeschke, Marc G
2007-05-15
Growth factors affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study, we thought to determine the interaction between keratinocyte growth factor (KGF) administered as liposomal cDNA with other dermal and epidermal growth factors and collagen synthesis in an acute wound. Rats received an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and Lac-Z gene (0.22 microg). Histological and immunohistochemical techniques were used to determine growth factor, collagen expression, and dermal and epidermal structure. KGF cDNA increased insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and fibroblast growth factor (FGF), decreased transforming growth factor-beta (TGF-beta), while it had no effect on platelet-derived growth factor (PDGF) levels in the wound. KGF cDNA significantly increased collagen Type IV at both the wound edge as well as the wound bed, while it had no effect on collagen Type I and III. KGF cDNA increased re-epithelialization, improved dermal regeneration, and increased neovascularization. Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III.
NASA Astrophysics Data System (ADS)
Arif, Mohd.; Sanger, Amit; Vilarinho, Paula M.; Singh, Arun
2018-04-01
Nanocrystalline ZnO thin films were deposited on glass substrate via sol-gel dip-coating technique then annealed at 300°C, 400°C, and 500°C for 1 h. Their optical, structural, and morphological properties were studied using ultraviolet-visible (UV-Vis) spectrophotometry, x-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). XRD diffraction revealed that the crystalline nature of the thin films increased with increasing annealing temperature. The c-axis orientation improved, and the grain size increased, as indicated by increased intensity of the (002) plane peak at 2θ = 34.42° corresponding to hexagonal ZnO crystal. The average crystallite size of the thin films ranged from 13 nm to 23 nm. Increasing the annealing temperature resulted in larger crystallite size and higher crystallinity with increased surface roughness. The grain size according to SEM analysis was in good agreement with the x-ray diffraction data. The optical bandgap of the thin films narrowed with increasing annealing temperature, lying in the range of 3.14 eV to 3.02 eV. The transmission of the thin films was as high as 94% within the visible region. The thickness of the thin films was 400 nm, as measured by ellipsometry, after annealing at the different temperatures of 300°C, 400°C, and 500°C.
Ren, Tingting; Zhu, Juanjuan; Zhu, Lili; Cheng, Mingliang
2017-01-01
Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α. PMID:28264426
Ren, Tingting; Zhu, Juanjuan; Zhu, Lili; Cheng, Mingliang
2017-02-27
Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets ( p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models ( p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) ( p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α.
Evaluation of epidural and peripheral nerve catheter heating during magnetic resonance imaging.
Owens, Sean; Erturk, M Arcan; Ouanes, Jean-Pierre P; Murphy, Jamie D; Wu, Christopher L; Bottomley, Paul A
2014-01-01
Many epidural and peripheral nerve catheters contain conducting wire that could heat during magnetic resonance imaging (MRI), requiring removal for scanning. We tested 2 each of 6 brands of regional analgesia catheters (from Arrow International [Reading, Pennsylvania], B. Braun Medical Inc [Bethlehem, Pennsylvania], and Smiths Medical/Portex [Keene, New Hampshire]) for exposure to clinical 1.5- and 3-T MRI. Catheters testing as nonmagnetic were placed in an epidural configuration in a standard human torso-sized phantom, and an MRI pulse sequence applied at the maximum scanner-allowed radiofrequency specific absorption rate (SAR) for 15 minutes. Temperature and SAR exposure were sampled during MRI using multiple fiberoptic temperature sensors. Two catheters (the Arrow StimuCath Peripheral Nerve and B. Braun Medical Perifix FX Epidural) were found to be magnetic and not tested further. At 3 T, exposure of the remaining 3 epidural and 1 peripheral nerve catheter to the scanner's maximum RF exposure elicited anomalous heating of 4°C to 7°C in 2 Arrow Epidural (MultiPort and Flex-Tip Plus) catheters at the entry points. Temperature increases for the other catheters at 3 T, and all catheters at 1.5 T were 1.4°C or less. When normalized to the body-average US Food and Drug Administration guideline SAR of 4 W/kg, maximum projected temperature increases were 0.1°C to 2.5°C at 1.5 T and 0.7°C to 2.7°C at 3 T, except for the Arrow MultiPort Flex-Tip Plus catheter at 3 T whose increase was 14°C. Most but not all catheters can be left in place during 1.5-T MRI scans. Heating of less than 3°C during MRI for most catheters is not expected to be injurious. While heating was lower at 1.5 T versus 3 T, performance differences between products underscore the need for safety testing before performing MRI.
