Sample records for heat shock-induced apoptosis

  1. Heat shock-induced apoptosis in germ line cells of Triatoma infestans Klug

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    Maria Luiza S. Mello


    Full Text Available The survival of Triatoma infestans and of somatic cells from this species is affected by heat shock. In this study, we examined the cell death responses of male germ line cells from 5th instar nymphs 7 and 30 days after heat shock exposure (40ºC, 1 h. The preparations were stained by the Feulgen reaction and the TUNEL immunocytochemical assay. Apoptosis was elicited by heat shock, with positive TUNEL responses in spermatogonial chromatin and chromosomes, spermatids and sperm cells. Spermatogonia were most affected seven days after the shock whereas some spermatids and sperm cells exhibited DNA fragmentation only thirty days after heat shock. The rate of cell death varied among the cells. In some cases, cellular differentiation was unaffected by heat shock, with DNA fragmentation occurring towards the end of spermatogenesis.Uma vez que em Triatoma infestans a sobrevivência de células somáticas e dos próprios espécimes é afetada por choques de temperatura, foi estudada a indução de morte celular em células da linhagem germinativa masculina de ninfas de 5o. estadio 7 e 30 dias após choque de 1 h a 40ºC. Os preparados foram submetidos à reação de Feulgen e ao teste imunocitoquímico TUNEL. Foi encontrada apoptose induzida pelo choque de temperatura, sendo que respostas positivas ao TUNEL foram vistas na cromatina e em cromossomos de espermatogônias e em espermátides e espermatozóides. As espermatogônias foram afetadas principalmente 7 dias após o choque, enquanto algumas espermátides e espermatozóides exibiram fragmentação de DNA apenas 30 dias após o choque. Admite-se que a velocidade com a qual avança o processo de morte celular varie nessas células. Diferenciação celular não é impedida em parte das células afetadas, permitindo que a fragmentação de seu DNA ocorra mais tardiamente, inclusive no fim da espermatogênese.

  2. Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70. (United States)

    Hsu, Shu-Fen; Hsu, Chuan-Chih; Cheng, Bor-Chih; Lin, Cheng-Hsien


    Cathepsin B is one of the major lysosomal cysteine proteases that plays an important role in apoptosis. Herein, we investigated whether Cathepsin B is involved in cardiomyocyte apoptosis caused by hyperthermic injury (HI) and heat shock protein (HSP)-70 protects these cells from HI-induced apoptosis mediated by Cathepsin. HI was produced in H9C2 cells by putting them in a circulating 43 °C water bath for 120 min, whereas preinduction of HSP-70 was produced in H9C2 cells by mild heat preconditioning (or putting them in 42 °C water bath for 30 min) 8 h before the start of HI. It was found that HI caused both cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. E-64-c, in addition to reducing Cathepsin B activity, significantly attenuated HI-induced cardiomyocyte apoptosis (evidenced by increased apoptotic cell numbers, increased tuncated Bid (t-Bid), increased cytochrome C, increased caspase-9/-3, and decreased Bcl-2/Bax) in H9C2 cells. In addition, preinduction of HSP-70 by mild heat preconditioning or inhibition of HSP-70 by Tripolide significantly attenuated or exacerbated respectively both the cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. Furthermore, the beneficial effects of pre-induction of HSP-70 by mild heat production in reducing both cardiomyocyte apoptosis and increased Cathepsin B activity caused by HI can be significantly reduced by Triptolide preconditioning. These results indicate that Cathepsin B is involved in HI-induced cardiomyocyte apoptosis in H9C2 cells and HSP-70 protects these cells from HI-induced cardiomyocyte apoptosis through Cathepsin B pathways.

  3. Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1. (United States)

    Kim, Hee-Jung; Lee, Jae-Jin; Cho, Jin-Hwan; Jeong, Jaeho; Park, A Young; Kang, Wonmo; Lee, Kong-Joo


    When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated, and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE-based proteome analysis to screen for heat shock-induced post-translationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged. We next tested whether hnRNP K plays a role in HSR by regulating HSF1 and found that hnRNP K inhibits HSF1 activity, resulting in reduced expression of hsp70 and hsp27 mRNAs. hnRNP K also reduced binding affinity of HSF1 to the heat shock element by directly interacting with HSF1 but did not affect HSF1 phosphorylation-dependent activation or nuclear localization. hnRNP K lost its ability to induce these effects when its Cys132 was substituted with Ser, Asp, or Glu. These findings suggest that hnRNP K inhibits transcriptional activity of HSF1 by inhibiting its binding to heat shock element and that the oxidation status of Cys132 in hnRNP K is critical for this inhibition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Development of a heat-shock inducible gene expression system in the red alga Cyanidioschyzon merolae.

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    Nobuko Sumiya

    Full Text Available The cell of the unicellular red alga Cyanidioschyzon merolae contains a single chloroplast and mitochondrion, the division of which is tightly synchronized by a light/dark cycle. The genome content is extremely simple, with a low level of genetic redundancy, in photosynthetic eukaryotes. In addition, transient transformation and stable transformation by homologous recombination have been reported. However, for molecular genetic analyses of phenomena that are essential for cellular growth and survival, inducible gene expression/suppression systems are needed. Here, we report the development of a heat-shock inducible gene expression system in C. merolae. CMJ101C, encoding a small heat shock protein, is transcribed only when cells are exposed to an elevated temperature. Using a superfolder GFP as a reporter protein, the 200-bp upstream region of CMJ101C orf was determined to be the optimal promoter for heat-shock induction. The optimal temperature to induce expression is 50°C, at which C. merolae cells are able to proliferate. At least a 30-min heat shock is required for the expression of a protein of interest and a 60-min heat shock yields the maximum level of protein expression. After the heat shock, the mRNA level decreases rapidly. As an example of the system, the expression of a dominant negative form of chloroplast division DRP5B protein, which has a mutation in the GTPase domain, was induced. Expression of the dominant negative DRP5B resulted in the appearance of aberrant-shaped cells in which two daughter chloroplasts and the cells are still connected by a small DRP5B positive tube-like structure. This result suggests that the dominant negative DRP5B inhibited the final scission of the chloroplast division site, but not the earlier stages of division site constriction. It is also suggested that cell cycle progression is not arrested by the impairment of chloroplast division at the final stage.

  5. Jasmonic acid is a crucial signal transducer in heat shock induced sesquiterpene formation in Aquilaria sinensis (United States)

    Xu, Yan-Hong; Liao, Yong-Cui; Zhang, Zheng; Liu, Juan; Sun, Pei-Wen; Gao, Zhi-Hui; Sui, Chun; Wei, Jian-He


    Agarwood, a highly valuable resinous and fragrant heartwood of Aquilaria plants, is widely used in traditional medicines, incense and perfume. Only when Aquilaria trees are wounded by external stimuli do they form agarwood sesquiterpene defensive compounds. Therefore, understanding the signaling pathway of wound-induced agarwood formation is important. Jasmonic acid (JA) is a well-characterized molecule that mediates a plant’s defense response and secondary metabolism. However, little is known about the function of endogenous JA in agarwood sesquiterpene biosynthesis. Here, we report that heat shock can up-regulate the expression of genes in JA signaling pathway, induce JA production and the accumulation of agarwood sesquiterpene in A. sinensis cell suspension cultures. A specific inhibitor of JA, nordihydroguaiaretic acid (NDGA), could block the JA signaling pathway and reduce the accumulation of sesquiterpene compounds. Additionally, compared to SA and H2O2, exogenously supplied methyl jasmonate has the strongest stimulation effect on the production of sesquiterpene compounds. These results clearly demonstrate the central induction role of JA in heat-shock-induced sesquiterpene production in A. sinensis. PMID:26902148

  6. Prevention of Trauma/Hemorrhagic Shock-Induced Mortality,Apoptosis, Inflammation and Mitochondrial Dysfunction (United States)


    including identification of the ER membrane bound sensors of ER stress8–11. Homologues for these sensors and their targets have been identified in mammals...a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the...followed by Pseudomonas aeruginosa 25 (PA) pneumonia to assess the effect of alveolar epithelial cell (AEC) apoptosis, and its 26 prevention by IL-6

  7. Heat shock-induced dissociation of TRF2 from telomeres does not initiate a telomere-dependent DNA damage response. (United States)

    Petrova, Nadezhda V; Velichko, Artem K; Kantidze, Omar L; Razin, Sergey V


    Telomeric repeat binding factor 2 (TRF2) is a well-studied shelterin complex subunit that plays a major role in the protection of chomosome ends and the prevention of the telomere-associated DNA damage response. We show that heat shock induces the dissociation of TRF2 from telomeres in human primary and cancer cell cultures. TRF2 is not simply degraded in response to heat shock, but redistributed thoughout the nucleoplasm. This TRF2 depletion/redistribution does not initiate the DNA damage response at chomosome termini. © 2014 International Federation for Cell Biology.

  8. Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae.

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    Tomas Grousl

    Full Text Available In response to severe environmental stresses eukaryotic cells shut down translation and accumulate components of the translational machinery in stress granules (SGs. Since they contain mainly mRNA, translation initiation factors and 40S ribosomal subunits, they have been referred to as dominant accumulations of stalled translation preinitiation complexes. Here we present evidence that the robust heat shock-induced SGs of S. cerevisiae also contain translation elongation factors eEF3 (Yef3p and eEF1Bγ2 (Tef4p as well as translation termination factors eRF1 (Sup45p and eRF3 (Sup35p. Despite the presence of the yeast prion protein Sup35 in heat shock-induced SGs, we found out that its prion-like domain is not involved in the SGs assembly. Factors eEF3, eEF1Bγ2 and eRF1 were accumulated and co-localized with Dcp2 foci even upon a milder heat shock at 42°C independently of P-bodies scaffolding proteins. We also show that eEF3 accumulations at 42°C determine sites of the genuine SGs assembly at 46°C. We suggest that identification of translation elongation and termination factors in SGs might help to understand the mechanism of the eIF2α factor phosphorylation-independent repression of translation and SGs assembly.

  9. Gamma-effects on 2-dimensional transonic aerodynamics. [specific heat ratio due to shock induced separation (United States)

    Tuzla, K.; Russell, D. A.; Wai, J. C.


    Nonlifting 10% biconvex airfoils are mounted in a 30 x 40 cm Ludwieg-tube-driven transonic test-section and the flow field recorded with a holographic interferometer. Nitrogen, argon, and carbon dioxide are used as the principal test gases. Experiments are conducted with Reynolds number based on chord of (0.5-3.5) x 10 to the 6th with Mach numbers of 0.70, 0.75, and 0.80. Supporting calculations use inviscid transonic small-disturbance and full-potential computer codes coupled with simple integral boundary-layer modeling. Systematic studies show that significant gamma-effects can occur due to shock-induced separation.

  10. Prediction and measurement of heat transfer rates for the shock-induced unsteady laminar boundary layer on a flat plate (United States)

    Cook, W. J.


    The unsteady laminar boundary layer induced by the flow-initiating shock wave passing over a flat plate mounted in a shock tube was theoretically and experimentally studied in terms of heat transfer rates to the plate for shock speeds ranging from 1.695 to 7.34 km/sec. The theory presented by Cook and Chapman for the shock-induced unsteady boundary layer on a plate is reviewed with emphasis on unsteady heat transfer. A method of measuring time-dependent heat-transfer rates using thin-film heat-flux gages and an associated data reduction technique are outlined in detail. Particular consideration is given to heat-flux measurement in short-duration ionized shocktube flows. Experimental unsteady plate heat transfer rates obtained in both air and nitrogen using thin-film heat-flux gages generally agree well with theoretical predictions. The experimental results indicate that the theory continues to predict the unsteady boundary layer behavior after the shock wave leaves the trailing edge of the plate even though the theory is strictly applicable only for the time interval in which the shock remains on the plate.

  11. Quercetin suppresses heat shock-induced nuclear translocation of Hsp72

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    Antoni Gawron


    Full Text Available The effect of quercetin and heat shock on the Hsp72 level and distribution in HeLa cells was studied by Western blotting, indirect immunofluorescence and immunogold electron microscopy. In control cells and after quercetin treatment, Hsp72 was located both in the cytoplasm and in the nucleus in comparable amounts. After hyperthermia, the level of nuclear Hsp72 raised dramatically. Expression of Hsp72 in cytoplasm was also higher but not to such extent as that observed in the nucleus. Preincubation of heated cells with quercetin inhibited strong Hsp72 expression observed after hyperthermia and changed the intracellular Hsp72 distribution. The cytoplasmic level of protein exceeded the nuclear one, especially around the nucleus, where the coat of Hsp72 was noticed. Observations indicating that quercetin was present around and in the nuclear envelope suggested an involvement of this drug in the inhibition of nuclear translocation. Our results indicate that pro-apoptotic activity of quercetin may be correlated not only with the inhibition of Hsp72 expression but also with suppression of its migration to the nucleus.

  12. Characterization of a heat-shock-inducible hsp70 gene of the green alga Volvox carteri. (United States)

    Cheng, Qian; Hallmann, Armin; Edwards, Lisseth; Miller, Stephen M


    The green alga Volvox carteri possesses several thousand cells, but just two cell types: large reproductive cells called gonidia, and small, biflagellate somatic cells. Gonidia are derived from large precursor cells that are created during embryogenesis by asymmetric cell divisions. The J domain protein GlsA (Gonidialess A) is required for these asymmetric divisions and is believed to function with an Hsp70 partner. As a first step toward identifying this partner, we cloned and characterized V. carteri hsp70A, which is orthologous to HSP70A of the related alga Chlamydomonas reinhardtii. Like HSP70A, V. carteri hsp70A contains multiple heat shock elements (HSEs) and is highly inducible by heat shock. Consistent with these properties, Volvox transformants that harbor a glsA antisense transgene that is driven by an hsp70A promoter fragment express Gls phenotypes that are temperature-dependent. hsp70A appears to be the only gene in the genome that encodes a cytoplasmic Hsp70, so we conclude that Hsp70A is clearly the best candidate to be the chaperone that participates with GlsA in asymmetric cell division.

  13. H2Av facilitates H3S10 phosphorylation but is not required for heat shock-induced chromatin decondensation or transcriptional elongation. (United States)

    Li, Yeran; Wang, Chao; Cai, Weili; Sengupta, Saheli; Zavortink, Michael; Deng, Huai; Girton, Jack; Johansen, Jørgen; Johansen, Kristen M


    A model has been proposed in which JIL-1 kinase-mediated H3S10 and H2Av phosphorylation is required for transcriptional elongation and heat shock-induced chromatin decondensation. However, here we show that although H3S10 phosphorylation is indeed compromised in the H2Av null mutant, chromatin decondensation at heat shock loci is unaffected in the absence of JIL-1 as well as of H2Av and that there is no discernable decrease in the elongating form of RNA polymerase II in either mutant. Furthermore, mRNA for the major heat shock protein Hsp70 is transcribed at robust levels in both H2Av and JIL-1 null mutants. Using a different chromatin remodeling paradigm that is JIL-1 dependent, we provide evidence that ectopic tethering of JIL-1 and subsequent H3S10 phosphorylation recruits PARP-1 to the remodeling site independently of H2Av phosphorylation. These data strongly suggest that H2Av or H3S10 phosphorylation by JIL-1 is not required for chromatin decondensation or transcriptional elongation in Drosophila. © 2017. Published by The Company of Biologists Ltd.

  14. Role of heat shock proteins in cell apoptosis

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    Arleta Kaźmierczuk


    Full Text Available Apoptosis is, apart from necrosis and autophagy, one of the possible cell death mechanisms eliminating needless, not normal or infected cells. This process ensures quantitative and qualitative cell control of organisms. Apoptosis is tightly regulated, it requires both activation of a large number of genes and energy input. Up-to-date two main apoptotic pathways have been recognized – external/receptor and internal, processed with the participation of mitochondria. Heat shock proteins HSPs, the molecules known from their chaperone activity and molecular conservatism, play essential functions in the course of apoptosis. Among that proteins family, i.e. HSP100, 90, 70, 60, 40 and small molecular (sHSP, there are agents mainly protective against programmed cell death. However, in some conditions some of these proteins may promote apoptosis. This review describes different key apoptotic proteins interacting with main members of HSP family and the consequence of these events for cell survival or apoptosis.

  15. Heat shock induced excision of selectable marker genes in transgenic banana by the Cre-lox site-specific recombination system. (United States)

    Chong-Pérez, Borys; Kosky, Rafael G; Reyes, Maritza; Rojas, Luis; Ocaña, Bárbara; Tejeda, Marisol; Pérez, Blanca; Angenon, Geert


    Selectable marker genes are indispensable for efficient production of transgenic events, but are no longer needed after the selection process and may cause public concern and technological problems. Although several gene excision systems exist, few have been optimized for vegetatively propagated crops. Using a Cre-loxP auto-excision strategy, we obtained transgenic banana plants cv. Grande Naine (Musa AAA) devoid of the marker gene used for selection. We used T-DNA vectors with the cre recombinase gene under control of a heat shock promoter and selectable marker gene cassettes placed between two loxP sites in direct orientation, and a gene of interest inserted outside of the loxP sites. Heat shock promoters pGmHSP17.6-L and pHSP18.2, from soybean and Arabidopsis respectively, were tested. A transient heat shock treatment of primary transgenic embryos was sufficient for inducing cre and excising cre and the marker genes. Excision efficiency, as determined by PCR and Southern hybridization was 59.7 and 40.0% for the GmHSP17.6-L and HSP18.2 promoters, respectively. Spontaneous excision was not observed in 50 plants derived from untreated transgenic embryos. To our knowledge this is the first report describing an efficient marker gene removal system for banana. The method described is simple and might be generally applicable for the production of marker-free transgenic plants of many crop species. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Shock-induced phase transformation in tantalum. (United States)

    Hsiung, Luke L


    A TEM study of pure tantalum and tantalum-tungsten alloys explosively shocked at a peak pressure of 30 GPa is presented. While no omega phase was found in shock-recovered pure Ta and Ta-5W which mainly contain a cellular dislocation structure, a shock-induced omega phase was found in Ta-10W which contains evenly distributed dislocations with a density higher than 1 × 10(12) cm( - 2). The shock-induced [Formula: see text] (hexagonal) transition occurs when the dynamic recovery of dislocations becomes largely suppressed in Ta-10W shocked under dynamic-pressure conditions. A dislocation-based mechanism is proposed for the shock-induced phase transformation.

  17. Benjamin Franklin and Shock-Induced Amnesia (United States)

    Finger, Stanley; Zaromb, Franklin


    Shock-induced amnesia received considerable attention after Cerletti popularized electroconvulsive shock therapy in the late 1930s. Yet, often overlooked is the fact that Benjamin Franklin recognized that passing electricity through the head could affect memory for the traumatic event. Franklin described his findings on himself and others in…

  18. Shock-induced chemistry in organic materials

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    Dattelbaum, Dana M [Los Alamos National Laboratory; Sheffield, Steve [Los Alamos National Laboratory; Engelke, Ray [Los Alamos National Laboratory; Manner, Virginia [Los Alamos National Laboratory; Chellappa, Raja [Los Alamos National Laboratory; Yoo, Choong - Shik [WASHINGTON STATE UNIV


    The combined 'extreme' environments of high pressure, temperature, and strain rates, encountered under shock loading, offer enormous potential for the discovery of new paradigms in chemical reactivity not possible under more benign conditions. All organic materials are expected to react under these conditions, yet we currently understand very little about the first bond-breaking steps behind the shock front, such as in the shock initiation of explosives, or shock-induced reactivity of other relevant materials. Here, I will present recent experimental results of shock-induced chemistry in a variety of organic materials under sustained shock conditions. A comparison between the reactivity of different structures is given, and a perspective on the kinetics of reaction completion under shock drives.

  19. Pressure-Temperature History of Shock-Induced Melt Veins (United States)

    Decarli, P. S.; Sharp, T. G.; Xie, Z.; Aramovich, C.


    Shock-induced melt veins that occur in chondrites commonly contain metastable high-pressure phases such as (Mg,Fe)SiO3-perovskite, akimotoite, ringwoodite, and majorite, that crystallized from the melt at high pressure. The metastable high-pressure minerals invert rapidly to stable low-pressure phases if they remain at high temperatures after the pressure is released. Although shock compression mechanisms permit rapid heating of the vein volume, adiabatic cooling on decompression is negligible because of the relative incompressibility of the material in the vein. The presence of metastable mantle minerals in a vein thus implies that the vein was quenched via thermal conduction to adjacent cooler material at high pressure. The quenching time of the vein can be determined from ordinary heat flow calculations (Langenhorst and Poirier, 2000), given knowledge of the vein dimensions and the temperatures at the time of vein formation in both the vein and the surrounding material. We have calculated a synthetic Hugoniot for the Tenham L6 chondrite to estimate bulk post-shock and shock temperatures as a function of shock pressure. Assuming a superliquidus temperature of 2500°C for the melt vein, we use a simple thermal model to investigate then thermal histories of melt veins during shock. The variation in crystallization assemblages within melt veins can be explained in terms of variable cooling rates. Survival of (Mg,Fe)SiO3-perovskite in Tenham (Tomioka and Fugino, 1997) requires that melt veins cooled to below 565°C before pressure release, which further constrains shock pressure, duration of the pressure pulse and cooling histories.

  20. Heat shock-induced biphasic Ca(2+) signature and OsCaM1-1 nuclear localization mediate downstream signalling in acquisition of thermotolerance in rice (Oryza sativa L.). (United States)

    Wu, Hui-Chen; Luo, Dan-Li; Vignols, Florence; Jinn, Tsung-Luo


    We investigated heat shock (HS)-triggered Ca(2+) signalling transduced by a Ca(2+) sensor, calmodulin (CaM), linked to early transcriptome changes of HS-responsive genes in rice. We observed a biphasic [Ca(2+) ](cyt) signature in root cells that was distinct from that in epicotyl and leaf cells, which showed a monophasic response after HS. Treatment with Ca(2+) and A23187 generated an intense and sustained increase in [Ca(2+) ](cyt) in response to HS. Conversely, treatment with Ca(2+) chelator, L-type Ca(2+) channel blocker and CaM antagonist, but not intracellular Ca(2+) release inhibitor, strongly inhibited the increased [Ca(2+) ](cyt) . HS combined with Ca(2+) and A23187 accelerated the expression of OsCaM1-1 and sHSPC/N genes, which suggests that the HS-induced apoplastic Ca(2+) influx is responsible for the [Ca(2+) ](cyt) response and downstream HS signalling. In addition, the biphasic response of OsCaM1-1 in the nucleus followed the Ca(2+) signature, which may provide the information necessary to direct HS-related gene expression. Overexpression of OsCaM1-1 induced the expression of Ca(2+) /HS-related AtCBK3, AtPP7, AtHSF and AtHSP at a non-inducing temperature and enhanced intrinsic thermotolerance in transgenic Arabidopsis. Therefore, HS-triggered rapid increases in [Ca(2+) ](cyt) , together with OsCaM1-1 expression and its nuclear localization, are important in mediating downstream HS-related gene expression for the acquisition of thermotolerance in rice. © 2012 Blackwell Publishing Ltd.

  1. Intermittency and Topology of Shock Induced Mixing (United States)

    Tellez, Jackson; Redondo, Jose M.; Ben Mahjoub, Otman; Malik, Nadeem; Vila, Teresa


    The advance of a Rayleigh-Taylor front is described in Linden & Redondo (1991),[1-3] and may be shown to follow a quadratic law in time where the width of the growing region of instability depends on the local mixing efficiency of the different density fluids that accelerate against each other g is the acceleration and A is the Atwood number defined as the diference of densities divided by their sum. This results show the independence of the large amplitude structures on the initial conditions the width of the mixing region depends also on the intermittency of the turbulence. Then dimensional analysis may also depend on the relevant reduced acceleration driven time and the molecular reactive time akin to Damkholer number and the fractal structure of the contact zone [2,4]. Detailed experiments and simulations on RT and RM shock induced fronts analized with respect to structure functions are able to determine which mechanisms are most effective in local mixing which increase the effective fractal dimension, as well as the effect of higher order geometrical parameters, such as the structure functions, in non-homogeneous fluids (Mahjoub et al 1998)[5]. The structure of a Mixing blob shows a relatively sharp head with most of the mixing taking place at the sides due to what seems to be shear instability very similar to the Kelvin-Helmholtz instabilities, but with sideways accelerations. The formation of the blobs and spikes with their secondary instabilities produces a turbulent cascade, evident just after about 1 non-dimensional time unit, from a virtual time origin that takes into account the linear growth phase, as can be seen by the growth of the fractal dimension for different volume fractions. Two-dimensional cuts of the 3D flow also show that vortex flows have closed or spiral streamlines around their core. Examples of such flows can be also seen in the laboratory, for example at the interface of atwo-layer stratified fluid in a tank in which case streamlines

  2. Numerical Simulations of Shock-Induced Mixing and Combustion

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    Bell, J B; Day, M; Kuhl, A L


    In this paper we use numerical simulation to investigate shock-induced ignition and combustion of a hydrocarbon gas. The focus of this paper is on quantifying the effect of fidelity in the chemical kinetics on the overall solution. We model the system using the compressible Navier Stokes equations for a reacting mixture. These equations express conservation of species mass, momentum, total energy.

  3. Thermal shock induced oxidation of beryllium (United States)

    Spilker, B.; Linke, J.; Pintsuk, G.; Wirtz, M.


    Beryllium has been chosen as a plasma facing material for the first wall of the experimental fusion reactor ITER, mainly because of its low atomic number and oxygen getter capabilities, which are favorable for a high plasma performance. While the steady state operational temperature of 250 °C has no deteriorating effect on the beryllium surface, transient plasma events can deposit power densities of up to 1 GW m‑2 on the beryllium armor tiles. Previous research has shown that the oxidation of beryllium can occur under these thermal shock events. In the present study, S-65 grade beryllium specimens were exposed to 100 thermal shocks with an absorbed power density of 0.6 GW m‑2 and a pulse duration of 1 ms, leading to a peak surface temperature of ∼800 °C. The induced surface morphology changes were compared to a steady state heated specimen at the same surface temperature with a holding time of 150 s. As a result, a pitting structure with an average pit diameter of ∼0.45 μm was observed on the thermal shock loaded surface, which was caused by beryllium oxide grain nucleation and subsequent erosion of the weakly bound beryllium oxide particles. In contrast, the steady state heated surface exhibited a more homogeneous beryllium oxide layer featuring small pits with diameters of tens of nm and showed the beryllium oxide grain nucleation in a beginning stage. The experiment demonstrated that thermal shock loading conditions can significantly accelerate the beryllium oxide grain nucleation. The resulting surface morphology change can potentially alter the fusion application relevant erosion, absorption, and retention characteristics of beryllium.

  4. Ghrelin inhibits apoptosis signal-regulating kinase 1 activity via upregulating heat-shock protein 70. (United States)

    Yang, Min; Hu, Shengdi; Wu, Bin; Miao, Yanying; Pan, Hui; Zhu, Shigong


    Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), which has been originally isolated from rat stomach. It has been reported that ghrelin inhibited apoptosis in several cells, such as cardiomyocytes, endothelial cells, adipocyte, adrenal zona glomerulosa cells, pancreatic beta-cells, osteoblastic MC3T3-E1 cells, intestinal epithelial cells and hypothalamic neurons. However, it is unknown whether heat-shock protein 70 (HSP70) or apoptosis signal-regulating kinase 1 (ASK1) is the important target molecule which mediates the anti-apoptotic effects of ghrelin. We show that ghrelin inhibited ASK1 activity induced by sodium nitroprusside (SNP), inhibited ASK1-mediated caspase 3 activation and apoptosis in PC12 cells. Ghrelin promoted expression of HSP70. Quercetin, an inhibitor of HSP70, blocked the effects of ghrelin on ASK1 activity. Thus, ghrelin inhibits ASK1-mediated apoptosis and ASK1 activation by a mechanism involving induction of HSP70 expression. The results of the present study suggest the therapeutic potential of ghrelin for some pathological processes or disorders.

  5. Heat-Labile Enterotoxin-Induced PERK-CHOP Pathway Activation Causes Intestinal Epithelial Cell Apoptosis

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    Xi Lu


    Full Text Available Enterotoxigenic Escherichia coli (ETEC is a leading cause of diarrhea among children and travelers in developing countries, and heat-labile enterotoxin (LT is one of the most important virulence factors. The pathogenesis of and virulence factors associated with ETEC have been well-characterized; however, the extent to which ETEC damages host cells remains unclear. In this study, we found that LT could induce decreases in intestinal epithelial cell viability and induce apoptosis in a dose- and time- dependent manner in both HCT-8 and Caco-2 cells. We analyzed the expression profiles of apoptosis-related proteins via protein array technology and found that Bax, p-p53(S46, cleaved caspase-3, and TNFRI/TNFRSF1A expression levels were significantly up-regulated in wild-type ETEC- but not in ΔLT ETEC-infected HCT-8 cells. Bax is essential for endoplasmic reticulum (ER stress-triggered apoptosis, and our RNAi experiments showed that the PERK-eIF2-CHOP pathway and reactive oxygen species (ROS are also main participants in this process. LT-induced ROS generation was decreased in CHOP-knockdown HCT-8 cells compared to that in control cells. Moreover, pretreatment with the ROS inhibitor NAC down-regulated GRP78, CHOP, Bim, and cleaved caspase-3 expression, resulting in a reduction in the apoptosis rate from 36.2 to 20.3% in LT-treated HCT-8 cells. Furthermore, ROS inhibition also attenuated LT-induced apoptosis in the small intestinal mucosa in the ETEC-inoculation mouse model.

  6. Differential effects of catalase on apoptosis induction in human promonocytic cells. Relationships with heat-shock protein expression. (United States)

    Sancho, Patricia; Troyano, Alfonso; Fernández, Carlos; De Blas, Elena; Aller, Patricio


    The administration of the H(2)O(2)-specific scavenger catalase attenuated the generation of apoptosis by the antitumor drugs etoposide, camptothecin, doxorubicin, and cisplatin in U-937 human promonocytic cells. By contrast, the antioxidant potentiated the generation of apoptosis by the inducers of the stress response, heat shock and cadmium, in this and other myeloid cell types. Catalase also increased the heat shock-provoked stimulation of caspase-3 and -9 activities, as well as the release of cytochrome c from mitochondria to the cytosol. The potentiation of cell death by catalase correlated with its capacity to inhibit the stress response, as demonstrated by the suppression of 70- or 27-kDa heat-shock protein expression and the inhibition of heat-shock transcription factor 1 binding activity. Conversely, the toxicity of catalase plus heat shock was attenuated when the cells were preconditioned with a soft heating, which elevated the 70-kDa heat-shock protein levels. By contrast with catalase, the antioxidants superoxide dismutase and probucol did not inhibit heat-shock protein expression or affect apoptosis in U-937 cells. Finally, it was observed that the antitumor drugs did not activate the stress response in U-937 cells and that catalase failed to inhibit HSP expression and to potentiate apoptosis in heat shock-treated RPMI 8866 lymphoblastic cells. Taken together, these results provide the first demonstration of a proapoptotic action of catalase, suggest that H(2)O(2) is a critical regulator of both apoptosis and the stress response, and corroborate the antiapoptotic action of heat-shock proteins in myeloid cells.

  7. Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein

    Directory of Open Access Journals (Sweden)

    Sack Ragna


    Full Text Available Abstract Background The serine/threonine protein kinase B (PKB/Akt is involved in insulin signaling, cellular survival, and transformation. Carboxyl-terminal modulator protein (CTMP has been identified as a novel PKB binding partner in a yeast two-hybrid screen, and appears to be a negative PKB regulator with tumor suppressor-like properties. In the present study we investigate novel mechanisms by which CTMP plays a role in apoptosis process. Results CTMP is localized to mitochondria. Furthermore, CTMP becomes phosphorylated following the treatment of cells with pervanadate, an insulin-mimetic. Two serine residues (Ser37 and Ser38 were identified as novel in vivo phosphorylation sites of CTMP. Association of CTMP and heat shock protein 70 (Hsp70 inhibits the formation of complexes containing apoptotic protease activating factor 1 and Hsp70. Overexpression of CTMP increased the sensitivity of cells to apoptosis, most likely due to the inhibition of Hsp70 function. Conclusion Our data suggest that phosphorylation on Ser37/Ser38 of CTMP is important for the prevention of mitochondrial localization of CTMP, eventually leading to cell death by binding to Hsp70. In addition to its role in PKB inhibition, CTMP may therefore play a key role in mitochondria-mediated apoptosis by localizing to mitochondria.

  8. Shock-induced temperatures of MgO


    Svendsen, Bob; Ahrens, Thomas J.


    Shock-compressed MgO radiates thermally at temperatures between 2900 and 3700 K in the 170–200 GPa pressure range. A simple energy-transport model of the shocked-MgO-targets distinguishes between different shock-induced radiation sources in these targets and provides estimates of spectral absorption-coefficients, α_(λMgO), for shocked MgO (e.g. at 203 GPa, α_(λMgO) ~ 630, 7500, 4200 and 3800 m^(−1), at 450, 600, 750 and 900 nm, respectively). The experimentally inferred temperatures of the sh...

  9. The role of heat shock protein (HSP as inhibitor apoptosis in hypoxic conditions of bone marrow stem cell culture

    Directory of Open Access Journals (Sweden)

    Sri Wigati Mardi Mulyani


    Full Text Available Background: The concept of stem cell therapy is one of the new hope as a medical therapy on salivary gland defect. However, the lack of viability of the transplanted stem cells survival rate led to the decrease of effectiveness of stem cell therapy. The underlying assumption in the decrease of viability and function of stem cells is an increase of apoptosis incidence. It suggests that the microenvironment in the area of damaged tissues is not conducive to support stem cell viability. One of the microenvironment is the hypoxia condition. Several scientific journals revealed that the administration of hypoxic cell culture can result in stress cells but on the other hand the stress condition of the cells also stimulates heat shock protein 27 (HSP 27 as antiapoptosis through inhibition of caspase 9. Purpose: The purpose of this study was to examine the role of heat shock protein 27 as inhibitor apoptosis in hypoxic conditions of bone marrow stem cell culture. Methods: Stem cell culture was performed in hypoxic conditions (O2 1% and measured the resistance to apoptosis through HSP 27 and caspase 9 expression of bone marrow mesenchymal stem cells by using immunoflorecence and real time PCR. Results: The result of study showed that preconditioning hypoxia could inhibit apoptosis through increasing HSP 27 and decreasing level of caspase 9. Conclusion: The study suggested that hypoxic precondition could reduce apoptosis by increasing amount of heat shock protein 27 and decreasing caspase 9.Latar belakang: Konsep terapi stem cell merupakan salah satu harapan baru sebagai terapi medis kelainan kelenjar ludah. Namun, rendahnya viabilitas stem cell yang ditransplantasikan menyebabkan penurunan efektivitas terapi. Asumsi yang mendasari rendahnya viabilitas dan fungsi stem cell adalah tingginya kejadian apoptosis. Hal ini menunjukkan bahwa lingkungan mikro di daerah jaringan yang rusak tidak kondusif untuk mendukung viabilitas stem cell. Salah satu lingkungan

  10. Shock induced endotheliopathy (SHINE) in acute critical illness

    DEFF Research Database (Denmark)

    Johansson, Pär Ingemar; Stensballe, Jakob; Ostrowski, Sisse Rye


    One quarter of patients suffering from acute critical illness such as severe trauma, sepsis, myocardial infarction (MI) or post cardiac arrest syndrome (PCAS) develop severe hemostatic aberrations and coagulopathy, which are associated with excess mortality. Despite the different types of injurious...... "hit", acutely critically ill patients share several phenotypic features that may be driven by the shock. This response, mounted by the body to various life-threatening conditions, is relatively homogenous and most likely evolutionarily adapted. We propose that shock-induced sympatho......-adrenal hyperactivation is a critical driver of endothelial cell and glycocalyx damage (endotheliopathy) in acute critical illness, with the overall aim of ensuring organ perfusion through an injured microvasculature. We have investigated more than 3000 patients suffering from different types of acute critical illness...

  11. Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage. (United States)

    Hsu, Chuan-Chih; Chen, Sheng-Hsien; Lin, Cheng-Hsien; Yung, Ming-Chi


    Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 µg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1β, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage

  12. Heat shock protein 70, heat shock protein 32, and vascular endothelial growth factor production and their effects on lipopolysaccharide-induced apoptosis in porcine aortic endothelial cells. (United States)

    Bernardini, Chiara; Zannoni, Augusta; Turba, Maria Elena; Fantinati, Paolo; Tamanini, Carlo; Bacci, Maria Laura; Forni, Monica


    Lipopolysaccharide (LPS) is a highly proactive molecule that causes in vivo a systemic inflammatory response syndrome and activates in vitro the inflammatory pathway in different cellular types, including endothelial cells (EC). Because the proinflammatory status could lead to EC injury and apoptosis, the expression of proinflammatory genes must be finely regulated through the induction of protective genes. This study aimed at determining whether an LPS exposure is effective in inducing apoptosis in primary cultures of porcine aortic endothelial cells and in stimulating heat shock protein (Hsp)70 and Hsp32 production as well as vascular endothelial growth factor (VEGF) secretion. Cells between third and eighth passage were exposed to 10 microg/mL LPS for 1, 7, 15, and 24 hours (time-course experiments) or to 1, 10, and 100 microg/mL LPS for 7 and 15 hours (dose-response experiments). Apoptosis was not affected by 1 microg/mL LPS but significantly increased in a dose-dependent manner with the highest LPS doses. Furthermore, apoptosis rate increased only till 15 hours of LPS exposure. LPS stimulated VEGF secretion in a dose-dependent manner; its effect became significant after 7 hours and reached a plateau after 15 hours. Both Hsp70 and Hsp32 expressions were induced by LPS in a dose-dependent manner after 7 hours. Subsequent studies were addressed to evaluate the protective role of Hsp32, Hsp70, and VEGF. Hemin, an Hsp32 inducer (5, 20, 50 microM), and recombinant VEGF (100 and 200 ng/mL), were added to the culture 2 hours before LPS (10 microg/mL for 24 hours); to induce Hsp70 expression, cells were heat shocked (42 degrees C for 1 hour) 15 hours before LPS (10 microg/mL for 24 hours). Hemin exposure upregulated Hsp32 expression in a dose-dependent manner and protected cells against LPS-induced apoptosis. Heat shock (HS) stimulated Hsp70 expression but failed to reduce LPS-induced apoptosis; VEGF addition did not protect cells against LPS-induced apoptosis at any

  13. Formation mechanism of the shock-induced particle jetting (United States)

    Xue, Kun

    Granular shells or rings dispersed by the impulsive shock loadings disintegrate into macroscopic particle agglomerates which soon protrude into particle jets. Predicting the number of shock-induced particle jets requires the knowledge of the formation mechanism of the particle jetting. We carried out the numerical simulations of the shock dispersal of the semi-two dimensional particle rings using the discrete element method. The simulations reveal a two-staged jetting formation process. The first phase features the transition of the homogeneous particle flows to the localized shear flows which are the precursors of the incipient jets. The incipient jets undergo the substantial annihilation. The number of jets equals to the number of incipient jets subtracted by that of eliminated ones. The former depends on the heterogeneous structure of the network of force chains which is a function of the perimeter of the inner surface, the packing density and the material properties. The latter is determined by the shock loading, the packing density and the thickness of the ring. A physics based model has been proposed to account for the number of jet, which formularizes the initiation and the elimination processes of the incipient jets.

  14. High Strain Rate and Shock-Induced Deformation in Metals (United States)

    Ravelo, Ramon


    Large-scale non-equilibrium molecular Dynamics (MD) simulations are now commonly used to study material deformation at high strain rates (10^9-10^12 s-1). They can provide detailed information-- such as defect morphology, dislocation densities, and temperature and stress profiles, unavailable or hard to measure experimentally. Computational studies of shock-induced plasticity and melting in fcc and bcc single, mono-crystal metals, exhibit generic characteristics: high elastic limits, large directional anisotropies in the yield stress and pre-melting much below the equilibrium melt temperature for shock wave propagation along specific crystallographic directions. These generic features in the response of single crystals subjected to high strain rates of deformation can be explained from the changes in the energy landscape of the uniaxially compressed crystal lattice. For time scales relevant to dynamic shock loading, the directional-dependence of the yield strength in single crystals is shown to be due to the onset of instabilities in elastic-wave propagation velocities. The elastic-plastic transition threshold can accurately be predicted by a wave-propagation stability analysis. These strain-induced instabilities create incipient defect structures, which can be quite different from the ones, which characterize the long-time, asymptotic state of the compressed solid. With increase compression and strain rate, plastic deformation via extended defects gives way to amorphization associated with the loss in shear rigidity along specific deformation paths. The hot amorphous or (super-cooled liquid) metal re-crystallizes at rates, which depend on the temperature difference between the amorphous solid and the equilibrium melt line. This plastic-amorphous transition threshold can be computed from shear-waves stability analyses. Examples from selected fcc and bcc metals will be presented employing semi-empirical potentials of the embedded atom method (EAM) type as well as

  15. Long- but not short-term heat acclimation produces an apoptosis-resistant cardiac phenotype: a lesson from heat stress and ischemic/reperfusion insults (United States)

    Assayag, Miri; Gerstenblith, Gary; Stern, Michael D.


    Long-term heat acclimation (AC, 30d/34°C) is a phenotypic adaptation leading to increased thermotolerance during heat stress (HS, 2 h 41°C). AC also renders protection against ischemic/reperfusion (I/R, 30′ global ischemia/40′ reperfusion) insult via cross-tolerance mechanisms. In contrast to the protected AC phenotype, the onset of acclimation (34°C, AC2d) is characterized by cellular perturbations, suggesting increased susceptibility to HS and I/R insults. In this investigation, we tested the hypothesis that apoptosis resistance is part of the AC repertoire and that, at the initial phase of acclimation (AC2d), cytoprotection is impaired. TUNEL staining and caspase 3 levels in HS and I/R insulted hearts affirmed this hypothesis. To examine the role of the mitochondria in life/death decision in AC2d and 30d AC settings vs. control hearts, we studied the Bcl-2 apoptotic cascade and found increased levels of the anti-apoptotic Bcl-XL and decreased levels of the pro-apoptotic death promoter Bad in hearts from AC2d and AC animals. In these groups, cytochrome c (cyt c) was elevated in the mitochondria and remained unchanged in the cytosol. This adaptation was insufficient to negate apoptosis in AC2d rats. At this early acclimation phase (and in controls), increased caspase 8 activity confirmed activation of the extrinsic (Fas ligand) apoptosis pathway. In conclusion, the elevated Bcl-XL/Bad ratio and decreased cyt c leakage to the cytosol are insufficient to protect the heart and interactions with additional cytoprotective pathways involved in acclimation (elevated HSP70, ROS, and sarcolemmal adaptations to abolish extrinsic apoptosis pathways) are required to induce the apoptosis-resistant AC phenotype. Electronic supplementary material The online version of this article (doi:10.1007/s12192-010-0178-x) contains supplementary material, which is available to authorized users. PMID:20221856

  16. Heat shock preconditioning protects against ER stress-induced apoptosis through the regulation of the BH3-only protein BIM

    Directory of Open Access Journals (Sweden)

    Donna Kennedy


    Full Text Available A mild heat shock (HS preconditioning and acquisition of thermotolerance protects cells against a variety of cytotoxic agents that otherwise induce apoptosis. Here we tested whether there is a molecular link between HS preconditioning and endoplasmic reticulum (ER stress-induced apoptosis. ER stress results from a loss of ER lumen homeostasis, culminating in an accumulation of unfolded/misfolded proteins in the ER and activation of unfolded protein response (UPR. Unresolved, ER stress leads to activation of BH3-only proteins, mitochondrial membrane permeabilization, caspase activation and apoptotic cell death. HS preconditioning (1 h at 42 °C induced a rapid increase in HSPA1 (HSP70 levels which remained elevated for at least 48 h post-HS. HS preconditioning significantly reduced BAX, caspase activation and apoptosis in cell cultures treated with the ER stress-inducing agents thapsigargin (TG and tunicamycin (TM. HS-mediated protection was found to be due to regulation of the BH3-only protein BIM. Further, overexpression of HSPA1 could not mimic the effect of HS on BIM expression, suggesting that other HS factors may play a role in inhibiting ER stress-induced apoptosis by regulating BIM.

  17. What a Shock: No Apoptosis without Heat Shock Protein 90α | Center for Cancer Research (United States)

    Apoptosis, also known as programmed cell death, consists of a series of reactions designed to systematically chop up a cell and its contents. The process is used to eliminate specific cells during development or to remove old or damaged cells without harming any surrounding cells. Since cancer cells can develop mechanisms to avoid apoptosis, researchers may be able to identify new targets to combat cancer by better understanding the details of the apoptotic process.

  18. Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction (United States)


    Toll-like receptor (TLR) agonists. Surfac- tant therapy has been used extensively and successfully in reducing mortality from respiratory distress...JR. Sur- factant protein D stimulates phagocytosis of Pseudomonas aer - uginosa by alveolar macrophages. American Journal of Respiratory Cell and...pharmacodynamic concepts, and antibiotic therapy . Chest 2011 May;139(5):1172e85 [Review]. 39. Fujitani S, Sun HY, Yu VL, Weingarten JA. Pneumonia

  19. Boundary-layer development and transition due to free-stream exothermic reactions in shock-induced flows (United States)

    Hall, J. L.


    A study of the effect of free-stream thermal-energy release from shock-induced exothermic reactions on boundary-layer development and transition is presented. The flow model is that of a boundary layer developing behind a moving shock wave in two-dimensional unsteady flow over a shock-tube wall. Matched sets of combustible hydrogen-oxygen-nitrogen mixtures and inert hydrogen-nitrogen mixtures were used to obtain transition data over a range of transition Reynolds numbers from 1,100,000 to 21,300,000. The heat-energy is shown to significantly stabilize the boundary layer without changing its development character. A method for application of this data to flat-plate steady flows is included.

  20. Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90. (United States)

    Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun


    Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Germ cell apoptosis and expression of Bcl-2 and Bax in porcine testis under normal and heat stress conditions. (United States)

    Fan, Xiaorui; Xi, Huaming; Zhang, Zhen; Liang, Yajun; Li, Qinghong; He, Junping


    The aim of this study was to examine whether an elevated ambient temperature (37-40°C) had an effect on the apoptosis of germ cells and the expression of Bcl-2 and Bax in porcine testis. Six boars were used. Three boars were subjected to an elevated ambient temperature (37-40°C, 7days, 3h per day) as a heat stress (HS) group. The other 3 boars were kept in a room temperature house (20-27°C) as a control group. All boars were castrated and the testes were harvested. TUNEL assay was used for the detection of apoptotic cells. Immunohistochemistry, Western blotting and quantitative real-time PCR were used to analyze protein and mRNA levels of Bcl-2 and Bax in response to heat treatment. The results showed that apoptotic signals increased under heat stress conditions compared with the control (Pheat treatment were spermatocytes and spermatids. In both the control and experimental groups, Bcl-2 was expressed in the cytoplasm and nucleus of spermatogonia, spermatocytes and differentiating spermatids and Bcl-2 preferentially localized close to the seminiferous tubule's luminal surface in late spermatocytes and spermatids. Compared with the control group, the expression levels of Bcl-2 protein and mRNA significantly increased in heat treatment group, while the expression levels of Bax protein and mRNA did not show significant changes between the control and experimental group. Low to moderate Bax immunoreactivity staining was observed in all kinds of germ cells in the control group. Strong staining was observed in spermatogonia, and low to moderate Bax staining was observed in spermatocytes and spermatids. A redistribution of Bax from a cytoplasmic to perinuclear or nuclear localization could be observed in the spermatogonia, spermatocytes and spermatids obtained in the heat treated group. These results showed that elevated ambient temperatures induced germ cell apoptosis. In response to heat stress, the expression of Bcl-2 increased and a redistribution of Bax from a

  2. Experimental and Theoretical Investigation of Shock-Induced Reactions in Energetic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Jeffrey J. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Park, Samuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kohl, Ian Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Knepper, Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Farrow, Darcie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tappan, Alexander S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    In this work, shock-induced reactions in high explosives and their chemical mechanisms were investigated using state-of-the-art experimental and theoretical techniques. Experimentally, ultrafast shock interrogation (USI, an ultrafast interferometry technique) and ultrafast absorption spectroscopy were used to interrogate shock compression and initiation of reaction on the picosecond timescale. The experiments yielded important new data that appear to indicate reaction of high explosives on the timescale of tens of picoseconds in response to shock compression, potentially setting new upper limits on the timescale of reaction. Theoretically, chemical mechanisms of shock-induced reactions were investigated using density functional theory. The calculations generated important insights regarding the ability of several hypothesized mechanisms to account for shock-induced reactions in explosive materials. The results of this work constitute significant advances in our understanding of the fundamental chemical reaction mechanisms that control explosive sensitivity and initiation of detonation.

  3. Effect of sequential heat and cold shocks on nuclear phenotypes of the blood-sucking insect, Panstrongylus megistus (Burmeister (Hemiptera, Reduviidae

    Directory of Open Access Journals (Sweden)

    Garcia Simone L


    Full Text Available Thermal shocks induce changes in the nuclear phenotypes that correspond to survival (heterochromatin decondensation, nuclear fusion or death (apoptosis, necrosis responses in the Malpighian tubules of Panstrongylus megistus. Since thermal tolerance increased survival and molting rate in this species following sequential shocks, we investigated whether changes in nuclear phenotypes accompanied the insect survival response to sequential thermal shocks. Fifth instar nymphs were subjected to a single heat (35 or 40°C, 1 h or cold (5 or 0°C, 1 h shock and then subjected to a second shock for 12 h at 40 or 0°C, respectively, after 8, 18, 24 and 72 h at 28°C (control temperature. As with specimen survival, sequential heat and cold shocks induced changes in frequency of the mentioned nuclear phenotypes although their patterns differed. The heat shock tolerance involved decrease in apoptosis simultaneous to increase in cell survival responses. Sequential cold shocks did not involve cell/nuclear fusion and even elicited increase in necrosis with advancing time after shocks. The temperatures of 40 and 0ºC were more effective than the temperatures of 35 and 5ºC in eliciting the heat and cold shock tolerances, respectively, as shown by cytological analysis of the nuclear phenotypes. It is concluded that different sequential thermal shocks can trigger different mechanisms of cellular protection against stress in P. megistus, favoring the insect to adapt to various ecotopes.

  4. Proof-of-principle experiment of a shock-induced combustion ramjet

    NARCIS (Netherlands)

    Veraar, R.G.; Mayer, A.E.H.J.; Verreault, J.; Stowe, R.A.; Farinaccio, R.; Harris, P.G.


    By injecting and mixing the fuel upstream of the combustor and initiating the combustion of the fuel-air mixture by a shock wave in the combustor, shock-induced combustion ramjets offer the potential to drastically reduce the length and mass of scramjet propulsion systems. Based on extensive

  5. Proof-of-principle experiment of a shock-induced combustion ramjet

    NARCIS (Netherlands)

    Veraar, R.G.; Mayer, A.E.H.J.; Verreault, J.; Stowe, R.A.; Farinaccio, R.; Harris, P.G.


    By injecting and mixing the fuel upstream of the combustor and initiating the combustion of the fuel-air mixture by a shock wave in the combustor, shock-induced combustion ramjets offer the potential to drastically reduce the length and mass of scramjet propulsion systems. Based on extensive

  6. Design of a shock-induced combustion experiment in an axisymmetric configuration with hydrogen injection

    NARCIS (Netherlands)

    Verreault, J.; DeChamplain, A.; Mayer, A.E.H.J.; Veraar, R.G.; Stowe, R.A.; Farinaccio, R.; Harris, P.G.


    This work presents a design for a shock-induced combustion experiment using a two-angle cone configuration. Three injector geometries were considered: a cone surface, a dual stage configuration with rectangular gaps (DSRG) and a cylindrical ramp (CR). Four parameters were investigated: the

  7. Shock-induced spall in copper: the effects of anisotropy, temperature, loading pulse and defect

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Shengnian [Los Alamos National Laboratory; Germann, Timothy C [Los Alamos National Laboratory; An, Qi [Los Alamos National Laboratory; Han, Li - Bo [USTC


    Shock-induced spall in Cu is investigated with molecular dynamics simulations. We examine spallation in initially perfect crystals and defective solids with grain boundaries (columnar bicrystals), stacking faults or vacancies, as well as the effect of temperature and loading pulses. Spall in single crystal Cu is anisotropic, and defects and high temperature may reduce the spall strength. Taylor-wave (triangular shock-release wave) loading is explored in comparison with square wave shock loading.

  8. The role of intracellular oxidation in death induction (apoptosis and necrosis) in human promonocytic cells treated with stress inducers (cadmium, heat, X-rays). (United States)

    Galán, A; García-Bermejo, L; Troyano, A; Vilaboa, N E; Fernández, C; de Blas, E; Aller, P


    Treatment of U-937 human promonocytic cells with the stress inducers cadmium chloride (2 h at 200 microM), heat (2 h at 42.5 C) or X-rays (20 Gy), followed by recovery, caused death by apoptosis and stimulated caspase-3 activity. In addition, all stress agents caused intracellular oxidation, as measured by peroxide and/or anion superoxide accumulation. However, while pre-incubation with antioxidants (N-acetyl-L-cysteine or butylated hydroxyanisole) inhibited the induction of apoptosis by cadmium and X-rays, it did not affect the induction by heat-shock. Pre-incubation for 24 h with the GSH-depleting agent L-buthionine-[S,R]-sulfoximine (BSO) switched the mode of death from apoptosis to necrosis in cadmium-treated cells. By contrast, BSO only caused minor modifacions in the rate of apoptosis without affecting the mode of death in heat- and X-rays-treated cells. BSO potentiated peroxide accumulation in cells treated with both cadmium and X-rays. However, while the accumulation of peroxides was stable in the case of cadmium, it was transient in the case of X-rays. Moreover, the administration of antioxidants during the recovery period sufficed to prevent necrosis and restore apoptosis in BSO plus cadmium-treated cells. Cadmium and X-rays caused a decrease in intracellular ATP levels, but the decrease was similar in both apoptotic and necrotic cells. Taken together, these results demonstrate that (i) stress inducers cause intracellular oxidation, but oxidation is not a general requirement for apoptosis; and (ii) the duration of the oxidant state seems to be critical in determining the mode of death.

  9. Association of nuclear-localized Nemo-like kinase with heat-shock protein 27 inhibits apoptosis in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Gina Shaw-Hallgren

    Full Text Available Nemo-like kinase (NLK, a proline-directed serine/threonine kinase regulated by phosphorylation, can be localized in the cytosol or in the nucleus. Whether the localization of NLK can affect cell survival or cell apoptosis is yet to be disclosed. In the present study we found that NLK was mainly localized in the nuclei of breast cancer cells, in contrast to a cytosolic localization in non-cancerous breast epithelial cells. The nuclear localization of NLK was mediated through direct interaction with Heat shock protein 27 (HSP27 which further protected cancer cells from apoptosis. The present study provides evidence of a novel mechanism by which HSP27 recognizes NLK in the breast cancer cells and prevents NLK-mediated cell apoptosis.

  10. Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model

    Directory of Open Access Journals (Sweden)

    Ariadna Bargiela


    Full Text Available Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1 disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor or muscleblind, or by RNA interference (RNAi-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis.

  11. Shock-induced collapse of a bubble inside a deformable vessel (United States)

    Coralic, Vedran; Colonius, Tim


    Shockwave lithotripsy repeatedly focuses shockwaves on kidney stones to induce their fracture, partially through cavitation erosion. A typical side effect of the procedure is hemorrhage, which is potentially the result of the growth and collapse of bubbles inside blood vessels. To identify the mechanisms by which shock-induced collapse could lead to the onset of injury, we study an idealized problem involving a preexisting bubble in a deformable vessel. We utilize a high-order accurate, shock- and interface-capturing, finite-volume scheme and simulate the three-dimensional shock-induced collapse of an air bubble immersed in a cylindrical water column which is embedded in a gelatin/water mixture. The mixture is a soft tissue simulant, 10% gelatin by weight, and is modeled by the stiffened gas equation of state. The bubble dynamics of this model configuration are characterized by the collapse of the bubble and its subsequent jetting in the direction of the propagation of the shockwave. The vessel wall, which is defined by the material interface between the water and gelatin/water mixture, is invaginated by the collapse and distended by the impact of the jet. The present results show that the highest measured pressures and deformations occur when the volumetric confinement of the bubble is strongest, the bubble is nearest the vessel wall and/or the angle of incidence of the shockwave reduces the distance between the jet tip and the nearest vessel surface. For a particular case considered, the 40 MPa shockwave utilized in this study to collapse the bubble generated a vessel wall pressure of almost 450 MPa and produced both an invagination and distention of nearly 50% of the initial vessel radius on a 𝒪(10) ns timescale. These results are indicative of the significant potential of shock-induced collapse to contribute to the injury of blood vessels in shockwave lithotripsy. PMID:24015027

  12. Shock-induced kelyphite formation in the core of a complex impact crater (United States)

    Deseta, Natalie; Boonsue, Suporn; Gibson, Roger L.; Spray, John G.


    We present a compositional and textural analysis of shock-induced microtextures in garnet porphyroblasts in migmatitic garnet-cordierite-biotite paragneisses from the centre of the Vredefort impact structure, South Africa. Detailed imaging and major element analysis of deformation features in, and adjacent to, the garnet porphyroblasts record a complex, heterogeneous distribution of shock effects at the microscale. As the most competent silicate mineral in the assemblage, with the highest Hugoniot Elastic Limit and a wide pressure-temperature stability field, the porphyroblastic garnet preserves a more diverse shock deformation response compared to minerals such as quartz and feldspar, which underwent more comprehensive shock metamorphism and subsequent annealing. The garnet porphyroblasts display pre-impact fractures that are overprinted by later intra-granular Hertzian and distinctive planar fractures associated with the impact event. Shock-induced strain localization occurred along internal slip planes and defects, including pre-existing fractures and inclusion boundaries in the garnet. Symplectitic (kelyphitic) coronas commonly enclose the garnet porphyroblasts, and inhabit intra-granular fractures. The kelyphite assemblage in fractures with open communication beyond garnet grain boundaries is characterized by orthopyroxene—cordierite—sapphirine. Conversely, the kelyphite assemblage in closed-off intra-granular fractures is highly variable, comprising spatially restricted combinations of a secondary garnet phase with a majoritic component, Al-rich orthopyroxene, sapphirine and cordierite. The impedance contrast between garnet porphyroblasts and their inclusions further facilitated the formation of shock-induced features (Al-rich orthopyroxene coronas). Together, the textural and mineralogical data suggest that these features provide a record of oscillatory shock perturbations initiated under confining pressure beneath the transient crater floor. This

  13. Quantification of shock-induced melting and its distribution in the Ejecta (United States)

    Engelmann, J.; Wünnemann, K.; Luther, R.; Zhu, M.-H.


    In contrast to lunar regolith, which is dominated by impact melt particles (agglutinates), samples from the asteroid Itokawa (25143), collected by the Hayabusa mission, exhibit a strong deficit in agglutinates. To investigate the amount of shock-induced melting and its distribution in the ejecta we simulate hypervelocity impacts into targets with varying gravity and quantify the amount and distribution of generated melt that is ejected. We find that even at relatively low impact velocities and high target porosity (representing asteroidal condition) a significant amount of melting occurs. Our models also predict that in case of vertical impacts a significant amount of the generated melt remains inside the crater and is not ejected.

  14. Shock-induced optical emission and high-pressure phase transformation of sapphire (United States)

    Zhang, Ning-Chao; Liu, Fu-Sheng; Wang, Wen-Peng; Sun, Yan-Yun; Liu, Qi-Jun; Peng, Xiao-Juan; Chen, Jun-Xiang


    Emission from sapphire window material was measured by spontaneous spectroscopic and multi-wavelength pyrometer techniques. The spectral distribution as a function of wavelength fit well to the grey-body spectrum. We analyzed the emissions and discovered that they arise from shear banding, which is a typical thermal radiation. It was found that the color temperature of shocked sapphire changes linearly and regularly with stress increases from 40 GPa to 59 GPa but becomes monotonic for stresses from 87 GPa to 120 GPa. The change in behavior indicates that a shock-induced phase transformation occurs between 59 GPa and 87 GPa.

  15. Shock-induced optical emission and high-pressure phase transformation of sapphire

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ning-Chao [Laboratory of High Temperature and High Pressure Physics, Southwest Jiaotong University, Chengdu 610031 (China); Liu, Fu-Sheng, E-mail: [Laboratory of High Temperature and High Pressure Physics, Southwest Jiaotong University, Chengdu 610031 (China); Wang, Wen-Peng; Sun, Yan-Yun; Liu, Qi-Jun [Laboratory of High Temperature and High Pressure Physics, Southwest Jiaotong University, Chengdu 610031 (China); Peng, Xiao-Juan; Chen, Jun-Xiang [National Key Laboratory of Shock Wave and Detonation Physics, Institute of Fluid Physics, CAEP, Mianyang 621900 (China)


    Emission from sapphire window material was measured by spontaneous spectroscopic and multi-wavelength pyrometer techniques. The spectral distribution as a function of wavelength fit well to the grey-body spectrum. We analyzed the emissions and discovered that they arise from shear banding, which is a typical thermal radiation. It was found that the color temperature of shocked sapphire changes linearly and regularly with stress increases from 40 GPa to 59 GPa but becomes monotonic for stresses from 87 GPa to 120 GPa. The change in behavior indicates that a shock-induced phase transformation occurs between 59 GPa and 87 GPa.

  16. Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis in rheumatoid arthritis - a potential role for heat shock protein 70

    Directory of Open Access Journals (Sweden)

    Chuturgoon Anil A


    Full Text Available Abstract Background Rheumatoid arthritis (RA is a chronic autoimmune disease, which causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid synovium has been attributed to abnormal apoptosis. While not comprehensively investigated, perturbations in peripheral blood lymphocyte (PBL apoptosis may also be involved in perpetuation of autoimmune processes in RA. Methods We investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by monitoring the translocation of phosphatidylserine using the Annexin-V assay. To examine the role of death receptor mediated apoptosis as well as activation-induced-cell-death (AICD, PBLs were labeled with CD95/Fas and CD69 markers and enumerated by flow cytometry. Proteolytic activity of initiator and executioner caspases was determined by luminometry. DNA fragmentation assays were used to examine whether apoptotic signals were transduced to the nucleus. Quantitative PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs. Since heat-shock-protein-70 (HSP70 is an inducible protein which modulates apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry and western blots. Results The RA-PBLs showed signs of elevated apoptosis whilst in circulation. These include increases in the loss of plasma membrane asymmetry, indicated by increased externalization of phosphatidylserine (especially in B-lymphocytes. RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but low levels of the CD69 marker suggested that this was not associated with immune activation. Although downstream markers of apoptosis such as caspase-3/7 activity, were increased, no DNA fragmentation was observed in RA-PBLs. Interestingly, elevated levels of apoptosis did not correlate with absolute lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs compared to controls. Conclusion The results suggest that while apoptosis may be initiated in RA

  17. Shock induced ignition and DDT in the presence of mechanically driven fluctuations (United States)

    Wang, Wentian; McDonald, James G.; Radulescu, Matei I.


    The present study addresses the problem of shock induced ignition and transition to detonation in the presence of mechanical and thermal fluctuations. These departures from a homogeneous medium are of significant importance in practical situations, where such fluctuations may promote hot-spot ignition and favor the flame transition to detonation. The problem is studied in 1D, where a piston-induced shock ignites the gas. The fluctuations in the shock-compressed medium are controlled by allowing the piston's speed to oscillate around a mean, with controllable frequency and amplitude. A Lagrangian numerical formulation is used, which allows to treat exactly the transient boundary condition at the piston head. The hydrodynamic solver is coupled with the reactive dynamics of the gas using Cantera. The code was verified by comparison with steady state ZND solutions and previous shock induced ignition results in homogeneous media. Results obtained for different fuels illustrate the strong relation of the DDT amplification length to mechanical fluctuations in systems with a high effective activation energy and fast rate of energy deposition, consistent with experiments performed on fast flame acceleration in the presence of strong mechanical perturbations. Financial support from NSERC and Shell, with A. Pekalski and M. Levin as technical monitors, are greatly acknowledged.

  18. An investigation of passive control methods for shock-induced separation at hypersonic speeds (United States)

    Rallo, R.; Walsh, M.; Van Leer, Bram


    The effectiveness of several passive control techniques on shock-induced boundary-layer separation at hypersonic speed was investigated. Two approaches for alleviating the turbulent separation losses were examined: porous surface mass transfer and surface grooving. A total of four perforated surfaces with varying porosities were evaluated, and three groove orientations with respect to the freestream direction were studied. A comparison of the results from passive control techniques with those from an 'uncontrolled' shock impingement showed that the porous surface with the greatest porosity provided the greatest reduction in the pressure rise across the oblique shock wave. The grooved surface tested were found to be not effective; each of the grooved configurations examined increased the peak pressure value.

  19. Structural characteristics of the shock-induced boundary layer separation extended to the leading edge (United States)

    Tao, Y.; Liu, W. D.; Fan, X. Q.; Zhao, Y. L.


    For a better understanding of the local unstart of supersonic/hypersonic inlet, a series of experiments has been conducted to investigate the shock-induced boundary layer separation extended to the leading edge. Using the nanoparticle-based planar laser scattering, we recorded the fine structures of these interactions under different conditions and paid more attention to their structural characteristics. According to their features, these interactions could be divided into four types. Specifically, Type A wave pattern is similar to the classic shock wave/turbulent boundary layer interaction, and Type B wave configuration consists of an overall Mach reflection above the large scale separation bubble. Due to the gradual decrease in the size of the separation bubble, the separation bubble was replaced by several vortices (Type C wave pattern). Besides, for Type D wave configuration which exists in the local unstart inlet, there appears to be some flow spillage around the leading edge.

  20. Shock-Induced Transformation Exsolution Lamellae in Olivine in Black Veins of the Mbale Meteorite (United States)

    Chen, M.; Wopenka, B.; El Goresy, A.


    Mbale is a shocked L6 chondrite [1]. Some shock-induced veins of 0.1 to 2 mm width intersect the meteorite. The veins consist of diaplectic plagioclase glass, unmelted silicate fragments including olivines and pyroxenes, and the shock-induced melt materials consisting of metal-troilite intergrowths, microcrystalline pyroxene and olivine, and silicate glass. Here we report the first finding of shock-induced exsolutions in olivine that appear as compositionally different lamellae which presumably formed at high pressure by inversion of olivine (alpha) to the beta+gamma polymorphs. Olivine compositions in the chondritic part of Mbale range from Fa(sub)22.5 to Fa(sub)26 (average Fa(sub)24). In contrast, the exsolved olivines in the shock-induced veins (30 to 100 mm in diameter) consist of alternating Fe-rich (Fa(sub)22-32) and Fe-poor (Fa(sub)9.9-18.5) lamellae that range in width from less than 0.5 micrometers to up to 10 micrometers. Each individual lamella actually consists of microcrystals of less than 0.5 micrometers in diameter with rather diffuse borders within the lamella. The lamellae occur in ~30 micrometer segments which were formed by faulting and displacement. Micro-Raman spectroscopy confirms that both types of exsolution lamellae currently have the olivine (alpha) structure. The partially melted veins of Mbale may have reached a post-shock peak temperature of 1473 K >= T ringwoodite(gamma) transformations in the system Mg(sub)2SiO(sub)4-Fe(sub)2SiO(sub)4 at 1473 K [2], olivine of composition ~Fa(sub)24 should exsolve at equilibrium conditionsins to beta- + gamma-phases at P >12.7 GPa, and transform to a single gamma-phase at >15 GPa. Figure 1 shows that the determined compositions of the Fe-rich and Fe-poor lamellae in Mbale match perfectly the compositions at the beta + gamma/gamma and the beta + gamma/beta phase boundaries, respectively. Since these grains depict well ordered lamellar structure displaced by several faults, the exsolution lamellae of

  1. Hyperthermia-induced apoptosis

    NARCIS (Netherlands)

    Nijhuis, E.H.A.


    This thesis describes a number of studies that investigated several aspects of heat-induced apoptosis in human lymphoid malignancies. Cells harbour both pro- and anti-apoptotic proteins and the balance between these proteins determines whether a cell is susceptible to undergo apoptosis. In this

  2. A Novel Porcine Model of Septic Shock Induced by Acute Respiratory Distress Syndrome due to Methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Shuo Wang


    Conclusions: In the present study, we developed a novel porcine model of septic shock induced by ARDS due to severe MRSA pneumonia with characteristic hyperdynamic and hypodynamic phases in 24 h, which mimicked the hemodynamic changing of septic shock in human.

  3. Assessment of expressions of heat shock protein (HSP 72) and apoptosis after ArF excimer laser ablation of the cornea. (United States)

    Ishihara, Miya; Sato, Masato; Sato, Shunichi; Arai, Tsunenori; Obara, Minoru; Kikuchi, Makoto


    We immunohistochemically studied expressions of inducible heat shock protein 70 (HSP 72) and apoptosis of corneas ablated with an ArF excimer laser. The temperature of corneal surfaces and laser-induced optical emission spectra were measured in real time as direct physical parameters related to the ablation mechanism. To the best of the authors' knowledge, there have been no experimental studies regarding the influence of physical parameters directly related to the ablation mechanism on corneal reactions at the cell level after laser ablation. The expression of HSP 72 was mainly localized in the regenerative epithelium, which was confirmed to be caused by laser ablation. The HSP 72 positive cell ratios had a correlation with thermal dose, which was derived from the measured time courses of temperature. Expressions of both HSP 72 and apoptosis depended on the thermal dose and elapsed time after ablation. HSP 72 and apoptosis could be seen up to a few hundred micrometers into the stroma, only at a fluence with an optical breakdown emission. This could have been caused by shock waves induced by the optical breakdown. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

  4. Shock-induced deformation of Shergottites: Shock-pressures and perturbations of magmatic ages on Mars (United States)

    El Goresy, Ahmed; Gillet, Ph.; Miyahara, M.; Ohtani, E.; Ozawa, S.; Beck, P.; Montagnac, G.


    Shergottites and Chassignites practiced major deformation effects whose nature, magnitude and relevance were controversially evaluated and disputatively debated. Our studies of many shocked shergottites present, contrary to numerous previous reports, ample evidence for pervasive shock-induced melting amounting of at least 23 vol.% of the shergottite consisting of maskelynite and pyrrhotite, partial melting of pyroxene, titanomagnetite, ilmenite and finding of several high-pressure polymorphs and pressure-induced dissociation reactions. Our results cast considerable doubt on using the refractive index (RI) or cathodoluminescence (CL) spectra of maskelynite, in estimating the magnitudes of peak-shock pressure in both shergottites and ordinary chondrites. RI of maskelynite was set after quenching of the feldspar liquid before decompression to maskelynite glass followed by glass relaxation after decompression at the closure temperature of relaxation. The RI procedure widely practiced in the past 38 years revealed unrealistic very high-pressure estimates discrepant with the high-pressure mineral inventory in shocked shergottites and ordinary chondrites and with results obtained by robust laboratory static experiments. Shergottites contain the silica high-pressure polymorphs: the scrutinyite-structured polymorph seifertite, a monoclinic ultra dense polymorph of silica with ZrO2-structure, stishovite, a dense liquidus assemblage consisting of stishovite + Na-hexa-aluminosilicate (Na-CAS) and both K-lingunite and Ca-lingunite. Applying individual high-pressure silica polymorphs alone like stishovite, to estimate the equilibrium shock pressure, is inadequate due to the considerable shift of their nominal upper pressure bounds intrinsically induced by spatially variable absorptions of minor oxides like Al2O3, Na2O, FeO, MgO and TiO2. This practice revealed variable pressure estimates even within the same shergottite subjected to the same peak-shock pressure. Occurrence of Na

  5. Puerarin ameliorates heat stress-induced oxidative damage and apoptosis in bovine Sertoli cells by suppressing ROS production and upregulating Hsp72 expression. (United States)

    Cong, Xia; Zhang, Qian; Li, Huatao; Jiang, Zhongling; Cao, Rongfeng; Gao, Shansong; Tian, Wenru


    Puerarin, a bioactive isoflavone glucoside extracted from radix Puerariae, has been proven to possess many biological activities. However, the role of puerarin in protecting bovine Sertoli cells (bSCs) under heat stress conditions remains to be clarified. The present study aimed to explore the possible protective mechanism of puerarin for primary cultured bSCs subjected to heat stress. Bovine Sertoli cells were treated with 15 μM of puerarin before they were exposed to 42 °C for 1 hour. The dose of puerarin (15 μM) was determined on the basis of cell viability. The results showed that puerarin treatment suppressed the production of reactive oxygen species and decreased the oxidative damage of the bSCs subjected to heat stress, as indicated by changes in superoxide dismutase, catalase, and glutathione peroxidase activities and malondialdehyde content. Moreover, puerarin treatment also suppressed the initiation of mitochondria-dependent apoptotic pathway, as revealed by changes in Bax to Bcl-2 ratio, mitochondrial membrane potential, cytochrome C release, caspase-3 activation, and apoptotic rate compared with the heat stress group. In addition, puerarin treatment increased Hsp72 expression in the bSCs with no apparent cellular cytotoxicity compared with the control group. Furthermore, increased Hsp72 was detected in the heat stress plus puerarin group compared with the heat stress group. In conclusion, puerarin attenuates heat stress-induced oxidative damage and apoptosis of bSCs by suppressing reactive oxygen species production and upregulating Hsp72 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma (United States)

    Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick


    Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

  7. Heat Killed Attenuated Leishmania Induces Apoptosis of HepG2 Cells Through ROS Mediated p53 Dependent Mitochondrial Pathway. (United States)

    Bose, Dipayan; Banerjee, Somenath; Das, Subhadip; Chatterjee, Nabanita; Saha, Krishna Das


    Cytotoxic effect of attenuated Leishmania on liver cancer cells by inducing ROS generation. Spectrophotometric study to analyze cell death and levels of different active caspases. Flow cytometric study was done to analyze apoptosis induction and ROS generation and levels of different protein. Western blot analysis was performed to study the levels of protein. Confocal microscopy was done to ascertain the expression of different apoptotic markers. We have now observed that attenuated Leishmania donovani UR6 also has potentiality towards growth inhibition of HepG2 cells and investigated the mechanism of action. The effect is associated with increased DNA fragmentation, rise in number of annexinV positive cells, and cell cycle arrest at G1 phase. The detection of unregulated levels of active PARP, cleaved caspases 3 and 9, cytosolic cytochrome C, Bax, and Bad, along with the observed downregulation of Bcl-2 and loss of mitochondrial membrane potential suggested the involvement of mitochondrial pathway. Enhanced ROS and p53 levels regulate the apoptosis of HepG2 cells. NAC was found to inhibit p53 production but PFT-α has no effect on ROS generation. In conclusion, Leishmania donovani UR6 efficiently induces apoptosis in HepG2 cells through ROS mediated p53 dependent mitochondrial pathway. It has been reported earlier that some parasites show prominent cytotoxic effect and prevent tumor growth. From our study we found that Leishmania donovani UR6 efficiently induced apoptosis in HepG2 cells through ROS mediated p53 dependent mitochondrial pathway. This study has rejuvenated the age old idea of bio-therapy. © 2016 The Author(s) Published by S. Karger AG, Basel.

  8. Heat Killed Attenuated Leishmania Induces Apoptosis of HepG2 Cells Through ROS Mediated p53 Dependent Mitochondrial Pathway

    Directory of Open Access Journals (Sweden)

    Dipayan Bose


    Full Text Available Background/Aims: Cytotoxic effect of attenuated Leishmania on liver cancer cells by inducing ROS generation. Methods: Spectrophotometric study to analyze cell death and levels of different active caspases. Flow cytometric study was done to analyze apoptosis induction and ROS generation and levels of different protein. Western blot analysis was performed to study the levels of protein. Confocal microscopy was done to ascertain the expression of different apoptotic markers. Results: We have now observed that attenuated Leishmania donovani UR6 also has potentiality towards growth inhibition of HepG2 cells and investigated the mechanism of action. The effect is associated with increased DNA fragmentation, rise in number of annexinV positive cells, and cell cycle arrest at G1 phase. The detection of unregulated levels of active PARP, cleaved caspases 3 and 9, cytosolic cytochrome C, Bax, and Bad, along with the observed downregulation of Bcl-2 and loss of mitochondrial membrane potential suggested the involvement of mitochondrial pathway. Enhanced ROS and p53 levels regulate the apoptosis of HepG2 cells. NAC was found to inhibit p53 production but PFT-α has no effect on ROS generation. In conclusion, Leishmania donovani UR6 efficiently induces apoptosis in HepG2 cells through ROS mediated p53 dependent mitochondrial pathway. Conclusion: It has been reported earlier that some parasites show prominent cytotoxic effect and prevent tumor growth. From our study we found that Leishmania donovani UR6 efficiently induced apoptosis in HepG2 cells through ROS mediated p53 dependent mitochondrial pathway. This study has rejuvenated the age old idea of bio-therapy.

  9. [Effect of moxa-burning heat stimulating Liangmen (ST 21) and Zusanli (ST 36) on proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer]. (United States)

    Peng, Li; Wang, Yadong; Chang, Xiaorong; Wu, Huangan; Liu, Mi; Wang, Hong; Chen, Jiaolong; Wang Chao; Quan, Renfu; Yang, Zongbao


    To observe the effect of moxa-burning heat stimulating acupoints of Liangmen (ST 21) and Zusanli (ST 36) on the proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer. Forty rats were randomly divided into four groups: negative control (NC), ulcer control (UC), acupoints of stomach meridian (ASM), and acupoints control (AC). The acute gastric ulcer model was established by bound and water immersion. Rats in NC and UC groups didn't receive any moxa-burning heat stimulating treatment, while rats in ASM and AC groups were treated with buringmoxa heat stimulating the acupoints of Liangmen (ST 21) and Zusanli (ST 36) and their controlled points, respectively. Rats in all groups were sacrificed after 12 consecutive days treatment. The ulcer index was evaluated by using Guth's method. The expression of tumor necrosis factor-alpha (TNF-α), apoptotic protease activating facter-1 (Apaf-1), Caspase-3, p21 activated kinase 1 (PAK1), extracellular regulated protein kinases 2 (ERK2), phosphorylated ERK2 (pERK2), phosphoinositide 3-kinase (PI3K) and RAC-alpha serine/threonine-protein kinase (Akt) in gastric mucosa was detected by enzyme linked immunosorbent assay (ELISA). Compared with UC group, the ulcer index of ASM and AC groups decreased, and the injured gastric mucosa was improved, the expression of TNF-α, Apaf-1 and Caspase-3 in gastric mucosa was significantly reduced (P gastric mucosa was significantly increased (P gastric mucosal lesion probably by inhibiting cell apoptosis and promoting cell proliferation in stress-induced gastric ulcer.

  10. Supplementary heat-killed Lactobacillus reuteri GMNL-263 ameliorates hyperlipidaemic and cardiac apoptosis in high-fat diet-fed hamsters to maintain cardiovascular function. (United States)

    Ting, Wei-Jen; Kuo, Wei-Wen; Kuo, Chia-Hua; Yeh, Yu-Lan; Shen, Chia-Yao; Chen, Ya-Hui; Ho, Tsung-Jung; Viswanadha, Vijaya Padma; Chen, Yi-Hsing; Huang, Chih-Yang


    Obesity and hyperlipidaemia increase the risk of CVD. Some strains of probiotics have been suggested to have potential applications in cardiovascular health by lowering serum LDL-cholesterol. In this work, high-fat diet-induced hyperlipidaemia in hamsters was treated with different doses (5×108 and 2·5×109 cells/kg per d) of heat-killed Lactobacillus reuteri GMNL-263 (Lr263) by oral gavage for 8 weeks. The serum lipid profile analysis showed that LDL-cholesterol and plasma malondialdehyde (P-MDA) were reduced in the GMNL-263 5×108 cells/kg per d treatment group. Total cholesterol and P-MDA were reduced in the GMNL-263 2·5×109 cells/kg per d treatment group. In terms of heart function, the GMNL-263 2·5×109 cells/kg per d treatments improved the ejection fraction from 85·71 to 91·81 % and fractional shortening from 46·93 to 57·92 % in the high-fat diet-fed hamster hearts. Moreover, the GMNL-263-treated, high-fat diet-fed hamster hearts exhibited reduced Fas-induced myocardial apoptosis and a reactivated IGF1R/PI3K/Akt cell survival pathway. Interestingly, the GMNL-263 treatments also enhanced the heat-shock protein 27 expression in a dose-dependent manner, but the mechanism for this increase remains unclear. In conclusion, supplementary heat-killed L. reuteri GMNL-263 can slightly reduce serum cholesterol. The anti-hyperlipidaemia effects of GMNL-263 may reactivate the IGF1R/PI3K/Akt cell survival pathway and reduce Fas-induced myocardial apoptosis in high-fat diet-fed hamster hearts.

  11. The shock-induced star formation sequence resulting from a constant spiral pattern speed

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-García, Eric E.; Puerari, Ivânio, E-mail:, E-mail: [Instituto Nacional de Astrofísica, Óptica y Electrónica (INAOE), Aptdo. Postal 51 y 216, 72000 Puebla, Puebla (Mexico)


    We utilize a suite of multiwavelength data of nine nearby spirals to analyze the shock-induced star formation sequence that may result from a constant spiral pattern speed. The sequence involves tracers as the H I, CO 24 μm, and FUV, where the spiral arms were analyzed with Fourier techniques in order to obtain their azimuthal phases as a function of radius. It was found that only two of the objects, NGC 628 and NGC 5194, present coherent phases resembling the theoretical expectations, as indicated by the phase shifts of CO- 24 μm. The evidence is more clear for NGC 5194 and moderate for NGC 628. It was also found that the phase shifts are different for the two spiral arms. With the exception on NGC 3627, a two-dimensional Fourier analysis showed that the rest of the objects do not exhibit bi-symmetric spiral structures of stellar mass, i.e., grand-design spirals. A phase order inversion indicates a corotation radius of ∼89'' for NGC 628 and ∼202'' for NGC 5194. For these two objects, the CO-Hα phase shifts corroborate the CO-24 μm azimuthal offsets. Also for NGC 5194, the CO-70 μm, CO-140 μm, and CO-250 μm phase shifts indicate a corotation region.

  12. Shock-induced bubble collapse in a vessel: Implications for vascular injury in shockwave lithotripsy (United States)

    Coralic, Vedran; Colonius, Tim


    In shockwave lithotripsy, shocks are repeatedly focused on kidney stones so to break them. The process leads to cavitation in tissue, which leads to hemorrhage. We hypothesize that shock-induced collapse (SIC) of preexisting bubbles is a potential mechanism for vascular injury. We study it numerically with an idealized problem consisting of the three-dimensional SIC of an air bubble immersed in a cylindrical water column embedded in gelatin. The gelatin is a tissue simulant and can be treated as a fluid due to fast time scales and small spatial scales of collapse. We thus model the problem as a compressible multicomponent flow and simulate it with a shock- and interface-capturing numerical method. The method is high-order, conservative and non-oscillatory. Fifth-order WENO is used for spatial reconstruction and an HLLC Riemann solver upwinds the fluxes. A third-order TVD-RK scheme evolves the solution. We evaluate the potential for injury in SIC for a range of pressures, bubble and vessel sizes, and tissue properties. We assess the potential for injury by comparing the finite strains in tissue, obtained by particle tracking, to ultimate strains from experiments. We conclude that SIC may contribute to vascular rupture and discuss the smallest bubble sizes needed for injury. This research was supported by NIH Grant No. 2PO1DK043881 and utilized XSEDE, which is supported by NSF Grant No. OCI-1053575.

  13. Formation of a disordered solid via a shock-induced transition in a dense particle suspension. (United States)

    Petel, Oren E; Frost, David L; Higgins, Andrew J; Ouellet, Simon


    Shock wave propagation in multiphase media is typically dominated by the relative compressibility of the two components of the mixture. The difference in the compressibility of the components results in a shock-induced variation in the effective volume fraction of the suspension tending toward the random-close-packing limit for the system, and a disordered solid can take form within the suspension. The present study uses a Hugoniot-based model to demonstrate this variation in the volume fraction of the solid phase as well as a simple hard-sphere model to investigate the formation of disordered structures within uniaxially compressed model suspensions. Both models are discussed in terms of available experimental plate impact data in dense suspensions. Through coordination number statistics of the mesoscopic hard-sphere model, comparisons are made with the trends of the experimental pressure-volume fraction relationship to illustrate the role of these disordered structures in the bulk properties of the suspensions. A criterion for the dynamic stiffening of suspensions under high-rate dynamic loading is suggested as an analog to quasi-static jamming based on the results of the simulations. © 2012 American Physical Society

  14. Shock-induced stacking fault pyramids in Ni/Al multilayers (United States)

    Xiang, Henggao; Li, Haitao; Fu, Tao; Zhu, Weibin; Huang, Cheng; Yang, Bo; Peng, Xianghe


    The formations of stacking fault tetrahedra in {111}fcc/{111}fcc multilayers have been studied extensively, but the researches related to {001}fcc/{001}fcc interfaces can rarely be found in the literature. Using molecular dynamics (MD) simulations, the shock-induced dislocation structure in Ni/Al multilayers was studied in this article, the stacking fault pyramids (SFPs) initiated from Ni/Al interface was firstly observed, and the corresponding mechanism was explored. It was shown that the Shockley partial dislocations dissociated from the rectangular misfit dislocations along Ni/Al interface are first emitted into the Al interlayer and subsequently intersect with each other to form SFPs. With the propagation of the shock front in the multilayers, two adjacent SFPs interact with each other and form Lomer-Cottrell locks. The dislocation sheet composed of SFPs and Lomer-Cottrell locks can act as a barrier to dislocation transmission. The effect of shock piston velocity on the nucleation site of dislocation was also studied. It was shown that dislocations would originate from the interface at a low piston speed (<1.1 km/s), and appear at the shock front if the piston speed exceeds 1.2 km/s.

  15. Finite element modelling of shock-induced damages on ceramic hip prostheses

    CERN Document Server

    Uribe, Juliana; Geringer, Jean; 10.5402/2011/121486


    The aim of this work was to simulate the behaviour of hip prostheses under mechanical shocks. When hip joint is replaced by prosthesis, during the swing phase of the leg, a microseparation between the prosthetic head and the cup could occur. Two different sizes of femoral heads were studied: 28 and 32 mm diameter, made, respectively, in alumina and zirconia. The shock-induced stress was determined numerically using finite element analysis (FEA), Abaqus software. The influence of inclination, force, material, and microseparation was studied. In addition, an algorithm was developed from a probabilistic model, Todinov's approach, to predict lifetime of head and cup. Simulations showed maximum tensile stresses were reached on the cup's surfaces near to rim. The worst case was the cup-head mounted at 30^{\\circ}. All simulations and tests showed bulk zirconia had a greater resistance to shocks than bulk alumina. The probability of failure could be bigger than 0.9 when a porosity greater than 0.7% vol. is present in...

  16. A level set approach for shock-induced α-γ phase transition of RDX (United States)

    Josyula, Kartik; Rahul; De, Suvranu


    We present a thermodynamically consistent level sets approach based on regularization energy functional which can be directly incorporated into a Galerkin finite element framework to model interface motion. The regularization energy leads to a diffusive form of flux that is embedded within the level sets evolution equation which maintains the signed distance property of the level set function. The scheme is shown to compare well with the velocity extension method in capturing the interface position. The proposed level sets approach is employed to study the α-γ phase transformation in RDX single crystal shocked along the (100) plane. Example problems in one and three dimensions are presented. We observe smooth evolution of the phase interface along the shock direction in both models. There is no diffusion of the interface during the zero level set evolution in the three dimensional model. The level sets approach is shown to capture the characteristics of the shock-induced α-γ phase transformation such as stress relaxation behind the phase interface and the finite time required for the phase transformation to complete. The regularization energy based level sets approach is efficient, robust, and easy to implement.

  17. Dynamic behaviour and shock-induced martensite transformation in near-beta Ti-5553 alloy under high strain rate loading

    Directory of Open Access Journals (Sweden)

    Wang Lin


    Full Text Available Ti-5553 alloy is a near-beta titanium alloy with high strength and high fracture toughness. In this paper, the dynamic behaviour and shock-induced martensite phase transformation of Ti-5553 alloy with alpha/beta phases were investigated. Split Hopkinson Pressure Bar was employed to investigate the dynamic properties. Microstructure evolutions were characterized by Scanning Electronic Microscopy and Transmission Electron Microscope. The experimental results have demonstrated that Ti-5553 alloy with alpha/beta phases exhibits various strain rate hardening effects, both failure through adiabatic shear band. Ti-5553 alloy with Widmannstatten microstructure exhibit more obvious strain rate hardening effect, lower critical strain rate for ASB nucleation, compared with the alloy with Bimodal microstructures. Under dynamic compression, shock-induced beta to alpha” martensite transformation occurs.

  18. High-Pressure Phases in Shock-Induced Melt Veins from the Umbarger L6 Chondrite: Constraints on Shock Conditions (United States)

    Xie, Z.; Tomioka, N.; Sharp, T. G.


    Shock-induced melt veins in the Umbarger L6 (S6) chondrite contain a previously unknown set of high-pressure phases consisting of ringwoodite ((Mg, Fe)2SiO4), akimotoite ((Mg, Fe)SiO3-ilmenite), augite ((Ca, Na)(Mg, Fe, Al)(Si, Al)2O6), and hollandite-structured plagioclase ((Na, K, Ca)(Al, Si)4O8). Crystallization of akimotoite suggests supercooling of the melt vein during adiabatic decompression. High-pressure minerals are common in highly shocked (S6) L6 chondrites. These minerals, which occur within or adjacent to shock-induced melt veins, provide evidence of very high pressure and temperature conditions during impact events. The goal of this study is to characterize the high-pressure mineral assemblages of the melt veins in the L6 chondrite Umbarger to better understand crystallization conditions, and the shock history of meteorite parent body. Mineral assemblages in shock-induced melt veins have been used to estimate crystallization conditions during shock metamorphism. based on phase equilibrium data. Umbarger was previously classified as shock stage S4, based on deformation features not associated with melt veins. Based on previously unrecognized ringwoodite in the melt veins of Umbarger, we classified the shock stage as S6. Further transmission electron microscopy (TEM) study reveals several other high-pressure phases in melt veins that can be used to infer crystallization and shock conditions.

  19. Heat shock genes–integrating cell survival and death

    Indian Academy of Sciences (India)


    Mar 22, 2007 ... Heat shock induced gene expression and other cellular responses help limit the damage caused by stress and thus facilitate cellular recovery. Cellular damage also triggers apoptotic cell death through several pathways. This paper briefly reviews interactions of the major heat shock proteins with ...

  20. Fractional crystallization of olivine melt inclusion in shock-induced chondritic melt vein (United States)

    Miyahara, M.; El Goresy, A.; Ohtani, E.; Kimura, M.; Ozawa, S.; Nagase, T.; Nishijima, M.


    The formation of ringwoodite, wadsleyite and majorite from their parental low-pressure polymorphs in melt veins in chondritic meteorites is usually interpreted to be the result of shock-induced solid-state phase transformation. Formation and survival of individual mineral melt enclaves in the chondritic high-pressure melt was not considered a viable possibility. We report evidence for melting of individual large olivine fragments entrained in melt veins, their survival as melt enclaves in the chondritic melts and their subsequent fractional crystallization at high-pressures and temperatures. The fractionally crystallized olivine melt enclaves appear to be ubiquitous in chondrites. In contrast, Ca-poor pyroxene fragments in the same veins and Ca-poor pyroxene in chondrules entrained do not show any sign of melting. Texture and compositions of olivine fragments are indicative of fractional crystallization from individual olivine melts alone. Fragments of original unzoned olivine (Fa 24-26) melted, and melts subsequently fractionally crystallized to Mg-rich wadsleyite (Fa 6-10) and Mg-poor ringwoodite (Fa 28-33) with a compositional gap of ≤26 mol% fayalite. In contrast, compositions of ringwoodite and wadsleyite that emerged from solid-sate phase transformations are identical to that of parental olivine thus erasing any source of enigma. The olivine monomineralic melts barely show any signs of mixing with the chondritic liquid prior to or during their individual fractional crystallization. Our findings demonstrate that the formation of high-pressure minerals during shock events in asteroids also results from melting and fractional crystallization from some individual mineral melts that barely mixed with the chondritic melt host, a mechanism previously not recognized or accepted.

  1. Estimating Shock Pressures in Chondrites From High-Pressure Minerals in Shock-induced Melt Veins (United States)

    Xie, Z.; Sharp, T. G.


    High-pressure minerals are common in highly shocked (S6) L6 chondrites, occurring within or adjacent to shock-induced melt veins and melt pockets. They provide natural examples of high-pressure minerals that make up the Earth's transition zone (410 to 660 km depth) and lower mantle, as well as a record of high-pressure and temperature conditions during impact events on chondrite parent bodies. The high-pressure minerals that crystallize in melt veins and pockets can be used as an alternative means of investigating shock pressure. We used transmission electron microscopy (TEM) to characterize the shock-vein mineralogy in seven L6 chondrites ranging from shock stage S6 to S3: Tenham (S6), Umbarger (S6), Roy (S3-5), Ramsdorf (S4), Kunashak (S4), Nakhon Pathon (S4) and La Lande (S4). Tenham contains assemblages that reflect variable cooling rates during crystallization. Majorite plus magnesiow\\x81stite occur in the center of melt veins, whereas ringwoodite, akimotoite and round amorphous grains (probably vitrified MgSiO3-pervoskite) occur along melt-vein edges. In addition, a symplectitic intergrowth of majorite and an amorphous phase has been observed, which probably represents clinopyroxene that has disassociated into majorite plus CaSiO3-pervoskite. High pressure minerals in the Umbarger melt veins include: ringwoodite, akimotoite ((Mg,Fe)SiO3-ilmenite), augite, and hollandite-structured plagioclase. In addition, Fe2SiO4-spinel (new mineral) and stishovite occur in SiO2-FeO rich melt. High-pressure minerals in the Roy melt veins include ringwoodite and majorite. Melt veins in Ramsdorf, Kunashak, Nakhon Pathon and La lande contain fine-grained olivines and pyroxenes that are defect free and interpreted as having crystallized from the melt. Crystallization pressures can be inferred from the mineral assemblages in the melt veins and available phase equilibrium data. Melt veins in Tenham crystallized at pressure of approximately 25 GPa; Umbarger at pressure between 18

  2. Heat

    CERN Document Server

    Lawrence, Ellen


    Is it possible to make heat by rubbing your hands together? Why does an ice cube melt when you hold it? In this title, students will conduct experiments to help them understand what heat is. Kids will also investigate concepts such as which materials are good at conducting heat and which are the best insulators. Using everyday items that can easily be found around the house, students will transform into scientists as they carry out step-by-step experiments to answer interesting questions. Along the way, children will pick up important scientific skills. Heat includes seven experiments with detailed, age-appropriate instructions, surprising facts and background information, a "conclusions" section to pull all the concepts in the book together, and a glossary of science words. Colorful, dynamic designs and images truly put the FUN into FUN-damental Experiments.

  3. High-pressure phases in shock-induced melt of the unique highly shocked LL6 chondrite Northwest Africa 757 (United States)

    Hu, Jinping; Sharp, Thomas G.


    Northwest Africa 757 is unique in the LL chondrite group because of its abundant shock-induced melt and high-pressure minerals. Olivine fragments entrained in the melt transform partially and completely into ringwoodite. Plagioclase and Ca-phosphate transform to maskelynite, lingunite, and tuite. Two distinct shock-melt crystallization assemblages were studied by FIB-TEM analysis. The first melt assemblage, which includes majoritic garnet, ringwoodite plus magnetite-magnesiowüstite, crystallized at pressures of 20-25 GPa. The other melt assemblage, which consists of clinopyroxene and wadsleyite, solidified at ~15 GPa, suggesting a second veining event under lower pressure conditions. These shock features are similar to those in S6 L chondrites and indicate that NWA 757 experienced an intense impact event, comparable to the impact event that disrupted the L chondrite parent body at 470 Ma.

  4. Synchronized turbo apoptosis induced by cold-shock (United States)

    Fransen, J. H.; Dieker, J. W.; Hilbrands, L. B.; Berden, J. H.


    In our research on the role of apoptosis in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE), we aim to evaluate the effects of early and late apoptotic cells and blebs on antigen presenting cells. This requires the in vitro generation of sufficiently large and homogeneous populations of early and late apoptotic cells. Here, we present a quick method encountered by serendipity that results in highly reproducible synchronized homogeneous apoptotic cell populations. In brief, granulocytic 32Dcl3 cells are incubated on ice for 2 h and subsequently rewarmed at 37°C. After 30–90 min at 37°C more than 80–90% of the cells become early apoptotic (Annexin V positive/propidium iodide negative). After 24 h of rewarming at 37°C 98% of the cells were late apoptotic (secondary necrotic; Annexin V positive/propidium iodide positive). Cells already formed apoptotic blebs at their cell surface after approximately 20 min at 37°C. Inter-nucleosomal chromatin cleavage and caspase activation were other characteristics of this cold-shock-induced process of apoptosis. Consequently, apoptosis could be inhibited by a caspase inhibitor. Finally, SLE-derived anti-chromatin autoantibodies showed a high affinity for apoptotic blebs generated by cold-shock. Overall, cold-shock induced apoptosis is achieved without the addition of toxic compounds or antibodies, and quickly leads to synchronized homogeneous apoptotic cell populations, which can be applied for various research questions addressing apoptosis. PMID:20972831

  5. Thermal shock induced dynamics of a spacecraft with a flexible deploying boom (United States)

    Shen, Zhenxing; Li, Huijian; Liu, Xiaoning; Hu, Gengkai


    The dynamics in the process of deployment of a flexible extendible boom as a deployable structure on the spacecraft is studied. For determining the thermally induced vibrations of the boom subjected to an incident solar heat flux, an axially moving thermal-dynamic beam element based on the absolute nodal coordinate formulation which is able to precisely describe the large displacement, rotation and deformation of flexible body is presented. For the elastic forces formulation of variable-length beam element, the enhanced continuum mechanics approach is adopted, which can eliminate the Poisson locking effect, and take into account the tension-bending-torsion coupling deformations. The main body of the spacecraft, modeled as a rigid body, is described using the natural coordinates method. In the derived nonlinear thermal-dynamic equations of rigid-flexible multibody system, the mass matrix is time-variant, and a pseudo damping matrix which is without actual energy dissipation, and a heat conduction matrix which is relative to the moving speed and the number of beam element are arisen. Numerical results give the dynamic and thermal responses of the nonrotating and spinning spacecraft, respectively, and show that thermal shock has a significant influence on the dynamics of spacecraft.

  6. Shock-induced ringwoodite rims around olivine fragments in melt vein of Antarctic chondrite GRV022321 : Transforma-tion Mechanism (United States)

    Xie, Z.; Liu, X.; Sharp, T. G.; De Carli, P. S.


    Here we report electron microprobe (EMAP), Raman spectroscopy, and FIB-transmission electron microscopy (TEM) results of the ringwoodite rims around olivine cores in shock-induced melt veins of the Antarctic chondrites GRV022321. The purpose of this study is to elucidate the mechanisms of transformation and Mg-Fe diffusion of the olivine to ringwoodite, and estimate the shock duration using kinetics. GRV022321 chondrite has a network of black veins which enclose abundant host-rock fragments of olivine, partially trans-formed to ringwoodite. Most of the enclosed fragments have sizes ranging from 5 μm to 30 μm, with a brighter rim up to several μm wide and a dark core in reflected light and BSE images. The Raman data reveal that the rim mineral is ringwoodite, and the core minerals are dominated by olivine with minor ringwoodite. EMAP data confirm that the ringwoodite in rim is richer in fay-lite (Fa50) than the olivine core (Fa10). The olivine-rich cores are heterogeneous with variable BSE contrast, and some points have the same Fa value as the host olivine Fa 23. The occurrence of the rounded and smooth grains of partially transformed olivine embedded in the fine matrix in shock-induced melt veins indicates that they were host-rock fragments entrained into the shock melt. The rims of these entrained oli-vines transformed to ringwoodite by solid-state transformation. The variable extent of transformation is likely a result of local temperature variations within the entrained olivines, with the hotter rim regions transforming to ringwoodite. Iron partitioned into the ringwoodite from the cooler olivine core by Mg-Fe interdiffusion. This Fe interdiffusion implies that either the diffusion was very rapid or that the shock duration was very long. We are using ringwoodite growth rates and Fe-Mg diffusion to explore transformation temperatures and times for the growth of fayalite-rich ringwoodite rims. This will be discussed in the context of impact processes.

  7. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2. (United States)

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan


    Tumor necrosis factor alpha (TNFα) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNFα on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNFα stimulus. We observed that HepG2 cell revealed a higher resistance to TNFα-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNFα, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNFα/control ratio>2.0 or expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNFα might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNFα. Collectively, these findings indicate that TNFα alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells.

  8. Shock-Induced Disappearance and Subsequent Recovery of Plasmaspheric Hiss: Coordinated Observations of RBSP, THEMIS, and POES Satellites (United States)

    Liu, Nigang; Su, Zhenpeng; Gao, Zhonglei; Reeves, G. D.; Zheng, Huinan; Wang, Yuming; Wang, Shui


    Plasmaspheric hiss is an extremely low frequency whistler-mode emission contributing significantly to the loss of radiation belt electrons. There are two main competing mechanisms for the generation of plasmaspheric hiss: excitation by local instability in the outer plasmasphere and origination from chorus outside the plasmasphere. Here on the basis of the analysis of an event of shock-induced disappearance and subsequent recovery of plasmaspheric hiss observed by RBSP, THEMIS, and POES missions, we attempt to identify its dominant generation mechanism. In the preshock plasmasphere, the local electron instability was relatively weak and the hiss waves with bidirectional Poynting fluxes mainly originated from the dayside chorus waves. On arrival of the shock, the removal of preexisting dayside chorus and the insignificant variation of low-frequency wave instability caused the prompt disappearance of hiss waves. In the next few hours, the local instability in the plasmasphere was greatly enhanced due to the substorm injection of hot electrons. The enhancement of local instability likely played a dominant role in the temporary recovery of hiss with unidirectional Poynting fluxes. These temporarily recovered hiss waves were generated near the equator and then propagated toward higher latitudes. In contrast, both the enhancement of local instability and the recurrence of prenoon chorus contributed to the substantial recovery of hiss with bidirectional Poynting fluxes.

  9. Effect of Shock-Induced Cavitation Bubble Collapse on the damage in the Simulated Perineuronal Net of the Brain. (United States)

    Wu, Yuan-Ting; Adnan, Ashfaq


    The purpose of this study is to conduct modeling and simulation to understand the effect of shock-induced mechanical loading, in the form of cavitation bubble collapse, on damage to the brain's perineuronal nets (PNNs). It is known that high-energy implosion due to cavitation collapse is responsible for corrosion or surface damage in many mechanical devices. In this case, cavitation refers to the bubble created by pressure drop. The presence of a similar damage mechanism in biophysical systems has long being suspected but not well-explored. In this paper, we use reactive molecular dynamics (MD) to simulate the scenario of a shock wave induced cavitation collapse within the perineuronal net (PNN), which is the near-neuron domain of a brain's extracellular matrix (ECM). Our model is focused on the damage in hyaluronan (HA), which is the main structural component of PNN. We have investigated the roles of cavitation bubble location, shockwave intensity and the size of a cavitation bubble on the structural evolution of PNN. Simulation results show that the localized supersonic water hammer created by an asymmetrical bubble collapse may break the hyaluronan. As such, the current study advances current knowledge and understanding of the connection between PNN damage and neurodegenerative disorders.

  10. Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction Using IL-6 as a Resuscitation Adjuvant (United States)


    target cell type as well as the pro-inflammatory stimulus. This is illustrated by the fact that Stat3a, not Stat3b, is known to mediate anti...Constitutive STAT3 activation in intestinal T cells from patients with Crohn’s disease. J Biol Chem 278: 16777–16781. 50. Mudter J, Weigmann B, Bartsch B

  11. Estimating shock pressures based on high-pressure minerals in shock-induced melt veins of L chondrites (United States)

    Xie, Zhidong; Sharp, Thomas G.; de Carli, Paul S.

    Here we report the transmission electron microscopy (TEM) observations of the mineral assemblages and textures in shock-induced melt veins from seven L chondrites of shock stages ranging from S3 to S6. The mineral assemblages combined with phase equilibrium data are used to constrain the crystallization pressures, which can be used to constrain shock pressure in some cases. Thick melt veins in the Tenham L6 chondrite contain majorite and magnesiowüstite in the center, and ringwoodite, akimotoite, vitrified silicate-perovskite, and majorite in the edge of the vein, indicating crystallization pressure of ˜25 GPa. However, very thin melt veins (5-30 μm wide) in Tenham contain glass, olivine, clinopyroxene, and ringwoodite, suggesting crystallization during transient low-pressure excursions as the shock pressure equilibrated to a continuum level. Melt veins of Umbarger include ringwoodite, akimotoite, and clinopyroxene in the vein matrix, and Fe2SiO4-spinel and stishovite in SiO2-FeO-rich melt, indicating a crystallization pressure of ˜18 GPa. The silicate melt veins in Roy contain majorite plus ringwoodite, indicating pressure of ˜20 GPa. Melt veins of Ramsdorf and Nakhon Pathon contain olivine and clinoenstatite, indicating pressure of less than 15 GPa. Melt veins of Kunashak and La Lande include albite and olivine, indicating crystallization at less than 2.5 GPa. Based upon the assemblages observed, crystallization of shock veins can occur before, during, or after pressure release. When the assemblage consists of high-pressure minerals and that assemblage is constant across a larger melt vein or pocket, the crystallization pressure represents the equilibrium shock pressure.

  12. High-pressure phases in shock-induced melt veins of the Umbarger l6 chondrite: Constraints of shock pressure (United States)

    Xie, Zhidong; Sharp, Thomas G.


    We report a previously undocumented set of high-pressure minerals in shock-induced melt veins of the Umbarger L6 chondrite. High-pressure minerals were identified with TEM using selected-area electron diffraction, and energy-dispersive X-ray spectroscopy. Ringwoodite (Fa30), akimotoite (En11Fs89), and augite (En42Wo33Fs25) were found in the silicate matrix of the melt vein, representing the crystallization from a silicate melt during the shock pulse. Ringwoodite (Fa27) and hollandite-structured plagioclase were also found as polycrystalline aggregates in the melt vein, representing solid-state transformation or melting with subsequent crystallization of entrained host-rock fragments in the vein. In addition, Fe2SiO4-spinel (Fa66-Fa99) and stishovite crystallized from a FeO-SiO2-rich zone in the melt vein, which formed by shock melting of FeO-SiO2-rich material that had been altered and metasomatized prior to shock. Based on the pressure stabilities of the high-pressure minerals, ringwoodite, akimotoite, and Ca-clinopyroxene, the melt vein crystallized at approximately 18 GPa. The Fe2SiO4-spinel + stishovite assemblage in the FeO-SiO2-rich melts is consistent with crystallization of the melt-vein matrix at the pressure up to 18 GPa. The crystallization pressure of ?18 GPa is much lower than the 45-90 GPa pressure one would conclude from the S6 shock effects in melt veins (St?ffler et al. 1991) and somewhat less than the 25-30 GPa inferred from S5 shock effects (Schmitt 2000) found in the bulk rock.

  13. RNA-Seq-based analysis of the physiologic cold shock-induced changes in Moraxella catarrhalis gene expression.

    Directory of Open Access Journals (Sweden)

    Violeta Spaniol

    Full Text Available BACKGROUND: Moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. The prevalence of pharyngeal colonization and respiratory tract infections caused by M. catarrhalis is greatest in winter. We investigated how M. catarrhalis uses the physiologic exposure to cold air to regulate pivotal survival systems that may contribute to M. catarrhalis virulence. RESULTS: In this study we used the RNA-seq techniques to quantitatively catalogue the transcriptome of M. catarrhalis exposed to a 26 °C cold shock or to continuous growth at 37 °C. Validation of RNA-seq data using quantitative RT-PCR analysis demonstrated the RNA-seq results to be highly reliable. We observed that a 26 °C cold shock induces the expression of genes that in other bacteria have been related to virulence a strong induction was observed for genes involved in high affinity phosphate transport and iron acquisition, indicating that M. catarrhalis makes a better use of both phosphate and iron resources after exposure to cold shock. We detected the induction of genes involved in nitrogen metabolism, as well as several outer membrane proteins, including ompA, m35-like porin and multidrug efflux pump (acrAB indicating that M. catarrhalis remodels its membrane components in response to downshift of temperature. Furthermore, we demonstrate that a 26 °C cold shock enhances the induction of genes encoding the type IV pili that are essential for natural transformation, and increases the genetic competence of M. catarrhalis, which may facilitate the rapid spread and acquisition of novel virulence-associated genes. CONCLUSION: Cold shock at a physiologically relevant temperature of 26 °C induces in M. catarrhalis a complex of adaptive mechanisms that could convey novel pathogenic functions and may contribute to enhanced colonization and virulence.

  14. Overload of the heat shock protein H11/HspB8 triggers melanoma cell apoptosis through activation of Transforming Growth Factor β activated kinase 1 (TAK1) (United States)

    Li, Baiquan; Smith, Cynthia C.; Laing, Jennifer M.; Gober, Michael D.; Liu, Ling; Aurelian, Laure


    Molecular therapeutics is a recognized promising approach for melanoma, but relevant target genes remain elusive. We report that overload of the recently cloned H11/HspB8 induces apoptosis in 55% of examined melanoma cultures. Apoptosis was determined by activation of caspases-9 and -3 and TUNEL, and was not seen in normal melanocytes. It was associated with H11/HspB8 complexation with TAK1 and activation of TAK1 and p38MAPK. TAK1 was not bound, nor activated by the H11/HspB8 mutant W51C, which has dominant anti-apoptotic activity. β-catenin was phosphorylated by activated TAK1, inhibiting its nuclear accumulation and MITF and CDK2 expression. The dominant negative TAK1 mutant K63W inhibited β-catenin phosphorylation and caspase activation. The data indicate that H11/HspB8 overload causes melanoma growth arrest and apoptosis through TAK1 activation and suggest that H11/HspB8 is a promising molecular therapy target. PMID:17173073

  15. Shock induced cavity collapse (United States)

    Skidmore, Jonathan; Doyle, Hugo; Tully, Brett; Betney, Matthew; Foster, Peta; Ringrose, Tim; Ramasamy, Rohan; Parkin, James; Edwards, Tom; Hawker, Nicholas


    Results from the experimental investigation of cavity collapse driven by a strong planar shock (>6km/s) are presented. Data from high speed framing cameras, laser backlit diagnostics and time-resolved pyromety are used to validate the results of hydrodynamic front-tracking simulations. As a code validation exercise, a 2-stage light gas gun was used to accelerate a 1g Polycarbonate projectile to velocities exceeding 6km/s; impact with a PMMA target containing a gas filled void results in the formation of a strong shockwave with pressures exceeding 1Mbar. The subsequent phenomena associated with the collapse of the void and excitation of the inert gas fill are recorded and compared to simulated data. Variation of the mass density and atomic number of the gas fill is used to alter the plasma parameters furthering the extent of the code validation.