Carter, W J; Benjamin, W S; Faas, F H
1982-01-01
The effect of T3 (3,3',5-tri-iodothyronine) on protein turnover in skeletal and cardiac muscle was measured in intact rats by means of a 6 h [14C]tyrosine-infusion technique. Treatment with 25-30 micrograms of T3/100 g body wt. daily for 4-7 days increased the fractional rate of protein synthesis in skeletal muscle. Since the fractional growth rate of the muscle was decreased or unchanged, T3 treatment increased the rate of muscle protein breakdown. These findings suggest that increased protein degradation is an important factor in decreasing skeletal-muscle mass in hyperthyroidism. In contrast with skeletal muscle, T3 treatment for 7 days caused an equivalent increase in the rate of cardiac muscle growth and protein synthesis. This suggests that hyperthyroidism does not increase protein breakdown in heart muscle as it does in skeletal muscle. The failure of T3 to increase proteolysis in heart muscle may be due to a different action on the cardiac myocyte or to systemic effects of T3 which increase cardiac work. PMID:7115332
Carter, W J; Benjamin, W S; Faas, F H
1982-04-15
The effect of T3 (3,3',5-tri-iodothyronine) on protein turnover in skeletal and cardiac muscle was measured in intact rats by means of a 6 h [14C]tyrosine-infusion technique. Treatment with 25-30 micrograms of T3/100 g body wt. daily for 4-7 days increased the fractional rate of protein synthesis in skeletal muscle. Since the fractional growth rate of the muscle was decreased or unchanged, T3 treatment increased the rate of muscle protein breakdown. These findings suggest that increased protein degradation is an important factor in decreasing skeletal-muscle mass in hyperthyroidism. In contrast with skeletal muscle, T3 treatment for 7 days caused an equivalent increase in the rate of cardiac muscle growth and protein synthesis. This suggests that hyperthyroidism does not increase protein breakdown in heart muscle as it does in skeletal muscle. The failure of T3 to increase proteolysis in heart muscle may be due to a different action on the cardiac myocyte or to systemic effects of T3 which increase cardiac work.
Oxidation Resistance of Materials Based on Ti3AlC2 Nanolaminate at 600 °C in Air.
Ivasyshyn, Andrij; Ostash, Orest; Prikhna, Tatiana; Podhurska, Viktoriya; Basyuk, Tatiana
2016-12-01
The oxidation behavior of Ti3AlC2-based materials had been investigated at 600 °C in static air for 1000 h. It was shown that the intense increase of weight gain per unit surface area for sintered material with porosity of 22 % attributed to oxidation of the outer surface of the specimen and surfaces of pores in the bulk material. The oxidation kinetics of the hot-pressed Ti3AlC2-based material with 1 % porosity remarkably increased for the first 15 h and then slowly decreased. The weight gain per unit surface area for this material was 1.0 mg/cm(2) after exposition for 1000 h. The intense initial oxidation of Ti3AlC2-based materials can be eliminated by pre-oxidation treatment at 1200 °C in air for 2 h. As a result, the weight gain per unit surface area for the pre-oxidized material did not exceed 0.11 mg/cm(2) after 1000 h of exposition at 600 °C in air. It was demonstrated that the oxidation resistance of Ti3AlC2-based materials can be significantly improved by niobium addition.
NASA Astrophysics Data System (ADS)
Yu, Fengling; Zong, Yongqiang; Lloyd, Jeremy M.; Huang, Guangqing; Leng, Melanie J.; Kendrick, Christopher; Lamb, Angela L.; Yim, Wyss W.-S.
2010-05-01
Preservation of organic matter in estuarine and coastal areas is an important process in the global carbon cycle. This paper presents bulk δ 13C and C/N of organic matter from source to sink in the Pearl River catchment, delta and estuary, and discusses the applicability of δ 13C and C/N as indicators for sources of organic matter in deltaic and estuarine sediments. In addition to the 91 surface sediment samples, other materials collected in this study cover the main sources of organic material to estuarine sediment. These are: terrestrial organic matter (TOM), including plants and soil samples from the catchment; estuarine and marine suspended particulate organic carbon (POC) from both summer and winter. Results show that the average δ 13C of estuarine surface sediment increases from -25.0 ± 1.3‰ in the freshwater environment to -21.0 ± 0.2‰ in the marine environment, with C/N decreasing from 15.2 ± 3.3 to 6.8 ± 0.2. In the source areas, C 3 plants have lower δ 13C than C 4 plants (-29.0 ± 1.8‰ and -13.1 ± 0.5‰ respectively). δ 13C increases from -28.3 ± 0.8‰ in the forest soil to around -24.1‰ in both riverbank soil and mangrove soil due to increasing proportion of C 4 grasses. The δ 13C POC increases from -27.6 ± 0.8‰ in the freshwater areas to -22.4 ± 0.5‰ in the marine-brackish-water areas in winter, and ranges between -24.0‰ in freshwater areas and -25.4‰ in brackish-water areas in summer. Comparison of the δ 13C and C/N between the sources and sink indicates a weakening TOM and freshwater POC input in the surface sedimentary organic matter seawards, and a strengthening contribution from the marine organic matter. Thus we suggest that bulk organic δ 13C and C/N analysis can be used to indicate sources of sedimentary organic matter in estuarine environments. Organic carbon in surface sediments derived from anthropogenic sources such as human waste and organic pollutants from industrial and agricultural activities accounts for less than 10% of the total organic carbon (TOC). Although results also indicate elevated δ 13C of sedimentary organic matter due to some agricultural products such as sugarcane, C 3 plants are still the dominant vegetation type in this area, and the bulk organic δ 13C and C/N is still an effective indicator for sources of organic matter in estuarine sediments.