  16. Induction of endothelial cell apoptosis by heat-shock protein 60-reactive antibodies from anti-endothelial cell autoantibody-positive systemic lupus erythematosus patients. (United States)

    Dieudé, Mélanie; Senécal, Jean-Luc; Raymond, Yves


    To determine whether anti-endothelial cell autoantibodies (AECAs) from systemic lupus erythematosus (SLE) patients with the antiphospholipid syndrome are involved in the initial endothelial cell (EC) membrane perturbation effect that is postulated to provide a target for antiphospholipid antibody (aPL) binding and, hence, to trigger the thrombotic cascade. To identify the AECA antigenic target on ECs and to determine the mechanism whereby the EC membrane is disrupted. AECAs from SLE patients were assayed for binding to ECs by flow cytometry. Positive AECAs were assayed by immunoblotting, and a consensus antigen was identified by mass spectrometry. This candidate antigen was tested in recombinant form for AECA recognition. AECAs were affinity-purified on this antigen and incubated with ECs to determine their physiologic effects. Anti-Hsp60 antibody titers were determined by enzyme-linked immunosorbent assay. The relationship of anti-Hsp60 status and lupus anticoagulant (LAC) status to thrombotic manifestations between disease onset and the last followup visit were analyzed. Most of the SLE sera (73%) possessed IgG that bound to the surface of ECs. These positive IgG shared reactivity against a 60-kd EC surface polypeptide that was identified as human Hsp60. The presence of Hsp60 at the EC surface was established using anti-Hsp60 antibodies from commercial sources or affinity-purified from SLE sera that bound ECs. Incubation of ECs with these anti-Hsp60 antibodies induced apoptosis in a time- and dose-dependent manner, as determined by Hoechst 33342 dye staining of condensed nuclei and by annexin V binding to surface phosphatidylserine. Anti-Hsp60 antibodies were not restricted to SLE patients, but were found in patients with other autoimmune diseases. However, anti-Hsp60 antibodies were significantly associated with an increased frequency of thrombosis when present in combination with LAC in the SLE patients. The presence of Hsp60 at the surface of ECs serves as a

  17. Effect of cinnamon (Cinnamomum zeylanicum) bark oil on heat stress-induced changes in sperm production, testicular lipid peroxidation, testicular apoptosis, and androgenic receptor density in developing Japanese quails. (United States)

    Türk, Gaffari; Şimşek, Ülkü G; Çeribaşı, Ali O; Çeribaşı, Songül; Özer Kaya, Şeyma; Güvenç, Mehmet; Çiftçi, Mehmet; Sönmez, Mustafa; Yüce, Abdurrauf; Bayrakdar, Ali; Yaman, Mine; Tonbak, Fadime


    The aim of this study was to investigate the effect of cinnamon bark oil (CBO) on heat stress (HS)-induced changes in sperm production, testicular lipid peroxidation, testicular apoptosis, and androgenic receptor (AR) density in developing Japanese quails. Fifteen-day-old 90 male chicks were assigned to two main groups. The first group (45 chicks) was kept in a thermoneutral room at 22 °C for 24 h/day. The second group (45 chicks) was kept in a room with high ambient temperature at 34 °C for 8 h/day (from 9 AM-5 PM) and at 22 °C for 16 h/day. Each of these two main groups was then divided into three subgroups (CBO groups 0, 250, 500 ppm) consisting of 15 chicks (six treatment groups in 2 × 3 factorial order). Each of subgroups was replicated for three times and each replicate included five chicks. Heat stress caused significant decreases in body weight, spermatid and testicular sperm numbers, the density of testicular Bcl-2 (antiapoptotic marker) and AR immunopositivity, and significant increases in testicular lipid peroxidation level, the density of testicular Bax (apoptotic marker) immunopositivity, and a Bax/Bcl-2 ratio along with some histopathologic damages. However, 250 and 500 ppm CBO supplementation provided significant improvements in HS-induced increased level of testicular lipid peroxidation, decreased number of spermatid and testicular sperm, decreased densities of Bcl-2 and AR immunopositivity, and some deteriorated testicular histopathologic lesions. In addition, although HS did not significantly affect the testicular glutathione level, addition of both 250 and 500 ppm CBO to diet of quails reared in both HS and thermoneutral conditions caused a significant increase when compared with quails without any consumption of CBO. In conclusion, HS-induced lipid peroxidation causes testicular damage in developing male Japanese quails and, consumption of CBO, which has antiperoxidative effect, protects their testes against HS. Copyright © 2015 Elsevier

  18. Effects of Early Continuous Venovenous Hemofiltration on E-Selectin, Hemodynamic Stability, and Ventilatory Function in Patients with Septic-Shock-Induced Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Jian-biao Meng


    Full Text Available Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS (not acute kidney injury, AKI with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group (n=24 and a non-ECVVH group (n=27. Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2 ratio, extravascular lung water index (EVLWI, and E-selectin level were not significantly different between groups (all P>0.05. Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVH group (all P<0.05 at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU were shorter in ECVVH group (all P<0.05, but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI, treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU.

  19. Hyperthermia: an effective strategy to induce apoptosis in cancer cells. (United States)

    Ahmed, Kanwal; Tabuchi, Yoshiaki; Kondo, Takashi


    Heat has been used as a medicinal and healing modality throughout human history. The combination of hyperthermia (HT) with radiation and anticancer agents has been used clinically and has shown positive results to a certain extent. However, the clinical results of HT treatment alone have been only partially satisfactory. Cell death following HT treatment is a function of both temperature and treatment duration. HT induces cancer cell death through apoptosis; the degree of apoptosis and the apoptotic pathway vary in different cancer cell types. HT-induced reactive oxygen species production are responsible for apoptosis in various cell types. However, the underlying mechanism of signal transduction and the genes related to this process still need to be elucidated. In this review, we summarize the molecular mechanism of apoptosis induced by HT, enhancement of heat-induced apoptosis, and the genetic network involved in HT-induced apoptosis.

  20. Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination (United States)

    Brewer-Jensen, Paul; Wilson, Carrie B.; Abernethy, John; Mollison, Lonna; Card, Samantha


    Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process. We previously showed that Su(s) promotes exosome-mediated degradation of transcripts from endogenous repeated elements at an Hsp70 locus (Hsp70-αβ elements). In this report, we identify Wdr82 as a component of this process and show that it works with Su(s) to inhibit Pol II elongation through Hsp70-αβ elements. Furthermore, we show that the unstable transcripts produced during this process are polyadenylated at heterogeneous sites that lack canonical polyadenylation signals. We define two distinct regions that mediate this regulation. These results indicate that the Su(s) pathway promotes RNA degradation and transcription termination through a novel mechanism. PMID:26577379

  1. High-Resolution TVD Schemes for the Analysis of 1. Inviscid Supersonic and Transonic Flows. 2. Viscous Flows with Shock-Induced Separation and Heat Transfer (United States)


    induce.! beal tiansem1 p~rolem. These SOILtit ion are ot atdagainst solutions comp~uted with le Be, m- \\-Vrmin- lgorithim and die ’ PVI soltions are shown...the conser-vation laws for mass, Mifleti- mci- assemin l5~li n inviscid. lnconduItcting’ gais. hnteEue turn, an ’hen. th0ueretdto ar ara~clsuhtht , pvp

  2. The synthetic heat shock protein 90 (Hsp90) inhibitor EC141 induces degradation of Bcr-Abl p190 protein and apoptosis of Ph-positive acute lymphoblastic leukemia cells. (United States)

    Tong, Wei-Gang; Estrov, Zeev; Wang, Yongtao; O'Brien, Susan; Faderl, Stefan; Harris, David M; Van Pham, Quin; Hazan-Halevy, Inbal; Liu, Zhiming; Koch, Patricia; Kantarjian, Hagop; Keating, Michael J; Ferrajoli, Alessandra


    The prognosis of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is poor. Chemotherapy is rarely curative and tyrosine kinase inhibitors (TKIs) induce only transient responses. Heat shock protein 90 (Hsp90) is a chaperone protein that is important in signal transduction, cell cycle control, and transcription regulation in both normal and leukemia cells. In the current study, we tested the growth inhibitory and apoptotic effects of a novel Hsp90 inhibitor, EC141 on the Ph+ ALL lines Z-119, Z-181, and Z-33, as well as primary bone marrow-derived blasts from patients with newly diagnosed Ph+ ALL. We found that EC141 inhibited the growth of Ph+ ALL cells in a concentration-dependent manner with IC(50) ranged from 1 to 10 nM. EC141 also inhibited the proliferation of primary bone marrow-derived blasts using the ALL blast colony assay. EC141 down-regulated Hsp90 and up-regulated Hsp70 protein levels, inhibited CrkL phosphorylation, and induced degradation of Bcr-Abl p190 protein through ubiquitin-dependent proteasomal pathway. Furthermore, exposure of Ph+ ALL cells to EC141 resulted in activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and induction of apoptosis. In conclusion, our data suggest that EC141 is a potent Hsp90 inhibitor with activity against Ph+ ALL. Further studies to investigate the anticancer effect of EC141 either as a single agent, or in combination in Ph+ ALL and other hematological malignancies are warranted.

  3. Acidic pH shock induces the expressions of a wide range of stress-response genes

    Directory of Open Access Journals (Sweden)

    Hong Soon-Kwang


    Full Text Available Abstract Background Environmental signals usually enhance secondary metabolite production in Streptomycetes by initiating complex signal transduction system. It is known that different sigma factors respond to different types of stresses, respectively in Streptomyces strains, which have a number of unique signal transduction mechanisms depending on the types of environmental shock. In this study, we wanted to know how a pH shock would affect the expression of various sigma factors and shock-related proteins in S. coelicolor A3(2. Results According to the results of transcriptional and proteomic analyses, the major number of sigma factor genes were upregulated by an acidic pH shock. Well-studied sigma factor genes of sigH (heat shock, sigR (oxidative stress, sigB (osmotic shock, and hrdD that play a major role in the secondary metabolism, were all strongly upregulated by the pH shock. A number of heat shock proteins including the DnaK family and chaperones such as GroEL2 were also observed to be upregulated by the pH shock, while their repressor of hspR was strongly downregulated. Oxidative stress-related proteins such as thioredoxin, catalase, superoxide dismutase, peroxidase, and osmotic shock-related protein such as vesicle synthases were also upregulated in overall. Conclusion From these observations, an acidic pH shock was considered to be one of the strongest stresses to influence a wide range of sigma factors and shock-related proteins including general stress response proteins. The upregulation of the sigma factors and shock proteins already found to be related to actinorhodin biosynthesis was considered to have contributed to enhanced actinorhodin productivity by mediating the pH shock signal to regulators or biosynthesis genes for actinorhodin production.

  4. [The application of combined central venous pressure and oxygen metabolism parameters monitoring in diagnosing septic shock-induced left ventricular dysfunction]. (United States)

    Cui, Keliang; Wang, Xiaoting; Zhang, Hongmin; Chai, Wenzhao; Liu, Dawei


    To evaluate the value of central venous pressure (CVP), central venous oxygen saturation (ScvO₂) and venous-arterial carbon dioxide partial pressure gradient (Pv-aCO₂)) in the diagnosis of septic shock-induced left ventricular dysfunction. Consecutive patients with septic shock were enrolled from September 2013 to September 2014 in ICU at Peking Union Medical College Hospital. The data of CVP, Pv-aCO₂) and ScvO₂) were recorded and analyzed. According to the left ventricular ejection fraction (LVEF) tested by bedside echocardiography, the patients were divided into two groups: new onset of left ventricular dysfunction (LVEF < 50%) group and non-left ventricular dysfunction (LVEF ≥ 50%) group. A diagnostic model was created by logistic regression. The diagnostic performance and cut-off values of CVP, Pv-aCO₂, ScvO₂) were determined using receiver operating characteristic (ROC) curve analysis. Among 93 patients enrolled, 39 were diagnosed with left ventricular dysfunction. In the new onset group, CVP [(12.5 ± 3.9) mmHg (1 mmHg = 0.133 kPa) vs (10.4 ± 2.5) mmHg; P = 0.005] and Pv-aCO₂[(7.5 ± 3.9) mmHg vs (4.5 ± 2.6) mmHg; P < 0.001] were significantly higher than those in the non-left ventricular dysfunction group, while Scv2 [(62.4 ± 10.5)% vs (72.6 ± 9.0)%; P < 0.001] was significantly lower. As far as the diagnostic value of these three parameters were concerned for left ventricular dysfunction, the sensitivity of CVP ≥ 12.5 mmHg was 46.2%, specificity 81.5% with an area under ROC curve (AUCROC) 0.674; the sensitivity of Pv-aCO₂≥ 5.0 mmHg 76.9%, specificity 37.0%, AUCROC 0.738; the sensitivity of ScvO₂≤ 65.8% 64.1%, specificity 78.6%, AUCROC 0.775. When the cut-off values were determined by ROC, the diagnostic performance of the model was ≥ 0.377 with the sensitivity, specificity and AUCROC 82.1%, 79.6% and 0.835, respectively. In patients with septic shock, the logistic regression model established by CVP, Pv-aCO₂and Scv

  5. Ringwoodite rim around olivine core in shock-induced melt veins of Antarctic chondrite : Mechanisms of transformation and Fe-Mg diffusion (United States)

    Xie, Z.; Li, X.; Sharp, T. G.; de Carli, P. S.


    Introduction: High-pressure minerals, produced by shock metamorphism, are common in and around melt veins in highly shocked chondrites. The shock duration can be constrained by using transformation kinetics, such as the crystallization rate of the melt-vein matrix[1-2], or growth rate of the high-pressure minerals [3-4], or using elements diffusion rate between two minerals [5]. Using transformation kinetics to constrain shock duration de-pend on the details of the transformation mechanism. For example, growth of topotaxial ringwoodite in olivine with coherent interfaces is slower than growth of inclusions with incoherent interfaces [4-5]. Similarly, diffusion-controlled growth, where rates are determined by long-range diffusion, is generally much slower than interface-controlled growth, which is only dependent on diffusion across the interface [6-8]. The occurrences of the high-pressure mineral rims were recently reported in shock-induced melt veins in several heavily shocked (S6) chondrites, ALH78003, Peace River and GRV052049 [9-11]. Here we report EMAP and Raman results of the ringwoodite rims around olivine cores in shock veins of the Antarctic chondrites GRV 022321, and to elucidate the mechanisms of transformation and Mg-Fe diffusion of the olivine to ringwoodite. Results: GRV022321 has a network of black veins which enclose abundant host-rock fragments. The enclosed fragments have sizes ranging from 5 µm to 30 µm, with a brighter rim up to several µm wide and a dark core in reflected light and BSE image. The Raman data reveal that the rim mineral is ringwoodite signature, and the core minerals are dominated by olivine and mixed minor ringwoodite. EMAP data confirm that the ringwoodite in rim is richer in faylite (Fa) than the olivine core. The Fa values range from 50 to 10 with the outer rim having highest Fa value, and the inside darker area with a lower value. Discussion: The occurrence of the rounded shape grains with smooth edges embedded in the fine

  6. Ubiquitination in apoptosis signaling

    NARCIS (Netherlands)

    van de Kooij, L.W.


    The work described in this thesis focuses on ubiquitination and protein degradation, with an emphasis on how these processes regulate apoptosis signaling. More specifically, our aims were: 1. To increase the understanding of ubiquitin-mediated regulation of apoptosis signaling. 2. To identify the E3

  7. Apoptosis of neutrophils

    NARCIS (Netherlands)

    Maianski, N. A.; Maianski, A. N.; Kuijpers, T. W.; Roos, D.


    Regulation of the neutrophil life span by apoptosis provides a fine balance between their function as effector cells of host defense and a safe turnover of these potentially harmful cells. Alterations of neutrophil apoptosis are associated with a number of diseases. As do other cell types,

  8. Apoptosis and plastic surgery. (United States)

    Gastman, Brian R; Futrell, J William; Manders, Ernest K


    Apoptosis, or programmed cell death, is a phenomenon that is integral to development and cellular homeostasis. In the last decade, many of the essential molecules and pathways that control this phenomenon have been elucidated. Because apoptosis is involved in almost all physiologic and pathologic processes, the understanding of its regulation has significant clinical ramifications. This article reviews the basic understanding of programmed cell death in terms of the effector molecules and pathways. Areas of interest to plastic surgeons are reviewed as they pertain to apoptosis. These areas include allotransplantation, craniofacial and limb development, flap survival, wound healing, stem cell science, and physiologic aging. These topics have not yet been studied extensively in the context of cell death. In this review article, other related and more comprehensively studied scientific areas are used to extrapolate their relevance to apoptosis. Apoptosis is an increasingly better understood process. With the knowledge of how programmed cell death is controlled, combined with the improved ability to effectively perform genetic manipulation and to design specific chemical approaches, apoptosis is gaining clinical relevance. In the next few years, practical clinical breakthroughs will help the medical community to understand the phenomenon of apoptosis and how it relates to the needs of patients.

  9. Caspases: An apoptosis mediator

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Palai


    Full Text Available The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy - dependent biochemical mechanisms. Apoptosis is a widely conserved phenomenon helping many processes, including normal cell turnover, proper development and functioning of the immune system, hormone dependent atrophy etc. Inappropriate apoptosis (either low level or high level leads to many developmental abnormalities like, neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. To use cells for therapeutic purposes through generating cell lines, it is critical to study the cell cycle machinery and signalling pathways that controls cell death and apoptosis. Apoptotic pathways provide a fundamental protective mechanism that decreases cellular sensitivity to damaging events and allow proper developmental process in multi-cellular organisms. Major mediator of apoptosis is a family of proteins known as caspases. There are mainly fourteen types of caspases but out of them only ten caspasese have got essential role in controlling the process of apoptosis. These ten caspases have been categorized into either initiator caspases (caspase 2, 8, 9, 10 or executioner caspases (caspase 3, 6, 7. Although various types of caspases have been identified so far, the exact mechanisms of action of these groups of proteins is still to be fully understood. The aim of this review is to provide a detail overview of role of different caspases in regulating the process of apoptosis.

  10. Reaper-Induced Apoptosis

    National Research Council Canada - National Science Library

    Perry, Jennifer


    Reaper is a central regulator of apoptosis in the fly, Drosophila melanogaster. At the start of this proposal our laboratory identified what was believed to be a pro-apoptotic human homolog of Reaper...

  11. Apoptosis in Pneumovirus Infection

    Directory of Open Access Journals (Sweden)

    Reinout A. Bem


    Full Text Available Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung epithelial cells may also exacerbate lung injury, depending on the extent, the timing and specific location in the lungs. Differential apoptotic responses of epithelial cells versus innate immune cells (e.g., neutrophils, macrophages during pneumovirus infection can further contribute to the complex and delicate balance between host defense and disease pathogenesis. The purpose of this manuscript is to give an overview of the role of apoptosis in pneumovirus infection. We will examine clinical and experimental data concerning the various pro-apoptotic stimuli and the roles of apoptotic epithelial and innate immune cells during pneumovirus disease. Finally, we will discuss potential therapeutic interventions targeting apoptosis in the lungs.

  12. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2


    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan


    Tumor necrosis factor alpha (TNF?) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNF? on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNF? stimulus. We observed that HepG2 cell revealed a higher resistance to TNF?-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By usin...

  13. Heat Shock Partially Dissociates the Overlapping Modules of the Yeast Protein-Protein Interaction Network: A Systems Level Model of Adaptation (United States)

    Mihalik, Ágoston; Csermely, Peter


    Network analysis became a powerful tool giving new insights to the understanding of cellular behavior. Heat shock, the archetype of stress responses, is a well-characterized and simple model of cellular dynamics. S. cerevisiae is an appropriate model organism, since both its protein-protein interaction network (interactome) and stress response at the gene expression level have been well characterized. However, the analysis of the reorganization of the yeast interactome during stress has not been investigated yet. We calculated the changes of the interaction-weights of the yeast interactome from the changes of mRNA expression levels upon heat shock. The major finding of our study is that heat shock induced a significant decrease in both the overlaps and connections of yeast interactome modules. In agreement with this the weighted diameter of the yeast interactome had a 4.9-fold increase in heat shock. Several key proteins of the heat shock response became centers of heat shock-induced local communities, as well as bridges providing a residual connection of modules after heat shock. The observed changes resemble to a ‘stratus-cumulus’ type transition of the interactome structure, since the unstressed yeast interactome had a globally connected organization, similar to that of stratus clouds, whereas the heat shocked interactome had a multifocal organization, similar to that of cumulus clouds. Our results showed that heat shock induces a partial disintegration of the global organization of the yeast interactome. This change may be rather general occurring in many types of stresses. Moreover, other complex systems, such as single proteins, social networks and ecosystems may also decrease their inter-modular links, thus develop more compact modules, and display a partial disintegration of their global structure in the initial phase of crisis. Thus, our work may provide a model of a general, system-level adaptation mechanism to environmental changes. PMID:22022244

  14. Apoptosis and cell cycle

    Directory of Open Access Journals (Sweden)

    Petrović Marija


    Full Text Available Apoptosis, a form of programmed cell death, is used to eliminate individual cells surrounded by normal cell population. It is a controlled way of cell death in which the cell actively participates by conducting precise, gene-regulated program of self-destruction, that is, cell 'suicide.' Active synthesis of macromolecules is necessary during this process. Death of individual cells is necessary to maintain a balance in living systems, so the process of apoptosis is continuously present in the body, which allows normal development, tissue homeostasis, and many other physiological processes. The molecular mechanisms that regulate apoptosis are functionally linked to other cellular mechanisms, such as control of the cell cycle, cell proliferation and differentiation, genomic stability and cellular metabolism. Damage to the DNA molecule, caused both spontaneously and under the influence of various chemical and physical agents, leads to the cell cycle arrest and activation of mechanisms that repair the damage. Depending on the type and extent of the damage, the cell either continues progression through the cell cycle, or activates the mechanisms that lead to apoptosis. Disturbances in the regulation of apoptosis and cell cycle present the molecular and biological basis of many diseases. Because of the importance of these processes during the development and progression of tumors, their use as biological markers is one of the main strategies in the formation of therapeutic approaches for the treatment of cancer.

  15. Spaceflight Associated Apoptosis (United States)

    Ichiki, Albert T.; Gibson, Linda A.; Allebban, Zuhair


    Lymphoid tissues have been shown to atrophy in rats flown on Russian spaceflights. Histological examination indicated evidence for cell degradation. Lymphoid tissues from rats flown on Spacelab Life Sciences-2 mission were analyzed for apoptosis by evidence of fragmented lymphocytes, which could be engulfed by macrophages, or DNA strand breaks using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Apoptosis was not detected in the thymus and spleen collected inflight or from the synchronous ground rats but was detected in the thymus, spleen and inguinal lymph node of the flight animals on recovery. These results indicate that the apoptosis observed in the lymphatic tissues of the rats on recovery could have been induced by the gravitational stress of reentry, corroborating the findings from the early space-flight observations.


    Directory of Open Access Journals (Sweden)

    О. M. Kapuler


    Full Text Available Abstract. Forty-two patients with progressive vulgar psoriasis (PASI = 19.7 ± 1.5 and 40 healthy volunteers were under investigation. Psoriatic patients were characterized by increased number of CD4+ CD95+ peripheral blood T lymphocytes, which correlates with clinical psoriatic score, and by increased levels of soluble Fas (sFas in serum, as compared to controls (resp., 1868.1 ± 186.8 pg/ml vs. 1281.4 ± 142.5 pg/ml, PLSD = 0.019. The levels of spontaneous lymphocyte apoptosis and anti-Fas (Mab-induced apoptosis in psoriatic patients did not differ from the controls. However, apoptosis induced by “oxidative stress” (50 M Н202, 4 hrs was depressed in the patients. Moreover, a simultaneous assessment of cell cycle structure (metachromatic staining with Acridine Orange, apoptosis and Fas receptor expression (AnnV-FITC/antiFas mAbs-PE staining following a short-term mitogenic stimulation (PHA-P, 5 µg/ml, 24 hrs were performed. We found no marked differences in mitogenic reactivity, activation-induced apoptosis, and activation-induced Fas receptor expression when studying lymphocytes from healthy donors and psoriatic patients. However, PHA-activated lymphocytes from psoriatic patients displayed a significantly decreased ratio of AnnV+CD95+ to the total AnnV+ subpopulation, thus suggesting a decreased role of Fas-dependent mechanisms of apoptosis during the cell activation. The data obtained confirm a view, that an abnormal lymphocyte “apoptotic reactivity”, which plays a crucial role in the mechanisms of autoimmunity, may also of importance in the pathogenesis of psoriasis.

  17. Racemization of Valine by Impact-Induced Heating (United States)

    Furukawa, Yoshihiro; Takase, Atsushi; Sekine, Toshimori; Kakegawa, Takeshi; Kobayashi, Takamichi


    Homochirality plays an important role in all living organisms but its origin remains unclear. It also remains unclear whether such chiral molecules survived terrestrial heavy impact events. Impacts of extraterrestrial objects on early oceans were frequent and could have affected the chirality of oceanic amino acids when such amino acids accumulated during impacts. This study investigated the effects of shock-induced heating on enantiomeric change of valine with minerals such as olivine ([Mg0.9, Fe0.1]2SiO4), hematite (Fe2O3), and calcite (CaCO3). With a shock wave generated by an impact at 0.8 km/s, both uc(d)- and uc(l)-enriched valine were significantly decomposed and partially racemized under all experimental conditions. Different minerals had different shock impedances; therefore, they provided different P-T conditions for identical impacts. Furthermore, the high pH of calcite promoted the racemization of valine. The results indicate that in natural hypervelocity impacts, amino acids in shocked oceanic water would have decomposed completely, since impact velocity and the duration of shock compression and heating are typically greater in hypervelocity impact events than those in experiments. Even with the shock wave by the impact of small and decelerated projectiles in which amino acids survive, the shock heating may generate sufficient heat for significant racemization in shocked oceanic water. However, the duration of shock induced heating by small projectiles is limited and the population of such decelerated projectiles would be limited. Therefore, even though impacts of asteroids and meteorites were frequent on the prebiotic Earth, impact events would not have significantly changed the ee of proteinogenic amino acids accumulated in the entire ocean.

  18. Apoptosis and inflammation

    Directory of Open Access Journals (Sweden)

    C. Haanen


    Full Text Available During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972 introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed. Apoptosis, in contrast to necrosis, is not harmful to the host and does not induce any inflammatory reaction. The principal event that leads to inflammatory disease is cell damage, induced by chemical/physical injury, anoxia or starvation. Cell damage means leakage of cell contents into the adjacent tissues, resulting in the capillary transmigration of granulocytes to the injured tissue. The accumulation of neutrophils and release of enzymes and oxygen radicals enhances the inflammatory reaction. Until now there has been little research into the factors controlling the accumulation and the tissue load of granulocytes and their histotoxic products in inflammatory processes. Neutrophil apoptosis may represent an important event in the control of intlamtnation. It has been assumed that granulocytes disintegrate to apoptotic bodies before their fragments are removed by local macrophages. Removal of neutrophils from the inflammatory site without release of granule contents is of paramount importance for cessation of inflammation. In conclusion, apoptotic cell death plays an important role in inflammatory processes and in the resolution of inflammatory reactions. The facts known at present should stimulate further research into the role of neutrophil, eosinophil and macrophage apoptosis in inflammatory diseases.

  19. Apoptosis induced by Staphylococcus aureus in human monocytic ...

    African Journals Online (AJOL)



    May 23, 2011 ... Unfortunately, the cellular and molecular mechanisms responsible for this phenomenon are still poorly understood. The present study .... An annexin V apoptosis detection kit was purchased from RD Systems ..... Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 ...


    Directory of Open Access Journals (Sweden)

    A.G. Gasanov


    Full Text Available Research into molecular apoptosis mechanisms in patients with cardio-vascular diseases is one of the pressing issues in modern medicine. Many mechanisms of this phenomenon still remain unexamined, the role of inductors and regulators in cardiomyocyte apoptosis has not yet been fully explained. This review summarizes research data that analyze the role that various groups of cell death inductors and regulators, such as FasL, Fas-R and mitochondrial apoptosis factors. Influence of the Bcl-2 protein family as apoptosis regulators is described. Developments in programmed cell death are reviewed.Key words: apoptosis, cell death mechanisms, mitochondria, cardiamyocytes.

  1. Fullerene and apoptosis

    Directory of Open Access Journals (Sweden)

    M. A. Orlova


    Full Text Available Fullerene derivatives superfamily attracts a serious attention as antiviral and anticancer agents and drug delivery carriers as well. A large number of such fullerene С60 derivatives obtained to date. However, there is an obvious deficit of information about causes and mechanisms of immediately and long-term consequences of their effects in vivo which is a true obstacle on the way leading to practical medical use of them. First, this concerns their impact on the proliferation, apoptosis and necrosis regulation. Fullerene nanoparticle functionalization type, their sizes and surface nanopathology are of great importance to further promoting of either cytoprotective or cytotoxic effects. This lecture provides modern concept analysis regarding fullerenes effects on apoptosis pathway in normal and tumor cells.

  2. Cl- channels in apoptosis

    DEFF Research Database (Denmark)

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida


    A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K(+), Cl(-), and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl(-) channels LRRC8, TMEM16/anoctamin......, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also......(-) channels or as regulators of other apoptotic Cl(-) channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated...

  3. Apoptosis and DNA Methylation

    Directory of Open Access Journals (Sweden)

    Richard R. Meehan


    Full Text Available Epigenetic mechanisms assist in maintaining gene expression patterns and cellular properties in developing and adult tissues. The molecular pathology of disease states frequently includes perturbation of DNA and histone methylation patterns, which can activate apoptotic pathways associated with maintenance of genome integrity. This perspective focuses on the pathways linking DNA methyltransferases and methyl-CpG binding proteins to apoptosis, and includes new bioinformatic analyses to characterize the evolutionary origin of two G/T mismatch-specific thymine DNA glycosylases, MBD4 and TDG.

  4. Reassessing apoptosis in plants. (United States)

    Dickman, Martin; Williams, Brett; Li, Yurong; de Figueiredo, Paul; Wolpert, Thomas


    Cell death can be driven by a genetically programmed signalling pathway known as programmed cell death (PCD). In plants, PCD occurs during development as well as in response to environmental and biotic stimuli. Our understanding of PCD regulation in plants has advanced significantly over the past two decades; however, the molecular machinery responsible for driving the system remains elusive. Thus, whether conserved PCD regulatory mechanisms include plant apoptosis remains enigmatic. Animal apoptotic regulators, including Bcl-2 family members, have not been identified in plants but expression of such regulators can trigger or suppress plant PCD. Moreover, plants exhibit nearly all of the biochemical and morphological features of apoptosis. One difference between plant and animal PCD is the absence of phagocytosis in plants. Evidence is emerging that the vacuole may be key to removal of unwanted plant cells, and may carry out functions that are analogous to animal phagocytosis. Here, we provide context for the argument that apoptotic-like cell death occurs in plants.

  5. Apoptosis Resistance in Endometriosis

    Directory of Open Access Journals (Sweden)

    Liselotte Mettler


    Full Text Available Introduction: In a cytological analysis of endometriotic lesions neither granulocytes nor cytotoxic T-cells appear in an appreciable number. Based on this observation we aimed to know, whether programmed cell death plays an essential role in the destruction of dystopic endometrium. Disturbances of the physiological mechanisms of apoptosis, a persistence of endometrial tissue could explain the disease. Another aspect of this consideration is the proliferation competence of the dystopic mucous membrane. Methods: Endometriotic lesions of 15 patients were examined through a combined measurement of apoptosis activity with the TUNEL technique (terminal deoxyribosyltransferase mediated dUTP Nick End Labeling and the proliferation activity (with the help of the Ki-67-Antigens using the monoclonal antibody Ki-S5. Results: Twelve out of 15 women studied showed a positive apoptotic activity of 3-47% with a proliferation activity of 2-25% of epithelial cells. Therefore we concluded that the persistence of dystopic endometrium requires proliferative epithelial cells from middle to lower endometrial layers. Conclusion: A dystopia misalignment of the epithelia of the upper layers of the functionalism can be rapidly eliminated by apoptotic procedures.

  6. Nucleolus and apoptosis. (United States)

    Horký, M; Kotala, V; Anton, M; Wesierska-Gadek, J


    The nucleolus represents a highly dynamic nuclear compartment of the interphase nucleus. It plays a key role in ribosome biogenesis. The number of nucleoli, their size, and their activity increase in exponentially growing cells; therefore these parameters reflect the proliferating activity of the cells. A variety of staining techniques have been employed to vizualize nucleolar changes in malignant cells. Staining of so-called nucleolar organizer regions (NORs), based upon a strong avidity of nucleolar proteins to bind silver ions, represents the technique most frequently used by pathologists. Nucleolar changes and pleomorphism associated with overt proliferation of tumor cells have also been documented by immunohistochemical and ultrastructural studies. Contrary to cell proliferation, cytostatics-induced changes of nucleolar phenotype in malignant cells point to a potential role of nucleolar components in the execution of active cell death. Recent studies have provided direct clues that so-called death domains and other apoptosis-related proteins are accumulated in nucleoli upon induction of active cell death. It can be concluded that the plurifunctionality of nucleoli regarding cell proliferation and apoptosis could open new vistas toward understanding dysregulation in malignant cells.

  7. Heat Islands (United States)

    EPA's Heat Island Effect Site provides information on heat islands, their impacts, mitigation strategies, related research, a directory of heat island reduction initiatives in U.S. communities, and EPA's Heat Island Reduction Program.

  8. Heat Waves (United States)

    Heat Waves Dangers we face during periods of very high temperatures include: Heat cramps: These are muscular pains and ... having trouble with the heat. If a heat wave is predicted or happening… - Slow down. Avoid strenuous ...

  9. High-pressure phases in a shock-induced melt vein of the Tenham L6 chondrite: Constraints on shock pressure and duration (United States)

    Xie, Zhidong; Sharp, Thomas G.; DeCarli, Paul S.


    The microtexture and mineralogy of a 580-μm-wide melt vein in the Tenham L6 chondrite were investigated using field-emission scanning electron microscopy and transmission electron microscopy to better understand the shock conditions. The melt vein consists of a matrix of silicate plus metal-sulfide grains that crystallized from immiscible melts, and sub-rounded fragments of the host chondrite that have been entrained in the melt and transformed to polycrystalline high-pressure silicates. The melt-vein matrix contains two distinct textures and mineral assemblages corresponding to the vein edge and interior. The 30-μm-wide vein edge consists of vitrified silicate perovskite + ringwoodite + akimotoite + majorite with minor metal-sulfide. The 520-μm-wide vein interior consists of majorite + magnesiowüstite with irregular metal-sulfide blebs. Although these mineral assemblages are distinctly different, the pressure stabilities of both assemblages are consistent with crystallization from similar pressure conditions: the melt-vein edge crystallized at about 23-25 GPa and the vein interior crystallized at about 21-25 GPa. This relatively narrow pressure range suggests that the melt vein either crystallized at a constant equilibrium shock pressure of ˜25 GPa or during a relatively slow pressure release. Using a finite element heat transfer program to model the thermal history of this melt vein during shock, we estimate that the time required to quench this 580-μm-wide vein was ˜40 ms. Because the entire vein contains high-pressure minerals that crystallized from the melt, the shock-pressure duration was at least 40 ms. Using a synthetic Hugoniot for Tenham and assuming that the sample experienced a peak-shock pressure of 25 GPa near the impact site, we estimate that the Tenham parent body experienced an impact with collision velocity ˜2 km/s. Based on a one-dimensional planar impact model, we estimate that the projectile size was >150 m in thickness.

  10. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan


    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  11. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan


    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  12. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan


    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  13. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan


    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of PCa cells by methyl selenium (Se...

  14. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan


    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of PCa cells by methyl selenium (Se)/selenol...

  15. Methylselenium and Prostate Cancer Apoptosis

    National Research Council Canada - National Science Library

    Lu, Junxuan


    The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer (PCa...

  16. Heat Stress (United States)

    ... Publications and Products Programs Contact NIOSH NIOSH HEAT STRESS Recommend on Facebook Tweet Share Compartir NEW OSHA- ... hot environments may be at risk of heat stress. Exposure to extreme heat can result in occupational ...

  17. Heat pumps

    CERN Document Server

    Macmichael, DBA


    A fully revised and extended account of the design, manufacture and use of heat pumps in both industrial and domestic applications. Topics covered include a detailed description of the various heat pump cycles, the components of a heat pump system - drive, compressor, heat exchangers etc., and the more practical considerations to be taken into account in their selection.

  18. Broad targeting of resistance to apoptosis in cancer (United States)

    Mohammad, Ramzi M.; Muqbil, Irfana; Lowe, Leroy; Yedjou, Clement; Hsu, Hsue-Yin; Lin, Liang-Tzung; Siegelin, Markus David; Fimognari, Carmela; Kumar, Nagi B.; Dou, Q. Ping; Yang, Huanjie; Samadi, Abbas K.; Russo, Gian Luigi; Spagnuolo, Carmela; Ray, Swapan K.; Chakrabarti, Mrinmay; Morre, James D.; Coley, Helen M.; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, William G.; Yang, Xujuan; Boosani, Chandra S.; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I.; Keith, W. Nicol; Bilsland, Alan; Halicka, Dorota; Nowsheen, Somaira; Azmi, Asfar S.


    Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer. PMID:25936818

  19. Placental apoptosis in recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    Tarek A. Atia


    Full Text Available Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. We aimed to study the effect of placental apoptosis on recurrent miscarriage (RM. Placental tissue samples were collected from 40 women with RM (study group and 30 women with sporadic spontaneous abortion (control group. Samples were prepared and stained immunohistochemically with markers for both the apoptotic protein (p53 and anti-apoptotic Bcl-2 antibodies. Our results showed that expression of the apoptotic (p53 protein was significantly increased in the placental tissues of the RM group (p = 0.003. By contrast, the expression of anti-apoptotic (Bcl-2 antibodies was significantly increased in the placental tissues of the control group (p = 0.025. We concluded that placental apoptosis plays a crucial role in pregnancy continuation. However, increased p53 expression in placental tissue in early pregnancy could negatively affect pregnancy continuation.

  20. Tonic shock induces detachment of Giardia lamblia.

    Directory of Open Access Journals (Sweden)

    Wendy R Hansen

    Full Text Available BACKGROUND: The parasite Giardia lamblia must remain attached to the host small intestine in order to proliferate and subsequently cause disease. However, little is known about the factors that may cause detachment in vivo, such as changes in the aqueous environment. Osmolality within the proximal small intestine can vary by nearly an order of magnitude between host fed and fasted states, while pH can vary by several orders of magnitude. Giardia cells are known to regulate their volume when exposed to changes in osmolality, but the short-timescale effects of osmolality and pH on parasite attachment are not known. METHODOLOGY AND PRINCIPAL FINDINGS: We used a closed flow chamber assay to test the effects of rapid changes in media osmolality, tonicity, and pH on Giardia attachment to both glass and C2(Bbe-1 intestinal cell monolayer surfaces. We found that Giardia detach from both surfaces in a tonicity-dependent manner, where tonicity is the effective osmolality experienced by the cell. Detachment occurs with a characteristic time constant of 25 seconds (SD = 10 sec, n = 17 in both hypo- and hypertonic media but is otherwise insensitive to physiologically relevant changes in media composition and pH. Interestingly, cells that remain attached are able to adapt to moderate changes in tonicity. By exposing cells to a timed pattern of tonicity variations and adjustment periods, we found that it is possible to maximize the tonicity change experienced by the cells, overcoming the adaptive response and resulting in extensive detachment. CONCLUSIONS AND SIGNIFICANCE: These results, conducted with human-infecting Giardia on human intestinal epithelial monolayers, highlight the ability of Giardia to adapt to the changing intestinal environment and suggest new possibilities for treatment of giardiasis by manipulation of tonicity in the intestinal lumen.

  1. Shock Induced Starting of Gasdynamic Laser Nozzles. (United States)


    0.069 inch Total Length = 0.902 inch Design Mach = 3.23 Large Single Nozzle is 4 times all dimensions. V Fig 2. Small Single Nozzle Profile 7 -- 250...the presence of time-stable oblique shocks originating at the exit plane edges of the nozzle profile and extending downstream to form the classi- cal...test section was essentially the same in series 4, 7, 8, and 10. Part A of Fig 15 depicts the small single- nozzle profile , nozzle block holders

  2. Shock-induced deformation twinning in tantalum

    Energy Technology Data Exchange (ETDEWEB)

    Murr, L.E.; Niou, C.S.; Pappu, S.; Kennedy, C. [Univ. of Texas, El Paso, TX (United States). Dept. of Metallurgical and Materials Engineering; Meyers, M.A.; Chen, Y.J. [Univ. of California, San Diego, La Jolla, CA (United States). Dept. of Applied Mechanics and Engineering Sciences


    Shock-wave deformation of tantalum to a pressure of 45 GPa and duration of 1.8 {micro}s generates profuse twinning. The post-shock mechanical response is significantly affected, with shock hardening exceeding the expected hardening due to the transient shock strain {epsilon}{sub s} = (4/3)ln(V/V{sub 0}); this enhanced hardening, and other alterations in response, are attributed to the barriers presented to plastic deformation by the deformation twins. A constitutive model is proposed that predicts the threshold shock stress for mechanical twinning; it is based on the application of the Swegle-Grady relationship between shock stress and strain rate to constitute equations describing the critical stress for slip and twinning. This constitutive model incorporates grain-size effects and predicts a threshold twinning stress that is a function of temperature and grain size; predictions of the model are in qualitative agreement with experimental results.

  3. Ultrafast shock induced chemistry in hydrogen peroxide (United States)

    Armstrong, Michael; Zaug, Joseph; Goldman, Nir; Kuo, I.-Feng; Crowhurst, Jonathan; Howard, W. Michael; Carter, Jeffrey; Kashgarian, Michaele; Chesser, John; Barbee, Troy; Bastea, Sorin


    Although strong compression waves have been used to study the equilibrium high pressure and temperature properties of materials for more than half a century, the study of ultrafast strain rate dependent material transformations, while promising, is only beginning to be fully explored. Shock waves can change the thermodynamic state of a material over a picosecond time scale, i.e. faster than the time scale of quasi-equilibrium reaction kinetics for many reactive systems. This fundamental property of shock compression suggests the possibility of selecting reaction paths via modulation of applied compression waves on a time scale that is faster than the time scale of reaction kinetics. Here we present experiments and thermochemical and molecular dynamics simulations on a model system, hydrogen peroxide, which demonstrate that the applied strain rate can be used alongside the pressure and temperature to control reactivity in bulk matter, thus enabling the exploration of otherwise inaccessible chemical reaction paths.

  4. Heat pumps

    CERN Document Server

    Brodowicz, Kazimierz; Wyszynski, M L; Wyszynski


    Heat pumps and related technology are in widespread use in industrial processes and installations. This book presents a unified, comprehensive and systematic treatment of the design and operation of both compression and sorption heat pumps. Heat pump thermodynamics, the choice of working fluid and the characteristics of low temperature heat sources and their application to heat pumps are covered in detail.Economic aspects are discussed and the extensive use of the exergy concept in evaluating performance of heat pumps is a unique feature of the book. The thermodynamic and chemical properties o

  5. The mechanism of PDT-induced apoptosis (United States)

    Cai, Xiongwei; Liu, Timon C.; Ding, Xin-Min; Gu, Ying; Liu, Fan-Guang; Liu, Song-Hao


    Photodynamic therapy (PDT) can induce apoptosis in many cancer cells in vitro and in tumors in vivo. Cells become more oxidation with PDT, and maintain differentiation and proliferation, go apoptosis and necrosis with the increase of reactive oxygen species (ROS) concentration. ROS can induce apoptosis through mitochondria by inhibiting respiration chain or oxidative phosphorylation or damaging mitochondrial membrane. ROS can initiate apoptosis through endoplamic reticulum(ER) by opening Ca2+ channel or starting unfold protein response (UPR). ROS can also induce apoptosis through Golgi by producing ganglioside GD3 by use of ceramide, which induces apoptosis by activating caspase-3, JNK and p38 MAPK. It can also induce apoptosis by activating Bip (mitochondria-dependant) or preocaspase-12 (mitochondria- independent) or inhibiting protein synthesizing. There are so complicated cross-talking among different signal pathways or organnells that we think PDT-induced apoptosis is mediated by multiplex pathways and excessive levels in a refined network.

  6. Anti-apoptotic signaling and failure of apoptosis in the ischemic rat hippocampus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Lassmann, Hans; Johansen, Flemming Fryd


    colchicine injection severed as a reference for classical apoptosis. Heat shock protein 70 (Hsp70), neuronal apoptosis inhibitory protein (NAIP) and manganese superoxide dismutase (MnSOD) were upregulated in the majority of intact CA1 neurons paralleling the occurrence of CA1 neuronal death (days 3......-7) as well as in a proportion of apoptosis-(Colchicine did not provoke an anti-apoptotic response in DGC at all. In addition, more than 70% of apoptosis- and necrosis-like CA1 neurons had completely lost their RCC subunits suggesting bioenergetic failure......; by contrast, following colchicine injection, 88% of all apoptotic DGC presented RCC subunits. Thus, anti-apoptotic proteins may, in a subset of ischemic CA1 neurons, prevent cell death, while in others, affected by pronounced energy failure, they may cause secondary necrosis....

  7. Plasma membrane protein OsMCA1 is involved in regulation of hypo-osmotic shock-induced Ca2+ influx and modulates generation of reactive oxygen species in cultured rice cells

    Directory of Open Access Journals (Sweden)

    Kurusu Takamitsu


    Full Text Available Abstract Background Mechanosensing and its downstream responses are speculated to involve sensory complexes containing Ca2+-permeable mechanosensitive channels. On recognizing osmotic signals, plant cells initiate activation of a widespread signal transduction network that induces second messengers and triggers inducible defense responses. Characteristic early signaling events include Ca2+ influx, protein phosphorylation and generation of reactive oxygen species (ROS. Pharmacological analyses show Ca2+ influx mediated by mechanosensitive Ca2+ channels to influence induction of osmotic signals, including ROS generation. However, molecular bases and regulatory mechanisms for early osmotic signaling events remain poorly elucidated. Results We here identified and investigated OsMCA1, the sole rice homolog of putative Ca2+-permeable mechanosensitive channels in Arabidopsis (MCAs. OsMCA1 was specifically localized at the plasma membrane. A promoter-reporter assay suggested that OsMCA1 mRNA is widely expressed in seed embryos, proximal and apical regions of shoots, and mesophyll cells of leaves and roots in rice. Ca2+ uptake was enhanced in OsMCA1-overexpressing suspension-cultured cells, suggesting that OsMCA1 is involved in Ca2+ influx across the plasma membrane. Hypo-osmotic shock-induced ROS generation mediated by NADPH oxidases was also enhanced in OsMCA1-overexpressing cells. We also generated and characterized OsMCA1-RNAi transgenic plants and cultured cells; OsMCA1-suppressed plants showed retarded growth and shortened rachises, while OsMCA1-suppressed cells carrying Ca2+-sensitive photoprotein aequorin showed partially impaired changes in cytosolic free Ca2+ concentration ([Ca2+]cyt induced by hypo-osmotic shock and trinitrophenol, an activator of mechanosensitive channels. Conclusions We have identified a sole MCA ortholog in the rice genome and developed both overexpression and suppression lines. Analyses of cultured cells with altered


    Directory of Open Access Journals (Sweden)

    S. L. Rovin


    Full Text Available Heat recovery is an effective method of shortening specific energy consumption. new constructions of recuperators for heating and cupola furnaces have been designed and successfully introduced. two-stage recuperator with computer control providing blast heating up to 600 °C and reducing fuel consumption by 30% is of special interest.

  9. Apoptosis in oral erythema multiforme. (United States)

    Chrysomali, E; Lozada-Nur, F; Dekker, N P; Papanicolaou, S I; Regezi, J A


    Cell death was evaluated in oral erythema multiforme to test the hypothesis that apoptosis may be a mechanism by which keratinocytes die in this condition. Ten erythema multiforme and five control oral mucosa biopsy specimens were evaluated in immunohistochemically stained sections for apoptosis-regulating proteins Bcl-2, Bcl-x, Bax, p53, Fas, and Fas-ligand. Apoptotic keratinocytes, determined by a detection method for DNA fragmentation (TUNEL) and by conventional morphologic criteria were counted per high power field. Keratinocyte staining for Bcl-2 protein was comparable in erythema multiforme and controls. Bcl-x expression was reduced in five erythema multiforme cases. Staining for Bax protein differed in six erythema multiforme cases and showed variable intensity in layers under the parakeratin. Only slight differences in staining patterns of Fas and Fas-ligand proteins were noted between erythema multiforme and controls. The number of apoptotic keratinocytes evaluated by morphologic examination was significantly higher in erythema multiforme (mean per high power field, 0.90 +/- 0.2; controls, 0.06 +/- 0.04; p erythema multiforme, 0.43 +/- 0.1; controls, 0.02 +/- 0.02). Overexpression of p53 protein was seen in basal keratinocytes in five erythema multiforme specimens (mean, 17.5 +/- 4.03 per high power field; controls 1.2 +/- 0.3). There is evidence that cell death in erythema multiforme is at least in part due to apoptosis. The apoptotic mechanism may be related to an altered expression of apoptosis-regulating proteins. Although measurable alterations in the phenotypic expression of Fas and Fas-ligand proteins were not apparent, activation of Fas/Fas-ligand system could still be involved in the induction of apoptosis in erythema multiforme.

  10. Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2 (United States)

    Bissinger, Rosi; Lang, Elisabeth; Ghashghaeinia, Mehrdad; Singh, Yogesh; Zelenak, Christine; Fehrenbacher, Birgit; Honisch, Sabina; Chen, Hong; Fakhri, Hajar; Umbach, Anja T.; Liu, Guilai; Rexhepaj, Rexhep; Liu, Guoxing; Schaller, Martin; Mack, Andreas F.; Lupescu, Adrian; Birnbaumer, Lutz; Lang, Florian; Qadri, Syed M.


    Putative functions of the heterotrimeric G-protein subunit Gαi2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca2+ activity and ceramide. In the present study, we show that Gαi2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from Gαi2-deficient mice (Gαi2−/−) and corresponding wild-type mice (Gαi2+/+). Our data show that plasma erythropoietin levels, erythrocyte maturation markers, erythrocyte counts, hematocrit and hemoglobin concentration were similar in Gαi2−/− and Gαi2+/+ mice but the mean corpuscular volume was significantly larger in Gαi2−/− mice. Spontaneous PS exposure of circulating Gαi2−/− erythrocytes was significantly lower than that of circulating Gαi2+/+ erythrocytes. PS exposure was significantly lower in Gαi2−/− than in Gαi2+/+ erythrocytes following ex vivo exposure to hyperosmotic shock, bacterial sphingomyelinase or C6 ceramide. Erythrocyte Gαi2 deficiency further attenuated hyperosmotic shock-induced increase of cytosolic Ca2+ activity and cell shrinkage. Moreover, Gαi2−/− erythrocytes were more resistant to osmosensitive hemolysis as compared to Gαi2+/+ erythrocytes. In conclusion, Gαi2 deficiency in erythrocytes confers partial protection against suicidal cell death. PMID:27499046

  11. The role of apoptosis in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    B. D. Uhal


    Full Text Available Apoptosis has been defined as "gene-directed cellular self-destruction" and is an active process that is tightly regulated by a number of gene products, which promote or block cell death. Apoptotic death can be triggered by a wide variety of stimuli and, importantly, not all cells necessarily undergo apoptosis in response to the same stimulus. Abnormal regulation of apoptosis has been implicated in a wide range of diseases and approaches to modifying apoptosis represent important future therapeutic strategies. Idiopathic pulmonary fibrosis (IPF is a progressive and relentless disease involving scarring of the lung, which has been recognised as the most lethal interstitial lung disease. In the lungs of IPF patients, increased epithelial apoptosis, together with decreased apoptosis of myofibroblasts, represents persistent findings (particularly in areas of collagen deposition supporting an interaction between altered apoptosis and the pathogenesis of the disease. Data from human tissues and animal models are refining current knowledge of the processes involved in this pathogenesis. This has challenged the dogma that IPF is purely a disease of unresolved inflammation by emphasising the central roles played by the alveolar epithelial cell and myofibroblasts and, as part of that role, the importance of altered apoptosis. Evidence suggests blockade of epithelial cell apoptosis can prevent subsequent collagen deposition, and induction of myofibroblast apoptosis, at least theoretically, would be expected to resolve ongoing fibrosis. These two concepts raise the prospect of therapeutic intervention aimed at modifying apoptosis and, thus, fibrosis in idiopathic pulmonary fibrosis.

  12. Heated Goggles (United States)


    The electrically heated ski goggles shown incorporate technology similar to that once used in Apollo astronauts' helmet visors, and for the same reason-providing fogfree sight in an activity that demands total vision. Defogging is accomplished by applying heat to prevent moisture condensation. Electric heat is supplied by a small battery built into the h goggles' headband. Heat is spread across the lenses by means of an invisible coating of electrically conductive metallic film. The goggles were introduced to the market last fall. They were designed by Sierracin Corporation, Sylmar, California, specialists in the field of heated transparent materials. The company produces heated windshields for military planes and for such civil aircraft as the Boeing 747, McDonnell Douglas DC-10 and Lockheed L-1011 TriStar.

  13. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    Energy Technology Data Exchange (ETDEWEB)

    Tang, J.; Jiang, Y. [Southern Medical University, Nanfang Hospital, Department of Anesthesia, Guangzhou, China, Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou (China); Tang, Y.; Chen, B. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China); Sun, X. [Laboratory of Traditional Chinese Medicine Syndrome, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou (China); Su, L.; Liu, Z. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China)


    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.

  14. Heat Stroke

    DEFF Research Database (Denmark)

    Mørch, Sofie Søndergaard; Andersen, Johnny Dohn Holmgren; Bestle, Morten Heiberg


    Heat stroke is an acute, life-threatening emergency characterized clinically by elevated body temperature and central nervous system dysfunction. Early recognition and treatment including aggressive cooling and management of life-threatening systemic complications are essential to reduce morbidity...... and mortality. This case report describes two Danish patients diagnosed with heat stroke syndrome during a heat wave in the summer of 2014. Both patients were morbidly obese and had several predisposing illnesses. However since heat stroke is a rare condition in areas with temperate climate, they were...... not diagnosed until several days after admittance; hence treatment with cooling was delayed. Both patients were admitted to the intensive care unit, where they were treated with an external cooling device and received treatment for complications. Both cases ended fatally. As global warming continues, more heat...

  15. Automatic image analysis of multicellular apoptosis process. (United States)

    Ziraldo, Riccardo; Link, Nichole; Abrams, John; Ma, Lan


    Apoptotic programmed cell death (PCD) is a common and fundamental aspect of developmental maturation. Image processing techniques have been developed to detect apoptosis at the single-cell level in a single still image, while an efficient algorithm to automatically analyze the temporal progression of apoptosis in a large population of cells is unavailable. In this work, we have developed an ImageJ-based program that can quantitatively analyze time-lapse microscopy movies of live tissues undergoing apoptosis with a fluorescent cellular marker, and subsequently extract the temporospatial pattern of multicellular response. The protocol is applied to characterize apoptosis of Drosophila wing epithelium cells at eclosion. Using natural anatomic structures as reference, we identify dynamic patterns in the progression of apoptosis within the wing tissue, which not only confirms the previously observed collective cell behavior from a quantitative perspective for the first time, but also reveals a plausible role played by the anatomic structures in Drosophila apoptosis.

  16. Sun Ginseng Protects Endothelial Progenitor Cells From Senescence Associated Apoptosis (United States)

    Im, Wooseok; Chung, Jin-Young; Bhan, Jaejun; Lim, Jiyeon; Lee, Soon-Tae; Chu, Kon; Kim, Manho


    Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside Rg3 prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG), which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by β-galactosidase (β-gal) staining. Staining with 4′-6-Diamidino-2-phenylindole verified that most adherent cells (93±2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of β-gal-positive EPCs was decreased from 93.8±2.0% to 62.5±3.6% by SG treatment. A fluorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms. PMID:23717107

  17. Mycobacterium tuberculosis effectors interfering host apoptosis signaling. (United States)

    Liu, Minqiang; Li, Wu; Xiang, Xiaohong; Xie, Jianping


    Tuberculosis remains a serious human public health concern. The coevolution between its pathogen Mycobacterium tuberculosis and human host complicated the way to prevent and cure TB. Apoptosis plays subtle role in this interaction. The pathogen endeavors to manipulate the apoptosis via diverse effectors targeting key signaling nodes. In this paper, we summarized the effectors pathogen used to subvert the apoptosis, such as LpqH, ESAT-6/CFP-10, LAMs. The interplay between different forms of cell deaths, such as apoptosis, autophagy, necrosis, is also discussed with a focus on the modes of action of effectors, and implications for better TB control.

  18. Apoptosis and Molecular Targeting Therapy in Cancer (United States)

    Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki


    Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

  19. [Novel Anticancer Strategy Targeting Switch Mechanisms in Two Types of Cell Death: Necrosis and Apoptosis]. (United States)

    Sato, Akira


     Two types of cell death, necrosis and apoptosis, are defined in terms of cell death morphological features. We have been studying the mechanisms by which cell death processes are switched during the treatment of mouse tumor FM3A with anticancer, 5-fluoro-2'-deoxyuridine (FUdR): it induces original clone F28-7 to necrosis, but its sub-clone F28-7-A to apoptosis. We identified several such switch regulators of cell death: heat shock protein 90 (HSP90), lamin-B1, cytokeratin-19, and activating transcription factor 3 (ATF3), by using transcriptomic, proteomic analyses and siRNA screening. For example, the inhibition of HSP90 by its inhibitor geldanamycin in F28-7 caused a shift from necrosis to apoptosis. We also observed that the knockdown of lamin-B1, cytokeratin-19, or ATF3 expression in F28-7 resulted in a shift from necrosis to apoptosis. Recently, we used microRNA (miRNA, miR) microarray analyses to investigate the miRNA expression profiles in these sister cells. The miR-351 and miR-743a were expressed at higher levels in F28-7-A than in F28-7. Higher expression of miR-351 or miR-743a in F28-7, induced by transfecting the miR mimics, resulted in a switch of cell death mode: necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in morphological changes, and mode of cell death from apoptosis to necrosis. These findings suggest that the identified cell death regulators may have key roles in switching cell death mode. Possible mechanisms involving cell death regulators in the switch of necrosis or apoptosis are discussed. We propose a novel anticancer strategy targeting the switch regulators of necrosis or apoptosis.

  20. Heat pipes

    CERN Document Server

    Dunn, Peter D


    It is approximately 10 years since the Third Edition of Heat Pipes was published and the text is now established as the standard work on the subject. This new edition has been extensively updated, with revisions to most chapters. The introduction of new working fluids and extended life test data have been taken into account in chapter 3. A number of new types of heat pipes have become popular, and others have proved less effective. This is reflected in the contents of chapter 5. Heat pipes are employed in a wide range of applications, including electronics cooling, diecasting and injection mo

  1. Fas-induced apoptosis in malnourished infants

    African Journals Online (AJOL)


    regulation of the hematopoietic system6. Moreover, many studies have demonstrated that the apoptosis of immune cell in undernourished organisms may cause an increase in the organism's susceptibility to diseases related to immune suppression7,8,9. Lymphocyte apoptosis was described in peripheral blood and ...

  2. Apoptosis in mammalian oocytes: a review. (United States)

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K


    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals.

  3. Cortisol inhibits apoptosis in carp neutrophilic granulocytes.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Flik, G.; Verburg-van Kemenade, B.M.L.


    The direct effect of cortisol treatment on carp neutrophil viability was examined in vitro. Cortisol treatment caused an inhibition of neutrophil apoptosis. The effect was blocked by glucocorticoid receptor blocker RU486, showing that rescue from apoptosis was receptor mediated. Using binding

  4. Crosstalk between apoptosis and inflammation in atherosclerosis

    NARCIS (Netherlands)

    Westra, Marijke Marianne


    In this thesis the role of several apoptosis regulating proteins in the development of atherosclerosis and atherosclerotic plaque stability is investigated. Apoptosis of different cell types in atherosclerotic plaques, such as macrophages and smooth muscle cells may inhibit or promote plaque

  5. Targeted induction of apoptosis for cancer therapy

    NARCIS (Netherlands)

    Bremer, Edwin


    Introduction to the thesis Programmed cell death, known as apoptosis, is an essential cellular homeostasis mechanism that ensures correct development and function of multi-cellular organisms. The pivotal importance of correct execution of apoptosis is apparent from the many human diseases with

  6. Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That Survived Sublethal Heat Shock

    Directory of Open Access Journals (Sweden)

    A. E. Vinogradov


    Full Text Available High temperature is a critical environmental and personal factor. Although heat shock is a well-studied biological phenomenon, hyperthermia response of stem cells is poorly understood. Previously, we demonstrated that sublethal heat shock induced premature senescence in human endometrial mesenchymal stem cells (eMSC. This study aimed to investigate the fate of eMSC-survived sublethal heat shock (SHS with special emphasis on their genetic stability and possible malignant transformation using methods of classic and molecular karyotyping, next-generation sequencing, and transcriptome functional analysis. G-banding revealed random chromosome breakages and aneuploidy in the SHS-treated eMSC. Molecular karyotyping found no genomic imbalance in these cells. Gene module and protein interaction network analysis of mRNA sequencing data showed that compared to untreated cells, SHS-survived progeny revealed some difference in gene expression. However, no hallmarks of cancer were found. Our data identified downregulation of oncogenic signaling, upregulation of tumor-suppressing and prosenescence signaling, induction of mismatch, and excision DNA repair. The common feature of heated eMSC is the silence of MYC, AKT1/PKB oncogenes, and hTERT telomerase. Overall, our data indicate that despite genetic instability, SHS-survived eMSC do not undergo transformation. After long-term cultivation, these cells like their unheated counterparts enter replicative senescence and die.

  7. The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis

    DEFF Research Database (Denmark)

    Mollerup, Jens; Berchtold, Martin Werner


    The heat shock protein 90 co-chaperone p23 has recently been shown to be up-regulated in cancer cells and down-regulated in atheroschlerotic plaques. We found that p23 is degraded during apoptosis induced by several stimuli, including Fas and TNFa-receptor activation as well as staurosporine...... treatment. Caspase inhibition protected p23 from degradation in several cell lines. In addition, recombinant caspase-3 and 8 cleaved p23 at Asp 142 generating a degradation product of 18 kDa as seen in apoptotic cells. Truncated p23 is further degraded in a proteasome dependent process during apoptosis....... Furthermore, we found that the anti-aggregating activity of truncated p23 was reduced compared to full length p23 indicating that caspase mediated p23 degradation contributes to protein destabilisation in apoptosis....

  8. Modular Heat Exchanger With Integral Heat Pipe (United States)

    Schreiber, Jeffrey G.


    Modular heat exchanger with integral heat pipe transports heat from source to Stirling engine. Alternative to heat exchangers depending on integrities of thousands of brazed joints, contains only 40 brazed tubes.

  9. Autophagy and apoptosis: where do they meet? (United States)

    Mukhopadhyay, Subhadip; Panda, Prashanta Kumar; Sinha, Niharika; Das, Durgesh Nandini; Bhutia, Sujit Kumar


    Autophagy and apoptosis are two important cellular processes with complex and intersecting protein networks; as such, they have been the subjects of intense investigation. Recent advances have elucidated the key players and their molecular circuitry. For instance, the discovery of Beclin-1's interacting partners has resulted in the identification of Bcl-2 as a central regulator of autophagy and apoptosis, which functions by interacting with both Beclin-1 and Bax/Bak respectively. When localized to the endoplasmic reticulum and mitochondria, Bcl-2 inhibits autophagy. Cellular stress causes the displacement of Bcl-2 from Beclin-1 and Bax, thereby triggering autophagy and apoptosis, respectively. The induction of autophagy or apoptosis results in disruption of complexes by BH3-only proteins and through post-translational modification. The mechanisms linking autophagy and apoptosis are not fully defined; however, recent discoveries have revealed that several apoptotic proteins (e.g., PUMA, Noxa, Nix, Bax, XIAP, and Bim) modulate autophagy. Moreover, autophagic proteins that control nucleation and elongation regulate intrinsic apoptosis through calpain- and caspase-mediated cleavage of autophagy-related proteins, which switches the cellular program from autophagy to apoptosis. Similarly, several autophagic proteins are implicated in extrinsic apoptosis. This highlights a dual cellular role for autophagy. On one hand, autophagy degrades damaged mitochondria and caspases, and on the other hand, it provides a membrane-based intracellular platform for caspase processing in the regulation of apoptosis. In this review, we highlight the crucial factors governing the crosstalk between autophagy and apoptosis and describe the mechanisms controlling cell survival and cell death.

  10. Heat convection

    Energy Technology Data Exchange (ETDEWEB)

    Jiji, L.M. [City Univ. of New York, NY (United States). Dept. of Mechanical Engineering


    Professor Jiji's broad teaching experience lead him to select the topics for this book to provide a firm foundation for convection heat transfer with emphasis on fundamentals, physical phenomena, and mathematical modelling of a wide range of engineering applications. Reflecting recent developments, this textbook is the first to include an introduction to the challenging topic of microchannels. The strong pedagogic potential of Heat Convection is enhanced by the following ancillary materials: (1) Power Point lectures, (2) Problem Solutions, (3) Homework Facilitator, and, (4) Summary of Sections and Chapters. (orig.)

  11. High temperature induces apoptosis and oxidative stress in pufferfish (Takifugu obscurus) blood cells. (United States)

    Cheng, Chang-Hong; Yang, Fang-Fang; Liao, Shao-An; Miao, Yu-Tao; Ye, Chao-Xia; Wang, An-Li; Tan, Jia-Wen; Chen, Xiao-Yan


    Water temperature is an important environmental factor in aquaculture farming that affects the survival and growth of organisms. The change in culture water temperature may not only modify various chemical and biological processes but also affect the status of fish populations. In previous studies, high temperature induced apoptosis and oxidative stress. However, the precise mechanism and the pathways that are activated in fish are still unclear. In the present study, we investigated the effects of high temperature (34°C) on the induction of apoptosis and oxidative stress in pufferfish (Takifugu obscurus) blood cells. The data showed that high temperature exposure increased oxygen species (ROS), cytoplasmic free-Ca(2+) concentration and cell apoptosis. To test the apoptotic pathway, the expression pattern of some key apoptotic related genes including P53, Bax, caspase 9 and caspase 3 were examined. The results showed that acute high temperature stress induced up-regulation of these genes, suggesting that the p53-Bax pathway and the caspase-dependent apoptotic pathway could be involved in apoptosis induced by high temperature stress. Furthermore, the gene expression of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, CAT, GPx, and GR) and heat shock proteins (HSP90 and HSP70) in the blood cells were induced by high temperature stress. Taken together, our results showed that high temperature-induced oxidative stress may cause pufferfish blood cells apoptosis, and cooperatively activated p53-Bax and caspase-dependent apoptotic pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Epigallocatechin gallate induces apoptosis of monocytes. (United States)

    Kawai, Kazushige; Tsuno, Nelson H; Kitayama, Joji; Okaji, Yurai; Yazawa, Kentaro; Asakage, Masahiro; Sasaki, Shin; Watanabe, Toshiaki; Takahashi, Koki; Nagawa, Hirokazu


    Monocytes are the main effector cells of the immune system, and the regulation of their survival and apoptosis is essential for monocyte-involved immune responses. Green tea polyphenol catechin has been reported to have antiallergic and anti-inflammatory activities, but its effect on monocytes has not yet been explored. To elucidate the mechanisms of the anti-inflammatory effect of catechin, we studied the effect of catechin, especially epigallocatechin gallate (EGCG), on the apoptosis of monocytes. Isolated peripheral blood monocytes were incubated without or with catechin, and apoptosis was evaluated by annexin V and propidium iodide double-staining or terminal deoxynucleotidyl assay. The activation of caspases 3, 8, and 9 was also evaluated by flow cytometry. The influence of GM-CSF or LPS, the known monocyte survival factors, on the EGCG-induced apoptosis of monocytes was investigated. Among the 4 catechin derivatives tested, EGCG and epicatechin gallate induced apoptosis of monocytes. Caspases 3, 8, and 9, which play a central role in the apoptotic cascade, were dose-dependently activated by EGCG treatment. The EGCG-induced apoptosis of monocytes was not affected by GM-CSF or LPS. Catechin, especially EGCG, by promoting monocytic apoptosis, may be a new promising anti-inflammatory agent, and should be tested in clinical trials.

  13. Honey and Apoptosis in Human Gastric Mucosa

    Directory of Open Access Journals (Sweden)

    Alireza Ostadrahimi


    Full Text Available Background: Gastric cancer is the fourth most common malignancy in the world. Honey is acomplex mixture of special biological active constituents. Honey possesses antioxidant and antitumorproperties. Nutritional studies have indicated that consumption of honey modulates therisk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisiverole in precancerous changes. Our chief study was conducted to assess the relationship betweenconsumption of honey and apoptosis in human gastric mucosa.Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred totwo hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire(FFQ and apoptosis was detected by TUNEL technique. We tested polynomial curve tofind the best fit between honey consumption and apoptosis.Results: A positive relation between honey consumption and apoptosis was found (P=0.024.Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honeyamount - 0.533(honey amount2 +1.833×10-5(honey amount7.Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis ingastric mucosa.

  14. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... for signs of heat stroke or exhaustion. Heat Stroke and Exhaustion Symptoms of early heat exhaustion symptoms ... heavy sweating; nausea; and giddiness. Symptoms of heat stroke (late stage of heat illness) include flushed, hot, ...

  15. Renewable Heating and Cooling (United States)

    Renewable heating and cooling is a set of alternative resources and technologies that can be used in place of conventional heating and cooling technologies for common applications such as water heating, space heating, space cooling and process heat.

  16. Infrared heating (United States)

    IR heating was first industrially used in the 1930s for automotive curing applications and rapidly became a widely applied technology in the manufacturing industry. Contrarily, a slower pace in the development of IR technologies for processing foods and agricultural products was observed, due to lim...

  17. Evolutionary diversity of vertebrate small heat shock proteins.

    NARCIS (Netherlands)

    Franck, E.; Madsen, O.; Rheede, T. van; Ricard, G.; Huynen, M.A.; Jong, W.W.W. de


    All vertebrates express multiple small heat shock proteins (sHsps), which are important components of the cellular chaperoning machinery and display a spectacular diversity of functions. This ranges from remodeling the cytoskeleton and inhibiting apoptosis to serving as structural proteins in eye

  18. MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5). (United States)

    Li, Dong; Liu, Yu; Li, Hua; Peng, Jing-Jing; Tan, Yan; Zou, Qiang; Song, Xiao-Feng; Du, Min; Yang, Zheng-Hui; Tan, Yong; Zhou, Jin-Jun; Xu, Tao; Fu, Zeng-Qiang; Feng, Jian-Qiong; Cheng, Peng; chen, Tao; Wei, Dong; Su, Xiao-Mei; Liu, Huan-Yi; Qi, Zhong-Chun; Tang, Li-Jun; Wang, Tao; Guo, Xin; Hu, Yong-He; Zhang, Tao


    Although microRNA-1 (miR-1) is a known liver cancer suppressor, the role of miR-1 in apoptosis of hepatoma cells has remained largely unknown. Our study shows that ectopic miR-1 overexpression induced apoptosis of liver hepatocellular carcinoma (HepG2) cells. Apoptosis inhibitor 5 (API-5) was found to be a potential regulator of miR-1 induced apoptosis, using a bioinformatics approach. Furthermore, an inverse relationship between miR-1 and API-5 expression was observed in human liver cancer tissues and adjacent normal liver tissues. Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. Our study provides a novel regulatory mechanism of miR-1 in the apoptosis of hepatoma cells. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Apoptosis – is it good or bad?

    Directory of Open Access Journals (Sweden)

    Bakir Mehić


    Full Text Available The most widely used classification of mammalian cell death recognizes two types: apoptosis and necrosis. Autophagy, which has been proposed as a third mode of cell death allows a starving cell, or in situations when cell is deprived of growth factors, to survive. Apoptosis, autophagy and necrosis, a particular mode of cell death may predominate, depending of the injury and the type of cell. [1] One very important characteristic of all multicellular organisms is apoptosis, the controlled death of cells. In necrosis, early loss of integrity of the plasma membrane resultant with swelling of the cell and its organelles. A key morphologic feature of apoptosis is collapses of cell and its subcellular components.[2] The distinction between apoptosis and necrosis is due in part to differences in how the plasma membrane participates in these processes. In apoptosis, plasma membrane integrity persists until late in the process. In necrosis, early loss of integrity of the plasma membrane allows an influx of extracellular ions and fluid, with resultant swelling of the cell and its organelles. During that time, on the inside of cell there occurs the cleavage of cytoskeletal proteins by aspartate specific proteases, which thereby collapses subcellular components. Other characteristic features are chromatin condensation, nuclear fragmentation and the formation of plasma membrane blebs. The type and intensity of noxious signals, ATP concentration, cell type, and other factors determine how cell death occurs. Acute myocardial ischemia induces necrosis (because the ischemia precipitates rapid and profound decreases of ATP, whereas chronic congestive heart failure induces apoptosis (with more modest and chronic decreases of ATP. The blockade of a particular pathway of cell death may not prevent the destruction of the cell but may instead recruit an alternative path: antiapoptotic caspase inhibitors cause hyperacute necrosis of hepatocytes and kidney tubular cells

  20. Mitochondrial disfunction and apoptosis in leukemia cells

    Directory of Open Access Journals (Sweden)

    Annamaria PALLAG


    Full Text Available Apoptosis or programmed cell death is a process which involves the intentional degradation of the cell from the inside, the participation of the mitochondria to propagate the apoptotic signal, the alteration of the phospholipid cell membrane composition, the perturbation and alteration of the cell metabolism.The antineoplastic drugs is inducing the apoptotic process in the sensitive cells.It have been studied acute lymphoblastic leukemia cells. Using Annexin V-PE Apoptosis Detection Kit and flow cytometer, the amount of cells undergoing apoptosis, in various stages of the antineoplasic treatment, was detected. At the same time, were monitored, the serum level of malondialdehyde. The results obtained confirm the alteration of the mitochondrial metabolism. We can observed the mitochondrial dysfunction role in cell apoptosis.

  1. Liposomal Sphingolipids to Target Breast Adenocarcinoma Apoptosis

    National Research Council Canada - National Science Library

    Klostergaard, Jim


    We have observed that certain sphingolipids (e.g., dimethyl-sphingosine: DMSP) induce apoptosis in vitro in tumor cells despite the over-expression of HER-2/neu and other resistance mechanisms relevant to breast cancer...

  2. Molecular Analysis of Neurotoxin-Induced Apoptosis

    National Research Council Canada - National Science Library

    D'Mello, Santosh R


    Apoptosis is a cell-suicide process that is required for the normal development of the nervous system, but that can be aberrantly activated in neurodegenerative diseases and following exposure to neurotoxins...

  3. Apoptosis and Tumor Progressionin Prostate Cancer

    National Research Council Canada - National Science Library

    Tenniswood, Martin P


    ... (as measured by BrdU incorporation) and apoptosis as measured by TUNEL staining. We have standardized an efficient methodologies for isolating cells from primary tumors expressing REP by fluorescence activated cell sorting (FACS...

  4. Membranes as Sensitive Targets in Thymocyte Apoptosis (United States)


    characterized by a Abstract. The role of cellular mronbranes in thymocyte generalized breakdown of cellular structure and apoptosis has been examined. Trolox , a...when added to called cellular suicide or programmed cell death cells within 30min post-irradiation. Exposure to trolox only (Kerr el at. 1972). during...chemical changes have been described in apoptosis, generated during radiation exposure. Incubation of the irra- diated cell suspension with trolox

  5. Apoptosis in amphibian organs during metamorphosis (United States)

    Ishizuya-Oka, Atsuko; Hasebe, Takashi; Shi, Yun-Bo


    During amphibian metamorphosis, the larval tissues/organs rapidly degenerate to adapt from the aquatic to the terrestrial life. At the cellular level, a large quantity of apoptosis occurs in a spatiotemporally-regulated fashion in different organs to ensure timely removal of larval organs/tissues and the development of adult ones for the survival of the individuals. Thus, amphibian metamorphosis provides us a good opportunity to understand the mechanisms regulating apoptosis. To investigate this process at the molecular level, a number of thyroid hormone (TH) response genes have been isolated from several organs of Xenopus laevis tadpoles and their expression and functional analyses are now in progress using modern molecular and genetic technologies. In this review, we will first summarize when and where apoptosis occurs in typical larva-specific and larval-to-adult remodeling amphibian organs to highlight that the timing of apoptosis is different in different tissues/organs, even though all are induced by the same circulating TH. Next, to discuss how TH spatiotemporally regulates the apoptosis, we will focus on apoptosis of the X. laevis small intestine, one of the best characterized remodeling organs. Functional studies of TH response genes using transgenic frogs and culture techniques have shown that apoptosis of larval epithelial cells can be induced by TH either cell-autonomously or indirectly through interactions with extracellular matrix (ECM) components of the underlying basal lamina. Here, we propose that multiple intra- and extracellular apoptotic pathways are coordinately controlled by TH to ensure massive but well-organized apoptosis, which is essential for the proper progression of amphibian metamorphosis. PMID:20238476

  6. Heat pump


    Klíma, Martin


    Bakalářská práce popisuje a charakterizuje tepelné čerpadlo. Obsahuje souhrn jednotlivých druhů tepelných čerpadel z hlediska získávání energie, princip jejich funkce a popis odlišností mezi jednotlivými druhy kompresorů, použití pracovní látky a její vývin do budoucna. Závěrem je zde uveden můj vlastní názor na tepelné čerpadlo, které bych preferoval. Bachelor thesis describes and characterizes the heat pump. Summarizes the various types of heat pumps in terms of energy production, princi...

  7. Heat Exchange


    Bottomley, Stephen


    Heat Exchange’ is an international touring exhibition of enamel metalwork curated by Turrell.E (UK), Gegenwart (Germany/UK) and Cameron (Australia). Bottomley was one of twenty-three international artists invited to join a transcontinental on-line blog and forum that recorded individual contemporary approaches to working with vitreous enamel the year prior to the 2012 exhibition that coincided with the SNAG (Society of North American Goldsmiths) National Conference in Phoenix Arizona USA.Vitr...

  8. Effect of sevoflurane on human neutrophil apoptosis.

    LENUS (Irish Health Repository)

    Tyther, R


    BACKGROUND AND OBJECTIVE: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo. METHODS: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1. RESULTS: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane. CONCLUSIONS: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

  9. Molecular Mechanism of Apoptosis and Necrosis

    Directory of Open Access Journals (Sweden)

    Gulfidan Coskun


    Full Text Available Organismal homeostasis depends on an intricate balance between cell death and renewal. Apoptosis is a process of programmed cell death that plays a critical role in some normal and pathologic conditions beginning from embryologic development and ends at death. Apoptosis is initiated by morphological changes at the cell membrane, surface organels and nucleus. Apoptosis starts with death signals coming from outside or inside of the cell and continue to activate the mechanisms of apoptosis via cell death receptor or mitochondrial pathways. During apoptosis a group proteases are activated which cause DNA fragmentation, cytoplasmic shrinkage and membrane blebbing. Apoptotic cells divide into apoptotic bodies and then these apoptotic bodies are removed from tissue by phagocytes and adjacent cells In contrast to the “programmed” nature of apoptosis, necrotic cell death has always been believed to be a random, uncontrolled process that leads to death of the cell. Also necrosis, which is an other type of cell death, came to be used to describe pathologic cell death which cause inflamation. [Archives Medical Review Journal 2011; 20(3.000: 145-158

  10. Heat pump system (United States)

    Swenson, Paul F.; Moore, Paul B.


    An air heating and cooling system for a building includes an expansion-type refrigeration circuit and a heat engine. The refrigeration circuit includes two heat exchangers, one of which is communicated with a source of indoor air from the building and the other of which is communicated with a source of air from outside the building. The heat engine includes a heat rejection circuit having a source of rejected heat and a primary heat exchanger connected to the source of rejected heat. The heat rejection circuit also includes an evaporator in heat exchange relation with the primary heat exchanger, a heat engine indoor heat exchanger, and a heat engine outdoor heat exchanger. The indoor heat exchangers are disposed in series air flow relationship, with the heat engine indoor heat exchanger being disposed downstream from the refrigeration circuit indoor heat exchanger. The outdoor heat exchangers are also disposed in series air flow relationship, with the heat engine outdoor heat exchanger disposed downstream from the refrigeration circuit outdoor heat exchanger. A common fluid is used in both of the indoor heat exchangers and in both of the outdoor heat exchangers. In a first embodiment, the heat engine is a Rankine cycle engine. In a second embodiment, the heat engine is a non-Rankine cycle engine.

  11. Hippocampal Apoptosis in Major Depression Is a Minor Event and Absent from Subareas at Risk for Glucocorticoid Overexposure (United States)

    Lucassen, Paul J.; Müller, Marianne B.; Holsboer, Florian; Bauer, Jan; Holtrop, Anne; Wouda, Jose; Hoogendijk, Witte J. G.; De Kloet, E. Ron; Swaab, Dick F.


    Glucocorticoid (GC) overexposure in animals has been implicated in hippocampal dysfunctioning and neuronal loss. In major depression, hypercortisolemia, hypothalamic-pituitary-adrenocortical-axis alterations, and reduced hippocampal volumes are commonly observed; hence, hippocampal neurodegeneration is also expected. To study possible GC-related pathology, we investigated hippocampal tissue of 15 major-depressed patients, 16 matched controls, and 9 steroid-treated patients, using in situ-end-labeling for DNA fragmentation and apoptosis, and heat-shock protein 70 and nuclear transcription factor κB immunocytochemistry for damage-related responses. No obvious massive cell loss was observed in any group. In 11 of 15 depressed patients, rare, but convincing apoptosis was found in entorhinal cortex, subiculum, dentate gyrus, CA1, and CA4. Also in three steroid-treated patients, apoptosis was found. Except for several steroid-treated patients, heat-shock protein 70 staining was generally absent, nor was nuclear transcription factor-κB activation found. The detection in 11 of 15 depressed patients, in three steroid-treated, and in one control patient, demonstrates for the first time that apoptosis is involved in steroid-related changes in the human hippocampus. However, in absence of major pyramidal loss, its rare occurrence, that notably was absent from areas at risk for GC damage such as CA3, indicates that apoptosis probably only contributes to a minor extent to the volume changes in depression. PMID:11159183

  12. HSP27 Inhibits Homocysteine-Induced Endothelial Apoptosis by Modulation of ROS Production and Mitochondrial Caspase-Dependent Apoptotic Pathway

    Directory of Open Access Journals (Sweden)

    Xin Tian


    Full Text Available Objectives. Elevated plasma homocysteine (Hcy could lead to endothelial dysfunction and is viewed as an independent risk factor for atherosclerosis. Heat shock protein 27 (HSP27, a small heat shock protein, is reported to exert protective effect against atherosclerosis. This study aims to investigate the protective effect of HSP27 against Hcy-induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs and to determine the underlying mechanisms. Methods. Apoptosis, reactive oxygen species (ROS, and mitochondrial membrane potential (MMP of normal or HSP27-overexpressing HUVECs in the presence of Hcy were analyzed by flow cytometry. The mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR and western blot. Results. We found that Hcy could induce cell apoptosis with corresponding decrease of nitric oxide (NO level, increase of endothelin-1 (ET-1, intracellular adhesion molecule-1 (ICAM-1, vascular cellular adhesion molecule-1 (VCAM-1, and monocyte chemoattractant protein-1 (MCP-1 levels, elevation of ROS, and dissipation of MMP. In addition, HSP27 could protect the cell against Hcy-induced apoptosis and inhibit the effect of Hcy on HUVECs. Furthermore, HSP27 could increase the ratio of Bcl-2/Bax and inhibit caspase-3 activity. Conclusions. Therefore, we concluded that HSP27 played a protective role against Hcy-induced endothelial apoptosis through modulation of ROS production and the mitochondrial caspase-dependent apoptotic pathway.

  13. Effects of ammonia exposure on apoptosis, oxidative stress and immune response in pufferfish (Takifugu obscurus). (United States)

    Cheng, Chang-Hong; Yang, Fang-Fang; Ling, Ren-Zhi; Liao, Shao-An; Miao, Yu-Tao; Ye, Chao-Xia; Wang, An-Li


    Ammonia is one of major environmental pollutants in the freshwater aquatic system that affects the survival and growth of organisms. In the present study, we investigated the effects of ammonia exposure on apoptosis, oxidative stress and immune response in pufferfish (Takifugu obscurus). Fish were exposed to various concentrations of ammonia (0, 1.43, 3.57, 7.14mM) for 72h. The date showed that ammonia exposure could induce intracellular reactive oxygen species (ROS), interrupt intracellular Ca(2+) (cf-Ca(2+)) homeostasis, and subsequently lead to DNA damage and cell apoptosis. To test the apoptotic pathway, the expression patterns of some key apoptotic related genes including P53, Bax Bcl2, Caspase 9, Caspase 8 and Caspase 3 in the liver were examined. The results showed that ammonia stress could change these genes transcription, associated with increasing of cell apoptosis, suggesting that the P53-Bax-Bcl2 pathway and caspase-dependent apoptotic pathway could be involved in cell apoptosis induced by ammonia stress. In addition, ammonia stress could induced up-regulation of inflammatory cytokines (BAFF, TNF-α, IL-6 and IL-12) transcription, indicating that innate immune system play important roles in ammonia-induced toxicity in fish. Furthermore, the gene expressions of antioxidant enzymes (Mn-SOD, CAT, GPx, and GR) and heat shock proteins (HSP90 and HSP70) in the liver were induced by ammonia stress, suggesting that antioxidant system and heat shock proteins tried to protect cells from oxidative stress and apoptosis induced by ammonia stress. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in fish. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Heat shock increases oxidative stress to modulate growth and physico-chemical attributes in diverse maize cultivars (United States)

    Hussain, Iqbal; Ashraf, Muhammad Arslan; Rasheed, Rizwan; Iqbal, Muhammad; Ibrahim, Muhammad; Ashraf, Shamila


    The present investigation was conducted to appraise the physiochemical adjustments in contrasting maize cultivars, namely, PakAfgoi (tolerant) and EV-5098 (sensitive) subjected to heat shock. Seven-day-old seedlings were exposed to heat shock for different time intervals (1, 3, 6, 24, 48 and 72 h) and data for various physiochemical attributes determined to appraise time course changes in maize. After 72 h of heat shock, the plants were grown under normal conditions for 5 d and data for different growth attributes and photosynthetic pigments recorded. Exposure to heat shock reduced growth and photosynthetic pigments in maize cultivars. The plants exposed to heat shock for up to 3 h recovered growth and photosynthetic pigments when stress was relieved. A time course rise in the relative membrane permeability, hydrogen peroxide (H2O2) and malondialdehyde contents was recorded particularly in the EV-5098 indicating that heat shock-induced oxidative stress. Activities of different enzymatic antioxidants greatly altered due to heat shock. For instance, an increase in superoxide dismutase activity was recorded in both maize cultivars. The activity of ascorbate peroxidase was greater in Pak-Afgoi. However, the peroxidase and catalase activities were higher in plants of EV-5098. Heat shock caused a significant rise in the proline and decline in the total free amino acids. Overall, the performance of Pak-Afgoi was better in terms of having lesser oxidative damage and greater cellular levels of proline. The results suggested that oxidative stress indicators (relative membrane permeability, H2O2 and malondialdehyde) and proline can be used as markers for heat shock tolerant plants.

  15. Heat-Exchanger/Heat-Pipe Interface (United States)

    Snyder, H. J.; Van Hagan, T. H.


    Monolithic assembly reliable and light in weight. Heat exchanger and evaporator ends of heat pipes integrated in monolithic halves welded together. Interface assembly connects heat exchanger of furnace, reactor, or other power source with heat pipes carrying heat to radiator or power-consuming system. One of several concepts proposed for nuclear power supplies aboard spacecraft, interface useful on Earth in solar thermal power systems, heat engines, and lightweight cooling systems.

  16. Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells. (United States)

    Galán, A; García-Bermejo, M L; Troyano, A; Vilaboa, N E; de Blas, E; Kazanietz, M G; Aller, P


    Pulse treatment of U-937 promonocytic cells with cadmium chloride (2 h at 200 microM) provoked apoptosis and induced a rapid phosphorylation of p38 mitogen-activated protein kinase (p38(MAPK)) as well as a late phosphorylation of extracellular signal-regulated protein kinases (ERK1/2). However, although the p38(MAPK)-specific inhibitor SB203580 attenuated apoptosis, the process was not affected by the ERK-specific inhibitor PD98059. The attenuation of the cadmium-provoked apoptosis by SB203580 was a highly specific effect. In fact, the kinase inhibitor did not prevent the generation of apoptosis by heat shock and camptothecin, nor the generation of necrosis by cadmium treatment of glutathione-depleted cells, nor the cadmium-provoked activation of the stress response. The generation of apoptosis was preceded by intracellular H(2)O(2) accumulation and was accompanied by the disruption of mitochondrial transmembrane potential, both of which were inhibited by SB203580. On the other hand, the antioxidant agent butylated hydroxyanisole-inhibited apoptosis but did not prevent p38(MAPK) phosphorylation. In a similar manner, p38(MAPK) phosphorylation was not affected by the caspase inhibitors Z-VAD and DEVD-CHO, which nevertheless prevented apoptosis. These results indicate that p38(MAPK) activation is an early and specific regulatory event for the cadmium-provoked apoptosis in promonocytic cells.

  17. Heating systems for heating subsurface formations

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Scott Vinh [Houston, TX; Vinegar, Harold J [Bellaire, TX


    Methods and systems for heating a subsurface formation are described herein. A heating system for a subsurface formation includes a sealed conduit positioned in an opening in the formation and a heat source. The sealed conduit includes a heat transfer fluid. The heat source provides heat to a portion of the sealed conduit to change phase of the heat transfer fluid from a liquid to a vapor. The vapor in the sealed conduit rises in the sealed conduit, condenses to transfer heat to the formation and returns to the conduit portion as a liquid.

  18. Hydride heat pump with heat regenerator (United States)

    Jones, Jack A. (Inventor)


    A regenerative hydride heat pump process and system is provided which can regenerate a high percentage of the sensible heat of the system. A series of at least four canisters containing a lower temperature performing hydride and a series of at least four canisters containing a higher temperature performing hydride is provided. Each canister contains a heat conductive passageway through which a heat transfer fluid is circulated so that sensible heat is regenerated. The process and system are useful for air conditioning rooms, providing room heat in the winter or for hot water heating throughout the year, and, in general, for pumping heat from a lower temperature to a higher temperature.

  19. Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis (United States)

    Hwang, Hyun Sook; Kim, Hyun Ah


    Apoptosis is a highly-regulated, active process of cell death involved in development, homeostasis and aging. Dysregulation of apoptosis leads to pathological states, such as cancer, developmental anomalies and degenerative diseases. Osteoarthritis (OA), the most common chronic joint disease in the elderly population, is characterized by progressive destruction of articular cartilage, resulting in significant disability. Because articular cartilage depends solely on its resident cells, the chondrocytes, for the maintenance of extracellular matrix, the compromising of chondrocyte function and survival would lead to the failure of the articular cartilage. The role of subchondral bone in the maintenance of proper cartilage matrix has been suggested as well, and it has been proposed that both articular cartilage and subchondral bone interact with each other in the maintenance of articular integrity and physiology. Some investigators include both articular cartilage and subchondral bone as targets for repairing joint degeneration. In late-stage OA, the cartilage becomes hypocellular, often accompanied by lacunar emptying, which has been considered as evidence that chondrocyte death is a central feature in OA progression. Apoptosis clearly occurs in osteoarthritic cartilage; however, the relative contribution of chondrocyte apoptosis in the pathogenesis of OA is difficult to evaluate, and contradictory reports exist on the rate of apoptotic chondrocytes in osteoarthritic cartilage. It is not clear whether chondrocyte apoptosis is the inducer of cartilage degeneration or a byproduct of cartilage destruction. Chondrocyte death and matrix loss may form a vicious cycle, with the progression of one aggravating the other, and the literature reveals that there is a definite correlation between the degree of cartilage damage and chondrocyte apoptosis. Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid


    Directory of Open Access Journals (Sweden)

    Rade Čukuranović


    Full Text Available Kidney morphogenesis is a complex and stepwise process. The formation of mature kidney in mammals is preceded by two primitive embryonic kidneys known as pronephros and mesonephros. Metanephros develops as a result of reciprocal inductive interactions between two primordial mesodermal derivates: ureteric bud, an epithelial outgrowth of the Wolffian duct, and metanephric blastema, a group of mesenchymal cells. The ureteric bud induces the metanephric mesenchyme to differentiate and form nephrons, whilst the metanephric mesenchyme induces the ureteric bud to grow and branch to form collecting ducts. The nephron goes through four developmental stages, which are described as: 1 vesicle, 2 comma-shaped and S-shaped stages, 3 developing capillary loop, and finally 4 maturing glomerulus. Apoptosis (programmed cell death is a predominant form of physiological cell death, by which organism eliminate unwanted or damaged cells. It is the major component of normal development and disease. Apoptosis is the result of series of biochemical processes happening in certain order in a dying cell, among which the most important is activation of enzyme families called caspases which influence different cell components. Apoptosis is characterized by membrane blebbing, shrinkage of the cell, nuclear fragmentation and chromatin condensation. Organelles are preserved almost intact. Cell surface molecules change. A variety of physiological and pathological stimuli can initiate apoptosis. They act via receptor mechanisms, through biochemical agents, or cause DNA and cell membrane damage. Apoptosis is an important component of fetal development. It is thought that apoptosis is the one of the main regulatory events involved in kidney morphogenesis, considering that among great number of developed cells, only a few of them are involved in the developing program by escaping apoptosis. In any period during kidney development about 3 to 5%of cells are apoptotic. Thorough

  1. A novel conditional gene silencing method using a tumor-specific and heat-inducible siRNA system. (United States)

    Feng, Jing; Wang, Xiaoyu; Liao, Yi; Feng, Jianguo; Tang, Liling


    RNAi technology is an invaluable tool for investigating gene function. However, the non-temporal and non-spatial control is the primary limitation, which leads to siRNA leakiness and off-target effects. In this study, we inserted three kinds of HSE into tumor specific promoter hTERT, which aims to construct a temperature-inducible and tumor-specific RNAi plasmid vector. In our system, the expression of mature siRNA is tightly controlled by the heat shock-inducible and tumor-specific promoters. From the expression level of RNA and protein, we determined the efficiency of the inducible siRNA system by targeting SNCG gene in HepG2 and MCF-7 cells. Results showed that the controllable siRNA system could be induced to initiate siRNA expression by heat-induce. The silencing effect of SNCG is on a relative low level (10 %) at 37 °C, while it is significantly increased to 50 or 60 % after heat inducing at 43 °C. This new conditional siRNA system provides a novel approach to drive the siRNA expression by heat-inducible and tumor-specific promoter.

  2. Heat pipes

    CERN Document Server

    Dunn, Peter D


    A comprehensive, up-to-date coverage of the theory, design and manufacture of heat pipes and their applications. This latest edition has been thoroughly revised, up-dated and expanded to give an in-depth coverage of the new developments in the field. Significant new material has been added to all the chapters and the applications section has been totally rewritten to ensure that topical and important applications are appropriately emphasised. The bibliography has been considerably enlarged to incorporate much valuable new information. Thus readers of the previous edition, which has established

  3. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... Emergencies A-Z Share this! Home » Emergency 101 Heat-Related Illnesses Dr. Glenn Mitchell , Emergency physician at ... about heat cramps and heat stroke and exhaustion. Heat Cramps Symptoms include muscle spasms, usually in the ...

  4. Low temperature nuclear heat

    Energy Technology Data Exchange (ETDEWEB)

    Kotakorpi, J.; Tarjanne, R. (comps.)


    The meeting was concerned with the use of low grade nuclear heat for district heating, desalination, process heat, and agriculture and aquaculture. The sessions covered applications and demand, heat sources, and economics.

  5. Regenerative Hydride Heat Pump (United States)

    Jones, Jack A.


    Hydride heat pump features regenerative heating and single circulation loop. Counterflow heat exchangers accommodate different temperatures of FeTi and LaNi4.7Al0.3 subloops. Heating scheme increases efficiency.

  6. Apoptosis in chronic tonsillitis and tonsillar hypertrophy. (United States)

    Önal, Merih; Yılmaz, Taner; Bilgiç, Elif; Müftüoğlu, Sevda Fatma; Kuşçu, Oğuz; Günaydın, Rıza Önder


    Chronic tonsillitis is the persistent inflammation of the tonsillar tissue that occurs due to recurrent, acute or subclinical infection. The recurrent and chronic inflammation of palatine tonsils sometimes results in hypertrophy. Apoptosis provides an important balance between lymphocytes in tonsillar lymphoid tissue. The aim of this study is to investigate the apoptosis in tonsillar diseases. 43 patients with chronic tonsilitis and tonsillar hypertrophy underwent tonsillectomy. The specimens were examined immunohistochemically for apoptosis. Tonsils were assembled into groups according to their size. Specimens were compared for their apoptotic cell count. The apoptosis difference between the tonsil size groups is not statistically significant (p>0.05). However, when the study group was divided into two at age 6, the difference was not statistically significant for patients at and below 6 years of age; but, the difference was statistically significant for patients above 6 years of age (ptonsil tissue (intrafollicular, interfollicular, subepithelial and intraepithelial) between tonsil size stages and between chronic tonsillitis and tonsillar hypertrophy groups revealed no statistical significance (p>0.05). There was a statistically significant positive correlation between intrafollicular and interfollicular, interfollicular and intraepithelial & subepithelial and intraepithelial areas (ptonsil tissue. The association of apoptosis with tonsillar hypertrophy seemed to be age-dependent. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Sodium nitroprusside induces apoptosis of rabbit chondrocytes (United States)

    Liang, Qian; Wang, Xiao-Ping; Chen, Tong-Sheng


    Osteoarthritis (OA) is characterized by a slowly progressing degradation of the matrix and destruction of articular cartilage. Apoptosis of chondrocyte is accounted for the mechanism of OA. Nitric oxide (NO), as a stimulus, has been shown to induce chondrocyte apoptosis by activating the matrix metalloproteinases (MMPs), increasing the expression of cyclooxygenase 2 (COX-2) and the level of prostaglandin E2 (PGE2), inhibiting the proteoglycan synthesis and type II collagen expression. In this study, sodium nitroprusside (SNP) was administered to be the NO donor to explore the mechanism of NO-induced apoptosis of rabbit chondrocytes obtained from six weeks old New Zealand rabbits. CCK-8 assay revealed the inhibitory effect of SNP on cell viability. We used flow cytometry (FCM) to assess the form of cell death by Annexin-V/propidium iodide (PI) double staining, and evaluate the change of mitochondrial membrane potential (ΔΨm). We found that the SNP induced chondrocyte apoptosis in a dose- and time-dependent manner and an observable reduction of ΔΨm. In conclusion, our findings indicate that SNP induces apoptosis of rabbit chondrocytes via a mitochondria-mediated pathway.

  8. Tissue-specific induction of Hsp90 mRNA and plasma cortisol response in chinook salmon following heat shock, seawater challenge, and handling challenge (United States)

    Palmisano, Aldo N.; Winton, J.R.; Dickhoff, Walton W.


    In studying the whole-body response of chinook salmon (Oncorhynchus tshawytscha) to various stressors, we found that 5-hour exposure to elevated temperature (mean 21.6??C; + 10.6??C over ambient) induced a marked increase in Hsp90 messenger RNA accumulation in heart, brain, gill, muscle, liver, kidney, and tail fin tissues. The most vital tissues (heart, brain, gill, and muscle) showed the greatest Hsp90-mRNA response, with heart tissue increasing approximately 35-fold, Heat shock induced no increase in plasma cortisol. In contrast, a standard handling challenge induced high plasma cortisol levels, but no elevation in Hsp90 mRNA in any tissue, clearly separating the physiological and cellular stress responses. We saw no increase either in tissue Hsp90 mRNA levels or in plasma cortisol concentrations after exposing the fish to seawater overnight.

  9. Segmented heat exchanger (United States)

    Baldwin, Darryl Dean; Willi, Martin Leo; Fiveland, Scott Byron; Timmons, Kristine Ann


    A segmented heat exchanger system for transferring heat energy from an exhaust fluid to a working fluid. The heat exchanger system may include a first heat exchanger for receiving incoming working fluid and the exhaust fluid. The working fluid and exhaust fluid may travel through at least a portion of the first heat exchanger in a parallel flow configuration. In addition, the heat exchanger system may include a second heat exchanger for receiving working fluid from the first heat exchanger and exhaust fluid from a third heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the second heat exchanger in a counter flow configuration. Furthermore, the heat exchanger system may include a third heat exchanger for receiving working fluid from the second heat exchanger and exhaust fluid from the first heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the third heat exchanger in a parallel flow configuration.

  10. Dual source heat pump (United States)

    Ecker, Amir L.; Pietsch, Joseph A.


    What is disclosed is a heat pump apparatus for conditioning a fluid characterized by a fluid handler and path for circulating the fluid in heat exchange relationship with a refrigerant fluid; at least two refrigerant heat exchangers, one for effecting heat exchange with the fluid and a second for effecting heat exchange between refrigerant and a heat exchange fluid and the ambient air; a compressor for efficiently compressing the refrigerant; at least one throttling valve for throttling liquid refrigerant; a refrigerant circuit; refrigerant; a source of heat exchange fluid; heat exchange fluid circulating device and heat exchange fluid circuit for circulating the heat exchange fluid in heat exchange relationship with the refrigerant; and valves or switches for selecting the heat exchangers and direction of flow of the refrigerant therethrough for selecting a particular mode of operation. The heat exchange fluid provides energy for defrosting the second heat exchanger when operating in the air source mode and also provides a alternate source of heat.

  11. Extremely low frequency magnetic fields induce spermatogenic germ cell apoptosis: possible mechanism. (United States)

    Lee, Sang-Kon; Park, Sungman; Gimm, Yoon-Myoung; Kim, Yoon-Won


    The energy generated by an extremely low frequency electromagnetic field (ELF-EMF) is too weak to directly induce genotoxicity. However, it is reported that an extremely low frequency magnetic field (ELF-MF) is related to DNA strand breakage and apoptosis. The testes that conduct spermatogenesis through a dynamic cellular process involving meiosis and mitosis seem vulnerable to external stress such as heat, MF exposure, and chemical or physical agents. Nevertheless the results regarding adverse effects of ELF-EMF on human or animal reproductive functions are inconclusive. According to the guideline of the International Commission on Non-Ionizing Radiation Protection (ICNIRP; 2010) for limiting exposure to time-varying MF (1 Hz to 100 kHz), overall conclusion of epidemiologic studies has not consistently shown an association between human adverse reproductive outcomes and maternal or paternal exposure to low frequency fields. In animal studies there is no compelling evidence of causal relationship between prenatal development and ELF-MF exposure. However there is increasing evidence that EL-EMF exposure is involved with germ cell apoptosis in testes. Biophysical mechanism by which ELF-MF induces germ cell apoptosis has not been established. This review proposes the possible mechanism of germ cell apoptosis in testes induced by ELF-MF.

  12. Extremely Low Frequency Magnetic Fields Induce Spermatogenic Germ Cell Apoptosis: Possible Mechanism

    Directory of Open Access Journals (Sweden)

    Sang-Kon Lee


    Full Text Available The energy generated by an extremely low frequency electromagnetic field (ELF-EMF is too weak to directly induce genotoxicity. However, it is reported that an extremely low frequency magnetic field (ELF-MF is related to DNA strand breakage and apoptosis. The testes that conduct spermatogenesis through a dynamic cellular process involving meiosis and mitosis seem vulnerable to external stress such as heat, MF exposure, and chemical or physical agents. Nevertheless the results regarding adverse effects of ELF-EMF on human or animal reproductive functions are inconclusive. According to the guideline of the International Commission on Non-Ionizing Radiation Protection (ICNIRP; 2010 for limiting exposure to time-varying MF (1 Hz to 100 kHz, overall conclusion of epidemiologic studies has not consistently shown an association between human adverse reproductive outcomes and maternal or paternal exposure to low frequency fields. In animal studies there is no compelling evidence of causal relationship between prenatal development and ELF-MF exposure. However there is increasing evidence that EL-EMF exposure is involved with germ cell apoptosis in testes. Biophysical mechanism by which ELF-MF induces germ cell apoptosis has not been established. This review proposes the possible mechanism of germ cell apoptosis in testes induced by ELF-MF.

  13. The role of Fas mediated apoptosis in preeclampsia. (United States)

    Neale, Donna M; Mor, Gil


    It has become clear in recent years that apoptosis is a normal process in trophoblast turnover during pregnancy. Increased trophoblast apoptosis has been observed in the placenta of women with preeclampsia, serum from women with preeclampsia has been found to induce increased trophoblast sensitivity to Fas-mediated apoptosis, and serum from women with preeclampsia has elevated levels of various chemokines, growth factors and cytokines that are involved in the regulation of apoptosis. This review highlights the importance of apoptosis in normal placental development and explores the mechanisms whereby Fas-mediated apoptosis may play a role in conditions related to abnormal placentation, such as preeclampsia.

  14. Oxidative stress and apoptosis in preeclampsia. (United States)

    Can, Murat; Guven, Berrak; Bektas, Sibel; Arikan, Ilker


    We aimed to determine the oxidative stress and antioxidant status in preeclamptic placenta. Also, we investigated the apoptotic index of villous trophoblast and proliferation index of cytotrophoblasts. The study included 32 pregnant with preeclampsia and 31 normotensive healthy pregnant women. Malondialdehyde (MDA) and total antioxidant status (TAS) levels were measured in the placenta. For detection of apoptosis and proliferation in trophoblast, apoptosis protease activating factor 1 (APAF-1) and Ki-67 were used. Placental MDA levels in preeclamptic women were significantly higher than normal pregnancies (p=0.002). There was no significant difference between the groups in the TAS levels of placenta (p=0.773). Also, the apoptotic index in villous trophoblasts increased (ppreeclampsia (p=0.850). Increased oxidative stress and apoptosis in pathological placenta are not balanced by antioxidant systems and proliferation mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Apoptosis in Drosophila: which role for mitochondria? (United States)

    Clavier, Amandine; Rincheval-Arnold, Aurore; Colin, Jessie; Mignotte, Bernard; Guénal, Isabelle


    It is now well established that the mitochondrion is a central regulator of mammalian cell apoptosis. However, the importance of this organelle in non-mammalian apoptosis has long been regarded as minor, mainly because of the absence of a crucial role for cytochrome c in caspase activation. Recent results indicate that the control of caspase activation and cell death in Drosophila occurs at the mitochondrial level. Numerous proteins, including RHG proteins and proteins of the Bcl-2 family that are key regulators of Drosophila apoptosis, constitutively or transiently localize in mitochondria. These proteins participate in the cell death process at different levels such as degradation of Diap1, a Drosophila IAP, production of mitochondrial reactive oxygen species or stimulation of the mitochondrial fission machinery. Here, we review these mitochondrial events that might have their counterpart in human.

  16. Death penalty for keratinocytes: apoptosis versus cornification. (United States)

    Lippens, S; Denecker, G; Ovaere, P; Vandenabeele, P; Declercq, W


    Homeostasis implies a balance between cell growth and cell death. This balance is essential for the development and maintenance of multicellular organisms. Homeostasis is controlled by several mechanisms including apoptosis, a process by which cells condemned to death are completely eliminated. However, in some cases, total destruction and removal of dead cells is not desirable, as when they fulfil a specific function such as formation of the skin barrier provided by corneocytes, also known as terminally differentiated keratinocytes. In this case, programmed cell death results in accumulation of functional cell corpses. Previously, this process has been associated with apoptotic cell death. In this overview, we discuss differences and similarities in the molecular regulation of epidermal programmed cell death and apoptosis. We conclude that despite earlier confusion, apoptosis and cornification occur through distinct molecular pathways, and that possibly antiapoptotic mechanisms are implicated in the terminal differentiation of keratinocytes.

  17. Apoptosis: Therapeutic target in neurodegeneration and sepsis

    Directory of Open Access Journals (Sweden)

    Gonzalo Arboleda


    Full Text Available Cellular apoptosis has been considered as themain physiological mechanism underlyingneuronal demise associated to neurodegenerativediseases. Apoptosis has also been described inparenquimal and microvascular endotheliumin the acute phase of sepsis during multi-organicdysfunction. Therefore, strategies aimed toMuerte celular: blanco terapéutico enneurodegeneración y sepsisGonzalo Arboleda*, Luisa M. Matheus†prevent apoptosis (anti-apoptotic represent avaluable tool for prevention and/or retardationof the appearance of clinical symptoms in thesedisorders, which generate a large morbilitymortality,social and economic burden worldwide.The present review is aim to show that antiapoptoticstrategies hold a great therapeuticpotential. In this sense, we will review some ofthese potential therapies such as caspaseinhibitors, activated protein C, Bcl-2 family andthe PI3K/Akt signalling pathway.

  18. Integrative analysis of the heat shock response in Aspergillus fumigatus

    Directory of Open Access Journals (Sweden)

    Brakhage Axel A


    -like transcription factor upstream of some heat shock induced genes. Until now, this factor has only been found in vertebrates. Conclusions Our newly established DIGE data analysis workflow yields improved data quality and is widely applicable for other DIGE datasets. Our findings suggest that the heat shock response in A. fumigatus differs from already well-studied yeasts and other filamentous fungi.

  19. Apoptosis and Necrosis in the Liver (United States)

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.


    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  20. Small Heat Shock Proteins Can Release Light Dependence of Tobacco Seed during Germination1[OPEN (United States)

    Koo, Hyun Jo; Park, Soo Min; Kim, Keun Pill; Suh, Mi Chung; Lee, Mi Ok; Lee, Seong-Kon; Xinli, Xia


    Small heat shock proteins (sHSPs) function as ATP-independent molecular chaperones, and although the production and function of sHSPs have often been described under heat stress, the expression and function of sHSPs in fundamental developmental processes, such as pollen and seed development, have also been confirmed. Seed germination involves the breaking of dormancy and the resumption of embryo growth that accompany global changes in transcription, translation, and metabolism. In many plants, germination is triggered simply by imbibition of water; however, different seeds require different conditions in addition to water. For small-seeded plants, like Arabidopsis (Arabidopsis thaliana), lettuce (Lactuca sativa), tomato (Solanum lycopersicum), and tobacco (Nicotiana tabacum), light is an important regulator of seed germination. The facts that sHSPs accumulate during seed development, sHSPs interact with various client proteins, and seed germination accompanies synthesis and/or activation of diverse proteins led us to investigate the role of sHSPs in seed germination, especially in the context of light dependence. In this study, we have built transgenic tobacco plants that ectopically express sHSP, and the effect was germination of the seeds in the dark. Administering heat shock to the seeds also resulted in the alleviation of light dependence during seed germination. Subcellular localization of ectopically expressed sHSP was mainly observed in the cytoplasm, whereas heat shock-induced sHSPs were transported to the nucleus. We hypothesize that ectopically expressed sHSPs in the cytoplasm led the status of cytoplasmic proteins involved in seed germination to function during germination without additional stimulus and that heat shock can be another signal that induces seed germination. PMID:25604531

  1. Nonazeotropic Heat Pump (United States)

    Ealker, David H.; Deming, Glenn


    Heat pump collects heat from water circulating in heat-rejection loop, raises temperature of collected heat, and transfers collected heat to water in separate pipe. Includes sealed motor/compressor with cooling coils, evaporator, and condenser, all mounted in outer housing. Gradients of temperature in evaporator and condenser increase heat-transfer efficiency of vapor-compression cycle. Intended to recover relatively-low-temperature waste heat and use it to make hot water.

  2. High heat flux single phase heat exchanger (United States)

    Valenzuela, Javier A.; Izenson, Michael G.


    This paper presents the results obtained to date in a program to develop a high heat flux, single-phase heat exchanger for spacecraft thermal management. The intended application is a net generation interface heat exchanger to couple the crew module water thermal bus to the two-phase ammonia main thermal bus in the Space Station Freedom. The large size of the interface heat exchanger is dictated by the relatively poor water-side heat transfer characteristics. The objective of this program is to develop a single-phase heat transfer approach which can achieve heat fluxes and heat transfer coefficients comparable to those of the evaporation ammonia side. A new heat exchanger concept has been developed to meet these objecties. The main feature of this heat exchanger is that it can achieve very high heat fluxes with a pressure drop one to two orders of magnitude lower than those of previous microchannel or jet impingement high heat flux heat exchangers. This paper describes proof-of-concept experiments performed in air and water and presents analytical model of the heat exchanger.

  3. Epithelial apoptosis: cause or consequence of ulcerative colitis?

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Nielsen, Ole Haagen


    OBJECTIVE: Epithelial apoptosis rates are increased in ulcerative colitis (UC). The increased apoptosis rate could expose mucosal cells to luminal pathogens and thereby be regarded as a primary pathogenic factor in UC. On the other hand, the local inflammatory reaction could cause epithelial...... apoptosis secondary to the release of cytotoxic mediators. If apoptosis is a primary defect, apoptosis rates could influence the degree of spreading of inflammation and the clinical course of UC. If apoptosis is a side effect of local inflammation, apoptosis rates would be expected only to correlate...... with the degree of local inflammation. The aim of the study was to investigate the relationship between epithelial apoptosis and clinical characteristics of UC. MATERIAL AND METHODS: Twenty patients with UC (12 with active disease) and 20 control subjects were included. Freshly isolated colonic epithelial cells...

  4. Mitochondrial pathway of apoptosis and related proteins in placenta ...

    African Journals Online (AJOL)

    eclampsia (PE).This study aimed at evaluating the mitochondrial pathway of apoptosis in placenta of pregnant women with pre-eclampsia and correlate it with severity and pregnancy outcome . Apoptosis was assessed by measuring DNA ...