NASA Astrophysics Data System (ADS)
Šolić, Mladen; Krstulović, Nada; Šantić, Danijela; Šestanović, Stefanija; Kušpilić, Grozdan; Bojanić, Natalia; Ordulj, Marin; Jozić, Slaven; Vrdoljak, Ana
2017-09-01
The Mediterranean Sea (including the Adriatic Sea) has been identified as a 'hotspot' for climate change, with the prediction of the increase in water temperature of 2-4 °C over the next few decades. Being mainly oligotrophic, and strongly phosphorus limited, the Adriatic Sea is characterized by the important role of the microbial food web in production and transfer of biomass and energy towards higher trophic levels. We hypothesized that predicted 3 °C temperature rise in the near future might cause an increase of bacterial production and bacterial losses to grazers, which could significantly enlarge the trophic base for metazoans. This empirical study is based on a combined 'space-for-time substitution' analysis (which is performed on 3583 data sets) and on an experimental approach (36 in situ grazing experiments performed at different temperatures). It showed that the predicted 3 °C temperature increase (which is a result of global warming) in the near future could cause a significant increase in bacterial growth at temperatures lower than 16 °C (during the colder winter-spring period, as well as in the deeper layers). The effect of temperature on bacterial growth could be additionally doubled in conditions without phosphorus limitation. Furthermore, a 3 °C increase in temperature could double the grazing on bacteria by heterotrophic nanoflagellate (HNF) and ciliate predators and it could increase the proportion of bacterial production transferred to the metazoan food web by 42%. Therefore, it is expected that global warming may further strengthen the role of the microbial food web in a carbon cycle in the Adriatic Sea.
Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice.
Qu, Shen; Perdomo, German; Su, Dongming; D'Souza, Fiona M; Shachter, Neil S; Dong, H Henry
2007-07-01
Apolipoprotein A-V (apoA-V) and apoC-III are exchangeable constituents of VLDL and HDL. ApoA-V counteracts the effect of apoC-III on triglyceride (TG) metabolism with poorly defined mechanisms. To better understand the effects of apoA-V on TG and cholesterol metabolism, we delivered apoA-V cDNA into livers of hypertriglyceridemic APOC3 transgenic mice by adenovirus-mediated gene transfer. In response to hepatic apoA-V production, plasma TG levels were reduced significantly as a result of enhanced VLDL catabolism without alternations in VLDL production. This effect was associated with reduced apoC-III content in VLDL. Increased apoA-V production also resulted in decreased apoC-III and increased apoA-I content in HDL. Furthermore, apoA-V-enriched HDL was associated with enhanced LCAT activity and increased cholesterol efflux. This effect, along with apoE enrichment in HDL, contributed to HDL core expansion and alpha-HDL formation, accounting for significant increases in both the number and size of HDL particles. As a result, apoA-V-treated APOC3 transgenic mice exhibited decreased VLDL-cholesterol and increased HDL-cholesterol levels. ApoA-V-mediated reduction of apoC-III content in VLDL represents an important mechanism by which apoA-V acts to ameliorate hypertriglyceridemia in adult APOC3 transgenic mice. In addition, increased apoA-V levels accounted for cholesterol redistribution from VLDL to larger HDL particles. These data suggest that in addition to its TG-lowering effect, apoA-V plays a significant role in modulating HDL maturation and cholesterol metabolism.
Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice1
Qu, Shen; Perdomo, German; Su, Dongming; D’Souza, Fiona M.; Shachter, Neil S.; Dong, H. Henry
2009-01-01
Apolipoprotein A-V (apoA-V) and apoC-III are exchangeable constituents of VLDL and HDL. ApoA-V counteracts the effect of apoC-III on triglyceride (TG) metabolism with poorly defined mechanisms. To better understand the effects of apoA-V on TG and cholesterol metabolism, we delivered apoA-V cDNA into livers of hypertriglyceridemic APOC3 transgenic mice by adenovirus-mediated gene transfer. In response to hepatic apoA-V production, plasma TG levels were reduced significantly as a result of enhanced VLDL catabolism without alternations in VLDL production. This effect was associated with reduced apoC-III content in VLDL. Increased apoA-V production also resulted in decreased apoC-III and increased apoA-I content in HDL. Furthermore, apoA-V-enriched HDL was associated with enhanced LCAT activity and increased cholesterol efflux. This effect, along with apoE enrichment in HDL, contributed to HDL core expansion and α-HDL formation, accounting for significant increases in both the number and size of HDL particles. As a result, apoA-V-treated APOC3 transgenic mice exhibited decreased VLDL-cholesterol and increased HDL-cholesterol levels. ApoA-V-mediated reduction of apoC-III content in VLDL represents an important mechanism by which apoA-V acts to ameliorate hypertriglyceridemia in adult APOC3 transgenic mice. In addition, increased apoA-V levels accounted for cholesterol redistribution from VLDL to larger HDL particles. These data suggest that in addition to its TG-lowering effect, apoA-V plays a significant role in modulating HDL maturation and cholesterol metabolism PMID:17438339
Pirat, Bahar; Korkmaz, Mehmet Emin; Eroğlu, Serpil; Tayfun, Egemen; Yildirir, Aylin; Uluçam, Melek; Ozin, Bülent; Müderrisoğlu, Haldun
2004-12-01
This study was designed to compare the effects of simvastatin versus a combination of simvastatin with vitamin C or E on serum lipid profile, particularly, high-density lipoprotein (HDL)-cholesterol (C) level, in patients with a low HDL-C level. Fifty-nine women and 49 men, who had a baseline HDL-C level equal to or lower than 40 mg/dl were randomized to one of the following study treatment groups: Group S (n=39) simvastatin 20 mg/day, Group S+C (n=33) simvastatin 20 mg/day + vitamin C 500 mg/day, and Group S+E (n=36) simvastatin 20 mg/day + vitamin E 400 IU/day. The groups' lipid profiles were obtained at baseline, 3rd and 6th months. Comparing with baseline values, total-C and low-density cholesterol (LDL-C) values significantly reduced (p<0.001) and HDL-C values significantly increased (Group S--33.9+/-3.9 mg/dl vs. 39.8+/-6.9 mg/dl, Group S+C--34.2+/-3.5 mg/dl vs. 38.1+/-6.1 mg/dl, Group S+E--33.1+/-3.6 mg/dl vs. 34.8+/-5.9 mg/dl, p<0.001) on therapy within the groups; however, there were no significant differences among the groups with regards to these parameters. The HDL-C levels increased from baseline by 14.0%, 11.7% and 10.2% in Group S, S+C, and S+E, respectively (p>0.05). A combination of simvastatin with antioxidant vitamins does not offer any beneficial effect over simvastatin alone. Particularly vitamin E seems to blunt the simvastatin induced HDL-C increase.
Formation of graphitic carbon nitride and boron carbon nitride film on sapphire substrate
NASA Astrophysics Data System (ADS)
Kosaka, Maito; Urakami, Noriyuki; Hashimoto, Yoshio
2018-02-01
As a novel production method of boron carbon nitride (BCN) films, in this paper, we present the incorporation of B into graphitic carbon nitride (g-C3N4). First, we investigated the formation of g-C3N4 films via chemical vapor deposition (CVD) using melamine powder as the precursor. The formation of g-C3N4 films on a c-plane sapphire substrate was confirmed by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Raman spectroscopy measurements. The deposition temperature of g-C3N4 films was found to be suitable between 550 and 600 °C since the degradation and desorption of hexagonal C-N bonds should be suppressed. As for BCN films, we prepared BCN films via two-zone extended CVD using ammonia borane as the B precursor. Several XPS signals from B, C, and N core levels were detected from B-incorporated g-C3N4 films. While the N composition was almost constant, the marked tendencies for increasing B composition and decreasing C composition were achieved with the increase in the B incorporation, indicating the incorporation of B atoms by the substitution for C atoms. Optical absorptions were shifted to the high-energy side by B incorporation, which indicates the successful formation of BCN films using melamine and ammonia borane powders as precursors.