  5. Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF-related apoptosis-inducing ligand. (United States)

    Chen, Hui; Li, Liang-Qing; Pan, Dun


    The aim of the present study was to evaluate the effect of geldanamycin (GA) on the treatment of human gastric carcinomas and to investigate the molecular mechanism that provides the basis for the combination of GA with the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induction strategy. The expression of target proteins at the mRNA level was determined using reverse transcription-polymerase chain reaction (RT-PCR), and apoptosis was evaluated with the terminal deoxynucleotidyl transferase mediated digoxigenin-dUTP nick-end labeling and Annexin V/propidium iodide (PI) staining methods. Phosphorylation of targeted kinases was studied using immunocytochemistry methods, and malignant phenotypes were studied using in vitro assays. GA treatment inhibits proliferation, migration and invasion, and induces apoptosis in human gastric cancer SGC-7901 cells, most likely by decreasing the expression of B-RAF and by phosphorylation of protein kinase B (AKT) and ERK. The inhibitory role of AKT in TRAIL regulation holds considerable potential for achieving a synergic effect in clinical therapy, using a combination of GA treatment and TRAIL induction. The present study provides a basis for the future application of heat shock protein 90 (Hsp90) inhibitors, such as GA, in the clinical treatment of gastric cancer, particularly in combination therapies with TRAIL inducers.

  6. Multiple source heat pump (United States)

    Ecker, Amir L.


    A heat pump apparatus for conditioning a fluid characterized by a fluid handler and path for circulating a fluid in heat exchange relationship with a refrigerant fluid, at least three refrigerant heat exchangers, one for effecting heat exchange with the fluid, a second for effecting heat exchange with a heat exchange fluid, and a third for effecting heat exchange with ambient air; a compressor for compressing the refrigerant; at least one throttling valve connected at the inlet side of a heat exchanger in which liquid refrigerant is vaporized; a refrigerant circuit; refrigerant; a source of heat exchange fluid; heat exchange fluid circuit and pump for circulating the heat exchange fluid in heat exchange relationship with the refrigerant; and valves or switches for selecting the heat exchangers and directional flow of refrigerant therethrough for selecting a particular mode of operation. Also disclosed are a variety of embodiments, modes of operation, and schematics therefor.

  7. Cryogenic heat transfer

    CERN Document Server

    Barron, Randall F


    Cryogenic Heat Transfer, Second Edition continues to address specific heat transfer problems that occur in the cryogenic temperature range where there are distinct differences from conventional heat transfer problems. This updated version examines the use of computer-aided design in cryogenic engineering and emphasizes commonly used computer programs to address modern cryogenic heat transfer problems. It introduces additional topics in cryogenic heat transfer that include latent heat expressions; lumped-capacity transient heat transfer; thermal stresses; Laplace transform solutions; oscillating flow heat transfer, and computer-aided heat exchanger design. It also includes new examples and homework problems throughout the book, and provides ample references for further study.

  8. Heat pump technology

    CERN Document Server

    Von Cube, Hans Ludwig; Goodall, E G A


    Heat Pump Technology discusses the history, underlying concepts, usage, and advancements in the use of heat pumps. The book covers topics such as the applications and types of heat pumps; thermodynamic principles involved in heat pumps such as internal energy, enthalpy, and exergy; and natural heat sources and energy storage. Also discussed are topics such as the importance of the heat pump in the energy industry; heat pump designs and systems; the development of heat pumps over time; and examples of practical everyday uses of heat pumps. The text is recommended for those who would like to kno

  9. Norcantharidin (NCTD) induces mitochondria mediated apoptosis in ...

    African Journals Online (AJOL)



    60 by inducing apoptosis through the mitochondria-dependent pathway. Eur. J. Pharmacol. 645: 14-22. Zhang C, Peng Y, Wang F, Tan X, Liu N, Fan S (2010). A synthetic cantharidin analog for the enhancement of doxorubicin ...

  10. Signaling Pathways in Cardiac Myocyte Apoptosis (United States)

    Xia, Peng; Liu, Yuening


    Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation. PMID:28101515

  11. Bacterial DNA delays human eosinophil apoptosis



    Bacterial DNA delays human eosinophil apoptosis correspondance: Corresponding author. Tel.: +358 3 3551 6687; fax: +358 3 3551 8082. (Ilmarinen, Pinja) (Ilmarinen, Pinja) The Immunopharmacology Research Group--> , Medical School--> , University of Tampere and Research Unit--> , Tampere University Hospital--> , Tampere--> - FINLAND (Ilmarinen, Pinja) The Immunopharmacology ...

  12. Swainsonine promotes apoptosis in human oesophageal squamous ...

    Indian Academy of Sciences (India)

    Swainsonine, a natural indolizidine alkaloid, has been reported to have antitumour effects, and can induce apoptosis in human gastric and lung cancer cells. In the present study, we evaluated the antitumour effects of swainsonine on several oesophageal squamous cell carcinoma cells and investigated relative molecular ...

  13. Host-pathogen interactions during apoptosis

    Indian Academy of Sciences (India)

    Host pathogen interaction results in a variety of responses, which include phagocytosis of the pathogen, release of cytokines, secretion of toxins, as well as production of reactive oxygen species (ROS). Recent studies have shown that many pathogens exert control on the processes that regulate apoptosis in the host.


    Apoptosis, a form of programmed cell death, occurs in the nervous system throughout development, but with a preponderance of cell death occurring during the prenatal and perinatal periods. Aberrant periods of increased or decreased cell death, induced by toxicants in air, water,...

  15. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu


    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  16. Epac inhibits apoptosis of human leukocytes

    NARCIS (Netherlands)

    Grandoch, M.; Bujok, V.; Fleckenstein, D.; Schmidt, M.; Fischer, J. W.; Weber, A. -A.


    cAMP is known to participate in the regulation of apoptosis in leukocytes. Depending on the cell type, pro- and antiapoptotic effects of cAMP have been described. Thus far, most of the cAMP-dependent effects have been attributed to the activation of PKA. However, Epac proteins (direct cAMP targets

  17. Beta Catenin in Prostate Cancer Apoptosis (United States)


    C., Jacquin, M. A., Marchetti, S., Munoz- Pinedo, C., Auberger, P., Pende, M., and Ricci, J. E. (2010) Glycolysis inhibition sensitizes tumor cells...for TRAIL-TZD-induced apoptosis in prostate cancer cells. AMPK is a family of serine/threonine protein kinase and is highly conserved from yeast to

  18. HIV-1 protease-induced apoptosis

    Czech Academy of Sciences Publication Activity Database

    Rumlová, Michaela; Křížová, Ivana; Keprová, Alena; Hadravová, Romana; Doležal, Michal; Strohalmová, Karolína; Pichová, Iva; Hájek, Miroslav; Ruml, T.


    Roč. 11, May 20 (2014), 37/1-37/15 ISSN 1742-4690 R&D Projects: GA ČR GA204/09/1388 Institutional support: RVO:61388963 Keywords : HIV protease * BCA3 * AKIP-1 * apoptosis * mitochondria Subject RIV: EE - Microbiology, Virology Impact factor: 4.185, year: 2014

  19. Host-pathogen interactions during apoptosis

    Indian Academy of Sciences (India)


    The adenovirus E3-14⋅7 K protein, expressed early in the life cycle of human adenoviruses to protect the virus from the antiviral response of host cells, inhibits cell death mediated by TNF-α and FasL receptors. Specific induction of apoptosis in immune cells is seen in HIV infections (Pantaleo and Fauci 1995). HIV kills ...

  20. A novel method for detection of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zagariya, Alexander M., E-mail:


    There are two different Angiotensin II (ANG II) peptides in nature: Human type (ANG II) and Bovine type (ANG II*). These eight amino acid peptides differ only at position 5 where Valine is replaced by Isoleucine in the Bovine type. They are present in all species studied so far. These amino acids are different by only one atom of carbon. This difference is so small, that it will allow any of ANG II, Bovine or Human antibodies to interact with all species and create a universal method for apoptosis detection. ANG II concentrations are found at substantially higher levels in apoptotic, compared to non-apoptotic, tissues. ANG II accumulation can lead to DNA damage, mutations, carcinogenesis and cell death. We demonstrate that Bovine antiserum can be used for universal detection of apoptosis. In 2010, the worldwide market for apoptosis detection reached the $20 billion mark and significantly increases each year. Most commercially available methods are related to Annexin V and TUNNEL. Our new method based on ANG II is more widely known to physicians and scientists compared to previously used methods. Our approach offers a novel alternative for assessing apoptosis activity with enhanced sensitivity, at a lower cost and ease of use.

  1. Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Tang, Dean; Liu, Junwei


    ... (death, survival, proliferation/division, etc.). Our hypothesis is that, under normal, unstimulated conditions, with its apoptotic function blocked, the upregulated Bim in PCa cells plays an apoptosis-independent function...

  2. Apoptosis-Dependent and Apoptosis-Independent Functions Bim in Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Liu, Junwei


    ... (death, survival, proliferation/division, etc). Our hypothesis is that, under normal, unstimulated conditions, with its apoptotic function blocked, the upregulated Bim in PCa cells play an apoptosis-independent function...

  3. Spironolactone induces apoptosis in human mononuclear cells. Association between apoptosis and cytokine suppression

    DEFF Research Database (Denmark)

    Mikkelsen, Martin; Sønder, S U; Nersting, J


    Spironolactone (SPIR) has been described to suppress accumulation of pro-inflammatory cytokines. Here, the suppression of TNF-alpha in lipopolysaccharide (LPS)-stimulated mononuclear cell cultures was confirmed. However, SPIR was also found to induce apoptosis, prompting the investigations...... of a possible association between the two effects: The apoptosis-inducing and the cytokine-suppressive effects of SPIR correlated with regard to the effective concentration range. Also, pre-incubation experiments demonstrated a temporal separation of the two effects of .... In conclusion, suppression of cytokine production by SPIR may be associated with its apoptotic potential, either directly (apoptosis is a consequence of suppressed cytokine production, or vice-versa) or indirectly (suppressed cytokine production and apoptosis are parallel but otherwise unrelated phenomena)....

  4. Modulation of the stress response during apoptosis and necrosis induction in cadmium-treated U-937 human promonocytic cells. (United States)

    Galán, A; Troyano, A; Vilaboa, N E; Fernández, C; de Blas, E; Aller, P


    Treatment for 2 h with 200 microM cadmium chloride, followed by recovery, caused apoptosis and induced heat-shock protein 70 (HSP70) expression in U-937 promonocytic cells. However, pre-incubation with the GSH depleting agent L-buthionine-[S,R]-sulfoximine (BSO, 1 mM for 24 h) caused necrosis instead of apoptosis and failed to induce HSP70 expression. This failure was a consequence of necrosis instead of GSH depletion, since BSO allowed or even potentiated HSP70 induction when used in combination with heat shock (2 h at 42.5 degrees C) or with 50 microM cadmium, which caused apoptosis. The administration of N-acetyl-L-cysteine (NAC) at the beginning of recovery after BSO/200 microM cadmium treatment prevented the execution of necrosis and restored the execution of apoptosis, but did not restore HSP70 induction, indicating that the inhibition by BSO of HSP70 expression is an early regulated event. This contrasted with the capacity of NAC to prevent the alterations caused by BSO/200 microM cadmium in other proteins, namely the suppression of Bax expression and the increase in Bcl-2 and HSP-60 expression. Finally, it was observed that treatment with 200 microM cadmium rapidly increased the HSP70 mRNA level and stimulated heat-shock factor 1 (HSF1) trimerization and binding, and that these effects were prevented by pre-incubation with BSO. Taken together, these results indicate that the stress response is compatible with apoptosis but not with necrosis in cadmium-treated promonocytic cells. The suppression of the stress response is specifically due to the early inhibition of HSF1 activation.

  5. Induction of apoptosis in response to improved gedunin by ...

    African Journals Online (AJOL)

    Apoptosis detection assays and gene expression analysis revealed the transcriptional modulation of the apoptosis-related genes (p53, survivin and Bax), increased activity of caspase 3/7 and the condensation of nuclear chromatin, implying the induction of apoptosis by the nano-formulation in NCI-H292 cells. Conclusion: ...

  6. [Mechanism of eosinophil apoptosis and its regulation in allergic reaction]. (United States)

    Zhang, Hao; Liu, Yuehui; Zhu, Xinhua


    In allergic reaction activated eosinophils have been known to accumulate at the site of inflamma tion. Apoptosis of eosinophils may be involved in the inflammation resolution. In this review, we state that the apoptosis of eosinophils play a direct role in allergic reaction. Regulating the apoptosis of eosinophils can effectively alter the development of allergic inflammatory reaction.

  7. Relevancia de la apoptosis en la reproduccion femenina

    National Research Council Canada - National Science Library

    Meresman, Gabriela


    ... y al mantenimiento de los tejidos. A lo largo de la vida de un organismo, la apoptosis participa desde el desarrollo hasta la senescencia. El delicado equilibrio entre proliferacion celular y apoptosis asegura un correcto control sobre la homeostasis de los tejidos. Sin embargo una falla en ese balance dada tanto por niveles de apoptosis aumentados como...

  8. Assessment of radiation induced apoptosis in lymphocyte subpopulations; Evaluacion de la apoptosis radioinducidas en subpoblaciones linfocitarias

    Energy Technology Data Exchange (ETDEWEB)

    Perez, M. del R.; Dubner, Diana L.; Michelin, Severino; Gisone, Pablo A. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina). Gerencia de Apoyo Cientifico. Lab. de Radiopatologia; Barboza, Marcos [Hospital de Clinicas Jose San Martin, Buenos AIres (Argentina). Servicio de Imunogenetica. Citometria de Flujo


    Apoptosis is the main form of radioinduced cell death. The lymphocytes, highly radiosensitive cells, dead in interphase by apoptosis even after very low doses. It has been demonstrated that the various peripheral blood lymphocyte (PBL) types display clear differences in their radiosensitivity . The purpose of this work was the characterization of radioinduced apoptosis in total PBL and in helper and cytotoxic T-lymphocytes. Blood samples were irradiated with a gamma source with doses between 0,5 and 4 Gy, dose-rate 0,8 Gy/min. Apoptosis was evaluated at different times post irradiation (p.i.) by conventional and fluorescence microscopy. Fragmentation of DNA was determined by electrophoresis in agarose gels. Apoptosis was quantified flow cytometrically by light scatter gram and determining the percent of fixed cells stained with propidium iodide that exhibited a reduced DNA content. FITC-labelled Annexin V was used to bind cell membrane phosphatidylserine which is aberrantly exposed during apoptosis. As an additional approach for the evaluation of apoptosis we measured the mitochondrial transmembrane potential by using the cationic dye 3,3 dihexyl oxacarbocyanine iodide (DiOC{sub 6}). Chromatin condensation and apoptotic bodies were microscopically observed and internucleosomal fragmentation was revealed in electrophoresis gels. Apoptotic cell fraction displayed a dose-dependent increase with a higher radiosensitivity for CD8 T-lymphocytes. These results suggest that quantification of PBL apoptosis could be an useful biological indicator in accidental overexposures and could also provide an useful predictive test for individual radiosensitivity. The higher radiosensitivity revealed by CD8 subset could allow a better discrimination of this phenomenon. (author)

  9. Copper Oxide Nanoparticles Induced Mitochondria Mediated Apoptosis in Human Hepatocarcinoma Cells (United States)

    Siddiqui, Maqsood A.; Alhadlaq, Hisham A.; Ahmad, Javed; Al-Khedhairy, Abdulaziz A.; Musarrat, Javed; Ahamed, Maqusood


    Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2–50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level. PMID:23940521

  10. Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Maqsood A Siddiqui

    Full Text Available Copper oxide nanoparticles (CuO NPs are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2-50 µg/ml were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s of apoptosis due to CuO NPs exposure should be further invested at in vivo level.

  11. Spermine inhibits Endoplasmic Reticulum Stress - induced Apoptosis: a New Strategy to Prevent Cardiomyocyte Apoptosis

    Directory of Open Access Journals (Sweden)

    Can Wei


    Full Text Available Background/Aims: Endoplasmic reticulum stress (ERS plays an important role in the progression of acute myocardial infarction (AMI, in part by mediating apoptosis. Polyamines, including putrescine, spermidine, and spermine, are polycations with anti-oxidative, anti-aging, and cell growth-promoting activities. This study aimed to determine the mechanisms by which spermine protects against ERS-induced apoptosis in rats following AMI. Methods and Results: AMI was established by ligation of the left anterior descending coronary artery (LAD in rats, and exogenous spermine was administered by intraperitoneal injection (2.5 mg/ml daily for 7 days pre-AMI. Spermine treatment limited infarct size, attenuated cardiac troponin I and creatinine kinase-MB release, improved cardiac function, and decreased ERS and apoptosis related protein expression. Isolated cardiomyocytes subjected to hypoxia showed significant increase in reactive oxygen species (ROS and the expression of apoptosis and ERS related proteins; these effects occurred through PERK and eIF2α phosphorylation. The addition of spermine attenuated cardiomyocyte apoptosis, suppressed the production of ROS, and inhibited ERS related pathways. Conclusions: Spermine was an effective pre-treatment strategy to attenuate cardiac ERS injury in rats, and the cardioprotective mechanism occurring through inhibition of ROS production and down regulation of the PERK-eIF2α pathway. These findings provide a novel target for the prevention of apoptosis in the setting of AMI.

  12. Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis


    Shankar, Sharmila; Chen, Qinghe; Sarva, Krishna; Siddiqui, Imtiaz; Srivastava, Rakesh K


    Background: We have recently shown that curcumin (a diferuloylmethane) inhibits growth and induces apoptosis, and also demonstrated that TRAIL induces apoptosis by binding to specific cell surface death receptors in prostate cancer cells. The objectives of this paper were to investigate the molecular mechanisms by which curcumin enhanced the apoptosis-inducing potential of TRAIL in prostate cancer cells.Results: Curcumin enhanced the apoptosis-inducing potential of TRAIL in androgen-unrespons...

  13. The virus-induced HSPs regulate the apoptosis of operatus APCs that result in autoimmunity, not in homeostasis. (United States)

    Temajo, Norbert O; Howard, Neville


    The viruses stand salient as environmental factors that trigger autoimmunity. The virus realizes its effects through induction of heat-shock proteins (HSPs) as well as by the viral IE-axis-mediated conversion of organ epithelial cells into virgin de novo professional antigen-presenting cells (APCs). The HSP is the accomplished operator in homeostasis by the logic of it being the regulator of apoptosis. By virtue of its regulation of apoptosis, the HSP is also involved in autoimmunity: (1) adornment of viral IE-axis-generated virgin de novo professional APCs with HSP-induced co-stimulatory molecules which transform these otherwise epithelial cells to competent antigen presenters, the operatus APCs, liable to apoptosis that becomes the initiator of organ damages; (2) molecular mimicry mechanism: epitopes on the HSP may be mistaken for viral peptides and be presented by operatus APCs to autoreactive TCRs resulting in the apoptosis of the operatus APCs; (3) regulation of MHC class II DR-mediated apoptosis of operatus APCS which can result in organ-specific autoimmune syndromes. We should remember, however, that Nature's intended purpose for apoptosis of the professional APCs is benevolence: as a principal regulator of immune homeostasis. But the apoptosis of our postulated operatus APCs can result in autoimmunity. The transformation of virgin de novo professional APCs to operatus APCs mirrors the maturation of DCs through their acquisition of HSP-induced costimulatory molecules. What happens to mature DCs as antigen presenters that end in homeostasis is replicated by what happens to operatus APCs that ends instead in autoimmunity.

  14. Oscillating heat pipes

    CERN Document Server

    Ma, Hongbin


    This book presents the fundamental fluid flow and heat transfer principles occurring in oscillating heat pipes and also provides updated developments and recent innovations in research and applications of heat pipes. Starting with fundamental presentation of heat pipes, the focus is on oscillating motions and its heat transfer enhancement in a two-phase heat transfer system. The book covers thermodynamic analysis, interfacial phenomenon, thin film evaporation,  theoretical models of oscillating motion and heat transfer of single phase and two-phase flows, primary  factors affecting oscillating motions and heat transfer,  neutron imaging study of oscillating motions in an oscillating heat pipes, and nanofluid’s effect on the heat transfer performance in oscillating heat pipes.  The importance of thermally-excited oscillating motion combined with phase change heat transfer to a wide variety of applications is emphasized. This book is an essential resource and learning tool for senior undergraduate, gradua...

  15. Heat Related Illnesses

    National Research Council Canada - National Science Library

    Carter, R; Cheuvront, S. N; Sawka, M. N


    .... The risk of serious heat illness can be markedly reduced by implementing a variety of countermeasures, including becoming acclimated to the heat, managing heat stress exposure, and maintaining hydration...

  16. Heat Roadmap Europe 1

    DEFF Research Database (Denmark)

    Connolly, David; Mathiesen, Brian Vad; Østergaard, Poul Alberg


    Heat Roadmap Europe (Pre-study 1) investigates the role of district heating in the EU27 energy system by mapping local conditions across Europe, identifying the potential for district heating expansion, and subsequently simulating the potential resource in an hourly model of the EU27 energy system....... In 2010, approximately 12% of the space heating demand in Europe is met by district heating, but in this study four alternative scenarios are considered for the EU27 energy system: 1. 2010 with 30% district heating 2. 2010 with 50% district heating 3. 2030 with 30% district heating 4. 2050 with 50......% district heating These scenarios are investigated in two steps. Firstly, district heating replaces individual boilers by converting condensing power plants to combined heat and power plants (CHP) to illustrate how district heating improves the overall efficiency of the energy system. In the second step...

  17. Multidimensional Heat Conduction

    DEFF Research Database (Denmark)

    Rode, Carsten


    Analytical theory of multidimensional heat conduction. General heat conduction equation in three dimensions. Steay state, analytical solutions. The Laplace equation. Method of separation of variables. Principle of superposition. Shape factors. Transient, multidimensional heat conduction....

  18. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... sweating; nausea; and giddiness. Symptoms of heat stroke (late stage of heat illness) include flushed, hot, dry ... consciousness, vomiting or a high body temperature. For late stage heat stroke symptoms, cool the person further ...

  19. Absorption heat pump system (United States)

    Grossman, Gershon


    The efficiency of an absorption heat pump system is improved by conducting liquid from a second stage evaporator thereof to an auxiliary heat exchanger positioned downstream of a primary heat exchanger in the desorber of the system.

  20. The virus-induced HSPs regulate the apoptosis of operatus APCs that results in autoimmunity, not in homeostasis. (United States)

    Temajo, Norbert O; Howard, Neville


    The viruses are salient in the roles of environmental factors that trigger autoimmunity. The virus realizes its effects by the power of its induction of heat shock proteins (HSPs) as well as by the viral IE-axis-mediated conversion of organ epithelial cells into virgin de novo professional antigen-presenting cells (APCs). The HSP is the accomplished operator in homeostasis by the logic of it being the regulator of apoptosis. That HSP which regulates and controls different points in the pathways of apoptosis is rationally propitious as both HSP and apoptosis are highly conserved in multicellular organisms. By virtue of its regulation of apoptosis, the HSP is also involved in human autoimmunity and this involvement is tripartite: (i) adornment of viral IE-axis-generated virgin de novo professional APCs with HSP-induced co-stimulatory molecules which transform these otherwise epithelial cells to achieve the status of fledged competent antigen-presenters, the operatus APCs, which are liable to apoptosis that becomes the initiator of organ damages that can culminate in the autoimmune syndrome(s); apoptosis is a routine fate that befalls all APCs following their antigen presentation; (ii) molecular mimicry mechanism: epitopes on the HSP may be mistaken for viral peptides and be presented by operatus APCs to autoreactive TCRs resulting in the apoptosis of the operatus APCs; and (iii) regulation of MHC class II-DR-mediated apoptosis of operatus APCs which can ultimately consequent in organ-specific autoimmune syndromes. We should remember, however, that Nature's intended purpose for the apoptosis of the professional APCs is benevolence: as a principal regulator of homeostasis. It is only from the apoptosis of our postulated operatus APCs that the apoptotic consequence can be deleterious, an autoimmune syndrome(s). The transformation of virgin de novo professional APCs to operatus APCs mirrors the maturation of DCs, through their acquisition of HSP-induced co

  1. Down-regulation of HSP27 sensitizes TRAIL-resistant tumor cell to TRAIL-induced apoptosis

    DEFF Research Database (Denmark)

    Zhuang, Hongqin; Jiang, Weiwei; Cheng, Wei


    Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) has recently emerged as a cancer therapeutic agent because it preferentially induces apoptosis in human cancer over normal cells. Most tumor cells, including lung cancer cell line A549, unfortunately, are resistant to TRAIL...... treatment even at high dose. Recent studies indicated that TRAIL-resistant cancer cells could be sensitized to TRAIL by combination therapy. Stress and heat shock proteins such as HSP90, HSP70 and HSP27 are induced in response to a wide variety of physiological environmental insults including heat, reactive...... oxygen species or anticancer drugs. Their elevated expressions facilitate cells to survive in stress circumstances. The HSP27 expression is enhanced in many tumor cells, implying that it is involved in tumor progression and the development of treatment resistance in various tumors, including lung cancer...

  2. Regenerative adsorbent heat pump (United States)

    Jones, Jack A. (Inventor)


    A regenerative adsorbent heat pump process and system is provided which can regenerate a high percentage of the sensible heat of the system and at least a portion of the heat of adsorption. A series of at least four compressors containing an adsorbent is provided. A large amount of heat is transferred from compressor to compressor so that heat is regenerated. The process and system are useful for air conditioning rooms, providing room heat in the winter or for hot water heating throughout the year, and, in general, for pumping heat from a lower temperature to a higher temperature.

  3. The expression and function of hsp30-like small heat shock protein genes in amphibians, birds, fish, and reptiles. (United States)

    Heikkila, John J


    Small heat shock proteins (sHSPs) are a superfamily of molecular chaperones with important roles in protein homeostasis and other cellular functions. Amphibians, reptiles, fish and birds have a shsp gene called hsp30, which was also referred to as hspb11 or hsp25 in some fish and bird species. Hsp30 genes, which are not found in mammals, are transcribed in response to heat shock or other stresses by means of the heat shock factor that is activated in response to an accumulation of unfolded protein. Amino acid sequence analysis revealed that representative HSP30s from different classes of non-mammalian vertebrates were distinct from other sHSPs including HSPB1/HSP27. Studies with amphibian and fish recombinant HSP30 determined that they were molecular chaperones since they inhibited heat- or chemically-induced aggregation of unfolded protein. During non-mammalian vertebrate development, hsp30 genes were differentially expressed in selected tissues. Also, heat shock-induced stage-specific expression of hsp30 genes in frog embryos was regulated at the level of chromatin structure. In adults and/or tissue culture cells, hsp30 gene expression was induced by heat shock, arsenite, cadmium or proteasomal inhibitors, all of which enhanced the production of unfolded/damaged protein. Finally, immunocytochemical analysis of frog and chicken tissue culture cells revealed that proteotoxic stress-induced HSP30 accumulation co-localized with aggresome-like inclusion bodies. The congregation of damaged protein in aggresomes minimizes the toxic effect of aggregated protein dispersed throughout the cell. The current availability of probes to detect the presence of hsp30 mRNA or encoded protein has resulted in the increased use of hsp30 gene expression as a marker of proteotoxic stress in non-mammalian vertebrates. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Trovato, Francesca Maria; Weinberg, Annelie Martina; Al-Wasiyah, Mohammad K.; Alqahtani, Mohammed H.; Mobasheri, Ali


    Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA. PMID:26334269

  5. Molecular mechanisms of liver injury: apoptosis or necrosis. (United States)

    Wang, Kewei


    Hepatic apoptosis is thought of as a prevalent mechanism in most forms of liver injury. However, the role of hepatic apoptosis is often intermixed with the cellular necrosis. It remains unknown how apoptosis is relevant to the progression of the liver injury. This review summarizes the characteristics of both hepatic apoptosis and necrosis in pathogenesis of liver diseases. Apoptosis and necrosis represent alternative outcomes of different etiology during liver injury. Apoptosis is a main mode of cell death in chronic viral hepatitis, but is intermingled with necrosis in cholestatic livers. Necrosis is the principal type of liver cell killing in acetaminophen-induced hepatotoxicity. Anti-apoptosis as a strategy is beneficial to liver repair response. Therapeutic options of liver disease depend on the understanding toward pathogenic mechanisms of different etiology. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Heat pumps in district heating networks

    DEFF Research Database (Denmark)

    Ommen, Torben Schmidt; Markussen, Wiebke Brix; Elmegaard, Brian

    constraints limit the power plants. Efficient heat pumps can be used to decouple the constraints of electricity and heat production, while maintaining the high energy efficiency needed to match the politically agreed carbon emission goals. The requirements in terms of COP, location, capacity and economy...... are calculated using an energy system model which includes power plants, heat pumps and district heating consumption profiles. The model is developed with focus on accurate representation of the performance of the units in different locations and operating modes. The model can assist in investment decisions...... and strategic planning in the energy sector. The paper presents a case study of optimal implementation of heat pumps in the present energy system of the Copenhagen area. By introduction of the correct capacity of heat pumps, a 1,6 % reduction in fuel consumption for electricity and heat production can...

  7. Extracellular vesicles released following heat stress induce bystander effect in unstressed populations. (United States)

    Bewicke-Copley, Findlay; Mulcahy, Laura Ann; Jacobs, Laura Ann; Samuel, Priya; Akbar, Naveed; Pink, Ryan Charles; Carter, David Raul Francisco


    Cells naïve to stress can display the effects of stress, such as DNA damage and apoptosis, when they are exposed to signals from stressed cells; this phenomenon is known as the bystander effect. We previously showed that bystander effect induced by ionising radiation are mediated by extracellular vesicles (EVs). Bystander effect can also be induced by other types of stress, including heat shock, but it is unclear whether EVs are involved. Here we show that EVs released from heat shocked cells are also able to induce bystander damage in unstressed populations. Naïve cells treated with media conditioned by heat shocked cells showed higher levels of DNA damage and apoptosis than cells treated with media from control cells. Treating naïve cells with EVs derived from media conditioned by heat shocked cells also induced a bystander effect when compared to control, with DNA damage and apoptosis increasing whilst the level of cell viability was reduced. We demonstrate that treatment of naïve cells with heat shocked cell-derived EVs leads to greater invasiveness in a trans-well Matrigel assay. Finally, we show that naïve cells treated with EVs from heat-shocked cells are more likely to survive a subsequent heat shock, suggesting that these EVs mediate an adaptive response. We propose that EVs released following stress mediate an intercellular response that leads to apparent stress in neighbouring cells but also greater robustness in the face of a subsequent insult.

  8. Alcohol and Apoptosis: Friends or Foes? (United States)

    Rodriguez, Ana; Chawla, Karan; Umoh, Nsini A; Cousins, Valerie M; Ketegou, Assama; Reddy, Madhumati G; AlRubaiee, Mustafa; Haddad, Georges E; Burke, Mark W


    Alcohol abuse causes 79,000 deaths stemming from severe organ damage in the United States every year. Clinical manifestations of long-term alcohol abuse on the cardiac muscle include defective contractility with the development of dilated cardiomyopathy and low-output heart failure; which has poor prognosis with less than 25% survival for more than three years. In contrast, low alcohol consumption has been associated with reduced risk of cardiovascular disease, however the mechanism of this phenomenon remains elusive. The aim of this study was to determine the significance of apoptosis as a mediating factor in cardiac function following chronic high alcohol versus low alcohol exposure. Adult rats were provided 5 mM (low alcohol), 100 mM (high alcohol) or pair-fed non-alcohol controls for 4-5 months. The hearts were dissected, sectioned and stained with cresyl violet or immunohistochemically for caspase-3, a putative marker for apoptosis. Cardiomyocytes were isolated to determine the effects of alcohol exposure on cell contraction and relaxation. High alcohol animals displayed a marked thinning of the left ventricular wall combined with elevated caspase-3 activity and decreased contractility. In contrast, low alcohol was associated with increased contractility and decreased apoptosis suggesting an overall protective mechanism induced by low levels of alcohol exposure.

  9. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang


    Full Text Available Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

  10. Control of apoptosis by asymmetric cell division. (United States)

    Hatzold, Julia; Conradt, Barbara


    Asymmetric cell division and apoptosis (programmed cell death) are two fundamental processes that are important for the development and function of multicellular organisms. We have found that the processes of asymmetric cell division and apoptosis can be functionally linked. Specifically, we show that asymmetric cell division in the nematode Caenorhabditis elegans is mediated by a pathway involving three genes, dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail, that directly control the enzymatic machinery responsible for apoptosis. Interestingly, the MIDA1-like protein GlsA of the alga Volvox carteri, as well as the Snail-related proteins Snail, Escargot, and Worniu of Drosophila melanogaster, have previously been implicated in asymmetric cell division. Therefore, C. elegans dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail may be components of a pathway involved in asymmetric cell division that is conserved throughout the plant and animal kingdoms. Furthermore, based on our results, we propose that this pathway directly controls the apoptotic fate in C. elegans, and possibly other animals as well.

  11. Control of apoptosis by asymmetric cell division.

    Directory of Open Access Journals (Sweden)

    Julia Hatzold


    Full Text Available Asymmetric cell division and apoptosis (programmed cell death are two fundamental processes that are important for the development and function of multicellular organisms. We have found that the processes of asymmetric cell division and apoptosis can be functionally linked. Specifically, we show that asymmetric cell division in the nematode Caenorhabditis elegans is mediated by a pathway involving three genes, dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail, that directly control the enzymatic machinery responsible for apoptosis. Interestingly, the MIDA1-like protein GlsA of the alga Volvox carteri, as well as the Snail-related proteins Snail, Escargot, and Worniu of Drosophila melanogaster, have previously been implicated in asymmetric cell division. Therefore, C. elegans dnj-11 MIDA1, ces-2 HLF, and ces-1 Snail may be components of a pathway involved in asymmetric cell division that is conserved throughout the plant and animal kingdoms. Furthermore, based on our results, we propose that this pathway directly controls the apoptotic fate in C. elegans, and possibly other animals as well.

  12. Keratinocyte Apoptosis is Decreased in Psoriatic Epidermis

    Directory of Open Access Journals (Sweden)

    Fatma Eskioğlu


    Full Text Available Background and Design: Abnormal differentiation and hyperproliferation of keratinocytes are the hallmarks of psoriasis vulgaris. Although psoriasis vulgaris is generally accepted as a disease of decreased keratinocyte apoptosis, the results are contradictory. The aim of the current study is to investigate whether decreased keratinocyte apoptosis contributes to the formation of a thickened epidermis as increased keratinocyte proliferation. Material and Method: Forty-three untreated psoriasis vulgaris patients and 20 healthy control subjects were included into the study. Biopsy specimens taken from the enrollee were evaluated by immunohistochemical staining for Ki-67 expressions to show the proliferation of keratinocytes and by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL method to show the apoptotic keratinocytes. Results: Apoptotic index (percentage of the TUNEL positive cells was significantly lower in psoriatic epidermis (0.33±0.64 than in normal epidermis (0.75±0.85; whereas Ki-67 index (percentage of positively staining cells for Ki-67 was significantly higher in psoriatic epidermis (30.86±10.49 than in normal epidermis (11.65±2.98, (p=0.021 and p=0.00; respectively. Conclusion: Decreased keratinocyte apoptosis also contribute to increased epidermal thickness in psoriasis as well as increased keratinocyte proliferation.

  13. Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Pan Shiow-Lin


    Full Text Available Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1 in denbinobin-induced apoptosis in human lung adenocarcinoma (A549 cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN, two antioxidants (N-acetyl-L-cysteine (NAC and glutathione (GSH, a c-Jun N-terminal kinase (JNK inhibitor (SP600125, and an activator protein-1 (AP-1 inhibitor (curcumin. Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

  14. Nature's Heat Exchangers. (United States)

    Barnes, George


    Discusses the heat-transfer systems of different animals. Systems include heat conduction into the ground, heat transferred by convection, heat exchange in lizards, fish and polar animals, the carotid rete system, electromagnetic radiation from animals and people, and plant and animal fiber optics. (MDH)

  15. Transient Heat Conduction

    DEFF Research Database (Denmark)

    Rode, Carsten


    Analytical theory of transient heat conduction.Fourier's law. General heat conducation equation. Thermal diffusivity. Biot and Fourier numbers. Lumped analysis and time constant. Semi-infinite body: fixed surface temperature, convective heat transfer at the surface, or constant surface heat flux...

  16. Solar Heating Equipment (United States)


    Solar Unlimited, Inc.'s suncatcher line includes a variety of solar arrays, derived from NASA's satellite program: water heating only, partial home heating, or water and whole house central heating. Solar Unlimited developed a set of vigorous requirements to avoid problems common to solar heating technologies.

  17. Rotary magnetic heat pump (United States)

    Kirol, Lance D.


    A rotary magnetic heat pump constructed without flow seals or segmented rotor accomplishes recuperation and regeneration by using split flow paths. Heat exchange fluid pumped through heat exchangers and returned to the heat pump splits into two flow components: one flowing counter to the rotor rotation and one flowing with the rotation.

  18. Heat Roadmap Europe

    DEFF Research Database (Denmark)

    Hansen, Kenneth; Connolly, David; Lund, Henrik


    of supplying sustainable heating. Different heat production options are included in terms of individual and community heating systems. Furthermore, the levelised cost of supplying sustainable heat is estimated for both a single technology and from an energy system perspective. The results are analysed...... by assessing various parameters such as socio-economic costs and energy efficiency improvements in the national energy systems. The results demonstrate the economically feasible levels of heat savings and heat production for various European countries, highlighting differences in their national conditions......The cost of heat savings in buildings increase as more heat savings are achieved due to the state of the building stock and hence, alternatives other than savings typically become more economically feasible at a certain level of heat reductions. It is important to identify when the cost of heat...

  19. Heat Roadmap Europe 2

    DEFF Research Database (Denmark)

    Connolly, David; Mathiesen, Brian Vad; Østergaard, Poul Alberg

    Many strategies have already been proposed for the decarbonisation of the EU energy system by the year 2050. These typically focus on the expansion of renewable energy in the electricity sector and subsequently, electrifying both the heat and transport sectors as much as possible...... are identified and then, the EU27 energy system is modelled to investigate the impact of district heating. The results indicate that a combination of heat savings, district heating in urban areas, and individual heat pumps in rural areas will enable the EU27 to reach its greenhouse gas emission targets by 2050....... In these strategies, the role of district heating has never been fully explored system, nor have the benefits of district heating been quantified at the EU level. This study combines the mapping of local heat demands and local heat supplies across the EU27. Using this local knowledge, new district heating potentials...

  20. Heat Roadmap Europe

    DEFF Research Database (Denmark)

    Connolly, David; Mathiesen, Brian Vad; Lund, Henrik


    information systems (GIS) and energy system analyses. In this report, the inputs for other modelling tools such as PRIMES are presented, in order to enable other researches to generate similar heating scenarios for Europe. Although Heat Roadmap Europe presents a complete heat strategy for Europe, which...... includes energy efficiency, individual heating units (such as boilers and heat pumps), and heat networks, the recommendations here are primarily relating to the potential and modelling of district heating. Although other solutions will play a significant role in decarbonising the heating and cooling sector...... in a low-carbon energy system context, so we have focused on this area based on our extensive experience in this area [1-10]. This report includes guidelines on the potential heat demand in European buildings that can be met by district heating as well as some general guidelines on how this district...

  1. Role of apoptosis and necrosis in cell death induced by nanoparticle-mediated photothermal therapy (United States)

    Pattani, Varun P.; Shah, Jay; Atalis, Alexandra; Sharma, Anirudh; Tunnell, James W.


    Current cancer therapies can cause significant collateral damage due to a lack of specificity and sensitivity. Therefore, we explored the cell death pathway response to gold nanorod (GNR)-mediated photothermal therapy as a highly specific cancer therapeutic to understand the role of apoptosis and necrosis during intense localized heating. By developing this, we can optimize photothermal therapy to induce a maximum of `clean' cell death pathways, namely apoptosis, thereby reducing external damage. GNRs were targeted to several subcellular localizations within colorectal tumor cells in vitro, and the cell death pathways were quantitatively analyzed after photothermal therapy using flow cytometry. In this study, we found that the cell death response to photothermal therapy was dependent on the GNR localization. Furthermore, we demonstrated that nanorods targeted to the perinuclear region irradiated at 37.5 W/cm2 laser fluence rate led to maximum cell destruction with the `cleaner' method of apoptosis, at similar percentages as other anti-cancer targeted therapies. We believe that this indicates the therapeutic potential for GNR-mediated photothermal therapy to treat cancer effectively without causing damage to surrounding tissue.

  2. Role of apoptosis and necrosis in cell death induced by nanoparticle-mediated photothermal therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pattani, Varun P., E-mail:; Shah, Jay; Atalis, Alexandra; Sharma, Anirudh; Tunnell, James W. [The University of Texas at Austin, Department of Biomedical Engineering (United States)


    Current cancer therapies can cause significant collateral damage due to a lack of specificity and sensitivity. Therefore, we explored the cell death pathway response to gold nanorod (GNR)-mediated photothermal therapy as a highly specific cancer therapeutic to understand the role of apoptosis and necrosis during intense localized heating. By developing this, we can optimize photothermal therapy to induce a maximum of ‘clean’ cell death pathways, namely apoptosis, thereby reducing external damage. GNRs were targeted to several subcellular localizations within colorectal tumor cells in vitro, and the cell death pathways were quantitatively analyzed after photothermal therapy using flow cytometry. In this study, we found that the cell death response to photothermal therapy was dependent on the GNR localization. Furthermore, we demonstrated that nanorods targeted to the perinuclear region irradiated at 37.5 W/cm{sup 2} laser fluence rate led to maximum cell destruction with the ‘cleaner’ method of apoptosis, at similar percentages as other anti-cancer targeted therapies. We believe that this indicates the therapeutic potential for GNR-mediated photothermal therapy to treat cancer effectively without causing damage to surrounding tissue.

  3. The protective role of HSP90 against 3-hydroxykynurenine-induced neuronal apoptosis. (United States)

    Lee, M W; Park, S C; Chae, H S; Bach, J H; Lee, H J; Lee, S H; Kang, Y K; Kim, K Y; Lee, W B; Kim, S S


    3-hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the present study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- and time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrinkage, plasma membrane blebbing, chromatin condensation, and nuclear condensation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results show that the protective effect was abolished by HSP90 anti-sense oligonucleotides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our result shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neuroblastoma SK-N-SN cells and that HSP90 is major contributing protein component of protection against 3HK induced apoptosis. Copyright 2001 Academic Press.

  4. Introduction to heat transfer

    CERN Document Server



    Presenting the basic mechanisms for transfer of heat, Introduction to Heat Transfer gives a deeper and more comprehensive view than existing titles on the subject. Derivation and presentation of analytical and empirical methods are provided for calculation of heat transfer rates and temperature fields as well as pressure drop. The book covers thermal conduction, forced and natural laminar and turbulent convective heat transfer, thermal radiation including participating media, condensation, evaporation and heat exchangers.

  5. Spironolactone induces apoptosis in human mononuclear cells. Association between apoptosis and cytokine suppression

    DEFF Research Database (Denmark)

    Mikkelsen, Martin; Sønder, S U; Nersting, J


    Spironolactone (SPIR) has been described to suppress accumulation of pro-inflammatory cytokines. Here, the suppression of TNF-alpha in lipopolysaccharide (LPS)-stimulated mononuclear cell cultures was confirmed. However, SPIR was also found to induce apoptosis, prompting the investigations...... of a possible association between the two effects: The apoptosis-inducing and the cytokine-suppressive effects of SPIR correlated with regard to the effective concentration range. Also, pre-incubation experiments demonstrated a temporal separation of the two effects of ... preceding apoptosis. An association between the two effects was also seen when testing several SPIR analogues. Contrary to TNF-alpha, the levels of IL-1beta increased in SPIR-treated cultures. However, the amount of IL-1beta in the supernatants depended upon the order of SPIR and LPS addition, as IL-1beta...

  6. Heat cascading regenerative sorption heat pump (United States)

    Jones, Jack A. (Inventor)


    A simple heat cascading regenerative sorption heat pump process with rejected or waste heat from a higher temperature chemisorption circuit (HTCC) powering a lower temperature physisorption circuit (LTPC) which provides a 30% total improvement over simple regenerative physisorption compression heat pumps when ammonia is both the chemisorbate and physisorbate, and a total improvement of 50% or more for LTPC having two pressure stages. The HTCC contains ammonia and a chemisorbent therefor contained in a plurality of canisters, a condenser-evaporator-radiator system, and a heater, operatively connected together. The LTPC contains ammonia and a physisorbent therefor contained in a plurality of compressors, a condenser-evaporator-radiator system, operatively connected together. A closed heat transfer circuit (CHTC) is provided which contains a flowing heat transfer liquid (FHTL) in thermal communication with each canister and each compressor for cascading heat from the HTCC to the LTPC. Heat is regenerated within the LTPC by transferring heat from one compressor to another. In one embodiment the regeneration is performed by another CHTC containing another FHTL in thermal communication with each compressor. In another embodiment the HTCC powers a lower temperature ammonia water absorption circuit (LTAWAC) which contains a generator-absorber system containing the absorbent, and a condenser-evaporator-radiator system, operatively connected together. The absorbent is water or an absorbent aqueous solution. A CHTC is provided which contains a FHTL in thermal communication with the generator for cascading heat from the HTCC to the LTAWAC. Heat is regenerated within the LTAWAC by transferring heat from the generator to the absorber. The chemical composition of the chemisorbent is different than the chemical composition of the physisorbent, and the absorbent. The chemical composition of the FHTL is different than the chemisorbent, the physisorbent, the absorbent, and ammonia.

  7. Heat stroke and related heat stress disorders. (United States)

    Knochel, J P


    Medical disorders related to environmental heat exposure are exceptionally common in persons who perform hard work in hot climates. They are also common in competitive athletes as well as in persons who participate in casual exercise to maintain health. The important issue of salt and water disturbances consequent to heavy sweating in hot climates is discussed in detail as are mechanisms of potassium deficiency and its implications. The major forms of environmental heat illness including heat syncope, heat cramp, heat exhaustion, and heat stroke are presented in detail with relevant clinical examples. A discussion of the differential diagnosis of hyperthermia and rhabdomyolysis follows. Because of the difference in treatment and complications, heat stroke is subdivided into the classic variety that affects the elderly and very young and that form that follows heavy physical work and is always associated with rhabdomyolysis. Because severe heat exhaustion and heat stroke are life-threatening disorders, the chapter includes a detailed discussion of complications and plans for treatment.

  8. Glioma progression through the prism of heat shock protein mediated extracellular matrix remodeling and epithelial to mesenchymal transition. (United States)

    Rajesh, Y; Biswas, Angana; Mandal, Mahitosh


    Glial tumor is one of the intrinsic brain tumors with high migratory and infiltrative potential. This essentially contributes to the overall poor prognosis by circumvention of conventional treatment regimen in glioma. The underlying mechanism in gliomagenesis is bestowed by two processes- Extracellular matrix (ECM) Remodeling and Epithelial to mesenchymal transition (EMT). Heat Shock Family of proteins (HSPs), commonly known as "molecular chaperons" are documented to be upregulated in glioma. A positive correlation also exists between elevated expression of HSPs and invasive capacity of glial tumor. HSPs overexpression leads to mutational changes in glioma, which ultimately drive cells towards EMT, ECM modification, malignancy and invasion. Differential expression of HSPs - a factor providing cytoprotection to glioma cells, also contributes towards its radioresistance /chemoresistance. Various evidences also display upregulation of EMT and ECM markers by various heat shock inducing proteins e.g. HSF-1. The aim of this review is to study in detail the role of HSPs in EMT and ECM leading to radioresistance/chemoresistance of glioma cells. The existing treatment regimen for glioma could be enhanced by targeting HSPs through immunotherapy, miRNA and exosome mediated strategies. This could be envisaged by better understanding of molecular mechanisms underlying glial tumorigenesis in relation to EMT and ECM remodeling under HSPs influence. Our review might showcase fresh potential for the development of next generation therapeutics for effective glioma management. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Non-viable Borrelia burgdorferi induce inflammatory mediators and apoptosis in human oligodendrocytes. (United States)

    Parthasarathy, Geetha; Fevrier, Helene B; Philipp, Mario T


    In previous studies, exposure to live Borrelia burgdorferi was shown to induce inflammation and apoptosis of human oligodendrocytes. In this study we assessed the ability of non-viable bacteria (heat killed or sonicated) to induce inflammatory mediators and cell death. Both heat-killed and sonicated bacteria induced release of CCL2, IL-6, and CXCL8 from oligodendrocytes in a dose dependent manner. In addition, non-viable B. burgdorferi also induced cell death as evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and another cell viability assay. These results suggest that spirochetal residues left after bacterial demise, due to treatment or otherwise, may continue to be pathogenic to the central nervous system. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Artesunate induces AIF-dependent apoptosis in A549 cells (United States)

    Zhou, Chen-juan; Chen, Tong-Sheng


    Artesunate (ART), a semi-synthetic derivative of the sesquiterpene artemisinin extracted from the Chinese herb Artemisia annua, exerts a broad spectrum of clinical activity against human cancers. It has been shown that ART induces cancer cells death through apoptosis pathway. This study investigated whether ART treatment induced reactive oxygen species (ROS)-dependent cell death in the apoptosis fashion in human lung adenocarconoma A549 cell line and the proapoptotic protein apoptosis inducing factor (AIF) is involved in ART-induced apoptosis. Cells treated with ART exhibited typical apoptotic morphology as chromatin condensation, margination and shrunken nucleus. ART treatment also induced a loss of mitochondrial membrane potential and AIF release from mitochondria. Silencing AIF can remarkable attenuated ART-induced apoptosis. Collectively, ART induces apoptosis by caspase-independent intrinsic pathway in A549 cells.

  11. Heat Pipe Technology (United States)


    The heat pipe, a sealed chamber whose walls are lined with a "wick," a thin capillary network containing a working fluid in liquid form was developed for a heat distribution system for non-rotating satellites. Use of the heat pipe provides a continuous heat transfer mechanism. "Heat tubes" that improve temperature control in plastics manufacturing equipment incorporated the heat pipe technology. James M. Stewart, an independent consultant, patented the heat tubes he developed and granted a license to Kona Corporation. The Kona Nozzle for heaterless injection molding gets heat for its operation from an external source and has no internal heating bands, reducing machine maintenance and also eliminating electrical hazards associated with heater bands. The nozzles are used by Eastman Kodak, Bic Pen Corporation, Polaroid, Tupperware, Ford Motor Company, RCA, and Western Electric in the molding of their products.

  12. Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Yun-Ji Lim

    Full Text Available BACKGROUND: Apoptosis is thought to play a role in host defenses against intracellular pathogens, including Mycobacterium tuberculosis (Mtb, by preventing the release of intracellular components and the spread of mycobacterial infection. This study aims to investigate the role of endoplasmic reticulum (ER stress mediated apoptosis in mycobacteria infected macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that ER stress-induced apoptosis is associated with Mtb H37Rv-induced cell death of Raw264.7 murine macrophages. We have shown that Mtb H37Rv induced apoptosis are involved in activation of caspase-12, which resides on the cytoplasmic district of the ER. Mtb infection increase levels of other ER stress indicators in a time-dependent manner. Phosphorylation of eIF2α was decreased gradually after Mtb H37Rv infection signifying that Mtb H37Rv infection may affect eIF2α phosphorylation in an attempt to survive within macrophages. Interestingly, the survival of mycobacteria in macrophages was enhanced by silencing CHOP expression. In contrast, survival rate of mycobacteria was reduced by phosphorylation of the eIF2α. Futhermore, the levels of ROS, NO or CHOP expression were significantly increased by live Mtb H37Rv compared to heat-killed Mtb H37Rv indicating that live Mtb H37Rv could induce ER stress response. CONCLUSION/SIGNIFICANCE: These findings indicate that eIF2α/CHOP pathway may influence intracellular survival of Mtb H37Rv in macrophages and only live Mtb H37Rv can induce ER stress response. The data support the ER stress pathway plays an important role in the pathogenesis and persistence of mycobacteria.

  13. Identification of Aadnr1, a novel gene related to innate immunity and apoptosis in Aedes albopictus. (United States)

    Li, Xiaomei; Meng, Kun; Qiao, Jialu; Liu, Hao; Zhong, Chunyan; Liu, Qingzhen


    Innate immunity and apoptosis play critical roles in defending pathogens in insects. In Drosophila, Dnr1 was reported as a negative regulator of apoptosis and immune deficiency (Imd) pathway which belongs to innate immunity. Aedes albopictus is an important kind of arbovirus vector and becoming a significant threat to public health due to its rapid global expansion. Here we identified an ortholog of dnr1 from A. albopictus, named as Aadnr1. Aadnr1 encoded a putative protein containing an N-terminal FERM domain and a C-terminal RING domain. AaDnr1 shared high identity with dipteran insects Dnr1 orthologs. Phylogenetic analyses showed that the closest relative of AaDnr1 was Aedes aegypti Dnr1. Real-time PCR proved that Aadnr1 mRNA was expressed ubiquitously during developmental and adult stages. Transcriptional levels of Aadnr1 were decreased drastically in C6/36 cells underwent apoptosis induced by Actinomycin D (Act D) treatment. Partial silence of Aadnr1 enhanced Act D-induced caspase activity. When challenged by heat-inactivated E. coli, transcriptional level of Aadnr1 was also decreased dramatically in C6/36 cells. While when C6/36 cells were infected with Sindbis virus TE/GFP, transcriptional level of Aadnr1 was reduced and recovered repeatedly, with an overall decreasing trend. It was also shown in this study that similar to Drosophila Dnr1, RING domain destabilized AaDnr1 protein. Taken together, the study identified an innate immunity and apoptosis related gene Aadnr1 in A. albopictus. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Apoptosis and Its Significance in Oral Diseases: An Update

    Directory of Open Access Journals (Sweden)

    Megha Jain


    Full Text Available Apoptosis is a well defined mode of cell death which plays an imperative role in the development, regulation, and maintenance of the cell populations in multicellular organisms. Apoptosis is implicated in both health and diseases. Errors in apoptotic mechanisms have been allied to a wide range of pathologies including oral diseases. This review presents an update focused on the role and significance of apoptosis in various oral diseases ranging from reactive to benign and malignant pathologies.

  15. Overcoming Autophagy to Induce Apoptosis in Castration Resistant Prostate Cancer (United States)


    AWARD NUMBER: W81XWH-12-1-0529 TITLE: Overcoming Autophagy to Induce Apoptosis in Castration Resistant Prostate Cancer PRINCIPAL...survival mechanism and led cells to undergo apoptosis . Survival mechanisms elicited by CRPC C4-2B cells when treated with Enza may be blocked by...Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells. Cancer

  16. Cyclin-dependent kinases regulate apoptosis of intestinal epithelial cells. (United States)

    Bhattacharya, Sujoy; Ray, Ramesh M; Johnson, Leonard R


    Homeostasis of the gastrointestinal epithelium is dependent upon a balance between cell proliferation and apoptosis. Cyclin-dependent kinases (Cdks) are well known for their role in cell proliferation. Previous studies from our group have shown that polyamine-depletion of intestinal epithelial cells (IEC-6) decreases cyclin-dependent kinase 2 (Cdk2) activity, increases p53 and p21Cip1 protein levels, induces G1 arrest, and protects cells from camptothecin (CPT)-induced apoptosis. Although emerging evidence suggests that members of the Cdk family are involved in the regulation of apoptosis, their roles directing apoptosis of IEC-6 cells are not known. In this study, we report that inhibition of Cdk1, 2, and 9 (with the broad range Cdk inhibitor, AZD5438) in proliferating IEC-6 cells triggered DNA damage, activated p53 signaling, inhibited proliferation, and induced apoptosis. By contrast, inhibition of Cdk2 (with NU6140) increased p53 protein and activity, inhibited proliferation, but had no effect on apoptosis. Notably, AZD5438 sensitized, whereas, NU6140 rescued proliferating IEC-6 cells from CPT-induced apoptosis. However, in colon carcinoma (Caco-2) cells with mutant p53, treatment with either AZD5438 or NU6140 blocked proliferation, albeit more robustly with AZD5438. Both Cdk inhibitors induced apoptosis in Caco-2 cells in a p53-independent manner. In serum starved quiescent IEC-6 cells, both AZD5438 and NU6140 decreased TNF-α/CPT-induced activation of p53 and, consequently, rescued cells from apoptosis, indicating that sustained Cdk activity is required for apoptosis of quiescent cells. Furthermore, AZD5438 partially reversed the protective effect of polyamine depletion whereas NU6140 had no effect. Together, these results demonstrate that Cdks possess opposing roles in the control of apoptosis in quiescent and proliferating cells. In addition, Cdk inhibitors uncouple proliferation from apoptosis in a p53-dependent manner.

  17. Cell proliferation and apoptosis in gastric cancer and intestinal metaplasia


    Nora Manoukian Forones; Ana Paula Souza Carvalho; Oswaldo Giannotti-Filho; Laércio Gomes Lourenço; Celina Tizuko Fujiyama Oshima


    BACKGROUND: Higher proliferation is commonly observed in cancer cells. Apoptosis can be a useful measure of a tumor cell kinetic. Alteration of the balance between proliferation and apoptosis is associated with cancer. AIM: To study proliferation and apoptosis on gastric cancer and in intestinal metaplasia. METHODOLOGY: Twenty-two samples from gastric adenocarcinomas and 22 biopsies from intestinal metaplasia were studied. The apoptotic bodies in hematoxylin-eosin slides and the expression of...

  18. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells


    Ewelina Szliszka; Zenon P. Czuba; Bogdan Mazur; Lukasz Sedek; Andrzej Paradysz; Wojciech Krol


    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showe...

  19. Contrast agents and renal cell apoptosis. (United States)

    Romano, Giulia; Briguori, Carlo; Quintavalle, Cristina; Zanca, Ciro; Rivera, Natalia V; Colombo, Antonio; Condorelli, Gerolama


    Contrast media (CM) induce a direct toxic effect on renal tubular cells. This toxic effect may have a role in the pathophysiology of contrast nephropathy. We evaluated (i) the cytotoxicity of CM [both low-osmolality (LOCM) and iso-osmolality (IOCM)], of iodine alone, and of an hyperosmolar solution (mannitol 8%) on human embryonic kidney (HEK 293), porcine proximal renal tubular (LLC-PK1), and canine Madin-Darby distal tubular renal (MDCK) cells; and (ii) the effectiveness of various antioxidant compounds [n-acetylcysteine (NAC), ascorbic acid and sodium bicarbonate] in preventing CM cytotoxicity. The cytotoxicity of CM was assessed at different time points, with different methods: cell viability, DNA laddering, flow cytometry, and caspase activation. Both LOCM and IOCM produced a concentration- and time-dependent increase in cell death as assessed by the different methods. On the contrary, iodine alone and hyperosmolar solution did not induce any significant cytotoxic effect. There was not any significant difference in the cytotoxic effect between LOCM and IOCM. Furthermore, both LOCM and IOCM caused a marked increase in caspase-3 and -9 activities and poly(ADP-ribose) fragmentation, while no effect on caspase-8/-10 was observed, thus indicating that the CM activated apoptosis mainly through the intrinsic pathway. Both CM induced an increase in protein expression levels of pro-apoptotic members of the Bcl2 family (Bim and Bad). NAC and ascorbic acid but not sodium bicarbonate had a dose-dependent protective effect on renal cells after 3 h incubation with high dose (200 mg iodine/mL) of both LOCM and IOCM. Both LOCM and IOCM induce a dose-dependent renal cell apoptosis. NAC and ascorbic acid but not sodium bicarbonate prevent this contrast-induced apoptosis.

  20. Basic heat transfer

    CERN Document Server

    Bacon, D H


    Basic Heat Transfer aims to help readers use a computer to solve heat transfer problems and to promote greater understanding by changing data values and observing the effects, which are necessary in design and optimization calculations.The book is concerned with applications including insulation and heating in buildings and pipes, temperature distributions in solids for steady state and transient conditions, the determination of surface heat transfer coefficients for convection in various situations, radiation heat transfer in grey body problems, the use of finned surfaces, and simple heat exc

  1. Ideal Heat Exchange System (United States)

    Tsirlin, A. M.


    The requirements with which a heat exchange system should comply in order that at certain values of the total contact surface and heat load the entropy production in it should be minimal have been determined. It has been shown that this system can serve as a standard for real systems of irreversible heat exchange. We have found the conditions for physical realizability of a heat exchange system in which heat exchange occurs by a law linear with respect to the temperature difference between contacting flows. Analogous conditions are given without deriving for the case of heat exchange by the Fourier law.

  2. Microscale Regenerative Heat Exchanger (United States)

    Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred


    The device described herein is designed primarily for use as a regenerative heat exchanger in a miniature Stirling engine or Stirling-cycle heat pump. A regenerative heat exchanger (sometimes called, simply, a "regenerator" in the Stirling-engine art) is basically a thermal capacitor: Its role in the Stirling cycle is to alternately accept heat from, then deliver heat to, an oscillating flow of a working fluid between compression and expansion volumes, without introducing an excessive pressure drop. These volumes are at different temperatures, and conduction of heat between these volumes is undesirable because it reduces the energy-conversion efficiency of the Stirling cycle.

  3. Research Advances on Pathways of Nickel-Induced Apoptosis (United States)

    Guo, Hongrui; Chen, Lian; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan


    High concentrations of nickel (Ni) are harmful to humans and animals. Ni targets a number of organs and produces multiple toxic effects. Apoptosis is important in Ni-induced toxicity of the kidneys, liver, nerves, and immune system. Apoptotic pathways mediated by reactive oxygen species (ROS), mitochondria, endoplasmic reticulum (ER), Fas, and c-Myc participate in Ni-induced cell apoptosis. However, the exact mechanism of apoptosis caused by Ni is still unclear. Understanding the mechanism of Ni-induced apoptosis may help in designing measures to prevent Ni toxicity. PMID:26703593

  4. Carbamate Pesticide-Induced Apoptosis in Human T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Qing Li


    Full Text Available We previously found that carbamate pesticides induced significant apoptosis in human natural killer cells. To investigate whether carbamate pesticides also induce apoptosis in human T lymphocytes, in the present study Jurkat human T cells were treated in vitro with thiram, maneb, carbaryl or ziram. Apoptosis was determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspase 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that thiram, ziram, maneb and carbaryl also induced apoptosis in a time- and dose-dependent manner in the human T cells. However, the strength of the apoptosis-inducing effect differed among the pesticides, with the: thiram > ziram > maneb > carbaryl. Moreover, thiram significantly increased the intracellular level of active caspase 3 and caspase inhibitors significantly inhibited apoptosis. Thiram also significantly caused mitochondrial cytochrome-c release. These findings indicate that carbamate pesticides can induce apoptosis in human T cells, and the apoptosis is mediated by the activation of caspases and the release of mitochondrial cytochrome-c.

  5. Apoptosis in Acanthamoeba castellanii belonging to the T4 genotype. (United States)

    Baig, Abdul M; Lalani, Salima; Khan, Naveed A


    Here we describe features of apoptosis in unicellular Acanthamoeba castellanii belonging to the T4 genotype. When exposed to apoptosis-inducing compounds such as doxorubicin, A. castellanii trophozoites exhibited cell shrinkage and membrane blebbing as observed microscopically, DNA fragmentation using agarose gel electrophoresis, and phosphatidylserine (PS) externalization using annexin V immunostaining. Overall, these findings suggest the existence of apoptosis in A. castellanii possibly mediated by intrinsic apoptotic cascade. Further research in this field could provide avenues to selectively induce apoptosis in A. castellanii by triggering intrinsic apoptotic cascade. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Carbamate pesticide-induced apoptosis in human T lymphocytes. (United States)

    Li, Qing; Kobayashi, Maiko; Kawada, Tomoyuki


    We previously found that carbamate pesticides induced significant apoptosis in human natural killer cells. To investigate whether carbamate pesticides also induce apoptosis in human T lymphocytes, in the present study Jurkat human T cells were treated in vitro with thiram, maneb, carbaryl or ziram. Apoptosis was determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspase 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that thiram, ziram, maneb and carbaryl also induced apoptosis in a time- and dose-dependent manner in the human T cells. However, the strength of the apoptosis-inducing effect differed among the pesticides, with the: thiram > ziram > maneb > carbaryl. Moreover, thiram significantly increased the intracellular level of active caspase 3 and caspase inhibitors significantly inhibited apoptosis. Thiram also significantly caused mitochondrial cytochrome-c release. These findings indicate that carbamate pesticides can induce apoptosis in human T cells, and the apoptosis is mediated by the activation of caspases and the release of mitochondrial cytochrome-c.

  7. Shifting the balance of mitochondrial apoptosis: therapeutic perspectives

    Directory of Open Access Journals (Sweden)

    Simone eFulda


    Full Text Available Signaling via the intrinsic (mitochondrial pathway of apoptosis represents one of the critical signal transduction cascades that control the regulation of cell death. This pathway is typically altered in human cancers, thereby providing a suitable target for therapeutic intervention. Members of the Bcl-2 family of proteins as well as cell survival signaling cascades such as the PI3K/Akt/mTOR pathway are involved in the regulation of mitochondria-mediated apoptosis. Therefore, further insights into the molecular mechanisms that form the basis for the control of mitochondria-mediated apoptosis will likely open new perspectives to bypass evasion of apoptosis and treatment resistance in human cancers.

  8. Survival of fossils under extreme shocks induced by hypervelocity impacts. (United States)

    Burchell, M J; McDermott, K H; Price, M C; Yolland, L J


    Experimental data are shown for survival of fossilized diatoms undergoing shocks in the GPa range. The results were obtained from hypervelocity impact experiments which fired fossilized diatoms frozen in ice into water targets. After the shots, the material recovered from the target water was inspected for diatom fossils. Nine shots were carried out, at speeds from 0.388 to 5.34 km s(-1), corresponding to mean peak pressures of 0.2-19 GPa. In all cases, fragmented fossilized diatoms were recovered, but both the mean and the maximum fragment size decreased with increasing impact speed and hence peak pressure. Examples of intact diatoms were found after the impacts, even in some of the higher speed shots, but their frequency and size decreased significantly at the higher speeds. This is the first demonstration that fossils can survive and be transferred from projectile to target in hypervelocity impacts, implying that it is possible that, as suggested by other authors, terrestrial rocks ejected from the Earth by giant impacts from space, and which then strike the Moon, may successfully transfer terrestrial fossils to the Moon.

  9. Limits of metastability in shock-induced phase transitions (United States)

    Ravelo, Ramon


    In dynamic compression, kinetic effects may delay a phase transition and under extreme strain rates of deformation, the parent phase can be loaded into metastable states from which the transition takes place, beyond the equilibrium phase boundary. Large-scale atomistic simulations coupled with first-principles calculations can provide valuable insights in the study of phase changes under extreme conditions, such as those produced by strong shock waves. The size scale of systems that can be studied via atomistic simulations are now sufficient to study large defective or multiphase structures, and the time-scales sampled in non-equilibrium molecular dynamics (NEMD) are currently in the nanoseconds, a time scale accessible in high-energy laser driven shock experiments. Atomistic simulations of shocked single crystals, show that sub-nanoseconds rise times and strain rates >109s-1 can lead to deformation paths and transformation mechanisms different from homogeneous nucleation or thermally activated processes. We present a formulation of the limits of metastability of elastic-plastic and structural transitions in single crystals, including amorphization, under high strain-rates of deformation, based on large-scale atomistic simulations and ab-initio calculations. This work supported by the Air Force Office of Scientific Research under AFOSR Award FA9550-12-1-0476.

  10. Shock-induced explosive chemistry in a deterministic sample configuration.

    Energy Technology Data Exchange (ETDEWEB)

    Stuecker, John Nicholas; Castaneda, Jaime N.; Cesarano, Joseph, III (,; ); Trott, Wayne Merle; Baer, Melvin R.; Tappan, Alexander Smith


    Explosive initiation and energy release have been studied in two sample geometries designed to minimize stochastic behavior in shock-loading experiments. These sample concepts include a design with explosive material occupying the hole locations of a close-packed bed of inert spheres and a design that utilizes infiltration of a liquid explosive into a well-defined inert matrix. Wave profiles transmitted by these samples in gas-gun impact experiments have been characterized by both velocity interferometry diagnostics and three-dimensional numerical simulations. Highly organized wave structures associated with the characteristic length scales of the deterministic samples have been observed. Initiation and reaction growth in an inert matrix filled with sensitized nitromethane (a homogeneous explosive material) result in wave profiles similar to those observed with heterogeneous explosives. Comparison of experimental and numerical results indicates that energetic material studies in deterministic sample geometries can provide an important new tool for validation of models of energy release in numerical simulations of explosive initiation and performance.

  11. On the scaling and unsteadiness of shock induced separation

    NARCIS (Netherlands)

    Souverein, L.J.


    Shock wave boundary layer interactions (SWBLI) are a common phenomenon in transonic and supersonic flows. The presence of shock waves, induced by specific geometrical configurations, causes a rapid increase of the pressure, which can lead to flow separation. Examples of such interactions are found

  12. [Intraoperative anaphylactic shock induced by methylergometrine and oxytocin]. (United States)

    Shimo, Tomohiro; Nishiike, Satoshi; Masuoka, Miharu; Seki, Sumihiko; Tsuchida, Hideaki


    We report a case of intraoperative anaphylactic shock in a 32-year-old multigravida woman undergoing elective cesarean section for partial placenta previa. Anesthesia was performed using combined spinal and epidural technique. After the baby was born, methylergometrine was administered i.v. simultaneously with oxytocin, the latter injected directly into the uterine muscle by an obstetrician. Several minutes later, she presented with dyspnea and became agitated. Because of the potential risk of pulmonary embolism, the patient was immediately intubated and mechanical ventilation was started. Her systolic blood pressure decreased to 50 mmHg and SpO2 to 87% under 100% oxygen administration. After catecholamine infusion, however, her respiratory condition soon improved. Postoperatively, her conjunctiva and vulva were not edematous. From the clinical course, it was considered that the patient was very likely to have suffered an anaphylactic reaction to oxytocin or methylergometrine. Forty days later, serological examinations as well as skin tests for those two drugs were carried out. While the serological tests were negative, the skin tests indicated the patient was allergic to both drugs. It is concluded that the endogenous peptide oxytocin can induce anaphylactic shock in multiparous women.

  13. Mitigation of shock-induced flow separation using ...

    Indian Academy of Sciences (India)

    R Balasubramanian

    pressure, which is the thermodynamic or mechanical pres- sure term, and the ... used to remove the singularity of Jacobian matrix of the ideal MHD system. 3.2 Wave speeds of ideal MHD system. The ideal MHD system, which defines the convective part of ..... causes electric current to circulate inside the boundary layer.

  14. Shock-induced turbulent flow in baffle systems

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, A.L. [Lawrence Livermore National Lab., CA (United States); Reichenbach, H. [Fraunhofer-Institut fuer Kurzzeitdynamik - Ernst-Mach-Institut (EMI), Freiburg im Breisgau (Germany)


    Experiments are described on shock propagation through 2-D aligned and staggered baffle systems. Flow visualization was provided by shadow and schlieren photography, recorded by the Cranz-Schardin camera. Also single-frame, infinite-fringe, color interferograms were used. Intuition suggests that this is a rather simple 2-D shock diffraction problem. However, flow visualization reveals that the flow rapidly evolved into a complex 3-D turbulent mixing problem. Mushroom-shaped mixing regions blocked the flow into the next baffle orifice. Thus energy was transferred from the directed kinetic energy (induced by the shock) to rotational energy of turbulent mixing, and then dissipated by molecular effects. These processes dramatically dissipate the strength of the shock wave. The experiments provide an excellent test case that could be used to assess the accuracy of computer code calculations of such problems.

  15. Shock induced multi-mode damage in depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Koller, Darcie D [Los Alamos National Laboratory; Cerreta, Ellen K [Los Alamos National Laboratory; Gray, Ill, George T [Los Alamos National Laboratory


    Recent dynamic damage studies on depleted uranium samples have revealed mixed mode failure mechanisms leading to incipient cracking as well as ductile failure processes. Results show that delamination of inclusions upon compression may provide nucleation sites for damage initiation in the form of crack tip production. However, under tension the material propagates cracks in a mixed shear localization and mode-I ductile tearing and cracking. Cracks tips appear to link up through regions of severe, shear dominated plastic flow. Shock recovery experiments were conducted on a 50 mm single stage light gas gun. Serial metallographic sectioning was conducted on the recovered samples to characterize the bulk response of the sample. Experiments show delaminated inclusions due to uniaxial compression without damage propagation. Further results show the propagation of the damage through tensile loading to the incipient state, illustrating ductile processes coupled with mixed mode-I tensile ductile tearing, shear localization, and mode-I cracking in depleted uranium.

  16. New shock-induced transformations of olivines in Martian meteorites (United States)

    Reynard, B.; van de Moortele, B.; Beck, P.; Gillet, P.; McMillan, P. F.


    Transient high pressures and temperatures generated during the impact of meteors or asteroids on planetary surfaces can induce phase transformations in low-pressure minerals that mimic those occurring at depth within the silicate mantle of terrestrial planets. For olivine, phase transitions to the high-pressure polymorphs wadsleyite and ringwoodite are observed in shocked chondrites. Melting transitions have also been reported in some samples. We have investigated the transformations of the olivine presenting an unusually black color in two newly-described Martian meteorites NWA2737 and NWA1950. The shock conditions were not sufficient to cause melting or transformation into the high-pressure polymorphs. The black color of the olivines is due to the presence of Fe-Ni metallic nanoparticles that result from loss of oxygen during the shock event. Raman spectroscopy and high-resolution transmission electron microscopy indicate that the shocked "olivines" have a hexagonal close-packed (hcp) structure similar to that observed in the metastable transformations of olivine at high pressure and low temperature, and of wadsleyite at low pressure and moderate temperatures. We propose a metastable phase diagram of olivine including a new hcp phase that accounts for the observations in natural samples and the experimental results.

  17. TEM Investigation of Shock-Induced Polymorphic Transformation of Olivine (United States)

    Pittarello, L.; Ji, G.; Schryvers, D.; Yamaguchi, A.; Debaille, V.; Claeys, Ph.


    In a shock vein crosscutting a L6 chondrite, olivine clasts with a Fe-rich ringwoodite rim and with core consisting of Mg-rich wadsleyite and olivine domains and Fe-rich olivine veinlets were observed. The formation process is discussed.

  18. Characterization of Surfaces and the Estimation of Shock Induced Vorticity

    Energy Technology Data Exchange (ETDEWEB)

    Jameson, L; Ray, J; Peyser, T


    When shocks impinge on a surface separating fluids of two different densities, one observes the development and growth of various vortical structures. The flow induced by this Richtmyer-Meshkov (RM) instability depends on a variety of factors such as the shock strength, the density ratio of the fluids and the exact form of the surface perturbation. The most common way to model the form of the surface perturbation is through Fourier analysis which is suitable for large-scale sinusoidal structures and is straightforward mathematically. In surfaces of practical interest, however, to a wide range of application, there may also be a broad spectrum of high frequency modes in addition to the lower frequency modes described by Fourier methods. We propose here that these high frequency modes can be efficiently quantified in terms of wavelet analysis. From a numerical point of view, the scale that the roughness occurs at is far to small to numerically resolve and thus we propose that our new methodology can be used to model the subgrid scale generation of vorticity. Thus the combination of wavelet analysis and Fourier analysis will be used to model the generation of vorticity for the RM instability.

  19. The stress response against denatured proteins in the deletion of cytosolic chaperones SSA1/2 is different from heat-shock response in Saccharomyces cerevisiae (United States)

    Matsumoto, Rena; Akama, Kuniko; Rakwal, Randeep; Iwahashi, Hitoshi


    Background A yeast strain lacking the two genes SSA1 and SSA2, which encode cytosolic molecular chaperones, acquires thermotolerance as well as the mild heat-shocked wild-type yeast strain. We investigated the genomic response at the level of mRNA expression to the deletion of SSA1/2 in comparison with the mild heat-shocked wild-type using cDNA microarray. Results Yeast cDNA microarray analysis revealed that genes involved in the stress response, including molecular chaperones, were up-regulated in a similar manner in both the ssa1/2 deletion mutant and the mild heat-shocked wild-type. Genes involved in protein synthesis were up-regulated in the ssa1/2 deletion mutant, but were markedly suppressed in the mild heat-shocked wild-type. The genes involved in ubiquitin-proteasome protein degradation were also up-regulated in the ssa1/2 deletion mutant, whereas the unfolded protein response (UPR) genes were highly expressed in the mild heat-shocked wild-type. RT-PCR confirmed that the genes regulating protein synthesis and cytosolic protein degradation were up-regulated in the ssa1/2 deletion mutant. At the translational level, more ubiquitinated proteins and proteasomes were detected in the ssa1/2 deletion mutant, than in the wild-type, confirming that ubiquitin-proteasome protein degradation was up-regulated by the deletion of SSA1/2. Conclusion These results suggest that the mechanism for rescue of denatured proteins in the ssa1/2 deletion mutant is different from that in the mild heat-shocked wild-type: Activated protein synthesis in the ssa1/2 deletion mutant supplies a deficiency of proteins by their degradation, whereas mild heat-shock induces UPR. PMID:16209719

  20. Mechanisms of p53-Mediated Apoptosis (United States)


    terminus. Cell 81:1021–1029. 27. Juan , L. J., W. J. Shia, M. H. Chen, W. M. Yang, E. Seto, Y. S. Lin, and C. W. VOL. 25, 2005 THE C TERMINUS REGULATES p53...functionally resembles p53. Nat. Med. 4:839–843. 45. Pariat, M., S. Carillo, M. Molinari, C. Salvat , L. Debussche, L. Bracco, J. Milner, and M. Piechaczyk. 1997...apoptosis. Nature 2000;408:377-81. 27. Juan LJ, Shia WJ, Chen MH, et al. Histone deacetylases specifically down-regulate p53- dependent gene

  1. Lysosomal destabilization in p53-induced apoptosis


    Yuan, Xi-Ming; Li, Wei; Dalen, Helge; Lotem, Joseph; Kama, Rachel; Sachs, Leo; Brunk, Ulf T.


    The tumor suppressor wild-type p53 can induce apoptosis. M1-t-p53 myeloid leukemic cells have a temperature-sensitive p53 protein that changes its conformation to wild-type p53 after transfer from 37°C to 32°C. We have now found that these cells showed an early lysosomal rupture after transfer to 32°C. Mitochondrial damage, including decreased membrane potential and release of cytochrome c, and the appearance of apoptotic cells occurred later. Lysosomal rupture, mitochondrial damage, and apop...

  2. Molecular Analysis of Neurotoxin-Induced Apoptosis (United States)


    for 30min. ProteinA / G -agarose beadswere added to themixture, and further incubation was carried out at 4 °C overnight. After incuba- tion, beads were...the sampleswere centrifuged at 12,000 rpm for 10min. The resulting pellets were resuspended in 50l of Tris/EDTAbuffer containing proteinase K (300 g ...its discovery, Biochem. J. 359 (2001) 1–16. [16] C. Galli, O. Meucci, A. Scorziello, T.M. Werge, P. Calissano, G . Schettini, Apoptosis in cerebellar

  3. Apoptosis induced by low-intensity ultrasound in vitro: Alteration of protein profile and potential molecular mechanism (United States)

    Feng, Yi; Wan, Mingxi


    To analyze the potential mechanism related to the apoptosis induced by low intensity focused ultrasound, comparative proteomic method was introduced in the study. After ultrasound irradiation (3.0 W/cm2, 1 minute, 6 hours incubation post-irradiation), the human SMMC-7721 hepatocarcinoma cells were stained by trypan blue to detect the morphologic changes, and then the percentage of early apoptosis were tested by the flow cytometry with double staining of FITC-labelled Annexin V/Propidium iodide. Two-dimensional SDS polyacrylamide gel electrophoresis was used to get the protein profile and some proteins differently expressed after ultrasound irradiation were identified by MALDI-TOF mass spectrometry. It's proved early apoptosis of cells were induced by low intentisy focused ultrasound. After ultrasound irradiation, the expressing characteristics of several proteins changed, in which protein p53 and heat shock proteins are associated with apoptosis initiation. It is suggested that the low-intensity ultrasound-induced apoptotic cancer therapy has the potential application via understanding its relevant molecular signaling and key proteins. Moreover, the comparative proteomic method is proved to be useful to supply information about the protein expression to analyze the metabolic processes related to bio-effects of biomedical ultrasound.

  4. Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria. (United States)

    Zhang, Xiali; Lu, Hongfei; Wang, Yibing; Liu, Chunju; Zhu, Weifeng; Zheng, Shuangyan; Wan, Fusheng


    Taurine (Tau), the most abundant free amino acid in humans has numerous potential health benefits through its antioxidant and anti-inflammatory properties. However, limited studies have assessed its effect on tumors and the antitumor mechanism remains unknown. The present study investigated the cellular and molecular changes induced by Tau, leading to the induction of apoptosis in human breast cancer cell lines MCF-7 and MDA-MB-231. MCF-7 is p53 proficient (p53+/+) and MDA-MB-231 is a p53 null mutant (p53-/-). Cell proliferation and viability were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were employed to detect apoptosis. Spectrophotometry was used to detect caspase-3 activity. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect the levels of mRNA and proteins of p53-upregulated modulator of apoptosis (PUMA), Bax and Bcl-2. Finally, the affect of Tau on the growth of MDA-MB-231-cell-nude mice xenografts was examined. In the study, Tau inhibited growth and induced apoptosis of the two cell lines in a concentration- and time-dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer cells was clearly significant compared to the p53+/+ cancer cells. Further studies showed that Tau promoted apoptosis in human breast cancer cells and inhibited the growth of tumor in nude mice by inducing the expression of PUMA, which further up- and downregulated the expression of Bax and Bcl-2 protein, giving rise to increased activation of caspase-3. Collectively, these results indicate that Tau is a potent candidate for the chemotherapy of breast cancer through increasing the PUMA expression independent of p53 status.

  5. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... Be Prepared Safe Citizen Day Organize Important Medical Information ER Checklists Preparing for Emergencies Be ready to ... anyone can be affected. Here you will find information about heat cramps and heat stroke and exhaustion. ...

  6. Heat Roadmap Europe

    DEFF Research Database (Denmark)

    David, Andrei; Mathiesen, Brian Vad; Averfalk, Helge


    The Heat Roadmap Europe (HRE) studies estimated a potential increase of the district heating (DH) share to 50% of the entire heat demand by 2050, with approximately 25–30% of it being supplied using large-scale electric heat pumps. This study builds on this potential and aims to document...... that such developments can begin now with technologies currently available. We present a database and the status of the technology and its ability of expansion to other European locations by reviewing experiences aimed at further research or application in the heating industry. This is based on a survey of the existing...... capacity of electric large-scale heat pumps with more than 1 MW thermal output, operating in European DH systems. The survey is the first database of its kind containing the technical characteristics of these heat pumps, and provides the basis for the analysis of this paper. By quantifying the heat sources...

  7. Convective heat transfer

    CERN Document Server

    Kakac, Sadik; Pramuanjaroenkij, Anchasa


    Intended for readers who have taken a basic heat transfer course and have a basic knowledge of thermodynamics, heat transfer, fluid mechanics, and differential equations, Convective Heat Transfer, Third Edition provides an overview of phenomenological convective heat transfer. This book combines applications of engineering with the basic concepts of convection. It offers a clear and balanced presentation of essential topics using both traditional and numerical methods. The text addresses emerging science and technology matters, and highlights biomedical applications and energy technologies. What’s New in the Third Edition: Includes updated chapters and two new chapters on heat transfer in microchannels and heat transfer with nanofluids Expands problem sets and introduces new correlations and solved examples Provides more coverage of numerical/computer methods The third edition details the new research areas of heat transfer in microchannels and the enhancement of convective heat transfer with nanofluids....

  8. Heat resistant microorganism

    NARCIS (Netherlands)

    Berendsen, Erwin M.; Bennik, Maria H.J.; Kuipers, Oscar


    The invention relates to a kit and methods and means for the determination of the presence of heat resistant organisms. The invention further relates to the provision organisms wherein the heat resistance is modulated.

  9. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... heat stroke and exhaustion. Heat Cramps Symptoms include muscle spasms, usually in the legs and stomach area. ... Z Teeth (Dental Emergencies) Sprains and Strains Head Injury Resources Home Safety Checklist ACEP Coloring Book Download ...

  10. Endoplasmic Reticulum Stress and Apoptosis Mechanisms

    Directory of Open Access Journals (Sweden)

    G.Seyda Seydel


    Full Text Available Thhe endoplasmic reticulum (ER is the principal site for the synthesis, folding and maturation of most secreted proteins in the cell and essential for most cellular activities. Conditions that impair the folding capacity of the ER cause ER stress and induce a set of signaling pathways termed the unfolded protein response (UPR. If the protective mechanism activated by the UPR is not sufficient to restore normal ER function, cells die by apoptosis mechanism. Recent research suggests that ER stress and UPR play important roles in the metabolic disorders such as diabetes and obesity, cancer, immune response and in some neurodegenerative diseases such as Alzheimer, Parkinson, Huntington. Further studies on ER stress and UPR are necessary to clarify the exact role of this physiological mechanism and provide novel avenues to potential therapies. This review will provide an overview of ER stress, the UPR signaling pathways and ER stress induced apoptosis mechanism. [Archives Medical Review Journal 2012; 21(4.000: 221-235

  11. The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Diego Rodríguez-Penas


    Full Text Available Background: The adipokine chemerin has been associated with cardiovascular disease. We investigated the effects of chemerin on viability and intracellular signalling in murine cardiomyocytes, and the effects of insulin and TNF-α on cardiomyocyte chemerin production. Methods: Hoechst dye vital staining and cell cycle analysis were used to analyse the viability of murine cardiac cells in culture. Western blot was used to explore the phosphorylation of AKT and caspase-9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA and western blot were performed to examine chemerin and CMKLR1 expression after insulin and TNF-α treatment in cardiac cells. Results: Chemerin treatment increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media, while TNF-α treatment increased chemerin mRNA and protein levels but decreased expression of the CMKLR1 gene. Conclusion: Chemerin induces apoptosis, reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine cardiomyocytes. The expression of chemerin is regulated by important metabolic (insulin and inflammatory (TNF-α mediators at cardiac level. Our results suggest that chemerin could play a role in the physiopathology of cardiac diseases.

  12. Aloin induces apoptosis in Jurkat cells. (United States)

    Buenz, Eric J


    Aloe is widely used as a dietary supplement. However, there are continuing concerns over the toxicity and the purity of aloe-based products. The primary class of compounds responsible for aloe-induced toxicity are anthraquinones. One of these, aloe-emodin, has been extensively investigated for apoptosis inducing effects. Conversely, the precursor to aloe-emodin, aloin, has been subjected to only minimal investigation of any cytotoxic effects. Jurkat T cells, an established model for the study of compound toxicity, were used to evaluate the effect of aloin on cell viability. Cells were analyzed using flow cytometry and microscopy for cell size and granularity, cell membrane integrity, mitochondrial membrane potential, and cell cycle profile. Treatment with aloin resulted in a reduction in cell size, compromised membrane integrity, and loss of mitochondrial membrane potential in a dose-dependent manner. Additionally, treatment with aloin resulted in alteration of the cell cycle, specifically a block at G2/M phase. Importantly, the loss of cell membrane integrity was preceded by a loss of mitochondrial membrane potential, suggesting a mitochondrial-dependent pathway for aloin-induced apoptosis. These observations provide insight into the potential mechanisms of aloin-induced toxicity and thus, perhaps, aloe preparation-induced toxicity. Furthermore, because of the concern over the safety of aloe-based supplements, this work suggests that aloe supplements not containing aloin may be safer than aloe supplements containing aloin, and that aloin should be considered in addition to concentrations of aloe-emodin.

  13. Helicobacter pylori vacuolating toxin A and apoptosis

    Directory of Open Access Journals (Sweden)

    Rassow Joachim


    Full Text Available Abstract VacA, the vacuolating cytotoxin A of Helicobacter pylori, induces apoptosis in epithelial cells of the gastic mucosa and in leukocytes. VacA is released by the bacteria as a protein of 88 kDa. At the outer surface of host cells, it binds to the sphingomyelin of lipid rafts. At least partially, binding to the cells is facilitated by different receptor proteins. VacA is internalized by a clathrin-independent mechanism and initially accumulates in GPI-anchored proteins-enriched early endosomal compartments. Together with early endosomes, VacA is distributed inside the cells. Most of the VacA is eventually contained in the membranes of vacuoles. VacA assembles in hexameric oligomers forming an anion channel of low conductivity with a preference for chloride ions. In parallel, a significant fraction of VacA can be transferred from endosomes to mitochondria in a process involving direct endosome-mitochondria juxtaposition. Inside the mitochondria, VacA accumulates in the mitochondrial inner membrane, probably forming similar chloride channels as observed in the vacuoles. Import into mitochondria is mediated by the hydrophobic N-terminus of VacA. Apoptosis is triggered by loss of the mitochondrial membrane potential, recruitment of Bax and Bak, and release of cytochrome c.

  14. Isolated quantum heat engine. (United States)

    Fialko, O; Hallwood, D W


    We present a theoretical and numerical analysis of a quantum system that is capable of functioning as a heat engine. This system could be realized experimentally using cold bosonic atoms confined to a double well potential that is created by splitting a harmonic trap with a focused laser. The system shows thermalization, and can model a reversible heat engine cycle. This is the first demonstration of the operation of a heat engine with a finite quantum heat bath.

  15. Isolated quantum heat engine


    Fialko, O.; Hallwood, D.


    We present a theoretical and numerical analysis of a quantum system that is capable of functioning as a heat engine. This system could be realized experimentally using cold bosonic atoms confined to a double well potential that is created by splitting a harmonic trap with a focused laser. The system shows thermalization, and can model a reversible heat engine cycle. This is the first demonstration of the operation of a heat engine with a finite quantum heat bath.

  16. Solar heat receiver (United States)

    Hunt, Arlon J.; Hansen, Leif J.; Evans, David B.


    A receiver for converting solar energy to heat a gas to temperatures from C. The receiver is formed to minimize impingement of radiation on the walls and to provide maximum heating at and near the entry of the gas exit. Also, the receiver is formed to provide controlled movement of the gas to be heated to minimize wall temperatures. The receiver is designed for use with gas containing fine heat absorbing particles, such as carbon particles.

  17. The genomic underpinnings of apoptosis in the silkworm, Bombyx mori (United States)


    Background Apoptosis is regulated in an orderly fashion by a series of genes, and has a crucial role in important physiological processes such as growth development, immunological response and so on. Recently, substantial studies have been undertaken on apoptosis in model animals including humans, fruit flies, and the nematode. However, the lack of genomic data for silkworms limits their usefulness in apoptosis studies, despite the advantages of silkworm as a representative of Lepidoptera and an effective model system. Herein we have identified apoptosis-related genes in the silkworm Bombyx mori and compared them to those from insects, mammals, and nematodes. Results From the newly assembled genome databases, a genome-wide analysis of apoptosis-related genes in Bombyx mori was performed using both nucleotide and protein Blast searches. Fifty-two apoptosis-related candidate genes were identified, including five caspase family members, two tumor necrosis factor (TNF) superfamily members, one Bcl-2 family member, four baculovirus IAP (inhibitor of apoptosis) repeat (BIR) domain family members and 1 RHG (Reaper, Hid, Grim, and Sickle; Drosophila cell death activators) family member. Moreover, we identified a new caspase family member, BmCaspase-New, two splice variants of BmDronc, and Bm3585, a mammalian TNF superfamily member homolog. Twenty-three of these apoptosis-related genes were cloned and sequenced using cDNA templates isolated from BmE-SWU1 cells. Sequence analyses revealed that these genes could have key roles in apoptosis. Conclusions Bombyx mori possesses potential apoptosis-related genes. We hypothesized that the classic intrinsic and extrinsic apoptotic pathways potentially are active in Bombyx mori. These results lay the foundation for further apoptosis-related study in Bombyx mori. PMID:21040523

  18. Heat-Related Illnesses (United States)

    ... this! Home » Emergency 101 Heat-Related Illnesses Dr. Glenn Mitchell , Emergency physician at Mercy Health System in Chesterfield, Missouri Heat-related illness can be caused by overexposure to the sun or any situation that involves extreme heat. Young children and the elderly are most at risk, ...

  19. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... this! Home » Emergency 101 Heat-Related Illnesses Dr. Glenn Mitchell , Emergency physician at Mercy Health System in Chesterfield, Missouri Heat-related illness can be caused by overexposure to the sun or any situation that involves extreme heat. Young children and the elderly are most at risk, ...

  20. Heat roadmap China

    DEFF Research Database (Denmark)

    Xiong, Weiming; Wang, Yu; Mathiesen, Brian Vad


    District heating is regarded as a key element of energy saving actions in the Chinese national energy strategy, while space heating in China is currently still dominated by coal boilers. However, there is no existing quantitative study to analyse the future heat strategy for China. Therefore...

  1. Microwave processing heats up (United States)

    Microwaves are a common appliance in many households. In the United States microwave heating is the third most popular domestic heating method food foods. Microwave heating is also a commercial food processing technology that has been applied for cooking, drying, and tempering foods. It's use in ...

  2. Single Electrode Heat Effects

    DEFF Research Database (Denmark)

    Jacobsen, Torben; Broers, G. H. J.


    The heat evolution at a single irreversibly working electrode is treated onthe basis of the Brønsted heat principle. The resulting equation is analogous to the expression for the total heat evolution in a galvanic cellwith the exception that –DeltaS is substituted by the Peltier entropy, Delta...

  3. Champagne Heat Pump (United States)

    Jones, Jack A.


    The term champagne heat pump denotes a developmental heat pump that exploits a cycle of absorption and desorption of carbon dioxide in an alcohol or other organic liquid. Whereas most heat pumps in common use in the United States are energized by mechanical compression, the champagne heat pump is energized by heating. The concept of heat pumps based on other absorption cycles energized by heat has been understood for years, but some of these heat pumps are outlawed in many areas because of the potential hazards posed by leakage of working fluids. For example, in the case of the water/ammonia cycle, there are potential hazards of toxicity and flammability. The organic-liquid/carbon dioxide absorption/desorption cycle of the champagne heat pump is similar to the water/ammonia cycle, but carbon dioxide is nontoxic and environmentally benign, and one can choose an alcohol or other organic liquid that is also relatively nontoxic and environmentally benign. Two candidate nonalcohol organic liquids are isobutyl acetate and amyl acetate. Although alcohols and many other organic liquids are flammable, they present little or no flammability hazard in the champagne heat pump because only the nonflammable carbon dioxide component of the refrigerant mixture is circulated to the evaporator and condenser heat exchangers, which are the only components of the heat pump in direct contact with air in habitable spaces.

  4. Heat pipes for industrial waste heat recovery (United States)

    Merrigan, M. A.


    Development work on the high temperature ceramic recuperator at Los Alamos National Laboratory is described and involved material investigations, fabrication methods development, compatibility tests, heat pipe operation, and the modeling of application conditions based on current industrial usage. Solid ceramic heat pipes, ceramic coated refractory pipes, and high-temperature oxide protected metallic pipes are investigated. Economic studies of the use of heat pipe based recuperators in industrial furnaces are conducted and payback periods determined as a function of material, fabrication, and installation cost.

  5. Geothermal heat in a heat pump use (United States)

    Pavlova, A.; Hansen, J.; Obermeyer, H.; Pavlova, I.


    The considered innovative technology proposes to use alternative energy sources for the process efficiency in low-height construction. The world economy depends on price rises for energy sources and the danger of environmental pollution increases. Geothermal energy is the basic resource saving and environmentally safe renewable heat source that is characterized by inexhaustibility, permanent all the-year-round use, universal prevalence of resources and the ability to replace considerable volumes of traditional energy carriers. The expediency and power efficiency to apply a heat pump with the use of geothermal heat is proved for low-height construction.

  6. Intelligent urban heating

    Energy Technology Data Exchange (ETDEWEB)

    Dyrelund, A.


    In smart cities District heating is a precondition for large scale and cost effective integration of CHP and renewable energy for heating in urban areas. In particular, district heating systems combined with CHP, heat pumps, electric boilers and large thermal storages is important for efficient integration of fluctuating wind energy. In order to develop an intelligent and cost effective urban heating system it is important to integrate and optimize the total urban heating energy system including building envelope, heating installations, district heating networks, heat storages and renewable energy sources. Two examples: 1) the variable long term production cost is a basic parameter for the optimal building envelope. 2) efficient low temperature heating installations increases the efficiency of the district heating distribution network and all the low temperature heat sources. Besides, in districts with a cooling load, it is important to include the district cooling in the optimized energy system, both for production and end-use. In EU countries, the Renewable energy directive encourage all local authorities to plan for urban heating and cooling in order to provide the buildings with renewable energy for heating hot tap water and cooling via this infrastructure, whenever it is cost effective compared to individual solutions. Ramboll has in association with Aalborg University prepared an updated study of Heat Plan Denmark in 2010. The study demonstrates how the Danish Heating sector has reduced the fossil fuel consumption to 40% from 1980 to 2010 and how the sector can be independent of fossil fuels before 2030 in a cost effective way. The study concludes that it is necessary to optimize investments both at the supply and the demand side. It is estimated that an optimal combination could be 25 % additional heat demand reduction, further reduction of the return temperature in the building installations, expansion of district heating from 50 to 65 %, local heating up

  7. Chemical heat pump (United States)

    Greiner, Leonard


    A chemical heat pump system is disclosed for use in heating and cooling structures such as residences or commercial buildings. The system is particularly adapted to utilizing solar energy, but also increases the efficiency of other forms of thermal energy when solar energy is not available. When solar energy is not available for relatively short periods of time, the heat storage capacity of the chemical heat pump is utilized to heat the structure as during nighttime hours. The design also permits home heating from solar energy when the sun is shining. The entire system may be conveniently rooftop located. In order to facilitate installation on existing structures, the absorber and vaporizer portions of the system may each be designed as flat, thin wall, thin pan vessels which materially increase the surface area available for heat transfer. In addition, this thin, flat configuration of the absorber and its thin walled (and therefore relatively flexible) construction permits substantial expansion and contraction of the absorber material during vaporization and absorption without generating voids which would interfere with heat transfer. The heat pump part of the system heats or cools a house or other structure through a combination of evaporation and absorption or, conversely, condensation and desorption, in a pair of containers. A set of automatic controls change the system for operation during winter and summer months and for daytime and nighttime operation to satisfactorily heat and cool a house during an entire year. The absorber chamber is subjected to solar heating during regeneration cycles and is covered by one or more layers of glass or other transparent material. Daytime home air used for heating the home is passed at appropriate flow rates between the absorber container and the first transparent cover layer in heat transfer relationship in a manner that greatly reduce eddies and resultant heat loss from the absorbant surface to ambient atmosphere.

  8. Moringa oleifera: An apoptosis inducer in cancer cells

    African Journals Online (AJOL)

    *For correspondence: Email: Sent for review: 15 May 2015 ... Bcl2 proteins which leads to inactivation or reduction in cancer cell apoptosis, hence, agents that are capable of inducing apoptosis in ... quercetin, and kampferol. These compounds act by activating pro-apoptotic protein such as caspases,.

  9. Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus

    African Journals Online (AJOL)

    Background: Beta cell apoptosis has been associated with insulin dependent diabetes mellitus (IDDM) onset in newly diagnosed diabetic patients. There is an emerging evidence that T cell-induced apoptosis is a dominant effector mechanism in diabetes mellitus type 1 (DM1). Pancreatic β-cells derived from newly ...

  10. Gene Expression Profiling of Apoptosis Regulators in Patients with Sepsis

    NARCIS (Netherlands)

    Hoogerwerf, Jacobien J.; van Zoelen, Marieke A.; Wiersinga, W. Joost; van 't Veer, Cornelis; de Vos, Alex F.; de Boer, Anita; Schultz, Marcus J.; Hooibrink, Berend; de Jonge, Evert; van der Poll, Tom


    Introduction: Sepsis is associated with a dysregulation of apoptosis in immune cells, which has been implicated in both immunosuppression and multiple organ failure. We describe the expression profiles of genes encoding key regulators of apoptosis in highly purified monocytes, granulocytes and CD4+

  11. Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells. (United States)

    Shuid, Ahmad Naqib; Safi, Nikoo; Haghani, Amin; Mehrbod, Parvaneh; Haron, Mohd Syamsul Reza; Tan, Sheau Wei; Omar, Abdul Rahman


    Apoptosis has been postulated to play an important role during feline infectious peritonitis virus (FIPV) infection; however, its mechanism is not well characterized. This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p apoptosis at 12 hpi (p apoptosis cluster (80 down-regulated and 51 up-regulated) along with increase of apoptosis, p53, p38 MAPK, VEGF and chemokines/cytokines signaling pathways were probably involved in apoptosis process. Six of the de-regulated genes expression (RASSF1, BATF2, MAGEB16, PDCD5, TNFα and TRAF2) and TNFα protein concentration were analyzed by RT-qPCR and ELISA, respectively, at different time-points. Up-regulations of both pro-apoptotic (i.e. PDCD5) and anti-apoptotic (i.e. TRAF2) were detected from first hpi and continuing to deregulate during apoptosis process in the infected cells.

  12. Juglans regia Hexane Extract Exerts Antitumor Effect, Apoptosis ...

    African Journals Online (AJOL)

    Alterations in cell morphology following apoptosis were studied by inverted phase contrast microscope. Results: The extract of Juglans regia exhibited a potent and dose-dependent anti-proliferative activity against human prostate cancer cells in vitro. The extract also induced significant apoptosis in these PC3 cancer cells ...

  13. Juglans regia Hexane Extract Exerts Antitumor Effect, Apoptosis ...

    African Journals Online (AJOL)

    analysis, apoptosis and cancer cell morphology. Methods: Hexane extract of the leaves of Juglans ... Keywords: Prostate cancer, Juglans regia, Apoptosis, Flow cytometry, Cell cycle phase, Sub-G1 phase. Tropical Journal of Pharmaceutical ... Plant material and extraction procedure. Juglans regia leaves were collected ...

  14. Ebracteolatain A and Ebracteolatain B Induce Apoptosis of Human ...

    African Journals Online (AJOL)

    apoptosis in human chondrosarcoma cells through endoplasmic reticulum stress. Biochem Pharmacol. 2010; 79(10): 1410-1417. 10. Zhang Y, Luo M, Zu YG, Fu YJ, Gu CB, Wang W, Yao. LP, Efferth T. Dryofragin, a phloroglucinol derivative, induces apoptosis in human breast cancer MCF-7 cells through ROS-mediated ...

  15. Ethanolic extracts of Sophora moorcroftiana seeds induce apoptosis ...

    African Journals Online (AJOL)

    Ethanolic extracts of Sophora moorcroftiana seeds induce apoptosis of human stomach cancer cell line SGC-7901 in vitro. ... African Journal of Biotechnology ... apoptosis activity of Sophora moorcroftiana seeds, the ethanolic extracts from the seeds was prepared and added into the culture of human stomach cancer cell ...

  16. Apoptosis of lymphocytes in SLE: the level, correlation with ...

    African Journals Online (AJOL)

    Introduction: SLE is a systemic autoimmune disorder. One of the mechanisms by which elimination of autoreactive lymphocytes takes place is apoptosis. Adefect in apoptosis may thus contribute to the development of autoimmune disease. Patients and methods: The study included 34 Russian children patients with SLE in ...

  17. Quantification of microglial proliferation and apoptosis by flow cytometry

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Wirenfeldt, Martin; Finsen, Bente


    of proliferation and apoptosis maintain a low rate of microglial turnover. Here, we describe quantitative analysis of proliferation and apoptosis of microglial cells isolated from individual adult mice by flow cytometry, which allows distinction from perivascular or infiltrating macrophages, based on differential...

  18. Markers of apoptosis in cardiovascular tissues: focus on Annexin V

    NARCIS (Netherlands)

    van Heerde, W. L.; Robert-Offerman, S.; Dumont, E.; Hofstra, L.; Doevendans, P. A.; Smits, J. F.; Daemen, M. J.; Reutelingsperger, C. P.


    In the last decade, apoptosis (or programmed cell death) has become appreciated as an important process in the development of the cardiovascular system. Moreover, apoptosis contributes to the adaptation of the system to the environment. We are at the beginning of understanding its relevance to

  19. Fas-induced apoptosis in malnourished infants | Elsayh | Egyptian ...

    African Journals Online (AJOL)

    Background: Malnutrition in children is frequently associated with an increased incidence of infection. Apoptosis of immune cells in undernourished organisms may cause an increase in the organism's susceptibility to diseases related to immune suppression. Lymphocyte apoptosis was described in malnutrition. The role of ...

  20. (HIF-1α) on proliferation and apoptosis of adrenocorticotropic hormone

    African Journals Online (AJOL)



    Jul 25, 2011 ... hypoxia induced apoptosis, we investigated the effects of HIF-1α on proliferation and apoptosis of adrenocorticotropic hormone ... The effect of CoCl2 on the proliferation of AtT-20 cells was in a concentration and time dependent manner. When the ..... arrest by functionally counter-acting. Myc. Embo.

  1. Emodin inhibits proliferation and invasion, and induces apoptosis in ...

    African Journals Online (AJOL)

    Emodin inhibits proliferation and invasion, and induces apoptosis in human esophageal cancer cell line ECA109. ... Tropical Journal of Pharmaceutical Research ... Conclusion: These results suggest that emodin inhibits cell proliferation and cell invasion, but induces cell apoptosis in human esophageal cancer cell line ...

  2. Cell death in granulomata: the role of apoptosis. (United States)

    Cree, I A; Nurbhai, S; Milne, G; Beck, J S


    Unequivocal apoptosis were seen by light microscopy in examples of leprosy, sarcoidosis, tuberculosis, Crohn's disease and foreign body granulomata. A limited electron microscopic investigation showed typical apoptotic bodies in both sarcoid and leprosy granulomata. The number of apoptosis and mitoses in granulomata were counted and their densities calculated. The wide variation in the results between individual lesions may reflect differences in disease activity.

  3. Apoptosis of acinar cells in pancreas allograft rejection

    NARCIS (Netherlands)

    Boonstra, J. G.; Wever, P. C.; Laterveer, J. C.; Bruijn, J. A.; van der Woude, F. J.; ten Berge, I. J.; Daha, M. R.


    BACKGROUND: Recently it has been recognized that apoptosis of target cells may occur during liver and kidney allograft rejection and is probably induced by infiltrating cells. Pancreas rejection is also characterized by a cellular infiltrate, however, the occurrence of apoptosis has not been

  4. District Heating System Using Heat Pump Installations and CHP

    Directory of Open Access Journals (Sweden)

    Sit M.L.


    Full Text Available The article describes the district heating system, in which part of the heat of return water thermal power is used to supply heat to the district heating puThe article describes the district heating system, in which part of the heat of return water thermal power is used to supply heat to the district heating pumps, evaporators heating and hot water. Heat pumps use carbon dioxide as refrigerant. During the transitional period of the year, and the summer heat pump for preparing hot-water supply system uses the heat of the surrounding air. The heat of the ambient air is used in the intermediate heat exchanger between the first and second stages of the heat pump to cool the gas after the first stage of the compressor of the heat pump.

  5. "E" Heating Head (United States)

    Fox, Robert L.; Swaim, Robert J.; Johnson, Samuel D.; Coultrip, Robert H.; Phillips, W. Morris; Copeland, Carl E.


    Two separate areas heated inductively for adhesive bonding in single operation. "E" heating head developed to satisfy need for fast-acting and reliable induction heating device. Used in attaching "high-hat" stiffeners to aircraft panels. Incorporates principles and circuitry of toroid joining gun. Width and length configured to provide variously sized heat zones, depending on bonding requirements. Lightweight, portable and provides rapid, reliable heating of dual areas in any environment. Well suited for flight-line and depot maintenance, and battlefield repair. Also useful in automotive assembly lines to strengthen automobile panels.

  6. Absorption heat pump system (United States)

    Grossman, Gershon; Perez-Blanco, Horacio


    An improvement in an absorption heat pump cycle is obtained by adding adiabatic absorption and desorption steps to the absorber and desorber of the system. The adiabatic processes make it possible to obtain the highest temperature in the absorber before any heat is removed from it and the lowest temperature in the desorber before heat is added to it, allowing for efficient utilization of the thermodynamic availability of the heat supply stream. The improved system can operate with a larger difference between high and low working fluid concentrations, less circulation losses, and more efficient heat exchange than a conventional system.

  7. Heat Rash (Prickly Heat or Miliaria) (United States)

    ... Baby rashes Heat rash Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  8. Heat pipe cooling system with sensible heat sink (United States)

    Silverstein, Calvin C.


    A heat pipe cooling system which employs a sensible heat sink is discussed. With this type of system, incident aerodynamic heat is transported via a heat pipe from the stagnation region to the heat sink and absorbed by raising the temperature of the heat sink material. The use of a sensible heat sink can be advantageous for situations where the total mission heat load is limited, as it is during re-entry, and a suitable radiation sink is not available.

  9. Targeting adipocyte apoptosis: a novel strategy for obesity therapy. (United States)

    Zhang, Yu; Huang, Cheng


    Obesity is an increasing world problem that may cause several metabolic complications including insulin resistance, hyperlipidemia, hypertension, and atherosclerosis. Development of therapeutic drugs for obesity has been proven difficult. Current strategies for weight reduction are inhibition of food intake through the central nervous system or blocking the absorption of lipids in the gut. These therapies have many side effects, so new treatments are urgently needed. Fat loss could also be achieved through a decrease in the size and number of adipocytes through apoptosis. Apoptosis is a normal phenomenon of cell death for the purpose of maintaining homeostasis. Induction of apoptosis is a reasonable way to remove adipocytes in obese patients. It is reported that several adipokines and natural products play roles in induction of adipocyte apoptosis. Here we review the recent progress of the roles and mechanisms of adipocyte apoptosis induced by leptin, tumor necrosis factor-α (TNF-α), and natural compounds. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Regulation of Neutrophil Survival/Apoptosis by Mcl-1

    Directory of Open Access Journals (Sweden)

    Eric Milot


    Full Text Available Neutrophil granulocytes have the shortest lifespan among leukocytes in the circulation and die via apoptosis. At sites of infection or tissue injury, prolongation of neutrophil lifespan is critical for effective host defense. Apoptosis of inflammatory neutrophils and their clearance are critical control points for termination of the inflammatory response. Evasion of neutrophil apoptosis aggravates local injury and leads to persistent tissue damage. The short-lived prosurvival Bcl-2 family protein, Mcl-1 (myeloid cell leukemia-1, is instrumental in controlling apoptosis and consequently neutrophil lifespan in response to rapidly changing environmental cues during inflammation. This paper will focus on multiple levels of control of Mcl-1 expression and function and will discuss targeting Mcl-1 as a potential therapeutic strategy to enhance the resolution of inflammation through accelerating neutrophil apoptosis.

  11. Heat pump apparatus (United States)

    Nelson, Paul A.; Horowitz, Jeffrey S.


    A heat pump apparatus including a compact arrangement of individual tubular reactors containing hydride-dehydride beds in opposite end sections, each pair of beds in each reactor being operable by sequential and coordinated treatment with a plurality of heat transfer fluids in a plurality of processing stages, and first and second valves located adjacent the reactor end sections with rotatable members having multiple ports and associated portions for separating the hydride beds at each of the end sections into groups and for simultaneously directing a plurality of heat transfer fluids to the different groups. As heat is being generated by a group of beds, others are being regenerated so that heat is continuously available for space heating. As each of the processing stages is completed for a hydride bed or group of beds, each valve member is rotated causing the heat transfer fluid for the heat processing stage to be directed to that bed or group of beds. Each of the end sections are arranged to form a closed perimeter and the valve member may be rotated repeatedly about the perimeter to provide a continuous operation. Both valves are driven by a common motor to provide a coordinated treatment of beds in the same reactors. The heat pump apparatus is particularly suitable for the utilization of thermal energy supplied by solar collectors and concentrators but may be used with any source of heat, including a source of low-grade heat.

  12. Heat Roadmap Europe

    DEFF Research Database (Denmark)

    Connolly, David; Lund, Henrik; Mathiesen, Brian Vad


    for district heating in the EU between now and 2050 is identified, based on extensive and detailed mapping of the EU heat demand and various supply options. Subsequently, a new ‘district heating plus heat savings’ scenario is technically and economically assessed from an energy systems perspective. The results...... indicate that with district heating, the EU energy system will be able to achieve the same reductions in primary energy supply and carbon dioxide emissions as the existing alternatives proposed. However, with district heating these goals can be achieved at a lower cost, with heating and cooling costs......Six different strategies have recently been proposed for the European Union (EU) energy system in the European Commission's report, Energy Roadmap 2050. The objective for these strategies is to identify how the EU can reach its target of an 80% reduction in annual greenhouse gas emissions in 2050...

  13. Space Heating Equipment

    Energy Technology Data Exchange (ETDEWEB)

    Rafferty, Kevin D.


    The performance evaluation of space heating equipment for a geothermal application is generally considered from either of two perspectives: (a) selecting equipment for installation in new construction, or (b) evaluating the performance and retrofit requirements of an existing system. With regard to new construction, the procedure is relatively straightforward. Once the heating requirements are determined, the process need only involve the selection of appropriately sized hot water heating equipment based on the available water temperature. It is important to remember that space heating equipment for geothermal applications is the same equipment used in non-geothermal applications. What makes geothermal applications unique is that the equipment is generally applied at temperatures and flow rates that depart significantly from traditional heating system design. This chapter presents general considerations for the performance of heating equipment at non-standard temperature and flow conditions, retrofit of existing systems, and aspects of domestic hot water heating.

  14. Extension of Bacillus endospore gas dynamic heating studies to multiple species and test conditions. (United States)

    Gates, S D; McCartt, A D; Jeffries, J B; Hanson, R K; Hokama, L A; Mortelmans, K E


    Shock wave-induced damage to a variety of Bacillus endospore species is studied for a wide range of postshock temperatures and test times in oxidative and non-oxidative gas environments. Bacillus atrophaeus and Bacillus subtilis endospores are nebulized into an aqueous aerosol, loaded into the Stanford aerosol shock tube (SAST) and subjected to shock waves of controlled strength. Endospores experience uniform test temperatures between 500 and 1000 K and pressures ranging from 2 to 7 atm, for either a short test time (∼2·5 ms) or a relatively long test time (∼45 ms). During this process, the bioaerosol is observed using in situ laser absorption and scattering diagnostics. Additionally, shock-treated samples are extracted for ex situ analysis including viability plating and flow cytometry. For short test times, results are consistent with previous studies; all endospore species begin to lose the ability to form colonies when shock-heated to temperatures above 500 K, while significant breakdown in morphology is observed for postshock temperatures above 700 K. Oxidative bath gases did not affect viability losses or morphological breakdown rates. Experiments with extended postshock test time showed increased viability loss with minimal morphological damage for shocks between 600 and 700 K. Genetic differences between B. subtilis and B. atrophaeus endospores do not confer noticeable gains in resistance to shock heating. Oxidative environments do not exacerbate shock-induced damage to endospores. Extended test time experiments reinforce our hypothesis that a temperature/time-dependent inactivation mechanism that does not involve morphological breakdown exists at low-to-moderate postshock temperatures. The methodology and experiments described in this paper extend the study of the interactions of endospores with shock/blast waves to new species and environmental conditions. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied

  15. [Safty action of heat shock protein 27 in reperfusion after spinal marrow ischemia]. (United States)

    Xu, Jian-Ping; Guo, Wen-Rong; Lin, Guo-Bing


    Heat shock protein 27 belongs to the heat shock protein family in the small molecular weight family. This review collected a number of literature to analyze the expression meaning and mechanism of HSP27,expounded HSP27 with inhibition of NO production, maintenance of cell protein stability and accelerated cell damage repair function. At the same time, HSP27 also has a resistance to apoptosis, protecting mitochondria, inhibiting activation of nuclear factor and other related functions. The heat shock protein 27 has protection in spinal cord ischemia-reperfusion.

  16. Tumor necrosis factor related apoptosis inducing ligand triggers apoptosis in dividing but not in differentiating human epidermal keratinocytes

    NARCIS (Netherlands)

    Jansen, Bastiaan J. H.; van Ruissen, Fred; Cerneus, Stefanie; Cloin, Wendy; Bergers, Mieke; van Erp, Piet E. J.; Schalkwijk, Joost


    Using serial analysis of gene expression we have previously identified the expression of several pro-apoptotic and anti-apoptotic genes in cultured human primary epidermal keratinocytes, including tumor necrosis factor related apoptosis inducing ligand (TRAIL). TRAIL is a potent inducer of apoptosis

  17. Designed tumor necrosis factor-related apoptosis-inducing ligand variants initiating apoptosis exclusively via the DR5 receptor

    NARCIS (Netherlands)

    van der Sloot, Almer M.; Tur, Vicente; Szegezdi, Eva; Mullally, Margaret M.; Cool, Robbert H.; Samali, Afshin; Serrano, Luis; Quax, Wim J.


    Tumor necrosis factor-related apoptosis-inclucing ligand (TRAIL) is a potential anticancer drug that selectively induces apoptosis in a variety of cancer cells by interacting with death receptors DR4 and DR5. TRAIL can also bind to decoy receptors (DcR1, DcR2, and osteoprotegerin receptor) that

  18. Antitumorigenic effects of cannabinoids beyond apoptosis. (United States)

    Freimuth, Nadine; Ramer, Robert; Hinz, Burkhard


    According to the World Health Organization, the cases of death caused by cancer will have been doubled until the year 2030. By 2010, cancer is expected to be the number one cause of death. Therefore, it is necessary to explore novel approaches for the treatment of cancer. Over past years, the antitumorigenic effects of cannabinoids have emerged as an exciting field in cancer research. Apart from their proapoptotic and antiproliferative action, recent research has shown that cannabinoids may likewise affect tumor cell angiogenesis, migration, invasion, adhesion, and metastasization. This review will summarize the data concerning the influence of cannabinoids on these locomotive processes beyond modulation of cancer cell apoptosis and proliferation. The findings discussed here provide a new perspective on the antitumorigenic potential of cannabinoids.

  19. Quercetin-induced apoptosis prevents EBV infection (United States)

    Lee, Minjung; Son, Myoungki; Ryu, Eunhyun; Shin, Yu Su; Kim, Jong Gwang; Kang, Byung Woog; Sung, Gi-Ho; Cho, Hyosun; Kang, Hyojeung


    Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world's population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetin induced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma

  20. Apoptosis in thymus of teleost fish. (United States)

    Romano, Nicla; Ceccarelli, Giuseppina; Caprera, Cecilia; Caccia, Elisabetta; Baldassini, Maria Rosaria; Marino, Giovanna


    The presence and distribution of apoptotic cells during thymus development and in adult were studied by in situ end-labelling of fragmented DNA in three temperate species carp (Cyprinus carpio), sea bass (Dicentrarchus labrax) and dusky grouper (Epinephelus marginatus) and in the adult thymus of three Antarctic species belonging to the genus Trematomus spp. During thymus development some few isolated apoptotic cell (AC) firstly appeared in the central-external part of the organ (carp: 5 days ph; sea bass: 35 days ph grouper: 43 days ph). Initially the cells were isolated and then increased in number and aggregated in small groups in the outer-cortical region of the thymus larvae. The high density of apoptotic cells was observed in the junction between cortex and medulla from its appearance (border between cortex and medulla, BCM). ACs decreased in number in juveniles and adult as well as the ACs average diameter. In late juveniles and in adulthood, the apoptosis were restricted to the cortex. In Antarctic species the thymus is highly adapted to low temperature (high vascularisation to effort the circulation of glycoproteins enriched plasma and strongly compact parenchyma). The apoptosis process was more extended (4-7 fold) as compare with the thymus of temperate species, even if the distribution of ACs was similar in all examined species. Data suggested a common process of T lymphocyte negative-selection in BCM of thymus during the ontogeny. The selection process seems to be still active in adult polar fish, but restricted mainly in the cortex zone. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Quantitative evaluation of viability- and apoptosis-related genes in Ascaris suum eggs under different culture-temperature conditions. (United States)

    Yu, Yong-Man; Cho, You-Hang; Youn, Young-Nam; Quan, Juan Hua; Choi, In-Wook; Lee, Young-Ha


    Ascaris suum eggs are inactivated by composting conditions; however, it is difficult to find functional changes in heat-treated A. suum eggs. Here, unembryonated A. suum eggs were incubated at 20°C, 50°C, and 70°C in vitro, and the gene expression levels related to viability, such as eukaryotic translation initiation factor 4E (IF4E), phosphofructokinase 1 (PFK1), and thioredoxin 1 (TRX1), and to apoptosis, such as apoptosis-inducing factor 1 (AIF1) and cell death protein 6 (CDP6), were evaluated by real-time quantitative RT-PCR. No prominent morphological alterations were noted in the eggs at 20°C until day 10. In contrast, the eggs developed rapidly, and embryonated eggs and hatched larvae began to die, starting on day 2 at 50°C and day 1 at 70°C. At 20°C, IF4E, PFK1, and TRX1 mRNA expression was significantly increased from days 2-4; however, AIF1 and CDP6 mRNA expression was not changed significantly. IF4E, PFK1, and TRX1 mRNA expression was markedly decreased from day 2 at 50° and 70°C, whereas AIF1 and CDP6 mRNA expression was significantly increased. The expressions of HSP70 and HSP90 were detected for 9-10 days at 20°C, for 3-5 days at 50°C, and for 2 days at 70°C. Taken together, incremental heat increases were associated with the rapid development of A. suum eggs, decreased expression of genes related to viability, and earlier expression of apoptosis-related genes, and finally these changes of viability- and apoptosis-related genes of A. suum eggs were associated with survival of the eggs under temperature stress.

  2. Enhancement of hyperthermia-induced apoptosis by 5Z-7-oxozeaenol, a TAK1 inhibitor, in Molt-4 cells. (United States)

    Li, Peng; Zhao, Qing-Li; Jawaid, Paras; Rehman, Mati Ur; Ahmed, Kanwal; Sakurai, Hiroaki; Kondo, Takashi


    Transforming growth factor-β-activated kinase1 (TAK1) plays an anti-apoptotic role in response to multiple stresses. TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) has been studied for its apoptotic effects. However, the combined effect of OZ with physical stresses remains to be elusive. Therefore, in this study we focussed to determine the combined effects of OZ with hyperthermia (HT) using Molt-4 cell line. Molt-4 cells were pre-treated with OZ for 1 h followed by heat exposure (44 °C, 10 min) and harvested 24 h after incubation at 37 °C, apoptosis was measured by Annexin V-FITC/PI double staining assay using flow cytometry and cell growth was observed by cell counting assay. Further mechanism involved in the combination was investigated by measuring mitochondrial membrane potential (MMP), intracellular ROS generation, expression of apoptosis related protein, intracellular calcium ion level and Fas activity. Combination of OZ with HT significantly enhances MMP loss and superoxide generation. Furthermore, OZ pre-treatment promotes caspase-8 cleavage, Fas externalisation, caspase 3 activity and intracellular calcium ion levels. OZ pre-treatment decreased the expression of HT-induced Bcl-2 and increased the expression of pro-apoptotic Bax, while markedly suppressed the phosphorylation of JNK and p38. In addition, increased expression of CHOP following combined treatment indicates that ER stress may also involve in the enhancement of HT-induced apoptosis. Our data showed for the first time that OZ sensitizes Molt-4 cells to HT-induced apoptosis via extrinsic and intrinsic apoptotic pathways. Furthermore, ROS and ER stress may also play role in the enhancement of HT-induced apoptosis by OZ.

  3. Optimization of Heat Exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Ivan Catton


    The objective of this research is to develop tools to design and optimize heat exchangers (HE) and compact heat exchangers (CHE) for intermediate loop heat transport systems found in the very high temperature reator (VHTR) and other Generation IV designs by addressing heat transfer surface augmentation and conjugate modeling. To optimize heat exchanger, a fast running model must be created that will allow for multiple designs to be compared quickly. To model a heat exchanger, volume averaging theory, VAT, is used. VAT allows for the conservation of mass, momentum and energy to be solved for point by point in a 3 dimensional computer model of a heat exchanger. The end product of this project is a computer code that can predict an optimal configuration for a heat exchanger given only a few constraints (input fluids, size, cost, etc.). As VAT computer code can be used to model characteristics )pumping power, temperatures, and cost) of heat exchangers more quickly than traditional CFD or experiment, optimization of every geometric parameter simultaneously can be made. Using design of experiment, DOE and genetric algorithms, GE, to optimize the results of the computer code will improve heat exchanger disign.

  4. Heat pump system (United States)

    Swenson, Paul F.; Moore, Paul B.


    An air heating and cooling system for a building includes an expansion type refrigeration circuit and a vapor power circuit. The refrigeration circuit includes two heat exchangers, one of which is communicated with a source of indoor air from the building and the other of which is communicated with a source of air from outside the building. The vapor power circuit includes two heat exchangers, one of which is disposed in series air flow relationship with the indoor refrigeration circuit heat exchanger and the other of which is disposed in series air flow relationship with the outdoor refrigeration circuit heat exchanger. Fans powered by electricity generated by a vapor power circuit alternator circulate indoor air through the two indoor heat exchangers and circulate outside air through the two outdoor heat exchangers. The system is assembled as a single roof top unit, with a vapor power generator and turbine and compressor thermally insulated from the heat exchangers, and with the indoor heat exchangers thermally insulated from the outdoor heat exchangers.

  5. Floor heating maximizes residents` comfort

    Energy Technology Data Exchange (ETDEWEB)

    Tirkkanen, P.; Wikstroem, T.


    Storing heat in floors by using economical night-time electricity does not increase the specific consumption of heating. According to studies done by IVO, the optimum housing comfort is achieved if the room is heated mainly by means of floor heating that is evened out by window or ceiling heating, or by a combination of all three forms of heating. (orig.)

  6. Lack of trehalose accelerates H2O2-induced Candida albicans apoptosis through regulating Ca2+ signaling pathway and caspase activity.

    Directory of Open Access Journals (Sweden)

    Hui Lu

    Full Text Available Trehalose is a non-reducing disaccharide and can be accumulated in response to heat or oxidative stresses in Candida albicans. Here we showed that a C. albicans tps1Δ mutant, which is deficient in trehalose synthesis, exhibited increased apoptosis rate upon H(2O(2 treatment together with an increase of intracellular Ca(2+ level and caspase activity. When the intracellular Ca(2+ level was stimulated by adding CaCl(2 or A23187, both the apoptosis rate and caspase activity were increased. In contrast, the presence of two calcium chelators, EGTA and BAPTA, could attenuate these effects. Moreover, we investigated the role of Ca(2+ pathway in C. albicans apoptosis and found that both calcineurin and the calcineurin-dependent transcription factor, Crz1p, mutants showed decreased apoptosis and caspase activity upon H(2O(2 treatment compared to the wild-type cells. Expression of CaMCA1, the only gene found encoding a C. albicans metacaspase, in calcineurin-deleted or Crz1p-deleted cells restored the cell sensitivity to H(2O(2. Our results suggest that Ca(2+ and its downstream calcineurin/Crz1p/CaMCA1 pathway are involved in H(2O(2-induced C. albicans apoptosis. Inhibition of this pathway might be the mechanism for the protective role of trehalose in C. albicans.

  7. Plasma heat pump and heat engine (United States)

    Avinash, K.


    A model system where cold charged particles are locally confined in a volume VP within a warm plasma of volume V (VP≪V) is studied. Charged particles mutually repel via a shielded repulsion which is like an effective pressure, i.e., electrostatic pressure PE. The law of thermodynamics involving PE and an equation of state for PE are obtained. It is shown that the expansion/compression of electrostatic fields associated with charged particles is a new mechanism that converts mechanical work into plasma heat and vice versa. Two applications of this theory are, first we propose a pumping device which heats plasmas by an adiabatic/isothermal compression of fields. Heating power ranging from a few hundred watts to a few kilowatts is possible with the present day technology. Second, we discuss the feasibility of constructing an electrostatic heat engine which converts plasma heat into mechanical work via plasma electric fields. Effects of PE are shown to be observable in colloidal solutions.

  8. Azithromycin ameliorates airway remodeling via inhibiting airway epithelium apoptosis. (United States)

    Liu, Yuanqi; Pu, Yue; Li, Diandian; Zhou, Liming; Wan, Lihong


    Azithromycin can benefit treating allergic airway inflammation and remodeling. In the present study, we hypothesized that azithromycin alleviated airway epithelium injury through inhibiting airway epithelium apoptosis via down regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro. Ovalbumin induced rat asthma model and TGF-β1-induced BEAS-2B cell apoptosis model were established, respectively. In vivo experiments, airway epithelium was stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to histologically evaluate the airway inflammation and remodeling. Airway epithelium apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), while expression of apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR and western blotting, respectively. In vitro experiments, apoptosis were evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were also measured by qRT-PCR and western blotting. Compared with the OVA group, azithromycin significantly reduced the inflammation score, peribronchial smooth muscle layer thickness, epithelial thickening and goblet cell metaplasia (Pazithromycin-treated rats (Pazithromycin significantly suppressed TGF-β1-induced BEAS-2B cells apoptosis (PAzithromycin is an attractive treatment option for reducing airway epithelial cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting Caspase-3 level in airway epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Retinoids induce Nur77-dependent apoptosis in mouse thymocytes. (United States)

    Kiss, Beáta; Tóth, Katalin; Sarang, Zsolt; Garabuczi, Éva; Szondy, Zsuzsa


    Nur77 is a transcription factor, which plays a determinant role in mediating T cell receptor-induced cell death of thymocytes. In addition to regulation of transcription, Nur77 contributes to apoptosis induction by targeting mitochondria, where it can convert Bcl-2, an anti-apoptotic protein into a proapoptotic molecule. Previous studies have demonstrated that retinoids are actively produced in the mouse thymus and can induce a transcription-dependent apoptosis in mouse thymocytes. Here we show that retinoic acids induce the expression of Nur77, and retinoid-induced apoptosis is completely dependent on Nur77, as retinoids were unable to induce apoptosis in Nur77 null thymocytes. In wild-type thymocytes retinoids induced enhanced expression of the apoptosis-related genes FasL, TRAIL, NDG-1, Gpr65 and Bid, all of them in a Nur77-dependent manner. The combined action of these proteins led to Caspase 8-dependent Bid cleavage in the mitochondria. In addition, we could demonstrate the Nur77-dependent induction of STAT1 leading to enhanced Bim expression, and the mitochondrial translocation of Nur77 leading to the exposure of the Bcl-2/BH3 domain. The retinoid-induced apoptosis was dependent on both Caspase 8 and STAT1. Our data together indicate that retinoids induce a Nur77-dependent cell death program in thymocytes activating the mitochondrial pathway of apoptosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Role of Siglec-7 in apoptosis in human platelets.

    Directory of Open Access Journals (Sweden)

    Kim Anh Nguyen

    Full Text Available Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs are well-characterized I-type lectins, which control apoptosis.We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on α granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i mitochondrial inner transmembrane potential (ΔΨm depolarization; (ii elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii phosphatidylserine exposure and (iv, microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis.The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions, Siglec-7 might be a molecular target for therapeutic intervention/prevention.

  11. Recovering Drug-Induced Apoptosis Subnetwork from Connectivity Map Data

    Directory of Open Access Journals (Sweden)

    Jiyang Yu


    Full Text Available The Connectivity Map (CMAP project profiled human cancer cell lines exposed to a library of anticancer compounds with the goal of connecting cancer with underlying genes and potential treatments. Since the therapeutic goal of most anticancer drugs is to induce tumor-selective apoptosis, it is critical to understand the specific cell death pathways triggered by drugs. This can help to better understand the mechanism of how cancer cells respond to chemical stimulations and improve the treatment of human tumors. In this study, using CMAP microarray data from breast cancer cell line MCF7, we applied a Gaussian Bayesian network modeling approach and identified apoptosis as a major drug-induced cellular-pathway. We then focused on 13 apoptotic genes that showed significant differential expression across all drug-perturbed samples to reconstruct the apoptosis network. In our predicted subnetwork, 9 out of 15 high-confidence interactions were validated in the literature, and our inferred network captured two major cell death pathways by identifying BCL2L11 and PMAIP1 as key interacting players for the intrinsic apoptosis pathway and TAXBP1 and TNFAIP3 for the extrinsic apoptosis pathway. Our inferred apoptosis network also suggested the role of BCL2L11 and TNFAIP3 as “gateway” genes in the drug-induced intrinsic and extrinsic apoptosis pathways.

  12. Roles of Apoptosis and Cellular Senescence in Cancer and Aging. (United States)

    Cerella, Claudia; Grandjenette, Cindy; Dicato, Mario; Diederich, Marc


    Cancer and aging are two similar processes representing the final outcome of timedependent accumulation of various irreversible dysfunctions, mainly caused by stress-induced DNA and cellular damages. Apoptosis and senescence are two types of cellular response to damages that are altered in both cancer and aging, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the ability of the cells to trigger apoptosis and senescence. In contrast, in aging tissues, there is an increased accumulation of senescent cells, and the nature of apoptosis deregulation varies depending on the tissue. Thus, the prevailing model suggests that apoptosis and cellular senescence function as two essential tumor-suppressor mechanisms, ensuring the health of the individual during early and reproductive stages of life, but become detrimental and promote aging later in life. The recent discovery that various anticancer agents, including canonical inducers of apoptosis, act also as inducers of cellular senescence indicates that pro-senescence strategies may have applications in cancer prevention therapy. Therefore, dissection of the mechanisms mediating the delicate balance between apoptosis and cellular senescence will be beneficial in the therapeutic exploitation of both processes in the development of future anticancer and anti-aging strategies, including minimizing the side effects of such strategies. Here, we provide an overview of the roles of apoptosis and cellular senescence in cancer and aging.

  13. Mechanisms and Biomarkers of Apoptosis in Liver Disease and Fibrosis

    Directory of Open Access Journals (Sweden)

    Jayashree Bagchi Chakraborty


    Full Text Available Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD nonalcoholic liver disease (NAFLD including non-alcoholic steatohepatitis (NASH viral hepatitis B and C (HBV, HCV. The critical step in the development of scar is activation of hepatic stellate cells (HSCs, which become the primary source of extracellular matrix. Aberrant apoptosis is a feature of chronic liver diseases and is associated with worsening stages of fibrosis. However, apoptosis is also the main mechanism promoting the resolution of fibrosis, and spontaneous or targeted apoptosis of HSC is associated with regression of fibrosis in animal models and patients with chronic liver disease. Given the importance of apoptosis in disease progression and resolution, there is much interest in precisely delineating the mechanisms involved and also developing biomarkers that accurately reflect the underlying pathogenesis. Here, we review the mechanisms driving apoptosis in development of liver disease and use of apoptosis -related biomarkers to aid in clinical diagnosis. Finally, we will also examine the recent literature regarding new insights into mechanisms involved in apoptosis of activated HSCs as possible method of fibrosis regression.

  14. Heat Roadmap Europe

    DEFF Research Database (Denmark)

    Connolly, David


    This paper compares the electricity, heating, and cooling sectors at national level for various European countries. Annual energy demands are compared for all 28 EU countries, while peak hourly demands are compared for four countries that vary significantly. The results indicate that the heat...... to change significantly in the future with increasing electrification, energy efficiency (e.g. building insulation), and improved comfort (especially for cooling). Some extreme scenarios are presented here to quantify the potential impact of these changes on the electricity sector, with results revealing...... that the demand for electricity could double compared to today, depending on how these changes occur. Considering the scale of additional electricity required to electrify future heating and cooling demands, heat pumps should be prioritised over electric heating and other alternatives, such as district heating...

  15. Heat tolerance in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari

    climate, wheat is sensitive to heat stress. We need to understand how our crops will perform in these changing climatic conditions and how we can develop varieties, which are more tolerant. The PhD study focussed on understanding heat tolerance in wheat with a combined approach of plant physiology...... and quantitative genetics in particular, plant phenotyping based quantitative trait loci (QTL) discovery for a physiological trait under heat stress. Chlorophyll a fluorescence trait, Fv/Fm was used as a phenotyping tool, as it reflects the effect of heat stress on maximum photochemical efficiency of photosystem...... among cultivars due to heat stress as the GD of most of them remained similar in control and stress. The second study investigated if it was possible to use detached leaves to screen for heat tolerance instead of intact plants. The previously selected 41 cultivars, known to differ in v/Fm, were used...

  16. Counterflow Regolith Heat Exchanger (United States)

    Zubrin, Robert; Jonscher, Peter


    A problem exists in reducing the total heating power required to extract oxygen from lunar regolith. All such processes require heating a great deal of soil, and the heat energy is wasted if it cannot be recycled from processed material back into new material. The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat exchanger with internal and external augers attached to the inner rotating tube to move the regolith. Hot regolith in the outer tube is moved in one direction by a right-hand - ed auger, and the cool regolith in the inner tube is moved in the opposite direction by a left-handed auger attached to the inside of the rotating tube. In this counterflow arrangement, a large fraction of the heat from the expended regolith is transferred to the new regolith. The spent regolith leaves the heat exchanger close to the temperature of the cold new regolith, and the new regolith is pre-heated close to the initial temperature of the spent regolith. Using the CoRHE can reduce the heating requirement of a lunar ISRU system by 80%, reducing the total power consumption by a factor of two. The unique feature of this system is that it allows for counterflow heat exchange to occur between solids, instead of liquids or gases, as is commonly done. In addition, in variants of this concept, the hydrogen reduction can be made to occur within the counterflow heat exchanger itself, enabling a simplified lunar ISRU (in situ resource utilization) system with excellent energy economy and continuous nonbatch mode operation.

  17. Laser Processed Heat Exchangers (United States)

    Hansen, Scott


    The Laser Processed Heat Exchanger project will investigate the use of laser processed surfaces to reduce mass and volume in liquid/liquid heat exchangers as well as the replacement of the harmful and problematic coatings of the Condensing Heat Exchangers (CHX). For this project, two scale unit test articles will be designed, manufactured, and tested. These two units are a high efficiency liquid/liquid HX and a high reliability CHX.

  18. Heat transfer II essentials

    CERN Document Server

    REA, The Editors of


    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Heat Transfer II reviews correlations for forced convection, free convection, heat exchangers, radiation heat transfer, and boiling and condensation.

  19. Advances in heat transfer

    CERN Document Server

    Hartnett, James P; Cho, Young I; Greene, George A


    Heat transfer is the exchange of heat energy between a system and its surrounding environment, which results from a temperature difference and takes place by means of a process of thermal conduction, mechanical convection, or electromagnetic radiation. Advances in Heat Transfer is designed to fill the information gap between regularly scheduled journals and university-level textbooks by providing in-depth review articles over a broader scope than is allowable in either journals or texts.

  20. Convection heat transfer

    CERN Document Server

    Bejan, Adrian


    Written by an internationally recognized authority on heat transfer and thermodynamics, this second edition of Convection Heat Transfer contains new and updated problems and examples reflecting real-world research and applications, including heat exchanger design. Teaching not only structure but also technique, the book begins with the simplest problem solving method (scale analysis), and moves on to progressively more advanced and exact methods (integral method, self similarity, asymptotic behavior). A solutions manual is available for all problems and exercises.

  1. Pump Assisted Heat Pipe


    Miyazaki, Yoshiro; OSHIMA, Shigeto


    A labortory model of a pump assisted heat pipe has been fablicated and tested. An arterial heat pipe with axial grooves and a gear pump with a magnetic coupling have been developed for the model. The test has been carried out successfully. The reasonable thermal conductance has been obtained so far as the necessary working fluid flow rate is supplied. The necessary flow rate exceeds the theoretical one and the excess flow rate increases as the heat load increases.

  2. Hydride heat pump (United States)

    Cottingham, James G.


    Method and apparatus for the use of hydrides to exhaust heat from one temperature source and deliver the thermal energy extracted for use at a higher temperature, thereby acting as a heat pump. For this purpose there are employed a pair of hydridable metal compounds having different characteristics working together in a closed pressure system employing a high temperature source to upgrade the heat supplied from a low temperature source.

  3. Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis (United States)

    Joshi, Anjali; Lee, Raphael T. C.; Mohl, Jonathan; Sedano, Melina; Khong, Wei Xin; Ng, Oon Tek; Maurer-Stroh, Sebastian; Garg, Himanshu


    The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4+ T cell loss. However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. A specific role of these residues was also confirmed experimentally. These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4+ T cells. Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. PMID:24265318

  4. Delay of neutrophil apoptosis in acute coronary syndromes. (United States)

    Garlichs, C D; Eskafi, S; Cicha, I; Schmeisser, A; Walzog, B; Raaz, D; Stumpf, C; Yilmaz, A; Bremer, J; Ludwig, J; Daniel, W G


    Apoptosis of polymorphonuclear neutrophils (PMN) is currently discussed as a key event in the control of inflammation. This study determined PMN apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood (CD16, FcgammaRIII). Serum cytokines were determined by enzyme-linked immunosorbent assay. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or C (C, 51.2+/-12.6%; SAP, 44.9+/-13.6%; UAP, 28.4+/-10.1%; AMI, 20.3+/-8.5%; AMI or UAP vs. SAP or C, P<0.001). These results were confirmed by measurement of PMN apoptosis in cultured whole blood from patients and controls. Moreover, serum of patients with ACS markedly reduced apoptosis of PMN from healthy donors. Analysis of patients' sera revealed significantly elevated concentrations of tumor necrosis factor alpha, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-1beta in ACS (vs. C and SAP). IFN-gamma, GM-CSF, and IL-1beta significantly delayed PMN apoptosis in vitro. Furthermore, coincubation of PMN with adenosine 5'-diphosphate-activated platelets significantly inhibited PMN apoptosis as compared with coculture with unstimulated platelets. This study demonstrates a pronounced delay of PMN apoptosis in UAP and AMI, which may result from increased serum levels of IFN-gamma, GM-CSF, and IL-1beta and from enhanced platelet activation. Therapeutical modulation of these determinants of PMN lifespan may provide a new concept for the control of inflammation in ACS.

  5. Bisphenol A induces spermatocyte apoptosis in rare minnow Gobiocypris rarus

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingying; Cheng, Mengqian; Wu, Lang; Zhang, Guo; Wang, Zaizhao, E-mail:


    Highlights: • Adult male G. rarus were exposed to 225 μg/L BPA for 7, 21 and 63 days. • BPA could induce spermatocyte apoptosis in rare minnow testis. • The mitochondrial apoptotic pathway participated in the germ cell apoptosis. • The spermatocyte apoptosis was likely initiated by BPA induced meiosis arrest. - Abstract: Bisphenol A (BPA) is an endocrine disruptor, and could induce germ cells apoptosis in the testis of mammals. But whether it could affect fish in the same mechanism has not’ been studied till now. In the present study, to investigate the influence of BPA on testis germ cells in fish, adult male rare minnow Gobiocypris rarus were exposed to 225 μg L{sup −1} (0.99 μM) BPA for 1, 3 and 9 weeks. Through TdT-mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM) analysis, we found that the amount of apoptotic spermatocytes significantly increased in a time dependent manner following BPA exposure. Western Blot results showed that the ratio of Bcl2/Bax, the important apoptosis regulators in intrinsic mitochondrial apoptotic pathway, was significantly decreased. qPCR showed that mRNA expression of several genes in mitochondrial apoptotic pathway including bcl2, bax, casp9, cytc and mcl1b were significantly changed following BPA exposure. In addition, mRNA expression of meiosis regulation genes (kpna7 and wee2), and genes involved in both apoptosis and meiosis (birc5, ccna1, and gsa1a) were also affected by BPA. Taken together, the present study demonstrated that BPA could induce spermatocytes apoptosis in rare minnow testis, and the apoptosis was probably under regulation of intrinsic mitochondrial apoptotic pathway. Moreover, the spermatocyte apoptosis was likely initiated by BPA induced meiosis arrest.

  6. How do viruses control mitochondria-mediated apoptosis? (United States)

    Neumann, Simon; El Maadidi, Souhayla; Faletti, Laura; Haun, Florian; Labib, Shirin; Schejtman, Andrea; Maurer, Ulrich; Borner, Christoph


    There is no doubt that viruses require cells to successfully reproduce and effectively infect the next host. The question is what is the fate of the infected cells? All eukaryotic cells can "sense" viral infections and exhibit defence strategies to oppose viral replication and spread. This often leads to the elimination of the infected cells by programmed cell death or apoptosis. This "sacrifice" of infected cells represents the most primordial response of multicellular organisms to viruses. Subverting host cell apoptosis, at least for some time, is therefore a crucial strategy of viruses to ensure their replication, the production of essential viral proteins, virus assembly and the spreading to new hosts. For that reason many viruses harbor apoptosis inhibitory genes, which once inside infected cells are expressed to circumvent apoptosis induction during the virus reproduction phase. On the other hand, viruses can take advantage of stimulating apoptosis to (i) facilitate shedding and hence dissemination, (ii) to prevent infected cells from presenting viral antigens to the immune system or (iii) to kill non-infected bystander and immune cells which would limit viral propagation. Hence the decision whether an infected host cell undergoes apoptosis or not depends on virus type and pathogenicity, its capacity to oppose antiviral responses of the infected cells and/or to evade any attack from immune cells. Viral genomes have therefore been adapted throughout evolution to satisfy the need of a particular virus to induce or inhibit apoptosis during its life cycle. Here we review the different strategies used by viruses to interfere with the two major apoptosis as well as with the innate immune signaling pathways in mammalian cells. We will focus on the intrinsic mitochondrial pathway and discuss new ideas about how particular viruses could activately engage mitochondria to induce apoptosis of their host. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Dysregulated apoptosis and NFκB expression in COPD subjects

    Directory of Open Access Journals (Sweden)

    Ennis Madeleine


    Full Text Available Abstract Background The abnormal regulation of neutrophil apoptosis may contribute to the ineffective resolution of inflammation in chronic lung diseases. Multiple signalling pathways are implicated in regulating granulocyte apoptosis, in particular, NFκB (nuclear factor-kappa B signalling which delays constitutive neutrophil apoptosis. Although some studies have suggested a dysregulation in the apoptosis of airway cells in chronic obstructive pulmonary disease (COPD, no studies to date have directly investigated if NFκB is associated with apoptosis of airway neutrophils from COPD patients. The objectives of this study were to examine spontaneous neutrophil apoptosis in stable COPD subjects (n = 13, healthy smoking controls (n = 9 and non-smoking controls (n = 9 and to investigate whether the neutrophil apoptotic process in inflammatory conditions is associated with NFκB activation. Methods Analysis of apoptosis in induced sputum was carried out by 3 methods; light microscopy, Annexin V/Propidium iodide and the terminal transferase-mediated dUTP nick end-labeling (TUNEL method. Activation of NFκB was assessed using a flow cytometric method and the phosphorylation state of IκBα was carried out using the Bio-Rad Bio-Plex phosphoprotein IκBα assay. Results Flow cytometric analysis showed a significant reduction in the percentage of sputum neutrophils undergoing spontaneous apoptosis in healthy smokers and subjects with COPD compared to non-smokers (p Conclusion These results demonstrate that apoptosis is reduced in the sputum of COPD subjects and in healthy control smokers and may be regulated by an associated activation of NFκB.

  8. Introduction to Heat Pipes (United States)

    Ku, Jentung


    This is the presentation file for the short course Introduction to Heat Pipes, to be conducted at the 2015 Thermal Fluids and Analysis Workshop, August 3-7, 2015, Silver Spring, Maryland. NCTS 21070-15. Course Description: This course will present operating principles of the heat pipe with emphases on the underlying physical processes and requirements of pressure and energy balance. Performance characterizations and design considerations of the heat pipe will be highlighted. Guidelines for thermal engineers in the selection of heat pipes as part of the spacecraft thermal control system, testing methodology, and analytical modeling will also be discussed.


    Directory of Open Access Journals (Sweden)

    G. N. Lukyanov


    Full Text Available Subject of Study.We present a method for heat flux measuring with the use of polarization properties of ferroelectric ceramics. Heat flux innovative sensor is developed on the basis of the proposed method. Its experimental verification is carried out. Method. The measurements are based on maintaining a balance between the processes caused by thermal energy and the energy of the electric field in the ferroelectric ceramics. Main Results. The testing of the proposed heat flux sensor has been organized in two stages. At the first stage the primary calibration has been performed by calibrated sensors ITP MG4.03/x(y “Potok”. At the second stage the testing of heat flux sensor has been carried out for calculating the quantity of heat. The comparison of the results to the readings of serial heat meters VKT-7 and STK-15 has been performed. Experiments have shown that the polarization properties of the ferroelectric ceramics can be used to measure the heat flow. Practical Relevance. The proposed sensor can be recommended as an apartment-level heat meter. The calibration of the proposed heat flux sensor with more accurate measurement tools gives the possibility to include it on the State Register of Measuring Instruments.

  10. Mesoscopic photon heat transistor

    DEFF Research Database (Denmark)

    Ojanen, T.; Jauho, Antti-Pekka


    We show that the heat transport between two bodies, mediated by electromagnetic fluctuations, can be controlled with an intermediate quantum circuit-leading to the device concept of a mesoscopic photon heat transistor (MPHT). Our theoretical analysis is based on a novel Meir-Wingreen-Landauer-typ......We show that the heat transport between two bodies, mediated by electromagnetic fluctuations, can be controlled with an intermediate quantum circuit-leading to the device concept of a mesoscopic photon heat transistor (MPHT). Our theoretical analysis is based on a novel Meir...

  11. Microtube strip heat exchanger (United States)

    Doty, F. D.


    During the last quarter, Doty Scientific, Inc. (DSI) continued to make progress on the microtube strip (MTS) heat exchanger. The DSI completed a heat exchanger stress analysis of the ten-module heat exchanger bank; and performed a shell-side flow inhomogeneity analysis of the three-module heat exchanger bank. The company produced 50 tubestrips using an in-house CNC milling machine and began pressing them onto tube arrays. The DSI revised some of the tooling required to encapsulate a tube array and press tubestrips into the array to improve some of the prototype tooling.

  12. Solar assisted heat pumps


    Godbold, R; Paurine, A; Maidment, GG


    Solar Assisted Heat Pumps have the potential to provide low carbon heat for domestic hot water generation and low temperature heating. They have advantages over conventional solar thermal systems because they can generate heating and hot water during periods of low or zero solar, whist still maintain the advantage of not needing to be connected to the gas grid. They are simple in nature and can be installed in a wide range of applications. They are also currently uncommon in the UK so a thoro...

  13. Heated Tube Facility (United States)

    Federal Laboratory Consortium — The Heated Tube Facility at NASA GRC investigates cooling issues by simulating conditions characteristic of rocket engine thrust chambers and high speed airbreathing...

  14. Quantum heat traces (United States)

    Avramidi, Ivan G.


    We study new invariants of elliptic partial differential operators acting on sections of a vector bundle over a closed Riemannian manifold that we call the relativistic heat trace and the quantum heat traces. We obtain some reduction formulas expressing these new invariants in terms of some integral transforms of the usual classical heat trace and compute the asymptotics of these invariants. The coefficients of these asymptotic expansion are determined by the usual heat trace coefficients (which are locally computable) as well as by some new global invariants.

  15. ING1 induces apoptosis through direct effects at the mitochondria

    DEFF Research Database (Denmark)

    Bose, P; Thakur, S; Thalappilly, S


    The ING family of tumor suppressors acts as readers and writers of the histone epigenetic code, affecting DNA repair, chromatin remodeling, cellular senescence, cell cycle regulation and apoptosis. The best characterized member of the ING family, ING1,interacts with the proliferating cell nuclear...... translocates to the mitochondria of primary fibroblasts and established epithelial cell lines in response to apoptosis inducing stimuli, independent of the cellular p53 status. The ability of ING1 to induce apoptosis in various breast cancer cell lines correlates well with its degree of translocation...

  16. Cracking the death code: apoptosis-related histone modifications. (United States)

    Füllgrabe, J; Hajji, N; Joseph, B


    The degradation and compaction of chromatin are long-standing hallmark features of apoptosis. The histones, chief protein components of chromatin, are subjected to a wide range of post-translational modifications. An increasing body of evidence suggests that combinations of epigenetic histone modifications influence the overall chromatin structure and have clear functional consequences in cellular processes including apoptosis. This review describes the work to date on the post-translational modification of histones during apoptosis, their regulation by enzymatic complexes and discusses the existence of the apoptotic histone code.

  17. Extract from mistletoe, Viscum album L., reduces Hsp27 and 14-3-3 protein expression and induces apoptosis in C6 rat glioma cells. (United States)

    Uçar, E Ö; Arda, N; Aitken, A


    Extracts of mistletoe (Viscum album) are intensively used in complementary medicine, but their mechanisms are not fully understood in most cases, and the effects on metabolism have not been investigated in detail. However, some biologically active natural products are well known to provoke unexpected cellular responses. They reduce overexpression of heat shock proteins (Hsps) in cancer cells. The aim of the current study was to determine whether methanolic extract of V. album, which possesses antioxidant activity, has an effect on expression levels of Hsp27 and 14-3-3 proteins in a C6 glioma cell line. For the first time, the apoptosis-inducing effect of this extract was also determined via caspase-3 activation in the cells. Overexpression of Hsps was induced by heat shock at 42°C for 1 h. Expression levels of Hsp27 and 14-3-3 proteins were determined using Western blot analysis. The apoptosis-inducing effect was also evaluated via caspase-3 activation in C6 glioma cells. Pretreatment of the cells with a nontoxic dose (100 μg/mL) of V. album extract before heat shock significantly reduced expression levels of Hsp27 (73%) and 14-3-3β (124%), 14-3-3γ (23%), and 14-3-3ζ (84%) proteins. Pretreatment with the extract before heat shock increased apoptosis via caspase-3 activation (60%) in C6 glioma cells. This result suggested that the methanolic extract of V. album downregulates expression of Hsp27 and 14-3-3 chaperone proteins and induces apoptosis, which warrants further exploration as a potential bioactive compound for cancer therapy.

  18. Overexpressed TP73 induces apoptosis in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Perlaky Laszlo


    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. Methods We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Results Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and

  19. Heat Pipe Integrated Microsystems

    Energy Technology Data Exchange (ETDEWEB)

    Gass, K.; Robertson, P.J.; Shul, R.; Tigges, C.


    The trend in commercial electronics packaging to deliver ever smaller component packaging has enabled the development of new highly integrated modules meeting the demands of the next generation nano satellites. At under ten kilograms, these nano satellites will require both a greater density electronics and a melding of satellite structure and function. Better techniques must be developed to remove the subsequent heat generated by the active components required to-meet future computing requirements. Integration of commercially available electronics must be achieved without the increased costs normally associated with current generation multi chip modules. In this paper we present a method of component integration that uses silicon heat pipe technology and advanced flexible laminate circuit board technology to achieve thermal control and satellite structure. The' electronics/heat pipe stack then becomes an integral component of the spacecraft structure. Thermal management on satellites has always been a problem. The shrinking size of electronics and voltage requirements and the accompanying reduction in power dissipation has helped the situation somewhat. Nevertheless, the demands for increased onboard processing power have resulted in an ever increasing power density within the satellite body. With the introduction of nano satellites, small satellites under ten kilograms and under 1000 cubic inches, the area available on which to place hot components for proper heat dissipation has dwindled dramatically. The resulting satellite has become nearly a solid mass of electronics with nowhere to dissipate heat to space. The silicon heat pipe is attached to an aluminum frame using a thermally conductive epoxy or solder preform. The frame serves three purposes. First, the aluminum frame provides a heat conduction path from the edge of the heat pipe to radiators on the surface of the satellite. Secondly, it serves as an attachment point for extended structures attached

  20. Induction of Apoptosis and expression of Apoptosis-related gene products in response to radiation in murine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Seong, J. S. [Yonsei Univ., Seoul (Korea, Republic of). Coll. of Medicine; Hunter, N. R.; Milas, L. [Texas Univ., Houston, TX (United States)


    To analyze the involvement of apoptosis regulatory genes p53, p21{sup waf1/cip1}, bax and bcl-2 in induction of apoptosis by radiation in murine tumors. The radiation-sensitive ovarian carcinoma OCa-I and the radiation-resistant hepatocarcinoma HCa-I were used. Tumors, 8mm in diameter, were irradiated with 25Gy and at various times after irradiation, ranging from 1 to 48 h, were analyzed histologically for apoptosis and by western blot for alterations in the expression of these genes. The p53 status of the tumors were determined by the polymerase chain reaction-single strand conformation polymorphism assay. Both tumors were positive for wild-type p53. Radiation induced apoptosis in OCa-I but not in HCa-I. Apoptosis developed rapidly, peaked at 2 h after irradiation and returned to almost the background level at 48 h. In OCa-I radiation upregulated the expression of p53, p21{sup waf1/cip1}, and the bcl-2/bax ratio was decreased. In HCa-I radiation increased the expression of both p53 and p21{sup waf1/cip1}, although the increase of the latter was small. The bcl-2/bax ratio was greatly increased. In general the observed changes occurred within a few hours after irradiation, and either preceded or coincided with development of apoptosis. The development of apoptosis required upregulation of both p53 and p21{sup waf1/cip1} as well as a decrease in bcl-2/bax ratio. In contrast, an increase in bcl-2/bax ratio prevented apoptosis in the presence of upregulated p53 and p21{sup waf1/cip1}. These findings identified the involvement of multiple oncogenes in apoptosis regulation in vivo and demonstrate the complexity that may be associated with the use of a single oncogene assessment for predicting the outcome of cancer therapy with cytotoxic agents. (author).

  1. Lunar Base Heat Pump (United States)

    Walker, D.; Fischbach, D.; Tetreault, R.


    The objective of this project was to investigate the feasibility of constructing a heat pump suitable for use as a heat rejection device in applications such as a lunar base. In this situation, direct heat rejection through the use of radiators is not possible at a temperature suitable for lde support systems. Initial analysis of a heat pump of this type called for a temperature lift of approximately 378 deg. K, which is considerably higher than is commonly called for in HVAC and refrigeration applications where heat pumps are most often employed. Also because of the variation of the rejection temperature (from 100 to 381 deg. K), extreme flexibility in the configuration and operation of the heat pump is required. A three-stage compression cycle using a refrigerant such as CFC-11 or HCFC-123 was formulated with operation possible with one, two or three stages of compression. Also, to meet the redundancy requirements, compression was divided up over multiple compressors in each stage. A control scheme was devised that allowed these multiple compressors to be operated as required so that the heat pump could perform with variable heat loads and rejection conditions. A prototype heat pump was designed and constructed to investigate the key elements of the high-lift heat pump concept. Control software was written and implemented in the prototype to allow fully automatic operation. The heat pump was capable of operation over a wide range of rejection temperatures and cooling loads, while maintaining cooling water temperature well within the required specification of 40 deg. C +/- 1.7 deg. C. This performance was verified through testing.

  2. Solar Heating System with Building-Integrated Heat Storage

    DEFF Research Database (Denmark)

    Heller, Alfred


    Traditional solar heating systems cover between 5 and 10% of the heat demand fordomestic hot water and comfort heating. By applying storage capacity this share can beincreased much. The Danish producer of solar heating systems, Aidt-Miljø, markets such a system including storage of dry sand heated...... by PP-pipe heat exchanger. Heat demand is reduced due to direct solar heating, and due to storage. Heat demand is reduced due to direct solar heating, due to storage and due to lower heat losses through the ground. In theory, by running the system flow backwards through the sand storage, active heating...... can be achieved.The objective of the report is to present results from measured system evaluation andcalculations and to give guidelines for the design of such solar heating systems with building integrated sand storage. The report is aimed to non-technicians. In another report R-006 the main results...

  3. Histopatología de la apoptosis. principios generales de la apoptosis o el “suicidio celular”


    Contreras Villa, Dimas Denis


    Con bastante frecuencia se habla de los mecanismos celulares implicados en la Apoptosis; sin embargo, pocas veces se ilustra el aspecto microscópico de esta forma de muerte celular. El objetivo de este artículo es ese: mostrar, las características histológicas de la apoptosis con el microscopio de luz, y con las coloraciones corrientes de Hematoxilina- Eosina. No se tratarán los mecanismos celulares y ultraestructurales de la Apoptosis, los cuales serán objeto de un próximo artículo.

  4. Boolean model of yeast apoptosis as a tool to study yeast and human apoptotic regulations. (United States)

    Kazemzadeh, Laleh; Cvijovic, Marija; Petranovic, Dina


    Programmed cell death (PCD) is an essential cellular mechanism that is evolutionary conserved, mediated through various pathways and acts by integrating different stimuli. Many diseases such as neurodegenerative diseases and cancers are found to be caused by, or associated with, regulations in the cell death pathways. Yeast Saccharomyces cerevisiae, is a unicellular eukaryotic organism that shares with human cells components and pathways of the PCD and is therefore used as a model organism. Boolean modeling is becoming promising approach to capture qualitative behavior and describe essential properties of such complex networks. Here we present large literature-based and to our knowledge first Boolean model that combines pathways leading to apoptosis (a type of PCD) in yeast. Analysis of the yeast model confirmed experimental findings of anti-apoptotic role of Bir1p and pro-apoptotic role of Stm1p and revealed activation of the stress protein kinase Hog proposing the maximal level of activation upon heat stress. In addition we extended the yeast model and created an in silico humanized yeast in which human pro- and anti-apoptotic regulators Bcl-2 family and Valosin-contain protein (VCP) are included in the model. We showed that accumulation of Bax in silico humanized yeast shows apoptotic markers and that VCP is essential target of Akt Signaling. The presented Boolean model provides comprehensive description of yeast apoptosis network behavior. Extended model of humanized yeast gives new insights of how complex human disease like neurodegeneration can initially be tested.

  5. Moxibustion Reduces Ovarian Granulosa Cell Apoptosis Associated with Perimenopause in a Natural Aging Rat Model

    Directory of Open Access Journals (Sweden)

    Xiao-Lan Shi


    Full Text Available In recent years, concerns about the adverse effects of hormone replacement therapy have increased interest in alternative therapies for the management of the symptoms of perimenopause. Here, we investigated the effects of moxibustion, a traditional Chinese practice that is involved in heated Artemisia vulgaris (mugwort stimulation, on hormonal imbalance and ovarian granulosa cell (GC apoptosis in a rat model of perimenopause. Our results showed that mild warm moxibustion (MWM modulated the circulating levels of estradiol and follicle-stimulating hormone and their receptors and inhibited apoptosis in the ovaries of perimenopausal rats, similar to the effect of estrogen. Further investigation revealed that the effects of MWM on ovary tissues and cultured GCs were mediated by the modulation of the activity of Forkhead box protein O1 and involved the JAK2/STAT3 pathway. Our results provide information on the factors and pathways modulated by MWM and shed light on the mechanism underlying the beneficial effect of moxibustion on the symptoms of perimenopause.

  6. Heat pipes and use of heat pipes in furnace exhaust (United States)

    Polcyn, Adam D.


    An array of a plurality of heat pipe are mounted in spaced relationship to one another with the hot end of the heat pipes in a heated environment, e.g. the exhaust flue of a furnace, and the cold end outside the furnace. Heat conversion equipment is connected to the cold end of the heat pipes.

  7. Scraped surface heat exchangers. (United States)

    Rao, Chetan S; Hartel, Richard W


    Scraped surface heat exchangers (SSHEs) are commonly used in the food, chemical, and pharmaceutical industries for heat transfer, crystallization, and other continuous processes. They are ideally suited for products that are viscous, sticky, that contain particulate matter, or that need some degree of crystallization. Since these characteristics describe a vast majority of processed foods, SSHEs are especially suited for pumpable food products. During operation, the product is brought in contact with a heat transfer surface that is rapidly and continuously scraped, thereby exposing the surface to the passage of untreated product. In addition to maintaining high and uniform heat exchange, the scraper blades also provide simultaneous mixing and agitation. Heat exchange for sticky and viscous foods such as heavy salad dressings, margarine, chocolate, peanut butter, fondant, ice cream, and shortenings is possible only by using SSHEs. High heat transfer coefficients are achieved because the boundary layer is continuously replaced by fresh material. Moreover, the product is in contact with the heating surface for only a few seconds and high temperature gradients can be used without the danger of causing undesirable reactions. SSHEs are versatile in the use of heat transfer medium and the various unit operations that can be carried out simultaneously. This article critically reviews the current understanding of the operations and applications of SSHEs.

  8. Electron heat flux instability (United States)

    Saeed, Sundas; Sarfraz, M.; Yoon, P. H.; Lazar, M.; Qureshi, M. N. S.


    The heat flux instability is an electromagnetic mode excited by a relative drift between the protons and two-component core-halo electrons. The most prominent application may be in association with the solar wind where drifting electron velocity distributions are observed. The heat flux instability is somewhat analogous to the electrostatic Buneman or ion-acoustic instability driven by the net drift between the protons and bulk electrons, except that the heat flux instability operates in magnetized plasmas and possesses transverse electromagnetic polarization. The heat flux instability is also distinct from the electrostatic counterpart in that it requires two electron species with relative drifts with each other. In the literature, the heat flux instability is often called the 'whistler' heat flux instability, but it is actually polarized in the opposite sense to the whistler wave. This paper elucidates all of these fundamental plasma physical properties associated with the heat flux instability starting from a simple model, and gradually building up more complexity towards a solar wind-like distribution functions. It is found that the essential properties of the instability are already present in the cold counter-streaming electron model, and that the instability is absent if the protons are ignored. These instability characteristics are highly reminiscent of the electron firehose instability driven by excessive parallel temperature anisotropy, propagating in parallel direction with respect to the ambient magnetic field, except that the free energy source for the heat flux instability resides in the effective parallel pressure provided by the counter-streaming electrons.

  9. Basic Comfort Heating Principles. (United States)

    Dempster, Chalmer T.

    The material in this beginning book for vocational students presents fundamental principles needed to understand the heating aspect of the sheet metal trade and supplies practical experience to the student so that he may become familiar with the process of determining heat loss for average structures. Six areas covered are: (1) Background…

  10. Passive Vaporizing Heat Sink (United States)

    Knowles, TImothy R.; Ashford, Victor A.; Carpenter, Michael G.; Bier, Thomas M.


    A passive vaporizing heat sink has been developed as a relatively lightweight, compact alternative to related prior heat sinks based, variously, on evaporation of sprayed liquids or on sublimation of solids. This heat sink is designed for short-term dissipation of a large amount of heat and was originally intended for use in regulating the temperature of spacecraft equipment during launch or re-entry. It could also be useful in a terrestrial setting in which there is a requirement for a lightweight, compact means of short-term cooling. This heat sink includes a hermetic package closed with a pressure-relief valve and containing an expendable and rechargeable coolant liquid (e.g., water) and a conductive carbon-fiber wick. The vapor of the liquid escapes when the temperature exceeds the boiling point corresponding to the vapor pressure determined by the setting of the pressure-relief valve. The great advantage of this heat sink over a melting-paraffin or similar phase-change heat sink of equal capacity is that by virtue of the =10x greater latent heat of vaporization, a coolant-liquid volume equal to =1/10 of the paraffin volume can suffice.

  11. Microchannel heat sink assembly (United States)

    Bonde, Wayne L.; Contolini, Robert J.


    The present invention provides a microchannel heat sink with a thermal range from cryogenic temperatures to several hundred degrees centigrade. The heat sink can be used with a variety of fluids, such as cryogenic or corrosive fluids, and can be operated at a high pressure. The heat sink comprises a microchannel layer preferably formed of silicon, and a manifold layer preferably formed of glass. The manifold layer comprises an inlet groove and outlet groove which define an inlet manifold and an outlet manifold. The inlet manifold delivers coolant to the inlet section of the microchannels, and the outlet manifold receives coolant from the outlet section of the microchannels. In one embodiment, the manifold layer comprises an inlet hole extending through the manifold layer to the inlet manifold, and an outlet hole extending through the manifold layer to the outlet manifold. Coolant is supplied to the heat sink through a conduit assembly connected to the heat sink. A resilient seal, such as a gasket or an O-ring, is disposed between the conduit and the hole in the heat sink in order to provide a watetight seal. In other embodiments, the conduit assembly may comprise a metal tube which is connected to the heat sink by a soft solder. In still other embodiments, the heat sink may comprise inlet and outlet nipples. The present invention has application in supercomputers, integrated circuits and other electronic devices, and is suitable for cooling materials to superconducting temperatures.

  12. Mechanisms of Coronal Heating

    Indian Academy of Sciences (India)

    The Sun is a mysterious star. The high temperature of the chromosphere and corona present one of the most puzzling problems of solar physics. Observations show that the solar coronal heating problem is highly complex with many different facts. It is likely that different heating mechanisms are at work in solar corona.

  13. Heat pump unit. Waermepumpenaggregat

    Energy Technology Data Exchange (ETDEWEB)

    Gail, J.


    An internal combustion engine with an integrated heat pump and an electricity generator are combined in one engine housing. The internal combustion engine consists of a working cylinder parallel to the drive shaft with a double piston arrangement for swashplate operation, where at least the back of one piston works as the compressor of a heat pump. (orig.).

  14. Combined Heat and Power (United States)

    CHP is on-site electricity generation that captures the heat that would otherwise be wasted to provide useful thermal energy such as steam or hot water than can be used for space heating, cooling, domestic hot water and industrial processes.

  15. Heat-Related Illnesses

    Medline Plus

    Full Text Available ... Dr. Glenn Mitchell , Emergency physician at Mercy Health System in Chesterfield, Missouri Heat-related illness can be caused by overexposure to the sun or any situation that involves extreme heat. Young children and the elderly are most at risk, but anyone can be affected. ...

  16. Heat sterilization of wood (United States)

    Xiping Wang


    Two important questions should be considered in heat sterilizing solid wood materials: First, what temperature–time regime is required to kill a particular pest? Second, how much time is required to heat the center of any wood configuration to the kill temperature? The entomology research on the first question has facilitated the development of international standards...

  17. Plumbing and Heating Curriculum. (United States)

    EASTCONN Regional Educational Services Center, North Windham, CT.

    Theory and experience in the following areas are included in this plumbing curriculum: (1) plumbing fixtures and heating; (2) city water service; (3) fixture roughing; (4) venting; and (5) solar heating systems. The plumbing program manual includes the following sections: (1) general objectives for grades 10, 11, and 12; (2) a list of 33 major…

  18. Induction of apoptosis in response to improved gedunin by ...

    African Journals Online (AJOL)

    caspase 3/7 activities, DNA fragmentation and morphological changes after staining with Hoechst ... Keywords: Lung cancer, Gedunin, Liposome, Nanoencapsulation, Apoptosis, Anti-proliferative activity,. Nuclear chromatin. Tropical Journal of Pharmaceutical Research is ..... characteristics of successful encapsulation, as.

  19. Apoptosis and the target genes of microRNA-21. (United States)

    Buscaglia, Lindsey E Becker; Li, Yong


    MicroRNA-21 (miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors. Through functional suppression, miR-21 is implicated in practically every walk of oncogenic life: the promotion of cell proliferation, invasion and metastasis, genome instability and mutation, inflammation, replicative immortalization, abnormal metabolism, angiogenesis, and evading apoptosis, immune destruction, and growth suppressors. In particular, miR-21 is strongly involved in apoptosis. In this article, we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis. This suggests that miR-21 is an oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.

  20. Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia.

    NARCIS (Netherlands)

    Grieken, van N.C.T.; Meijer, G.A.; Hausen, A zur; Meuwissen, SG; Baak, J.P.A.; Kuipers, E.J.


    BACKGROUND: The biological processes involved in the development of gastric mucosal atrophy and intestinal metaplasia are still incompletely understood. Reports testing the hypothesis that apoptosis leads to atrophy have yielded conflicting results. The availability of new antibodies for the

  1. Structural Basis for Bc12-Regulated Mitochondrion-Dependent Apoptosis

    National Research Council Canada - National Science Library

    Marassi, Francesca M


    ...; by dimerization with other Bcl-2 family members; by binding to other non-homologous proteins; and by formation of membrane pores that are believed to regulate apoptosis by perturbing mitochondrial physiology...

  2. Induction of Apoptosis by Hypertension Via Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Yingying Sun


    Full Text Available Background/Aims: Endoplasmic reticulum (ER stress is one of the intrinsic apoptosis pathways, and cardiac apoptosis can occur in cardiovascular diseases, such as hypertension. However, the mechanisms by which ER stress leads to apoptosis remain enigmatic, particularly in the progression from cardiac hypertrophy to diastolic heart failure due to hypertension. Methods: We used spontaneously hypertensive rats (SHRs to investigate possible signalling pathways for ER stress. Results: We found that cardiac protein and mRNA levels of glucose-regulated protein 78 were up-regulated. In addition, the CHOP- and caspase-12-dependent pathways, but not that of JNK, were activated in the SHR rats. Conclusions: These results suggest that ER stress can contribute to myocardial apoptosis during hypertensive disease.

  3. Relevancia de la apoptosis en la reproduccion femenina

    National Research Council Canada - National Science Library

    Meresman, Gabriela


    .... Durante el desarrollo embrionario, la apoptosis esta implicada en procesos relacionados con la escultura de los diferentes organos, a traves de la eliminacion de estructuras innecesarias y con el...

  4. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells (United States)

    Szliszka, Ewelina; Czuba, Zenon P; Mazur, Bogdan; Sedek, Lukasz; Paradysz, Andrzej; Krol, Wojciech


    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer. PMID:20161998

  5. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ewelina Szliszka


    Full Text Available Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

  6. Induction of apoptosis in human breast adenocarcinoma MCF-7 ...

    African Journals Online (AJOL)

    Induction of apoptosis in human breast adenocarcinoma MCF-7 cells by tannic acid and resveratrol. Ahu Soyocak, Didem Turgut Cosan, Ayse Basaran, Hasan Veysi Gunes, Irfan Degirmenci, Fezan Sahin Mutlu ...

  7. Apoptosis: a process with a (beta)NAC for complexity. (United States)

    Shaham, Shai


    Most programmed cell deaths in the nematode C. elegans require ced-3 caspase activity. In a recent paper, reveal a new C. elegans death inhibitor, icd-1, whose loss can promote apoptosis independently of ced-3.

  8. Role of the nucleus in apoptosis: signaling and execution. (United States)

    Prokhorova, Evgeniia A; Zamaraev, Alexey V; Kopeina, Gelina S; Zhivotovsky, Boris; Lavrik, Inna N


    Since their establishment in the early 1970s, the nuclear changes upon apoptosis induction, such as the condensation of chromatin, disassembly of nuclear scaffold proteins and degradation of DNA, were, and still are, considered as the essential steps and hallmarks of apoptosis. These are the characteristics of the execution phase of apoptotic cell death. In addition, accumulating data clearly show that some nuclear events can lead to the induction of apoptosis. In particular, if DNA lesions resulting from deregulation during the cell cycle or DNA damage induced by chemotherapeutic drugs or viral infection cannot be efficiently eliminated, apoptotic mechanisms, which enable cellular transformation to be avoided, are activated in the nucleus. The functional heterogeneity of the nuclear organization allows the tight regulation of these signaling events that involve the movement of various nuclear proteins to other intracellular compartments (and vice versa) to initiate and govern apoptosis. Here, we discuss how these events are coordinated to execute apoptotic cell death.

  9. Apoptosis induced by granzyme B-glycosaminoglycan complexes: implications for granule-mediated apoptosis in vivo. (United States)

    Galvin, J P; Spaeny-Dekking, L H; Wang, B; Seth, P; Hack, C E; Froelich, C J


    Lymphocyte granule-mediated apoptosis occurs by perforin-mediated intracellular delivery of granule-associated serine proteases (granzymes). A granule-associated proteoglycan, namely serglycin, that contains chondroitin 4-sulfate (CS) glycosaminoglycans is present in the granules of cytotoxic cells. Serglycin acts as scaffold for packaging the positively charged granzymes and probably chaperones the proteases secreted extracellularly. To learn how the interaction of granzyme B (GrB) with serglycin might influence the apoptotic potential of this proteases, we have evaluated a model system where desalted CS is combined with isolated human granzyme. CS-GrB complexes were very stable, remaining undissociated in salt concentrations upwards to 500 mM (pH 7.4). On the basis of a capture enzyme immunoassay that accurately detects GrB, equivalent amounts of active free and CS-GrB, delivered by perforin or adenovirus, efficiently induced apoptosis in Jurkat cells and produced a similar time-dependent increase in caspase-3-like activity. CS-GrB processed isolated caspases-3 and -7 less efficiently than free granzyme. However, when added to cytosolic extracts, rates of processing were nearly equivalent for the two forms, suggesting cationic GrB may nonspecifically bind cytosolic proteins, leading to reduce proteolytic activity. Finally, GrB was found to be exocytosed from lymphocyte-activated killer cells as a neutral, high macromolecular weight complex, which possessed apoptotic activity. Collectively, the results indicate that neutral, high m.w. GrB has the capacity to induce cell death and will be useful to study the mechanism of cytotoxic cell-mediated apoptosis in vitro.

  10. [The study of apoptosis factors released from laser injured cartilage inducing apoptosis of chondrocyte]. (United States)

    Zheng, Min; Grogan, Sp; Schaffner, T; Mainil-Varlet, P


    To explore the role of pro-apoptotic signals following tissue injury and how these may promote a progression of further cell death. Laser treated porcine articular cartilage disks were maintained in culture media. The collected media at various time periods (3, 6, 9, 12, 24 and 48 h), was called treated conditioned media (TCM). Non-laser treated cartilage disks were used to create control conditioned media (CCM). Each disk was subsequently maintained for 28 days and used in confocal microscopic assessment to document the progression of the damaged area. Isolated porcine chondrocytes were cultured in monolayer, and were exposed to TCM, CCM or normal culture medium (NM). As a positive inducer of apoptosis, the monolayer cells were exposed to UV radiation for 10 min and cultured in NM. Following 24 h exposure, the cells were harvested and stained with the appropriate combination of fluorescent dyes and processed via flow cytometry. All cultured cells exposed to TCM displayed a caspase-3 positive subpopulation, a loss of CMXRos, and with a reduced or lost NO signal. CCM exposure signals were comparable to the NM treatments with all having retained CMXRos, NO and without evidence of caspase-3 activity. UV treatment also induced a reduction in NO, but both CMXRos and caspase-3 positive, representing an earlier stage of apoptosis and suggesting that the mode of cell death via UV and TCM exposure are via different processes. The investigation of a dose (100%, 50%, 25% and 12.5%) and time (0.5, 1, 3, 9, 12 h) response to TCM exhibited that all treatments observed an increase in caspase-3 positive cells and a reduction in NO and CMXRos. The usefulness of FCM can be used in the study of cell viability and apoptosis. Such a system may be useful in the study of mechanisms of disease such as osteoarthritis, thus may be of practical use for the pharmaceutical industry for screening associated drugs.

  11. Coronavirus infection, ER stress and Apoptosis

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    Full Text Available The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER. Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR, a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus-host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP kinases activation, autophagy, apoptosis and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling.

  12. Methylmercury-induced neurotoxicity and apoptosis. (United States)

    Ceccatelli, Sandra; Daré, Elisabetta; Moors, Michaela


    Methylmercury is a widely distributed environmental toxicant with detrimental effects on the developing and adult nervous system. Due to its accumulation in the food chain, chronic exposure to methylmercury via consumption of fish and sea mammals is still a major concern for human health, especially developmental exposure that may lead to neurological alterations, including cognitive and motor dysfunctions. Mercury-induced neurotoxicity and the identification of the underlying mechanisms has been a main focus of research in the neurotoxicology field. Three major mechanisms have been identified as critical in methylmercury-induced cell damage including (i) disruption of calcium homeostasis, (ii) induction of oxidative stress via overproduction of reactive oxygen species or reduction of antioxidative defenses and (iii) interactions with sulfhydryl groups. In vivo and in vitro studies have provided solid evidence for the occurrence of neural cell death, as well as cytoarchitectural alterations in the nervous system after exposure to methylmercury. Signaling cascades leading to cell death induced by methylmercury involve the release of mitochondrial factors, such as cytochrome c and AIF with subsequent caspase-dependent or -independent apoptosis, respectively; induction of calcium-dependent proteases calpains; interaction with lysosomes leading to release of cathepsins. Interestingly, several pathways can be activated in parallel, depending on the cell type. In this paper, we provide an overview of recent findings on methylmercury-induced neurotoxicity and cell death pathways that have been described in neural and endocrine cell systems. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Visualizing Vpr-induced G2 arrest and apoptosis.

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    Tomoyuki Murakami

    Full Text Available Vpr is an accessory protein of human immunodeficiency virus type 1 (HIV-1 with multiple functions. The induction of G2 arrest by Vpr plays a particularly important role in efficient viral replication because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. The regulation of apoptosis by Vpr is also important for immune suppression and pathogenesis during HIV infection. However, it is not known whether Vpr-induced apoptosis depends on the ability of Vpr to induce G2 arrest, and the dynamics of Vpr-induced G2 arrest and apoptosis have not been visualized. We performed time-lapse imaging to examine the temporal relationship between Vpr-induced G2 arrest and apoptosis using HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator2 (Fucci2. The dynamics of G2 arrest and subsequent long-term mitotic cell rounding in cells transfected with the Vpr-expression vector were visualized. These cells underwent nuclear mis-segregation after prolonged mitotic processes and then entered G1 phase. Some cells subsequently displayed evidence of apoptosis after prolonged mitotic processes and nuclear mis-segregation. Interestingly, Vpr-induced apoptosis was seldom observed in S or G2 phase. Likewise, visualization of synchronized HeLa/Fucci2 cells infected with an adenoviral vector expressing Vpr clearly showed that Vpr arrests the cell cycle at G2 phase, but does not induce apoptosis at S or G2 phase. Furthermore, time-lapse imaging of HeLa/Fucci2 cells expressing SCAT3.1, a caspase-3-sensitive fusion protein, clearly demonstrated that Vpr induces caspase-3-dependent apoptosis. Finally, to examine whether the effects of Vpr on G2 arrest and apoptosis were reversible, we performed live-cell imaging of a destabilizing domain fusion Vpr, which enabled rapid stabilization and destabilization by Shield1. The effects of Vpr on G2 arrest and subsequent apoptosis were reversible. This study is the first to

  14. Improved solar heating systems (United States)

    Schreyer, J.M.; Dorsey, G.F.


    An improved solar heating system is described in which the incident radiation of the sun is absorbed on collector panels, transferred to a storage unit and then distributed as heat for a building and the like. The improvement is obtained by utilizing a storage unit comprising separate compartments containing an array of materials having different melting points ranging from 75 to 180/sup 0/F. The materials in the storage system are melted in accordance with the amount of heat absorbed from the sun and then transferred to the storage system. An efficient low volume storage system is provided by utilizing the latent heat of fusion of the materials as they change states in storing ad releasing heat for distribution.

  15. Graphene heat dissipating structure (United States)

    Washburn, Cody M.; Lambert, Timothy N.; Wheeler, David R.; Rodenbeck, Christopher T.; Railkar, Tarak A.


    Various technologies presented herein relate to forming one or more heat dissipating structures (e.g., heat spreaders and/or heat sinks) on a substrate, wherein the substrate forms part of an electronic component. The heat dissipating structures are formed from graphene, with advantage being taken of the high thermal conductivity of graphene. The graphene (e.g., in flake form) is attached to a diazonium molecule, and further, the diazonium molecule is utilized to attach the graphene to material forming the substrate. A surface of the substrate is treated to comprise oxide-containing regions and also oxide-free regions having underlying silicon exposed. The diazonium molecule attaches to the oxide-free regions, wherein the diazonium molecule bonds (e.g., covalently) to the exposed silicon. Attachment of the diazonium plus graphene molecule is optionally repeated to enable formation of a heat dissipating structure of a required height.

  16. Solar heating system (United States)

    Schreyer, James M.; Dorsey, George F.


    An improved solar heating system in which the incident radiation of the sun is absorbed on collector panels, transferred to a storage unit and then distributed as heat for a building and the like. The improvement is obtained by utilizing a storage unit comprising separate compartments containing an array of materials having different melting points ranging from to F. The materials in the storage system are melted in accordance with the amount of heat absorbed from the sun and then transferred to the storage system. An efficient low volume storage system is provided by utilizing the latent heat of fusion of the materials as they change states in storing and releasing heat for distribution.

  17. Choline deficiency induced by Mycoplasma fermentans enhances apoptosis of rat astrocytes. (United States)

    Ben-Menachem, G; Mousa, A; Brenner, T; Pinto, F; Zähringer, U; Rottem, S


    A choline uptake system accumulating free choline in an energy-dependent process is described in Mycoplasma fermentans. The uptake system has a K(m) of 2.2x10(-5) M and a V(max) of 0.15 nmol 10 min(-1) mg(-1) cell protein and the choline incorporated could be recovered in the soluble fraction as free choline, phosphorylcholine and CDP-choline. Choline accumulation by M. fermentans resulted in a marked choline depletion of the growth medium. The choline depletion of an astrocyte cell culture induced by M. fermentans was associated with the apoptotic death of the cells. Apoptosis was not obtained with heat-inactivated mycoplasmas and could be reversed by the addition of free choline to the growth medium.

  18. Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) (United States)

    Elmallah, Mohammed I. Y.; Micheau, Olivier


    Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells has attracted much attention in oncology. This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells. PMID:26580630

  19. Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL

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    Mohammed I. Y. Elmallah


    Full Text Available Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells has attracted much attention in oncology. This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells.

  20. Novel pathogenesis: regulation of apoptosis by Apelin/APJ system. (United States)

    Liu, Jiaqi; Liu, Meiqing; Chen, Linxi


    Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways. In this review, we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase (PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (I/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointestinal diseases. Apelin/APJ system decreases myocardial infarction size and alleviates myocardial I/R injury by inhibiting cardiomyocytes apoptosis. However, Apelin/APJ system improves pulmonary artery hypertension via increasing apoptosis. Apelin/APJ system exerts neuroprotective effect by blocking apoptosis and participates in the recovery of retinal neovascular disease by suppressing apoptosis. Apelin/APJ system also shows anti-apoptotic effect against acute renal injury and plays a role in regulating skeletal homeostasis. In gastrointestinal disease, Apelin/APJ system plays a potential physiological role in gastrointestinal cytoprotection by regulating apoptosis. We hope that a better understanding of the Apelin/APJ system will help to discover new disease pathogenesis and find possible therapeutic targets of the Apelin/APJ system essential for various diseases. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail:

  1. Modulation of Acupuncture on Cell Apoptosis and Autophagy


    Luo, Dan; Chen, Rui; Liang, Feng-xia


    Acupuncture has been historically practiced to treat medical disorders by mechanically stimulating specific acupoints. Despite its well-documented efficacy, its biological basis largely remains elusive. Recent studies suggested that cell apoptosis and autophagy might play key roles in acupuncture therapy. Therefore, we searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI), aiming to find the potential relationship between acupuncture and cell apoptosis an...

  2. Drug-induced reactivation of apoptosis abrogates HIV-1 infection.

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    Hartmut M Hanauske-Abel

    Full Text Available HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of

  3. Oscillating-Coolant Heat Exchanger (United States)

    Scotti, Stephen J.; Blosser, Max L.; Camarda, Charles J.


    Devices useful in situations in which heat pipes inadequate. Conceptual oscillating-coolant heat exchanger (OCHEX) transports heat from its hotter portions to cooler portions. Heat transported by oscillation of single-phase fluid, called primary coolant, in coolant passages. No time-averaged flow in tubes, so either heat removed from end reservoirs on every cycle or heat removed indirectly by cooling sides of channels with another coolant. Devices include leading-edge cooling devices in hypersonic aircraft and "frost-free" heat exchangers. Also used in any situation in which heat pipe used and in other situations in which heat pipes not usable.

  4. 6-Gingerol induces autophagy to protect HUVECs survival from apoptosis. (United States)

    Wang, Shaopeng; Sun, Xiance; Jiang, Liping; Liu, Xiaofang; Chen, Min; Yao, Xiaofeng; Sun, Qinghua; Yang, Guang


    6-Gingerol, the major pharmacologically-active component of ginger, has the potential to prevent heart disease. However, the mechanisms are not well understood. In this study, the protective effect of 6-gingerol against hydrogen peroxide-induced apoptosis in human umbilical vein endothelial cells (HUVECs) was investigated. Apoptosis was detected by Hoechst 33342 and Flow cytometry analysis. To further elucidate the crosstalk between apoptosis and autophagy, we tested the expression of autophagy related proteins, LC3B, Bcl-2, Beclin1, AKT, p-AKT, mechanistic target of rapamycin (mTOR), and p-mTOR. Furthermore, mitochondrial membrane potential and the intracellular generation of reactive oxygen species (ROS) were also investigated. Our data revealed that 6-gingerol significantly reduced apoptosis by inducing autophagy. It has been demonstrated that 6-gingerol suppressed the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, increased the expression of Beclin1 to promote autophagy, and increased Bcl-2 expression to inhibit apoptosis. In addition, the damage of mitochondrial was protected, and ROS level was decreased by 6-gingerol. These firmly indicate 6-gingerol has a strong protective ability against the apoptosis caused by oxidative stress in HUVECs, and the mechanism may relate to the induction of autophagy. Our data suggest 6-gingerol may be beneficial in the prevention of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Signaling pathways of the ING proteins in apoptosis. (United States)

    Shah, Sitar; Riabowol, Karl


    Members of the ING family of type II tumor suppressors reside in different chromatin regulatory complexes and are stoichiometeric members of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes. It has been frequently observed that expressing ING proteins promotes apoptosis in both normal and transformed cells of different species. They have also been reported to either rely upon p53, or to add to its ability to promote programmed cell death (apoptosis) although whether ING proteins require p53 to induce apoptosis is now questionable based upon observations using knockout cell lines and animal models. Genetic studies in model organisms, and particularly in Caenorhabditis elegans, have identified different pathways involved in apoptosis during development, in the germ line and in response to various forms of stress including DNA damage. In this review we summarize structural features of the INGs and recent observations made in knockout models of Mus musculus and Caenorhabditis elegans that have helped to further clarify the functions of the ING proteins in biochemical pathways leading to apoptosis. Based upon these observations we propose a model for how ING proteins may act both independently and in concert with p53 to promote apoptosis.

  6. Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL pathway. (United States)

    Chamoux, Estelle; Houde, Nicolas; L'Eriger, Karine; Roux, Sophie


    Osteoprotegerin (OPG) is a secreted decoy receptor that recognizes RANKL, and blocks the interaction between RANK and RANKL, leading to the inhibition of osteoclast differentiation and activation. As OPG is a major inhibitor of bone resorption, we wondered whether OPG could modulate osteoclast survival/apoptosis. Osteoclast apoptosis was evaluated by adding various doses of OPG to human osteoclast cultures obtained from cord blood monocytes. Surprisingly, apoptosis decreased after adding the OPG. We hypothesized that OPG may block its second ligand, TRAIL, which is involved in osteoclast apoptosis. We showed that osteoclasts expressed TRAIL, and that TRAIL levels in the culture medium dose-dependently decreased in presence of OPG, as did the level of activated caspase-8 in osteoclasts. In addition, the expression of TRAIL by osteoclasts was not affected in the presence of OPG. Our findings suggest that OPG inhibits osteoclast apoptosis, at least in part, by binding and thus inhibiting endogenously produced TRAIL in human osteoclast cultures. TRAIL could be an autocrine factor for the regulation of osteoclast survival/apoptosis. (c) 2008 Wiley-Liss, Inc.

  7. Role of thymidine phosphorylase in Fas-induced apoptosis. (United States)

    Mori, S; Takao, S; Ikeda, R; Noma, H; Mataki, Y; Wang, X; Akiyama, S; Aiko, T


    Thymidine phosphorylase (TP) has chemotactic and angiogenic activity in vitro, and it promotes tumor growth and inhibits apoptosis in vivo. It plays a key role in the invasiveness and metastasis of TP-expressing solid tumors. KB/TP cells transfected with a TP cDNA have been shown to be resistant to hypoxia-induced apoptosis, suggesting that TP has effects on tumor growth and cell death independent of its effects on angiogenesis. However, the mechanisms of cell death inhibition by TP are unknown. In the present study, we demonstrate that caspase-8 is cleaved in control transfectant KB cells early on during Fas-induced apoptosis. Caspase-8 activation leads to the loss of mitochondrial membrane potential, followed by the release of cytochrome c, the activation of caspase-3, and apoptosis. In contrast, Fas-induced caspase-8 cleavage is inhibited in KB/TP cells, which lead to inhibition of the downstream apoptotic cascade and inhibition of apoptosis. These findings indicate that TP plays an important role in intracellular apoptotic signal transduction in the Fas-induced apoptotic pathway. Therefore, inhibition of TP may suppress the progression of TP-overexpressing solid tumors by inducing apoptosis.

  8. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation (United States)

    Dorward, David A.; Sharma, Sidharth; Rennie, Jillian; Felton, Jennifer M.; Alessandri, Ana L.; Duffin, Rodger; Schwarze, Jurgen; Haslett, Christopher; Rossi, Adriano G.


    Rationale: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. Objectives: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. Methods: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. Measurements and Main Results: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. Conclusions: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans. PMID:25629436

  9. Differential Apoptosis in Mucosal and Dermal Wound Healing. (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann


    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase-polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; pInnovation: Our observations indicate differential execution of apoptosis in oral wound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing.

  10. Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis. (United States)

    Sinha-Hikim, Indrani; Friedman, Theodore C; Falz, Mark; Chalfant, Victor; Hasan, Mohammad Kamrul; Espinoza-Derout, Jorge; Lee, Desean L; Sims, Carl; Tran, Peter; Mahata, Sushil K; Sinha-Hikim, Amiya P


    Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis. Given that CM apoptosis has been implicated as a potential mechanism in the development of cardiomyopathy and heart failure, we characterize the key signaling pathways in nicotine plus high-fat diet (HFD)-induced CM apoptosis. Adult C57BL6 male mice were fed a normal diet (ND) or HFD and received twice-daily intraperitoneal (IP) injections of nicotine (0.75 mg/kg body weight [BW]) or saline for 16 weeks. An additional group of nicotine-treated mice on HFD received twice-daily IP injections of mecamylamine (1 mg/kg BW), a non-selective nicotinic acetylcholine receptor antagonist, for 16 weeks. Nicotine when combined with HFD led to a massive increase in CM apoptosis that was fully prevented by mecamylamine treatment. Induction of CM apoptosis was associated with increased oxidative stress and activation of caspase-2-mediated intrinsic pathway signaling coupled with inactivation of AMP-activated protein kinase (AMPK). Furthermore, nicotine treatment significantly (P nicotine, when combined with HFD, triggers CM apoptosis through the generation of oxidative stress and inactivation of AMPK together with the activation of caspase-2-mediated intrinsic apoptotic signaling independently of FGF21 and SIRT1.

  11. Glycolaldehyde induces endoplasmic reticulum stress and apoptosis in Schwann cells

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    Keisuke Sato


    Full Text Available Schwann cell injury is caused by diabetic neuropathy. The apoptosis of Schwann cells plays a pivotal role in diabetic nerve dysfunction. Glycolaldehyde is a precursor of advanced glycation end products that contribute to the pathogenesis of diabetic neuropathy. In this study, we examined whether glycolaldehyde induces endoplasmic reticulum (ER stress and apoptosis in rat Schwann cells. Schwann cells treated with 500 μM glycolaldehyde showed morphological changes characteristic of apoptosis. Glycolaldehyde activated apoptotic signals, such as caspase-3 and caspase-8. Furthermore, it induced ER stress response involving RNA-dependent protein kinase-like ER kinase (PERK, inositol-requiring ER-to-nucleus signal kinase 1α (IRE1α, and eukaryotic initiation factor 2α (eIF2α. In addition, glycolaldehyde activated CCAAT/enhancer-binding homologous protein (CHOP, an ER stress response factor crucial to executing apoptosis. Knockdown of nuclear factor E2-related factor 2 (Nrf2, which is involved in the promotion of cell survival following ER stress, enhanced glycolaldehyde-induced cytotoxicity, indicating that Nrf2 plays a protective role in the cytotoxicity caused by glycolaldehyde. Taken together, these findings indicate that glycolaldehyde is capable of inducing apoptosis and ER stress in Schwann cells. The ER stress induced by glycolaldehyde may trigger the glycolaldehyde-induced apoptosis in Schwann cells. This study demonstrated for the first time that glycolaldehyde induced ER stress.

  12. Noxa couples lysosomal membrane permeabilization and apoptosis during oxidative stress. (United States)

    Eno, Colins O; Zhao, Guoping; Venkatanarayan, Avinashnarayan; Wang, Bing; Flores, Elsa R; Li, Chi


    The exact roles of lysosomal membrane permeabilization (LMP) in oxidative stress-triggered apoptosis are not completely understood. Here, we first studied the temporal relation between LMP and mitochondrial outer membrane permeabilization (MOMP) during the initial stage of apoptosis caused by the oxidative stress inducer H2O2. Despite its essential role in mediating apoptosis, the expression of the BH3-only Bcl-2 protein Noxa was dispensable for LMP. In contrast, MOMP was dependent on Noxa expression and occurred downstream of LMP. When lysosomal membranes were stabilized by the iron-chelating agent desferrioxamine, H2O2-induced increase in DNA damage, Noxa expression, and subsequent apoptosis were abolished by the inhibition of LMP. Importantly, LMP-induced Noxa expression increase was mediated by p53 and seems to be a unique feature of apoptosis caused by oxidative stress. Finally, exogenous iron loading recapitulated the effects of H2O2 on the expression of BH3-only Bcl-2 proteins. Overall, these data reveal a Noxa-mediated signaling pathway that couples LMP with MOMP and ultimate apoptosis during oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid. (United States)

    Zhao, Kai; Zhao, Xingyu; Tu, Yaping; Miao, Qi; Cao, Dongxu; Duan, Wenjuan; Sun, Yang; Wang, Jincheng; Wei, Taotao; Yang, Fuyu


    We have reported that chymotrypsin B (CtrB) is not just a digestive enzyme but is also stored in lysosomes. Herein, we demonstrated a broad distribution of CtrB and explored the involvement of CtrB in apoptosis. Exposure of RH-35 cells to H(2)O(2) or palmitate induced the redistribution of lysosomal CtrB into the cytoplasm as a result of lysosomal membrane permeabilization (LMP). Suppression of CtrB significantly blocked apoptosis, while overexpression of CtrB sensitized apoptosis markedly. CtrB could cleave Bid under neutral conditions. In RH-35 cells with Bid silenced, apoptosis induced by CtrB protein was attenuated, suggesting that CtrB mediates apoptosis of RH-35 cells mainly through processing Bid. Our data also suggest that LMP occurs earlier than mitochondrial outer membrane permeabilization; Bid activation initiated by caspase-8 might be reinforced by CtrB in consequence of LMP, which causes a positive feedback loop leading to the accumulation of tBid, and results in lysosome- and mitochondrion-dependent apoptosis.

  14. 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats. (United States)

    Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A


    Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. Copyright © 2016 Elsevier Ltd. All rights reserved.



    habibie, habibie


    - TNF-related apoptosis-inducing ligand merupakan salah satu pilihan pengobatan kanker yang secara efektif dapat menginduksi apoptosis melalui aktivasi death receptor (DR4 dan DR5). Penggunaan TNF-related apoptosis-inducing ligand menyebabkan efek samping yang jauh lebih kecil dibandingkan dengan penggunaan kemoterapi. Namun saat ini beberapa jenis kanker menunjukkan resistensi terhadap TNF-related apoptosis-inducing ligand. Penggunaan TNF-related apoptosis-inducing ligand yang dikombinasi...

  16. Ear fibroblasts derived from Taiwan yellow cattle are more heat resistant than those from Holstein cattle. (United States)

    Wu, Hung-Yi; Peng, Shao-Yu; Li, Hung; Lee, Jai-Wei; Kesorn, Piyawit; Wu, Hsi-Hsun; Ju, Jyh-Cherng; Shen, Perng-Chih


    The objective of this study was to compare the thermotolerances of ear fibroblasts derived from Holstein (H) and Taiwan yellow cattle (Y) and their apoptosis-related protein expressions with (1, 3, 6, 12, and 24h) or without heat shock treatment. The results showed that the vaginal temperatures of Y (38.4-38.5°C) were (Pderived from Y (6h: 1.1%; 12h: 1.6%; 24h: 2.6%) were lower (Pderived from H (6h: 1.8%; 12h: 4.0%; 24h: 6.9%), respectively, after heat shock (42°C). The expression level of apoptosis inducing factor (AIF) in ear fibroblasts derived from H was higher (Pderived from Y after the heat shock treatment for 6h and 12h, respectively. The level of cytochrome c of ear fibroblasts derived from H was higher (Pderived from Y after the heat shock treatment for 1-12h, respectively. The abundances of Caspase-3, Caspase-8 and Caspase-9 of ear fibroblasts derived from H were higher (Pderived from Y after 12h and 24h of heat shock, respectively; the Bcl-2/Bax ratios of ear fibroblasts derived from H were lower (Pderived fibroblasts after heated for 1-24h. The expression level of HSP-70 of Y-derived ear fibroblasts was also higher (Pderived from Taiwan yellow cattle was better than that of cells derived from Holstein cattle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Avenanthramides Prevent Osteoblast and Osteocyte Apoptosis and Induce Osteoclast Apoptosis in Vitro in an Nrf2-Independent Manner

    Directory of Open Access Journals (Sweden)

    Gretel G. Pellegrini


    Full Text Available Oats contain unique bioactive compounds known as avenanthramides (AVAs with antioxidant properties. AVAs might enhance the endogenous antioxidant cellular response by activation of the transcription factor Nrf2. Accumulation of reactive oxygen species plays a critical role in many chronic and degenerative diseases, including osteoporosis. In this disease, there is an imbalance between bone formation by osteoblasts and bone resorption by osteoclasts, which is accompanied by increased osteoblast/osteocyte apoptosis and decreased osteoclast apoptosis. We investigated the ability of the synthethic AVAs 2c, 2f and 2p, to 1-regulate gene expression in bone cells, 2-affect the viability of osteoblasts, osteocytes and osteoclasts, and the generation of osteoclasts from their precursors, and 3-examine the potential involvement of the transcription factor Nrf2 in these actions. All doses of AVA 2c and 1 and 5 µM dose of 2p up-regulated collagen 1A expression. Lower doses of AVAs up-regulated OPG (osteoprotegerin in OB-6 osteoblastic cells, whereas 100 μM dose of 2f and all concentrations of 2c down-regulated RANKL gene expression in MLO-Y4 osteocytic cells. AVAs did not affect apoptosis of OB-6 osteoblastic cells or MLO-Y4 osteocytic cells; however, they prevented apoptosis induced by the DNA topoisomerase inhibitor etoposide, the glucocorticoid dexamethasone, and hydrogen peroxide. AVAs prevented apoptosis of both wild type (WT and Nrf2 Knockout (KO osteoblasts, demonstrating that AVAs-induced survival does not require Nrf2 expression. Further, KO osteoclast precursors produced more mature osteoclasts than WT; and KO cultures exhibited less apoptotic osteoclasts than WT cultures. Although AVAs did not affect WT osteoclasts, AVA 2p reversed the low apoptosis of KO osteoclasts. These in vitro results demonstrate that AVAs regulate, in part, the function of osteoblasts and osteocytes and prevent osteoblast/osteocyte apoptosis and increase osteoclast

  18. Paste heat exchange

    Energy Technology Data Exchange (ETDEWEB)


    The subject of coal paste heat exchangers is discussed in this letter report from Gelsenberg A.G. to I.G. Farbenindustrie A.G. Gelsenberg had given little consideration to the heating of coal paste by means of regeneration (heat exchange) because of the lack of experience in paste regeneration with bituminous coal, especially at 700 atmospheres. At the I.G. Farben plant at Poelitz, paste regeneration was carried out so that low concentration coal paste was heated in the regenerator together with the process gas, and the remaining coal was fed into the cold pass of the preheater in a thicker paste. Later tests proved this process viable. Gelsenberg heated normal coal paste and the gas in heat exchangers with the goal of relieving the preheater. Good results were achieved without change in design. The coal paste was heated with process gas in the regenerator at up to 315 degrees with constant pressure difference, so that after three months no decrease in K-values and no deposition or thickening was observed. Through the omission of paste gas, the pressure difference of the system became more constant and did not rise above the former level. The temperature also was more controllable, the chamber smoother running. Principal thermal data are given in a table. 1 table, 1 graph.

  19. Elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma. (United States)

    Fan, Weibing; Fan, Shuang-Shi; Feng, Juan; Xiao, Desheng; Fan, Songqing; Luo, Jiadi


    Astrocytoma is the most common type of primary malignant brain tumor, with pretty lowly 5-year survival rate in patients. Although extended surgical removal of the tumor and postoperative chemotherapy/radiotherapy executed, still there is large recurrence rate, mainly because diffuse glioma tumor cells ubiquitously infiltrate into normal parenchyma. So it becomes a priority to hunt novel molecular and signaling pathway targets to suppress astrocyma progression. HSP10, an important member of Heat shock proteins (Hsps) family, classically works as molecular chaperone folding or degradating of target proteins. Evolutionarily, HSP10 is also reported to be involved in immunomodulation and tumor progression. Poly (ADP-ribose) polymerase (PARP), important in DNA repair, is one of the main cleavage targets of caspase. And cleaved PARP (c-PARP) can serve as a marker of cells undergoing apoptosis. So far, whether the expression of HSP10 or c-PARP is associated with clinicopathologic implication for astrocytoma has not been reported. Meanwhile, it is unclear about the relationship between HSP10 and cell apoptosis. The purpose of this research is to elucidate the association between the expression of HSP10 and c-PARP and clinicopathological characteristics of astrocytoma by immunohistochemistry. The results showed that positive percentage of high HSP10 expression in astrocytoma 42/103, 40.8%) was significantly higher than that in the non-tumor control brain tissues (8/43, 18.6%) (P = 0.01). While no apparent difference of high c-PARP expression existed between astrocytoma and non-tumor control brain tissues. Furthermore, elevated expression of HSP10 was negative related to low expression of c-PARP (r = -0.224, P = 0.023), indicating high expression of HSP10 in astrocytoma inhibited apoptosis process effectively. And overexpression of HSP10 was proved to be the independent poor prognostic factor for astrocytoma by multivariate analysis. Taken together, our results suggest that

  20. Proteomic Investigation of the Sinulariolide-Treated Melanoma Cells A375: Effects on the Cell Apoptosis through Mitochondrial-Related Pathway and Activation of Caspase Cascade

    Directory of Open Access Journals (Sweden)

    Yu-Jen Wu


    Full Text Available Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinulariolide on A375 melanoma cell growth and protein expression. Sinulariolide suppressed the proliferation and migration of melanoma cells in a concentration-dependent manner and was found to induce both early and late apoptosis by flow cytometric analysis. Comparative proteomic analysis was conducted to investigate the effects of sinulariolide at the molecular level by comparison between the protein profiles of melanoma cells treated with sinulariolide and those without treatment. Two-dimensional gel electrophoresis (2-DE master maps of control and treated A375 cells were generated by analysis with PDQuest software. Comparison between these maps showed up- and downregulation of 21 proteins, seven of which were upregulated and 14 were downregulated. The proteomics studies described here identify some proteins that are involved in mitochondrial dysfunction and apoptosis-associated proteins, including heat shock protein 60, heat shock protein beta-1, ubiquinol cytochrome c reductase complex core protein 1, isocitrate dehydrogenase (NAD subunit alpha (down-regulated, and prohibitin (up-regulated, in A375 melanoma cells exposed to sinulariolide. Sinulariolide-induced apoptosis is relevant to mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome c, and activation of Bax, Bad and caspase-3/-9, as well as suppression of p-Bad, Bcl-xL and Bcl-2. Taken together, our results show that sinulariolide-induced apoptosis might be related to activation of the caspase cascade and mitochondria dysfunction pathways. Our results suggest that sinulariolide merits further evaluation as a chemotherapeutic agent for human melanoma.

  1. Pioneering Heat Pump Project

    Energy Technology Data Exchange (ETDEWEB)

    Aschliman, Dave [Indiana Inst. of Technology, Inc., Fort Wayne, IN (United States); Lubbehusen, Mike [Indiana Inst. of Technology, Inc., Fort Wayne, IN (United States)


    This project was initiated at a time when ground coupled heat pump systems in this region were limited in size and quantity. There were economic pressures with costs for natural gas and electric utilities that had many organizations considering ground coupled heat pumps; The research has added to the understanding of how ground temperatures fluctuate seasonally and how this affects the performance and operation of the heat pumps. This was done by using a series of temperature sensors buried within the middle of one of the vertical bore fields with sensors located at various depths below grade. Trending of the data showed that there is a lag in ground temperature with respect to air temperatures in the shoulder months, however as full cooling and heating season arrives, the heat rejection and heat extraction from the ground has a significant effect on the ground temps; Additionally it is better understood that while a large community geothermal bore field serving multiple buildings does provide a convenient central plant to use, it introduces complexity of not being able to easily model and predict how each building will contribute to the loads in real time. Additional controllers and programming were added to provide more insight into this real time load profile and allow for intelligent shedding of load via a dry cooler during cool nights in lieu of rejecting to the ground loop. This serves as a means to ‘condition’ the ground loop and mitigate thermal creep of the field, as is typically observed; and It has been observed when compared to traditional heating and cooling equipment, there is still a cost premium to use ground source heat pumps that is driven mostly by the cost for vertical bore holes. Horizontal loop systems are less costly to install, but do not perform as well in this climate zone for heating mode

  2. An analytical dynamic model of heat transfer from the heating body to the heated room

    Directory of Open Access Journals (Sweden)

    Mižáková Jana


    Full Text Available On the base of mathematical description of thermal balance the dynamic model of the hot-water heating body (radiator was designed. The radiator is mathematically described as a heat transfer system between heating water and warmed-up air layer. Similarly, the dynamic model of heat transfer through the wall from the heated space to the outdoor environment was design. Both models were interconnected into dynamic model of heat transfer from the heating body to the heated room and they will be implemented into simulation model of the heating system in Matlab/Simulink environment.

  3. Advances on heat shock protein 27 and heat shock protein 70 in retinopathy and optical neuropathy

    Directory of Open Access Journals (Sweden)

    Mao-Ren Wang


    Full Text Available Heat shock protein(HSPis a family of high expressed proteins under the different stimulus. This family is highly conserved in structure and can protect cells in function. In recent years, there are some researches illustrate that HSP 27 and HSP 70 have protective effect on retinal cells and optical nerve cells, while the HSP-27 Ab and HSP-70 Ab can promote the apoptosis of these cells. In the cell culture and animal experiment, we have observed that it is beneficial to protect retinal cells and optical cells through blocking the express of HSP-27 Ab and HSP-70 Ab. This article reviews the relationship between HSP 27 and HSP 70 with retinal diseases and optical nerve diseases.

  4. Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells. (United States)

    Choi, Sung Hoon; Park, Jun Yong; Kang, Wonseok; Kim, Seung Up; Kim, Do Young; Ahn, Sang Hoon; Ro, Simon Wonsang; Han, Kwang-Hyub


    A local hypoxic microenvironment is one of the most important characteristics of solid tumors. Hypoxia inducible factor-1α (HIF-1α) and Interleukin-8 (IL-8) activate tumor survival from hypoxic-induced apoptosis in each pathway. This study aimed to evaluate whether knockdown of HIF-1α and IL-8 induced apoptosis of the hepatocellular carcinoma (HCC) and endothelial cell lines. HCC cell lines were infected with adenovirus-expressing shRNA for HIF-1α and IL-8 and maintained under hypoxic conditions (1% O2, 24 h). The expression levels of HIF-1α and both apoptotic and growth factors were examined by real-time quantitative PCR and western blot. We also investigated apoptosis by TUNEL assay (FACS and Immunofluorescence) and measured the concentration of cytochrome C. Inhibition of HIF-1α and IL-8 up-regulated the expression of apoptotic factors while downregulating anti-apoptotic factors simultaneously. Knockdown of HIF-1α and IL-8 increased the concentration of cytochrome C and enhanced DNA fragmentation in HCC cell lines. Moreover, culture supernatant collected from the knockdown of HIF-1α and IL-8 in HCC cell lines induced apoptosis in human umbilical vein endothelial cells under hypoxia, and the expression of variable apoptotic ligand increased from HCC cell lines, time-dependently. These data suggest that adenovirus-mediated knockdown of HIF-1α and IL-8 induced apoptosis in HCC cells and triggered apoptosis of vascular endothelial cells.

  5. Transient heat conduction in a heat fin (United States)

    Brody, Jed; Brown, Max


    We immerse the bottom of a rod in ice water and record the time-dependent temperatures at positions along the length of the rod. Though the experiment is simple, a surprisingly difficult problem in heat conduction must be solved to obtain a theoretical fit to the measured data. The required equipment is very inexpensive and could be assigned as a homework exercise or a hands-on component of an online course.

  6. Elementary heat transfer analysis

    CERN Document Server

    Whitaker, Stephen; Hartnett, James P


    Elementary Heat Transfer Analysis provides information pertinent to the fundamental aspects of the nature of transient heat conduction. This book presents a thorough understanding of the thermal energy equation and its application to boundary layer flows and confined and unconfined turbulent flows. Organized into nine chapters, this book begins with an overview of the use of heat transfer coefficients in formulating the flux condition at phase interface. This text then explains the specification as well as application of flux boundary conditions. Other chapters consider a derivation of the tra

  7. Heat exchanger design handbook

    CERN Document Server

    Thulukkanam, Kuppan


    Completely revised and updated to reflect current advances in heat exchanger technology, Heat Exchanger Design Handbook, Second Edition includes enhanced figures and thermal effectiveness charts, tables, new chapter, and additional topics--all while keeping the qualities that made the first edition a centerpiece of information for practicing engineers, research, engineers, academicians, designers, and manufacturers involved in heat exchange between two or more fluids.See What's New in the Second Edition: Updated information on pressure vessel codes, manufacturer's association standards A new c

  8. Heat pump planning handbook

    CERN Document Server

    Bonin, Jürgen


    The Heat Pump Planning Handbook contains practical information and guidance on the design, planning and selection of heat pump systems, allowing engineers, designers, architects and construction specialists to compare a number of different systems and options. Including detailed descriptions of components and their functions and reflecting the current state of technology this guide contains sample tasks and solutions as well as new model calculations and planning evaluations. Also economic factors and alternative energy sources are covered, which are essential at a time of rising heat costs. T

  9. Ventilation with heat recovery

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Svendsen, Svend


    This paper presents the experiences from the use of ventilation with heat recovery in several experimental single-family houses developed and built within the last four years to meet the new Danish energy requirements of 2005. Included are descriptions of the ventilation system components...... and the main functional demands as well as measurements of the thermal efficiency, electricity consumptions and building air tightness. The paper addresses the aspects of minimizing the heat loss from the duct system and the heat recovery unit (when placed in an unheated attic space) in order to obtain...

  10. Heat treatment furnace

    Energy Technology Data Exchange (ETDEWEB)

    Seals, Roland D; Parrott, Jeffrey G; DeMint, Paul D; Finney, Kevin R; Blue, Charles T


    A furnace heats through both infrared radiation and convective air utilizing an infrared/purge gas design that enables improved temperature control to enable more uniform treatment of workpieces. The furnace utilizes lamps, the electrical end connections of which are located in an enclosure outside the furnace chamber, with the lamps extending into the furnace chamber through openings in the wall of the chamber. The enclosure is purged with gas, which gas flows from the enclosure into the furnace chamber via the openings in the wall of the chamber so that the gas flows above and around the lamps and is heated to form a convective mechanism in heating parts.

  11. [Clothing and heat disorder]. (United States)

    Satsumoto, Yayoi


    The influence of the clothing material properties(like water absorbency and rapid dryness, water vapor absorption, water vapor permeability and air permeability) and the design factor of the clothing(like opening condition and fitting of clothing), which contributed to prevent heat disorder, was outlined. WBGT(wet-bulb globe temperature) is used to show a guideline for environmental limitation of activities to prevent heat disorder. As the safety function is more important than thermal comfort for some sportswear and protective clothing with high cover area, clothing itself increases the risk of heat disorder. WBGT is corrected by CAF (clothing adjustment factor) in wearing such kind of protective clothing.

  12. Molecular heat pump. (United States)

    Segal, Dvira; Nitzan, Abraham


    We propose a molecular device that pumps heat against a thermal gradient. The system consists of a molecular element connecting two thermal reservoirs that are characterized by different spectral properties. The pumping action is achieved by applying an external force that periodically modulates molecular levels. This modulation affects periodic oscillations of the internal temperature of the molecule and the strength of its coupling to each reservoir resulting in a net heat flow in the desired direction. The heat flow is examined in the slow and fast modulation limits and for different modulation wave forms, thus making it possible to optimize the device performance.

  13. Apoptosis in ovarian cells in postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Maria Laszczyńska


    Full Text Available Apoptosis is a natural process which accompanies human ovary from the moment of birth until old age. While it is a well-known process at the reproductive age, it still needs to be thoroughly examined when referring to the postmenopausal age. The study involved 30 postmenopausal women who had their ovaries removed by laparotomy due to nonneoplastic diseases of the uterus. The women were divided into 3 groups depending on the time that had passed since the last menstruation. Group A consisted of women who had their last menstruation no more than 5 years earlier. In group B menopause occurred 5 to 10 years earlier. Group C was composed of patients who had the last menstruation over 10 years earlier. In all the patients concentrations of follitropin (FSH and estradiol (E2 in blood plasma were measured. Ovarian tissue was obtained during surgery. For morphological studies, ovaries were fixed in Bouin's solution and 4% formalin and embedded in paraffin. Morphological analysis was carried out after hematoxylin-eosin (H-E staining. For histochemical detection of apoptotic cells (in situ localization of fragment DNA, the TUNEL method was used. The expression of caspase-3 positive cells was determined immunohistochemically in paraffin-embedded specimens. Comparing to groups A and B, the ovaries in group C contained small number of corpora albicantia located in the medullary part as well as thinned blood vessels and few lymphatic vessels and nerves. In contrast to group A where the number of TUNEL-positive cells was high and caspase-3 expression was observed, no TUNEL-positive nuclei and caspase-3 expression were found in the examined ovaries of group C women.

  14. Enoxacin directly inhibits osteoclastogenesis without inducing apoptosis. (United States)

    Toro, Edgardo J; Zuo, Jian; Ostrov, David A; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R; Neubert, John K; Wronski, Thomas J; Wallet, Shannon M; Holliday, L Shannon


    Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 μM) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the "housekeeping" a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein L-plastin was altered in cells treated with 50 μM enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments.

  15. Enoxacin Directly Inhibits Osteoclastogenesis without Inducing Apoptosis* (United States)

    Toro, Edgardo J.; Zuo, Jian; Ostrov, David A.; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R.; Neubert, John K.; Wronski, Thomas J.; Wallet, Shannon M.; Holliday, L. Shannon


    Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 μm) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the “housekeeping” a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein l-plastin was altered in cells treated with 50 μm enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments. PMID:22474295

  16. Design of serially connected district heating heat pumps utilising a geothermal heat source

    DEFF Research Database (Denmark)

    Jensen, Jonas Kjær; Ommen, Torben Schmidt; Markussen, Wiebke Brix


    The design of two heat pumps (HP), connected in series, was investigated for operation in the district heating (DH) network of the Greater Copenhagen area, Denmark. The installation was dimensioned to supply 7.2 MW of heat at a temperature of 85 °C. The heat pumps utilise a geothermal heat source...

  17. Counterflow Regolith Heat Exchanger Project (United States)

    National Aeronautics and Space Administration — The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat...

  18. Early Contact Stage of Apoptosis: Its Morphological Features and Function

    Directory of Open Access Journals (Sweden)

    Etheri Mikadze


    Full Text Available Apoptosis has been a biological phenomenon of intense interest for 20 years, but the earlier morphological features of apoptosis have not been determined hitherto. Using the methods of semi- and ultrathin sections, the livers of intact embryos and young rats have been studied under the effect of cycloheximide to determine morphological features of an early stage of apoptosis. It is discovered that both in hepatoblasts and hepatocytes, apoptosis, besides the well-known stages, also includes an early contact stage, distinguishing features of which are agglutination of bound ribosomes (breaking of translation, elimination of the nucleolus, reduction of free polysomes (and in hepatocytes, reduction of cisterns of rough endoplasmic reticulum, formation of cytoplasmic excrescences, and cell shape changes. The early stage of apoptosis is characterized by close contact with neighboring cells. At a certain phase of the contact stage of apoptosis, the nucleolus reappears in the nucleus and the number of free polysomes in the cytoplasm increases, which suggests the renewal of synthesis of new RNA and proteins. Close contact of differentiating and mitotic hepatoblasts with apoptotic cells indicates a certain functional relationship between these cells that is realized not only by micropinocytosis, but through gap junctions as well. We assume that the apoptotic cell, besides proteolytic products, can contain newly synthesized, low-molecular substances, the relocation of which from apoptotic to neighboring cells may contribute to both functional activity and proliferation of adjacent hepatoblasts and, therefore, the function of apoptosis may not be limited only to the elimination of harmful, damaged, and unwanted cells.

  19. Neuronal apoptosis in herpes simplex virus - 1 encephalitis (HSE). (United States)

    Athmanathan, S; Vydehi, B V; Sundaram, C; Vemuganti, G K; Murthy, J M


    Herpes simplex virus infections are encountered often due to their ubiquitous nature. Common sites involved include skin, mucous membrane, genitalia, eye and the nervous system. HSV infection of the central nervous system can be life threatening. Little is known about the pathogenesis of this cataclysmic disease, at the cellular level. Virus induced apoptosis may play a role in the molecular pathogenesis of encephalitis. This study aims to detect the presence of apoptosis: a) In the brain tissue obtained at autopsy from a patient who succumbed to Herpes simplex virus - 1 encephalitis (HSE) and b) In a human glioblastoma cell line (SNB 19). Wedge tissue samples were obtained from the inferior surface of the frontal lobe and fixed in buffered formalin. Tissue sections were stained with haematoxylin and eosin for histopathological analysis. An indirect immunoperoxidase assay was performed for the detection of HSV -1 antigen in the tissue sections. Apoptosis in the brain tissue was detected employing the TUNEL assay (Terminal deoxynucleotidyl Transferase (TdT) mediated deoxy Uridine Triphosphate Nick End Labeling) using a commerically available kit (TdT Fragel DNA fragmentation detection kit, Oncogene Research Products, CA). HSV-1 induced apoptosis of SNB 19 cells were detected in-vitro by: a) Membrane blebbing assay and b) Hoechst 33258 staining. Classical features of viral encephalitis including the presence of intranuclear inclusions, neuronal loss and perivascular cuffing were seen in the tissue sections. The immunoperoxidase assay revealed the presence of abundant viral antigen in the neurons, microglial and satellite cells. TUNEL assay revealed many apoptotic neurons, microglial and satellite cells. In-vitro assays showed evidence of HSV-1 induced apoptosis in the SNB 19 cell line. These results suggest that virus induced apoptosis may play a role in the molecular pathogenesis of HSE. Further studies are warranted to elucidate the role of HSV-1 induced apoptosis

  20. BIGH3 protein and macrophages in retinal endothelial cell apoptosis. (United States)

    Mondragon, Albert A; Betts-Obregon, Brandi S; Moritz, Robert J; Parvathaneni, Kalpana; Navarro, Mary M; Kim, Hong Seok; Lee, Chi Fung; LeBaron, Richard G; Asmis, Reto; Tsin, Andrew T


    Diabetes is a pandemic disease with a higher occurrence in minority populations. The molecular mechanism to initiate diabetes-associated retinal angiogenesis remains largely unknown. We propose an inflammatory pathway of diabetic retinopathy in which macrophages in the diabetic eye provide TGFβ to retinal endothelial cells (REC) in the retinal microvasculature. In response to TGFβ, REC synthesize and secrete a pro-apoptotic BIGH3 (TGFβ-Induced Gene Human Clone 3) protein, which acts in an autocrine loop to induce REC apoptosis. Rhesus monkey retinal endothelial cells (RhREC) were treated with dMCM (cell media of macrophages treated with high glucose and LDL) and assayed for apoptosis (TUNEL), BIGH3 mRNA (qPCR), and protein (Western blots) expressions. Cells were also treated with ΤGFβ1 and 2 for BIGH3 mRNA and protein expression. Inhibition assays were carried out using antibodies for TGFβ1 and for BIGH3 to block apoptosis and mRNA expression. BIGH3 in cultured RhREC cells were identified by immunohistochemistry (IHC). Distribution of BIGH3 and macrophages in the diabetic mouse retina was examined with IHC. RhRECs treated with dMCM or TGFβ showed a significant increase in apoptosis and BIGH3 protein expression. Recombinant BIGH3 added to RhREC culture medium led to a dose-dependent increase in apoptosis. Antibodies (Ab) directed against BIGH3 and TGFβ, as well as TGFβ receptor blocker resulted in a significant reduction in apoptosis induced by either dMCM, TGFβ or BIGH3. IHC showed that cultured RhREC constitutively expressed BIGH3. Macrophage and BIGH3 protein were co-localized to the inner retina of the diabetic mouse eye. Our results support a novel inflammatory pathway for diabetic retinopathy. This pathway is initiated by TGFβ released from macrophages, which promotes synthesis and release of BIGH3 protein by REC and REC apoptosis.